Vitamin D3 derivative and its production method

• US 6,982,257 B1
• Filed: 04/30/1998
• Issued: 01/03/2006
• Est. Priority Date: 05/02/1997
• Status: Expired due to Fees

• Current Assignee: Teijin Limited
• Original Assignee: Teijin Limited
• Inventors: Konno, Katsuhiro, Fujishima, Toshie, Takayama, Hiroaki
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US09/214,155
• Time in Patent Office: 2,805 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61P 19/10 for osteoporosis
• 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

Provided are 1,25-dihydroxy-2-methylvitamin D3 derivatives expressed by the general formula (I),
[wherein each of R₁ and R₂ is independently a hydrogen atom or a tri(C₁ to C₇ alkyl)silyl group; herein configurations of asymmetric carbons at the 1-, 2- and 3-positions are each independently α-configuration or β-configuration] and their production methods.

The compound is useful as a treating agent for osteoporosis, rickets, hyperthyroidism, etc.

Claims

1. A 1,25-dihydroxy-2-methylvitamin D₃ compound, wherein the compound is

(i) (20S)-1α

,25-dihydroxy-2β

-methyl-3β

-vitamin D₃;

(ii) (20S)-1β

,25-dihydroxy-2β

-methyl-3α

-vitamin D₃;

(iii) (20S)-1α

,25-dihydroxy-2α

-methyl-3β

-vitamin D₃;

or

(iv) (20S)-1α

,25-dihydroxy-2α

-methyl-3α

-vitamin D₃.

2. A method for producing a vitamin D₃ compound described in claim 1, comprising reacting an exo-methylene compound of formula (II):

wherein X is a bromine atom or an iodine atom, with an eneyne compound of formula (III);

wherein R₃ and R₄ are each independently a hydrogen atom or a tri(C₁ to C₇ hydrocarbon)silyl group in the presence of a palladium catalyst, and optionally removing the protecting group of the tri(C₁ to C₇ hydrocarbon)silyl group, and further wherein the vitamin D₃ compound is

(i) (20S)-1α

,25-dihydroxy-2β

-methyl-3β

-vitamin D₃;

(ii) (20S)-1β

,25-dihydroxy-2β

-methyl-3α

-vitamin D₃;

(iii) (20S)-1α

,25-dihydroxy-2α

-methyl-3β

-vitamin D₃;

or

(iv) (20S)-1α

,25-dihydroxy-2α

-methyl-3α

-vitamin D₃.