Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1990-09-20
1991-12-24
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540112, 540117, 552522, C07J 3300, C07J 4100, C07J 4300
Patent
active
050754343
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
This invention encompasses novel halogenated estranes substituted with an aminoalkyl sidechain that are useful for treating hyperglycemia associated diseases such as diabetes and obesity.
BACKGROUND
Hyperglycemia refers to a condition commonly found in patients suffering from mature-onset diabetes mellitus or other diseases which cause impairment of pancreatic function. Hyperglycemic patients with non-insulin dependent diabetes mellitus (NIDDM) with insulin resistance exhibit elevated serum glucose levels. Failure to adequately control elevated serum glucose levels can cause myocardioischemia, stroke, peripheral vascular disease, lethargy, coma, blindness, kidney failure or death. While conventional treatment for hyperglycemic conditions may include restriction of carbohydrate intake and insulin injection, one important means of treating hyperglycemic patients is with oral hypoglycemic agents. Hypoglycemic agents which would be particularly useful to treat hyperglycemia would be highly effective and exhibit no detrimental long term side effects.
INFORMATION DISCLOSURE
Steroidal compounds useful as hypoglycemic agents are described in the International Application PCT/US86/02116 which has an International Publication Date of Apr. 23, 1987.
SUMMARY OF THE INVENTION
This invention is a compound of formula 1 and pharmaceutically acceptable salts thereof; wherein R.sub.1 is fluorine, chlorine or bromine; wherein R.sub.2 is hydrogen or (C.sub.1 -C.sub.3) alkyl; wherein n is one or 2; wherein R.sub.3 is phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl; wherein phenyl is optionally substituted with one substituent selected from the group consisting of halogen, trifluoromethyl or sulfonamide. Compounds represented by formula I are useful as hypoglycemic agents in treating patients suffering from elevated serum glucose levels resulting from an impairment of tissue response to insulin and/or an impairment of pancreatic islet function such as non-insulin dependent diabetes mellitus (NIDDM) with insulin resistance .
DETAILED DESCRIPTION
The compounds of this invention are identified in two ways: by common name and by numerical identification which corresponds to the appropriate structure contained in the structure charts. In appropriate situations, the proper stereochemistry is represented in the structure charts as well.
The term alkyl means an aliphatic hydrocarbon radical and includes branched or unbranched forms such as methyl, ethyl, n-propyl, or isopropyl. In this document the parenthetical term (C.sub.n -C.sub.m) is inclusive such that a compound of (C.sub.1 -C.sub.3) would include compounds with 1, 2, or 3 carbon atoms and their isomeric forms.
It will be apparent to those skilled in the art that compounds of this invention may contain chiral centers. The scope of this invention includes all enantiomeric or diastereomeric forms of formula I compounds either in pure form or as mixtures of enantiomers or diastereomers.
Both organic and inorganic acids can be employed to form non-toxic pharmaceutically acceptable salts of the compounds of this invention. Illustrative acids are sulfuric, nitric, phosphoric, hydrochloric, citric, acetic, lactic, tartaric, palmoic, ethanedisulfonic, sulfamic, succinic, cyclohexylsulfamic, fumaric, maleic, and benzoic acid. These salts are readily prepared by methods known in the art.
The compounds of this invention are prepared by the general scheme shown in Chart 1. The compounds of this invention are prepared from the halogenated estranone, C-1, by reacting the estranone with a commercially available or known amine of the formula H--N(--R.sub.2)(--(CH.sub.2).sub.n --R.sub.3); when R.sub.2 is hydrogen or (C.sub.1 -C.sub.3) alkyl, n is one or 2 and R.sub.3 is a furyl, thienyl, pyridinyl or optionally substituted phenyl moiety, in the presence of sodium cyanoborohydride in a suitable solvent. The halogenated estranone, C-1; when R.sub.1 is fluorine, chlorine or bromine, is prepared from the commercially available hyd
Koivuniemi Paul J.
Shah Mukund J.
The Upjohn Company
Ward E. C.
Wright Debbie K.
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