495-42-1Relevant academic research and scientific papers
Method for synthesizing chiral alpha-amino alcohol compound
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Paragraph 0083-0091, (2021/07/28)
The invention discloses a method for synthesizing a chiral alpha-amino alcohol compound. The method comprises the following steps: sequentially adding an iron catalyst, a ligand, ketone, an organic solvent and silane into a reaction system at 20-30 DEG C in a nitrogen atmosphere, then stirring the obtained mixture, and carrying out column chromatography separation on the obtained product to obtain a product, namely chiral alpha-amino alcohol. According to the invention, the most high-yield iron catalyst in earth crust is used, and cheap silane (PMHS, 500 g/298 yuan) is adopted as a reducing agent, so the asymmetric reduction reaction of alpha-amino ketone can be efficiently achieved under mild conditions so as to obtain the high-yield optically-active chiral alpha-amino alcohol compound; and moreover, through the creative labor of the inventor, reaction yield can reach 99%, and meanwhile, the content of the target product in the generated reaction product is 99%.
AMIDO THIADIAZOLE DERIVATIVES AS NADPH OXIDASE INHIBITORS
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Page/Page column 83; 84, (2016/07/05)
The present invention is related to amino thiazole derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).
Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors
Langford, H. Marie,Williams, Peter D.,Homnick, Carl F.,Vacca, Joseph P.,Felock, Peter J.,Stillmock, Kara A.,Witmer, Marc V.,Hazuda, Daria J.,Gabryelski, Lori J.,Schleif, William A.
, p. 721 - 725 (2008/12/23)
A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was synthesized and tested for their inhibition of HIV-1 integrase catalytic activity and HIV-1 replication in cells. Structure-activity studies around lead compound 5 indicated that a coplanar relationship of metal-binding heteroatoms provides optimal binding to the integrase active site. Identification of potency-enhancing substituents and adjustments in lipophilicity provided 17b which inhibits integrase-catalyzed strand transfer with an IC50 value of 74 nM and inhibits HIV-1 replication in cell culture in the presence of 50% normal human serum with an IC95 value of 63 nM.
Asymmetric hydrogenation of α-primary and secondary amino ketones: Efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine
Shang, Gao,Liu, Duan,Allen, Scott E.,Yang, Qin,Zhang, Xumu
, p. 7780 - 7784 (2008/04/03)
Two ss-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of α-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation repI resents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.
2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases
Schnute, Mark E.,Anderson, David J.,Brideau, Roger J.,Ciske, Fred L.,Collier, Sarah A.,Cudahy, Michele M.,Eggen, MariJean,Genin, Michael J.,Hopkins, Todd A.,Judge, Thomas M.,Kim, Euibong J.,Knechtel, Mary L.,Nair, Sajiv K.,Nieman, James A.,Oien, Nancee L.,Scott, Allen,Tanis, Steven P.,Vaillancourt, Valerie A.,Wathen, Michael W.,Wieber, Janet L.
, p. 3349 - 3353 (2008/02/07)
A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent antivirals against human herpesviruses. These compounds demonstrate broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.
Solvent and in situ catalyst preparation impacts upon Noyori reductions of aryl-chloromethyl ketones: application to syntheses of chiral 2-amino-1-aryl-ethanols
Tanis, Steven P.,Evans, Bruce R.,Nieman, James A.,Parker, Timothy T.,Taylor, Wendy D.,Heasley, Steven E.,Herrinton, Paul M.,Perrault, William R.,Hohler, Richard A.,Dolak, Lester A.,Hester, Matthew R.,Seest, Eric P.
, p. 2154 - 2182 (2007/10/03)
As part of medicinal chemistry efforts we found it necessary to develop general syntheses of highly enantiomerically enriched 1-aryl-2-chloroethanols and 1-aryl-2-methylaminoethanols. A survey of literature methods suggested that a truly general approach had not yet been reported, encouraging us to undertake the development of such a methodology. This study describes the design, development, and reduction to practice of a general synthesis of chiral 1-aryl-2-chloroethanols and the transformation of these entities to highly enantiomerically enriched 1-aryl-2-methylaminoethanols. Of particular importance were observations of the impact of solvent and the method of catalyst preparation on the yield and enantiomerical excess of chlorohydrins prepared via Noyori transfer hydrogenations of aryl-chloromethyl ketones.
HIV INTEGRASE INHIBITORS
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Page/Page column 82, (2008/06/13)
Bicyclic pyrazoles of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: (I), wherein Z is O or N(R8); n is an integer equal to zero or 1; and R1, R2, R3, R4, R5, R6, R7 and R8 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
Stereoselective synthesis of (1R)- and (1R,2S)-1-aryl-2-alkylamino alcohols from (R)-cyanohydrins
Effenberger, Franz,Gutterer, Beate,Jaeger, Juergen
, p. 459 - 467 (2007/10/03)
Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without racemization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alcohols (1R,2S)-4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 and (1R,2S)-9 can be prepared either by reductive alkylation of the corresponding 2-amino alcohols (R)-3 and (1R,2S)-4, respectively, or by a transimination reaction of the Grignard addition products with primary amines and subsequent hydrogenation with NaBH4. The lower diastereoselectivity of hydrogenation in case of the N-alkylmino compounds in comparison to the N-unsubstituted imines is explained by a weaker chelating effect.
Method of preparing vicinal aminoalcohols
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, (2008/06/13)
The present invention is concerned with the preparation of N-substituted vicinal aminoalcohol derivatives from the corresponding hydroxyl-protected cyanohydrin derivatives by successive partial reduction, transimination using a primary amine, reduction of the resulting imine and optional removal of the hydroxyl-protecting group. The products are obtained either as a racemate or in an optically pure form, depending upon the stereochemical composition of the starting cyanohydrin derivatives. The present invention is also concerned with certain new enantiomerically pure hydroxyl-protected vicinal aminoalcohols.
