Sankyo Company, Limited

Sankko Company, Limited

Yasuteru Iijima

Hiroyuki Koike

Takeshi Oshima

Masakatsu Kaneko

Mitsuo Yamazaki

Misako Kimura

Yoshinobu Murofushi

Norio Nakamura

Nobuyuki Ohkawa

Masaaki Miyamoto

Yasuhiro Morisawa

Mitsuru Kataoka

Yuichiro Yabe

Tatsuo Kokubu

Kunio Hiwada

Hidekuni Takahagi

Hiroaki Yanagisawa

Sadao Ishihara

Akiko Ando

Takeshi Yamaguchi

Toshiaki Sakamoto

Fumitoshi Asai

Hiroshi Fukumi

Mitsuo Sugiyama

Takuro Kanazaki

Kaori Nakahara

Kazuishi Kubota

Ayako Hara

Yohei Ozeki

Polypeptides having 2',5&#x2032;-oligoadenylate phosphodiesterase activity, antibodies against the polypeptides, polynucleotides coding for the polypeptides, recombinant plasmid DNAs into which the polynucleotides have been inserted, host cells transformed by the recombinant plasmid DNAs, processes for screening for 2&#x2032;,5&#x2032;-oligoadenylate phosphodiesterase activity inhibitor substances, and processes for screening for 2&#x2032;,5&#x2032;-oligoadenylate phosphodiesterase expression regulation inhibitor substances. The polypeptides, polynucleotides and host cells are useful for searching for therapeutic agents for viral infections and tumors.

2', 5&#x2032;-oligoadenylate phosphodiesterase

New griseolic acid derivatives have various groups attached to the sugar part in place of the adenine group of griseolic acid itself. These groups are all purine derivatives or ring-opened purine analogs. The compounds are useful as inhibitors of phosphodiesterases.

Griseolic acid derivatives, their preparation and their use

A compound of the formula (I) is provided ##STR1## wherein A represents a group of the formula: ##STR2## R.sup.1 and R.sup.2 are independently hydrogen, halogen or a group of the formula --OR.sup.9 ; R.sup.9 is hydrogen, alkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl or a hydroxy-protecting group; R.sup.3 and R.sup.4 are independently carbamoyl or carboxy; R.sup.5 and R.sup.6 both represent hydrogen or together represent an extra carbon-carbon bond between the carbon atoms to which they are attached; and Z represents hydrogen or unsubstituted or substituted hydroxy; or a pharmaceutically acceptable salt or ester thereof. The compounds are useful as inhibitors of phosphodiesterases.

Griseolic acid compounds and their use as a phosphodiesterase inhibitor

A method of treating a PAF-mediated pathology or for treating or preventing psoriasis, nephritis, asthma, inflammation or shock by administering an effective amount of a PAF antagonist of the formula ##STR1## wherein R.sup.1 and R.sup.2 are each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5 ; R.sup.5 is an unsubstituted or substituted C.sub.6 -C.sub.14 carbocyclic aryl of an aromatic heterocyclic having from 5 to 14 ring atoms, of which from 1 to 5 are hetero-atoms selected from the group consisting of nitrogen, oxygen and sulfur, the heterocyclic group being unsubstituted or substituted; R.sup.3 is hydrogen, a C.sub.1 -C.sub.6 alkyl, cyano, or --R.sup.5 ; X is oxygen or sulfur; A is a 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B is a C.sub.1 -C.sub.6 alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is an unsubstituted or substituted phenyl group.

Method of treating a PAF-mediated pathology or for treating or

A compound of the formula (I) is provided ##STR1## wherein A represents a group of the formula: ##STR2## R.sup.1 and R.sup.2 are independently hydrogen, halogen or a group of the formula --OR.sup.9 ; R.sup.3 and R.sup.4 are independently carbamoyl or carboxy; R.sup.5 and R.sup.a both represent hydrogen or together represent an extra carbon-carbon bond between the carbon atoms to which they are attached; and R.sup.9 is hydrogen, alkyl, alkysulfonyl, haloalkylsulfonyl, arylsulfonyl or a hydroxy-protecting group; or a pharmaceutically acceptable salt or ester thereof. The compounds are useful as inhibitors of phosphodiesterases.

Griseolic acid derivatives

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur A is 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl: and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity.

N-acryloylpiperazine compounds

A compound of the formula (I) is provided ##STR1## wherein A represents a group of the formula: ##STR2## R.sup.1 and R.sup.2 are independently hydrogen, halogen or a group of the formula --OR.sup.9 ; R.sup.9 is hydrogen, alkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl or a hydroxy-protecting group; R.sup.3 and R.sup.4 are independently carbamoyl or carboxy; R.sup.5 and R.sup.6 both represent hydrogen or together represent an extra carbon-carbon bond between the carbon atoms to which they are attached; and W represents an alkoxy or aralkoxy; or a pharmaceutically acceptable salt or ester thereof. The compounds are useful as inhibitors of phosphodiesterases.

Intermediates for griseolic acid derivatives

Thiazolidinecarboxylic acid amides having combined antiallergic and antiasthmatic activities with an antagonist activity against platelet Activating Factor and having the following general formula (I) ##STR1##

Thiazolidinecarboxylic acid amide derivatives and their therapeutic uses

Oligopeptides of formula (I): ##STR1## where R.sup.1 -R.sup.5 are various organic groups, and A represents a group of formula --NH-- or --(CH.sub.2).sub.n --, in which n represents an integer of from 1 to 3, have renin-inhibitory activity and are particularly suitable for oral administration. They may be prepared by condensing their component amino acids or lower oligopeptides using conventional peptide synthesis reactions.

New renin-inhibitory oligopeptides, their preparation and their use

Compounds of formula (I): ##STR1## [in which: R.sup.1 is heterocyclic group having 5 or 6 ring atoms, or --NR.sup.7 R.sup.8, where R.sup.7 is alkyl and R.sup.8 is optionally substituted phenyl, optionally substituted phenylalkyl or cycloalkyl; R.sup.2 is optionally substituted phenyl or naphthyl; R.sup.3 is thiazolyl; R.sup.4 is cyclohexyl or isopropyl; R.sup.5 is alkyl; and R.sup.6 is alkyl] and salts thereof have renin-inhibitory and, hence, hypotensive activities and are of value in the diagnosis and treatment of hypertension induced by failures in the renin-angiotensin system. They may be prepared by reacting together appropriate amino acids or derivatives thereof.

Peptides having renin inhibitory activity, their preparation and use

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur; A a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity, and may be prepared by reacting a compound containing the homopiperazine part of the molecule with a compound containing the other part of the molecule.

N-acryloylpiperazine derivatives, their preparation and their use of PAF

Compounds of formula (I): ##STR1## A is a carbon-carbon bond or C.sub.1 -C.sub.3 alkylene; B is imino group or C.sub.1 -C.sub.2 alkylene; R.sup.1 is C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, heterocyclic or optionally substituted amino; R.sup.2 is optionally substituted phenyl or optionally substituted naphthyl; R.sup.3 is thiazolyl, isoxazolyl or imidazolyl; R.sup.4 is isopropyl or cyclohexyl; R.sup.5 and R.sup.6 are C.sub.1 -C.sub.4 alkyl, or, together with the carbon atom to which they are attached, C.sub.3 -C.sub.7 cycloalkyl; R.sup.7 is hydrogen, optionally substituted C.sub.1 -C.sub.6 alkyl group; and R.sup.8 is hydrogen or C.sub.1 -C.sub.4 alkyl. These compounds have renin-inhibitory and, hence, hypotensive activities. The invention also provides a method for the treatment or prophylaxis of hypertension induced by failures in the renin-angiotensin system.

Renin-inhibitory oligopeptides, their preparation and use

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur; A is 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity, and may be prepared by reacting a compound containing the piperazine or homopiperazine part of the molecular with a compound containing the other part of the molecule.

N-acryloylpiperazine derivatives, their preparation and their use as PAF

Compounds of formula (I): ##STR1## (wherein A is an alkylene group substituted by an optionally substituted amino or heterocyclic group and optionally interrupted by an oxygen or sulfur atom, R.sup.2 is various organic groups, B is C.sub.1 -C.sub.2 alkylene and Y is sulfur or methylene) and pharmaceutically acceptable salts and esters thereof are valuable hypotensive agents which may be prepared by a condensation reaction of the corresponding compound having an amino group in place of the group A--CH(COOH)--NH--.

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Tokyo, Japan

Yasuteru Iijima