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
AKERLUND, M
STROMBERG, P
HAUKSSON, A
ANDERSEN, LF
LYNDRUP, J
TROJNAR, J
MELIN, P
[J]. 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
CHIBBAR, R
MILLER, FD
MITCHELL, BF
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) : 185 - 192
[5] AN EFFICIENT CHEMOSELECTIVE SYNTHESIS OF NITRILES FROM PRIMARY AMIDES
CLAREMON, DA
PHILLIPS, BT
[J]. TETRAHEDRON LETTERS, 1988, 29 (18) : 2155 - 2158
[6] DIMETHYLSULFOXONIUM METHYLIDE
COREY, EJ
CHAYKOVSKY, M
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1962, 84 (05) : 867 - &
[7] ALPHA-NITRO KETONES AND ESTERS FROM ACYLIMIDAZOLES
CRUMBIE, RL
NIMITZ, JS
MOSHER, HS
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1982, 47 (21) : 4040 - 4045
[8] ORALLY ACTIVE, NONPEPTIDE OXYTOCIN ANTAGONISTS
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
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (21) : 3919 - 3927
[9] METHODS FOR DRUG DISCOVERY - DEVELOPMENT OF POTENT, SELECTIVE, ORALLY EFFECTIVE CHOLECYSTOKININ ANTAGONISTS
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
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (12) : 2235 - 2246
[10] MK-329 - A NONPEPTIDE CHOLECYSTOKININ-A ANTAGONIST
EVANS, BE
[J]. DRUG DEVELOPMENT RESEARCH, 1993, 29 (04) : 255 - 261

← 1 2 3 →