Amidinophenol derivatives
AssigneeOno Pharmaceutical Co., Ltd.
InventorsHisao Nakai, Koumei Kamiyasu, Masanori Kawamura
Life of this patent
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Abstract
Disclosed are amidinophenol derivatives of the formula (I) and acid-addition salts thereof (in which R.sup.1 and R.sup.2 are alkyl, alkoxy, acyl, halogen, nitro, benzoyl, COOR.sub.4 ; A is bond, alkylene, group of the formula (II); R.sup.3 is group of the formula (III), (IV)) ##STR1## Compounds of the formula (I) have inhibitory activities on phospholipase A.sub.2 and proteases (especially trypsin), and are useful for the prevention and/or the treatment of inflammatory diseases, allergic diseases, disseminated intravascular coagulation, pancreatitis, severity in pancreatitis and multiple organ failure.
Claims12
A compound of the formula (I):
- ##STR111## wherein R.sup.1 and R.sup.2 each, independently, is:
- (i) hydrogen,
- (ii) C1-4 alkyl,
- (iii) C1-4 alkoxy,
- (iv) C2-5 acyl,
- (v) halogen,
- (vi) nitro,
- (vii) benzoyl, or
- (viii) COOR.sup.4 (in which R.sup.4 is C1-3 alkyl);
- A is bond, C1-4 alkylene, or ##STR112## in which R.sup.5 and R.sup.6 each, independently, is hydrogen or C1-4 alkyl;
- R.sup.3 is ##STR113## in which R.sup.7 and R.sup.8 each, independently, is (1) hydrogen,
- (2) phenyl,
- (3) C7-10 phenylalkyl,
- (4) phenyl or C7-10 phenylalkyl each of which is substituted by one or two substituents selected from C1-4 alkyl, halogen and R.sup.11 --COOR.sup.12
- in which R.sup.11 is a
- ! bond,
- 2! C1-8 alkylene,
- 3! C2-8 alkenylene, or
- 4! C2-8 alkynylene;
- R.sup.12 is
- 1! hydrogen,
- 2! C1-4 alkyl,
- 3! C7-10 phenylalkyl,
- 4! phenyl,
- 5! allyl, or
- 6! propargyl,
- (5) C1-10 alkyl,
- (6) C2-10 alkenyl having one to three double bonds,
- (7) C2-10 alkynyl having one or two triple bonds,
- (8) R.sup.11a --COXR.sup.12
- in which R.sup.11a is a
- ! bond,
- 2! C1-8 alkylene,
- 3! C2-8 alkylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
- 4! C2-8 alkenylene,
- 5! C4-8 alkenylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
- 6! C2-8 alkynylene, or
- 7! C4-8 alkynylene in which one or two carbon atoms in the main chain are replaced by sulfur, or sulfur and phenylene,
- X is oxygen or --NH--, and R.sup.12 has the same meaning as hereinbefore defined,
- (9) C1-4 alkyl which is substituted by a 7-14 membered, bi- or tri-cyclic hetero ring containing one nitrogen,
- (10) C3-7 cycloalkyl, or
- (11) C1-6 alkyl which is substituted by C1-4 alkoxy;
- R.sup.9 is
- (1) hydrogen,
- (2) C1-8 alkyl,
- (3) C7-10 phenylalkyl,
- (4) C2-10 alkenyl having one to three double bonds,
- (5) C2-10 alkynyl having one or two triple bonds,
- (6) R.sup.11 --COOR.sup.12 in which R.sup.11 and R.sup.12 have the same meaning as hereinbefore defined,
- (7) C3-7 cycloalkyl, or
- (8) C1-6 alkyl which is substituted by C1-4 alkoxy;
- with the proviso that
- (i) at least one group in R.sup.7, R.sup.8 and R.sup.9 represents C1-6 alkyl which is substituted by C1-4 alkoxy,
- (ii) both R.sup.7 and R.sup.8 do not represent hydrogen at the same time, and
- (iii) when at least one group in R.sup.7, R.sup.8 and R.sup.9 represents groups containing t-butyl ester, the other groups in R.sup.7, R.sup.8 and R.sup.9 do not represent groups containing carboxy;
- or acid-addition salts thereof.
Dependencies are inferred from the claim text.