25-Carboxylic acid derivatives in the vitamin D series, process for their production, intermediate products for these processes, pharmaceutical preparations containing these derivatives as well as their use for the production of pharmaceutical agents

• US 5,583,125 A
• Filed: 10/06/1993
• Issued: 12/10/1996
• Est. Priority Date: 10/06/1992
• Status: Expired due to Term

• Current Assignee: Intendis GmbH (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Neef, G unter, Thieroff-Ekerdt, Ruth, Haberey, Martin, Kirsch, Gerald, Steinmeyer, Andreas, Wiesinger, Herbert, Schwarz, Katica
• Primary Examiner(s): PRIOR, KIMBERLY
• Application Number:
  US08/132,176
• Time in Patent Office: 1,161 Days
• Field of Search: 552/653, 514/167
• US Class Current: 514/167
• 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 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• 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 25-carboxylic acid derivatives of general formula I, ##STR1## R¹⁹ and R^19a each mean a hydrogen atom or together form an exocyclic methylene group,

R²¹ and R^21a independently of one another mean a hydrogen atom, a chlorine or fluorine atom, an alkyl group with 1 to 4 carbon atoms, together a methylene group, together with quaternary carbon atom 20 mean a 3-7 membered, saturated or unsaturated carboxylic ring,

Y preferably means a derivatized carboxyl radical, and the other substituents have the meanings indicated in the description as well as process for their production, are described.

The new compounds have vitamin D activity as well as proliferation-inhibiting and cell-differentiating effects and are suitable for the production of pharmaceutical agents.

Claims

1. A 25-carboxylic acid compound of formula I, ##STR34## in which R¹ and R³ independently of one another are each a hydrogen atom, a straight-chain or branched-chain saturated alkanoyl group with 1 to 9 carbon atoms or an aroyl group;

R¹⁹ and R^19a are each a hydrogen atom or together form an exocyclic methylene group;

A and B together are a keto oxygen atom or A is a group OR²⁴ and B is a hydrogen atom, or A is a hydrogen atom and B is a group OR²⁴ ;

R²⁴ is a hydrogen atom or a straight-chain or branched-chain saturated alkanoyl group with up to 9 carbon atoms or an aroyl group;

R²¹ and R^21a independently of one another are each a hydrogen atom, a chlorine or fluorine atom, an alkyl group with 1 to 4 carbon atoms, together are a methylene group, or together with carbon atom 20 are a 3-7 membered, saturated or unsaturated carbocyclic ring;

R⁴ and R^4a simultaneously are each a hydrogen atom, a chlorine or fluorine atom, a trifluoromethyl group, a straight-chain or branched-chain, saturated or unsaturated hydrocarbon radical with up to 4 carbon atoms, or R⁴ and R^4a together with carbon atom 25 are a 3 to 7 membered, saturated or unsaturated carboxylic ring;

Y is --C(O)--NR⁵ --R^5'"'"', --C(O)OR⁶, --C(O)SR⁶, or --CN; and

R⁵ and R^5'"'"', independently of one another, are each a hydrogen atom or a linear or branched alkyl group with up to 8 carbon atoms; and

R⁶ is a hydrogen atom, a linear or branched alkyl group with up to 8 carbon atoms, an unsaturated, linear or branched hydrocarbon radical with 3 to 8 carbon atoms or ##STR35## m is 0 or 1; and

n is 2, 3, 4, 5 or 6, and if m is 1 n can also be 1.

2. A compound of formula I according to claim 1 wherein R¹, R³ and R²⁴ each mean a hydrogen atom.

3. A compound of formula I according to claim 1, wherein R¹, R³ and R²⁴ each stand for a acetyl, propionyl, n-butyryl, iso-butyryl, pivaloyl or valeryl radical.

4. A compound of formula I according to claim 1, wherein R¹, R³ and R²⁴ each stand for a benzoyl radical.

5. A compound of formula I according to claim 1, wherein R⁴ and R^4a each stand for methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert-butyl radical.

6. A compound of formula I according to claim 1, wherein R²¹ stands for a hydrogen atom and R^21a stands for a methyl group.

7. A compound of formula I according to claim 1, wherein substituent R²¹ or R^21a stands for a methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert-butyl radical and the other substituent for a methyl group.

8. A compound of formula I according to claim 1, wherein R²¹ or R^21a together with tertiary carbon atom 20 form a cyclopropyl ring.

9. A compound of formula I according to claim 1, wherein R.sup. 21 or R^21a together stand for a methylene group.

10. A compound of formula I according to claim 1, wherein R²¹ means a fluorine atom and R^21a means a methyl group or R.sup. 21 means a methyl group and R^21a means a fluorine atom.

11. A compound of formula I according to claim 1, wherein R⁴ and R^4a each mean a methyl or ethyl group or together with tertiary carbon atom 25 form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring.

12. A compound according to claim 1, wherein said compound is:

(5Z,7E,22E)-(1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-26,27-Dimethyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10 (19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R) -1,3,24-Trihydroxy-9,10-secocholesta-5,7,10 (19),22-tetraene-25-carboxylic acid-1-methyl ethyl esters,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19), 22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secochola-5,7,10(19),22-tetraene-24-acetic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid nitrile,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10 (19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-2methyl propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid pentyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid hexyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid dimethyl amide,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10 (19), 22 -tetraene-25 -carboxylic acid diethyl amide,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid diethyl amide,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-26,27-cyclo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-n-butylamide,

(5Z,7E,22E) - (1S,3R,24R)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19 ),22 -tetraene-25 -carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-1-methyl ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-1-methyl ethyl esters,

(5Z,7E,22E) - (1S,3R,24R)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20-Methyl-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxyllc acid methyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxyllc acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxylic acid ethyl esters,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxylic acid propyl esters,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxyllc acid propyl esters,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxylic acid-1-methyl ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxyllc acid-1-methyl ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22 -pentaene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),20,22-pentaene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxyllc acid methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-1methyl ethyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-1methyl ethyl ester,

(5Z,7E,22E) - (1S,3R,24R)-20,21-Methylene-1,3,24-trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24S)-20,21-Methylene1,3,24-trihydroxy9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid methyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid methyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid propyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid propyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid methyl ester,

(7E,22E)-(1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid methyl ester,

(7E,22E)-(1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid ethyl ester,

(7E,22E)-(1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid ethyl ester,

(7E,22E)-(1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid propyl ester,

(7E,22E)-(1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid propyl ester,

(7E,22E)-(1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,24R)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R,24S)-1,3,24-Trihydroxy-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid methyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid propyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,2 2-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid methyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid propyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R)-1,3-Dihydroxy-24-oxo-19-nor-9,10-secocholesta-5,7,20,22-tetraene-25-carboxylic acid butyl ester,

(7E,22E) - (1R,3R,20S,24R)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R,20S,24S)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R,20R,24R)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxyllc acid ethyl ester,

(7E,22E) - (1R,3R,20R,24S)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid ethyl ester,

(7E,22E) - (1R,3R,20S,24R)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,20S,24S)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,20R,24R)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid-1-methyl ethyl ester,

(7E,22E) - (1R,3R,20R,24S)-20-Fluoro-1,3,24-trihydroxy-19-nor-9,10-secocholesta-5,7,22-triene-25-carboxylic acid ethyl-1methyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-2-methyl propyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-2-methyl propyl ester,

(5Z,7E,22E) - (1S,3R,24R)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid pentyl ester,

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid pentyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid methyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22 -tetraene-25 -carboxylic acid propyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-1-methyl ethyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid butyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid-2-methyl propyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid pentyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-20-methyl-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E,22E) - (1S,3R)-1,3-Dihydroxy-20-methyl-24-oxo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxyllc acid-1-methyl ethyl ester,

(5Z,7E, 22 E) - (1S,3R,24R)-1,3,24-Trihydroxy-26a,27-cyclo-26a-homo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E, 22 E) - (1S,3R,24S)-1,3,24-Trihydroxy-26a,27-cyclo-26a-homo-9,10- secocholesta-5,7,10(19),22-tetraene-25-carboxylic acid ethyl ester,

(5Z,7E, 22 E) - (1S,3R,24R)-1,3,24-Trihydroxy-26a,27-cyclo-26a-homo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic-1-methyl ethyl ester, or

(5Z,7E,22E) - (1S,3R,24S)-1,3,24-Trihydroxy-26a,27-cyclo-a-homo-9,10-secocholesta-5,7,10(19),22-tetraene-25-carboxylic-1-methyl ethyl ester.

13. A compound of formula I according to claim 1, wherein R¹⁹ and R^19a each stand for a hydrogen atom.

14. A compound of claim 13, wherein R²¹ stands for a hydrogen atom and R^21a stands for a methyl group.

15. A compound of claim 13, wherein R²¹ and R^21a together stand for a methylene group.

16. A compound of claim 13, wherein R²¹ and R^21a each stand for a methyl group.

17. A compound of claim 13, wherein R²¹ stands for a hydrogen atom and R^21a stands for a fluorine atom or vice versa.

18. A compound of formula I according to claim 1, wherein R¹⁹ and R^21a together stand for a methylene group.

19. A compound of claim 18, wherein R²¹ stands for a hydrogen atom and R^21a stands for a methyl group.

20. A compound of claim 18, wherein R²¹ and R^21a together stand for a methylene group.

21. A compound of claim 18, wherein R²¹ and R^21a each stand for a methyl group.

22. A compound of formula I according to claim 1, wherein at least, one of R⁵, R^5'"'"' and R⁶ a methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert.-butyl group.

23. A compound according to claim 1, wherein

R⁵ is methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert-butyl;

R^5'"'"' is methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert-butyl; and

R⁶ is methyl, ethyl, n-propyl, n-butyl, i-propyl, i-butyl or tert-butyl.

24. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically compatible vehicle.

25. A composition according to claim 24, wherein said composition contains 0.1-1,000 μ

g.

26. A composition according to claim 24, wherein said composition contains 1-500 μ

g.