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Updated: May 10, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Heterocyclic modification of a novel bicyclo[3.1.0]hexane NPY1 receptor antagonist
Guanglin Luo1, Ling Chen, Shuanghua Hu
1Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, USA. guanglin.luo@bms.com
Abstract:
A convergent synthesis route for the heterocyclic modification of a novel bicyclo[3.1.0]hexane NPY1 antagonist 2 was developed and the structure activity relationship of these modifications on NPY1 binding is reported. Two heterocyclic analogs 9 and 10 showed comparable Y1 binding potency to 2, but with improved aqueous solubility. Compound 9 demonstrated reduced spontaneous nocturnal food intake in a rat model when dosed ip. Compound 9 was also shown to be orally bioavailable and brain penetrable.
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