Meiosis regulating compounds

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai

Reexamination Certificate

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Details

C514S178000, C514S182000, C514S841000

Reexamination Certificate

active

06486145

ABSTRACT:

FIELD OF THIS INVENTION
The present invention relates to pharmacologically active compounds and to their use as medicaments. More particularly it has been found that the sterol derivatives described herein can be used for regulating meiosis.
BACKGROUND OF THIS INVENTION
In L. F. Fieser & M. Fieser: Steroids; Reinhold Publishing Corporation, 1967, 5&agr;-bromocholest-ane-3&bgr;,6&bgr;-diol; 7&agr;-bromocholestane-3&bgr;,6&agr;-diol; 7&agr;-bromocholestane-3&bgr;,6&bgr;diol; 7&agr;-bromo-cholestane-3&bgr;,5&agr;-diol-6-one; 7&bgr;-bromocholestane-3&bgr;,5&agr;-diol-6-one; 3&bgr;-bromocholestane-2&agr;-ol; 5&agr;-chlorocholestane-3&bgr;,6&agr;-diol; 5&agr;-chlorocholestane-3&bgr;,6&bgr;-diol; 6&bgr;-chlorocholestane-3&bgr;,-5&agr;-diol; &Dgr;
7,9(11)
-cholestadiene-3&bgr;,6&agr;-diol; &Dgr;
7,9(11)
-cholestadiene-3&bgr;,6&bgr;diol; cholestane-2&agr;,3&agr;-diol; cholestane-2&agr;,3&bgr;-diol; cholestane-2&bgr;,3&agr;-diol; cholestane-2&bgr;,3&bgr;-diol; cholestane-3&agr;,4&agr;-diol; cholestane-3&agr;,4&bgr;-diol; cholestane-3&bgr;,4&bgr;-diol; cholestane-3&agr;,5&agr;-diol; cholestane-3&bgr;,5&agr;-diol; cholestane-3&bgr;,6&agr;-diol; cholestane-3&bgr;,6&bgr;-diol; cholestane-3&bgr;,22&agr;-diol, cholestane-3&bgr;,22&bgr;-diol; cholestane-3&bgr;,7&agr;,8&agr;-triol; &Dgr;
5
-cholestene-3&bgr;,4&agr;-diol; &Dgr;
5
-cholestene-3&bgr;,4&bgr;-diol; &Dgr;
5
-cholestene-3&bgr;,20&agr;-diol; &Dgr;
5
-cholestene-3&bgr;,22&agr;-diol; &Dgr;
5
-cholestene-3&bgr;,22&bgr;-diol; &Dgr;
5
-cholestene-3&bgr;,24&agr;-diol; &Dgr;
5
-cholestene-3&bgr;,24&bgr;-diol; &Dgr;
6
-cholestene-3&bgr;,5&agr;-diol; &Dgr;
8(14)
-cholestene-3&bgr;,9&agr;-diol; &Dgr;
11
-cholestene-3&agr;,24-diol; &Dgr;
5
-cholestene-3&bgr;,6-diol-7-one; &Dgr;
5
-cholestene-4&agr;-ol-3-one; &Dgr;
5
-cholestene-3&bgr;,4&bgr;,7&agr;-triol; coprostane-3&agr;,5&bgr;-diol; coprostane-3&bgr;,5&bgr;-diol; coprostane-3&bgr;,6&bgr;-diol; coprostane-4&bgr;,5&bgr;-diol-3-one and 20&bgr;-hydroxy-20-isocholesterol are mentioned in the subject index.
In German patent application having publication no. 1,183,079, a process for preparing 4&agr;-hydroxy-5a-cholestan-3-one is mentioned in Example 5. This compound is not stated to have any utility other than as an intermediate.
In German patent application having publication no. 1,224,738, cholestan-3&bgr;,5&agr;,6&bgr;-triol-3&bgr;-hemisuccinate; cholestan-3&bgr;,5&agr;,6&bgr;-triol-3&bgr;-hemisuccinate-6&bgr;-acetate; cholestan-3&bgr;,5&agr;,6&bgr;-triol-3&bgr;-hemisuccinate-6&bgr;-formiate; cholestan-3&bgr;,5&agr;,6&bgr;-triol-3&bgr;-sulphate and cholestan-3&bgr;,5&agr;,6&bgr;-triol-3&bgr;-phosphate are mentioned in Examples 1-5, respectively. It is mentioned that the compounds described therein can be used for the treatment of arteriosclerosis.
In German patent application having publication no. 2,201,991 C2, a process for the preparation of insecticides such as 2&bgr;,3&bgr;,14&agr;,22(R),25-pentahydroxycholest-7-en-6-one is described.
German patent application having publication no. 2,236,778 B2 relates to a novel insecticide, i.e., cholest-7-en-2&bgr;,3&bgr;,5&bgr;, 11&agr;,14&agr;,20(R)-heptahydroxy-6-one.
In German patent application having publication no. 2,409,971 B2, 5,24-cholestadien-3&bgr;-ol; 5-cholesten-3&bgr;,24,25-triol-3&bgr;-acetate; 5-cholesten-3&bgr;,24,25-triol-3&bgr;,24-diacetate; 5,25-cholestadien-3&bgr;-ol acetate; 5-cholesten-3&bgr;,25,26-triol-3&bgr;-acetate and 5-cholesten-3&bgr;,25,26-triol are mentioned in Examples 1, 1, 2, 3, 3 and 6, respectively. It is mentioned that the compounds described therein are valuable intermediates for the technical preparation of 24,25(or 25,26)-dihydroxycholecalciferol.
In German patent application having publication no. 2,453,648B2, cholest-5&agr;-an-3&bgr;,6&agr;-diol; cholest-5&bgr;-an-3&bgr;,6&bgr;-diol; cholest-5&agr;-an-3,6-dione; cholest-5&agr;-an-6&bgr;-ol-3-one and cholest-5&agr;-an-2&agr;-bromo-6&bgr;-ol-3-one are mentioned as intermediates in column 6.
In German patent application having publication no. 2,415,676, cholestan-3p,25-diol-3&bgr;-acetate; cholestan-3&bgr;,5&agr;,25-triol-3&bgr;-acetate; cholestan-3&bgr;,5&agr;,25-triol; cholestan-5&agr;,25-diol-3-one; cholest-4-en-25-ol-3-one and cholesta-4,6-dien-25-ol-3-one are mentioned as compounds III, IV, X, Xl XII and XIII, respectively. It is suggested that the compounds described therein may be substantially stronger that vitamin D
3
.
In German patent application having publication no. 2,546,715 A1, a process for preparing 1&agr;,3&bgr;dihydroxycholest-5-en and 1&agr;,3&bgr;-dihydroxycholest-6-en is mentioned in Example 1 (compounds V and II). It is suggested that the compounds described therein are useful additives to foodstuff and can be used in vitamin compositions.
In German patent application having publication no. 2,822,486A1, 3&agr;,6&agr;-dihydroxy-5&bgr;-cholestan-24-one; 3&agr;,6&agr;,24-trihydroxy-5&bgr;-cholestan; 3-chlorocholest-5,24-dien; 3&bgr;-hydroxycholest-5-en-24-on acetate and 3-chlorocholest-5-en-24-on are mentioned in Example 3,4,5
a
and 6
c
and as formula VlI, respectively. It is mentioned that the compounds described therein can be used as intermediates for the preparation of desmosterin, derivatives thereof and other active vitamin D.
In German patent application having publication no. 3,241,172 A1, cholestan-25-fluoro-3&bgr;,22(S)-diol; cholestan-25-chloro-3&bgr;,22(S)-diol; cholestan-25-methyl-3&bgr;,22-diol; cholestan-25-methyl-3&bgr;,22-diol-3-hydrogenbutandioate and cholestan-25-methyl-3&bgr;,22-diol-bis-hydrogenbutandioate are mentioned in claims
2
,
3
,
5
,
6
and
7
, respectively. It is mentioned that the compounds described therein inhibit the activity of HMGCOA reductase and the formation of blood cholesterol.
In German patent application having publication no. 3,390,016C2, a process for preparing 1&agr;,25-dihydroxy-26,26,26,27,27,27-hexafluorocholes-5-en is described. It is mentioned that this compound can easily be converted into a compound having vitamin D
3
like activity.
In Danish patent application having publication no. 123,767, a process for preparing 2&bgr;,3&bgr;,14&agr;,22,25-pentahydroxy-&Dgr;
7
-5&bgr;-cholesten-6-one is mentioned. It is mentioned that the compounds described therein have an action on the central nervous system.
In European patent application having publication no. 15,122 B1, 25-hydroxy-3&bgr;-[(tetrahydro-2H-pyran-2-yl)oxy]cholest-5-en-24-on; 3&bgr;[(tetrahydro-2H-pyran-2-yl)oxy]cholest-5-en-24-on; 25-hydroxy-24-oxocholesterol-3&bgr;-acetate; 24-oxocholesterol-3&bgr;-acetate; 25-hydroxy-24-oxocholesterol; 24,25-dihydroxycholesterol; 3&agr;,6&agr;,25-trihydroxy-24-oxo-5&bgr;-cholestane; 1&agr;,25-dihydroxy-24-oxocholesterol; 1&agr;,24,25-trihydroxycholesterol; 3&bgr;-hydroxy-24-oxo-cholesta-5,7-dien; 3&bgr;,25-dihydroxy-24-oxocholesta-5,7-dien; 3&bgr;-hydroxy-24-oxocholesta-5,7-dien; 1&agr;,3&bgr;-dihydroxy-24-oxocholesta-5,7-dien and 1&agr;,3&bgr;,25-trihydroxy-24-oxocholesta-5,7-dien are mentioned in Examples 1, 1, 4, 4, 5ii, 5(1), 6i, 7, 7(2), 8iii, 8iv, 8iv, 9iii and 9iv, respectively. It is mentioned that the compounds described therein are useful intermediates convertible into active vitamin D
3
.
In European patent application having publication :no. 63,678B1, (24R)-3&bgr;,24,25-trihydroxycholest-5-en; (24RS)-3&bgr;,24,25-trihydroxycholest-5-en and (24R)-1&bgr;,3&bgr;,24,25-tetrahydroxycholest-5-en are mentioned in Examples 1
e,
3
e
and 4
f,
respectively. It is mentioned that the compounds described therein can be used as intermediates in the preparation of vitamin D
3
derivatives.
In European patent application having publication no. 322,036A1, 4,4-dimethyl-24-methylene-3&bgr;-sulphooxy-12&agr;-acetoxycholesta-8,14-dien-2&agr;,11&bgr;-diol; 4,4-dimethyl-24-methylene-3&bgr;-sulphooxy-12&agr;-acetoxycholest-8-en-2&agr;,11&bgr;-diol; 4,4-dimethyl-24-methylene-12&agr;-acetoxycholesta-8,14-dien-2&agr;,3&bgr;,11&bgr;-triol; 4,4-dimethyl-24-methylene-12&agr;-acetoxycholesta-8,14-dien-3&bgr;,11&bgr;-diol; 4,4-dimethyl-24-methylene-12&agr;-acetoxycholesta-8-en-2&agr;,3&bgr;

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