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Synthetic Approaches to Inhibitors of Isoprenoid Biosynthesis
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Pedro Merino, Loredana Maiuolo, Ignacio Delso, Vincenzo Algieri, Antonio De Nino, Tomas Tejero
Amino acids as starting material of bisphosphonates may be extremely complicated to use, failing in most reactions when the direct method is employed. α-Amino acid-derived bisphosphonates (38) have been prepared by using N-phthalimido-protected amino acids (35) and using sequentially tri- and diethyl phosphite as P-reagents (Scheme 2.12) (Mizrahi et al., 2001). The reaction was carried out in good yields without isolating intermediate (37). Reagents and conditions: (i) N-(ethoxycarbonyl)phthalimide, NaHCO3, 0°C, 5 min. (ii) SOCl2, CH2Cl2, 5 h, reflux. (iii) triethyl phosphite, toluene, 1 h, 0°C; (iv) diethylphosphite, Et3N, 1–3 h, 0–5°C. (v) 6N HCl, reflux, overnight; (vi) 5N NaOH, pH = 4.4.
Phosphonic Acids And Phosphonates As Antimetabolites
Published in Richard L. Hilderbrand, The Role of Phosphonates in Living Systems, 2018
Phosphonoformic acid (89) was first prepared by Nylen264 by basic hydrolysis of the corresponding triethyl ester; acidic hydrolysis leads to decarboxylation. The triethyl ester had previously been generated265 via reaction of triethyl phosphite with ethyl chloroformate.
Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Myoung-Soon Park, Hyun-Ju Park, Young Jae An, Joon Hun Choi, Geunyoung Cha, Hwa Jeong Lee, So-Jung Park, Purushottam M. Dewang, Dae-Kee Kim
The 11a–h were prepared as shown in Scheme 2. The 2-(6-alkylpyridin-2-yl)-1-(quinoxalin-6-yl)ethanones 8a–d33 were treated with NaNO2 in 5 N HCl to give the 2-(6-alkylpyridin-2-yl)-2-(hydroxyimino)-1-(quinoxalin-6-yl)ethanones 9a–d in 88–99% yields. Condensation of 9a–d with either 5a or 3-(2-oxoethyl)benzonitrile (5d)34 and NH4OAc in a mixture of t-BuOMe and MeOH at room temperature afforded the 5-(6-alkylpyridin-2-yl)-1-hydroxy-4-(quinoxalin-6-yl)-1H-imidazoles 10a–h in 37–77% yields. Conversion of the carbonitrile group of 10a–h to the carboxamide group and subsequent dehydroxylation with triethyl phosphite in anhydrous DMF at 110 °C for 3 days gave the target compounds 11a–h in 23–44% yields.