US 2011/0034689 A1Published application

N4-Phenyl-Quinazoline-4-Amine Derivatives and Related Compounds as ErbB Type I Receptor Tyrosine Kinase Inhibitors for the Treatment of Hyperproliferative Diseases

AssigneeArray BioPharma Inc.

InventorsJoseph P. Lyssikatos, Julie Marie Greschuk, Fredrik P. Marmsater, Quian Zhao, D. David Hennings, Weidong Liu

Life of this patent

Estimating the term…

Abstract

This invention provides compounds of Formula I wherein B, G, A, E, R1, R2, R3, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.

Claims43

Dependent claims

A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein:
A is O, C(═O), S, SO or SO2;
G is N or C—CN;
B represents a fused 6-membered aryl ring or a 5-6 membered heteroaryl ring;
E is
X is N or CH;
D1, D2 and D3 are independently N or CR19;
D4 and D5 are independently N or CR19 and D6 is O, S, or NR20, wherein at least one of D4 and D5 is not CR19;
D7, D8, D9 and D10 are independently N or CR19, wherein at least one of D7, D8, D9 and D10 is N;
R1 is H or alkyl;
each R2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15, —NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR15C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R3 is independently Q, Z, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR15, NR15R16, NR15OR16, NR15C(═O)OR18, NR15C(═O)R16, SO2NR15R16, SOR15, SO2R15, C(═O)R15, C(═O)OR15, OC(═O)R15, C(═O)NR15R16, NR15C(═O)NR16R17, NR15C(═NCN)NR16R17, or NR15C(═NCN)R16,
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl are optionally substituted with one or more groups independently selected from halogen, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR15, NR15R16, NR15OR16, NR15C(═O)OR18, NR15C(═O)R16, SO2NR15R16, SR15, SOR15, SO2R15, C(═O)R15, C(═O)OR15, OC(═O)R15, C(═O)NR15R16, NR15C(═O)NR16R17, NR15C(═NCN)NR16R17, NR15C(═NCN)R16, (C1-C4 alkyl)NRaRb and NR15C(O)CH2ORa;
or R3 is a 5-6 membered heterocyclic ring containing from 1 to 4 heteroatoms selected from N, O, S, SO and SO2 and substituted with -M1-M2-M3-M4 or -M1-M5, wherein M1 is C1-C4 alkyl, wherein optionally a CH2 is replaced by a C(═O) group;
M2 is NRe or CReRf;
M3 is C1-C4 alkyl;
M4 is CN, NReS(O)0-2Rf, S(O)0-2NRgRh, CORgRh, S(O)0-2Rf, or CO2Rf, and M5 is NRgRh, wherein Re, Rf, Rg and Rh are independently H or C1-C4 alkyl, or Rg and Rh together with the nitrogen atom to which they are attached form a 5- or 6-membered ring optionally containing 1 or 2 additional heteroatoms selected from N, O, S, SO and SO2 in which any ring nitrogen atom present is optionally substituted with a C1-C4 alkyl group and which ring may optionally have one or two oxo or thiooxo substituents;
Q is
Z is selected from
and tautomers thereof;
W and V are independently O, NR6, S, SO, SO2, CR7R8, CR8R9 or C═O;
W2 is O or S;
Y is S, SO, SO2, CR7CR8, or CR8R9,
provided that when W is O, NR6, S, SO, or SO2, then V is CR8R9, and
when V is O, NR6, S, SO, or SO2, then W and Y are each CR8R9;
R8b is H or C1-C6 alkyl;
each R6, R8, R8a and R9 are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
R7 is hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16, —NR15C(O)NR16R17, —OR15, —S(O)R15, —SO2R15, or SR15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl, are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16, —NR15C(O)NR16R17, —OR15, —S(O)R15, —SO2R15, SR15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl;
R10 is hydrogen, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, —NR15C(O)OR18, —NR15C(O)R16, —NR15R16, —OR15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16NR17, —OR15, —S(O)R15, —SO2R15, SR15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R7 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R8 and R9 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R6 and R10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R8 and R10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
each R12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
R13 and R14 are independently hydrogen or alkyl, or
R13 and R14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heteorcyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R15, R16 and R17 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or any two of R15, R16 and R17 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R13 and R15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R18 is CF3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc,
or R15 and R18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
each R19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R20 is independently C1-C4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl;
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms;
j is 0, 1, 2 or 3;
m is 1, 2, 3, or 4;
n is 0, 1, 2, 3, or 4;
q is 0, 1, 2, 3, 4, or 5;
and
p is 0, 1 or 2;
wherein when said compound of Formula I is represented by the formula
and R3 is other than Q or Z, then E is not a benzofuranyl, indolyl, quinazolinyl, quinolinyl, or isoquinolinyl ring.

53 more elements

A compound of Formula 8:

wherein each R6, R8, and R8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15 trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
R15 and R16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or R15 and R16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
and
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or hetetoaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms.

6 more elements

A compound of Formula 9:

wherein A is O, C(═O), S, SO or SO2;
E is:
X is N or CH;
D1, D2 and D3 are independently N or CR19;
D4 and D5 are independently N or CR19 and D6 is O, S, or NR20, wherein at least one of D4 and D5 is not CR19;
D7, D8, D9 and D10 are independently N or CR19, wherein at least one of D7, D8, D9 and D10 is N;
R1 is H or alkyl;
each R2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15, —NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR15C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R6, R8, and R8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
each R12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
R13 and R14 are independently hydrogen or alkyl, or
R13 and R14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heteorcyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R15 and R16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(—O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or R15 and R16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R13 and R15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(—O)Rb, and NRaC(═O)NRbRc;
R18 is CF3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(—O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc,
or R15 and R18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
each R19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R20 is independently C1-C4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl;
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms;
j is 0, 1, 2 or 3;
n is 0, 1, 2, 3, or 4;
q is 0, 1, 2, 3, 4, or 5;
and
p is 0, 1 or 2.

26 more elements

A process for preparing a compound of Formula 9:

comprising condensing a compound of Formula 8:
with a compound of Formula 2:
in the presence of an acid in a suitable solvent to provide a compound of Formula 9;
wherein A is O, C(═O), S, SO or SO2;
E is:
X is N or CH;
D1, D2 and D3 are independently N or CR19;
D4 and D5 are independently N or CR19 and D6 is O, S, or NR20, wherein at least one of D4 and D5 is not CR19;
D7, D8, D9 and D10 are independently N or CR19, wherein at least one of D7, D8, D9 and D10 is N;
R1 is H or alkyl;
each R2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15, —NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR15C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R6, R8, and R8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
each R12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
R13 and R14 are independently hydrogen or alkyl, or
R13 and R14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heteorcyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R15 and R16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or R15 and R16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R13 and R15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R18 is CF3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc,
or R15 and R18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
each R19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R20 is independently C1-C4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl;
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms;
j is 0, 1, 2 or 3;
n is 0, 1, 2, 3, or 4;
q is 0, 1, 2, 3, 4, or 5;
and
p is 0, 1 or 2.

29 more elements

A process for preparing a compound of Formula 10:

comprising:
(a) condensing a compound of Formula 8:
with a compound of Formula 2:
in the presence of an acid in a suitable solvent to provide a compound of Formula 9:
and
(b) cyclizing the thiourea of Formula 9 to provide a compound of Formula 10;
wherein A is O, C(═O), S, SO or SO2;
E is:
X is N or CH;
D1, D2 and D3 are independently N or CR19;
D4 and D5 are independently N or CR19 and D6 is O, S, or NR20, wherein at least one of D4 and D5 is not CR19;
D7, D8, D9 and D10 are independently N or CR19, wherein at least one of D7, D8, D9 and D10 is N;
R1 is H or alkyl;
each R2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15, —NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR15C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R6, R8, and R8a are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
each R12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
R13 and R14 are independently hydrogen or alkyl, or
R13 and R14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heteorcyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R15 and R16 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or R15 and R16 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R13 and R15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R18 is CF3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc,
or R15 and R18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
each R19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R20 is independently C1-C4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl;
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms;
j is 0, 1, 2 or 3;
n is 0, 1, 2, 3, or 4;
q is 0, 1, 2, 3, 4, or 5;
and
p is 0, 1 or 2.

32 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/085,048Filed 15 Nov 2006
Priority: 15 Nov 2005
Published: 10 Feb 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification42 codes

A61K 31/337
Having oxygen as the only ring hetero atom, e.g. fungichromin: having four-membered rings, e.g. taxol
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/517
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines

Family

Application60/736,289Us provisional application · filed 15 Nov 2005
Application60/817,019Us provisional application · filed 28 Jun 2006
US 8,648,087 B2Related patent
US 2011/0034689 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein:
A is O, C(═O), S, SO or SO2;
G is N or C—CN;
B represents a fused 6-membered aryl ring or a 5-6 membered heteroaryl ring;
E is
X is N or CH;
D1, D2 and D3 are independently N or CR19;
D4 and D5 are independently N or CR19 and D6 is O, S, or NR20, wherein at least one of D4 and D5 is not CR19;
D7, D8, D9 and D10 are independently N or CR19, wherein at least one of D7, D8, D9 and D10 is N;
R1 is H or alkyl;
each R2 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15, —NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR15C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R3 is independently Q, Z, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR15, NR15R16, NR15OR16, NR15C(═O)OR18, NR15C(═O)R16, SO2NR15R16, SOR15, SO2R15, C(═O)R15, C(═O)OR15, OC(═O)R15, C(═O)NR15R16, NR15C(═O)NR16R17, NR15C(═NCN)NR16R17, or NR15C(═NCN)R16,
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl are optionally substituted with one or more groups independently selected from halogen, oxo, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, trifluoromethoxy, difluoromethoxy, fluoromethoxy, trifluoromethyl, difluoromethyl, fluoromethyl, OR15, NR15R16, NR15OR16, NR15C(═O)OR18, NR15C(═O)R16, SO2NR15R16, SR15, SOR15, SO2R15, C(═O)R15, C(═O)OR15, OC(═O)R15, C(═O)NR15R16, NR15C(═O)NR16R17, NR15C(═NCN)NR16R17, NR15C(═NCN)R16, (C1-C4 alkyl)NRaRb and NR15C(O)CH2ORa;
or R3 is a 5-6 membered heterocyclic ring containing from 1 to 4 heteroatoms selected from N, O, S, SO and SO2 and substituted with -M1-M2-M3-M4 or -M1-M5, wherein M1 is C1-C4 alkyl, wherein optionally a CH2 is replaced by a C(═O) group;
M2 is NRe or CReRf;
M3 is C1-C4 alkyl;
M4 is CN, NReS(O)0-2Rf, S(O)0-2NRgRh, CORgRh, S(O)0-2Rf, or CO2Rf, and M5 is NRgRh, wherein Re, Rf, Rg and Rh are independently H or C1-C4 alkyl, or Rg and Rh together with the nitrogen atom to which they are attached form a 5- or 6-membered ring optionally containing 1 or 2 additional heteroatoms selected from N, O, S, SO and SO2 in which any ring nitrogen atom present is optionally substituted with a C1-C4 alkyl group and which ring may optionally have one or two oxo or thiooxo substituents;
Q is
Z is selected from
and tautomers thereof;
W and V are independently O, NR6, S, SO, SO2, CR7R8, CR8R9 or C═O;
W2 is O or S;
Y is S, SO, SO2, CR7CR8, or CR8R9,
provided that when W is O, NR6, S, SO, or SO2, then V is CR8R9, and
when V is O, NR6, S, SO, or SO2, then W and Y are each CR8R9;
R8b is H or C1-C6 alkyl;
each R6, R8, R8a and R9 are independently hydrogen, trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, OR15, NR15R16, SR15, S(═O)R15, SO2R15, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R8 and R8a together with the atom to which they are attached form a 3 to 6 membered carbocyclic ring;
R7 is hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16, —NR15C(O)NR16R17, —OR15, —S(O)R15, —SO2R15, or SR15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl, are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16, —NR15C(O)NR16R17, —OR15, —S(O)R15, —SO2R15, SR15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl;
R10 is hydrogen, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, —NR15C(O)OR18, —NR15C(O)R16, —NR15R16, —OR15, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylalkyl, are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —NR15SO2R16—SO2NR15R16, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR15C(O)OR18, —NR15C(O)R16, —C(O)NR15R16, —NR15R16NR17, —OR15, —S(O)R15, —SO2R15, SR15, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl;
or R6 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R7 and R8 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R8 and R9 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated cycloalkyl or heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said carbocyclic and heterocyclic rings are optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R6 and R10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
or R8 and R10 together with the atoms to which they are attached form a 3 to 10 membered saturated or partially unsaturated heterocyclyl ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, OR15, NR15R16, SR15, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl;
each R12 is independently halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated and partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
R13 and R14 are independently hydrogen or alkyl, or
R13 and R14 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl, or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heteorcyclyl portions are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R15, R16 and R17 are independently H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc, OC(═O)NRaRb, and C(═O)CH2ORa;
or any two of R15, R16 and R17 together with the atom to which they are attached form a heterocyclic ring optionally containing one or more additional heteroatoms selected from N, O, S, SO, SO2 and NR6, wherein said heterocyclic ring is optionally substituted with one or more groups independently selected from oxo, halogen, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, cycloalkylalkyl, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, aryl, ORa, NRaRb, SRa, heteroaryl, arylalkyl, heteroarylalkyl, and heterocyclylalkyl,
or R13 and R15 together with the atom to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
R18 is CF3, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, saturated or partially unsaturated heterocyclyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, aryl, heteroaryl, halogen, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, NRaC(═O)NRbRc,
or R15 and R18 together with the atoms to which they are attached form a saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocyclyl ring, wherein said alkyl, cycloalkyl and heterocyclyl are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, oxo, ORa, NRaRb, NRaORb, NRaCO2Rb, NRaCORb, SO2NRaRb, SRa, SORa, SO2Ra, S—S—Ra, C(═O)Ra, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRaC(═O)Rb, and NRaC(═O)NRbRc;
each R19 is independently H, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —SR18, —OR15, —C(O)R15, —C(O)OR15, —NR14C(O)OR18, —OC(O)R15—NR14SO2R18, —SO2NR15R14, —NR14C(O)R15, —C(O)NR15R14, —NR13C(O)NR15R14, —NR13C(NCN)NR15R14, —NR15R14, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, —S(O)p(alkyl), —S(O)p(CR13R14)q-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, heterocyclylalkyl, —O(CR13R14)q-aryl, —NR15(CR13R14)q-aryl, —O(CR13R14)q-heteroaryl, —NR13(CR13R14)q-heteroaryl, —O(CR13R14)q-heterocyclyl or —NR15(CR13R14)q-heterocyclyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR13SO2R18, —SO2NR15R13, —C(O)R15, —C(O)OR15, —OC(O)R15, —NR13C(O)OR18, —NR13C(O)R15, —C(O)NR15R13, —NR15R13, —NR14C(O)NR15R13, —NR14C(NCN)NR15R13, —OR15, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocyclyl, and heterocyclylalkyl, and wherein said aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated and partially unsaturated cycloalkyl, saturated and partially unsaturated heterocyclyl, NR15R13 and OR15;
each R20 is independently C1-C4 alkyl, saturated or partially unsaturated cycloalkyl, trifluoromethyl, difluoromethyl, or fluoromethyl;
Ra, Rb and Rc are independently H, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocyclyl, aryl, or heteroaryl,
or NRaRb forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms and optionally substituted with (C1-C3 alkyl),
or NRbRc forms a 5-6 membered heterocyclic ring having 1-2 ring nitrogen atoms;
j is 0, 1, 2 or 3;
m is 1, 2, 3, or 4;
n is 0, 1, 2, 3, or 4;
q is 0, 1, 2, 3, 4, or 5;
and
p is 0, 1 or 2;
wherein when said compound of Formula I is represented by the formula
and R3 is other than Q or Z, then E is not a benzofuranyl, indolyl, quinazolinyl, quinolinyl, or isoquinolinyl ring.

53 more elements

Facts

Application

12/085,048Filed 15 Nov 2006

Priority

15 Nov 2005

Published

10 Feb 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification42 codes

A61K 31/337
Having oxygen as the only ring hetero atom, e.g. fungichromin: having four-membered rings, e.g. taxol
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/517
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines