Mitsubishi Kasei Corporation

Mitsubishi Chemical Corporation

Mitsubishi Yuka Pharmaceutical Co., Ltd.

Mitsubishi Chemical Industries Limited

Yasuhiro Morinaka

Yoshikuni Tamao

Hisao Takayanagi

Yasunori Kitano

Akihiro Tobe

Ryoichi Ando

Chizuko Takahashi

Hiroyoshi Nishi

Toshiaki Watanabe

Naoko Ando

Yoshio Hayashi

Hiroko Sakurai

Nobuko Fukushima

Satoshi Yuki

Mamoru Sugano

Toshiji Kanayama

Norimichi Iwase

Tomoko Bessho

Hirokazu Masuda

Kazuo Takahashi

Kunihiro Ninomiya, Deceased

Haruko Harada

Ken-ichi Saito

Haruyuki Chaki

Katsuhiko Iseki

Ken-Ichi Saito

Tomoko Yugami

Rie Yoshida

Eiichi Nakamura

Toshiro Sasaki

Toshiro Sakaki

Masaki Shinoda

Koichi Sugawara

Masahiro Ohshima

Misao Okitsu

Kumi Yamada

Shigeo Sugiyama

Tomei Oguri

Shuichiro Kadowaki

Kazutoshi Watanabe

Ken-ichi Sato

A novel 4-acylaminopyridine derivative represented by the following formula (I) is disclosed. ##STR1## The 4-acylaminopyridine derivative of the present invention is useful as a medicine for treating disturbances of memory such as senile dementia and Alzheimer's disease, since it has an action of directly activating malfunctioned cholinergic neuron.

4-Acylaminopyridine derivative

A novel ketone derivative (I) which possesses a potent inhibitory activity against thiol protease such as papain, cathepsin B, cathepsin H, cathepsin L, calpain or the like with excellent properties regarding oral absorbance, tissue transference and cell membrane permeability, and are clinically useful in the treatment of various diseases such as muscular dystrophy, amyotrophy. Also provided are a process for producing the compound (I) and a pharmaceutical composition containing the same.

Ketone derivatives

Sialic acid derivatives represented by the general formula (I): wherein

Sialic acid derivatives

A prolineamide derivative represented by the formula (I): ##STR1## or a salt or hydrate thereof or a pharmaceutically acceptable salt thereof, which has a protease inhibition activity and is useful as an active ingredient of pharmaceutical compositions is provided.

Prolineamide derivatives

Sialic acid derivatives represented by the general formula (I): ##STR1## wherein R.sup.1 is a steroidal compound residue; R.sup.2 is H or alkyl; R.sup.3 is alkyl; ##STR2## wherein each of R.sup.6 and R.sup.7 is H, alkyl or the like and I is an integer of 0 to 6; or the like; X is O or S; R.sup.4 is H or acyl; and R.sup.5 is R.sup.14 O-- (R.sup.14 is H or acyl) or R.sup.15 NH--(R.sup.15 is acyl or the like); their salts, hydrates or solvates are provided. Sialic acid derivatives of the present invention are expected to be effective medicines for the prevention and therapy of senile dementia including Alzheimer's disease and the like, because they increase ChAT activity in cholinergic neurons.

4-acylaminopyridine derivative

A 3,6-disubstituted pyridazine derivative having excellent platelet agglutination inhibitory effects. It is useful for a preventive medicine or a therapeutic medicine for a cerebrovascular disorder such as cerebral thrombosis and cerebral embolism, an ischemic heart disease such as myocardial infarction, and a circulation disorder such as peripheral circulation disorder. A pharmaceutical composition containing a compound of the present invention as an effective ingredient and a process for preparing the same are also disclosed. The compound has the formula (I) ##STR1## wherein A represents an alkyl group having 3 to 6 carbon atoms; a cycloalkyl group having 5 to 7 carbon atoms; a phenyl group, a thienyl group, a furyl group, a thiazolyl group, a phenoxy group, a phenylalkyl group having 7 to 9 carbon atoms, a phenylthio group, a 5-6 membered saturated heterocyclic group containing one or more nitrogen atoms, a pyridyl group or an imidazolyl group each of which may have at least one substituent selected from the group consisting of an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms and a halogen atom; B represents (a) --NH--D wherein D represents ##STR2## (4) --CH.sup.3 R.sup.4 ; or (5) an alkyl group having 3 to 8 carbon atoms; or ##STR3## and the ring C represents a benzene ring.

3,6-disubstituted pyradazine derivatives

Aminoketone derivatives according to the present invention strongly inhibit thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L or the like and have excellent properties concerning absorbance on oral administration, tissue distribution and cell membrane permeability. The aminoketone derivatives cart thus be used as therapeutic agents for treating muscular dystrophy, cataract, cardiac infarction, stroke, Alzheimer's disease, amyotrophy, osteoporosis and hypercalcemia and so on. It may also be used as therapeutic agents for preventing metastasis of cancer. In addition, the present derivatives are also applicable as intermediates for the preparation of ketone derivatives, which have inhibitory activity against thiol protease.

Aminoketone derivatives

Alpha-aminoketone derivatives of the present invention strongly inhibit thiol protease such as papain, cathepsin B, cathepsin H, cathepsin L and calpain or the like and have excellent properties in absorbance on oral administration, tissue distribution and cell membrane permeability. The alpha-aminoketone derivatives can thus be used as therapeutic agents for treating muscular dystrophy, amyotrophy, cardiac infarction, stroke, Alzheimer's disease, disturbance of consciousness or dyskinesia caused upon brain trauma, multiple sclerosis, peripheral nervous neuropathy, cataract, inflammation, allergosis, fulminant hepatitis, osteoporosis, hypercalcemia, breast carcinoma, prostatic carcinoma or prostatomegaly. They may also be used as therapeutic agents for suppressing growth of cancer cells, preventing metastasis of cancer or suppressing aggregation of plaques.

.alpha.-aminoketone derivatives

A novel cyclopropenone derivative (I) which possesses a potent inhibitory activity against thiol protease such as papain, cathepsin B, cathepsin H, cathepsin L, calpain or the like with excellent properties regarding oral absorbance, tissue transference and cell membrane permeability, and are clinically useful in the treatment of various diseases such as muscular dystrophy, amyotrophy. Also provided are a process for producing the compound (I) and a pharmaceutical composition containing the same.

Cyclopropenone derivatives

Novel acyclic terpene compounds useful as intermediates for producing sarcophytol A which have an anti-carcinogenic promotor activity and anti-tumor activity, which compounds are shown by the following general formula (I): ##STR1## [wherein R.sup.1 is a hydrogen atom, 1-alkoxyalkyl group, tetrahydrofuryl group, tetrahydropyranyl group or acyl group; R.sup.2 is a group of formula: --CHO, --CH.sub.2 OR.sup.3 or ##STR2## (wherein R.sup.3 is a hydrogen atom, 1-alkoxyalkyl group, tetrahydrofuryl group, tetrahydropyranyl group or acyl group; and R.sup.4 is C.sub.1 to C.sub.4 alkyl group) with the proviso that R.sup.1 and R.sup.3 do not represent the same substituents simultaneously; when R.sup.1 is a hydrogen atom, R.sup.3 is not acetyl group or tetrahydropyranyl group; and when R.sup.2 is a group of formula: ##STR3## R.sup.1 is not a hydrogen atom).

Acyclic terpene compound

The cyclopropene derivatives of the present invention are useful as the intermediates for producing cyclopropenone derivatives exhibiting strong inhibition activity of thiol protease such as calpain, papain, cathepsin B, cathepsin H, cathepsin L and the like.

Cyclopropene derivatives

Acyclic terpene compounds useful as intermediates for producing sarcophytol A which have an anti-carcinogenic promotor activity and anti-tumor activity, which compounds are shown by the general formula (I): ##STR1##

Substituted-acyclic terpene compound

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Tsuchiura, Japan

Yasuhiro Morinaka