Yoshitomi Pharmaceutical Industries, Ltd.

Hiroyuki Kitani

Minoru Moriwaki

Michio Terasawa

Hirotsugu Komatsu

Syuji Ehara

Syuji Yuasa

Mariko Amano

N-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno �3,2-f!�1,2,4!triazolo�4,3-a!�1,4!diazepin-6-yl )-N'- (2-methoxyphenyl)urea, optical isomers thereof and pharmaceutically acceptable salts thereof. The compounds of the present invention strongly and selectively inhibit the expression of VCAM-1 and have an inhibitory effect on leukocyte adhesion to vascular endothelial cells. Accordingly, the compounds of the present invention can be used as cell adhesion inhibitors for prophylaxis or treatment of various diseases in which cell adhesion is involved in the onset and progress thereof.

Thienotriazolodiazepine compound and pharmaceutical use thereof

Stable crystals of an acid addition salt of an optically active thienotriazolodiazepine compound or its hydrate of the formula ##STR1## wherein R.sup.1 is hydrogen, R.sup.2 is 2-phenylethyl substituted by alkyl having 1 to 5 carbon atoms, 2-morpholinocarbonylethyl or alkyl having 6 to 12 carbon atoms, or R.sup.1 and R.sup.2 may combinedly form a saturated 5-membered ring having one substituent selected from the group consisting of morpholinomethyl, morpholinocarbonyl and N,N-dipropylcarbamoyl, R.sup.3 is halogen, alkyl having 1 to 5 carbon atoms or alkoxy having 1 to 5 carbon atoms, R.sup.4 is trifluoromethyl or alkyl having 1 to 5 carbon atoms, R.sup.5 is hydrogen or methyl, m is 1-2, and n is 0-2. The present invention provides optically active thienotriazolodiazepine compounds having strong PAF-antagonistic activity as markedly stable crystals which are excellent in crystalline property, permit purification by recrystallization, and have high chemical purity and optical purity, thereby rendering industrial large-scale synthesis attainable. In addition, crystallization thereof facilitates medicinal standardization and pharmaceutical formulation.

Optically active thienotriazolodiazepine compounds

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Oita, Japan

Hiroyuki Kitani