18,19-dinor-vitamin D compounds

• US 5,843,927 A
• Filed: 09/27/1996
• Issued: 12/01/1998
• Est. Priority Date: 11/21/1994
• Status: Expired due to Fees

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: DeLuca, Hector F., Sicinski, Rafal R., Perlman, Kato L.
• Primary Examiner(s): Dees, Jose G.
• Assistant Examiner(s): PRYOR, ALTON NATHANIEL
• Application Number:
  US08/722,488
• Time in Patent Office: 795 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896

Abstract

18,19-dinor-vitamin D₃ analogs in which the angular methyl group attached to carbon 13 of the CD-ring and the exocyclic methylene group attached to carbon 10 of the A-ring have been removed and replaced by a hydrogen atom. The 18,19-dinor vitamin D compounds are characterized by relatively high cell differentiation activity, and marked intestinal calcium transport activity while exhibiting lower activity than 1α,25-dihydroxyvitamin D₃ in their ability to mobilize calcium from bone. These compounds would be useful for the treatment of diseases where bone formation is desired, such as osteoporosis, because of their preferential calcemic activity, and for the treatment of psoriasis due to their cell differentiation activity.

Claims

1. A compound having the formula:

##STR9## where X¹ and X², which may be the same or different, are each selected from hydrogen and a hydroxy protecting group, and where the group R is represented by the structure;

##STR10## where the stereochemical center at carbon 20 may have the R or S configuration, and where Z is selected from Y, --OY, --CH₂ OY, --C≡

CY and --CH=CHY, where the double bond may have the cis or trans geometry, and where Y is selected from hydrogen, methyl, --CR⁵ O and a radical of the structure;

##STR11## where m and n, independently, represent the integers from 0 to 5, where R¹ is selected from hydrogen, deuterium, hydroxy, protected hydroxy, fluoro, trifluoromethyl, and C_1-5 -alkyl, which may be straight chain or branched and, optionally, bear a hydroxy or protected-hydroxy substituent, and where each of R², R³, and R⁴, independently, is selected from deuterium, deuteroalkyl, hydrogen, fluoro, trifluoromethyl and C_1-5 alkyl, which may be straight-chain or branched, and optionally, bear a hydroxy or protected-hydroxy substituent, and where R¹ and R², taken together, represent an oxo group, or an alkylidene group, =CR² R³, or the group --(CH₂)_p --, where p is an integer from 2 to 5, and where R³ and R⁴, taken together, represent an oxo group, or the group --(CH₂)_q --, where q is an integer from 2 to 5, and where R⁵ represents hydrogen, hydroxy, protected hydroxy, or C_1-5 alkyl.

2. A pharmaceutical composition containing at least one compound as claimed in claim 1 together with a pharmaceutically acceptable excipient.

3. The pharmaceutical composition of claim 2 containing 18,19-dinor-1α

,25-dihydroxvvitamin D₃ in an amount from about 0.1 μ

g to about 50 μ

g.

4. 18,19-dinor-1α

,25-dihydroxyvitamin D₃.

5. 18,19-dinor-1α

-hydroxyvitamin D₃.