New Generation of Selective Androgen Receptor Degraders: Our Initial Design, Synthesis, and Biological Evaluation of New Compounds with Enzalutamide-Resistant Prostate Cancer Activity was written by Hwang, Dong-Jin;He, Yali;Ponnusamy, Suriyan;Mohler, Michael L.;Thiyagarajan, Thirumagal;McEwan, Iain J.;Narayanan, Ramesh;Miller, Duane D.. And the article was included in Journal of Medicinal Chemistry in 2019.Electric Literature of C8H6N2O2 This article mentions the following:
In our effort to find small-mol. treatments of advanced prostate cancers (PCs), a novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced submicromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV). II and III maintained potency against enzalutamide-resistant (Enz-R) mutant ARs and PC cells and were efficacious in Enz-R xenografts, suggesting their potential to treat advanced PCs. Design, synthesis, and biol. activity of novel SARDs that could potentially be used for the treatment of a wide spectrum of PCs including castration-resistant, Enz-R, and/or AR SV-dependent advanced PCs that are often untreatable with known hormone therapies are discussed. In the experiment, the researchers used many compounds, for example, 6-Nitro-1H-indole (cas: 4769-96-4Electric Literature of C8H6N2O2).
6-Nitro-1H-indole (cas: 4769-96-4) belongs to indole derivatives. Indole is an important structural motif of various drugs, therapeutic leads besides its prevalence in numerous natural products, agrochemicals, perfumery, and dyes. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Electric Literature of C8H6N2O2
Referemce:
Indole alkaloid derivatives as building blocks of natural products from闂佽壈浜崹淇沜illus thuringiensis闂佽壈浜粋鍧闂佽壈浜崹淇沜illus velezensis闂佽壈浜粋鍧 their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles