9, 10-secopregnane derivative and pharmaceutical

• US 8,796,246 B2
• Filed: 06/01/2007
• Issued: 08/05/2014
• Est. Priority Date: 06/02/2006
• Status: Expired due to Fees

• Current Assignee: Nippon Shinyaku Company Limited
• Original Assignee: Nippon Shinyaku Company Limited
• Inventors: Fujieda, Hiroki, Otsu, Hironori, Yasufuku, Shoji, Shirai, Masaaki
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US12/302,975
• Publication Number:
  US 20100016263A1
• Time in Patent Office: 2,622 Days
• Field of Search: 514/167, 552/653
• 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

Abstract

A main object of the invention is to provide a novel useful vitamin D₃ derivative, which has an excellent vitamin D₃ activity and, as compared with conventional vitamin D₃ derivatives, has a relatively small amount of influence on the systemic calcium metabolism. The invention includes a 9,10-secopregnane derivative of the following general formula [1] and a pharmaceutical composition containing it as active ingredient.

In the general formula [1], the following partial structure between the 16-position and the 17-position means a single bond or a double bond:

Y is a single bond, an alkylene, an alkenylene or phenylene; R¹ and R² are the same or different, each represents hydrogen, an alkyl or a cycloalkyl; or R¹ and R², taken together with the adjacent carbon atom, form a cycloalkyl; R³ is hydrogen or methyl; Z is hydrogen, hydroxy or —NR¹¹R¹².

Claims

1. A 9,10-secopregnane compound of formula [1]:

2. The 9,10-secopregnane compound or the pharmaceutically acceptable salt thereof as claimed in claim 1, which is a compound of the following (1) to (16):

(1) (1S,3R,20S)-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,10(19),16-tetraene-1,3-diol,

(2) (1R,3R,20S)-19-nor-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(3) (1R,3R,20S)-2-methylene-19-nor-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(4) (1R,3R,20S)-19-nor-20-[(2E)-4-ethyl-4-hydroxyhex-2-enoyloxy]-9,10-secopregna-5Z,7E-diene-1,3-diol,

(5) (1R,3R,20S)-19-nor-20-(5,5,5-trifluoro-4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(6) (1R,3R,20S)-2-methylene-19-nor-20-(5,5,5-trifluoro-4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(7) (1R,3R,20S)-2-methylene-19-nor-20-[(2E)-4-ethyl-4-hydroxyhex-2-enoyloxy]-9,10-secopregna-5Z,7E-diene-1,3-diol,

(8) (1R,3R,20S)-19-nor-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,16-triene-1,3-diol,

(9) (1R,3R,20S)-19-nor-20-(5,5,5-trifluoro-4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,16-triene-1,3-diol,

(10) (1R,3R,20S)-19-nor-2-methylene-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,16-triene-1,3-diol,

(11) (1 S,3R,20S)-20-(5 ,5 ,5-trifluoro-4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,10(19),16-tetraene-1,3-diol,

(12) (1R,2α

,3R,20S)-2-methyl-19-nor-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(13) (1R,2β

,3R,20S)-2-methyl-19-nor-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(14) (1R,3R,20S)-2-methyl-19-nor-20-(5,5,5-trifluoro-4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E-diene-1,3-diol,

(15) (1R,3R,20S)-2-methyl-19-nor-20-[(2E)-4-ethyl-4-hydroxyhex-2-enoyloxy]-9,10-secopregna-5Z,7E-diene-1,3-diol,

(16) (1R,3R,20S)-19-nor-2-methyl-20-(4-hydroxy-4-methylpentanoyloxy)-9,10-secopregna-5Z,7E,16-triene-1,3-diol.

3. A pharmaceutical composition, comprising a 9,10-secopregnane compound or a pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutically acceptable carrier.

4. A method of treating dyskeratosis, which comprises administering an effective amount of a 9,10-secopregnane compound or a pharmaceutically acceptable salt thereof of claim 1 to a patient in need thereof.

5. A method of treating psoriasis vulgaris, which comprises administering an effective amount of a 9,10-secopregnane compound or a pharmaceutically acceptable salt thereof of claim 1 to a patient in need thereof.