A method for treating an individual suffering from rheumatoid arthritis, psoriasis, graft v. host disease, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, complications following percutaneous transluminal coronary angioplasty, thrombosis of the major organs, or vein thrombosis comprising administering to said individual an effective amount of a compound of formula (1a):
- wherein:
- Ar is a monocyclic or bicyclic C6-12aryl group which is optionally substituted with one or more substituents selected from R5 and -Alk(R5)m;
- R2 is a hydrogen or halogen atom or a group —X1R2a;
- X1 is a direct bond or a linker atom or group selected from —O—, —S—, —C(O)—, —C(S)—, —S(O)—, —S(O)2—, —N(R7)—, —CON(R7)—, —OC(O)N(R7)—, —CSN(R7)—, —N(R7)CO—, —N(R7)C(O)O—, —N(R7)CS—, —SON(R7)—, —SO2N(R7)—, —N(R7)SO2—, —N(R)CON(R7)—, —N(R7)CSN(R7)—, —N(R7)SON(R7)— and —N(R7)SO2N(R7)—;
- R2a is a straight or branched chain alkyl, alkenyl or alkynyl group which is optionally substituted with one or more substituents selected from halogen, hydroxyl, alkoxy, thiol, alkylthio, amino, alkylamino and dialkylamino;
- R3 is an optionally substituted azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, morpholinyl or thiomorpholinyl group, wherein said optional R3 substituents are one or more R4 groups;
- R4 is an optionally substituted straight or branched chain alkyl group, an optionally substituted straight or branched chain alkoxy group, hydroxyl (—OH), amino (—NH2), —NHR1a, —NR1aR1b, carboxyl (—CO2H), esterified carboxyl (—CO2Alk1), —COR1a, carboxamido (—CONH2) thiocarboxamido (—CSNH2), —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a or optionally substituted monocyclic or bicyclic C6-12aryl, wherein said optional alkyl and alkoxy substituents are one or more groups selected from alkoxy, —OH, NH2, —NHR1a, —NR1aR1b, —CO2H, —CO2Alk1, —COR1a, —CONH2, —CSNH2, —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a and optionally substituted monocyclic or bicyclic C6-12aryl, and said optional aryl group substituents are selected from R5 and -Alk(R5)m;
- R5 is a halogen atom;
- amino (—NH2);
- substituted amino;
- nitro;
- cyano;
- hydroxyl (—OH);
- substituted hydroxyl;
- formyl;
- carboxyl (—CO2H);
- esterified carboxyl;
- thiol (—SH);
- substituted thiol;
- —COR6;
- —CSR6;
- —SO3H;
- —SO2R6;
- —SO2NH2;
- —SO2NHR6;
- —SO2N(R6)2;
- —CONH2;
- —CSNH2;
- —CONHR6;
- —CSNHR6;
- —CON(R6)2;
- —CSN(R6)2;
- —NHSO2H;
- —NHSO2R6;
- —N(SO2R6)2;
- —NHSO2NH2;
- —NHSO2NHR6;
- —NHSO2N(R6)2;
- —NHCOR6;
- —NHCONH2;
- —NHCONHR6;
- —NHCON(R6)2;
- NHCSR6;
- —NHC(O)OR6;
- C5-7cycloalkyl;
- optionally substituted azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, morpholinyl or thiomorpholinyl group;
- monocyclic or bicyclic C6-12aryl;
- or optionally substituted pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazole, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, benzofuryl, (2,3-dihydro)benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, isobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl, imidazo(1,2-a)pyridyl, benzothiazolyl, benzoxazolyl, quinolizinyl, quinazolinyl, phthalazinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, pyrido(3,4-b)pyridyl, pyrido(3,2-b)pyridy, pyrido(4,3-b)pyridyl, quinolyl, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl and 5,6,7,8-tetrahydroisoquinolyl, purinyl, or pteridinyl groups, wherein optional substituents are an optionally substituted straight or branched chain alkyl group, an optionally substituted straight or branched chain alkoxy group, hydroxyl (—OH), amino (—NH2), —NHR1a, —NR1aR1b, carboxyl (—CO2H), esterified carboxyl (—CO2Alk1), COR1a, carboxamido (—CONH2) thiocarboxamido (—CSNH2), —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSN1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a, wherein said optional alkyl and alkoxy substituents are one or more groups selected from alkoxy, —OH, NH2, —NHR1a, —NR1aR1b, —CO2H, —CO2Alk1, —COR1a, —CONH2, —CSNH2, —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a;
- R6 is -Alk(R5)m, monocyclic or bicyclic C6-12aryl or optionally substituted pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazole, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, benzofuryl, (2,3-dihydro)benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, isobenzothienyl, indolyl, isoindolyl, 3H-indolyl, benzimidazolyl, imidazo(1,2-a)pyridyl, benzothiazolyl, benzoxazolyl, quinolizinyl, quinazolinyl, phthalazinyl, quinoxalinyl, cinnolinyl, naphthyridinyl, pyrido(3,4-b)pyridyl, pyrido(3,2-b)pyridy, pyrido(4,3-b)pyridyl, quinolyl, isoquinolyl, tetrazolyl, 5,6,7,8-tetrahydroquinolyl and 5,6,7,8-tetrahydroisoquinolyl, purinyl, or pteridinyl groups, wherein optional substituents are an optionally substituted straight or branched chain alkyl group, an optionally substituted straight or branched chain alkoxy group, hydroxyl (—OH), amino (—NH2), —NHR1a, —NR1aR1b, carboxyl (—CO2H), esterified carboxyl (—CO2Alk1), —COR1a, carboxamido (—CONH2) thiocarboxamido (—CSNH2), —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a, wherein said optional alkyl and alkoxy substituents are one or more groups selected from alkoxy, —OH, NH2, —NHR1a, —NR1aR1b, —CO2H, —CO2Alk1, —COR1a, —CONH2, —CSNH2, —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a;
- R7 is a hydrogen atom or an alkyl group;
- Alk is a straight or branched alkylene, alkenylene or alkynylene chain optionally interrupted by one to three —O— or —S— atoms or groups selected from —S(O)—, —S(O)2— or —N(R7)—;
- Alk1 is a straight or branched chain alkyl group which is optionally substituted with one or more R5 substituents;
- R1a and R1b, which may be the same or different, is each an optionally substituted straight or branched chain alkyl group, wherein said optional substituents are one or more groups selected from alkoxy, —OH, NH2, —NHR1a, —NR1aR1b, —CO2H, —CO2Alk1, —COR1a, —CONH2, —CSNH2, —CONHR1a, —CONR1aR1b, —CSNHR1a, —CSNR1aR1b, —SO2R1a, —SO2NH2, —SO2NHR1a, —SO2NR1aR1b, imido, —SC(NH)NH2, —NHC(NH)NH2, —NHC(NH)R1a and optionally substituted monocyclic or bicyclic C6-12aryl, wherein said optional aryl group substituents are selected from R5 and -Alk(R5)m;
- m is zero or an integer 1 to 3;
- or the salts, hydrates and N-oxides thereof.