Dainippon Pharmaceutical Company, Limited

Haruki Nishimura

Masanao Shimizu

Hitoshi Uno

Hideo Nakamura

Kagayaki Natsuka

Noriaki Shimokawa

Hiroaki Kinugasa

Yoshinobu Masuda

Toshiaki Kadokawa

Mikio Kurokawa

Tadahiro Sawayama

Katsuyoshi Kawashima

Shunsuke Naruto

Kanoo Hosoki

Kunihiko Takeyama

Naonobu Hatano

Hiroko Kon

Hiroyuki Mizuta

Tetsuo Hirooka

Katsuyoshi Nakatsuzi

Novel 2-cyclic amino-2-(1,2-benzisoxazol-3-yl)acetic acid derivatives of the formula: ##STR1## wherein R.sub.1 is hydrogen or a halogen atom, R.sub.2 is a lower alkyl group, Am is a 5- to 9-membered saturated cyclic amino group which may be substituted by a lower alkyl group, and the group: ##STR2## binds to the piperidine moiety at 3- or 4-position of the latter, and their pharmaceutically acceptable acid addition salts and quaternary ammonium salts, process for their preparation, and pharmaceutical compositions containing these compounds. They have potent anticholinergic antispasmodic activity, while they are weak in side effects such as mydriasis, inhibition of salivary secretion and tachycardia.

2-Cyclic amino-2-(1,2-benzisoxazol-3-yl)acetic acid ester derivatives,

1-(3-Mercapto-2-methylpropanoyl)prolyl amino acid derivatives of the formula ##STR1## wherein R represents a hydrogen atom, a lower alkyl group, a phenyl-lower alkyl group or a substituted phenyl-lower alkyl group, R.sub.1 represents a hydrogen atom, R.sub.4 CO--, R.sub.5 S--, or ##STR2## R.sub.2 represents a hydrogen atom or a lower alkyl group, R.sub.3 represents a hydrogen atom, a phenyl group, a lower alkyl group, or a substituted lower alkyl group, or R.sub.2 and R.sub.3 form a heterocyclic ring together with the nitrogen and carbon atoms to which they are respectively bonded; salts of these compounds; compositions comprising these compounds or salts; and processes for preparing these compounds or salts. These compounds and salts have excellent antihypertensive activity.

1-(3-Mercapto-2-methylpropanoyl)prolyl amino acid derivatives and salts

1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives of the formula: ##STR1## wherein X is 2- or 3-hydroxy, 2-methoxy, 3-methyl, 3-alkoxy having 1 to 4 carbon atoms, or 2- or 3-alkanoyloxy having 2 to 5 carbon atoms; R is allyl, 3-hydroxyisoamyl, 3-methyl-2-butenyl, 3-methyl-3-butenyl, propyl, an unsubstituted monocycloalkyl having 5 to 8 carbon atoms, 2-chlorophenyl, or a phenyl substituted by hydroxy or methoxy; with proviso that when X is a substituent at position 2, R is cyclohexyl and when X is 3-methyl, R is 2-methoxyphenyl or an unsubstituted monocycloalkyl having 6 to 8 carbon atoms, and their pharmaceutically acceptable salts, and the preparation thereof, and analgesic or antitussive compositions containing the same as the essentially active ingredient.

1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives and

A compound of the formula ##STR1## wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, and R.sub.2 represents a hydrogen or halogen atom or a trifluoromethyl group, And its pharmaceutically acceptable salt. The compound is prepared by reacting the corresponding 1,2,4-benzothiadiazine 1,1-dioxide with a piperazine compound or alkylating 1,2,4-benzothiadiazine 1,1-dioxide whose corresponding 3-position is substituted by a piperazinyl group. The above compound has superior antihypertensive activity separated from diuretic, antidiuretic and hyperglycemic activities, and is free from side-effects.

3-Piperazinyl 1,2,4-benzothiadiazine 1,1-dioxide derivatives their

1,2-Diphenylethanolamine derivatives of the formula: ##SPC1## Wherein R.sub.1 and R.sub.2 are each hydrogen, a halogen, nitro, hydroxy, an alkyl or methoxy; R.sub.3 is a group of the formula: ##SPC2## Wherein R.sub.4, R.sub.5 and R.sub.6 are each hydrogen, a halogen or methoxy and n is an integer of 0 to 3, or a pyridyl; and Z is hydroxy or an acyloxy; with proviso that when R.sub.1 and/or R.sub.2 are hydroxy, Z is hydroxy, and their pharmaceutically acceptable salts, which have excellent analgesic and anti-tussive activities, and a process for the preparation thereof.

1,2-Diphenylethanolamine derivatives and their salts and the preparation

1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives of the formula: ##SPC1## Wherein X is hydroxy, methoxy, methyl or trifluoromethyl; and R is an unsubstituted monocycloalkyl group having 6 to 8 carbon atoms or 2-methoxyphenyl; provided that when X is hydroxy, R is cyclohexyl, and when X is trifluoromethyl, R is 2-methoxyphenyl, And their pharmaceutically acceptable salts, which have excellent analgesic, anti-tussive and anti-inflammatory activities, without undesirable side effect such as narcotic activity, and a process for the preparation thereof.

1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives and their

3-Substituted-1,2-benzisoxazole derivative of the following formula: ##SPC1## Wherein R.sub.1 is hydrogen, hydroxy, nitro, alkyl, alkoxy, halogen or amino; R.sub.2 is hydroxyamino, amino, hydrazino, mono- or di- alkyl substituted amino, aralkylamino, acyloxyamino, morpholino, piperazine which is unsubstituted or substituted with alkyl, aralkyl or aryl at 4 position, or pyrrolidino, or R.sub.2 may combine with imino group and form together with the adjacent carbon atom a heterocyclic ring such as imidazoline or tetrahydropyrimidine; and n is an integer of 0 to 3, and its pharmaceutically acceptable acid addition salt, and preparation thereof. The present compounds show valuable pharmacological properties, such as anti-reserpine activity, central nervous depressing activity, anti-hypertensive activity and l-dopa potentiating activity.

3-Substituted-1,2-benzisoxazoles and pharmaceutically acceptable acid

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Ikeda, Japan

Haruki Nishimura