In:
Helvetica Chimica Acta, Wiley, Vol. 80, No. 4 ( 1997-06-30), p. 1244-1259
Abstract:
The synthesis of a variety of potent macrocyclic growth hormone secretagogues, i.e. 5 , 9 , 12 , and 20 – 22 , based on the known lead structure L‐692,429 ( 1 ) is described. These conformationally constrained growth hormone secretagogues were prepared by joining the two essential pharmacophores, the amino‐acid side chain at the 1 H ‐1‐benzazepine moiety and the 1,1′‐biphenyl moiety with a variety of linkers. The most potent analog was found to be L‐744,080 ( 21 ), a derivative in which a 2′‐carboxamide moiety at 1,1‐biphenyl is N , O ‐joined to the OH group of the (2‐hydroxypropyl)amino‐acid side chain by a C 4 ester linker. This potent analog may be useful in determining the bound conformation of the benzolactam class of growth hormone secretagogues at the newly identified GHS receptor, L‐744,080 ( 21 ) with an ED 50 of 20 n M was up to fifty times more potent than the seco‐acid precursor and 3‐fold more potent than the parent 2′‐tetrazole compound L‐692, 429 ( 1 ).
Type of Medium:
Online Resource
ISSN:
0018-019X
,
1522-2675
DOI:
10.1002/hlca.19970800421
Language:
English
Publisher:
Wiley
Publication Date:
1997
detail.hit.zdb_id:
74-7
detail.hit.zdb_id:
1475013-2
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