- β-Hydroxy- A nd β-Aminophosphonate Acyclonucleosides as Potent Inhibitors of Plasmodium falciparum Growth
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Malaria is an infectious disease caused by a parasite of the genus Plasmodium, and the emergence of parasites resistant to all current antimalarial drugs highlights the urgency of having new classes of molecules. We developed an effective method for the synthesis of a series of β-modified acyclonucleoside phosphonate (ANP) derivatives, using commercially available and inexpensive materials (i.e., aspartic acid and purine heterocycles). Their biological evaluation in cell culture experiments and SAR revealed that the compounds' effectiveness depends on the presence of a hydroxyl group, the chain length (four carbons), and the nature of the nucleobase (guanine). The most active derivative inhibits the growth of Plasmodium falcIParum in vitro in the nanomolar range (IC50 = 74 nM) with high selectivity index (SI > 1350). This compound also showed remarkable in vivo activity in P. berghei-infected mice (ED50 ~0.5 mg/kg) when administered by the IP route and is, although less efficient, still active via the oral route. It is the first ANP derivative with such potent antimalarial activity and therefore has considerable potential for development as a new antimalarial drug.
- Cheviet, Thomas,Wein, Sharon,Bourchenin, Gabriel,Lagacherie, Manon,Périgaud, Christian,Cerdan, Rachel,Peyrottes, Suzanne
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p. 8069 - 8087
(2020/08/12)
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- Enantioselective Hydrogenation of Racemic α-Arylamino Lactones to Chiral Amino Diols with Site-Specifically Modified Chiral Spiro Iridium Catalysts
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A protocol for highly enantioselective hydrogenation of racemic α-arylamino lactones with catalysis by site-specifically modified chiral spiro iridium complexes has been developed. With the optimized catalyst, racemic α-arylamino-γ-lactones and α-arylamino-δ-lactones could be hydrogenated to the corresponding chiral 2-amino diols with good to excellent enantioselectivities.
- Gu, Xue-Song,Yu, Na,Yang, Xiao-Hui,Zhu, An-Te,Xie, Jian-Hua,Zhou, Qi-Lin
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supporting information
p. 4111 - 4115
(2019/06/07)
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- Preparation method of sitagliptin intermediate
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The invention discloses a preparation method of a sitagliptin intermediate and belongs to the field of medicine synthesis. The invention provides a preparation method of a compound 2; the compound 2 is prepared without the need of a catalyst and a resolving agent which have a high price and harsh low-temperature conditions, so that the cost is reduced to the great extent; the preparation method has the advantages of simple technology, high purity and high yield and is suitable for mass production.
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Paragraph 0064; 0066
(2018/04/01)
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- THIADIAZOLE MODULATORS OF S1P AND METHODS OF MAKING AND USING
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The invention is directed to compounds of the formula: wherein each of the variables are defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance treating an autoimmune disease.
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Paragraph 0143
(2017/01/26)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
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Page/Page column 76
(2010/11/27)
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- A new stereocontrolled approach to a key intermediate in the synthesis of (25,3R)-capreomycidine
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A new stereocontrolled approach to the synthesis of advanced intermediate in the synthesis of nonproteinogenic amino acid (2S,3R)-capreomycidine via the novel domino reaction has been developed.
- Martinkova, Miroslava,Gonda, Jozef,Dzoganova, Martina
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p. 1199 - 1210
(2008/03/27)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
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Page/Page column 266-268
(2008/06/13)
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- 3-(Imidazolyl)-2-aminopropanoic acids
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Compounds according to formula (I) wherein n is 1-4, R1 is optionally substituted C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R2, R3,
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- A stereocontrolled synthetic route to anti-β-amino alcohols
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A physiologically indispensable β-amino hydroxy functionality has been constructed with complete anti-stereoselectivity by intramolecular iodoamidation of (Z)-olefinic homoallylic trichloroacetimidates 4-6, 18, 20, 30 and 32, which comprise bulky substituents at the vinylic positions.
- Kang, Sung Ho,Hwang, Yu Sang,Youn, Joo-Hack
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p. 7599 - 7603
(2007/10/03)
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- An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines
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Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.
- Moon, Sung-Hwan,Lee, Sujin
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p. 3919 - 3926
(2007/10/03)
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