22819-07-4Relevant articles and documents
Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
supporting information, p. 3672 - 3690 (2021/08/07)
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.
A Direct approach to a 6-hetarylamino[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazine library
Palysaeva, Nadezhda V.,Kumpan, Katerina P.,Struchkova, Marina I.,Dalinger, Igor L.,Kormanov, Aleksandr V.,Aleksandrova, Nataly S.,Chernyshev, Victor M.,Pyreu, Dmitrii F.,Suponitsky, Kyrill Yu.,Sheremetev, Aleksei B.
supporting information, p. 406 - 409 (2014/04/03)
The synthesis of 6-hetarylamino[1,2,4]triazolo[4,3-b]-[1,2,4,5]tetrazines is reported. The functionalized secondary amines were constructed via a K 2CO3-mediated SNAr reaction of weakly basic hetarylamines with 3-(3,5-dimethylpyrazol-1-yl)[1,2,4]triazolo[4,3-b]-[1,2,4,5]tetrazines, which allowed displacement 3,5-dimethylpyrazolyl leaving group. Significantly, the reaction exhibited a broad substrate scope and proceeded in good yields.
Synthesis of amino-1,2,4-triazoles by reductive ANRORC rearrangements of 1,2,4-oxadiazoles
Palumbo Piccionello, Antonio,Guarcello, Annalisa,Buscemi, Silvestre,Vivona, Nicolo,Pace, Andrea
, p. 8724 - 8727 (2011/03/19)
The reaction of various 1,2,4-oxadiazoles with an excess of hydrazine in DMF has been investigated. 3-Amino-1,2,4-triazoles are produced through a reductive ANRORC pathway consisting of the addition of hydrazine to the 1,2,4-oxadiazole followed by ring-opening, ring-closure, and final reduction of the 3-hydroxylamino-1,2,4-triazole intermediate. The general applicability of 1,2,4-oxadiazoles ANRORC reactivity is demonstrated also in the absence of C(5)-linked electron-withdrawing groups.