Nissan Chemical Industries Limited

Kiyotomo Seto

Ryozo Sakoda

Hiroo Matsumoto

Yoshimasa Kamikawaji

Kazuhiko Ohrai

Yukinori Masuda

Sakuya Tanaka

Norimasa Shudo

Shin-ichi Akiyama

Isao Hashiba

Toru Yamashita

Masami Kozawa

Keisuke Ohdoi

Kyoko Nakayama

Method for optical resolution of piperidine carboxylic acid derivative

Medicines for cardiac insufficiency

An agent for enhancing the drug effects of an antitumor drug, which comprises a compound of the formula I: ##STR1## or a pharmaceutically acceptable salt of the compound.

Phosphorus pyridine compound

A process for the optical resolution of a pyranobenzoxadiazole compound represented by the formula [(.+-.)I]: ##STR1## which comprises reacting the compound [(.+-.)I] with an optically active carboxylic acid represented by the formula [II]: ##STR2## and separating the diastereomeric salt thus formed is disclosed.

Process for the optical resolution of pyranobenzoxadiazole compounds

Compounds of the formula (I): ##STR1## in which the nitrogen-containing hetero ring portion is 1,4-dihydropyridine ring or a pyridine ring, R.sup.1 is only present when the nitrogen-containing hetero ring is a 1,4-dihydropyridine ring, and Z is a group of the formula (II): ##STR2## in which R.sup.4 and R.sup.5 may be the same or different and together may form one divalent group, are effective agents for enhancing the antitumor effect of antitumor drugs.

Drug effect-enhancing agent for antitumor drug

A compound of the formula (I): ##STR1## wherein X.sup.1 and X.sup.2 do not exist or represent oxygen atom; A represents OH or acyloxy group having 1 to 4 carbon atoms; B represents hydrogen atom; A and B together represent a bond; R.sup.1 and R.sup.2 represent hydrogen atom or alkyl group having 1 to 4 carbon atoms, or R.sup.1 and R.sup.2 together represent 1,2-ethylene, 1,3-propylene, 1,4-butylene or 1,5-pentylene, and these alkylene groups may be substituted by alkyl group having 1 to 4 carbon atoms; R.sup.3 represents amido group of the formula: ##STR2## wherein n, R.sup.4, R.sup.5, R.sup.6, R.sup.7. R.sup.8. R.sup.9, R.sup.10 and R.sup.11 represent specific groups, and the pharmacological acceptable salts of the compounds which can form salts have strong activity for lowering blood pressure, and process therefor and pharmaceutical use of the compounds.

Pyranobenzoxadiazole derivatives

A hydrazine derivative having the formula: ##STR1## wherein R is a hydrogen atom or ##STR2##

Hydrazine derivatives useful as intermediates in the synthesis of

Compounds of the formula (I): ##STR1## in which the nitrogen-containing hetero ring portion is a 1,4-dihydropyridine ring or a pyridine ring, R.sup.1 is only present when the nitrogen-containing hetero ring is a 1,4-dihydropyridine ring, and Z is either a CO.sub.2 R.sup.8 group or a group of the formula (II): ##STR2## in which R.sup.4 and R.sup.5 may be the same or different and together may form one divalent group, are effective agents for enhancing the antitumor effect or antitumor drugs.

A compounds of the formula (I): ##STR1## wherein A represents OH or OC(O)CH.sub.3-n X.sub.n, B represents hydrogen atom, or A and B together represent a bond; R.sup.1 represents hydrogen atom, R.sup.2 represents hydrogen atom, C(Z)CH.sub.3-n X.sub.n or C(Z)NHCH.sub.3-n X.sub.n or R.sup.1 and R.sup.2 together represents (CH.sub.2).sub.m, (CH.sub.2).sub.m-1 C(Z), N(R.sup.3)(CH.sub.2).sub.2 C(Z), (CH.sub.2).sub.m-2 NHC(Z) or (CH.sub.2).sub.m-2 OC(Z) in which X represents fluorine atom, chlorine atom, bromine atom, a methyl group or a methoxy group and n represents 0 or an integer of 1 to 3, Z represents oxygem atom or sulfur atom, m represents an integer of 4 or 5 and R.sup.3 represents hydrogen atom or a methyl group, and pharmacological acceptable salts of the compounds which can form salts, processes therefor and pharmaceutical use of the compounds.

A compound of the formula: ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 which may be the same or different, is hydrogen or C.sub.1 -C.sub.4 alkyl; one of X.sup.1 and X.sup.2 is nitro, fluroine, chlorine, difluoromethyoxy or trifluoromethyl and the other is hydrogen, or both of X.sup.1 and X.sup.2 are chlorine; and Y is ##STR2## wherein A is C.sub. -C.sub.6 alkylene, each of Ar.sup.1 and Ar.sup.2 which may be the same or different, is phenyl which may be substituted by chlorine, fluorine or C.sub.1 -C.sub.3 alkoxy, and m is an integer of from 0 to 4, or Y is ##STR3## wherein A, Ar.sup.1 and Ar.sup.2 are as defined above when that both X.sup.1 and X.sup.2 are chlorine; or a pharmaceutically acceptable salt thereof.

Dihydropyridine-5-phosphonic acid cyclic propylene ester

A process for producing an .alpha.-(benzylidene)acetonylphosphonate of the formula: ##STR1## wherein Ar is phenyl substituted by at least one substituent selected from the group consisting of fluorine, chlorine, bromine, nitro, chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, --CO.sub.2 R.sup.7 wherein R.sup.7 is C.sub.1 -C.sub.5 alkyl, --CONR.sup.7 R.sup.8 wherein R.sup.7 is as defined above and R.sup.8 is C.sub.1 -C.sub.5 alkyl, --C(O)R.sup.7 wherein R.sup.7 is as defined above, --OC(O)R.sup.7 wherein R.sup.7 is as defined above, --OSO.sub.3 R.sup.7 wherein R.sup.7 is as defined above, --OCF.sub.3, --S(.dbd.O).sub.2 R.sup.7 wherein R.sup.7 is as defined above, --CN and --SO.sub.3 R.sup.7 wherein R.sup.7 is as defined above, and each of R.sup.1 and R.sup.2 which may be the same or different is a saturated or unsaturated C.sub.1 -C.sub.12 aliphatic group, or R.sup.1 and R.sup.2 together form 1,2-ethylene, 1,3-propylene or 1,4-butylene, which is unsubstituted or substituted by from one to four C.sub.1 -C.sub.3 alkyl groups, which comprises: (a) reacting an aldehyde of the formula:

Process for producing alpha-(benzylidene)acetonylphosphonates

An optical isomer of a compound having the formula: ##STR1## wherein the two methyl groups at 4- and 6-positions of the dioxaphosphorinane ring assume trans configurations to each other, which has a levo-rotatory angle of optical rotation attributable to the asymmetric carbon atom at 4-position of the dihydropyridine ring, and a pharmaceutically acceptable salt thereof.

Dihydropyridine-5-phosphonic acid cyclic ester

A compound of the formula: ##STR1## where X is hydrogen, nitro, trifluoromethyl, fluorine, chlorine, bromine or iodine; A is 1,3-propylene or 1,4-butylene which may be substituted by C.sub.1 -C.sub.3 alkyl, R is C.sub.1 -C.sub.4 alkyl, --Y--N(R.sup.1)(R.sup.2) or ##STR2## where each of R.sup.1, R.sup.2 and R.sup.3, which may be the same or different are hydrogen, C.sub.1 -C.sub.6 alkyl, or aralkyl, and Y is C.sub.2 -C.sub.6 alkylene, and Me is methyl, or its pharmaceutically acceptable salt. These compounds have utility as anti-hypertensive agents and coronary or peripheral vasodilators.

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Funabashi, Japan

Kiyotomo Seto