LOW-MOLECULAR-WEIGHT NEUROKININ-NK(2) ANTAGONISTS

被引：14
|
作者：
SMITH, PW
MCELROY, AB
PRITCHARD, JM
DEAL, MJ
EWAN, GB
HAGAN, RM
IRELAND, SJ
BALL, D
BERESFORD, I
SHELDRICK, R
JORDAN, CC
WARD, P
机构：
[1] GLAXO GRP RES LTD, DEPT MED CHEM, GREENFORD UB6 0HE, MIDDX, ENGLAND
[2] GLAXO GRP RES LTD, DIV PHARMACOL, WARE SG12 0DP, HERTS, ENGLAND
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 05期
关键词：
D O I：
10.1016/S0960-894X(00)80695-2
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A deletion - optimization strategy based on an initial heptapeptide lead structure 1 led to potent and selective neurokinin NK2 antagonists 5 (pK(B)=9.3) and 9 (pK(B)=7.9) of substantially reduced molecular size. Tetrapeptide 5 (0.1 mumol/Kg i.v.) potently inhibits NK2 agonist-induced bronchoconstriction in guinea-pigs. Whilst less potent than 5 in vivo, the dipeptoid 9 (5 mumol/Kg i.v.) had a significantly longer biological half-life (> 2 h), and provides a potential lead towards non-peptide analogues.
引用
下载
收藏
页码：931 / 936
页数：6
相关论文
共 50 条
  • [1] LOW-MOLECULAR-WEIGHT, NONPEPTIDE FIBRINOGEN RECEPTOR ANTAGONISTS
    ALIG, L
    EDENHOFER, A
    HADVARY, P
    HURZELER, M
    KNOPP, D
    MULLER, M
    STEINER, B
    TRZECIAK, A
    WELLER, T
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1993, 205 : 1 - MEDI
  • [2] LOW-MOLECULAR-WEIGHT, NONPEPTIDE FIBRINOGEN RECEPTOR ANTAGONISTS
    ALIG, L
    EDENHOFER, A
    HADVARY, P
    HURZELER, M
    KNOPP, D
    MULLER, M
    STEINER, B
    TRZECIAK, A
    WELLER, T
    JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (23) : 4393 - 4407
  • [3] Low-Molecular-Weight Ligands of Luteinizing Hormone Receptor with the Activity of Antagonists
    Derkach, K., V
    Dar'in, D., V
    Shpakov, A. O.
    BIOCHEMISTRY MOSCOW SUPPLEMENT SERIES A-MEMBRANE AND CELL BIOLOGY, 2020, 14 (03) : 223 - 231
  • [4] Low-Molecular-Weight Ligands of Luteinizing Hormone Receptor with the Activity of Antagonists
    K. V. Derkach
    D. V. Dar’in
    A. O. Shpakov
    Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2020, 14 : 223 - 231
  • [5] Studies on the functional reversibility of antagonists active at neurokinin NK2 and NK3 neurokinin receptors
    von Mentzer, B.
    Ahlstedt, I.
    Kakol-Palm, D.
    Pahlman, I.
    Lindstrom, E.
    NEUROPEPTIDES, 2008, 42 (04) : 493 - 494
  • [6] THE DISCOVERY OF NONPEPTIDE, LOW-MOLECULAR-WEIGHT, ET(B) SELECTIVE ENDOTHELIN ANTAGONISTS
    CHAN, MF
    KOIS, A
    RAJU, B
    CASTILLO, RS
    VERNER, EJ
    WU, CD
    VENKATACHALAPATHI, YV
    OKUN, I
    STAVROS, FD
    BALAJI, VN
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1995, 209 : 168 - MEDI
  • [7] LOW-MOLECULAR-WEIGHT DEXTRAN
    BOSLEY, PGH
    LANCET, 1964, 2 (734): : 41 - &
  • [8] LOW-MOLECULAR-WEIGHT HEPARIN
    GOUGH, S
    BRITISH MEDICAL JOURNAL, 1991, 303 (6805): : 784 - 784
  • [9] LOW-MOLECULAR-WEIGHT HEPARIN
    THOMAS, DP
    NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (11): : 817 - 818
  • [10] LOW-MOLECULAR-WEIGHT HEPARINS
    DROUET, L
    PRESSE MEDICALE, 1993, 22 (40): : 2002 - 2008
12345