Leukotriene B4 antagonist compounds and method for treatment
AssigneeOno Pharmaceutical Co., Ltd.
InventorsHisao Nakai, Koumei Kamiyasu
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Abstract
Novel amidinophenol derivatives of formula (IB) and processes for the preparation thereof; compositions containing a compound of formula (IB) as active ingredient useful as antagonists of leukotine B4 and inhibitors of phospholipase A2 and/or trypsin; methods for preventing or treating diseases induced by phospholipase A2 and/or trypsin comprising administering to a patient a compound of formula (IB); and methods for treating diseases induced by leukotine B4 comprising administering to a patient a compound of formula (IB) or a known amidinophenol derivative of formula (IA)
Claims10
A new amidinophenol derivative of formula (IB):
- wherein:
- is a group of the formula:
- wherein
- R0 is hydrogen, or C1-4 alkyl, or C1-4 alkoxy, and
- R100 and R200 each independently is hydrogen or C1-4 alkyl;
- T is oxygen;
- E is a single bond;
- A0 is a single bond, C1-4 alkylene, vinylene optionally substituted by one or two C1-4 alkyl, -oxy-(C1-4)alkylene-, -thio-(C1-4)alkylene-, C2-8 alkenylene, or C2-8 alkenylene substituted by carboxy or by C1-4 alkoxycarbonyl;
- R is a group of the formula:
- wherein
- R50, R60 and R70 each independently, is,
- (i) hydrogen,
- (ii) C1-8 alkyl,
- (iii) C2-8 alkenyl
- (iv) —COOR110 (in which R110 is hydrogen or C1-4 alkyl optionally substituted by phenyl),
- (v) —(C1-8 alkylene)-COOR100 (in which R110 has the same meaning as hereinbefore defined),
- (vi) —(C2-8 alkenylene)-COOR110 (in which R110 is the same meaning as hereinbefore defined),
- (vii) C4-7 cycloalkyl,
- (viii) —(C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
- (ix) —(C1-4 alkylene)-(4-7 membered hetero ring containing one nitrogen),
- (x) phenyl,
- (xi) C1-8 alkyl substituted by one or two phenyl,
- (xii) —(C1-4 alkylene)-O-benzoyl,
- (xiii) —(C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130,
- (xiv) —(C1-4 alkylene)-COO—(C1-4 alkylene)-NR120R130,
- (xv) —(C1-4 alkylene)-COO-amidinophenyl,
- (xvi) —(C1-4 alkylene)-CONH—(C1-4 alkyl substituted by one or two COOR110) (in which R110 has the same meaning as hereinbefore defined),
- (xvii) —(C1-4 alkylene)-CONR120R130, or
- (xviii) (C1-4)alkoxy (C1-4)alkyl,
- R80 and R90 each independently, is C1-4 alkyl or —(C1-4 alkylene)-phenyl,
- R120 and R130 each independently, is hydrogen, C1-4 alkyl, or C2-8 alkenyl, with the provisos that:
- (1) R50 and R60 in the formula (1), and R50, R60 and R70 in the formula (2), are not hydrogen at the same time,
- (2) when at least one substituent in R50, R60, R70 and A0 is a substituent containing —COO-t-Bu, the other groups are not groups containing carboxy,
- (3) R120 and R130 are not hydrogen at the same time,
- (4) when
- A0 is a single bond, C1-4 alkylene or vinylene optionally substituted by one or two C1-4 alkyl, and
- R is
- then
- at least one group in R50 and R60 is
- (viii) —(C1-4 alkylene)-(4-7 membered hetero ring containing one oxygen),
- (ix) —(C1-4 alkylene)-(4-7 membered hetero ring containing one nitrogen),
- (xi) C1-8 alkyl substituted by one or two phenyl,
- (xii) —(C1-4 alkylene)-O-benzoyl,
- (xiii) —(C1-4 alkylene)-CONH—(C1-4 alkylene)-NR120R130,
- (xiv) —(C1-4 alkylene)-COO—(C1-4 alkylene)-NR120R130,
- (xv) —(C1-4 alkylene)-COO-amidinophenyl,
- (xvi) —(C1-4 alkylene)-CONH—(C1-4 alkyl substituted by one or two —COOR110) (in which R110 has the same meaning as hereinbefore defined), or
- (xvii) —(C1-4 alkylene)-CONR120R130,
- (5) when the formula:
- A0 is a bond, C1-4 alkylene or vinylene optionally subsituted by one or two C1-4 alkyl, and
- R is
- then R50, R60 and R70 are not hydrogen;
- or a non-toxic salt thereof or a non-toxic acid addition salt thereof.
Dependencies are inferred from the claim text.