Low brain CB1 receptor occupancy by a second generation CB1 receptor antagonist TM38837 in comparison with rimonabant in nonhuman primates: a PET study.

Both central and peripheral cannabinoid receptor type 1 (CB1R) have been considered to be among the key targets for obesity treatment. First generation CB1R antagonists/inverse agonists such as rimonabant and taranabant exhibited severe CNS side effects such as anxiety and depression, which are considered to be related to the compounds' ability to access central CB1R. Recently, several compounds have been developed as second generation antagonists with a profile of restriction to peripheral CB1R.

6-Acylamino-2-amino-4-methylquinolines as potent melanin-concentrating hormone 1 receptor antagonists: structure-activity exploration of eastern and western parts.

SAR explorations of the eastern and western parts of recently disclosed 2-aminoquinoline MCH1R-antagonists are reported. Eastern part investigations confirmed a high degree of structural freedom, and a number of additional single digit nanomolar antagonists were identified. Investigations of the western part also confirmed the initial SAR analysis, requiring a para-substituted phenyl ring spaced from the 6-amide by two connecting atoms.

6-Acylamino-2-aminoquinolines as potent melanin-concentrating hormone 1 receptor antagonists. Identification, structure-activity relationship, and investigation of binding mode.

Novel 6-acylamino-2-aminoquinoline melanin-concentrating hormone 1 receptor (MCH1R) antagonists were identified by sequential in silico screening with 3D pharmacophore models derived from a series of benzamide antagonists. The structure-activity relationship exploration by synthesis of analogues found structural demands around the western part of the compounds to be quite specific, whereas much structural freedom was found in the eastern part. While these compounds in general suffered from poor solubility properties, the 4-trifluoromethoxyphenoxyacetamide western appendage provided a favorable combination of activity and solubility properties.

4-Acylamino-and 4-ureidobenzamides as melanin-concentrating hormone (MCH) receptor 1 antagonists.

Synthesis, in vitro biological evaluation and structure-activity relationships of 4-acylamino-and 4-ureidobenzamides as novel hMCH1R-antagonists are disclosed. The nature of the amine side chains could be varied considerably in contrast to the central benzamide scaffold and aromatic substituents.