- A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles
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Novel 5-pyridinyl-1,2,4-triazoles were designed as dual inhibitors of histone deacetylase 2 (HDAC2) and focal adhesion kinase (FAK). Compounds 5d, 6a, 7c, and 11c were determined as potential inhibitors of both HDAC2 (IC50 = 0.09–1.40 μM) and F
- Mustafa, Muhamad,Abd El-Hafeez, Amer Ali,Abdelhamid, Dalia,Katkar, Gajanan D.,Mostafa, Yaser A.,Ghosh, Pradipta,Hayallah, Alaa M.,Abuo-Rahma, Gamal El-Din A.
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- Design, synthesis and antibacterial evaluation of 1-[(1R,2S)-2-Fluorocyclopropyl] Ciprofloxacin-(4-Methyl-3-Aryl)-1,2,4-Triazole-5(4H)-Thione Hybrids
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Fourteen novel 1-[(1R,2S)-2-Fluorocyclopropyl]ciprofloxac in-(4-methyl-3-aryl)-1,2,4-triazole-5(4H)-thione hybrids 6a-n were designed, synthesized and assessed for their in vitro antibacterial activities against representative Gram-positive and Gram-negat
- Geng, Yun-He,Wei, Zeng-Quan,Xu, Zhi,Na, Lu-Xin,Zhang, Shu,Guo, Hui-Yuan,Liu, Ming-Liang,Feng, Lian-Shun,You, Xue-Fu
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p. 101 - 107
(2019/08/01)
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- 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
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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.
- 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
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p. 6942 - 6990
(2017/09/07)
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- Narrow SAR in odorant sensing Orco receptor agonists
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The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure-activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a 'mix-and-match' strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification.
- Romaine, Ian M.,Taylor, Robert W.,Saidu, Samsudeen P.,Kim, Kwangho,Sulikowski, Gary A.,Zwiebel, Laurence J.,Waterson, Alex G.
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p. 2613 - 2616
(2015/02/19)
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- Synthesis and evaluation of antimicrobial activity of some new hetaryl-azoles derivatives obtained from 2-aryl-4-methylthiazol-5- carbohydrazides and isonicotinic acid hydrazide
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A series of new 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole derivatives have been synthesized starting from 2-aryl-4-methylthiazol-5-carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, 1
- Tiperciuc, Brindusa,Zaharia, Valentin,Colosi, Ioana,Moldovan, Cristina,Crisan, Ovidiu,Pirnau, Adrian,Vlase, Laurian,Duma, Mihaela,Oniga, Ovidiu
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p. 1407 - 1414
(2013/02/22)
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- A NEW PROCESS FOR PREPARING 4- [4-METHYL-5- (CL- 10ALKYLTHIO/C5-10ARYL-CL-6ALKYLTHIO) -4H-1, 2, 4-TRIAZOL-3- YL] PYRIDINES.
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The invention relates to a method of manufacturing a compound according to formula (I) wherein R is C1-6alkylor C5-10aryl-C1-6alkyl, comprising the steps of: a) reacting isonicotinohydrazide and methyl isothiocyanate, ther
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Page/Page column 7-8
(2010/07/02)
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- 5- (PHENYLISOXAZOLYLETHOXY) -TRIAZOL- 3 -YL SUBSTITUTED PYRIDINE COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC OR PAIN DISORDERS
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The present invention is directed to novel compounds of formula (I) / (I1) / (III), their use in therapy and pharmaceutical compositions comprising said novel compounds.
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Page/Page column 14; 21
(2008/06/13)
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- Isonicotinoylhydrazothiazoles and isonicotinoyl-N4-substituted thiosemicarbazides: Synthesis, characterization, and anti-mycobacterial activity
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Differently substituted isonicotinoylhydrazothiazoles and isonicotinoyl-N4-substituted thiosemicaibazides have been prepared and characterized by means of elemental analysis, 1H-NMR, 13C-NMR, and Mass spectrometry. All the
- Cardia, Maria Cristina,Distinto, Simona,Maccioni, Elias,Plumitallo, Antonio,Saddi, Manuela,Sanna, Maria Luisa,DeLogu, Alessandro
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p. 1337 - 1342
(2007/10/03)
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- TRIAZOLE COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS
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The present invention relates to new compounds of formula (I), wherein P, Q, X1, X2, X3, X4 X7, X8, R1, R2, R3, m, n, and p are as defined as in formula (I)
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Page/Page column 39
(2010/02/13)
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- 3-aryl-5-alkylthio-4H-1,2,4-triazoles
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This invention relates to derivatives of 3-aryl-5-alkylthio-4H-1,2,4-triazoles, to their pharmacological properties and to their use as muscle relaxants, spasmolytics, anticonvulsants and anxiolytics.
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