Claims
- 1. A compound of formula (I) whereinR1 and R2 independently represent hydrogen, C1 to 6 alkyl, C2 to 6 alkenyl, C2 to 6 alkynyl, C1 to 6 alkoxy, C1 to 6 alkylthio, halogen, hydroxy, trifluoromethyl or amino; R3 represents one or more substituents independently selected from hydrogen, C1 to 6 alkyl, C2 to 6 alkenyl, C2 to 6 alkynyl, C1 to 6 alkoxy, C1 to 6 alkylthio, halogen, hydroxy, trifluoromethyl, amino, cyano, nitro, trifluoromethoxy, methanesulphonyl, sulphamoyl, —NR4R5, —COOR6, —CONR7R8, benzyloxy, phenyl, or a 5-membered heterocyclic aromatic ring containing 1 to 3 heteroatoms which may be the same or different and are selected from O, N and S, which phenyl or 5-membered heterocyclic aromatic ring is optionally substituted, the optional substituents being C1 to 6 alkyl, halogen, cyano, nitro, hydroxy, C1 to 6 alkoxy, trifluoromethyl and trifluoromethoxy; R4, R5 and R6 independently represent hydrogen or C1 to 6 alkyl; R7 and R8 independently represent hydrogen, C1 to 6 alkyl or phenyl, which phenyl is optionally substituted by one or more groups independently selected from C1 to 6 alkyl, halogen, cyano, nitro, hydroxy, C1 to 6 alkoxy, trifluoromethyl and trifluoromethoxy; X represents —(CH2)n—, wherein n represents zero or 1; and A represents a 5- or 6membered heterocyclic aromatic ring containing 1 to 3 heteroatoms which may be the same or different and are selected from O, N and S; or a pharmaceutically acceptable salt, enantiomer, racemate or tautomer thereof.
- 2. A compound of formula (I), according to claim 1, wherein R1 represents hydrogen.
- 3. A compound of formula (I), according to claim 1, wherein R1 represents fluoro.
- 4. A compound of formula (I), according to claim 1, wherein R2 represents fluoro.
- 5. A compound of formula (I), according to claim 1, wherein X represents —(CH2)n— and n represents zero.
- 6. A compound of formula (I) which is:(R*R*)-4-amino-5-fluoro-3b′,4′,6′,7′-tetrahydrospiro[quinazoline-2,5′(2H,9′H)-thieno[3,2-a]indolizine]-9′-one; (R*S*)-4-amino-5-fluoro-3b′,4′,6′,7′-tetrahydrospiro[quinazoline-2,5′(2H,9′H)-thieno[3,2-a]indolizine]-9′-one; (R*R*)-4-amino-5-fluoro-6′,7′,9′,9a′-tetrahydrospiro[quinazoline-2,8′(2H,4′H)-thieno[2,3-a]indolizine]-4′-one; (R*S*)-4-amino-5-fluoro-6′,7′,9′,9a′-tetraydrospiro[quinazoline-2,8′(2H,4′H)-thieno[2,3-a]indolizine]-4′-one; (R*R*)-4-amino-5′-fluoro-7,8,10,10a-tetrahydrospiro[pyrido[3,4-a]indolizine-9,2′(1′H)-quinazoline]-5-one; (R*S*)-4′-amino-5′-fluoro-7,8,10,10a-tetrahydrospiro[pyrido[3,4-a]indolizine-9,2′(1′H)quinazoline]-5-one; or a pharmaceutically acceptable salt, enantiomer or tautomer thereof.
- 7. A pharmaceutical composition comprising a compound of formula (I) according to any claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.
- 8. A method of treating, or reducing the risk of, human diseases or conditions in which inhibition of nitric oxide syntase activity is beneficial which comprises administering a therapeutically effective amount of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, to a person suffering from, or at increased risk of, such diseases or conditions.
- 9. A method of treatment according to claim 8 in which it is predominantly inducible nitric oxide synthase that is inhibited.
- 10. A method of treating, or reducing the risk of, inflammatory disease in a person suffering from, or at risk of, said disease, wherein the method comprises administering to the person a therapeutically effective amount of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof.
- 11. The method of treatment as claimed in claim 10 wherein the disease is asthma or rheumatoid arthritis.
- 12. A method of treating, or reducing the risk of, pain in a person suffering from, or at risk of, said condition, wherein the method comprises administering to the person a therapeutically effective amount of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof.
- 13. A method of treating, or reducing the risk of, inflammatory disease in a person suffering from, or at risk of, said disease, wherein the method comprises administering to the person a therapeutically effective amount of a combination of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, with a COX-2 inhibitor.
- 14. A process for the preparation of a compound of formula (I), as defined in claim 1, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein the process comprises reaction of a compound of formula (II), or a salt thereof: wherein R1 and R2 are as defined in claim 1,with a compound of formula (III) or a protected derivative thereof: wherein R3, A and X are as defined in claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9702534 |
Jul 1997 |
SE |
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Parent Case Info
This is a divisional of application Ser. No. 09/125,174, filed Aug. 11, 1998, now U.S. Pat. No. 6,083,952, which is a 371 of PCT/SE98/101206, filed Jun. 22, 1998 the entire content of which is hereby incorporated by reference in this application.
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Foreign Referenced Citations (1)
Number |
Date |
Country |
9714686 |
Apr 1997 |
WO |
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Entry |
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