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US 6,143,736 AGranted
Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series
AssigneeCoCensys, Inc.
InventorsRavindra B. Upasani, Haiji Xia, Derk Hogenkamp
Life of this patent
Estimating the term…
Abstract
Methods, compositions, and compounds for modulating the GABA.sub.A receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, PMS and PND and to induce anesthesia.
Claims35
A compound of the formula:
- ##STR2## wherein:
- R is hydrogen, halogen, lower alkoxy, alkyl, optionally substituted 1-alkynyl or substituted alkyl;
- R.sub.1 is a substituted aralkynyl, arylalkyl, arylalkenyl, aryl, optionally substituted aralkylalkynyl, alkanoyloxyalkynyl, optionally substituted heteroaryloxyalkynyl, oxoalkynyl or a ketal thereof, cyanoalkynyl, optionally substituted heteroarylalkynyl, hydroxyalkynyl, alkoxyalkynyl, aminoalkynyl, acylaminoalkynyl, mercaptoalkynyl, hydroxyalkynyl dioic acid hemi-ester or a salt thereof, or alkynyloxyalkynyl;
- R.sub.2 is hydrogen, hydroxy, alkoxy, alkanoyloxy, carbalkoxyl, a keto group or amino group;
- R.sub.3 is an acetyl group, a ketal of an acetyl group;
- an alkoxyacetyl group, an alkylthioacetyl group, an alkylsulfinylacetyl group, an alkylsulfonylacetyl group, an aminoacetyl group, a trifluoroacetyl group;
- a hydroxyacetyl group;
- an alkoxyalkylacetyl group;
- a hydroxyalkyl group;
- a hydroxyacetyl dioic acid hemi-ester salt;
- an alkanoyloxyacetyl group;
- a sulfoxyacetyl group;
- an alkylacetyl group;
- a haloacetyl group;
- an ethynyl group;
- an optionally substituted heteroaralkylacetyl group which may also optionally be substituted on the alkylene with a hydroxy, alkoxy, alkanoyloxy or carbalkoxyl group;
- an optionally substituted heterocyclic-acetyl group;
- an acetyl thiosulfate salt;
- a cyano group;
- a methylene group (together with R.sub.7);
- an alkylmethylene group (together with R.sub.7);
- or an alkoxymethylene group (together with R.sub.7);
- R.sub.4 is hydrogen or methyl,
- R.sub.5 is hydrogen;
- R.sub.6 is hydrogen, alkanoyl, aminocarbonyl or alkoxycarbonyl;
- R.sub.7 is hydrogen, halogen, hydroxy, alkoxy, alkanoyloxy, carbalkoxyl, a methylene group (together with R.sub.3), or an alkoxymethylene group (together with R.sub.3);
- R.sub.8 is hydrogen or halogen;
- R.sub.9 is hydrogen, halogen, alkyl, alkoxy, arylalkoxy or amino;
- and
- R.sub.10 is hydrogen, halogen;
- alkyl, haloalkyl, hydroxy, alkoxy, alkanoyloxy, carbalkoxyl, cyano, thiocyano or mercapto;
- with the proviso that when R.sub.3 is an acetylthiosulfate salt or when R is an optionally substituted 1-alkynyl group, then R.sub.1 may further be hydrogen, alkyl, alkenyl, aryl, aralkyl, alkynyl, optionally substituted aralkynyl, alkoxyalkyl, aminoalkyl, cyano, cyanoalkyl, thiocyanoalkyl, or azidoalkyl;
- or a physiologically acceptable 3-ester, 20-ester, 21-ester, 3,20-diester, or 3,21-diester thereof.
30 more elements
A compound of the formula:
- ##STR3## or a physiologically acceptable 3-ester, 20-ester, 21-ester, 3,20-diester, or 3,21-diester thereof;
- wherein:
- R is hydrogen, halogen, lower alkoxy, dialkylamino, alkyl or substituted alkyl;
- R.sub.1 is a substituted aralkynyl, arylalkyl, arylalkenyl, optionally substituted aralkylalkynyl, alkanoyloxyalkynyl, optionally substituted heteroaryloxyalkynyl, oxoalkynyl or a ketal thereof, cyanoalkynyl, substituted heteroarylalkynyl, hydroxyalkynyl, alkoxyalkynyl, aminoalkynyl, acylaminoalkynyl, mercaptoalkynyl, hydroxyalkynyl dioic acid hemi-ester or a salt thereof, or alkynyloxyalkynyl;
- R.sub.2 is hydrogen, hydroxy, alkoxy, alkanoyloxy, carbalkoxy, a keto group or amino group;
- R.sub.3 is an acetyl group, a ketal of an acetyl group;
- an alkoxyacetyl group, an alkylthioacetyl group, an alkylsulfinylacetyl group, an alkylsulfonylacetyl group, an aminoacetyl group, a trifluoroacetyl group;
- a hydroxyacetyl group;
- an alkoxyalkylacetyl group;
- a hydroxyalkyl group;
- a hydroxyacetyl dioic acid hemi-ester salt;
- an alkanoyloxyacetyl group;
- a sulfoxyacetyl group;
- an alkylacetyl group;
- a haloacetyl group;
- an ethynyl group;
- or a cyano group;
- or R.sub.3 together with R.sub.7 is a methylene group;
- or R.sub.3 together with R.sub.7 is an alkylmethylene group;
- or R.sub.3 together with R.sub.7 is an alkoxymethylene group;
- R.sub.4 is hydrogen or methyl,
- R.sub.5 is hydrogen;
- R.sub.6 is hydrogen, alkanoyl, aminocarbonyl or alkoxycarbonyl;
- R.sub.7 is hydrogen, halogen, hydroxy, alkoxy, alkanoyloxy, or carbalkoxyl, or R.sub.7 together with R.sub.3 is a methylene group, or R.sub.7 together with R.sub.3 is an alkoxymethylene group;
- R.sub.8 is hydrogen or halogen;
- R.sub.9 is hydrogen, halogen, alkyl, alkoxy, arylalkoxy or amino;
- and
- R.sub.10 is hydrogen, halogen, alkyl, haloalkyl, hydroxy, alkoxy, alkanoyloxy, carbalkoxyl, cyano, thiocyano or mercapto.
25 more elements
Dependencies are inferred from the claim text.