- A first-in-class anticancer dual HDAC2/FAK inhibitors bearing hydroxamates/benzamides capped by pyridinyl-1,2,4-triazoles
-
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.
-
-
- Discovery of antiproliferative and anti-FAK inhibitory activity of 1,2,4-triazole derivatives containing acetamido carboxylic acid skeleton
-
Small molecule inhibitors of the focal adhesion kinase are regarded as promising tools in our armamentarium for treating cancer. Here, we identified four 1,2,4-triazole derivatives that inhibit FAK kinase significantly and evaluated their therapeutic pote
- Mustafa, Muhamad,Abuo-Rahma, Gamal El-Din A.,Abd El-Hafeez, Amer Ali,Ahmed, Esam R.,Abdelhamid, Dalia,Ghosh, Pradipta,Hayallah, Alaa M.
-
supporting information
(2021/03/30)
-
- Design, synthesis and antibacterial evaluation of 1-[(1R,2S)-2-Fluorocyclopropyl] Ciprofloxacin-(4-Methyl-3-Aryl)-1,2,4-Triazole-5(4H)-Thione Hybrids
-
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
-
p. 101 - 107
(2019/08/01)
-
- DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A MORPHOLINE MOIETY
-
The disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof: The disclosure also provides processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them, and their use
- -
-
Paragraph 0234-0235
(2018/11/21)
-
- 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
-
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
-
p. 6942 - 6990
(2017/09/07)
-
- DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A BICYCLO MOIETY
-
The disclosure provides compounds having formula (I), wherein the substituents are as defined herein. The compounds are useful for modulating the dopamine D3 receptor and for treating conditions associated therewith, such as addictions, drug dependency, and psychiatric conditions.
- -
-
Paragraph 0555; 0556
(2017/02/28)
-
- Novel morpholine scaffolds as selective dopamine (DA) D3 receptor antagonists
-
A new series of morpholine derivatives has been identified as selective DA D3 receptor antagonists; their in vitro profile and pharmacokinetic data are provided.
- Micheli, Fabrizio,Cremonesi, Susanna,Semeraro, Teresa,Tarsi, Luca,Tomelleri, Silvia,Cavanni, Paolo,Oliosi, Beatrice,Perdon, Elisabetta,Sava, Anna,Zonzini, Laura,Feriani, Aldo,Braggio, Simone,Heidbreder, Christian
-
p. 1329 - 1332
(2016/02/23)
-
- 1,2,4-Triazolyl octahydropyrrolo[2,3-b]pyrroles: A new series of potent and selective dopamine D3 receptor antagonists
-
A novel series of 1,2,4-triazolyl octahydropyrrolo[2,3-b]pyrroles showing high affinity and selectivity at the DA D3 receptor is reported here. Compounds endowed with high selectivity over the hERG channel were identified and their pharmacokinetic properties thoroughly analyzed. A few derivatives with appropriate developability characteristics were selected for further studies and progression along the screening cascade. In particular, derivative 60a, (DA D3 pKi = 8.4, DA D2 pKi = 6.0 and hERG fpKi = 5.2) showed a balanced profile and further refinements are in progress around this molecule.
- Micheli, Fabrizio,Bernardelli, Andrea,Bianchi, Federica,Braggio, Simone,Castelletti, Laura,Cavallini, Palmina,Cavanni, Paolo,Cremonesi, Susanna,Cin, Michele Dal,Feriani, Aldo,Oliosi, Beatrice,Semeraro, Teresa,Tarsi, Luca,Tomelleri, Silvia,Wong, Andrea,Visentini, Filippo,Zonzini, Laura,Heidbreder, Christian
-
p. 1619 - 1636
(2016/04/05)
-
- 1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists
-
A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.
- Micheli, Fabrizio,Bacchi, Alessia,Braggio, Simone,Castelletti, Laura,Cavallini, Palmina,Cavanni, Paolo,Cremonesi, Susanna,Dal Cin, Michele,Feriani, Aldo,Gehanne, Sylvie,Kajbaf, Mahmud,Marchió, Luciano,Nola, Selena,Oliosi, Beatrice,Pellacani, Annalisa,Perdonà, Elisabetta,Sava, Anna,Semeraro, Teresa,Tarsi, Luca,Tomelleri, Silvia,Wong, Andrea,Visentini, Filippo,Zonzini, Laura,Heidbreder, Christian
-
p. 8549 - 8576
(2016/10/03)
-
- DOPAMINE D3 RECEPTOR ANTAGONISTS COMPOUNDS
-
The disclosure is directed to novel dopamine D3 receptor antagonists, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, including treating drug dependency and psychosis.
- -
-
Page/Page column 113; 115
(2016/05/19)
-
- Narrow SAR in odorant sensing Orco receptor agonists
-
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.
-
p. 2613 - 2616
(2015/02/19)
-
- Narrow SAR in odorant sensing Orco receptor agonists
-
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.
-
p. 2613 - 2616
(2014/06/09)
-
- Synthesis and evaluation of antimicrobial activity of some new hetaryl-azoles derivatives obtained from 2-aryl-4-methylthiazol-5- carbohydrazides and isonicotinic acid hydrazide
-
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
-
p. 1407 - 1414
(2013/02/22)
-
- A NEW PROCESS FOR PREPARING 4- [4-METHYL-5- (CL- 10ALKYLTHIO/C5-10ARYL-CL-6ALKYLTHIO) -4H-1, 2, 4-TRIAZOL-3- YL] PYRIDINES.
-
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
- -
-
Page/Page column 7-8
(2010/07/02)
-
- 5- (PHENYLISOXAZOLYLETHOXY) -TRIAZOL- 3 -YL SUBSTITUTED PYRIDINE COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC OR PAIN DISORDERS
-
The present invention is directed to novel compounds of formula (I) / (I1) / (III), their use in therapy and pharmaceutical compositions comprising said novel compounds.
- -
-
Page/Page column 14; 21
(2008/06/13)
-
- TETRAZOLE COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR ANTAGONITS
-
The present invention relates to new compounds of formula I, wherein P, Q, X1, X2, X3, X4, R1, R2, m and p, are as defined as in formula I, or salts, solvates or solvated salts thereof, processes for their preparation and new intermediates used in the preparation thereof, pharmaceutical compositions containing said compounds, and to the use of said compounds in therapy.
- -
-
Page/Page column 57
(2010/02/13)
-
- TRIAZOLE COMPOUNDS AND THEIR USE AS METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS
-
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)
- -
-
Page/Page column 39
(2010/02/13)
-
- NEW COMPOUNDS
-
The present invention relates to new compounds of formula I, (I) a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
- -
-
-
- 3-aryl-5-alkylthio-4H-1,2,4-triazoles
-
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.
- -
-
-