US 2003/0114502 A1Published application

Substituted thiazoles and oxazoles as corticotropin releasing hormone ligands

AssigneeBristol-Myers Squibb Pharma Company

InventorsAndreas Termin, Peter Grootenhuis, Dean Wilson, Valentina Molteni

Life of this patent

Estimating the term…

Abstract

Provided herein are novel substituted thiazoles and oxazoles of the Formula (I): 1 as well as compositions, including pharmaceutical compositions, containing the same, and the use thereof in the treatment of various neurological and psychological disorders, e.g., affective disorder, anxiety and depression, treatable by antagonizing CRF receptors.

Claims13

Dependent claims

A compound of Formula (I):

54
or a pharmaceutically acceptable salt form thereof, wherein:
X is 0 or S;
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR6R7, —NR6COR7, —COR6, —CO2R6, —OR6, —SR6, —S(O)nR6, —CH(OH)R6, or —CH2COR6;
each R2 and R4 is, independently, H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR8R9, —NR8COR9, —COR8, —CO2R8, —OR8, —SR8, —S(O)nR8, —CH(OH)R8, or —CH2COR8;
each R3 and R5 is, independently, H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR10R11, —NR10COR11, —COR10, —CO2R10, —OR10, —SR10, —S(O)nR10, —CH(OH)R10, or —CH2COR10;
each R6 and R7 is, independently, at each occurance, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each of said R6 and R7 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R8 and R9 is, independently, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R8 and R9 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R10 and R11 is, independently, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R10 and R11 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R12 and R13 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R12 and R13 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R14 and R15 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R14 and R15 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R16 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl-C1-C6 alkyl, —CN, —CH2CN, —CH2OR12, CH2NR12R13, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR12R13, —NR12COR13, —NHSO2R, —COR12, —CO2R12, —OR12, —OC2H4OR12, —SR12, —S(O)nR12, —S(O)nNR12R13, —CH(OH)R12, —CH2COR12, —OC(O)R12, —OCHR12CO2R13, —OCHR12COR13, —NR12CONR12R13, —NR12CO2R13, —CONR12R13, or —CH(OH)C(R12)3;
R17 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR14, CH2NR14R15, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR14R15, —NR14COR15, —NHSO2R, —COR14, —CO2R14, —OR14, —OC2H4OR14, —SR14, —S(O)nR14, —S(O)nNR14R15, —CH(OH)R14, —CH2COR14, —OC(O)R14, —OCHR14CO2R15, —OCHR14COR15, —NR14CONR14R15, —NR14CO2R15, —CONR14R15, or —CH(OH)C(R14)3;
each R18 and R19 is, independently, at each occurance, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R18 and R19 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R20 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR21, CH2NR21R22, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR21R22, —NR21COR22, —NHSO2R, —COR21, —CO2R21, —OR21, —OC2H4OR21, —SR21, —S(O)nR21, —S(O)nNR21R22, —CH(OH)R21, —CH2COR21, —OC(O)R21, —OCHR21CO2R22, —OCHR21COR22, —NR21CONR21R22, —NR21CO2R22, —CONR21R22, or —CH(OH)C(R21)3;
each R21 and R22 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R21 and R22 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R23 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR24, CH2NR24R25, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR24R25, —NR24COR25, —NHSO2R, —COR24, —CO2R24, —OR24, —OC2H4OR24, —SR24, —S(O)nR24, —S(O)nNR24R25, —CH(OH)R24, —CH2COR24, —OC(O)R24, —OCHR24CO2R25, —OCHR24COR25, —NR24CONR24R25, —NR24CO2R25, —CONR24R25, or —CH(OH)C(R24)3;
each R24 and R25 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl or heterocyclyl, wherein each R24 and R25 is optionally substituted with one or more halogen, hydroxyl, or —CN;
Ar1 is phenyl, benzyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl 3,4-dihydro-2H-benzo[1,4]oxazine, benzo[1,3]dioxole, or heterocyclyl, wherein Ar1 is optionally substituted with 1 to 5 R16 groups;
and wherein two of said R16 groups, each attached to adjacent carbon atoms of said Ar1, are optionally taken together along with the carbon atoms to which they are attached to form a fused saturated, fused partially unsaturated, or fused unsaturated 5 or 6 membered carbocyclic or heterocyclic ring, wherein said carbocyclic or heterocyclic ring is optionally substituted with 1 to 3 R20 groups;
Ar2 is phenyl, benzyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 3,4-dihydro-2H-benzo[1,4]oxazine, benzo[1,3]dioxole, or heterocyclyl, wherein each Ar2 is optionally substituted with 1 to 5 R17 groups;
and wherein two of said R17 groups, each attached to adjacent carbon atoms of said Ar2, are optionally taken together along with the carbon atoms to which they are attached to form a fused saturated, fused partially unsaturated, or fused unsaturated 5 or 6 membered carbocyclic or heterocyclic ring, wherein said carbocyclic or heterocyclic ring is optionally substituted with 1 to 3 R23 groups;
n is 0,1, or 2;
aryl is phenyl or naphthyl, wherein said aryl is optionally substituted with 1 to 10 substituents independently selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18, —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3;
heteroaryl is pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl , pyrazolyl, triazolyl, tetrazolyl, or indazolyl, wherein said heteroaryl is optionally substituted with 1 to 10 substituents selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18 or —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3;
and
heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 10 substituents selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18, —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3.

24 more elements

A compound of Formula (Ia):

55
or a pharmaceutically acceptable salt form thereof, wherein:
R1 is Me, R16a is benzyl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is m-CN-benzyl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is —C.CH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is —C.CH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is —C.CH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is F and R17e is H;
or
R1 is Me, R16a is —C.CH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is H, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is F, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is Br and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is Cl, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is Cl, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is H, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is F, R17b is H, R17c is F, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is Cl and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is NMe2, R17d is Br and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OCHF2, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OEt, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is H, R17b is H, R17c is SMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is Br and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is F, R16d is H, R16e is H, R17a is F, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is F, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is Cl, R17b is H, R17c is H, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is F, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is H, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Cl, R16b is H, R16c is H, R16d is H, R16e is F, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is 5-tetrazolyl, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is CO2Me, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is F, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is F, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, H is R17d and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is F, R16e is H, R17a a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is F, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is F, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is F, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is F, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is F, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is F and R17e is H;
or
R1 is Me, R16a is H, R16b is CF3, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is Cl, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is Cl, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is Cl, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is F, R16c is H, R16d is F, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is is H, R16b is F, R16c is H, R16d is H, R16e is H, R17a as H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is Cl, R16d H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is Cl, R16d is H, R16e H, R17a is H, R17b is H, R17c is OEt, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is F, R17b is H, R17c is H, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Et, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is Me, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is OMe, R16d is H, H16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is OMe, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is H, R16c is OMe, R16d is H, R16e is H, R17a is H, R17b is H, R17c is SMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is Me, R16c is F, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is H, R16b is OMe, R16c is OMe, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is I, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is I, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is I, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Me, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Me, R16b is H, R16c is H, R16d is F, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Me, R16b is H, R16c is H, R16d is H, R16e is F, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H ;
or
R1 is Me, R16a is Me, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OBn, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OBn, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OC2H4OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH2C.CH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH2CHCH2, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH2CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OCH2CN, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH2CO2Me, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OCH(Me)COMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH(Me)CO2Et, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OCH(Me)CO2Me, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OH, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Br, R16e is H, R17a is Cl, R17b is H, R17c is Cl R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Br, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Br, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Br, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Br, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CH2COMe, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CH(OH)Me, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CH(OH)CMe3, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CN, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CN, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is COMe, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is CONMe2, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is F, R16e is F, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is F, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CF3, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CH2OH, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is H, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CN, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CO2Me, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is F, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is F and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is I, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is Me, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OMe, R16b is OMe, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is OPh, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is Ph, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is Ph, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is SCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is SCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is Me, R16a is SCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Me, R16a is SCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Me, R16a is SMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Br, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CHO, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is (CH(OH)Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CN, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is COMe, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is I, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is SCF3, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is Cl, R16b is H, R16c is Cl, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CHO, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is (C═O)cPr, R16a is H, R16b is H, R16c is F, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CHO, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is CH(OH)Me, R16a is OCF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is CH(OH)Me, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is I, R16a is OEt, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is Br, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is Br, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is CF3, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CH2CHO, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is H, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CH2OH, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CHF2, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CHO, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CHO, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is CHO, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is CHO, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is CH(OH)Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CF3, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is CH(OH)Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is CH(OH)Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is CH(OH)Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is CH(OH)Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is COMe, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is COMe, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me ad R17e is H;
or
R1 is CO2Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is I, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is CF3, R17b is H, R17c is CF3, R17d is H and R17e is H;
or
R1 is I, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is I, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is OMe, R17d is Me and R17e is H;
or
R1 is I, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is I, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is OMe, R17b is H, R17c is OMe, R17d is H and R17e is H;
or
R1 is NH2, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is NO2, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is SMe, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Cl, R17b is H, R17c is Cl, R17d is H and R17e is H;
or
R1 is SMe, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is H;
or
R1 is Me, R16a is CF3, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is Me;
or
R1 is Me, R16a is Cl, R16b is H, R16c is F, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is Me;
or
R1 is Me, R16a is F, R16b is H, R16c is H, R16d is H, R16e is Cl, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is Me;
or
R1 is Me, R16a is H, R16b is H, R16c is H, R16d is H, R16e is H, R17a is F, R17b is H, R17c is H, R17d is H and R17e is CF3;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is F, R17b is H, R17c is H, R17d is H and R17e is CF3;
or
R1 is Me, R16a is OMe, R16b is H, R16c is H, R16d is H, R16e is H, R17a is Me, R17b is H, R17c is Me, R17d is H and R17e is Me.

450 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/192,055Filed 10 Jul 2002
Priority: 13 Jul 2001
Published: 19 Jun 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 277/22
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
C07D 263/32
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
C07D 277/24
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms: radicals substituted by oxygen…
C07D 277/26
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms: radicals substituted by sulfur…

Family

Application60/305,067Us provisional application · filed 13 Jul 2001
US 7,276,526 B2Related patent
US 2003/0114502 A1This patent

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

Timeline

Citations

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Abstract

A compound of Formula (I):

54
or a pharmaceutically acceptable salt form thereof, wherein:
X is 0 or S;
R1 is H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR6R7, —NR6COR7, —COR6, —CO2R6, —OR6, —SR6, —S(O)nR6, —CH(OH)R6, or —CH2COR6;
each R2 and R4 is, independently, H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR8R9, —NR8COR9, —COR8, —CO2R8, —OR8, —SR8, —S(O)nR8, —CH(OH)R8, or —CH2COR8;
each R3 and R5 is, independently, H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —CN, —NO2, C3-C6 cycloalkyl, —NR10R11, —NR10COR11, —COR10, —CO2R10, —OR10, —SR10, —S(O)nR10, —CH(OH)R10, or —CH2COR10;
each R6 and R7 is, independently, at each occurance, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each of said R6 and R7 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R8 and R9 is, independently, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R8 and R9 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R10 and R11 is, independently, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R10 and R11 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R12 and R13 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R12 and R13 is optionally substituted with one or more halogen, hydroxyl, or —CN;
each R14 and R15 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R14 and R15 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R16 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl-C1-C6 alkyl, —CN, —CH2CN, —CH2OR12, CH2NR12R13, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR12R13, —NR12COR13, —NHSO2R, —COR12, —CO2R12, —OR12, —OC2H4OR12, —SR12, —S(O)nR12, —S(O)nNR12R13, —CH(OH)R12, —CH2COR12, —OC(O)R12, —OCHR12CO2R13, —OCHR12COR13, —NR12CONR12R13, —NR12CO2R13, —CONR12R13, or —CH(OH)C(R12)3;
R17 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR14, CH2NR14R15, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR14R15, —NR14COR15, —NHSO2R, —COR14, —CO2R14, —OR14, —OC2H4OR14, —SR14, —S(O)nR14, —S(O)nNR14R15, —CH(OH)R14, —CH2COR14, —OC(O)R14, —OCHR14CO2R15, —OCHR14COR15, —NR14CONR14R15, —NR14CO2R15, —CONR14R15, or —CH(OH)C(R14)3;
each R18 and R19 is, independently, at each occurance, H, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl, wherein each R18 and R19 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R20 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR21, CH2NR21R22, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR21R22, —NR21COR22, —NHSO2R, —COR21, —CO2R21, —OR21, —OC2H4OR21, —SR21, —S(O)nR21, —S(O)nNR21R22, —CH(OH)R21, —CH2COR21, —OC(O)R21, —OCHR21CO2R22, —OCHR21COR22, —NR21CONR21R22, —NR21CO2R22, —CONR21R22, or —CH(OH)C(R21)3;
each R21 and R22 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein each R21 and R22 is optionally substituted with one or more halogen, hydroxyl, or —CN;
R23 is, at each occurrence, H, halogen, aryl, heteroaryl, heterocyclyl, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —CH2CN, —CH2OR24, CH2NR24R25, —CH2OH, —NO2, C3-C6 cycloalkyl, —NR24R25, —NR24COR25, —NHSO2R, —COR24, —CO2R24, —OR24, —OC2H4OR24, —SR24, —S(O)nR24, —S(O)nNR24R25, —CH(OH)R24, —CH2COR24, —OC(O)R24, —OCHR24CO2R25, —OCHR24COR25, —NR24CONR24R25, —NR24CO2R25, —CONR24R25, or —CH(OH)C(R24)3;
each R24 and R25 is, independently, at each occurrence, H, —NH2, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, aryl, heteroaryl or heterocyclyl, wherein each R24 and R25 is optionally substituted with one or more halogen, hydroxyl, or —CN;
Ar1 is phenyl, benzyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl 3,4-dihydro-2H-benzo[1,4]oxazine, benzo[1,3]dioxole, or heterocyclyl, wherein Ar1 is optionally substituted with 1 to 5 R16 groups;
and wherein two of said R16 groups, each attached to adjacent carbon atoms of said Ar1, are optionally taken together along with the carbon atoms to which they are attached to form a fused saturated, fused partially unsaturated, or fused unsaturated 5 or 6 membered carbocyclic or heterocyclic ring, wherein said carbocyclic or heterocyclic ring is optionally substituted with 1 to 3 R20 groups;
Ar2 is phenyl, benzyl, naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 3,4-dihydro-2H-benzo[1,4]oxazine, benzo[1,3]dioxole, or heterocyclyl, wherein each Ar2 is optionally substituted with 1 to 5 R17 groups;
and wherein two of said R17 groups, each attached to adjacent carbon atoms of said Ar2, are optionally taken together along with the carbon atoms to which they are attached to form a fused saturated, fused partially unsaturated, or fused unsaturated 5 or 6 membered carbocyclic or heterocyclic ring, wherein said carbocyclic or heterocyclic ring is optionally substituted with 1 to 3 R23 groups;
n is 0,1, or 2;
aryl is phenyl or naphthyl, wherein said aryl is optionally substituted with 1 to 10 substituents independently selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18, —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3;
heteroaryl is pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl , pyrazolyl, triazolyl, tetrazolyl, or indazolyl, wherein said heteroaryl is optionally substituted with 1 to 10 substituents selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18 or —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3;
and
heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 10 substituents selected from H, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, —CN, —NO2, —CH2OH, C3-C6 cycloalkyl, —NR18R19, —NR18COR19, —COR18, —CO2R18, —OR18, —SR18, —S(O)nR18, —CH(OH)R18, —CH2COR18, —OC(O)R18, —NR18CONR18R19, —NR18CO2R19, —CONR18R19, or —CH(OH)C(R18)3.

24 more elements

Facts

Application

10/192,055Filed 10 Jul 2002

Priority

13 Jul 2001

Published

19 Jun 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 277/22
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
C07D 263/32
Having two or three double bonds between ring members or between ring members and non-ring members: with only hydrogen atoms, hydrocarbon or…
C07D 277/24
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms: radicals substituted by oxygen…
C07D 277/26
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms: radicals substituted by sulfur…