79561-82-3Relevant articles and documents
Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins
Cai, Yue-Ming,Martin, Ruben,Rui, Xi-Yan,Shang, Ming,Sun, Shang-Zheng,Wang, Jia-Bao,Yao, Hong-Qing,Zhang, De-Liang
supporting information, p. 1130 - 1137 (2022/02/05)
Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched sp3-sp3 linkages via sp3 C-N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization. In addition, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is within reach, thus providing a useful entry point for forging enantioenriched sp3-sp3 centers at remote sp3 C-H sites.
Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L
Aggarwal, Anupriya,Ashhurst, Anneliese S.,Bedding, Max J.,Beretta, Laura,Drelich, Aleksandra,Gerwick, William H.,Hook, Vivian,Larance, Mark,Li, Linfeng,McKerrow, James H.,Meek, Thomas D.,O'Donoghue, Anthony J.,Payne, Richard J.,Pwee, Dustin,Skinner, Danielle,Stoye, Alexander,Tang, Arthur H.,Tseng, Chien-Te,Turville, Stuart,Yoon, Michael C.,Fajtová, Pavla
supporting information, (2021/11/18)
Cathepsin L is a key host cysteine protease utilized by coronaviruses for cell entry and is a promising drug target for novel antivirals against SARS-CoV-2. The marine natural product gallinamide A and several synthetic analogues were identified as potent inhibitors of cathepsin L with IC50 values in the picomolar range. Lead molecules possessed selectivity over other cathepsins and alternative host proteases involved in viral entry. Gallinamide A directly interacted with cathepsin L in cells and, together with two lead analogues, potently inhibited SARS-CoV-2 infection in vitro, with EC50 values in the nanomolar range. Reduced antiviral activity was observed in cells overexpressing transmembrane protease, serine 2 (TMPRSS2); however, a synergistic improvement in antiviral activity was achieved when combined with a TMPRSS2 inhibitor. These data highlight the potential of cathepsin L as a COVID-19 drug target as well as the likely need to inhibit multiple routes of viral entry to achieve efficacy.
Preparation method of 2-NH-Boc-3-(3',4'-dimethyl-[1,1'-biphenyl]-4)propionic acid
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Paragraph 0006-0007, (2018/05/01)
The invention relates to a preparation method of 2-NH-Boc-3-(3',4'-dimethyl-[1,1'-biphenyl]-4)propionic acid, and mainly solves the technical problem of lack of industrial preparation of the 2-NH-Boc-3-(3',4'-dimethyl-[1,1'-biphenyl]-4)propionic acid at p
CRYSTALLINE(2S,4R)-5-(5'-CHLORO-2'-FLUORO-[1,1'-BIPHENYL]-4-YL)-2-(ETHOXYMETHYL)-4-(3-HYDROXYISOXAZOLE-5-CARBOXAMIDO)-2-METHYLPENTANOIC ACID AND USES THEREOF
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Page/Page column 57, (2017/09/27)
In one aspect, the invention relates to a crystalline form of the structure: or a pharmaceutically acceptable salt thereof, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising this crys
NOVEL PROCESS FOR THE PREPARATION OF SACUBITRIL AND ITS INTERMEDIATES
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Page/Page column 27, (2016/09/26)
A process for the preparation of sacubitril and its intermediates is disclosed. By practicing the methods disclosed herein, a solid form of sacubitril may be generated. A crystalline form of sacubitril is also disclosed.
(2S,4R)-5-(5'-CHLORO-2'-FLUOROBIPHENYL-4-YL)-4-(ETHOXYOXALYLAMINO)-2-HYDROXYMETHYL-2-METHYLPENTANOIC ACID
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Paragraph 0243; 0244, (2016/09/08)
In one aspect, the invention relates to a compound of the structure: or a pharmaceutically acceptable salt thereof, and a crystalline form of this compound, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical
Synthesis of an amidosulfonate-tagged biphenyl phosphine and its application in the Suzuki-Miyaura reaction affording biphenyl-substituted amino acids in water
Schulz, Ji?í,Císa?ová, Ivana,?těpni?ka, Petr
, p. 65 - 72 (2015/03/04)
An amidosulfonate-tagged phosphinobiphenyl, viz triethylammonium 2-(dicyclohexylphosphino)-4′-{[(sulfonatomethyl)amino]carbonyl}biphenyl (3), was prepared in two steps from 2-(dicyclohexylphosphino)biphenyl-4′-carboxylic acid and fully characterized including the crystal structure determination. As a highly polar phosphine ligand, compound 3 was employed in the Pd-catalyzed Suzuki-Miyaura cross-coupling of N-Boc protected 4-bromo and 4-chlorophenylalanine with aromatic boronic acids to afford the corresponding biphenyls in aqueous N,N-dimethylformamide or pure water. The coupling was demonstrated to proceed very well and without the loss of the Boc protecting group when the bromo-substituted substrate is reacted in the presence of 1 mol.% of Pd/3 catalyst in water at 40 °C. Reactions with boronic acids bearing electron-withdrawing substituents and, mainly, those with the less reactive chlorophenylalanine substrate required slightly higher reaction temperature and more catalyst to achieve similar results.
Chemoenzymatic Synthesis of Optically Pure l- and d-Biarylalanines through Biocatalytic Asymmetric Amination and Palladium-Catalyzed Arylation
Ahmed, Syed T.,Parmeggiani, Fabio,Weise, Nicholas J.,Flitsch, Sabine L.,Turner, Nicholas J.
, p. 5410 - 5413 (2015/09/15)
A chemoenzymatic approach was developed and optimized for the synthesis of a range of N-protected nonnatural l- and d-biarylalanine derivatives. Starting from 4-bromocinnamic acid and 4-bromophenylpyruvic acid using a phenylalanine ammonia lyase (PAL) and an evolved d-amino acid dehydrogenase (DAADH), respectively, both enantiomers of 4-bromophenylalanine were obtained and subsequently coupled with a panel of arylboronic acids to give the target compounds in high yield and optical purity under mild aqueous conditions.
PEPTIDYL NITRIL COMPOUNDS AS DIPEPTIDYL PEPTIDASE I INHIBITORS
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Page/Page column 26, (2015/03/28)
The invention relates to compounds of Formula (I) and its use as a selective dipeptidyl peptidase I inhibitor, as well as pharmaceutical compositions comprising said compounds, and methods of treatment involving said compounds.
NEPRILYSIN INHIBITORS
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Paragraph 0242-0243, (2015/08/04)
In one aspect, the invention relates to compounds having the formula I: where R1, R2a, R2b, and R3-R6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compound