Claims
- 1. A compound of formula (I) wherein:one of A1, A2 and A3 represents NR2 and the others represent C(R3)(R4); R1 represents R6N(R7)—C(═O)—NH—Ar2—; R2 represents —(═O)—R8, —C(═O)—OR8a or R8b; R3 and R4 each represent hydrogen or R8; R6 represents hydrogen or lower alkyl and R7 represents arylor arylalkyl; R8 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, or alkyl substituted by an acidic functional group or a protecting group, or by —Z3H, —Z2R10, —C(═O)—NY1Y2 or —NY1Y2; R8a represents alkyl, aryl or arylalkyl; R8b represents alkyl, aryl, arylalkyl or alkyl substituted by an acidic functional group or a protecting group; R9 represents aryl, cycloalkyl or cycloalkenyl; R10 represents alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl or cycloalkenylalkyl; R11 represents hydrogen or lower alkyl; R12 is a direct bond or an alkylene chain, an alkenylene chain or an alkynylene chain; R13 is —C(═O)—NH—; Ar1 represents aryldiyl; Ar2 represents aryldiyl; L1 represents a —R12—R13— linkage; Y is carboxy; Y1 and Y2 are independently hydrogen, alkenyl, alkyl, aryl, arylalkyl or cycloalkyl; Z1 represents NH; Z2 is O or S(O)n; Z3 is O or S; and n is zero or an integer 1 or 2; provide that in these compounds an oxygen, nitrogen or sulphur atom is not attached directly to a carbon carbon multiple bond of an alkenyl or alkynyl residue;or a prodrug thereof, or a pharmaceutically acceptable salt or solvate thereof or prodrug.
- 2. A compound according to claim 1 in which R7 is optionally substituted phenyl.
- 3. A compound according to claim 1 in which R6 is hydrogen.
- 4. A compound according to claim 1 in which R6 is hydrogen and R7 is phenyl or ortho substituted phenyl.
- 5. A compound according to claim 4 in which R7 is phenyl substituted in the ring ortho position by C1-4 alkyl.
- 6. A compound according to claim 1 in which Ar2 is optionally substituted phenylene.
- 7. A compound according to claim 6 in which Ar2 is phenylene substituted by C1-4 alkyl or C1-4alkoxy.
- 8. A compound according to claim 6 in which Ar2 is optionally substituted p-phenylene.
- 9. A compound according to claim 7 in which Ar2 is p-phenylene substituted in the 3-position by C1-4alkyl or C1-4alkoxy.
- 10. A compound according to claim 1 in which L1 represents a —R12—R13— linkage wherein R12 represents a straight or branched C1-4alkylene chain and R13 represents —C(═O)—NH—.
- 11. A compound according to claim 10 in which R12 represents methylene.
- 12. A compound according to claim 1 in which Ar1 represents optionally substituted p-phenylene.
- 13. A compound according to claim 12 in which Ar1 represents unsubstituted p-phenylene.
- 14. A compound according to claim 1 in which one of A1, A2 and A3 represents NR2 and the others represent CH2.
- 15. A compound according to claim 14 in which R2 is —C(═O)—R8 wherein R8 is as defined in claim 1.
- 16. A compound according to claim 15 in which R8 is C1-4alkyl or phenyl.
- 17. A compound according to claim 14 in which R2 is arylC1-4alkyl.
- 18. A compound according to claim 17 in which R2 is benzyl.
- 19. A compound according to claim 1 of formula (Ia): in which A1, A2, A3, R12, Ar1 and Y are as defined in claim 1, R15 is hydrogen, halogen, lower alkyl or lower alkoxy, X1 represents CR16 (where R16 is hydrogen, lower alkyl or lower alkoxy), X2 and X3 independently represent CR17 (where R17 is hydrogen, amino, halogen, hydroxy, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulphinyl, lower alkylsulphonyl, nitro or trifluoromethyl), and the group containing R12 is attached at the ring 3 or 4 position, or a prodrug of such compound, or a pharmaceutically acceptable salt or solvate of such compound or prodrug.
- 20. A compound according to claim 19 in which R15 is hydrogen; X1 represents CR16 (where R16 is C1-4alkyl); X2 represents CR17 (where R17 is C1-4alkoxy); X3 represents CH; R12 is a straight C1-4alkylene chain; Ar1 is p-phenylene; Y represents carboxy; and the group containing R12 is attached at the ring 4 position.
- 21. A compound according to claim 19 in which one of A1, A2 and A3 represents NR2 and the others represent CH2.
- 22. A compound according to claim 21 in which R2 is —C(═O)—R8 wherein R8 is as defined in claim 1.
- 23. A compound according to claim 22 in which R8 is C1-4alkyl or phenyl.
- 24. A compound according to claim 21 in which R2 is arylC1-4alkyl.
- 25. A compound according to claim 24 in which R2 is benzyl.
- 26. A compound according to claim 1 selected from the group consisting of:1-acetyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; 1-benzoyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; 1-(3-carboxy-propionyl)-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; 1-benzoyl-2-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; 1-benzyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; 1-acetyl-2-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; (−) 1-benzoyl-4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid; and 4-(4-{2-[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-phenyl)-pyrrolidine-3-carboxylic acid, or a prodrug of such compound, or a pharmaceutically acceptable salt or solvate of such compound or prodrug.
- 27. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a corresponding N-oxide, or a prodrug thereof or a pharmaceutically acceptable salt or solvate of such a compound or its N-oxide or a prodrug thereof, with a pharmaceutically acceptable carrier or excipient.
- 28. A method for the treatment of a human or non-human animal patient suffering from, or subject to, a condition which can be ameliorated by the administration of an inhibitor of α4β1 mediated cell adhesion comprising administering to said patient an effective amount of a compound according to claim 1 or a corresponding N-oxide or prodrug, or a pharmaceutically acceptable salt or solvate of such a compound or an N-oxide or prodrug thereof.
- 29. A method for the treatment of a patient suffering from, or subject to, asthma comprising administering to said patient an effective amount of a compound according to claim 1 or a corresponding N-oxide or prodrug, or a pharmaceutically acceptable salt or solvate of such a compound or an N-oxide or prodrug thereof.
- 30. A method for the treatment of a patient suffering from, or subject to, an inflammatory disease comprising administering to said patient an effective amount of a compound according to claim 1 or a corresponding N-oxide or prodrug, or a pharmaceutically acceptable salt or solvate of such a compound or an N-oxide or prodrug thereof.
- 31. A method for the treatment of a human or non-human animal patient suffering from, or subject to, a condition which can be ameliorated by the administration of an inhibitor of α4β1 mediated cell adhesion comprising administering to said patient an effective amount of a composition according to claim 27.
- 32. A method for the treatment of a patient suffering from, or subject to, asthma comprising administering to said patient an effective amount of a composition according to claim 27.
- 33. A method for the treatment of a patient suffering from, or subject to, an inflammatory disease comprising administering to said patient an effective amount of a composition according to claim 27.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9910419 |
May 1999 |
GB |
|
Parent Case Info
This application is a continuation of PCT/GB00/01730, filed May 5, 2000, which claims priority from GB Application No. 9910419.2, filed May 5, 1999, and U.S. Provisional Application No. 60/176,191, filed Jan. 14, 2000; all these applications incorporated herein by reference.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
20020065391 |
Stilz et al. |
May 2002 |
A1 |
Foreign Referenced Citations (6)
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Date |
Country |
100 06 453 |
Aug 2001 |
DE |
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DE |
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WO |
9954321 |
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WO |
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WO |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/176191 |
Jan 2000 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/GB00/01730 |
May 2000 |
US |
Child |
10/002246 |
|
US |