Kowa Company Limited

Eizou Hattori

Setsuro Fujii

Mitsuteru Hirata

Koichiro Watanabe

Hiroshi Ishihama

Masahiko Nagakura

Hisashi Kunieda

Kazuhiro Onogi

Tomio Ohta

Nobuo Yokoo

A benzopylpiperazine ester of the following formula: ##STR1## wherein A represents a single bond or an alkylene group, vinylene group, --O--alkylene group or methine group, R.sub.1 represents a bicyclic carbon ring residue which may be substituted with a lower alkyl group, lower alkoxy group, oxo group or nitro group or a halogen atom, or may be partially saturated; a fluorene residue which may contain an oxo group; a fluorenylidene group; an anthracene residue; a phenanthrene residue which may be substituted with a lower alkyl group, or may be partially saturated; a benzofuran residue or thianaphthene residue which may be substituted with a lower alkyl group or lower alkoxy group; a benzopyran residue or benzoazine residue which may be substituted with an oxo group or phenyl group and partially saturated; a phthalimide residue; a benzodiazine residue; an isozazole residue which may be substituted with a lower alkyl group or phenyl group; or an alkylene dioxybenzene residue or xanthene residue; and R.sub.2 represents an alkyl group, cycloalkyl group, cycloalkylalkyl group or aralkyl group, excepting the case where A is a single bond, R.sub.1 is ##STR2## and R.sub.2 is a methyl group, exhibits excellent chymotrypsin inhibitive activity.

Benzoylpiperazine esters and a process for their production

Novel benzoyl esters of the following formula (I), and acid addition salts thereof, ##STR1## in which R.sub.1 and R.sub.2 are the same or different and represent a hydrogen atom or a lower alkoxy group, A represents a single bond, a linear or branched lower alkylene group, a lower alkenylene group, R.sub.3 and R.sub.4 are the same or different and represent a hydrogen atom or a lower alkyl group, or R.sub.3 and R.sub.4 join together to form a lower alkylene group, R.sub.5 represents a group of the formula, --X--(CO).sub.n --Y in which X represents a single bond, a linear or branched lower alkylene group or an alkenylene group, n is 0 or 1, Y represents a hydrogen atom, a cycloalkyl group, an aryl group, a hydroxyl group, a lower alkoxy group and the like are prepared by reacting para-nitrobenzoic acid or its derivative with a compound of the general formula (III) or its derivative ##STR2## to obtain a compound of the general formula (IV) ##STR3## followed by reducing the compound of the formula (IX) ##STR4## and subjecting the compound (IX) to guanidylation reaction, or by reaction para-guanidinobenzoic derivative with compound (III) or its derivative. The benzoyl esters have strong anti-trypsin activity, anti-thrombin activity and anticoagulant activity with low toxicity and are useful as a medicine for treatment of pancreatitis and disseminated intravascular coagulation (DIC).

Phenyl guanidinobenzoate derivatives which have protease inhibitory

Phenyl tetrahydronaphthylcarboxylate of the formula: ##STR1## wherein A is a direct bond, or a lower alkylene, vinylene or imino group; B is a direct bond, a lower alkylene or --NH-lower alkylene group, or an --OCH.sub.2 CO-- residual group; and R is a lower alkyl group, with the proviso that A and B are not direct bonds simultaneously, and A, B and R are not a lower alkylene group, a direct bond and a methyl group, respectively, at the same time, are effectively useful as chymotrypsin inhibitors.

1-isopropyl-4[(4-tetrahydro-1-naphthoyloxy

Benzoyl indolecarboxylates of the formula: ##STR1## where R.sup.1 is hydrogen, halogen, lower alkyl or lower alkoxy; R.sup.2 is hydrogen, lower alkyl, acetyl or benzoyl; R.sup.3 is hydrogen or lower alkyl; and A is a direct bond, or lower alkylene or vinylene substituted at the 2-, 3- or 5-position of the indole nucleus, are effective agents as chymotrypsin inhibitors.

Benzoyl indolecarboxylates

A piperazine derivartive represented by the following formula: ##STR1## wherein R.sub.1 : an indolyl group which may optionally be substituted by one or more lower alkyl and/or lower alkoxy groups, naphthyl group which may optionally be saturated partially with 2 or 4 hydrogen atoms, or phenyl or cyclohexyl group which may optionally be substituted by one or more lower alkyl groups;

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Sakado, Japan

Eizou Hattori