Eisai Company, Limited

Kazutoshi Miyake

Norio Minami

Motosuke Yamanaka

Hitoshi Oinuma

Yoshiharu Daiku

Kenichi Nomoto

Naoki Yoneda

Tadao Shoji

Tomonori Hoshiko

Shigeru Souda

Masayuki Matsukura

Kohei Sawada

Shinji Suda

Toshiaki Ogawa

Toshiyuki Matsuoka

Hiroki Ishihara

Hideyuki Adachi

Nobuyuki Mori

Masanori Mizuno

Hideto Ohhara

Sachiyuki Hamano

Makoto Kotake

Mamoru Saito

Takashi Musha

Osamu Hiroshima

Masayuki Namiki

Takeshi Sudo

Shigeto Negi

Fumihiro Ozaki

Makoto Okita

Nobuhisa Watanabe

Yasuhiro Akiyama

Kazuki Miyazaki

Tomohiro Matsushima

Yasuhiro Kabasawa

Keiji Ishibashi

Yasutaka Takase

Yoshio Fukuda

Noriyasu Hirose

Makoto Kaino

Hidetoshi Kawashima

Shizuo Kuriyama

Tadanobu Takamura

Kohtaro Kodama

Naoya Kishi

Koichi Nose

Fusayo Yoshida

Keizoh Satoh

Mikio Tomimatsu

Kazuyasu Usuki

Kenji Hayashi

Naoko Nagaoka

Naoko Sakabe

Motosuki Yamanaka

Fused pyridazine compounds

The present invention relates to a substituted thiazolo[3,2-a] azepine derivative having inhibitory activity against angiotensin I converting enzyme and neutral endpeptidase and is represented by the following general formula (I): ##STR1##

Substituted thiazolo[3,2-a]azepine derivatives

Substituted thiazolo �3,2-a!azepine derivatives

The present invention relates to an amino acid derivative having an angiotensin I-converting enzyme inhibition activity, a vasopressin antagonism and an atrial natriuretic peptide hydrolase inhibition activity. This amino acid derivative is represented by the following general formula (I): ##STR1## wherein R.sup.1 represents a hydrogen atom or an acyl group; R.sup.2 represents a hydrogen atom, a lower alkyl group, a cycloalkyl group, an ary group which may have a substituent, a heteroaryl group which may have a substituent, an arylalkyl group which may have a substituent or a heteroarylalkyl group which may have a substituent;

Amino acid derivative

Propenoic acid derivatives of the formula: ##STR1## where R.sup.15 and R.sup.17 are aryl or heteroalkyl groups and R.sup.16 and R.sup.18 are hydrogen, a lower alkyl or the like are intermediates used to prepare pharmaceutically active diazole propenoic acid compounds.

Diazole-propenoic acid compounds

A novel propenoic acid derivative which exhibits adenosine A1 antagonism is defined by the general formula (I): ##STR1## (wherein A represents an aromatic ring; R.sup.1 represents aryl or the like; R.sup.2, R.sup.3 and R.sup.4 each represent hydrogen, lower alkyl or the like; and R.sup.7 and R.sup.8 each represent lower alkyl or the like) or a pharmacologically acceptable salt thereof.

Propenoic acid derivatives diazole propenoic acid compounds which have

The biphenylmethane derivative having the formula (I) is useful to prevent and treat hypertension and cardiac failure. ##STR1## in which R1 is hydrogen, an alkyl, a cycloalkyl, a halogenated alkyl, --S--R7, --SO2--R7, --C.tbd.C--R7 or --(CH2)p--OR7, R7 being hydrogen, an alkyl, a cycloalkyl or a halogenated alkyl, p being zero or 1, --A1=A2--A3=A4-- is --CH=CH--CH=CH--, --N=CH--CH=CH--, --CH=N--CH=CH--, --CH=CH--N=CH--, --CH=CH--CH=N-- or --CH=N--CH=N--, R2 and R3 are each hydrogen, a halogen, a lower alkyl, a lower alkoxy, a carbamoyl or cyano, R4 is hydrogen or a lower alkyl, R5 is 1H-tetrazol-5-yl, carboxyl (--COOH) or a carboxylic ester and R6 is hydrogen, a halogen, hydroxyl or a lower alkoxy, or a pharmacologically acceptable salt thereof.

Biphenylmethane derivative and pharmacological use

The biphenylmethane derivative having the formula (I) is useful to prevent and treat hypertension and cardiac failure. ##STR1## in which R1 is hydrogen, an alkyl, a cycloalkyl, a halogenated alkyl, --S--R7, --SO2--R7, --C.tbd.C--R7 or --(CH2)p--OR7, R7 being hydrogen, an alkyl, a cycloalkyl or a halogenated alkyl, p being zero or 1, --A1.dbd.A2--A3.dbd.A4-- is --CH.dbd.CH--CH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--, --CH.dbd.N--CH.dbd.CH--, --CH.dbd.CH--N.dbd.CH--, --CH.dbd.CH--CH.dbd.N-- or --CH.dbd.N--CH.dbd.N--, R2 and R3 are each hydrogen, a halogen, a lower alkyl, a lower alkoxy, a carbamoyl or cyano, R4 is hydrogen or a lower alkyl, R5 is 1H-tetrazol-5-yl, carboxyl (--COOH) or a carboxylic ester and R6 is hydrogen, a halogen, hydroxyl or a lower alkoxy, or a pharmacologically acceptable salt thereof.

The biphenylmethane derivative having the formula (I) is useful to prevent and treat hypertension and cardiac failure. ##STR1## in which R1 is hydrogen, an alkyl, a cycloalkyl, a halogenated alkyl, --S--R7, --SO2--R7, --C.tbd.C--R7 or --(CH2)--OR7, R7 being hydrogen, an alkyl, a cycloalkyl or a halogenated alkyl, p being zero or 1, --A1.dbd.A2--A3.dbd.A4-- is CH.dbd.CH--CH.dbd.CH--, --N.dbd.CH--CH.dbd.CH--, --CH.dbd.N--CH.dbd.CH--, --CH.dbd.CH--N.dbd.CH--, --CH.dbd.CH--CH.dbd.N-- or --CH.dbd.N--CH.dbd.N--, R2 and R3 are each hydrogen, a halogen, a lower alkyl, a lower alkoxy, a carbamoyl or cyano, R4 is hydrogen or a lower alkyl, R5 is 1H-tetrazol-5-yl, carboxyl (--COOH) or a carboxylic ester and R6 is hydrogen, a halogen, hydroxyl or a lower alkoxy, or a pharmacologically acceptable salt thereof.

A piperidine compound has the generic formula and is useful to treat arrhythmia. ##STR1## in which R1 is a lower alkyl and W is: ##STR2## X is --S--, --SO-- or --SO2--, R2 is hydrogen or --(CH2)n--Y, n is an integer of 1 to 5, Y is an aryl, pyridyl or a substituted pyridyl, X' is --CO-- or --CH(OH)--,

Piperidine derivatives and therapeutic and preventive agents for

A new piperidine compound is pharmacologically effective for treatment of the arrythmia and is defined by the formula: ##STR1## in which R.sup.1 is a lower alkyl or a tolyl, R.sup.2 is hydrogen, hydroxyl, a lower alkoxy or a lower alkyl, R.sup.3 is hydrogen, a lower alkyl, a lower alkenyl, a cycloalkyl or a cycloalkylalkyl, X is --CO--, --CH.sup.2 -- or --CHOH--, g is an integer of 1 to 3, h is an integer of 1 to 3, Y is hydrogen, a lower alkyl, a lower alkenyl, cyano, CH.sup.2 COOR, R being hydrogen or a lower alkyl, a cycloalkyl, a cycloalkylalkyl, ##STR2## 1 being 1 or 2, --A--B, A being --(CH.sub.2).sub.n --, n being an integer of 1 to 5,

Piperidine derivative and pharmaceutical composition containing the same

A new piperidine compound is pharmacologically effective for treatment of arrythmia and has the formula: ##STR1## in which R.sup.1 is lower alkyl or tolyl; R.sup.2 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl or cycloalkylalkyl; X is --CO--, --CH.sub.2 -- or --CHOH--; the sum of g plus h equals the integer 3 or 4 with g and h being 1, 2 or 3; A is substituted or unsubstituted alkylene, alkenylene, --(CH.sub.2).sub.k --S--, wherein k is an integer of 2 to 5, or --(CH.sub.2).sub.p CO--, wherein p is an integer of 1 to 4; and B is a compound having at least one heterocyclic ring containing a nitrogen atom.

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Ushiku, Japan

Kazutoshi Miyake