Novel Piperidinyl-Azetidines as Potent and Selective CCR4 Antagonists Elicit Antitumor Response as a Single Agent and in Combination with Checkpoint Inhibitors.

The C-C chemokine receptor 4 (CCR4) is broadly expressed on regulatory T cells (T) as well as other circulating and tissue-resident T cells. T can be recruited to the tumor microenvironment (TME) through the C-C chemokines CCL17 and CCL22. T accumulation in the TME has been shown to dampen the antitumor immune response and is thought to be an important driver in tumor immune evasion.

Carbazole-containing amides and ureas: Discovery of cryptochrome modulators as antihyperglycemic agents.

A series of novel carbazole-containing amides and ureas were synthesized. A structure-activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the desired pharmacokinetic/pharmacodynamic parameters and the results of efficacy studies in db/db mice, compound 50 was selected for further profiling.

Carbazole-containing sulfonamides and sulfamides: Discovery of cryptochrome modulators as antidiabetic agents.

A series of novel carbazole-containing sulfonamides and sulfamides were synthesized. A structure-activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the results of efficacy studies in diet-induced obese (DIO) mice, and the desired pharmacokinetic parameters, compound 41 was selected for further profiling.