21928-11-0Relevant articles and documents
Direct carbamoylation of aryl halides
Cunico, Robert F.,Maity, Bikash C.
, p. 4357 - 4359 (2002)
(Equation presented) A carbamoylsilane is shown to carry out the direct carbamoylation of aryl chlorides, bromides, and iodides under catalysis by phosphinepalladium-(0) complexes.
KCNT1 INHIBITORS AND METHODS OF USE
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Paragraph 000317, (2020/11/23)
The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.
Novel betrixaban intermediate and preparation method and application thereof
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Paragraph 0061; 0062; 0064, (2019/07/10)
The invention discloses a novel betrixaban intermediate and a preparation method and application thereof. The structure of the intermediate is shown in formula I. The intermediate can achieve efficient and high-yield construction of an N,N-dimethylcarbamimidoyl structure fragment in the betrixaban structure through a bio-enzyme catalysis method, and has the advantages of being green and environmentally friendly.
Novel Human Aminopeptidase N Inhibitors: Discovery and Optimization of Subsite Binding Interactions
Lee, Jisook,Vinh, Natalie B.,Drinkwater, Nyssa,Yang, Wei,Kannan Sivaraman, Komagal,Schembri, Luke S.,Gazdik, Michelle,Grin, Peter M.,Butler, Georgina S.,Overall, Christopher M.,Charman, Susan A.,McGowan, Sheena,Scammells, Peter J.
supporting information, p. 7185 - 7209 (2019/08/28)
Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-M1 inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.
MONONUCLEAR IRON COMPLEX AND ORGANIC SYNTHESIS REACTION USING SAME
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, (2016/02/19)
Provided is a mononuclear iron complex that comprises an iron-silicon bond that is represented by formula (1) and that exhibits excellent catalyst activity in each of a hydrosilylation reaction, a hydrogenation reaction, and reduction of a carbonyl compound. In formula (1), R1-R6 either independently represent an alkyl group, an aryl group, an aralkyl group or the like that may be substituted with a hydrogen atom or X, or represent a crosslinking substituent in which at least one pair comprising one of R1-R3 and one of R4-R6 is combined. X represents a halogen atom, an organoxy group, or the like. L represents a two-electron ligand other than CO. When a plurality of L are present, the plurality of L may be the same as or different from each other. When two L are present, the two L may be bonded to each other. n and m independently represent an integer of 1 to 3 with the stipulation that n+m equals 3 or 4.
Copper-catalyzed amide bond formation from formamides and carboxylic acids
Liu, Hong-Qiang,Liu, Jun,Zhang, Yang-Hui,Shao, Chang-Dong,Yu, Jing-Xun
, p. 11 - 14 (2015/01/30)
A highly efficient copper-catalyzed approach to form amide bonds from formamides and carboxylic acids was developed. This protocol shows broad substrate scopes and high yields in the presence of 1 mol% catalyst and 4.0 equiv. formamides.
Syntheses of amides via iodine-catalyzed multiple sp3 C-H bonds oxidation of methylarenes and sequential coupling with N,N-dialkylformamides
Du, Bingnan,Sun, Peipei
, p. 1176 - 1182 (2014/08/18)
The oxidative coupling of methylarenes and N,N-dialkylformamides was developed, and the appropriate reaction conditions were established. By using I2 as the catalyst, and tert-butyl hydroperoxide (TBHP) as the oxidant, the reaction provided N,N
Identification of a potent sodium hydrogen exchanger isoform 1 (NHE1) inhibitor with a suitable profile for chronic dosing and demonstrated cardioprotective effects in a preclinical model of myocardial infarction in the rat
Huber, John D.,Bentzien, J?rg,Boyer, Stephen J.,Burke, Jennifer,De Lombaert, Stéphane,Eickmeier, Christian,Guo, Xin,Haist, James V.,Hickey, Eugene R.,Kaplita, Paul,Karmazyn, Morris,Kemper, Raymond,Kennedy, Charles A.,Kirrane, Thomas,Madwed, Jeffrey B.,Mainolfi, Elizabeth,Nagaraja, Nelamangara,Soleymanzadeh, Fariba,Swinamer, Alan,Eldrup, Anne B.
, p. 7114 - 7140 (2012/11/07)
Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl- piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.
Cross coupling of acyl and aminyl radicals: Direct synthesis of amides catalyzed by Bu4NI with TBHP as an oxidant
Liu, Zhaojun,Zhang, Jie,Chen, Shulin,Shi, Erbo,Xu, Yuan,Wan, Xiaobing
experimental part, p. 3231 - 3235 (2012/05/05)
A radical solution: A Bu4NI/tert-butyl hydroperoxide (TBHP) catalyzed synthesis of amides through a cross-coupling reaction between acyl and aminyl radicals is described. This method involves the combination of aldehyde C-H bond functionalization and decarbonylation of N,N-disubstituted formamides (see scheme). The cross-coupling is metal-free, has a wide substrate scope, operational simplicity, and gives high yields on scale-up. Copyright
NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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Page/Page column 63, (2012/03/27)
A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar