Banyu Pharmaceutical Co. Ltd

Other

Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Junji Yoshizawa

Ikuo Matsumoto

Hamao Umezawa

Tomio Takeuchi

Hajime Morishima

Mitsuo Yano

Yoshimi Tsuchiya

Hiroyoshi Hidaka

Kyoko Nakamichi

Yukio Hirayama

Shigenori Kotani

Takaaki Aoyagi

Masaaki Ishizuka

Kiyofumi Ishikawa

Toshiharu Nagatsu

Masaaki Hosoi

Nobuo Harada

Shuichi Iwadare

Takuzo Yamamoto

Kaoru Shimada

Nobuyuki Mino

Hirotaro Narabayashi

Koji Tomimoto

DL- or L-Threo-3-(3,4-dihydroxyphenyl)-N-methyl-serine which may also be termed as DL- or L-threo-adrenalinecarboxylic acid are now provided, which are new compounds useful for therapeutic treatment of Parkinson's disease and mental depression disease. DL-Adrenalinecarboxylic acid may be produced by a new process comprising reacting glycine with O-protected 3,4-dihydroxybenzaldehyde, hydrolyzing the resultant reaction product under acidic conditions to form O-protected DL-3-(3,4-dihydroxyphenyl)serine, isolating the O-protected DL-3-(3,4-dihydroxyphenyl)serine into the threo isomer and the erythro isomer by recrystallization from a suitable organic solvent, introducing an unsubstituted or substituted benzyl group into the 2-amino group of the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine, then N-methylating the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl )-N-benzylserine, and removing the O-protecting groups as well as the unsubstituted or substituted benzyl group at the 2-methylamino group of the N-methylation product. L-Adrenalinecarboxylic acid may be produced by a new process comprising introducing a p-methoxybenzyloxycarbonyl group into the 2-amino group of the O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine obtained as an intermediate product, optically resolving the resultant O-protected DL-threo-3-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine by reacting the latter with an optically active amine and recrystallizing the resultant amine salt products from a suitable organic solvent, removing the p-methoxy-benzyloxycarbonyl group from the resultant O-protected L-threo-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine, reacting the resultant O-protected L-threo-(3,4-dihydroxyphenyl)serine with dimethyl sulfate in dry acetone to form an O-protected L- or D-threo-(3,4-dihydroxyphenyl)-N-methylserine methyl ester, saponifying this methyl ester and then removing the O-protecting groups from the saponification product.

Threo-adrenalinecarboxylic acid, and the production and uses thereof

A 1,3-dithiole derivative having the formula: ##STR1## wherein each of R.sup.1 and R.sup.2 is a substituted or unsubstituted alkyl, cycloalkyl, lower alkenyl, lower alkynyl, aryl or aralkyl group or R.sup.1 and R.sup.2 together form a substituted or unsubstituted alkylene or alkenylene group having from 3 to 6 carbon atoms, which may contain a cycloalkylene group, an o-phenylene group or a hetero atom selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom which may have a substituent, and Q is an acid residue useful for the treatment of liver diseases.

1,3-dithiole derivatives and pharmaceutical compositions

A 1,3-dithiol-2-ylidene derivative of the formula: ##STR1## wherein each of R and R.sup.1 which may be the same or different, is a lower alkyl group, a lower alkenyl group, a cycloalkyl group, a lower alkoxyalkyl group, or a substituted or unsubstituted aryl, aralkyl or heterocyclic group, or R and R.sup.1 together form a substituted or unsubstituted ethylene or trimethylene group.

Anti-hepatitis and anti-cirrhotic 1,3-dithiol-2-ylidene derivatives, and

An .alpha.-tocopheryl 5-substituted picolinate of the formula ##STR1## wherein R represents an alkyl group which may have a substituent, a lower alkenyl group, a phenyl(lower alkyl) group, or a phenyl group which may have a substituent, and Q represents a methylene group or an oxygen or sulfur atom, or a pharmaceutically acceptable acid addition salt thereof. This compound can be produced by reacting a substituted picolinic acid of the formula ##STR2## wherein R and Q are as defined above, or its reactive derivative with .alpha.-tocopherol of the formula ##STR3## and as required, contacting the resulting compound with a pharmaceuticlly acceptable acid. A pharmaceutical composition comprising said compound as an active ingredient is useful for the treatment of hypertension.

.alpha.-Tocopheryl ester of 5-substituted picolinic acid and hypotensive

An N-acyl-3-[4-(benzoylalkyl)piperazin-1-yl]-sydnonimine compound represented by the following formula ##STR1## wherein R.sup.1 represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms,

N-Acyl-3-[4-(benzoylalkyl)piperazin-1-yl]-sydnonimine compound, process

A 3-[4-(benzoylalkyl)piperazin-1-yl]sydnonimine compound represented by the following formula ##STR1## wherein R represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and n represents zero or an integer of 1 to 10, and its acid addition salt. The above sydnonimine compounds are useful for the treatment of troubles of the circulatory system and can be produced by contacting a 4-(benzoylalkyl)-1-(N-nitrosocyanomethylamino)piperazine represented by the following formula ##STR2## wherein R and n are as defined, with an acid.

Syndonimine derivatives, process for production thereof, and use thereof

A new compound is produced which has the general formula: ##STR1## wherein R represents hydrogen atom or a lower alkyl group and which exhibits an immunopotentiating activity. This new compound as well as its pharmaceutically acceptable salts and hydrates are useful for immunotherapy and treatment of immune diseases and disorders in living animals including human beings. The new compound can be produced by reduction of a hydroxyterephthalic acid alkyl ester or by esterification of the corresponding 3-hydroxy-4-(hydroxymethyl)-benzoic acid.

Compound with immunopotentiating activity and production and uses thereof

Growing community of inventors

Machida, Japan

Junji Yoshizawa