Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-06-17
1997-02-18
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514357, 514372, 514403, 514427, 514438, 514459, 514471, 544401, 546246, 546247, 546334, 548214, 5483731, 548516, 549 75, 549426, 549495, 549472, 564336, 564340, 564342, 564346, 564374, 564383, 564454, 564123, C07C21100, C07D33320, A01N 4340, A01N 3302
Patent
active
056042299
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP93/01515 filed Oct. 18, 1993 and published as WO94/08943 Apr. 28, 1994.
TECHNICAL FIELD
The present invention relates to 2-amino-1,3-propanediol compounds useful as pharmaceuticals, particularly as an immunosuppressant.
BACKGROUND ART
In recent years, cyclosporin is in use for suppressing rejection developed in transplanting organs. Inclusive of the compounds currently under development, the so-called immunosuppressants are expected to be useful as therapeutic agents for articular rheumatism and so on. Said cyclosporin, however, also poses problems of side effects such as renal disorders.
Meanwhile, Japanese Patent Unexamined Publication No. 104087/1989 discloses that an immunosuppressive substance is obtained from a liquid culture of Isaria sinclairii and said substance has been confirmed to be (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyl-14-oxoicosa-6-enoic acid of the formula ##STR2## disclosed in U.S. Pat. No. 3928572. In addition, Japanese Patent Unexamined Publication No. 128347/1991 states that a series of said compound has an immunosuppressive action.
Referring to Merck Index, 11th edition, it is described that 2-amino-2-methyl-1,3-propanediol (Index No. 460), 2-amino-2-ethyl-1,3-propanediol (Index No. 451) and 2-amino-2-hydroxymethyl-1,3-propanediol (also called tromethamine, Index No. 9684) can be used as surfactants, intermediates for pharmaceuticals, emulsifiers or gas adsorbents and that tromethamine is medically usable as an alkalization agent. In Japanese Patent Unexamined Publication No. 416/1987, a hair dye containing 2-amino-2-(C1-C5 alkyl)-1,3-propanediol is disclosed. U.S. Pat. No. 4,910,218 and J. Med. Chem., vol. 33, 2385-2393 (1990) teach 2-amino-2-(methyl or ethyl)-1,3-propanediol as an intermediate for an antitumor agent. Also, Japanese Patent Unexamined Publication No. 192962/1984 teaches that the aforementioned 2-amino-2-(C1-C5 alkyl)-1,3-propanediol or 2-amino-1,3-propanediol can be used as a stabilizer for an antigen or antibody-sensitized latex reagent. Moreover, U.S. Pat. No. 3,062,839 teaches 2-methyl- or ethyl-amino-2-(furylmethyl, phenylmethyl or phenylmethyl substituted by lower alkyl, lower alkoxy, chloro, hydroxy or unsubstituted amine)-1,3-propanediol having a tranquilizer action and J. Org. Chem., vol. 25, 2057-2059 (1960) teaches 2-methylamino-2-(phenylmethyl or phenylmethyl substituted by 2-methyl, 3-methyl, 4-methyl, 4-methoxy or 4-hydroxy)-1,3-propanediol. It is not known, however, that these compounds have immunosuppressive actions such as suppression of rejection developed in organ transplantation, prevention and treatment of autoimmune diseases and the like.
An object of the present invention is to provide novel 2-amino-1,3-propanediol compounds having superior immunosuppressive action with less side effects.
DISCLOSURE OF THE INVENTION
The present invention relates to ##STR3## wherein R is an optionally substituted straight- or branched carbon chain which may have, in the chain, a bond, a hetero atom or a group selected from the group consisting of a double bond, a triple bond, oxygen, sulfur, sulfinyl, sulfonyl, --N(R.sup.6)-- where R.sup.6 is hydrogen, alkyl, aralkyl, acyl or alkoxycarbonyl, carbonyl, optionally substituted arylene, optionally substituted cycloalkylene, optionally substituted heteroarylene and an alicycle thereof, and which may be substituted, at the chain end thereof, by a double bond, a triple bond, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heteroaryl or an alicycle thereof; an optionally substituted aryl, an optionally substituted cycloalkyl, an optionally substituted heteroaryl or an alicycle thereof; and a hydrogen, an alkyl, an aralkyl, an acyl or an alkoxycarbonyl, or R.sup.4 and R.sup.5 may be bonded to form an alkylene chain which may be substituted by alkyl, aryl or aralkyl; have a substituent selected from the group consisting of alkoxy, alkenyloxy, alkynyloxy, aralkyloxy, alkylenedioxy, acyl, alkylamino, alkylthio, acylamino, alkoxyca
REFERENCES:
patent: 3062839 (1962-11-01), Shetty et al.
patent: 3324043 (1967-01-01), Krum
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patent: 4910218 (1990-03-01), Bair
patent: 5068247 (1991-11-01), Fujita et al.
Merck Index, No. 460 (2-Amino-2-methyl-1,3-propane diol) p. 73 1989.
Bair et al., J. Med.Chem., "1-Pyrenylmethyl)amino alcohols, a New Class Antitumor DNA Intercalators. Discovery and Initial Amine Side Chain Structure-Activity Studies", 1990, 33, pp. 2385-2393.
Shetty et al., J. Org. Chem. Nov. 1960, pp. 2057-2059.
Rembarz et al., J. Prakt. Chem., 68; vol. 37 (1-2); pp. 59-63. 1968.
Chemical Abstracts, vol. 85, No. 23, Dec. 6, 1976, Columbus, Ohio, U.S. abstract No. 177498z, 2,4-Di-1-aziridinyl-6-amino-s-triazines & Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye znaki,vol. 53, No. 26, 1976, pp. 78-79, Malyugina, L. L. et al., & Chemical Abstracts 9th coll. Index page 8505cs, 1,4-Butanediol, 2-amino-2-(hydroxymethyl)-.
Derwent Abstract of Japan Patent Unexamined Pub. No. 416/1987 published Jan. 1986.
Derwent abstract of Japan Patent Unexamined Pub. No. 192962/1984 published Nov. 1984.
Merck Index, 11th Edition, No. 9684 (Tromethamine), pp. 1536-1537 (1989).
Derwent abstract of Japan Patent Unexamined Pub. 104087/1989 published Apr., 1989.
Merck Index, No. 451 (2-Amino-2-ethyl-1,3-propanediol) 1989.
Adachi Kunitomo
Chiba Kenji
Fujita Tetsuro
Mishina Tadashi
Sasaki Shigeo
Covington Raymond
Ivy C. Warren
Taito Co., Ltd.
Yoshitomi Pharmaceutical Industries Ltd.
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