| 摘要 |
Novel pentacyclic steroids and pentacyclic D-homosteroids comprising: (i) the tetracyclic steroid ring system or tetracyclic D-homosteroid ring system, respectively; (ii) a C(3) substituent selected from the group consisting of (a) a hydroxyl or carboxyl in the α-configuration and (b) a sulfate or other negatively charged moiety; and (iii) a fused fifth ring, the fused fifth ring comprising a hydrogen bond acceptor, and (a) in the case of the pentacyclic steroid the C(13) and C(17) carbons, or (b) in the case of the pentacyclic D-homosteroid the C(13) and C(17a) carbons, having utility as anesthetics and in the treatment of disorders relating to GABA function and activity. |
| 主权项 |
1. A method of treating convulsions related to GABAA receptor function in a mammal, said method comprising administering to a mammal in need thereof a therapeutically effective amount of a pharmaceutical composition containing a steroid or D-homosteroid and at least one pharmaceutically acceptable carrier, wherein the steroid or D-homosteroid is a compound of Formula (A)wherein
R2 is selected from the group consisting of hydrogen, alkoxy, and substituted or unsubstituted morpholine R3a is hydroxyl or carboxyl; R3b is hydrogen, alkyl, alkenyl, or alkynyl optionally substituted with halo, hydroxyl, or substituted or unsubstituted aryl; R5 is α- or β-hydrogen; R10 is hydrogen or C1-4 alkyl; R15 is hydrogen or oxo; R6, R11 and R12 are independently hydrogen or oxo; L3a is selected from the group consisting of a bond, C1-3 alkyl, heterosubstituted C1-3 alkyl, or alkoxy; X4-X5-X6 is selected from the group consisting of X9-X11-X12 is selected from the group consisting ofX40 is a bond or a carbon atom; andE is a 5- or 6-membered carbocyclic ring in the β-configuration in relation to the C and D rings, comprising a hydrogen bond acceptor and (i) the carbons at C(13) and C(17) when X40 is a bond, or (ii) the carbons at C(13) and C(17a) when X40 is carbon.
|
