Zhang, Zhuming; Connolly, Peter J.; Lim, Heng Keang; Pande, Vineet; Meerpoel, Lieven; Teleha, Christopher; Branch, Jonathan R.; Ondrus, Janine; Hickson, Ian; Bush, Tammy; Luistro, Leopoldo; Packman, Kathryn; Bischoff, James R.; Ibrahim, Salam; Parrett, Christopher; Chong, Yolanda; Gottardis, Marco M.; Bignan, Gilles published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC)》.Related Products of 109384-19-2 The article contains the following contents:
Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clin. relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clin. stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC). The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Related Products of 109384-19-2)
tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Related Products of 109384-19-2
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem