COA of Formula: C4H7BrIn 2019 ,《Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic μ-Opioid Receptor (MOR) Agonist/δ-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability》 was published in Journal of Medicinal Chemistry. The article was written by Henry, Sean P.; Fernandez, Thomas J.; Anand, Jessica P.; Griggs, Nicholas W.; Traynor, John R.; Mosberg, Henry I.. The article contains the following contents:
We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in mice, and do not produce dependence. Although these attributes are promising, these analogs exhibit poor metabolic stability in mouse liver microsomes, likely due to the central tetrahydroquinoline scaffold in this series. As such, a structure-activity relationship (SAR) campaign was pursued to improve their metabolic stability. This resulted in a shift from our original bicyclic tetrahydroquinoline core to a monocyclic benzylic-core system. By eliminating one of the rings in this scaffold and exploring the SAR of this new core, two promising analogs were discovered. These analogs (5l and 5m) had potency and efficacy values at MOR better or comparable to morphine, retained their DOR-antagonist properties, and showed a 10-fold improvement in metabolic stability. The experimental part of the paper was very detailed, including the reaction process of (Bromomethyl)cyclopropane(cas: 7051-34-5COA of Formula: C4H7Br)
(Bromomethyl)cyclopropane(cas: 7051-34-5) is used as a synthetic building block for the introduction of the cyclopropylmethyl group. It was also used in the synthesis of 1,4-dienes via iron-catalyzed cross-coupling with alkenyl Grignard reagents.COA of Formula: C4H7Br
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary