7170-01-6Relevant academic research and scientific papers
Seco C-nucleoside analogs of the 1,2,4-triazole
El Ashry,Awad
, p. 901 - 902 (2001)
The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and D-galacto-pentitol-1-yl)-1H-1,2,4-triazoles (6 and 7) were obtained in one pot by deamination and dethiolation of 4-amino-3-(D-gluco- and D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazoles (
Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir
Wang, Tao,Ueda, Yasu,Zhang, Zhongxing,Yin, Zhiwei,Matiskella, John,Pearce, Bradley C.,Yang, Zheng,Zheng, Ming,Parker, Dawn D.,Yamanaka, Gregory A.,Gong, Yi-Fei,Ho, Hsu-Tso,Colonno, Richard J.,Langley, David R.,Lin, Pin-Fang,Meanwell, Nicholas A.,Kadow, John F.
, p. 6308 - 6327 (2018/06/27)
The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species. However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.
The synthesis of nebularine and its analogs via oxidative desulfuration in aqueous nitric acid
Xia, Ran,Sun, Li-Ping,Qu, Gui-Rong
, p. 88 - 91 (2016/12/24)
The synthesis of nebularine and its analogs has been achieved via oxidative desulfuration in H2O for the first time. With 50% HNO3as an oxidant and solvent, 18 products were obtained in good yields (70%–94%). The oxidative desulfuration system could tolerate different functional groups including fluoro, chloro, amino, alkyl, allyl, ribosyl, deoxyribosyl, and arabinofuranosyl groups.More importantly, the drug nebularine could be obtained successfully on a 20 g scale, which made this route more attractive for industrial applications.
3-Mercapto-1,2,4-triazoles and N-acylated thiosemicarbazides as metallo-β-lactamase inhibitors
Faridoon,Hussein, Waleed M.,Vella, Peter,Islam, Nazar Ul,Ollis, David L.,Schenk, Gerhard,McGeary, Ross P.
supporting information; experimental part, p. 380 - 386 (2012/02/04)
The production of β-lactamases is an effective strategy by which pathogenic bacteria can develop resistance against β-lactam antibiotics. While inhibitors of serine-β-lactamases are widely used in combination therapy with β-lactam antibiotics, there are no clinically available inhibitors of metallo-β-lactamases (MBLs), and so there is a need for the development of such inhibitors. This work describes the optimisation of a lead inhibitor previously identified by fragment screening of a compound library. We also report that thiosemicarbazide intermediates in the syntheses of these compounds are also moderately potent inhibitors of the IMP-1 MBL from Pseudomonas aeruginosa. The interactions of these inhibitors with the active site of IMP-1 were examined using in silico methods.
Process for preparing triazole substituted azaindoleoxoacetic piperazine derivatives and novel salt forms produced therein
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Page/Page column 31, (2008/06/13)
A process is provided for preparing triazole substituted azaindoleoxoacetic piperazine derivative. Novel intermediates produced in the above process, and novel N-1 and amorphous forms of a 1,2,3-triazole substituted azaindoloxoacetic piperazine derivatives and processes for producing such novel forms are also provided.
Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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, (2008/06/13)
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiv
Prodrugs of piperazine and substituted piperidine antiviral agents
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Page/Page column 27, (2010/02/14)
This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R1 does not exist; W is C or N with the proviso that when W is N, R2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C1-C6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.
Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
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Page 219, (2008/06/13)
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.
Novel synthesis of seco type of acyclo C-nucleosides of 1,2,4-triazole and 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine
El Ashry,Awad
, p. 103 - 116 (2007/10/03)
The seco C-nucleosides 3-(1,2,3,4,5-penta-O-acetyl-D-gluco- and Dgalacto-pentitol-1-yl)-1 H-1,2,4-triazoles (8 and 9) were obtained in a one pot by deamination and dethiolation of 4-amino-3-(.D-gluco- and D-galactopentitol-1-yl)-5-mercapto-1,2,4-triazoles (1 and 2), respectively, using sodium nitrite in orthophosphoric acid and subsequent acetylation. Condensation of 1, 2, and 4-amino-3-(D-glycero-D-gulo-hexitol-1-yl)-5-mercapto- 1,2,4-triazole (12) with phenacylbromide (11) afforded the corresponding 3-(D-gluco-, D-galactopentitol-1-yl) and 3-(D-glycero-D-gulo-hexitol-1-yl)-6-phenyl-7 H- 1,2,4triazolo[3,4-b][1,3,4] thiadiazines (15, 16, and 17). Acetylation of 15-17 gave the penta- and hexa-O-acetyl derivatives 18-20, respectively. The structures were confirmed by using 1H, 13C, and 2D NMR spectra, DQFCOSY, HMQC, and HMBC experiments. The favored conformational structures were deduced from the vicinal coupling constants of the protons.
Synthesis of 3(5)-substituted 1,2,4-triazoles by lithiation of 1-(1-pyrrolidinomethyl)-1,2,4-triazole
Katritzky, Alan R.,Lue, Ping,Yannakopoulou, Konstantina
, p. 641 - 648 (2007/10/02)
1,2,4-Triazole 1 is readily converted into 3(5)-substituted 1,2,4-triazoles 4 by a three-step sequence: (i) Mannich reaction with formaldehyde and pyrrolidine; (ii) lithiation of 1-(1-pyrrolidinomethyl)-1, 2,4-triazole 2, followed by addition of an electrophile; (iii) deprotection of the N-aminal groups of the N-protected 3-substituted 1,2,4-triazoles 3 using sodium borohydride (NaBH4) in ethanol. 3(5)-Substituted 1,2,4-triazoles 4 result in good overall yields.
