Sankyo Company, Limited

Daiichi Sankyo Company, Limited

Takahide Nishi

Futoshi Nara

Takaichi Shimozato

Takeshi Yamaguchi

Shojiro Miyazaki

Toshiyasu Takemoto

Akira Yoshida

Hiroo Koyama

Koichi Hirai

Kozo Oda

Yuji Iwano

Katsuyoshi Nakajima

Hitoshi Kurata

Koki Ishibashi

Tetsuya Fukazawa

Kazuhiro Ito

Takashi Fujita

Kiyoshi Morimoto

Takao Yoshioka

Yuichi Aizawa

Hiroyoshi Horikoshi

Tsuyoshi Nakamura

Kunio Wada

Takuya Ikeda

Tsutomu Kanai

Takashi Kagari

Yukiko Sekiguchi

Takashi Izumi

Yukiko Iio

Yumiko Mizuno

Hiromi Doi

A method for treating an immunology-related disease. The method involves administering to a mammal in need thereof a pharmaceutically effective amount of an amino acid compound, a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof. The compound has the following formula: wherein Rand Rare each hydrogen; Ris hydrogen; Ris C-Calkyl; n is 2; X is &#x2550;N-D, wherein D is hydrogen, C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CHor phenylene; Z is ethylene or trimethylene; Ris unsubstituted C-Ccycloalkyl, unsubstituted C-Caryl, or C-Ccycloalkyl or C-Caryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and Rand Rare each hydrogen.

Method for treating a immunology-related disease

A compound having a formula II(a): wherein Rand Rare hydrogen lower alkyl, lower aliphatic acyl, or lower alkoxycarbonyl; Ris C-Calkyl; n is 2 or 3; X is a formula &#x2550;N-D, wherein D is hydrogen, C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CH&#x2014;, &#x2014;CH(OH)&#x2014;CH&#x2014; or phenylene; Z is C-Calkylene; Ris C-Ccycloalkyl or C-Caryl; Rand Rare hydrogen, lower alkyl, halogeno lower alkyl, lower alkoxy or lower alkylthio; and Rand Rare hydrogen or lower alkyl.

Amino alcohol compounds or phosphonic acid derivatives thereof

A method for suppressing the number of peripheral blood lymphocytes involving administering to a human in need thereof a pharmaceutically effective amount of a compound which is (2R) -2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol or a pharmacologically acceptable salt thereof, such as the hydrochloride salt.

Method for suppressing the number of peripheral blood lymphocytes using an amino alcohol compound

A compound having immunosuppressive activity with low toxicity or a pharmacological salt thereof. The compound has a general formula (I) shown below or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable prodrug thereof 

Heterocyclic compound

A method for the prevention or treatment of an immunology-related disease, which is not rheumatoid arthritis or psoriasis, in a mammal in need thereof which involves administering to the mammal a pharmaceutically effective amount of a compound, a pharmacologically acceptable salt of the compound or a pharmacologically acceptable ester of the compound, wherein the compound is a compound having a formula (Ia): wherein Rand Rare each a hydrogen, Ris hydrogen; Ris C-Calkyl; n is 2; X is &#x2550;N&#x2014;D, wherein D is hydrogen C-Calkyl or phenyl; Y is ethylene, ethynylene, &#x2014;CO&#x2014;CHor phenylene; Z is ethylene or trimethylene; Ris an unsubstituted C-Ccycloalkyl, an unsubstituted C-Caryl, or a C-Ccycloalkyl or a C-Caryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and Rand Rare each hydrogen.

The present invention provides a compound having the following general formula (I) which is useful as a neurokinin receptor antagonist: (wherein,

Indanol derivative

Amino alcohol compounds and phosphonic acid compounds having excellent immunosuppressive activity, pharmacologically acceptable salts thereof and pharmacologically acceptable esters thereof, and pharmaceutical compositions comprising such compounds, the compounds having the following formula: wherein Rand Reach represent hydrogen, or a protecting group of the amino group; Rrepresents hydrogen, or a protecting group of the hydroxyl group; Rrepresents a lower alkyl group; n is 1 to 6; X represents oxygen or nitrogen, which is unsubstituted or substituted with a lower alkyl group; Y represents ethylene; Z represents a C&#x2013;Calkylene; Rrepresents an aryl group; and Rand Reach represents hydrogen; provided that when Rrepresents hydrogen, then Z represents a group other than a single bond or a straight chain C&#x2013;Calkylene group.

Amino alcohol compounds

Compounds of formula (I) which exhibit excellent immune suppression activity, pharmacologically acceptable salts thereof, esters thereof or other derivatives:wherein Rand Rare a hydrogen atom, an amino protecting group; Ris a hydrogen atom, a hydroxy protecting group; Ris a lower alkyl group; n is an integer from 1 to 6; X is an ethylene group; Y is a C-Calkylene group, a C-Calkylene group substituted with 1 to 3 substituents selected from substituent group a and b; Ris an aryl group; Rand Rare a hydrogen atom, a group selected from substituent group a; with the proviso when Ris a hydrogen atom, Y is not a single bond or a straight chain C-Calkylene group.

Amino alcohol derivatives

Spiropiperidine derivatives

Method for treating an inflammatory disease

Hydrochloride of fumarate of 1-&lcub;2-&lsqb;(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethyoxybenzoyl)morpholin-2-yl&rsqb;ethyl&rcub;spiro&lsqb;benzo(c)thiophene-1(3H),4&prime;-piperidin&rsqb;-(2S)-oxide. These compounds have good oral adsorption and exhibit markedly excellent antagonistic action against both NK receptors and NK receptors. These compounds are useful as an active ingredient in pharmaceutical compositions for administering to patients for treatment of tachykinin-medicated diseases.

Salts of an optically-active sulfoxide derivative

A compound of formula (I), a pharmaceutically acceptable salt or ester or other derivative thereof:

Acylated hetero-alicyclic derivatives

Compounds of the formula and quaternary ammonium ions thereof, wherein R.sup.1 and R.sup.2 are the same or different and are carbocyclic aryl or aromatic heterocyclic; A is methylene, carbonyl or sulfonyl; B is a single bond, C.sub.1 -C.sub.4 alkylene or C.sub.2 -C.sub.4, alkenylene; D is oxygen; E is C.sub.2 alkylene; G is C.sub.1 -C.sub.4 alkylene or C.sub.2 -C.sub.4 alkenylene; and L is --C(R.sup.4)(R.sup.5), wherein R.sup.4 and R.sup.5 together with the carbon atom to which they are attached represent a C.sub.5 -C.sub.10 cycloalkyl or a C.sub.5 -C.sub.10 heterocyclic. Especially preferred are compounds wherein L represents ##STR1## wherein J is a C.sub.1 -C.sub.6 alkylene; Ar is a ring carbocyclic or aromatic heterocyclic and S*.fwdarw.O is a sulfoxide in which the sulfur atom is in the 5-configuration. The compounds have tachykinin receptor antagonist activity and exhibit an activity against both the NK.sub.1 and NK.sub.2 receptors.

Heterocyclic compounds having tachykinin receptor antagonist activity

A method for preparing compounds of formula (I): ##STR1## wherein: R.sup.1 is hydrogen or a hydroxy-protecting group; R.sup.2 is alkyl, alkoxy, halogen, optionally substituted phenyl or optionally substituted phenoxy; R.sup.3 is optionally substituted pyridyl, optionally substituted quinolyl or phenyl group which has a substituent of formula --CYNR.sup.5 R.sup.6, where Y is oxygen or sulfur, and R.sup.5 and R.sup.6 are each alkyl, aryl or aralkyl, or R.sup.5 and R.sup.6 and the nitrogen to which they are attached together form a heterocyclic group; R.sup.4 is hydrogen or an amino-protecting group; and Z is sulfur or oxygen. The process comprises reacting a compound of formula (II): ##STR2## in which R.sup.8, R.sup.9 and R.sup.10 are the same or different and each represents an alkyl group having from 1 to 4 carbon atoms or a phenyl group, with a compound of formula (III): ##STR3## in which R.sup.11 represents an acyloxy, alkylsulfonyl, arylsulfonyl, alkylsulfinyl or arylsulfinyl group.

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Tokyo, Japan

Takahide Nishi