NANOMOLAR-AFFINITY, NONPEPTIDE OXYTOCIN RECEPTOR ANTAGONISTS

被引：18

作者：

EVANS, BE ^{[1
]}

LUNDELL, GF ^{[1
]}

GILBERT, KF ^{[1
]}

BOCK, MG ^{[1
]}

RITTLE, KE ^{[1
]}

CARROLL, LA ^{[1
]}

WILLIAMS, PD ^{[1
]}

PAWLUCZYK, JM ^{[1
]}

LEIGHTON, JL ^{[1
]}

YOUNG, MB ^{[1
]}

ERB, JM ^{[1
]}

HOBBS, DW ^{[1
]}

GOULD, NP ^{[1
]}

DIPARDO, RM ^{[1
]}

HOFFMAN, JB ^{[1
]}

PERLOW, DS ^{[1
]}

WHITTER, WL ^{[1
]}

VEBER, DF ^{[1
]}

PETTIBONE, DJ ^{[1
]}

CLINESCHMIDT, BV ^{[1
]}

ANDERSON, PS ^{[1
]}

FREIDINGER, RM ^{[1
]}

机构：

[1] MERCK RES LABS,DEPT NEW LEAD PHARMACOL,W POINT,PA 19486

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 25期

关键词：

D O I：

10.1021/jm00077a002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Non-peptide antagonists of the peptide hormone oxytocin (OT) with nanomolar OT receptor affinities are described. These compounds incorporate novel amido- and amidoalkylcamphor variations to the lead structure L-366,509 (1) to achieve receptor affinity enhancements of 2-3 orders of magnitude over that compound. The new OT antagonist L-367,773 (35) is shown to be an orally bioavailable agent with good duration in vivo and to inhibit OT-stimulated uterine contractions effectively in several in vitro and in vivo models.

引用

页码：3993 / 4005

页数：13

共 24 条

[1] INHIBITION OF UTERINE CONTRACTIONS OF PREMATURE LABOR WITH AN OXYTOCIN ANALOG - RESULTS FROM A PILOT-STUDY [J].

AKERLUND, M ;

STROMBERG, P ;

HAUKSSON, A ;

ANDERSEN, LF ;

LYNDRUP, J ;

TROJNAR, J ;

MELIN, P .

BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 1987, 94 (11) :1040-1044

[2]

BENSON RC, 1982, OBSTET GYNECOL, P682

[3]

BERGSTAHLER AW, 1967, REAGENTS ORGANIC SYN, P729

[4] SYNTHESIS OF OXYTOCIN IN AMNION, CHORION, AND DECIDUA MAY INFLUENCE THE TIMING OF HUMAN PARTURITION [J].

CHIBBAR, R ;

MILLER, FD ;

MITCHELL, BF .

JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) :185-192

[5] AN EFFICIENT CHEMOSELECTIVE SYNTHESIS OF NITRILES FROM PRIMARY AMIDES [J].

CLAREMON, DA ;

PHILLIPS, BT .

TETRAHEDRON LETTERS, 1988, 29 (18) :2155-2158

[6] DIMETHYLSULFOXONIUM METHYLIDE [J].

COREY, EJ ;

CHAYKOVSKY, M .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1962, 84 (05) :867-&

[7] ALPHA-NITRO KETONES AND ESTERS FROM ACYLIMIDAZOLES [J].

CRUMBIE, RL ;

NIMITZ, JS ;

MOSHER, HS .

JOURNAL OF ORGANIC CHEMISTRY, 1982, 47 (21) :4040-4045

[8] ORALLY ACTIVE, NONPEPTIDE OXYTOCIN ANTAGONISTS [J].

EVANS, BE ;

LEIGHTON, JL ;

RITTLE, KE ;

GILBERT, KF ;

LUNDELL, GF ;

GOULD, NP ;

HOBBS, DW ;

DIPARDO, RM ;

VEBER, DF ;

PETTIBONE, DJ ;

CLINESCHMIDT, BV ;

ANDERSON, PS ;

FREIDINGER, RM .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (21) :3919-3927

[9] METHODS FOR DRUG DISCOVERY - DEVELOPMENT OF POTENT, SELECTIVE, ORALLY EFFECTIVE CHOLECYSTOKININ ANTAGONISTS [J].

EVANS, BE ;

RITTLE, KE ;

BOCK, MG ;

DIPARDO, RM ;

FREIDINGER, RM ;

WHITTER, WL ;

LUNDELL, GF ;

VEBER, DF ;

ANDERSON, PS ;

CHANG, RSL ;

LOTTI, VJ ;

CERINO, DJ ;

CHEN, TB ;

KLING, PJ ;

KUNKEL, KA ;

SPRINGER, JP ;

HIRSHFIELD, J .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (12) :2235-2246

[10] MK-329 - A NONPEPTIDE CHOLECYSTOKININ-A ANTAGONIST [J].

EVANS, BE .

DRUG DEVELOPMENT RESEARCH, 1993, 29 (04) :255-261

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