US 2003/0191143 A1Published application

Fused heterocyclic compounds and use thereof

AssigneeBristol-Myers Squibb Company

InventorsWilliam J. Pitts, Joseph Barbosa, Junqing Guo

Life of this patent

Estimating the term…

Abstract

Fused heterocylic compounds of the following Formula 1 wherein R1, R2, R5, Z, J1 and J2 are described herein which are useful in treating leukocyte activation-associated disorders.

Claims19

Dependent claims

A compound of Formula (I)

147
including enantiomers, diastereomers, and pharmaceutically acceptable salts, solvates and prodrugs thereof,
wherein:
R1 is hydrogen or alkyl;
R2 is
(a) heteroaryl, or heterocyclo, either of which may be optionally substituted with one to three groups T1, T2 and/or T3;
(b) aryl substituted with one to three groups T1, T2 and/or T3 provided that at least one of T1, T2 and/or T3 is other than H;
or
(c) aryl fused to a heteroaryl or heterocyclo ring wherein the combined ring system may be optionally substituted with one to three groups T1, T2 and/or T3;
Z is —NR3R4, —NR3SO2R4a, OR4, SR4, haloalkyl or halogen;
R3 and R4 are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
or R3 and R4 may be taken together with the nitrogen atom to which they are attached to form a heterocyclo or heteroaryl ring optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
R4a is alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
R3b and R4b are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl;
R5 is
(a) hydrogen or cyano;
(b) alkyl, alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, aryl, (aryl)alkyl, heterocyclo, (heterocyclo)alkyl, heteroaryl or (heteroaryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
or
(c) —C(O)R6, —C(O)OR6, —C(O)—C(O)OR6 or —SO2R6a;
R6 is H, alkyl, alkenyl, —NR3b R4b, heterocyclo, (heterocyclo)alkyl, (hydroxy)alkyl, (alkoxy)alkyl, (aryloxy)alkyl, (NR3bR4b)alkyl, heteroaryl, aryl or (aryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
R6a, is alkyl, alkenyl, —NR3bR4b, heterocyclo, (heterocyclo)alkyl, (hydroxy)alkyl, (alkoxy)alkyl, (aryloxy)alkyl, (NR3bR4b)alkyl, heteroaryl, aryl or (aryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
J1 and J2 are independently optionally substituted C1-3 alkylene, provided that J1 and J2 are not both greater than C2 alkylene;
and
T1-1b, T2-2b and T3-3b are each independently
(1) hydrogen or T6, where T6 is
(i) alkyl, (hydroxy)alkyl, (alkoxy)alkyl, alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, aryl, (aryl)alkyl, heterocyclo, (heterocyclo)alkyl, heteroaryl or (heteroaryl)alkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or
(iii) a group (i) or (ii) which is independently substituted by one or more of the following groups (2) to (13) of the definition of T1-1b, T2-2b and T3-3b,
(2) —OH or —OT6;
(3) —SH or —ST6;
(4) —C(O)tH, —C(O)tT6 or —O—C(O)T6, wherein t is 1 or 2;
(5) —SO3H, —S(O)tT6 or S(O)tN(T9)T6;
(6) halo;
(7) cyano;
(8) nitro;
(9) —T4—NT7T8;
(10) —T4—N(T9)—T5—NT7T8;
(11) —T4—N(T10)—T5—T6;
(12) —T4—N(T10)—T5—H;
or
(13) oxo;
T4 and T5 are each independently
(1) a single bond;
(2) —T11—S(O)t—T12—;
(3) —T11—C(O)—T12—;
(4) —T11—C(S)—T12—;
(5) —T11—O—T12;
(6) —T11—S—T12—;
(7) —T11—O—C(O)—T12—;
(8) —T11—C(O)—O—T12—;
(9) —T11—C(═NT9a)—T12—;
or
(10) —T11—C(O)—C(O)—T12—;
T7, T8, T9, T9a and T10
(1) are each independently hydrogen or a group provided in the definition of T6, or
(2) T7and T8 may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with one or more groups listed in the description of T1-1b, T2-2b and/or T3-3b;
or
(3) T7 or T8, together with T9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with one or more groups listed in the description of T1-1b, T2-2b and/or T3-3b;
or
(4) T7 and T8 or T9 and T10 together with the nitrogen atom to which they are attached may combine to form a group —N═CT13T14 where T13 and T14 are each independently H or a group provided in the definition of T6;
and
T11 and T12, are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene.

65 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/288,980Filed 6 Nov 2002
Priority: 1 May 2001
Published: 9 Oct 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/505
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrimidines; Hydrogenated…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings

Family

Application60/287,964Us provisional application · filed 1 May 2001
Application60/299,287Us provisional application · filed 19 Jun 2001
Application60/368,752Us provisional application · filed 29 Mar 2002
Application10/137,508Continuation in part · filed 1 May 2002
Application10/288,980Continuation in part · filed 6 Nov 2002
US 2003/0092908 A1Published application
US 7,105,667 B2Related patent
US 2003/0191143 A1This patent

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

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Abstract

Fused heterocylic compounds of the following Formula 1 wherein R1, R2, R5, Z, J1 and J2 are described herein which are useful in treating leukocyte activation-associated disorders.

A compound of Formula (I)

147
including enantiomers, diastereomers, and pharmaceutically acceptable salts, solvates and prodrugs thereof,
wherein:
R1 is hydrogen or alkyl;
R2 is
(a) heteroaryl, or heterocyclo, either of which may be optionally substituted with one to three groups T1, T2 and/or T3;
(b) aryl substituted with one to three groups T1, T2 and/or T3 provided that at least one of T1, T2 and/or T3 is other than H;
or
(c) aryl fused to a heteroaryl or heterocyclo ring wherein the combined ring system may be optionally substituted with one to three groups T1, T2 and/or T3;
Z is —NR3R4, —NR3SO2R4a, OR4, SR4, haloalkyl or halogen;
R3 and R4 are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
or R3 and R4 may be taken together with the nitrogen atom to which they are attached to form a heterocyclo or heteroaryl ring optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
R4a is alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1a, T2a and/or T3a;
R3b and R4b are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocyclo or (heterocyclo)alkyl;
R5 is
(a) hydrogen or cyano;
(b) alkyl, alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, aryl, (aryl)alkyl, heterocyclo, (heterocyclo)alkyl, heteroaryl or (heteroaryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
or
(c) —C(O)R6, —C(O)OR6, —C(O)—C(O)OR6 or —SO2R6a;
R6 is H, alkyl, alkenyl, —NR3b R4b, heterocyclo, (heterocyclo)alkyl, (hydroxy)alkyl, (alkoxy)alkyl, (aryloxy)alkyl, (NR3bR4b)alkyl, heteroaryl, aryl or (aryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
R6a, is alkyl, alkenyl, —NR3bR4b, heterocyclo, (heterocyclo)alkyl, (hydroxy)alkyl, (alkoxy)alkyl, (aryloxy)alkyl, (NR3bR4b)alkyl, heteroaryl, aryl or (aryl)alkyl, any of which may be optionally independently substituted where valance allows with one to three groups T1b, T2b and/or T3b;
J1 and J2 are independently optionally substituted C1-3 alkylene, provided that J1 and J2 are not both greater than C2 alkylene;
and
T1-1b, T2-2b and T3-3b are each independently
(1) hydrogen or T6, where T6 is
(i) alkyl, (hydroxy)alkyl, (alkoxy)alkyl, alkenyl, alkynyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, aryl, (aryl)alkyl, heterocyclo, (heterocyclo)alkyl, heteroaryl or (heteroaryl)alkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or
(iii) a group (i) or (ii) which is independently substituted by one or more of the following groups (2) to (13) of the definition of T1-1b, T2-2b and T3-3b,
(2) —OH or —OT6;
(3) —SH or —ST6;
(4) —C(O)tH, —C(O)tT6 or —O—C(O)T6, wherein t is 1 or 2;
(5) —SO3H, —S(O)tT6 or S(O)tN(T9)T6;
(6) halo;
(7) cyano;
(8) nitro;
(9) —T4—NT7T8;
(10) —T4—N(T9)—T5—NT7T8;
(11) —T4—N(T10)—T5—T6;
(12) —T4—N(T10)—T5—H;
or
(13) oxo;
T4 and T5 are each independently
(1) a single bond;
(2) —T11—S(O)t—T12—;
(3) —T11—C(O)—T12—;
(4) —T11—C(S)—T12—;
(5) —T11—O—T12;
(6) —T11—S—T12—;
(7) —T11—O—C(O)—T12—;
(8) —T11—C(O)—O—T12—;
(9) —T11—C(═NT9a)—T12—;
or
(10) —T11—C(O)—C(O)—T12—;
T7, T8, T9, T9a and T10
(1) are each independently hydrogen or a group provided in the definition of T6, or
(2) T7and T8 may together be alkylene or alkenylene, completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached, which ring is unsubstituted or substituted with one or more groups listed in the description of T1-1b, T2-2b and/or T3-3b;
or
(3) T7 or T8, together with T9, may be alkylene or alkenylene completing a 3- to 8-membered saturated or unsaturated ring together with the nitrogen atoms to which they are attached, which ring is unsubstituted or substituted with one or more groups listed in the description of T1-1b, T2-2b and/or T3-3b;
or
(4) T7 and T8 or T9 and T10 together with the nitrogen atom to which they are attached may combine to form a group —N═CT13T14 where T13 and T14 are each independently H or a group provided in the definition of T6;
and
T11 and T12, are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene.

65 more elements

Facts

Application

10/288,980Filed 6 Nov 2002

Priority

1 May 2001

Published

9 Oct 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/505
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrimidines; Hydrogenated…
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings

Family

Application60/287,964Us provisional application · filed 1 May 2001

Application60/299,287Us provisional application · filed 19 Jun 2001

Application60/368,752Us provisional application · filed 29 Mar 2002

Application10/137,508Continuation in part · filed 1 May 2002

Application10/288,980Continuation in part · filed 6 Nov 2002

US 2003/0092908 A1Published application

US 7,105,667 B2Related patent

US 2003/0191143 A1This patent

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