6829-41-0Relevant articles and documents
Isolation and characterization of a novel tetrahydro-[2,2′]bipyrrolyl dimer as an impurity from a Knorr reaction
Thompson, Alison,Alattar, Yousef,Beshara, Cory S.,Burley, Rodney K.,Cameron, T. Stanley,Robertson, Katherine N.
, p. 777 - 781 (2004)
A novel dimer, tetraethyl 2,2′,3,3′-tetramethyl-1,1′,2, 2′-tetrahydro-4H,4′H-2,2′-bipyrrolyl-5,5,5′, 5′-tetracarboxylate, has been isolated as an impurity (0.4% yield) from a Knorr reaction for the synthesis of ethyl 3,5-dimethylpyrrole-2-carboxylate from 2,4-pentanedione and diethyl oximinomalonate in a dissolving zinc reduction. The solid-state structure of this novel dimer was determined by X-ray crystallography. Knorr reactions typically rely upon the requisite pyrrole being the only water-insoluble crystalline material present in the reaction mixture, and so work-up and purification procedures for Knorr reactions should be monitored carefully given the water-insolubility of this dimer. Investigations regarding mechanistic implications and reductive dimerization are underway.
Scalable synthesis of favipiravir: Via conventional and continuous flow chemistry
Charoensetakul, Netnapa,Khamkhenshorngphanuch, Thitiphong,Srikun, Onsiri,Srimongkolpithak, Nitipol,Thongpanchang, Chawanee,Tiyasakulchai, Thanat,Yuthavong, Yongyuth
, p. 38691 - 38693 (2021/12/20)
Decagram scale synthesis of favipiravir was performed in 9 steps using diethyl malonate as cheap starting material. Hydrogenation and bromination steps were achieved by employing a continuous flow reactor. The synthetic process provided a total of 16% yield and it is suitable for larger-scale synthesis and production. This journal is
Discovery of 3,5-Dimethyl-4-Sulfonyl-1 H-Pyrrole-Based Myeloid Cell Leukemia 1 Inhibitors with High Affinity, Selectivity, and Oral Bioavailability
Zhu, Peng-Ju,Yu, Ze-Zhou,Lv, Yi-Fei,Zhao, Jing-Long,Tong, Yuan-Yuan,You, Qi-Dong,Jiang, Zheng-Yu
, p. 11330 - 11353 (2021/08/24)
Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound 11 with primary Mcl-1 inhibition (52%@30 μM) led to the discovery of the most potent compound 40 with high affinity (Kd = 0.23 nM) and superior selectivity over other Bcl-2 family proteins (>40,000 folds). Mechanistic studies revealed that 40 could activate the apoptosis signal pathway in an Mcl-1-dependent manner. 40 exhibited favorable physicochemical properties and pharmacokinetic profiles (F% = 41.3%). Furthermore, oral administration of 40 was well tolerated to effectively inhibit tumor growth (T/C = 37.3%) in MV4-11 xenograft models. Collectively, these findings implicate that compound 40 is a promising antitumor agent that deserves further preclinical evaluations.
