Claims
- 1. A compound of formula (I) (relative stereochemistry indicated) wherein: R1 represents C1-4 alkyl; R2 represents C2-4 alkyl or C2-4alkenyl; a represents 1 or 2; R3 represents C1-8 alkyl or (CH2)nAr; n represents 1 or 2; Ar represents optionally substituted phenyl; and salts and solvates thereof.
- 2. A compound of formula (I) according to claim 1 wherein R2 represents isopropyl or propyl.
- 3. A compound of formula (I) according to claim 2 wherein R2 represents isopropyl.
- 4. A compound of formula (I) according to claim 1 wherein a represents 1.
- 5. A compound of formula (I) according to claim 1 wherein R1 represents methyl or ethyl.
- 6. A compound of formula (I) according to claim 5 wherein R1 represents ethyl.
- 7. A compound of formula (I) according to claim 1 wherein R3 represents C1-8 alkyl or —CH2Ar.
- 8. A compound of formula (I) according to claim 7 wherein R3 represents a C1-8 alkyl group selected from n-butyl, cyclopropyl and t-butyl or a —CH2Ar group wherein Ar is selected from phenyl and phenyl substituted by one or more halogen groups.
- 9. A compound of formula (I) according to claim 1 which isrel-(3R,3aR,6aS)-4-(1-Cyclopropylmethyl-azetidine-3-carbonyl)-3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one; rel-(3R,3aR,6aS)-(1-Benzyl-azetidine-3-carbonyl)-3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one; rel-(3R,3aR,6aS)-4-[1-(2,6-Dichloro-benzyl)-azetidine-3-carbonyl]-3-4-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one; rel-(3R,3aR,6aS)-4-(1-Butyl-azetidine-3-carbonyl)-3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one; or a salt or solvate of any one thereof.
- 10. A compound of formula (I) according to claim 1 which is rel-(3R,3aR,6aS)-4-[1-(2,2-Dimethyl-propyl)-azetidine-3carbonyl]-3-isopropyl-1-methanesulfonyl-hexahydropyrrolo[3,2-b]pyrrol-2-one or a salt or solvate thereof.
- 11. A compound of formula (I) according to claim 1 which is rel-(3R,3aR,6aS)-4-[1-(2,2-Dimethyl-propyl)azetidine-3-carbonyl]-3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one hydrochloride.
- 12. A purified single enantiomer of a compound of formula (I) according to claim 1 having absolute stereochemistry as illustrated in formula (I).
- 13. A compound of formula (I) according to claim 1 which is (3S,3aS,6aR)-4-[1-(2,2-Dimethyl-propyl)-azetidine-3-carbonyl]3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one or a salt or solvate thereof.
- 14. A compound of formula (I) according to claim 1 which is (3S,3aS,6aR)-4-[1-(2,2-Dimethyl-propyl)-azetidine-3carbonyl]-3-isopropyl-1-methanesulfonyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one hydrochloride.
- 15. A compound of formula (I) according to claim 1 for use as a pharmaceutical.
- 16. A pharmaceutical composition comprising a compound formula (I) according to claim 1 in admixture with one or more physiologically acceptable diluents or carriers.
- 17. A method of treatment of chronic bronchitis or chronic obstructive pulmonary disease in a human or animal subject which comprises administering to said human or animal subject an effective amount of a compound of formula (I) according to claim 1.
- 18. A method of treatment of asthma in a human or animal subject which comprises administering to said human or animal subject an effective amount of a compound of formula (I) according to claim 1.
- 19. A compound of formula (III) (relative stereochemistry indicated) wherein R2, R3 and a are as defined in claim 1or a protected derivative thereof.
- 20. A compound of formula (V)(relative stereochemistry indicated) wherein R1, R2 and R3 are as defined in claim 1 and Xa represents sulphur or SO.
- 21. A compound of formula (VI) (relative stereochemistry indicated) wherein R1 and R2 are as defined in claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9719187 |
Sep 1997 |
GB |
|
Parent Case Info
This application is filed pursuant to 35 U.S.C. §371 as a United States National Phase Application of International Application No. PCT/EP98/05604 filed Sep. 7, 1998, which claims priority from GB9719187.8 filed Sep. 9, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP98/05604 |
|
WO |
00 |
6/2/2000 |
6/2/2000 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO99/12931 |
3/18/1999 |
WO |
A |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
3983245 |
Ladd et al. |
Sep 1976 |
|
6057457 |
Dowle et al. |
May 2000 |
|
Foreign Referenced Citations (5)
Number |
Date |
Country |
0201957A |
Nov 1996 |
EP |
WO9324519A |
Dec 1993 |
WO |
WO9521855A |
Aug 1995 |
WO |
WO9725309A |
Jul 1997 |
WO |
WO9736903A |
Oct 1997 |
WO |
Non-Patent Literature Citations (1)
Entry |
D.L. Lee et al., “Alpha-Methylenelactam Rearrangement”, vol. 39, No. 7, pp. 893-902, Easton, US, 1974. |