Sankyo Company, Limited

Mitsuo Nagano

Nobuyoshi Iwata

Kenji Yoshimi

Shinichi Sugawara

Hiroaki Yanagisawa

Masakatsu Kaneko

Hideo Nakao

Yoshiko Kubo

Masao Kozuka

Junichi Sakai

Bunji Shimizu

Hiroshi Yasuda

Kazuo Kobayashi

Takeo Kobayashi

Koichi Kitamura

Katsunori Kato

Koichi Hirai

Takashi Matsui

Tetsuo Miyadera

Fusaaki Shimizu

Kouichi Kitamura

Kenkichi Shinkai

Toshiyuki Tonohiro

Takao Hara

Compounds of formula (I): ##STR1## wherein R.sup.1 is hydrogen, halogen or alkyl; R.sup.2 is hydrogen, alkyl, optionally substituted phenyl or a heterocycle; or R.sup.1 and R.sup.2 together form a group of formula --CR.sup.4 .dbd.CR.sup.5 --CR.sup.6 .dbd.CR.sup.7 --, where R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are hydrogen, halogen, alkyl group, alkoxy, halomethyl, alkylamino, dialkylamino, hydroxy, nitro, aliphatic carboxylic acylamino or amino; and R.sup.3 is piperidyl, substituted piperidyl or quinuclidinyl. The compounds are useful in the treatment and prophylaxis of cognitive disorders, notably senile dementia, including Alzheimer's disease. Processes for preparing the compounds are also provided.

Quinuclidinyloxy-isoxazole compounds and their therapeutic uses

Compounds of formula (I): ##STR1## [in which: either (a) the dotted line ( ) is a single bond; A=is oxygen; and B is a group of formula (II): ##STR2## (in which m is 0 and n is 0 or 1) or (b) the dotted line ( ) is a double bond; A=is said group of formula (II) in which m is 1 and n is 0 or 1; and B is absent; and R.sup.1 is hydrogen, halogen, alkyl, alkenyl, alkynyl, optionally substituted benzyl or optionally substituted phenyl; R.sup.2 is hydrogen, halogen, alkyl, optionally substituted phenyl or heterocyclic; or R.sup.1 and R.sup.2, together with the carbon atoms to which they are attached, are a hydrocarbon ring fused to the isoxazole ring; R.sup.3 and R.sup.4 are each hydrogen, alkyl, optionally substituted benzyl or optionally substituted phenyl; or R.sup.3, R.sup.4 and the nitrogen atom to which they are attached together represent an alicyclic amino group]; and salts thereof may be used for the treatment of cerebral circulatory problems and for use as centrally acting muscle relaxants.

Isoxazole derivatives for use as cerebro-active drugs and central muscle

A method of treating depression comprising administering to a patient an effective amount of a compound of the formula (Ib): ##STR1## wherein R.sup.1b is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, an unsubstituted benzyl group, a substituted benzyl having at least one substitutent (b) selected from the group consisting of C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy, hydroxy, halogen, nitro, amino and C.sub.2 -C.sub.4 aliphatic carboxylic acylamino; unsubstituted phenyl or a substituted phenyl having at least one substitutent (b); R.sup.2b is hydrogen, C.sub.1 -C.sub.4 alkyl, unsubstituted phenyl, substituted phenyl having at least one substitutent (b), unsubstituted 5- or 6- membered heterocyclic having an oxygen, sulfur or nitrogen as a heteroatom, or substituted 5- or 6- membered heterocyclic having an oxygen, sulfur or nitrogen as a heteroatom and having at least one substitutent (b); and R.sup.3b and R.sup.4b are the same or different and each is hydrogen, C.sub.1 -C.sub.4 alkyl, unsubstituted benzyl, substituted benzyl having at least one substituent (b), unsubstituted phenyl, or substituted phenyl having at least one substitutent (b); or R.sup.3b, R.sup.4b and the nitrogen atom to which they are attached together represent an alicyclic amino group having a total of 5 or 6 ring atoms, or which one ring atom is the nitrogen atom and one ring atom is optionally an additional heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, the alicyclic amino group being unsubstituted or, where there is an additional nitrogen heteroatom, the alicyclic amino group having a C.sub.1 -C.sub.3 alkyl substitutent on the additional nitrogen heteroatom; or a pharmacologically acceptable acid addition salt thereof.

Use of isoxazolin-3-one derivatives as antidepressants

A method of treating depression comprising administering to a patient an effective antidepressive amount of a compound of the formula ##STR1## wherein either (i) the endocyclic dotted line (  ) is a double bond; the exoxyclic dotted line (  ) is a single bond;

A method of treating depression comprising administering to a patient an effective antidepressive amount of a compound of the formula (I) ##STR1## wherein the endocyclic dotted line ##STR2## is a single bond; the exocyclic dotted line ##STR3## is a double bond; A is oxygen; B is a group of the formula (II) ##STR4## wherein m is 0 and n is 0 or 1; R.sup.3, R.sup.4 and the nitrogen to which they are attached together represent an alicyclic amino having a total of 5 or 6 ring atoms, of which one ring atom is the nitrogen and one ring atom is optionally an additional heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, the alicyclic amino being unsubstituted or, where there is an additional nitrogen heteroatom, the alicyclic amino having as a substituent a C.sub.1 -C.sub.3 alkyl on the additional nitrogen heteroatom; R.sup.1 is hydrogen or halogen; and R.sup.2 is an unsubstituted phenyl, a substituted phenyl having a substituent selected from the group consisting of C.sub.1-3 alkyl, C.sub.1-3 alkoxy, halogen and nitro, an unsubstituted 5- or 6-membered heterocyclic group having one or more of oxygen, sulfur or a nitrogen as heteroatoms, or a substituted 5- or 6-membered heterocyclic group having one or more of oxygen, sulfur or a nitrogen as heteroatoms and having at least one substituent selected from the group consisting of C.sub.1 -C.sub.3 alkyl, C.sub.1-3 alkoxy, halogen and nitro; or a pharmaceutically acceptable acid addition salt thereof.

Amino acid amides of formula (I): ##STR1## wherein R.sup.1 -R.sup.5 and Y represent a variety of organic groups and atoms (including where R.sup.2, Y and the adjacent nitrogen atom together represent a thiazolidine or pyrrolidine group) and X represents carbonyl or sulfonyl are mostly new compounds and have valuable anti-tumor and immuno-regulatory activities. They may be formulated in compositions for pharmaceutical use.

Amino acid derivatives having anti-tumor activity and compositions

New compounds useful as immunoregulatory and antineoplastic agents are amino-acid derivatives of formula: ##STR1## wherein: n is an integer from 1 to 5;

Amino-acid derivatives, their preparation and their use as

Novel cephalosporin derivatives having a (1-alkyl-1H-tetrazol-5-yl)vinyl group at the 3-position of the cephem nucleus and showing an excellent antibacterial activity are disclosed. A process for preparing the cephalosporin derivatives is also disclosed.

7-D-(-)-mandelamido-3-(1-methyl-1H-tetrazol-5-yl)vinyl-

A compound having the formula ##STR1## wherein Y represents a 2-carboxyethylthio group or a trifluoromethylthio group and a nontoxic pharmaceutically acceptable salt thereof are useful as antibacterial agents. They may be prepared by (a) reacting a compound having the formula ##STR2## wherein X.sub.1 represents a halogen atom with a compound having the formula

7-Methoxycephalosporin derivatives

A compound of the formula ##STR1## wherein A represents acetoxy group, carbamoyloxy group or (1-metyl-1H-tetrazol-5-yl)thio group and Y represents propargylthio group, azidomethylthio group, 2-hydroxyethylthio group, 3-isoxazolyloxy group, 3-isoxazolylthio group, methylsulfonyl group, ethylsulfonyl group, 2-cyanoethyl-sulfonyl group or sydnon-3-yl group and nontoxic pharmaceutically acceptable salts thereof are prepared by a process which comprises reacting a compound of the formula ##STR2## wherein R represents a protective group for a carboxyl group and A has the same meaning as defined above with a carboxylic acid of the formula

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Tokyo, Japan

Mitsuo Nagano