Kaken Pharmaceutical Company, Ltd.

The University of British Columbia

Kakenyaku Kako Co., Ltd.

Jun Nakano

Tsutomu Nakamura

Tokiko Nishida

Yuji Suzuki

James P Kutney

Tadashi Arika

Michiko Nagahara

Hisato Senda

Mitsuru Watanuki

Michael McHugh

Hiroki Tsukamoto

Kiyoshi Kuriyama

Masahiro Suda

Kazuhiko Kimura

Hideto Fukui

Yoshihiro Ichikawa

Camille A Boulet

Katsuhiro Uchida

Teruo Nakanishi

Lewis S L Choi

Lewis S Choi

Mitsuo Hayashida

Toshiaki Okuda

Yoshiyuki Hiyama

Kiyoharu Ukai

Kiyoshi Ito

Terutake Nakagawa

Tetsuo Shibata

Kiyonosin Itikawa

Katsuro Ishizuki

Mamoru Inoue

Tetsuo Matsuda

Yukio Terashima

Yohichi Maruyama

Kiyomi Tanaka

Michio Nakanishi

Toshikazu Awaji

Hayami Debuchi

Kiyonoshin Itikawa

Hisamitsu Haigoh

Wakao Iwatani

Yayoi Watanuki

Tetsuro Maejima

2-sulfamoylbenzoic acid derivatives

The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.

Process of synthesis of 3&prime;,4&prime;-anhydrovinblastine, vinblastine and vincristine

2-Sulfamoylbenzoic acid derivatives of general formula (I):

Phenylamidinothiophene derivatives and anti-inflammatory agent

Quinolinecarboxylic acid derivatives and salts thereof

An oxime derivative of the formula: ##STR1## wherein R is a hydrogen atom or a C.sub.1-5 alkyl group, R.sub.1 is a hydrogen atom, a C.sub.1-5 alkyl group or a carboxyl-protecting group, R.sub.2 is a hydrogen atom, a halogen atom, a hydroxyl group or an amino group, R.sub.3 is a C.sub.3-7 cycloalkyl group, R.sub.4 is a hydrogen atom, a halogen atom or a C.sub.1-4 alkoxy group, each of R.sub.5 and R.sub.6 which may be the same or different, is a hydrogen atom or a C.sub.1-5 alkyl group, or R.sub.5 and R.sub.6 together represent a C.sub.2-4 alkylene group which forms together with the adjacent carbon atom a C.sub.3-5 ring, provided that when R.sub.2 is a hydrogen atom, R.sub.4 is a C.sub.1-4 alkoxy group, m is an integer of 0 or 1, and n is an integer of from 1 to 3; or its pharmaceutically acceptable salt.

Oxime derivatives

A 1,4-dihydropyridine derivative having the formula (I): ##STR1## wherein X is oxygen atom or nitrogen atom; when X is oxygen atom, R.sup.1 is hydrogen atom, a lower alkyl group, a lower cycloalkyl group, a lower alkenyl group or magnesium atom, when X is nitrogen atom, X-R.sup.1 group is NH.sub.2, NHR.sup.1', NR.sup.1' R.sup.1' or ##STR2## in which R.sup.1' is a lower alkyl group or a lower alkoxyalkyl group, R.sup.1' is a lower alkyl group and n is an integer of 2 to 6; R.sup.2 is a lower alkyl group, a lower cycloalkyl group or a lower alkoxyalkyl group and R.sup.3 is a lower alkyl group, formyl group, dimethoxymethyl group, cyano group or amino group, when X is oxygen atom and R.sup.1 is hydrogen atom or magnesium atom, R.sup.3 is methyl group, when X is nitrogen atom, R.sup.3 is methyl group, or a pharmaceutically acceptable salt thereof, some processes for preparing the same and a pharmaceutical composition containing the same. According to the present invention, a superior cerebral function improver can be provided.

1-4-dihydropyridine derivative, process for preparing the same and

Process of synthesis of vinblastine and vincristine

A chromene derivative having the general formula (I): ##STR1## wherein n is 1 to 5 and --O--CH.sub.2).sub.n CO.sub.2 H group is attached to 5-position, 6-position, 7-position or 8-position, or salts thereof, a process for preparing the same and antiallergic agents containing the same. The compounds of the present invention inhibit the immunological release of chemical mediators such as SRS-A and histamine from mast cell and have an excellent effect in preventing and treating the various allergic diseases such as allergic asthma, allergic dermatitis, allergic nasitis, hives, allergic enteritis and allergic conjunctivitis, especially allergic asthma.

Coumarin derivatives and antiallergic agents containing the same

A [2-hydroxy-3-(4-phenylpiperazinyl)propoxy]benzofuran derivative having the formula (I): ##STR1## wherein X is acetyl, carbamoyl, cyano, a lower alkoxycarbonyl, carboxyl or 1-hydroxyethyl group, R is hydrogen atom, a lower alkoxy group, a lower alkyl group or a halogen atom; R is attached to an arbitrary position of ortho-position, meta-position and para-position to N-phenyl group, and a group having the formula: ##STR2## is attached to an arbitrary position of 4, 5, 6 and 7 positions to benzofuran ring or the salt thereof, a process for preparing the same and an antihypertensive agent containing the same as an effective component. The benzofuran derivative has a strong .alpha.-adrenergic blockade effect and calcium antagonistic effect with a more decreased side-effect.

Benzofuran derivatives, processes for preparing the same and

[S]-(+)-2-acetyl-7-(2,3-epoxypropoxy)benzofuran (SEBF) is prepared by subjecting 2-acetyl-7-hydroxybenzofuran and [R]-glycidol to dehydration condensation in an inert organic solvent in the presence of triphenylphosphine and a dialkyl azodicarboxylate. The [S]-(+)-2-acetyl-7-(2,3-epoxypropoxy)benzofuran can be easily converted into [S]-2-acetyl-7-(2-hydroxy-3-isopropylaminopropoxy)benzofuran ([S]-befunolol) or salts thereof which are useful as a .beta.-adrenergic blocking agent, by reacting it with isopropylamine.

Process for preparing optically active

Tetrazolylcoumarin derivatives of the general formula: ##STR1## wherein R is hydrogen atom, an alkyl group, an alkenyl group, an alkoxyalkyl group or phenyl group, n is an integer of 2 to 4, and the R--O--(CH.sub.2).sub.n --O-- group is substituted at any of the 5, 6, 7 and 8 positions of the coumarin ring, and the salts thereof. The compounds are useful as antiallergic agents for preventing and treating allergic diseases.

Tetrazolylcoumarin derivatives and antiallergic compositions containing

Coumarin derivatives of the general formula: ##STR1## wherein R is hydrogen atom, an alkyl group or an alkenyl group, R.sup.1 is hydrogen atom, an alkyl group, an alkenyl group or an alkoxy group, and the OR and R.sup.1 groups each are substituted at any of the 5, 6, 7 and 8 positions of the coumarin ring, and the salt thereof. The compounds are useful as antiallergic agent for preventing and treating allergic diseases.

3-(Tetrazol-5-yl), 4-methyl-8-alkoxy coumarins and anti-allergic

Growing community of inventors

Kyoto, Japan

Jun Nakano