Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9) was written by Mussari, Christopher P.;Dodd, Dharmpal S.;Sreekantha, Ratna Kumar;Pasunoori, Laxman;Wan, Honghe;Posy, Shana L.;Critton, David;Ruepp, Stefan;Subramanian, Murali;Watson, Andrew;Davies, Paul;Schieven, Gary L.;Salter-Cid, Luisa M.;Srivastava, Ratika;Tagore, Debarati Mazumder;Dudhgaonkar, Shailesh;Poss, Michael A.;Carter, Percy H.;Dyckman, Alaric J.. And the article was included in ACS Medicinal Chemistry Letters in 2020.Formula: C9H5BrN2 This article mentions the following:
The toll-like receptor (TLR) family is an evolutionarily conserved component of the innate immune system, responsible for the early detection of foreign or endogenous threat signals. In the context of autoimmunity, the unintended recognition of self-motifs as foreign promotes initiation or propagation of disease. Overactivation of TLR7 and TLR9 have been implicated as factors contributing to autoimmune disorders such as psoriasis, arthritis, and lupus. In our search for small mol. antagonists of TLR7/9, 7f(I) was identified as possessing excellent on-target potency for human TLR7/9 as well as for TLR8, with selectivity against other representative TLR family members. Good pharmacokinetic properties and a relatively balanced potency against TLR7 and TLR9 in mouse systems (systems which lack functional TLR8) made this an excellent in vivo tool compound, and efficacy from oral dosing in preclin. models of autoimmune disease was demonstrated. In the experiment, the researchers used many compounds, for example, 5-Bromo-3-cyanoindole (cas: 90271-86-6Formula: C9H5BrN2).
5-Bromo-3-cyanoindole (cas: 90271-86-6) belongs to indole derivatives. Indole could be stereoselectively alkylated with chiral cyclopentyl sulfone reagent. Due to this activity, the indole ring system has become an important component or intermediate in the synthesis of heterocycles.Formula: C9H5BrN2
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles