Amino-spiro-quinazoline compounds
AssigneeAstraZeneca UK Limited
InventorsPeter Hamley, Austen Pimm, Alan Tinker
Life of this patent
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Abstract
There are provided novel compounds of formula (I) wherein A represents an aromatic carbocyclic ring or a 5- or 6-membered heterocyclic aromatic ring containing 1 to 3 heteroatoms which may be the same or different and are selected from O, N and S; X represents —(CH2)n— wherein n represents zero or 1; and R1, R2 and R3 are as defined in the specification, and pharmaceutically acceptable salts thereof, and enantiomers and tautomers thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of nitric oxide synthase and are thereby particularly useful in the treatment or prophylaxis of inflammatory disease and pain.
Claims14
A compound of formula (I)
- wherein
- R1 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.
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.
Dependencies are inferred from the claim text.