Structural modification of 19-norprogesterone I: 17-α-substituted-11-β-substituted-4-aryl and 21-substituted 19-norpregnadienedione as new antiprogestational agents
申请人:Kim Hyun K.
公开号:US06900193B1
公开(公告)日:2005-05-31
The present invention relates, inter alia, to compounds having the general formula:
in which: R
1
is a member selected from the group consisting of —OCH
3
, —SCH
3
, —N(CH
3
)
2
, —NHCH
3
, —NC
4
H
8
, —NC
5
H
10
, —NC
4
H
8
O, —CHO, —CH(OH)CH
3
, —C(O)CH
3
, —O(CH
2
)
2
N(CH
3
)
2
, and —O(CH
2
)
2
NC
5
H
10
; R
2
is a member selected from the group consisting of hydrogen, halogen, alkyl, acyl, hydroxy, alkoxy (e.g., methoxy, ethoxy, vinyloxy, ethynyloxy, cyclopropyloxy, etc.), acyloxy (e.g., acetoxy, glycinate, etc.), alkylcarbonate, cypionyloxy, S-alkyl, —SCN, S-acyl and —OC(O)R
6
, wherein R
6
is a functional group including, but not limited to, alkyl (e.g., methyl, ethyl, etc.), alkoxy ester (e.g., —CH
2
OCH
3
) and alkoxy (—OCH
3
); R
3
is a member selected from the group consisting of alkyl, hydroxy, alkoxy and acyloxy; R
4
is a member selected from the group consisting of hydrogen and alkyl; and X is a member selected from the group consisting of ═O and ═N—OR
5
, wherein R
5
is a member selected from the group consisting of hydrogen and alkyl.
In addition to providing the compounds of Formula I, the present invention provides methods wherein the compounds of Formula I are advantageously used, inter alia, to antagonize endogenous progesterone; to induce menses; to treat endometriosis; to treat dysmenorrhea; to treat endocrine hormone-dependent tumors; to treat meningiomas; to treat uterine leiomyomas; to treat uterine fibroids; to inhibit uterine endometrial proliferation; to induce cervical ripening; to induce labor; and for contraception.
本发明涉及具有以下一般式的化合物:
其中:R
1
是从羟甲基、硫甲基、二甲胺基、甲胺基、N-丁基、N-戊基、N-丁氧基、甲醛基、羟基乙氧基、乙酰基、氧代乙基二甲胺基和氧代乙基N-戊基等组成的群体中选择的成员;R
2
是从氢、卤素、烷基、酰基、羟基、烷氧基(例如,甲氧基、乙氧基、乙烯氧基、乙炔氧基、环丙氧基等)、乙酰氧基(例如,乙酰氧基、甘氨酸酯等)、烷基碳酸酯、环戊酰氧基、S-烷基、硫氰基、硫酰基和羰基氧基,其中R
6
是包括但不限于烷基(例如,甲基、乙基等)、烷氧酯(例如,-CH
2
OCH
3
)和烷氧基(-OCH
3
)在内的官能团;R
3
是从烷基、羟基、烷氧基和乙酰氧基等组成的群体中选择的成员;R
4
是从氢和烷基等组成的群体中选择的成员;X是从═O和═N-OR
5
等组成的群体中选择的成员,其中R
5
是从氢和烷基等组成的群体中选择的成员。
除了提供式I的化合物外,本发明还提供了使用式I的化合物的方法,其中这些化合物有利地用于拮抗内源孕酮;诱导月经;治疗子宫内膜异位症;治疗痛经;治疗内分泌激素依赖性肿瘤;治疗脑膜瘤;治疗子宫平滑肌瘤;治疗子宫肌瘤;抑制子宫内膜增生;诱导宫颈成熟;诱导分娩;以及避孕。