Vitamin D;lactone derivatives

• US 9,073,885 B2
• Filed: 01/29/2004
• Issued: 07/07/2015
• Est. Priority Date: 01/30/2003
• Status: Expired due to Fees

• Current Assignee: Teijin Limited
• Original Assignee: Teijin Pharma Limited (Teijin Limited)
• Inventors: Takenouchi, Kazuya, Anzai, Miyuki, Saito, Hiroshi, Okada, Kazuhisa, Ishizuka, Seiichi, Miura, Daishiro, Takayama, Hiroaki, Kittaka, Atsushi, Saito, Nozomi, Fujishima, Toshie
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US10/543,881
• Publication Number:
  US 20060148768A1
• Time in Patent Office: 4,177 Days
• Field of Search: 514/167, 549/502, 549/295, 552/653
• US Class Current: 1/1
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 307/58 One oxygen atom, e.g. butenolide

Abstract

A compound represented by the following Formula (1) that is effective for the treatment of Paget'"'"'s disease of bone or hypercalcemia or a medically acceptable solvate thereof;

[wherein R₁ refers to hydrogen atom, C₁-C₆ alkyl group optionally substituted with hydrogen group or C₁-C₆ alkoxy group optionally substituted with hydroxyl group, R^2a and R^2b refer to hydrogen atom, C₁-C₁₀ alkyl group optionally substituted with hydroxyl group, C₆-C₁₀ aryl group optionally substituted with hydroxyl group or C₇-C₁₂ aralkyl group optionally substituted with a hydroxyl group, or are combined to represent ethylene group. However, a compound in which R¹ is a hydrogen atom or a methyl group and R^2a and R^2b are hydrogen atoms is excluded].

Claims

1. A compound represented by the following Formula (1):

2. The compound according to claim 1, wherein in the above Formula (1), R¹ is methyl group and a combination of R^2a and R^2b is hydrogen atom and methyl group;

R¹ is methyl group and a combination of R^2a and R^2b is hydrogen atom and ethyl group;

R¹ is methyl group and a combination of R^2a and R^2b is hydrogen atom and butyl group;

R¹ is methyl group and a combination of R^2a and R^2b is hydrogen atom and isobutyl group;

or R¹ is methyl group and both R^2a and R^2b are methyl groups.

3. The compound according to claim 1, wherein in the above Formula (1), R¹ is 3-hydroxypropyl group and both R^2a and R^2b are hydrogen atoms;

R¹ is 3-hydroxypropyl group and a combination of R^2a and R^2b is hydrogen atom and methyl group;

R¹ is 3-hydroxypropyl group and a combination of R^2a and R^2b is hydrogen atom and ethyl group;

R¹ is 3-hydroxypropyl group and a combination of R^2a and R^2b is hydrogen atom and butyl group;

R¹ is 3-hydroxypropyl group and a combination of R^2a and R^2b is hydrogen atom and isobutyl group;

or R¹ is 3-hydroxypropyl group and both R^2a and R^2b are methyl groups.

4. The compound to claim 1, wherein in the above Formula (1), R¹ is 3-hydroxypropoxy group and both R^2a and R^2b are hydrogen atoms;

R¹ is 3-hydroxypropoxy group and a combination of R^2a and R^2b is hydrogen atom and methyl group;

R¹ is 3-hydroxypropoxy group and a combination of R^2a and R^2b is hydrogen atom and ethyl group;

R¹ is 3-hydroxypropoxy group and a combination of R^2a and R^2b is hydrogen atom and butyl group;

R¹ is 3-hydroxypropoxy group and a combination of R^2a and R^2b is hydrogen atom and isobutyl group;

or R¹ is 3-hydroxypropoxy group and both R^2a and R^2b are methyl groups.

5. A therapeutic agent for Paget'"'"'s disease of bone comprising the compound or the pharmaceutically acceptable solvate thereof according to claim 1 as an active ingredient.

6. A therapeutic agent for hypercalcemia comprising the compound or the pharmaceutically acceptable solvate thereof according to claim 1 as an active ingredient.

7. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier.

8. A process for synthesizing a compound represented by the following Formula (4syn-a), wherein the relative configuration of carbon a and carbon b is syn,

9. A process which comprises, in the following order, the steps of:

reducing a lactone ring of a lactone compound represented by the following Formula (4syn-b),