Synthesis and biological activities of camphor-based non-peptide growth hormone secretagogues

被引:20
作者
Nargund, RP [1 ]
Barakat, KH [1 ]
Cheng, K [1 ]
Chan, WWS [1 ]
Butler, BR [1 ]
Smith, RG [1 ]
Patchett, AA [1 ]
机构
[1] MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT PHYSIOL,RAHWAY,NJ 07065
关键词
D O I
10.1016/0960-894X(96)00213-2
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The synthesis and growth hormone (GH) releasing activities of a novel series of camphor-based non-peptide GH secretagogues is presented. Use of the (R)-nipecotic acid amino side-chain and N-terminal derivatization of it with an (R)-(2-hydroxy)propyl group provided a potent secretagogue 18 (EC(50) = 90 nM). An o-tolyl piperazine was identified as a good replacement for the spiroindanyl piperidine. Copyright (C) 1996 Elsevier Science Ltd
引用
收藏
页码:1265 / 1270
页数:6
相关论文
共 11 条
  • [1] ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE
    BOWERS, CY
    MOMANY, FA
    REYNOLDS, GA
    HONG, A
    [J]. ENDOCRINOLOGY, 1984, 114 (05) : 1537 - 1545
  • [2] SPIROPIPERIDINES AS HIGH-AFFINITY, SELECTIVE SIGMA-LIGANDS
    CHAMBERS, MS
    BAKER, R
    BILLINGTON, DC
    KNIGHT, AK
    MIDDLEMISS, DN
    WONG, EHF
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (11) : 2033 - 2039
  • [3] CHENG K, 1989, ENDOCRINOLOGY, V124, P2791
  • [4] NANOMOLAR-AFFINITY, NONPEPTIDE OXYTOCIN RECEPTOR ANTAGONISTS
    EVANS, BE
    LUNDELL, GF
    GILBERT, KF
    BOCK, MG
    RITTLE, KE
    CARROLL, LA
    WILLIAMS, PD
    PAWLUCZYK, JM
    LEIGHTON, JL
    YOUNG, MB
    ERB, JM
    HOBBS, DW
    GOULD, NP
    DIPARDO, RM
    HOFFMAN, JB
    PERLOW, DS
    WHITTER, WL
    VEBER, DF
    PETTIBONE, DJ
    CLINESCHMIDT, BV
    ANDERSON, PS
    FREIDINGER, RM
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (25) : 3993 - 4005
  • [5] TOTAL SYNTHESIS OF BIOLOGICALLY IMPORTANT AMINO-SUGARS VIA THE NITROALDOL REACTION
    HANESSIAN, S
    KLOSS, J
    [J]. TETRAHEDRON LETTERS, 1985, 26 (10) : 1261 - 1264
  • [6] STRUCTURE-ACTIVITY-RELATIONSHIPS OF THE NON-PEPTIDYL GROWTH-HORMONE SECRETAGOGUE L-692,429
    OK, D
    SCHOEN, WR
    HODGES, P
    DEVITA, RJ
    BROWN, JE
    CHENG, K
    CHAN, WWS
    BUTLER, BS
    SMITH, RG
    FISHER, MH
    WYVRATT, MJ
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (22) : 2709 - 2714
  • [7] DESIGN AND BIOLOGICAL-ACTIVITIES OF L-163,191 (MK-0677) - A POTENT, ORALLY-ACTIVE GROWTH-HORMONE SECRETAGOGUE
    PATCHETT, AA
    NARGUND, RP
    TATA, JR
    CHEN, MH
    BARAKAT, KJ
    JOHNSTON, DBR
    CHENG, K
    CHAN, WWS
    BUTLER, B
    HICKEY, G
    JACKS, T
    SCHLEIM, K
    PONG, SS
    CHAUNG, LYP
    CHEN, HY
    FRAZIER, E
    LEUNG, KH
    CHIU, SHL
    SMITH, RG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (15) : 7001 - 7005
  • [8] A NOVEL 3-SUBSTITUTED BENZAZEPINONE GROWTH-HORMONE SECRETAGOGUE (L-692,429)
    SCHOEN, WR
    PISANO, JM
    PRENDERGAST, TK
    WYVRATT, MJ
    FISHER, MH
    CHENG, K
    CHAN, WWS
    BUTLER, B
    SMITH, RG
    BALL, RG
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (07) : 897 - 906
  • [9] STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE AMINO-ACID SIDE-CHAIN OF L-692,429
    SCHOEN, WR
    OK, D
    DEVITA, RJ
    PISANO, JM
    HODGES, P
    CHENG, K
    CHAN, WWS
    BUTLER, BS
    SMITH, RG
    WYVRATT, MJ
    FISHER, MH
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1994, 4 (09) : 1117 - 1122
  • [10] A NONPEPTIDYL GROWTH-HORMONE SECRETAGOGUE
    SMITH, RG
    CHENG, K
    SCHOEN, WR
    PONG, SS
    HICKEY, G
    JACKS, T
    BUTLER, B
    CHAN, WWS
    CHAUNG, LYP
    JUDITH, F
    TAYLOR, J
    WYVRATT, MJ
    FISHER, MH
    [J]. SCIENCE, 1993, 260 (5114) : 1640 - 1643