Mitsubishi Chemical Corporation

Mitsubishi Kasei Corporation

Naoko Ando

Yasuhiro Morinaka

Yoshikuni Tamao

Akihiro Tobe

Ryoichi Ando

Chizuko Takahashi

Haruyuki Chaki

Hirokazu Masuda

Tomoko Yugami

Ken-Ichi Saito

Rie Yoshida

Toshiro Sasaki

Tetsuo Jikihara

Ken-ichi Saito

Sialic acid derivatives represented by the following general formula:

Sialic acid derivatives

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 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.

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.

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Machida, Japan

Naoko Ando