Shionogi Company Limited

Teruo Yamamori

Katsunori Sakai

Kiyoshi Nagata

Hiroshi Harada

Natsuki Ishizuka

Ikuo Adachi

Kunio Hayashi

Motohiko Ueda

Kazuki Matsunaga

Kazumi Iwaki

Yoshiharu Hiramatsu

Masami Doteuchi

Hatsuo Sato

Eiichi Oosugi

Compounds having an activity to enhance the expression of apoAI are provided. Compounds of formula (I): in which Arand Arare independently a phenyl, naphthyl, or monocyclic or bicyclic aromatic heterocyclic group, which may be optionally substituted; &#x2014;X&#x2014; is &#x2014;N&#x2550;CZ&#x2014;, &#x2014;CY&#x2550;CZ&#x2014;, &#x2014;CYY&#x2014;CHZ&#x2014;, &#x2014;S&#x2014;, &#x2014;O&#x2014;, or the like; Y, Y, Y, Zand Zare independently a hydrogen, a halogen, a lower alkyl, a phenyl, or the like; Zand Zmay be independently a linker group that may combine with Arand Arto form a condensed ring; m is 0 or 1, and n is 0 to 2; a prodrug thereof, a pharmaceutically acceptable salt or solvate thereof; are disclosed.

Method of enhancing the expression of apolipoprotein AI using olefin derivatives

Compounds having an activity to enhance the expression of apoAI are provided, which are used as medicaments. Compounds of formula (I): in which ring A and Arare independently a monocyclic or bicyclic aromatic carbocyclic group or aromatic heterocyclic group, each of which may be optionally substituted, or the like; R is a hydrogen or the like; Z is oxygen or the like; Yand Yare a hydrogen, a lower alkyl, or the like; n is an integer of 0 to 2; the broken line is the presence or absence of a bond; and the wavy line represents a cis- or trans-geometrical isomerism with respect to the double bond; are disclosed.

Utilities of amide compounds

Utilities of olefin derivatives

Process for stereoselectivity preparing a cis-form of 5-(aminoalkylamino)-1,5-benzothiazepine derivative represented by formula (VI): ##STR1## is provided, said process comprising carrying out a stereoselective addition reaction of an o-(aminoalkylamino) thiophenyl derivative with a trans-substituted glycidic ester at an elevated temperature in a nonpolar solvent in the presence of a divalent or trivalent iron ion to prepare a threo-form intermediate, hydrolyzing the ester group of said intermediate, acetylating the hydroxyl group of said hydrolyzed compound, and subjecting said acetylated compound to a ring closure reaction to obtain the objective compound (VI).

Process for preparing benzothiazepine derivatives

A compound of the formula: ##STR1## wherein X is .dbd.N--A--R.sup.1 or .dbd.C(R.sup.1)R.sup.2 ; A is a single bond, polymethylerie or --CO--; R.sup.1 and R.sup.2 are each hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, unsubstituted or substituted phenyl, optionally substituted benzhydryl, or optionally substituted 5 to 6 membered heterocyclic group; Y is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.1-6 alkoxy, optionally substituted phenoxy, optionally substituted benzyloxy, or optionally substituted benzyl; Z is hydrogen or acyl; n is an integer of from 2 to 6, and pharmaceutically acceptable salt thereof. A pharmaceutical composition containing the compound, which is useful for treating hypertension and cardiac diseases, is also provided.

Benzothiazepine derivatives

A compound of the formula: ##STR1## wherein X is .dbd.N--A--R.sup.1 or .dbd.C(R.sup.1)R.sup.2 ; A is a single bond, polymethylene or --CO--; R.sup.1 and R.sup.2 are each hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, unsubstituted or substituted phenyl, optionally substituted benzhydryl, or optionally substituted 5 to 6 membered heterocyclic group; Y is hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, optionally substituted phenoxy, optionally substituted benzyloxy, or optionally substituted benzyl; Z is hydrogen or acyl; n is an integer of from 2 to 6, and pharmaceutically acceptable salt thereof. A pharmaceutical composition containing the compound, which is useful for treating hypertension and cardiac diseases, is also provided.

Novel Ca-blockers, 4,7-dihydropyrazolo[3,4-b]pyridine derivatives having potent antihypertensive and coronary vasodilating actions and useful in treatment for diseases in circulatory system, but without systole inhibitory action.

4,7-dihydropyrazolo(3,4-b) pyridine derivatives

1,6-Dialkyl-3-substituted-4-nitrophenyl-4,7-dihydropyrazolo[3,4-b]pyridine- 5-carboxylic acid esters as Ca blocker having potent antihypertensive and coronary vasodilating actions and useful in treatment of diseases in circulatory system such as angina pectoris, hypertension, cerebrovascular dysfunction, arrhythmia, etc. with no systole inhibitory action, prepared from nitrobenzylideneacetoacetic acid esters on reaction with 3-substituted-5-amino-1-alkylpyrazoles.

1,6-Dialkyl-3-su

Lower alkyl 2-chloro-2-hydroxyiminoacetates are produced by (A) reacting chloral with a lower alkanol and a hydroxylamine salt in the presence of a Lewis acid or a metal oxide which is convertible into said Lewis acid during the course of the reaction to give a lower alkyl 2-hydroxyiminoacetate and then chlorinating the resulting product or (B) reacting chloral oxime with a lower alkanol in the presence of a base to give a lower alkyl 2-hydroxyiminoacetate and finally chlorinating the thus formed product.

Growing community of inventors

Takarazuka, Japan

Teruo Yamamori