3652-17-3Relevant academic research and scientific papers
Acylated 1 H-1,2,4-Triazol-5-Amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action
Korff, Marvin,Imberg, Lukas,Will, Jonas M.,Bückrei?, Nico,Kalinina, Svetlana A.,Wenzel, Benjamin M.,Kastner, Gregor A.,Daniliuc, Constantin G.,Barth, Maximilian,Ovsepyan, Ruzanna A.,Butov, Kirill R.,Humpf, Hans-Ulrich,Lehr, Matthias,Panteleev, Mikhail A.,Poso, Antti,Karst, Uwe,Steinmetzer, Torsten,Bendas, Gerd,Kalinin, Dmitrii V.
supporting information, p. 13159 - 13186 (2020/11/13)
We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-Triazol-5-Amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i, a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine proteases and also finding compound 21m with 27 nM inhibitory activity toward thrombin. For the first time, acylated 1,2,4-Triazol-5-Amines were proved to have anticoagulant properties and the ability to affect thrombin-And cancer-cell-induced platelet aggregation. Performed mass spectrometric analysis and molecular modeling allowed us to discover previously unknown interactions between the synthesized inhibitors and the active site of FXIIa, which uncovered the mechanistic details of FXIIa inhibition. Synthesized compounds represent a promising starting point for the development of novel antithrombotic drugs or chemical tools for studying the role of FXIIa and thrombin in physiological and pathological processes.
A green one-pot synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines as potential antimicrobial agents
Beyzaei, Hamid,Khosravi, Zahra,Aryan, Reza,Ghasemi, Behzad
, p. 2565 - 2573 (2019/07/04)
Abstract: An efficient procedure was proposed for the synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines via a one-pot reaction of thiourea, dimethyl sulfate and various hydrazides. 1,2,4-Triazole derivatives were prepared in aqueous media under mild conditions while adhering to some principles of green chemistry. The products were easily isolated in 83–95% yields without any need for further purification. Inhibitory activities of all synthetic compounds were assessed against a variety of Gram-positive and Gram-negative pathogenic bacteria as well as some fungal pathogens. The best antibacterial effects were observed with 3(5)-phenyl-1H-1,2,4-triazol-5(3)-amine according to its MIC values (4–8?μg?mL?1). All compounds were successful in blocking the growth of fungi. Acceptable antioxidant properties were observed only with 3(5)-(4-nitrophenyl)-1H-1,2,4-triazol-5(3)-amine. Graphic abstract: 3(5)-Substituted 1,2,4-triazol-5(3)-amines were efficiently prepared via a one-pot reaction of thiourea, dimethyl sulfate and various hydrazides in water as the solvent. Inhibitory activity of all synthesized derivatives was proved according to their MIC, MBC and MFC values. It is found that they are potential antifungal agents.[Figure not available: see fulltext.].
3-Aryl/Heteroaryl-5-amino-1-(3′,4′,5′-trimethoxybenzoyl)-1,2,4-triazoles as antimicrotubule agents. Design, synthesis, antiproliferative activity and inhibition of tubulin polymerization
Romagnoli, Romeo,Prencipe, Filippo,Oliva, Paola,Baraldi, Stefania,Baraldi, Pier Giovanni,Brancale, Andrea,Ferla, Salvatore,Hamel, Ernest,Bortolozzi, Roberta,Viola, Giampietro
, p. 361 - 374 (2018/07/13)
Many natural and synthetic substances are known to interfere with the dynamic assembly of tubulin, preventing the formation of microtubules. In our search for potent and selective antitumor agents, a novel series of 1-(3′,4′,5′-trimethoxybenzoyl)-5-amino-1,2,4-triazoles were synthesized. The compounds had different heterocycles, including thiophene, furan or the three isomeric pyridines, and they possessed a phenyl ring bearing electron-releasing or electron-withdrawing substituents at the 3-position of the 5-amino-1,2,4-triazole system. Most of the twenty-two tested compounds showed moderate to potent antiproliferative activities against a panel of solid tumor and leukemic cell lines, with four (5j, 5k, 5o and 5p) showing strong antiproliferative activity (IC50 50 values 2-100-fold lower for Jurkat and RS4;11 cells than those for the three lines derived from solid tumors (HeLa, HT-29 and MCF-7 cells). Compound 5k strongly inhibited tubulin assembly, with an IC50 value of 0.66 μM, half that obtained in simultaneous experiments with CA-4 (IC50 = 1.3 μM).
FUSED TRIAZOLO-PYRIMIDINE COMPOUNDS HAVING USEFUL PHARMACEUTICAL APPLICATION
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Paragraph 0082, (2018/10/19)
A compound and/or a pharmaceutically acceptable salt thereof has the following formula A: These compounds can be PIKfyve kinase inhibitors.
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
MULTISUBSTITUTED AROMATIC COMPOUNDS AS INHIBITORS OF THROMBIN
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Paragraph 0229-0231; 0234-0235, (2017/12/07)
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing a disease or disorder, which disease or disorder is amenable to treatment or prevention by the inhibition of thrombin.
MULTISUBSTITUTED AROMATIC COMPOUNDS AS SERINE PROTEASE INHIBITORS
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Paragraph 0211, (2014/09/29)
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of kallikrein, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of kallikrein.
Synthesis of 3-pyridyl-substituted 5-amino-1,2,4-triazoles from aminoguanidine and pyridinecarboxylic acids
Chernyshev,Tarasova,Chernysheva,Taranushich
experimental part, p. 1890 - 1896 (2012/03/12)
Effect of the molar ratio between reagents, temperature, and synthesis duration on the yield of 3-pyridylsubstituted 5-amino-1,2,4-triazoles in the reaction of aminoguanidine hydrochloride with pyridinecarboxylic acids under acid catalysis conditions was studied. A single-reactor method for synthesis of 3-pyridyl-substituted 5-amino-1,2,4-triazoles and their hydrochlorides was developed.
MULTISUBSTITUTED AROMATIC COMPOUNDS AS INHIBITORS OF THROMBIN
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Page/Page column 66, (2011/10/31)
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin, which compounds include substituted pyrazolyl or substituted triazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing a disease or disorder, which disease or disorder is amenable to treatment or prevention by the inhibition of thrombin.
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
experimental part, 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.
