Vitamin D derivatives

• US 7,074,777 B2
• Filed: 04/18/2001
• Issued: 07/11/2006
• Est. Priority Date: 04/19/2000
• Status: Expired due to Fees

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Shimizu, Hitoshi, Kawase, Akira, Emura, Takashi, Shimizu, Kazuki, Kinoshita, Kazutomo
• Primary Examiner(s): Badio, Barbara P.
• Application Number:
  US10/257,868
• Publication Number:
  US 20030195176A1
• Time in Patent Office: 1,910 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 17/06 Antipsoriatics
• 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
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The object of the present invention is to provide a vitamin D derivative exhibiting excellent physiological activity as medicines, in particular as therapeutic agents for skin disease including psoriasis, and having decreased hypercalcemic activity.

The present invention provides vitamin D derivatives represented by the general Formula (1):

wherein

• • in Formula (1), X is oxygen or sulfur;
  • R₁ is hydrogen or Formula (2)

• • R₂ is hydrogen or alkyl;
  • R₃ and R₄ are hydrogen or alkyl or R₃ and R₄ together form a double bond between the 16- and 17-positions;
  • R₅ is hydrogen or —OR₁₃ in which R₁₃ is hydrogen or a protecting group; and
  • R₆ is hydrogen or a protecting group.

Claims

1. A vitamin D derivative of Formula (1):

2. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen or sulfur;

R₁ is Formula (2) wherein A is —

CO—

, —

CH₂—

, —

CH(OH)—

, —

CH═

CH—

or —

C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, n is a number from 0 to 1;

R₂ is hydrogen or C_1-4 alkyl;

R₃ and R₄ is hydrogen or R₃ and R₄ together form a double bond between the 16- and 17-positions;

R₅ is hydroxy; and

R₆ is hydrogen.

3. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen or sulfur;

R₁ is Formula (2) wherein A is —

CO—

, —

CH₂—

, —

CH(OH)—

, —

CH═

CH—

or C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, n is a number from 0 to 1;

R₂ is hydrogen or methyl;

R₃ and R₄ together form a double bond between the 16- and 17-positions;

R₅ is hydroxy; and

R₆ is hydrogen.

4. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen or sulfur;

R₁ is Formula (2) wherein A is —

CO—

, —

CH₂—

, —

CH═

CH—

or —

C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, m is 1 and n is a number from 0 to 1;

R₂ is hydrogen or methyl, R₃ and R₄ together form a double bond between the 16- and 17-positions;

R₅ is hydroxy; and

R₆ is hydrogen.

5. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen;

R₁ is Formula (2) wherein A is —

CH₂—

or —

C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, m is 1 and n is a number from 0 to 1;

R₂ is hydrogen or methyl;

R₃ and R₄ together form a double bond between the 16- and 17-positions;

R₅ is hydroxy; and

R₆ is hydrogen.

6. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen;

R₁ is Formula (2) wherein A is —

C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, m is 1 and n is 0;

R₂ is hydrogen or methyl;

R₃ and R₄ together form a double bond between the 16- and 17-positions;

R₅ is hydroxy; and

R₆ is hydrogen.

7. The vitamin D derivative as set forth in claim 1, wherein in Formula (1), X is oxygen;

R₁ is Formula (2) wherein A is —

CH₂—

, R₇ is hydroxy, R₈ is hydrogen, n is a number from 0 to 1;

R₂ is hydrogen;

R₃ and R₄ are hydrogen;

R₅ is hydroxy; and

R₆ is hydrogen.

8. A pharmaceutical composition comprising the vitamin D derivative as set forth in any one of claims 1 to 7.

9. A method for the treatment of skin disease, comprising administering to a patient in need thereof an amount sufficient for said treatment of a vitamin D derivative as set forth in claim 1.

10. The method of claim 9 wherein said patient is one whose skin disease is psoriasis.

11. The pharmaceutical composition of claim 8 formulated as a topical preparation selected from the group consisting of an ointment, a cream and a lotion.