Vitamin d derivatives

• US 20030195176A1
• Filed: 10/17/2002
• Published: 10/16/2003
• Est. Priority Date: 04/19/2000
• Status: Active Grant

• 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
• Granted Patent: US 7,074,777 B2
• Time in Patent Office: Days
• 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 hydrogen or Formula (2) wherein A is —

CO—

, —

CH₂—

, —

CH(OH)—

, —

CH═

CH—

or —

C≡

C—

, R₇ is hydroxy, R₈ is hydrogen, m is a number from 0 to 2 and 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, m is a number from 0 to 2 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.

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 a number from 0 to 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 hydrogen or Formula (2) wherein A is —

CH₂—

, R₇ is hydroxy, R₈ is hydrogen, m is a number from 1 to 2 and 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 therapeutic agent for skin disease comprising the vitamin D derivative as set forth in any one of claims 1 to 7 as an active ingredient.

10. The therapeutic agent as set forth in claim 9, wherein the skin disease is psoriasis.