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Generated: January 22, 2018

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Title:Steroids as agonists for FXR
Abstract: The invention relates to compounds of formula (I): ##STR00001## wherein R is ethyl, propyl or allyl, and pharmaceutically acceptable salts, solvates or amino acid conjugates thereof. The compounds of formula (I) are useful as FXR agonists.
Inventor(s): Pellicciari; Roberto (Perugia, IT)
Assignee: Intercept Pharmaceuticals, Inc. (New York, NY)
Filing Date:Feb 07, 2013
Application Number:13/761,889
Claims:1. A process for preparing a compound of formula I: ##STR00007## or a pharmaceutically acceptable salt or amino acid conjugate thereof, comprising: a) reacting 3.alpha.-hydroxy-7-keto-5.beta.-cholan-24-oic acid with 3,4-dihydropyrane to prepare 3.alpha.-tetrahydropyranyloxy-7-keto-5.beta.-cholan-24-oic acid; b) reacting 3.alpha.-tetrahydropyranyloxy-7-keto-5.beta.-cholan-24-oic acid with an alkyl bromide of the formula R--Br, wherein R is ethyl, to prepare a compound of formula II: ##STR00008## c) reacting the compound of formula II with sodium borohydride to prepare a compound of formula III: ##STR00009## d) reacting the compound of formula II with sodium hydroxide to prepare the compound of formula I.

2. A method of increasing flow of bile acids from the liver to the intestine in a subject suffering from a cholestatic liver disease, comprising administering to the subject a therapeutically effective amount of a compound of formula I: ##STR00010## or a pharmaceutically acceptable salt or amino acid conjugate thereof.

3. The method of claim 2, wherein the compound is a glycine conjugate of the compound of formula I.

4. The method of claim 2, wherein the compound is a taurine conjugate of the compound of formula I.

5. The method of claim 2, wherein the compound is a pharmaceutically acceptable salt of the compound of formula I.

6. The method of claim 2, wherein the subject is a mammal.

7. The method of claim 6, wherein the mammal is a human.
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