Claims
- 1. A compound of formula I: in which:X is a bond, CH2 or a C1-3alkylene group optionally interrupted by oxygen; R is hydrogen, NO2, NH2, N(C1-6alkyl)2, CO2H, CH2OH, halogen, CO2C1-6alkyl, C1-8alkyl optionally interrupted by one or more oxygen, nitrogen or sulphur atoms and optionally substituted by CO2H or R is hydroxy, phenyl optionally substituted by CH2CO2H, or CONR3R4 where R3 and R4 are independently hydrogen, C1-6alkyl optionally substituted by hydroxy or CO2H and/or optionally interrupted by oxygen, nitrogen or sulphur; R1 is NR5R6 or CH2NR5R6 where R5 and R6 are independently hydrogen, CH2CO2H, CHPh2 or C(═S)CH2CH2CO2H, or R1 is CH2NR7CH2CO2H where R7 is hydrogen, C1-6 alkyl or CO2CH2PH, or R1 is C1-8alkyl optionally interrupted by one or more oxygen, nitrogen or sulphur atoms and optionally substituted by CO2H, or R1 is —R8—PO(OH)2, or —R8-tetrazol-5-yl where R8 is a bond, OCH2, SCH2, CONH, CONHCH2, CONHCH2CONH, NHCH2CONH, NHCH(R3), NR9(CH2)q where R9 is hydrogen or C1-6alkyl and q is 1 or 2 or R20—CO2H where R20 is a bond, CONHCH2 or NHCH(R3) where R3 is as defined above, or R1 is a group of formula (i): where B is a 4-, 5-, or 6-membered saturated ring containing a nitrogen atom optionally substituted by hydroxy and substituted by CO2H or CONH-Het where Het is tetrazol-5-yl, or a thiazole or thiadiazole ring substituted by CO2H or CH2CO2H, or B is phenyl or a 5-membered aromatic heterocylic ring containing 1 to 3 heteroatoms selected from nitrogen, oxygen or sulphur optionally substituted by one or more groups selected from CF3, CO2H, CH2OH, C1-6alkyl optionally interrupted by one or more oxygen atoms, CH2CH2CO2H, C(CO2H)═N—OMe, tetrazol-5-yl or CH2tetrazol-5-yl; and R10 is a bond, sulphur atom, —CONH—, CH2, CH2O, a group —NR11—CH(CO2H)—CH2—, or a group or —NR11—(CH2)p—CONR12—where R11 and R12 are independently hydrogen or C1-6alkyl and p is 1 or 2; R2 is a group of formula (ii) or (iii): where R13 groups are independently hydrogen, halogen, methoxy, methylthio or C1-2alkyl (optionally substituted by one or more fluorine atoms); R14 groups are independently hydrogen, halogen, hydroxy, C1-3alkylthio, C1-4alkyl (optionally substituted by one or more fluorine atoms, C3-4 cycloalkyl, MeOCH2, MeSCH2 or C1-2alkoxy; R15 groups are independently hydrogen, halogen or methyl (optionally substituted by one or more fluorine atoms); Z1 is CH═CH, CF═CH or CF═CF; Z2 is a single bond, oxygen, sulphur, CH2CH═CH, CH2CH═CHCH2 or a C1-4alkylene group optionally interrupted by an oxygen or sulphur atom; R16 are independently hydrogen, halogen, C1-2alkyl, CF3 or a methylthio group or hydroxy; Q1 and Q2 each independently represent an O or S; or a salt thereof,provided that when Q1 is oxygen, R2 is a group of formula (ii).
- 2. A compound according to claim 1 in which X is CH2, a bond or CH2CH2O.
- 3. A compound according to claim 1 in which R is hydrogen, C1-6alkoxy, C1-8alkyl optionally interrupted by one or two oxygen atoms and optionally substituted by CO2H, CH2OH, hydroxy and halogen.
- 4. A compound according to claim 1 in which R1 is CO2H, —PO(OH)2, C1-8alkyl optionally interrupted by one or two oxygen atoms and optionally substituted by CO2H, or R1 is a group of formula (i) where B is phenyl, thiazole, pyrazole optionally substituted by CO2H or C1-6alkyl optionally interrupted by one or two oxygen atoms, or R1 is NR5R6 or CH2NR5R6 where R5 and R6 are independently, CH2CO2H, CHPh2 or C(═S)CH2CH2CO2H—, or R1 is CH2NR7CH2CO2H where R7 is CO2CH2Ph.
- 5. A compound according to claim 1 in which R2 is a group of formula (ii) where Z1 is CH═CH.
- 6. A compound according to claim 1 in which Q1 is S and Q2 is O or S.
- 7. A compound according to claim 1 which is:3-[[5-[9H-Fluoren-9-yl]-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzeneacetic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzenephosphonic acid, 5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-2-methoxybenzoic acid, 2-[3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1-(2H)-pyrimidinyl]methyl]phenyl]-4-thiazolecarboxylic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[2-methoxyethoxymethyl]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[phenoxymethyl]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[ethoxymethyl]benzoic acid, 1-[[3-[[3-Carboxy-5-{5H-dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl]methyl]-4-pyrazolecarboxylic acid, 3-[[3-[[3-Carboxy-5-{5H-dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl]methyl]-5-ethoxybenzoic acid, 3-[[3-Carboxy-5-[[5-{5H-dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl]methoxy]-5-[2-methoxyethoxy]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[hydroxymethyl]benzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[methylbenzoic acid, 5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-2-hydroxybenzoic acid, 3-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenoxy]acetic acid, 2-Bromo-5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, 5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-2-[phenylmethyl]benzoic acid, 2-Butyl-5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, 4-[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]benzoic acid, 5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl-1,3-bis[oxyacetic acid], 4-[3-[Carboxymethoxy]-5-[[5-{5H-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl]oxybutanoic aid, 3-[[3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl][carboxymethyl]amino]-3-thioxobutanoic acid, N-[[3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]phenyl]methyl]-N-[phenylmethoxycarbonyl]glycine, 3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[[carboxymethyl][diphenylmethyl]amino]benzoic acid, 3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]-5-[carboxymethylamino]benzoic acid 2-[2-[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]ethoxy]benzoic acid, 2-[Carboxymethoxy]-[6-[2-[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]ethoxy]benzoic acid, 4-[2-[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]ethoxy]-benzenedioic acid, 3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, 3-[[5-{5-Dibenzo[a,d]cyclohepten-5-yl}-3,4-dihydro-2-oxo-4-thioxo-1(2H)-pyrimidinyl]methyl]benzoic acid, or a pharmaceutically acceptable salt thereof.
- 8. A pharmaceutical composition comprising a compound of formula I or a salt or solvate thereof as defined in claim 1 in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
- 9. A process for the preparation of compounds of formula I as defined in claim 1 which comprises: reacting a compound of formula (II): where Q1, Q2 and R2 are defined in formula (I) or are protected derivatives thereof with a compound of formula (III): where R, R1 and X are defined in formula (I) or are protected derivatives thereof and L is a leaving group, and optionally thereafter in any order:removing any protecting groups forming a salt.
- 10. A method of treating an inflammatory condition, which comprises the step of administering to a patient in need of such treatment an effective amount of a compound of formula (I) as defined in claim 1.
- 11. A method according to claim 10, wherein said compound of formula (I) is co-administered with another anti-inflammatory agent.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9702794 |
Jul 1997 |
SE |
|
Parent Case Info
This application is a 371 of PCT/SE98/01391 filed Jul. 15, 1998.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/SE98/01391 |
|
WO |
00 |
9/21/1999 |
9/21/1999 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO99/05123 |
2/4/1999 |
WO |
A |