Fleau, Charlotte published the artcileChagas Disease Drug Discovery: Multiparametric Lead Optimization against Trypanosoma cruzi in Acylaminobenzothiazole Series, COA of Formula: C7H5ClN2S, the publication is Journal of Medicinal Chemistry (2019), 62(22), 10362-10375, database is CAplus and MEDLINE.
Acylaminobenzothiazole hits were identified as potential inhibitors of T. cruzi replication, a parasite responsible for Chagas Disease. We selected compound 1, N-(6-chlorobenzo[d]thiazol-2-yl)cyclopropanecarboxamide, for lead optimization, aiming to improve in parallel its anti-T. cruzi activity (IC50 = 0.630μM) and its human metabolic stability (human clearance = 9.57mL/min/g). A total of 39 analogs of 1 were synthesized and tested in vitro. We established a multiparametric structure activity relationship, allowing optimization of both anti-parasite activity, physicochem. parameters and ADME properties. We identified compound 50, N-(5-Fluoro-6-(trifluoromethyl)benzothiazol-2-yl)cyclopropanecarboxamide, as an advanced lead with an improved anti-T. cruzi activity in vitro (IC50 = 0.079μM), an enhanced metabolic stability (Human Clearance = 0.413mL/min/g) and opportunity for oral route of administration. After tolerability assessment, compound 50 demonstrated a promising in vivo efficacy.
Journal of Medicinal Chemistry published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, COA of Formula: C7H5ClN2S.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica