58561-08-3Relevant articles and documents
Design and Synthesis of 2-(1-Alkylaminoalkyl)pyrazolo[1,5-a]pyrimidines as New Respiratory Syncytial Virus Fusion Protein Inhibitors
Abe-Kumasaka, Tomoko,Busujima, Tsuyoshi,Iwakiri, Kanako,Kanuma, Kosuke,Kawaguchi, Takanori,Kurosaka, Jun,Ogata, Yuya,Sugaya, Yutaka,Sugiyama, Hiroyuki,Takahashi, Ryo,Tamura, Yunoshin,Tanigawa, Eiji,Ueda-Yonemoto, Naoko,Yamaguchi-Sasaki, Toru
, p. 345 - 362 (2020/05/14)
Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections and a significant pathogen for both adults and children. Although two drugs have been approved for the treatment of RSV infections, the low therapeutic index of these drugs have led pharmaceutical companies to develop safe and effective small-molecule anti-RSV drugs. The pyrazolo[1,5-a]pyrimidine series of compounds containing a piperidine ring at the 2-position of the pyrazolo[1,5-a]pyrimidine scaffold are known as candidate RSV fusion (F) protein inhibitor drugs, such as presatovir and P3. The piperidine ring has been revealed to facilitate the formation of an appropriate dihedral angle between the pyrazolo[1,5-a]pyrimidine scaffold and the plane of the amide bond for exertion of anti-RSV activity. A molecular-dynamic study on newly designed compounds with an acyclic chain instead of the piperidine ring proposed and demonstrated a new series of pyrazolo[1,5-a]pyrimidine derivatives, such as 9c with a 1-methyaminopropyl moiety, showing similar dihedral angle distributions to those in presatovir. Compound 9c exhibited potent anti-RSV activity with an EC50 value of below 1nM, which was similar to that of presatovir. A subsequent optimization study on the benzene ring of 9c led to the potent RSV F protein inhibitor 14f with an EC50 value of 0.15nM. The possibility of improving the biological properties of anti-RSV agents by modification at the 7-position of pyrazolo[1,5-a]pyrimidine is also discussed.
N-1 BRANCHED CYCLOALKYL SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Page/Page column 44, (2019/12/15)
lmidazo[4,5-c]quinoline compounds of formula (II) having a substituent that is attached at the N-l position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds
Bioproduction of l-2-Aminobutyric Acid by a Newly-Isolated Strain of Aspergillus tamarii ZJUT ZQ013
An, Zhengfang,Gu, Xiaoxu,Liu, Yue,Ge, Jingyan,Zhu, Qing
, p. 837 - 844 (2017/03/24)
Abstract: l-2-Aminobutyric acid (l-ABA), an unnatural amino acid, is a key intermediate of several important drugs. Although some methods have been developed to prepare pure chiral l-ABA, there are still many drawbacks, including low catalytic efficiency, cumbersome steps and high cost due to the addition of some expensive catalysts or coenzymes. Herein, with chemical and biological approaches together, we discovered a newly isolated Aspergillus tamarii ZJUT ZQ013 strain containing a microbial lipase which could be employed to resolve racemic methyl N-Boc-2-aminobutyrate to produce l-ABA with high enantioselectivity (e.e.s?>?99.9%, E = 257). Moreover, the subsequent gram scale experiment confrimed that A. tamarii ZJUT ZQ013 could be an attractive biocatalyst for the efficient preparation of optically pure acid. Graphical Abstract: [Figure not available: see fulltext.]
NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS
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Paragraph 200, (2016/08/23)
The invention relates to novel heteroaryl and heterocycle compounds of formula I and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune diseases and cancer.
MaxPHOS ligand: PH/NH tautomerism and rhodium-catalyzed asymmetric hydrogenations
Cristobal-Lecina, Edgar,Etayo, Pablo,Doran, Sean,Reves, Marc,Martin-Gago, Pablo,Grabulosa, Arnald,Costantino, Andrea R.,Vidal-Ferran, Anton,Riera, Antoni,Verdaguer, Xavier
, p. 795 - 804 (2014/04/03)
MaxPHOS is an active and robust P-stereogenic ligand for asymmetric catalysis. The presence of an -NH- bridge between the two phosphine moieties allows the NH/PH tautomerism to take place. The neutral ligand, in which the NH form predominates, is an air-sensitive compound. However, protonation of MaxPHOS leads to the stable PH form of the ligand, in which the overall positive charge is distributed on both P centers. This protonation turns the MaxPHOS×HBF4 salt 3 into an air-stable compound both in the solid state and in solution. The salt 3 is also a convenient precursor for the preparation of rhodium(I) complexes by direct ligand exchange with the complex [Rh(acac)(cod)]. Finally, the corresponding rhodium(I)-MaxPHOS complex was tested in the asymmetric hydrogenation of a wide range of substrates. The complex proved to be a highly selective and robust system in these reactions.
Chiral rhodium complexes derived from electron-rich phosphine-phosphites as asymmetric hydrogenation catalysts
Etayo, Pablo,Nunez-Rico, Jose L.,Vidal-Ferran, Anton
experimental part, p. 6718 - 6725 (2012/02/05)
Two new chiral cationic rhodium(I) complexes derived from electron-rich dicyclohexylphosphine-phosphite ligands were prepared from enantiopure Sharpless epoxy ethers. The best-performing catalyst system, which bears a less bulky methyl ether moiety, exhibited remarkably high enantioselectivity (up to 99% ee) and reactivity (up to >2500 TON) in asymmetric hydrogenation reactions of various functionalized alkenes (α-(acylamino)acrylates, itaconic acid derivatives, α-substituted enol esters and α-arylenamides). Our synthetic methodology has been successfully applied to the enantioselective synthesis of the antiepileptic drug (R)-lacosamide (Vimpat).
Peptide-based inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase): Model compounds towards small molecule inhibitors
Oscarsson, Karin,Poliakov, Anton,Oscarson, Stefan,Danielson, U. Helena,Hallberg, Anders,Samuelsson, Bertil
, p. 2955 - 2963 (2007/10/03)
From L-α-aminobutyric acid (Abu) a set of electrophilic and non-electrophilic replacements for the P1 cysteine of substrate and product inhibitors of hepatitis C virus full-length NS3 (protease-helicase/NTPase) serine protease have been synthesised and co
On the stabilization of the syn-rotamer of amino acid carbamate derivatives by hydrogen bonding
Marcovici-Mizrahi, Dana,Gottlieb, Hugo E.,Marks, Vered,Nudelman, Abraham
, p. 8402 - 8406 (2007/10/03)
The syn-rotamers of carbamate derivatives of α-amino acids are shown to be stabilized by the formation of H-bond complexes with carboxylic acid moieties in solution. This effect is, as expected, concentration and temperature dependent. Thermodynamic parameters (both ΔG° and ΔG?) for N-Boc-alanine were determined by NMR in the ±60 °C range.
APPROACHES TOWARD THE TOTAL SYNTHESES OF ASTIN A, B, AND C
Jiang, Jianjun,Schumacher, Kelly K.,Joullie, Madeleine M.,Davis, Franklin A.,Reddy, Rajarathnam E.
, p. 2121 - 2124 (2007/10/02)
Two nonessential amino acids, (+)-(S)-2-aminobutanoic acid and the methyl ester of L-β-phenylalanine , were synthesized to provide a tripeptide which will be used in the total syntheses of astins A, B, and C.
LES ORGANOCUPRATES DANS UNE NOUVELLE SYNTHESE D'AMINOACIDES ENANTIOMERIQUEMENT PURS
Bajgrowicz, J. A.,Hallaoui, A. El,Jacquier, R.,Pigiere, Ch.,Viallefont, Ph.
, p. 1833 - 1845 (2007/10/02)
A new general method of synthesis of optically pure α- amino esters was elaborated during studies on the reaction of organocuprates with tosyl and halogeno derivatives of L-serine and L-homoserine.
