- Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
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Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
- Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
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supporting information
p. 3672 - 3690
(2021/08/07)
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- Cu2O/1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide catalyzed C-N cross-coupling reaction in aqueous media
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An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of imidazole, indole, pyrrole, alkyl alcohol amines, and alkyl amines with aryl iodides and bromides. The reaction proceeds in water-ethanol media at 120 °C for 12 h with Cu2O as the catalyst, 1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide (L2) as the ligand, NaOH as the base to generate a wide range of N-arylated products in moderate to excellent yields. Aqueous medium, ease of operation, and broad substrate scope give the process a benign environmental profile.
- Xie, Jian-Wei,Yao, Zhen-Bin,Wang, Xiao-Chuang,Zhang, Jie
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supporting information
p. 3788 - 3792
(2019/06/08)
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- Pd-containing organopolyoxometalates derived from Dawson polyoxometalate [P2W15V3O62]9-: Lewis acidity and dual site catalysis
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Grafting of a palladium complex to the Dawson vanadotungstate polyanion [P2W15V3O62]9- via an organic ligand generates a large family of pincer-type hybrid polyoxometalates. The palladium-POM derivatives have dual catalytic properties. Unlike their parent inorganic polyanions, they catalyze allylations while retaining their oxidant character, which leads to single-pot dual site catalysis. This opens a new route for multicatalytic reactions.
- Riflade, Benoit,Lachkar, David,Oble, Julie,Li, Joaquim,Thorimbert, Serge,Hasenknopf, Bernold,Lacote, Emmanuel
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supporting information
p. 3860 - 3863
(2014/08/18)
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- Orthogonal synthesis of isoindole and isoquinoline derivatives from organic azides
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(Chemical Equation Presented) α-Azido carbonyl compounds bearing a 2-alkenylaryl moiety at the α-position are found to be promising precursors for synthesis of isoindole and isoquinoline derivatives via 1,3-dipolar cycloaddrtion of azides onto alkenes and fcrelectrocyclization of N-H imine intermediates, respectively.
- Hui, Benjamin Wei-Qiang,Chiba, Shunsuke
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supporting information; experimental part
p. 729 - 732
(2009/08/12)
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- A novel synthesis of isoquinolines containing an electron withdrawing substituent
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3,4-Dihydroisoquinolines (10, 13) and isoquinolines (11), having various electron withdrawing substituent were synthesized in two steps from N- benzenesulfonyl- or N, N-dimethylsulfamoyl-β-phenethylamines (2 and 5). A novel cyclization method using ethyl chloro(methylthio)acetate (1) in the presence of SnCl4 as Lewis acid, followed by acid or base treatment provides the title compounds in good yield.
- Kohno, Harumichi,Yamada, Koichiro
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p. 103 - 117
(2007/10/03)
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- Simple and mild method for preparation of α-pyridinecarboxylates and α-pyridyl ketones via trimethylstannyl derivatives
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Alkoxycarbonylation and acylation at the α-position of pyridine, quinoline, and isoquinoline via the respective trimethylstannyl derivatives were satisfactorily performed by employing ethyl chloroglyoxylate and acylformyl chloride under mild conditions.
- Yamamoto,Ouchi,Tanaka
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p. 1028 - 1030
(2007/10/03)
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