24-homo vitamin D derivatives, process for their production and pharmaceutical preparations obtained therefrom

• US 5,665,716 A
• Filed: 10/02/1990
• Issued: 09/09/1997
• Est. Priority Date: 10/02/1989
• Status: Expired due to Fees

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Schwarz, Katicia, Rach, Petra, Thieroff-Ekerdt, Ruth, Kirsch, Gerald, Neef, Gunter, Brautigam, Matthias
• Primary Examiner(s): PRIOR, KIMBERLY
• Application Number:
  US07/592,017
• Time in Patent Office: 2,534 Days
• Field of Search: 204/157.67, 204/157.9, 204/158.87, 552/653, 514/167
• US Class Current: 514/167
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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

New 24-homo vitamin D derivatives of formula I ##STR1## are described, in which R¹ means a hydrogen atom, a hydroxy, an alkanoyloxy group with 1 to 8 carbon atoms or an aralkanoyloxy group with up to 8 carbon atoms,

R² and R³, independently of one another, mean a linear or branched alkyl group with 1 to 4 carbon atoms, a trifluoromethyl group or together mean a saturated carbocyclic ring with 3 to 9 carbon atoms formed with carbon atom 25,

R⁴ and R⁵, independently of one another, mean a hydrogen atom, an alkanoyl group with 1 to 8 carbon atoms or an aralkanoyl group with up to 8 carbon atoms, and

A and B each mean a hydrogen or together a second bond, and

n stands for 1, 2, 3,4 or 5.

Claims

1. A 24-homo vitamin D derivative of formula I ##STR10## in which R¹ is hydrogen, hydroxy, alkanoyloxy of 1 to 8 carbon atoms or benzoyloxy,

R² and R³, independently of one another, each is alkyl of 1 to 4 carbon atoms, or trifluoromethyl or together form a saturated carbocyclic ring of 3 to 9 carbon atoms formed with carbon atom 25,

R⁴ and R⁵, independently of one another, each is hydrogen, alkanoyl of 1 to 8 carbon atoms or benzoyl,

A and B each are hydrogen or together form a second bond, and

n is 1, 2, 3,4 or 5.

2. A 24-homo vitamin D derivative according to claim 1, wherein R¹ is a hydroxy group.

3. A 24-homo vitamin D derivative according to claim 1, wherein R⁴ and R⁵ each are a hydrogen atom.

4. A 24-homo vitamin D derivative according to claim 1, wherein R² and R³ each are a methyl group.

5. A 24-homo vitamin D derivative according to claim 1, wherein A and B together stand for a second bond.

6. A 24-homo vitamin D derivatives according to claim 1, wherein n is 1,2 or 3.

8. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically compatible vehicle.

9. A method of inhibiting cell proliferation and cell differentiation within a host which comprises administering to a host a compound of claim 1.

10. A method of claim 9, wherein the host has cells with calcitriol receptors.

13. A method of treating a malignant tumor within a host which comprises administering a compound of claim 1 to a host afflicted with malignant tumor cells.

14. A method of treating psoriasis which comprises administering a compound of claim 1 to a host afflicted with psoriasis.

15. A method of claim 13, wherein the tumor is located in a locus having calcitriol receptors.

16. A method of claim 14, wherein the host has cells with calcitriol receptors.

7. A 24-homo-vitamin D derivative of formula I ##STR11## in which R¹ is hydroxy,

R² and R³ each are methyl, ethyl, or together form a cyclopropyl, cyclopentyl, or cyclohexyl ring with carbon atom 25,

R⁴ and R⁵ each are a hydrogen atom,

A and B together each are hydrogen or together stand for a second bond and

n is 1, 2 or 3.

11. A compound selected from the group consisting of:

(5Z,7E,22E)-(1S,3R,24S)-24-cyclopropylmethyl-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol;

(5Z,7E,22E)-(1S,3R24S)-24-isoamyl-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol;

(5Z,7E,22E)-(1S,3R,24S)-24-cyclopentylmethyl-9,10,-secochola-5,7,10(19),22-tetraene-1,3,24-triol;

(5Z,7E,22E)-(1S,3R,24S)-24-(2-ethylbutyl)-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol; and

(5Z,7E,22E)-(1S,3R,24R)-24-(2-ethylbutyl)-9,10-secochola-5,7,10(19),22-tetraene-1,3,24-triol.

12. A pharmaceutical composition which comprises a compound of claim 11 and a pharmaceutically compatible vehicle.