Vitamin D compounds and method of preparing these compounds

• US 5,929,056 A
• Filed: 12/11/1995
• Issued: 07/27/1999
• Est. Priority Date: 12/14/1994
• Status: Expired due to Fees

• Current Assignee: Duphar International Research B.V. (Abbott Laboratories Incorporated)
• Original Assignee: Duphar International Research B.V. (Abbott Laboratories Incorporated)
• Inventors: Granja, Juan, Martinez, Jose Antonio, Angeles Rey, Maria de los, Halkes, Sebastianus J., Mourino, Antonio
• Primary Examiner(s): Dees, Jose' G.
• Assistant Examiner(s): Pryor, Alton
• Application Number:
  US08/570,560
• Time in Patent Office: 1,324 Days
• Field of Search: 552/653, 517/167
• US Class Current: 514/167
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/12 Antihypertensives
• 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

Abstract

The present invention relates to vitamin D compounds of the general formula ##STR1## wherein: R₁ is a hydrogen atom or a hydroxy group;

R₂ is a (C₁ -C₃)alkyl group, a hydroxy(C₁ -C₃)alkyl group, a (C₁ -C₂)alkoxymethyl group or a (C₂ -C₃)alkenyl or alkynyl group;

n is 1;

R₃ is a branched or non-branched, saturated or unsaturated, substituted or unsubstituted aliphatic (C₃ -C₇)hydrocarbon or oxyhydrocarbon biradical;

R₄ is a branched or straight (C₁ -C₆) alkyl group or a (C₃ -C₆)cycloalkyl group; and

A and B are each individually hydrogen atoms or methyl groups, or

A and B form together a methylene group.

The present compounds find use in cosmetic application and in human and veterinary pharmacotherapeutic practice in the treatment of skin and bone diseases, diseases related to cell differentiation/cell proliferation, imbalance in the immune system and inflammatory diseases.

Claims

1. A vitamin D compound of the general formula ##STR24## wherein:

R₁ is a hydrogen atom or a hydroxy group;

R₂ is a (C₁ -C₃)alkyl group, a hydro(C₁ -C₃)alkyl group, a (C₁ -C₂)alkoxymethyl group or a (C₂ -C₃)alkenyl or alkynyl group;

n is 1;

R₃ is a branched or non-branched, saturated or unsaturated aliphatic (C₃ -C₇) hydrocarbon or oxahydrocarbon biradical, having at least 3 atoms in the main chain and being optionally substituted with one or more substituents selected from fluoro, hydroxy, epoxy or methoxy;

R₄ is a branched or straight (C₁ -C₆)alkyl group or a (C₃ -C₆)cycloalkyl group; and

A and B are each individually hydrogen atoms or methyl groups, or

A and B form together a methylene group.

2. A vitamin D compound as claimed in claim 1, having the general formula ##STR25## wherein:

R₄ and n have the meanings given in claim 1;

R₂ '"'"' is CH₃, CH₂ CH₃, CH₂ OH or CH═

CH₂ ;

R₃ '"'"' is a biradical of the formula --CH₂ --CH₂ --(CH₂)_m --, --CH₂ --(CH₂)_m --CH(CH₃)-- or --(CH₂)_p --O--(CH₂)_q --, wherein m=1-3, p=0-3 and q=0-3 with the proviso that p+q≧

2; and

A'"'"' and B'"'"' are hydrogen atoms or form together a methylene group.

3. A vitamin D compound as claimed in claim 2, having the general formula ##STR26## wherein:

n is 1;

R₃ '"'"', A'"'"' and B'"'"' have the meanings given in claim 2; and

R₄ '"'"' is methyl, ethyl, propyl, isopropyl or cyclopropyl.

4. A vitamin D compound as claimed in any one of the preceding claims, wherein the (C-20)substituent, i.e. substituent R₃ --C(R₄)₂ --OH, is the E configuration.

5. A pharmaceutical composition comprising, in addition to a pharmaceutically acceptable carrier and/or at least one pharmaceutically acceptable auxiliary substance, as the active ingredient at least one compound as defined in claim 1, or 2 or 3 in an effective amount.

6. A vitamin D compound as claimed in any one of claims 1-3, where the (C-20) substituent, i.e. substituent R₃ --C(R₄)₂ --OH, is the Z configuration.

7. A pharmaceutical composition comprising an effective amount of at least one compound according to claim 4 and at least one member of the group consisting of a pharmaceutically acceptable carrier and a pharmaceutically acceptable auxiliary substance.

8. A pharmaceutical composition comprising an effective amount of at least one compound according to claim 6 and at least one member of the group consisting of a pharmaceutically acceptable carrier and a pharmaceutically acceptable auxiliary substance.