US 7,022,849 B2Granted

Quinazoline and pyrido[2,3-d]pyrimidine inhibitors of phosphodiesterase (PDE) 7

AssigneeBristol-Myers Squibb Company

InventorsWilliam J. Pitts, Joseph Barbosa

Life of this patent

Estimating the term…

Abstract

Quinazoline and pyrido[2,3-d]pyrimidine phosphodiesterase 7 (PDE 7) inhibitors of the following formula wherein R1, R2, L, Y1, Y2, Y3 and Z are as described herein, are provided which are useful in treating T-cell mediated diseases.

Claims21

Dependent claims

A compound of Formula I

wherein
R1 is H or alkyl;
R2 is
(a) heteroaryl or heterocyclo, either of which may be optionally substituted with one to three groups T1, T2, T3;
or
(b) aryl fused to a heteroaryl or heterocyclo ring wherein the combined ring system may be optionally substituted with one to three groups T1, T2, T3;
L is
(a) —OR4, —C(O)R4, —C(O)OR4, —SR4, —NR3R4, —C(O)NR3R4, —NR3SO2R4b halogen, nitro, or haloalkyl;
or
(b) alkyl, aryl, heteroaryl, heterocyclo, or cycloalkyl any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
Y1, Y2 and Y3 are independently
(a) hydrogen, halo, or —OR4a;
or
(b) alkyl, alkenyl, or alkynyl, any of which may be optionally substituted with one to three groups T1b, T2b and/or T3b;
R3 and R4 are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocylo, or (heterocyclo)alkyl, any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
or R3 and R4 together with the nitrogen atom to which they are attached may combine to form a 4- to 8-membered heterocyclo ring optionally substituted with one to three groups T1a, T2a and/or T3a;
R4a is hydrogen, alkyl, alkenyl, aryl, heteroaryl, (aryl)alkyl, (heteroaryl)alkyl, heterocylo, (heterocyclo)alkyl, cycloalkyl, or (cycloalkyl)alkyl, any of which may be optionally substituted with one to three groups T1b, T2b and/or T3b;
R4b is alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocylo, or (heterocyclo)alkyl, any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
Z is CH;
T1-1b, T2-2b, and T3-3b are 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, (heterocylco)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, where 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,
(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) T7 and 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 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 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
provided said compound is other than

57 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/173,322Filed 17 Jun 2002 · us provisional application
Priority: 19 Jun 2001
Published: US 2003/0092721 A115 May 2003
Granted: 4 Apr 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification42 codes

C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
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

Application60/299,287Us provisional application · filed 19 Jun 2001
Application60/368,752Us provisional application · filed 29 Mar 2002
US 2003/0092721 A1Pre-grant publication · published 15 May 2003
US 7,022,849 B2This patent

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

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Abstract

A compound of Formula I

wherein
R1 is H or alkyl;
R2 is
(a) heteroaryl or heterocyclo, either of which may be optionally substituted with one to three groups T1, T2, T3;
or
(b) aryl fused to a heteroaryl or heterocyclo ring wherein the combined ring system may be optionally substituted with one to three groups T1, T2, T3;
L is
(a) —OR4, —C(O)R4, —C(O)OR4, —SR4, —NR3R4, —C(O)NR3R4, —NR3SO2R4b halogen, nitro, or haloalkyl;
or
(b) alkyl, aryl, heteroaryl, heterocyclo, or cycloalkyl any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
Y1, Y2 and Y3 are independently
(a) hydrogen, halo, or —OR4a;
or
(b) alkyl, alkenyl, or alkynyl, any of which may be optionally substituted with one to three groups T1b, T2b and/or T3b;
R3 and R4 are independently H, alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocylo, or (heterocyclo)alkyl, any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
or R3 and R4 together with the nitrogen atom to which they are attached may combine to form a 4- to 8-membered heterocyclo ring optionally substituted with one to three groups T1a, T2a and/or T3a;
R4a is hydrogen, alkyl, alkenyl, aryl, heteroaryl, (aryl)alkyl, (heteroaryl)alkyl, heterocylo, (heterocyclo)alkyl, cycloalkyl, or (cycloalkyl)alkyl, any of which may be optionally substituted with one to three groups T1b, T2b and/or T3b;
R4b is alkyl, alkenyl, aryl, (aryl)alkyl, heteroaryl, (heteroaryl)alkyl, cycloalkyl, (cycloalkyl)alkyl, heterocylo, or (heterocyclo)alkyl, any of which may be optionally substituted with one to three groups T1a, T2a and/or T3a;
Z is CH;
T1-1b, T2-2b, and T3-3b are 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, (heterocylco)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, where 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,
(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) T7 and 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 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 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
provided said compound is other than

57 more elements

Facts

Application

10/173,322Filed 17 Jun 2002 · us provisional application

Priority

19 Jun 2001

Published

US 2003/0092721 A115 May 2003

Granted

4 Apr 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification42 codes

C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
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