Patent ID: 6403644
Filing Date: 2002-06-11
Classification: C07C,C07D

Abstract:
A method for the treatment of rheumatiod, arthrosteitis, unusual bone resorption, osteoporosis, peridontisis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion on or growth of tumor cells, autoimmune disease (Chrohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes, arterialization, which comprises the administration of an effective amount of a compound of the formula (Ia): whereinR1 is hydrogen, or C1-4 alkyl; R2 is (1) hydrogen, (2) C1-8 alkyl, (3) phenyl, or (4) C1-4 alkyl substituted by phenyl, â€”OCOR16, in which R16 is C1-4 alkyl; or â€”CONR17R18, in which R17 and R18 each, independently, is hydrogen or C1-4 alkyl; E is (1) â€”CONR3â€”, in which R3 is hydrogen, C1-4 alkyl, phenyl, C1-4 alkyl substituted by phenyl; (2) â€”NR3COâ€”, in which R3 is the same meaning as hereinbefore defined; (3) â€”COâ€”Oâ€”, (4) â€”Oâ€”COâ€”, (5) â€”NR3â€”COâ€”NR3â€”, in which R3 is the same meaning as hereinbefore defined; (6) â€”COâ€”CH2â€”, (7) â€”COâ€”, (8) â€”Oâ€”COâ€”NR3â€”, in which R3 is the same meaning as hereinbefore defined; (9) â€”NR3â€”COâ€”Oâ€”, in which R3 is the same meaning as hereinbefore defined; (10) â€”Oâ€”COâ€”Oâ€”, (11) â€”CSâ€”NR3â€”, in which R3 is the same meaning as hereinbefore defined; (12) â€”NR3â€”CSâ€”, in which R3 is the same meaning as hereinbefore defined; (13) â€”NR3â€”CSâ€”NR3â€”, in which R3 is the same meaning as hereinbefore defined; (14) â€”Oâ€”CSâ€”NR3â€”, in which R3 is the same meaning as hereinbefore defined; (15) â€”NR3â€”CSâ€”Oâ€”, in which R3 is the same meaning as hereinbefore defined; (16) â€”CSâ€”Oâ€”, (17) â€”Oâ€”CSâ€”, (18) â€”Oâ€”CSâ€”Oâ€”, A is (1) hydrogen, (2) C1-8 alkyl, (3) C3-7 cycloalkyl, or (4) Ar, in which Ar is carbocyclic aryl or heterocyclic aryl, and these rings are unsubstituted or substituted by 1-3 of C1-15 alkyl, C1-15 alkoxy, halogen, nitro, cyano, guanidino, amidino, hydroxy, benzyloxy, â€”NR9R10, in which R9 and R10 each, independently, is hydrogen or C1-4 alkyl; â€”COOR11, in which R11 is hydrogen or C1-4 alkyl; trifluoromethyl, phenyl or heterocyclic ring; J is (1) bond, (2) C2-4 alkylene, (3) C2-4 alkenylene, or (4) in which R4 and R5 each, independently, is (i) hydrogen, (ii) C1-4 alkyl, (iii) C1-4 alkoxy, or R4 and R5, taken together with the carbon to which they are attached, is C3-7 cycloalkyl,G is (1) â€”(CH2)mâ€”, in which m is 2, 3 or 4, or (2) in which R6 and R7 each, independently, is (i) hydrogen, (ii) C1-8 alkyl, (iii) â€”COOR8, in which R8 is hydrogen, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl; (iv) Ar, in which Ar is the same meaning as hereinbefore defined; (v) heterocyclic ring, (vi) C1-8 alkyl substituted by â€”COOR8, in which R8 is the same meaning as hereinbefore defined; C1-4 alkoxy, hydroxy, benzyloxy, â€”NR12R13, in which R12 and R13 each, independently, is hydrogen or C1-4 alkyl; â€”NR14COOR15, in which R14 is hydrogen or C1-4 alkyl, R15 is hydrogen, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl; Ar or heterocyclic ring; with the proviso that one of carbon in C1-8 alkyl may be replaced by one of sulfur; or R6 and R7, taken together with the carbon to which they are attached, is C3-7 cycloalkyl; a compound in which E is â€”Oâ€”COâ€”NR3â€”, â€”Oâ€”COâ€”Oâ€”, Oâ€”CSâ€”NR3â€”, or Oâ€”CSâ€”Oâ€”, J is a bond and A is hydrogen, is excluded or non-toxic salts thereof.