87700-65-0Relevant academic research and scientific papers
Process Development, Manufacture, and Understanding of the Atropisomerism and Polymorphism of Verinurad
Ring, Oliver T.,Hayter, Barry R.,Ronson, Thomas O.,Agnew, Lauren R.,Ashworth, Ian W.,Cherryman, Janette,Gall, Malcolm A. Y.,Hamilton, Peter R.,Inglesby, Phillip A.,Jones, Martin F.,Lamacraft, Alex L.,Leahy, Adam J.,McKinney, David,Miller-Potucka, Lucie,Powell, Lyn,Putra, Okky D.,Robbins, Andrew J.,Tomasi, Simone,Wordsworth, Rosemary A.
, p. 936 - 948 (2021/11/16)
The manufacturing route toward verinurad, an amphoteric, class II atropisomer that readily forms solvates, has proven to be highly complex. This previously required the isolation of intermediates with challenging physical properties and the application of cryogenic processes. New processes were designed and optimized, enabling the manufacture of 113 kg of verinurad in its desired polymorphic form. An interdisciplinary approach involving the synthesis, high-throughput experimentation, analytical chemistry, crystallization science, in silico modeling, and engineering was employed. Kinetic measurement of enantiomerically enriched verinurad salts confirmed that racemization occurred within the clearance time frame, thus mitigating safety concerns associated with inherent axial chirality in verinurad.
Palladium-catalyzed C–P bond activation of aroyl phosphine oxides without the adjacent “anchoring atom”
Chen, Xingyu,Liu, Xiaoyan,Zhu, Hong,Wang, Zhiqian
, (2021/01/14)
A novel palladium-catalyzed decarbonylation of aroyl phosphine oxides to prepare phosphine oxides from carboxylic acids is developed. Without the adjacent “anchoring atom”, the challenging C–P bond activation is achieved in high selectivity. The disclosure of this reaction provides a new example of C–P bond activation and helps to extend the understanding of the property of C–P bond.
Palladium-catalyzed directing group-assisted C8-triflation of naphthalenes
Yang, Zhi-Wei,Zhang, Qi,Jiang, Yuan-Ye,Li, Lei,Xiao, Bin,Fu, Yao
supporting information, p. 6709 - 6711 (2016/06/01)
The transition-metal-catalyzed direct triflation of naphthyl amides and naphthyl ketones has been accomplished for the first time. Benzophenone (BP) was found to be a suitable ligand for the cross-coupling reactions. Density functional theory (DFT) calculations revealed that excessive amounts of HOTf inhibit the reductive elimination of the C-F bond to realize the unusual reductive elimination of the C-OTf bond.
Rh-Catalyzed annulations of: N -methoxybenzamides with ketenimines: Synthesis of 3-aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation induced emission properties
Zhou, Xiaorong,Peng, Zhixing,Zhao, Hongyang,Zhang, Zhiyin,Lu, Ping,Wang, Yanguang
supporting information, p. 10676 - 10679 (2016/09/02)
Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin-1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran solution and strong green-yellow emissions in solids.
NAPHTHYL- OR ISOQUINOLINYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS
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Page/Page column 152, (2015/01/16)
The present invention relates to naphthyl-or isoquinolinyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in
Oligo(naphthylene-ethynylene) molecular rods
Cramer, Jacob R.,Ning, Yanxiao,Shen, Cai,Nuermaimaiti, Ajiguli,Besenbacher, Flemming,Linderoth, Trolle R.,Gothelf, Kurt V.
, p. 2813 - 2822 (2013/07/05)
Molecular rods designed for surface chirality studies have been synthesized in high yields. The molecules are composed of oligo(naphthylene-ethynylene) skeletons and functionalized at their two termini with carboxylic acids and hydrophobic groups. The molecular skeletons were constructed by means of palladium-catalyzed Sonogashira reactions between naphthyl halides and acetylenes. The triazene functionality was used as a protected iodine precursor to allow linear extension of the molecular rods during the syntheses. The carboxylic acid groups in the target molecules were protected as esters during the synthesis to keep the large aromatic molecules soluble during their syntheses. These rigid oligomers were designed to form lamella-like structures when adsorbed on a surface, through which multiple distinguishable surface conformations should be obtainable. Preliminary scanning tunneling microscopy imaging confirmed these properties. Copyright
Synthesis and pharmacology of 1-alkyl-3-(1-naphthoyl)indoles: Steric and electronic effects of 4- and 8-halogenated naphthoyl substituents
Wiley, Jenny L.,Smith, Valerie J.,Chen, Jianhong,Martin, Billy R.,Huffman, John W.
experimental part, p. 2067 - 2081 (2012/06/01)
To develop SAR at both the cannabinoid CB1 and CB2 receptors for 3-(1-naphthoyl)indoles bearing moderately electron withdrawing substituents at C-4 of the naphthoyl moiety, 1-propyl and 1-pentyl-3-(4-fluoro, chloro, bromo and iodo-1-naphthoyl) derivatives were prepared. To study the steric and electronic effects of substituents at the 8-position of the naphthoyl group, the 3-(4-chloro, bromo and iodo-1-naphthoyl)indoles were also synthesized. The affinities of both groups of compounds for the CB1 and CB2 receptors were determined and several of them were evaluated in vivo in the mouse. The effects of these substituents on receptor affinities and in vivo activity are discussed and structure-activity relationships are presented. Although many of these compounds are selective for the CB2 receptor, only three JWH-423, 1-propyl-3-(4-iodo-1-naphthoyl)indole, JWH-422, 2-methyl-1-propyl-3-(4-iodo-1-naphthoyl)indole, the 2-methyl analog of JWH-423 and JWH-417, 1-pentyl-3-(8-iodo-1-naphthoyl)indole, possess the desirable combination of low CB1 affinity and good CB2 affinity.
ANTIVIRAL COMPOUNDS
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Page/Page column 588, (2010/12/17)
The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
Synthesis and structure-activity relationship of a novel series of aminoalkylindoles with potential for imaging the neuronal cannabinoid receptor by positron emission tomography
Willis, Peter G.,Pavlova, Olga A.,Chefer, Svetlana I.,Vaupel, D. Bruce,Mukhin, Alexey G.,Horti, Andrew G.
, p. 5813 - 5822 (2007/10/03)
A new series of CB1 ligands with high binding affinity (K i = 0.7-100 nM) and moderate lipophilicity (cLogD7.4) in the range of 2.1-4.5 has been synthesized. A structure-activity relationship study demonstrated that for the studied set of aminoalkylindoles, the molecular dipole of the ground state conformation within the series was inversely related to the affinity. The racemic ligand with highest affinity (0.7 nM), 3-(4-fluoronaphthoyl)-1-(N-methylpiperidin-2-ylmethyl)indole, was radiolabeled with 18F. This radioligand specifically labeled CB1 receptors in mouse brain and accumulated in regions of high versus low CB 1 receptor density in a ratio of 1.6. The displaceable radioactivity of one enantiomer in the brains of mice determined in a pretreatment study using the CB1 antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) was nearly double that of the race-mate for the same determination; therefore, the active enantiomer is a candidate for PET studies in animals. A pretreatement study for the other enantiomer found no displaceable radioactivity in the same group of mice; this result suggested the enantiomer was inactive.
Discovery of novel, orally active dual NK1/NK2 antagonists
Bernstein, Peter R.,Aharony, David,Albert, Jeffrey S.,Andisik, Donald,Barthlow, Herbert G.,Bialecki, Russell,Davenport, Timothy,Dedinas, Robert F.,Dembofsky, Bruce T.,Koether, Gerard,Kosmider, Benedict J.,Kirkland, Karin,Ohnmacht, Cyrus J.,Potts, William,Rumsey, William L.,Shen, Lihong,Shenvi, Ashok,Sherwood, Scott,Stollman, David,Russell, Keith
, p. 2769 - 2773 (2007/10/03)
Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2 antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2 receptors, with high-affinity (Ki=0.12 and 0.62 nM, respectively). In functional assays ZD6021 had, at 10-7 M, in human pulmonary artery pKB=8.9 and in human bronchus pKB=7.3, for NK1 and NK2, respectively. Oral administration of ZD6021 to guinea pigs dose-dependently attenuated ASMSP induced extravasation of plasma proteins, ED50=0.5 mg/kg, and NK2 mediated bronchoconstriction, ED50=13 mg/kg.
