Syntheses of tetrahydrothiophenes and tetrahydrofurans and studies of their derivatives as melanocortin-4 receptor ligands.
Piperazinebenzylamine derivatives from trans-4-(4-chlorophenyl)tetrahydrothiophene-3-carboxylic acid 6 and its S-oxide 7 and sulfone 8, and the tetrahydrofuran 9 and its two regioisomers 11 and 13 were synthesized and studied for their binding affinities at the human melanocortin-4 receptor. These five-membered ring constrained compounds possessed similar or lower potency compared to the acyclic analogs.
Tran
Joe A
JA
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Chen
Caroline W
CW
Tucci
Fabio C
FC
Jiang
Wanlong
W
Fleck
Beth A
BA
Chen
Chen
C
D020650:Combinatorial Chemistry Techniques; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000187:drug effects*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D005663:Furans; D008024:Ligands; C470072:MC4R protein, human; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D013876:Thiophenes