ABSTRACT
During the synthesis of the bulk drug Raloxifene hydrochloride, eight impurities were observed, four of which were found to be new. All of the impurities were detected using the gradient high performance liquid chromatographic (HPLC) method, whose area percentages ranged from 0.05 to 0.1%. LCMS was performed to identify the mass number of these impurities, and a systematic study was carried out to characterize them. These impurities were synthesized and characterized by spectral data, subjected to co-injection in HPLC, and were found to be matching with the impurities present in the sample. Based on their spectral data (IR, NMR, and Mass), these impurities were characterized as Raloxifene-N-Oxide [Impurity: 1]; EP impurity A [Impurity: 2]; EP impurity B [Impurity: 3]; Raloxifene Dimer [Impurity: 4]; HABT (6-Acetoxy-2-[4-hydroxyphenyl]-1-benzothiophene or 6-Hydroxy-2-[4-acetoxyphenyl]-1-benzothiophene) [Impurity: 5]; PEBE (Methyl[4-[2-(piperidin-1-yl)ethoxy]]benzoate) [Impurity: 6]; HHBA (1-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl]ethanone) [Impurity: 7]; 7-MARLF (7-Acetyl-[6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl methanone) [Impurity: 8]; of which impurities 5-8 are reported for the first time.
ABSTRACT
Active site of reverse transcriptase contains carboxylate groups involved in the magnesium binding. We prepared some nucleoside analogs which could bind to these carboxylates preventing the binding of nucleotides. To the 3'-amino-3'-deoxy-thymidine, different N-protected omega-amino-acids were bound, the protection removed to give the 3'-(omega-amino-acyl-) amino-3'-deoxy-thymidines in good yield. Some showed moderate to low activity in HIV 1 replication test.
Subject(s)
HIV Reverse Transcriptase/antagonists & inhibitors , HIV Reverse Transcriptase/chemistry , Thymidine/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Catalytic Domain , Cell Line, Tumor , Drug Design , Drug Screening Assays, Antitumor , HIV Reverse Transcriptase/metabolism , HIV-1/drug effects , HIV-1/physiology , Humans , Magnesium/metabolism , Magnetic Resonance Spectroscopy , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Thymidine/chemical synthesis , Thymidine/pharmacology , Virus Replication/drug effectsABSTRACT
Two new bromotyrosine-derived metabolites (1, 2) have been isolated along with the known compounds 3,5-dibromo-4-methoxyphenylacetonitrile, 3-bromo-4-methoxyphenylacetonitrile, 3-bromo-4-hydroxyphenylacetonitrile, 1-hydroxyuracil, 1-methoxyhemibastadin 2, purpuramine H and a steroid 5alpha,8alpha-epidioxycholest-6-en-3beta-ol from the sponge Psammaplysilla purpurea. Compounds 1 and 2 were characterized by interpretation of their spectral data. The antibacterial activity of these compounds is summarized.
