Claims
- 1. A thiazole compound of the formula: ##STR1182## wherein T is a lower alkylene; u is 0 or 1;
- R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or a lower alkyl, or both combine to form a group: --(CH.sub.2).sub.n -- wherein n is 4 or 5 or to form a benzene ring which may optionally be substituted by a member selected from a lower alkyl, a lower alkoxy, a nitro, an amino having optionally a lower alkyl substituent, or a halogen atom;
- R.sup.3 is a group of the formula: ##STR1183## wherein A is a lower alkylene; Z is O or S; s is 0 or 1; m is 1 or 2; R.sup.4 is a hydrogen atom or a lower alkanoyloxy-lower alkyl;
- R.sup.5 is/are the same or different and are each a member selected from (a) a hydrogen atom, (b) an alkyl having optionally a hydroxy substituent, (c) a halogen atom, (d) a group of the formula: --(O).sub.t --A--(CO).sub.l --NR.sup.7 R.sup.8 wherein t is 0 or 1, A is a lower alkylene, l is 0 or 1, and R.sup.7 and R.sup.8 are the same or different and are each a hydrogen atom or a lower alkyl, or both combine together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group being optionally substituted by a member selected from a group of the formula: --(A).sub.l --NR.sup.9 R.sup.10 wherein A and l are as defined above, and R.sup.9 and R.sup.10 are the same or different and are each a hydrogen atom or a lower alkyl, or both combine together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group having optionally a lower alkyl substituent, a lower alkyl having optionally a hydroxy substituent, a hydroxy group, and a lower alkanoyl; (e) a lower alkoxycarbonyl-lower alkyl, (f) a lower alkanoyloxy-lower alkyl, (g) a lower alkoxy having optionally a halogen substituent, (h) a halogen-substituted lower alkyl, (i) a carboxyl-substituted lower alkyl, (j) a lower alkoxycarbonyl, (k) a lower alkenyloxy, (l) a phenyl-lower alkoxy, (m) a cycloalkyloxy, (n) a phenyl, (o) a phenyloxy, (p) a hydroxy, (q) a lower alkylthio, (r) a lower alkenyl, or (s) an amino having optionally a lower alkyl substituent;
- R.sup.6 is a group of the formula:
- --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a ( 1)
- or
- --CO--C.tbd.C--COR.sup.14 ; (2)
- p is 0 or 1;
- R.sup.11b is a hydrogen atom or a lower alkyl;
- R.sup.11a is a hydroxy, a lower alkoxy, or a 5- to 10-membered, monocyclic or dicyclic, saturated or unsaturated heterocyclic group which contains 1 to 4 hetero atoms selected from a nitrogen, oxygen or sulfur atom as a ring member, said heterocyclic group having optionally 1 to 3 substituents selected from the group consisting of (i) a lower alkyl, (ii) a group of the formula: --(B).sub.l --NR.sup.12 R.sup.13 wherein l is as defined above, B is --CO--A-- wherein A is as defined above, a carbonyl, or a lower alkylene, and R.sup.12 and R.sup.13 are the same or different and are each a hydrogen atom, a lower alkyl, or a lower alkyl substituted by an amino having optionally a lower alkyl substituent, or both combine together with the nitrogen atom to which they bond to form a 5- to 12-membered saturated, monocyclic, dicyclic or spirocyclic heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group having optionally a substituent selected from a lower alkyl, a lower alkoxycarbonyl, a lower alkoxy-substituted lower alkyl, an amino having optionally a lower alkyl substituent, and a hydroxy-substituted lower alkyl), (iii) a lower alkoxycarbonyl, (iv) a hydroxy-substituted lower alkyl, (v) a pyridyl being optionally substituted by a lower alkyl having optionally a halogen substituent on the pyridine ring, (vi) a halogen-substituted lower alkyl, (vii) a lower alkoxy, (viii) a cycloalkyl, (ix) a hydroxy, (x) a tetrahydropyranyloxy-substituted lower alkyl, (xi) a pyrimidyl, (xii) a lower alkoxy-substituted lower alkyl, (xiii) a carboxyl, (xiv) a phenyl-lower alkoxy, (xv) a phenyl-lower alkyl having optionally a lower alkylenedioxy on the phenyl ring, (xvi) a lower alkanoyloxy, and (xvii) a piperidinyl having optionally a lower alkyl substituent on the piperidine ring;
- R.sup.14 is a hydroxy or a lower alkoxy; and
- when m is 1, the groups A and R.sup.5 may combine to form a group of the formula: ##STR1184## wherein R.sup.6 is as defined above, and r is 0, 1 or 2, or when m is 2, two R.sup.5 groups may combine to form a lower alkylenedioxy, a lower alkylene, or a group of the formula: --(CH.sub.2).sub.2 --CONH--, or the groups R.sup.5 and R.sup.6 may combine to form a group of the formula: --CO--CH(R.sup.28)--CH(R.sup.28')--W-- wherein R.sup.28 and R.sup.28' are a hydrogen atom or a carboxyl group, provided that both R.sup.28 and R.sup.28 are not simultaneously a carboxyl group, and W is --N(R.sup.29a)-- or ##STR1185## wherein R.sup.29a is a hydrogen atom or a lower alkyl, R.sup.29b is a lower alkyl, and X is as defined above, or a salt thereof.
- 2. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or a lower alkyl; and R.sup.3 is a group of the formula: ##STR1186## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, and s is 0), or a salt thereof.
- 3. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or a lower alkyl; and R.sup.3 is a group of the formula: ##STR1187## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is O, or a salt thereof.
- 4. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or a lower alkyl; and R.sup.3 is a group of the formula: ##STR1188## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is S, or a salt thereof.
- 5. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 4; and R.sup.3 is a group of the formula: ##STR1189## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, and s is 0, or a salt thereof.
- 6. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 4; and R.sup.3 is a group of the formula: ##STR1190## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is O; or a salt thereof.
- 7. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- (n is 4); and R.sup.3 is a group of the formula: ##STR1191## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is S, or a salt thereof.
- 8. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 5; and R.sup.3 is a group of the formula: ##STR1192## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, and s is 0, or a salt thereof.
- 9. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 5; and R.sup.3 is a group of the formula: ##STR1193## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is O, or a salt thereof.
- 10. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- (n is 5); and R.sup.3 is a group of the formula: ##STR1194## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is S, or a salt thereof.
- 11. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a benzene ring which may optionally be substituted by a member selected from a lower alkyl, a lower alkoxy, a nitro, an amino having optionally a lower alkyl substituent, or a halogen atom; and R.sup.3 is a group of the formula: ##STR1195## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, and s is 0, or a salt thereof.
- 12. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a benzene ring which may optionally be substituted by a member selected from a lower alkyl, a lower alkoxy, a nitro, an amino having optionally a lower alkyl substituent, or a halogen atom; and R.sup.3 is a group of the formula: ##STR1196## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is O, or a salt thereof.
- 13. The thiazole compound according to claim 1, wherein u is 0; R.sup.1 and R.sup.2 combine to form a benzene ring which may optionally be substituted by a member selected from a lower alkyl, a lower alkoxy, a nitro, an amino having optionally a lower alkyl substituent, or a halogen atom; and R.sup.3 is a group of the formula: ##STR1197## wherein A, R.sup.5, R.sup.6 and m are as defined in claim 1, s is 1, and Z is S, or a salt thereof.
- 14. The thiazole compound according to claim 3, wherein R.sup.6 is a group of the formula: --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein R.sup.11a is a hydroxy or a lower alkoxy, or a salt thereof.
- 15. The thiazole compound according to claim 3, wherein R.sup.6 is a group of the formula: --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein p is 1, and R.sup.11a is a 5- to 10-membered, monocyclic or dicyclic, saturated or unsaturated heterocyclic group which contains 1 to 4 hetero atoms selected from a nitrogen, oxygen or sulfur atom as a ring member, said heterocyclic group having optionally 1 to 3 substituents selected from the group consisting of (i) a lower alkyl, (ii) a group of the formula: --(B).sub.l --NR.sup.12 R.sup.13 wherein B is --CO--A--, a carbonyl, or a lower alkylene, and R.sup.12 and R.sup.13 are the same or different and are each a hydrogen atom, a lower alkyl, or a lower alkyl substituted by an amino having optionally a lower alkyl substituent, or both combine together with the nitrogen atom to which they bond to form a 5- to 12-membered saturated, monocyclic, dicyclic or spirocyclic heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group having optionally a substituent selected from a lower alkyl, a lower alkoxycarbonyl, a lower alkoxy-substituted lower alkyl, an amino having optionally a lower alkyl substituent, and a hydroxy-substituted lower alkyl), (iii) a lower alkoxycarbonyl, (iv) a hydroxy-substituted lower alkyl, (v) a pyridyl being optionally substituted by a lower alkyl having optionally a halogen substituent on the pyridine ring, (vi) a halogen-substituted lower alkyl, (vii) a lower alkoxy, (viii) a cycloalkyl, (ix) a hydroxy, (x) a tetrahydropyranyloxy-substituted lower alkyl, (xi) a pyrimidyl, (xii) a lower alkoxy-substituted lower alkyl, (xiii) a carboxyl, (xiv) a phenyl-lower alkoxy, (xv) a phenyl-lower alkyl having optionally a lower alkylenedioxy on the phenyl ring, (xvi) a lower alkanoyloxy, and (xvii) a piperidinyl having optionally a lower alkyl substituent on the piperidine ring, or a salt thereof.
- 16. The thiazole compound according to claim 3, wherein R.sup.6 is a group of the formula: --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein p is 0, and R.sup.11a is as defined in claim 15, or a salt thereof.
- 17. The thiazole compound according to claim 3, wherein R.sup.6 is a group of the formula: --CO--C.tbd.C--COR.sup.14 or a salt thereof.
- 18. The thiazole compound according to claim 12, wherein R.sup.6 is a group of the formula: --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein R.sup.11a is a hydroxy or a lower alkoxy, or a salt thereof.
- 19. The thiazole compound according to claim 12, wherein R.sup.6 is a group of the formula --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein p is 1, and R.sup.11a is a 5- to 10-membered, monocyclic or dicyclic, saturated or unsaturated heterocyclic group which contains 1 to 4 hetero atoms selected from a nitrogen, oxygen or sulfur atom as a ring member, said heterocyclic group having optionally 1 to 3 substituents selected from the group consisting of (i) a lower alkyl, (ii) a group of the formula: --(B).sub.l NR.sup.12 R.sup.13 wherein l is O or 1, B is --CO--A-- wherein A is alkylene, a carbonyl, or a lower alkylene, and R.sup.12 and R.sup.13 are the same or different and are each a hydrogen atom, a lower alkyl, or a lower alkyl substituted by an amino having optionally a lower alkyl substituent, or both combine together with the nitrogen atom to which they bond to form a 5- to 12-membered saturated, monocyclic, dicyclic or spirocyclic heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group having optionally a substituent selected from a lower alkyl, a lower alkoxycarbonyl, a lower alkoxy-substituted lower alkyl, an amino having optionally a lower alkyl substituent, and a hydroxy-substituted lower alkyl, (iii) a lower alkoxycarbonyl, (iv) a hydroxy-substituted lower alkyl, (v) a pyridyl being optionally substituted by a lower alkyl having optionally a halogen substituent on the pyridine ring, (vi) a halogen-substituted lower alkyl, (vii) a lower alkoxy, (viii) a cycloalkyl, (ix) a hydroxy, (x) a tetrahydropyranyloxy-substituted lower alkyl, (xi) a pyrimidyl, (xii) a lower alkoxy-substituted lower alkyl, (xiii) a carboxyl, (xiv) a phenyl-lower alkoxy, (xv) a phenyl-lower alkyl having optionally a lower alkylenedioxy on the phenyl ring, (xvi) a lower alkanoyloxy, and (xvii) a piperidinyl having optionally a lower alkyl substitutent on the piperidine ring, or a salt thereof.
- 20. The thiazole compound according to claim 12, wherein R.sup.6 is a group of the formula: --CO--CH.dbd.CR.sup.11b --(CO).sub.p --R.sup.11a wherein p is 0, and R.sup.11a is a 5- to 10-membered, monocyclic or dicyclic, saturated or unsaturated heterocyclic group which contains 1 to 4 hetero atoms selected from a nitrogen, oxygen or sulfur atom as a ring member, said heterocyclic group having optionally 1 to 3 substituents selected from the group consisting of (i) a lower alkyl, (ii) a group of the formula: --(B).sub.l NR.sup.12 R.sup.13 wherein l is O or 1, B is --CO--A-- wherein A is alkylene, a carbonyl, or a lower alkylene, and R.sup.12 and R.sup.13 are the same or different and are each a hydrogen atom, a lower alkyl, or a lower alkyl substituted by art amino having optionally a lower alkyl substituent, or both combine together with the nitrogen atom to which they bond to form a 5- to 12-membered saturated, monocyclic, dicyclic or spirocyclic heterocyclic group which may be intervened with a nitrogen or oxygen atom, said heterocyclic group having optionally a substituent selected from a lower alkyl, a lower alkoxycarbonyl, a lower alkoxy-substituted lower alkyl, an amino having optionally a lower alkyl substituent, and a hydroxy-substituted lower alkyl, (iii) a lower alkoxycarbonyl, (iv) a hydroxy-substituted lower alkyl, (v) a pyridyl being optionally substituted by a lower alkyl having optionally a halogen substituent on the pyridine ring, (vi) a halogen-substituted lower alkyl, (vii) a lower alkoxy, (viii) a cycloalkyl, (ix) a hydroxy, (x) a tetrahydropyranyloxy-substituted lower alkyl, (xi) a pyrimidyl, (xii) a lower alkoxy-substituted lower alkyl, (xiii) a carboxyl, (xiv) a phenyl-lower alkoxy, (xv) a phenyl-lower alkyl having optionally a lower alkylenedioxy on the phenyl ring, (xvi) a lower alkanoyloxy, and (xvii) a piperidinyl having optionally a lower alkyl substitutent on the piperidine ring, or a salt thereof.
- 21. The thiazole compound according to claim 12, wherein R.sup.6 is a group of the formula: --CO--C.tbd.C--COR.sup.14 or a salt thereof.
- 22. The thiazole compound according to claim 1, wherein u is 1; R.sup.1 and R.sup.2 are the same or different and are each a hydrogen atom or a lower alkyl; and R.sup.3 is a group of the formula: ##STR1198## wherein A, Z, s, R.sup.5, R.sup.6 and m are as defined in claim 1, or a salt thereof.
- 23. The thiazole compound according to claim 1, wherein u is 1; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 4; and R.sup.3 is a group of the formula: ##STR1199## wherein A, Z, s, R.sup.5, R.sup.6 and m are as defined in claim 1, or a salt thereof.
- 24. The thiazole compound according to claim 1, wherein u is 1; R.sup.1 and R.sup.2 combine to form a group: --(CH.sub.2).sub.n -- wherein n is 5; and R.sup.3 is a group of the formula: ##STR1200## wherein A, Z, s, R.sup.5, R.sup.6 and m are as defined in claim 1, or a salt thereof.
- 25. The thiazole compound according to claim 1, wherein u is 1; R.sup.1 and R.sup.2 combine to form a benzene ring which may optionally be substituted by a member selected from a lower alkyl, a lower alkoxy, a nitro, an amino having optionally a lower alkyl substituent, or a halogen atom; and R.sup.3 is a group of the formula: ##STR1201## wherein A, Z, s, R.sup.5, R.sup.6 and m are as defined in claim 1, or a salt thereof.
- 26. The thiazole compound according to any one of claims 2, 5-7, 8-10, 11, 13 and 22-25, wherein the heterocyclic group for R.sup.11a is a member selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinyl, morpholino, 1-azacyclooctyl, homopiperazinyl, homomorpholino, 1,4-diazabicyclo[4.3.0]nonyl, 1,4-diazabicyclo[4.4.0]decyl, pyridyl, 1,2,5,6-tetrahydropyridyl, thienyl, 1,2,4-triazolyl, 1,2,3,4-tetrazolyl, 1,3,4-triazolyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, pyrrolinyl, carbostyril, 1,3-dioxolanyl, thiomorpholino, 3,4-dihydrocarbostyril, 1,2,3,4-tetrahydroquinolyl, 2,3,4,5-tetrahydrofuryl, indolyl, isoindolyl, 3H-indolyl, indolinyl, indolidinyl, indazolyl, benzimidazolyl, benzoxazolyl, imidazolinyl, imidazolidinyl, isoquinolyl, naphthylidinyl, quinazolidinyl, quinoxalinyl, cinnolinyl, phthalazinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, thienyl, imidazolyl, pyrazolidinyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, tetrahydropyranyl, 4H-chromenyl, 1H-indazolyl, isoindolinyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, pyranyl, pyrazolidinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroisoquinolyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, 1,4-dithianaphthalenyl, 2,5-dihydrofurano[3,4-c]pyridyl, 2,3,4,5,6,7-hexahydro-1H-azepinyl, 1,2,3,4,5,6,7,8-octahydroazocinyl, 1,2,3,4,5,6-hexahydrooxepinyl, 1,3-dioxolanyl, 3,4,5,6-tetrahydro-2H-pyranyl, and 5,6-dihydro-2H-pyranyl.
- 27. A thiazole compound selected from the group consisting of
- (1) 2-{(3-methoxy-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (2) 2-{(2-isopropyl-4-(3-(4-(4-methyl-1-piperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (3) 2-{(2-methoxy-4-(3-(2-(4-methyl-1-piperazinyl)-methyl-4-morpholinocarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (4) 2-{(2-ethoxy-4-(3-(4-(4-methyl-1-piperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (5) 2-{(3-methyl-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (6) 2-{(3-methoxy-6-ethyl-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (7) 2-{(3-methoxy-6-ethyl-4-(3-(4-methyl-1-piperazinyl)acryloyl)-phenoxy)methylcarbonylamino}benzothiazole,
- (8) 2-{(2-trifluoromethyl-4-(3-(4-hydroxy-1-piperazinyl)acryloyl)-phenoxy)methylcarbonylamino}benzothiazole,
- (9) 2-{(2-fluoro-4-(3-(2-(4-methyl-1-piperazinyl)methyl-4-morpholino-carbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (10) 2-{(2-methoxy-4-(3-(4-(4-methyl-1-piperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (11) 2-{(2,3-dimethyl-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (12) 2-{(3-methoxy-4-(3-(4-(3,4-dimethyl-1-piperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (13) 2-{(3-methoxy-6-isopropyl-4-(3-(4-methyl-1-piperazinyl)-carbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole,
- (14) 2-{(2-methoxy-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole, and
- (15) 2-{(2-n-butyl-4-(3-(4-(4-methyl-1-homopiperazinyl)-1-piperidinylcarbonyl)acryloyl)phenoxy)methylcarbonylamino}benzothiazole, or a salt thereof.
- 28. A protein kinase C inhibitor composition which comprises as an active ingredient a thiazole compound or a salt thereof as set forth in claim 1.
- 29. A process for preparing a thiazole compound as set forth in claim 1, which comprises the following steps of
- (a) reacting a compound of the formula (2): ##STR1202## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, with a compound of the formula (3): ##STR1203## wherein R.sup.11b is the same as defined in claim 1, or a compound of the formula (4): ##STR1204## wherein R.sup.15 is a group: --CH.dbd.C(R.sup.11b)(COR.sup.16) wherein R.sup.11b is the same as defined in claim 1, and R.sup.16 is a hydroxy group or a lower alkoxy group, or a group: --C.tbd.C--COR.sup.14 wherein R.sup.14 is the same as defined in claim 1, and X is a halogen atom, to give a compound of the formula (1a): ##STR1205## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.15 is the same as defined above;
- (b) reacting a compound of the formula (1b): ##STR1206## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.11b, Z, m, s, T, u and A are the same as defined in claim 1, with a compoud of the formula (5):
- R.sup.17 H (5)
- wherein R.sup.17 is the heterocyclic groups as defined for R.sup.11a of claim 1 but having at least one ##STR1207## in the heterocyclic nucleus, to give a compoud of the formula (1c): ##STR1208## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.11b, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.17 is the same as defined above;
- (c) reacting a compound of the formula (10): ##STR1209## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, R.sup.18 is a lower alkoxy group, with a compound of the formula (12): ##STR1210## wherein R.sup.16 is the same as defined above, to give a compound of the formula (1d): ##STR1211## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1 and R.sup.16 is the same as defined above;
- (d) reacting a compound of the formula (10): ##STR1212## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, S, T, u and A are the same as defined in claim 1, and R.sup.18 is the same as defined above, with a compound of the formula (20):
- R.sup.22 CHO (20)
- wherein R.sup.22 is a 5- to 10-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group said heteromonocyclic or heterobicyclic group optionally having 1 to 3 substituents selected from (i) a lower alkyl group; (ii) a group: --(B).sub.l NR.sup.12 R.sup.13, wherein l is O or 1, B is a group: --CO--A-- (wherein A is alkylene), a carbonyl group or a lower alkylene group, R.sup.12 and R.sup.13 are the same or different, and each are a hydrogen atom, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, or both combine together with the adjacent nitrogen atom to which they bond to form a 5- to 12-membered saturated heteromonocyclic, heterobicyclic or hetero-sprio ring with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group may optionally have a substituent selected from a lower alkyl group, a lower alkoxycarbonyl group, a lower alkoxy-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent and a hydroxy-substituted lower alkyl group); (iii) a lower alkoxycarbonyl group; (iv) a hydroxy-substituted lower alkyl group; (v) a pyridyl group being optionally substituted by a lower alkyl group having optionally a halogen substituent on the pyridine ring; (vi) a halogen-substituted lower alkyl group; (vii) a lower alkoxy group; (viii) a cycloalkyl group; (ix) a hydroxy group; (x) a tetrahydropyranyloxy-substituted lower alkyl group; (xi) a pyrimidyl group; (xii) a lower alkoxy-substituted lower alkyl group; (xiii) a carboxyl group; (xiv) a phenyl-lower alkoxy group; (xv) a phenyl-lower alkyl group having optionally a lower alkylenedioxy substituent on the phenyl ring; (xvi) a lower alkanoyloxy group; and (xvii) a piperidinyl group having optionally a lower alkyl substituent on the piperidine ring, to give a compound of the formula (1h): ##STR1213## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.18 and R.sup.22 are the same as defined above;
- (e) converting, a compound of the formula (11): ##STR1214## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.20 is a lower alkoxy group, into a compound of the formula (1d'): ##STR1215## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.16a is a lower alkoxy group, in the presence of a basic compound, optionally followed by converting the compound (1d') into a compound of the formula (1e): ##STR1216## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, in the presence of an acid or a basic compound;
- (f) converting a compound of the formula (11): ##STR1217## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.20 is a lower alkoxy group, into a compound of the formula (1f): ##STR1218## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u, and A are the same as defined in claim 1, and R.sup.20 is the same as defined above, in the presence of an oxidizing agent, optionally followed by converting, the compound (1f) into a compound of the formula (1g): ##STR1219## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, in the presence of an acid or a basic compound;
- (g) reacting a compound of the formula (19): ##STR1220## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.21 is a phenyl group, with a compound of the formula (20):
- R.sup.22 CHO (20)
- wherein R.sup.22 is the same as defined above, to give a compound of the formula (1h): ##STR1221## wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, Z, m, s, T, u and A are the same as defined in claim 1, and R.sup.22 is the same as defined above;
- (h) reacting a compound of the formula (23): ##STR1222## wherein R.sup.3 is the same as defined in claim 1, with a compound of the formula (24): ##STR1223## wherein R.sup.1, R.sup.2, R.sup.4, T and u are the same as defined in claim 1, to give a compound of the formula (1): ##STR1224## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, T and u are the same as defined in claim 1;
- (i) reacting a compound of the formula (19a): ##STR1225## wherein T, u, R.sup.1, R.sup.2, R.sup.4, Z, R.sup.5 and m are the same as defined in claim 1, and R.sup.21 is the same as defined above, and A' is a lower alkylene group, with a compound of the formula (44):
- OHC.COOH (44)
- to give a compound of the formula (1q): ##STR1226## wherein T, u, R.sup.1, R.sup.2, R.sup.4, Z, R.sup.5 and m are the same as defined in claim 1 and A' is a lower alkylene group.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 8-200898 |
Jul 1996 |
JPX |
|
Parent Case Info
This application is a 371 of PCT/JP97/02609 filed Jul. 29, 1997.
PCT Information
| Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
| PCT/JP97/02609 |
7/29/1997 |
|
|
3/24/1998 |
3/24/1998 |
| Publishing Document |
Publishing Date |
Country |
Kind |
| WO98/04536 |
2/5/1998 |
|
|
Foreign Referenced Citations (7)
| Number |
Date |
Country |
| 0 318 084 |
May 1989 |
EPX |
| 0 343 893 |
Nov 1989 |
EPX |
| 0 412 404 |
Feb 1991 |
EPX |
| 0 638 564 |
Feb 1995 |
EPX |
| 2306916 |
Dec 1990 |
JPX |
| 9321169 |
Oct 1993 |
WOX |
| 9321168 |
Oct 1993 |
WOX |
Patent Grant
6140330
