- Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides
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The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM).
- Demjén, András,Alf?ldi, Róbert,Angyal, Anikó,Gyuris, Márió,Hackler, László,Szebeni, Gábor J.,W?lfling, János,Puskás, László G.,Kanizsai, Iván
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- Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity
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With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC50 = 0.18–1.2 μM) at no toxic concentrations (CC50 > 250 μM). This study permitted to obtain among the most potent anti-flu compounds within the PA-PB1 interaction inhibitors, confirming the cHTC scaffold as particularly suitable to achieve innovative anti-flu agents.
- Desantis, Jenny,Nannetti, Giulio,Massari, Serena,Barreca, Maria Letizia,Manfroni, Giuseppe,Cecchetti, Violetta,Palù, Giorgio,Goracci, Laura,Loregian, Arianna,Tabarrini, Oriana
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p. 128 - 139
(2017/07/03)
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- Utility of cyanoacetamides as precursors to pyrazolo-[3,4-d]pyrimidin-4-ones, 2-aryl-6-substituted 1,2,3-triazolo-[4,5-d]pyrimidines and pyrazolo[1,5-a]pyrimidine-3-carboxamides
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Cyanoacetamides (7a-c) were prepared via reacting cyanoacetic acid (5) with amines in the presence of acetic anhydride. Compounds (7a-c) coupled with benzenediazonium chloride to yield the phenylhydrazones (8a-c). These reacted with chloroacetonitrile to yield aminopyrazolecarboxamides (11a-c). Reaction of (8a,b) with hydroxylamine hydrochloride in DMF in presence of anhydrous sodium acetate afforded the amino-1,2,3-triazolecarboxamides (36a,b). Also compounds (7a-c) reacted with dimethylformamide dimethylacetal (DMFDMA) to yield the enamines (9a-c) which react with hydrazine hydrate to afford the aminopyrazoles (16a-c). Compounds (16) and (36) reacted with DMFDMA to yield the title heterocyclic derivatives.
- Ibrahim, Hamada Mohamed,Makhseed, Saad,Abdel-Motaleb, Ramadan Maawad,Makhlouf, Abdel-Moneim Abdel-Salam,Elnagdi, Mohamed Hilmy
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p. 1951 - 1966
(2008/09/16)
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- 3-PHENYL-N- ((1, 3, 4) THIADIAZOL-2-YL) -ACRYLAMIDE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF ESTROGEN-RELATED RECEPTORS FOR THE TREATMENT OF E.G. CANCER, RHEUMATOID ARTHRITIS OR NEUROLOGICAL DISORDERS
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Compounds of formula (I) are provided as well as compositions and methods of using compounds of formula (I) for modulating the activity of the estrogen-related receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder related to the activity of the estrogen-related receptor. Considering the wide range of activity of the nuclear hormone receptor ERRα, the compounds described herein which are capable of modulating ERRα activity, are useful for treating a range of disease states including cancer, diabetes, obesity, hyperlipidermia, arthritis, atherosclerosis, osteoporosis, anxiety, depression, Parkinson’s disease and Alzheimer’s disease. Formula (I). The substituents are defined in the claims.
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Page/Page column 51
(2010/02/13)
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- Identification of a selective inverse agonist for the orphan nuclear receptor estrogen-related receptor α
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The estrogen-related receptor α (ERRα) is an orphan receptor belonging to the nuclear receptor superfamily. The physiological role of ERRα has yet to be established primarily because of lack of a natural ligand. Herein, we describe the discovery of the fi
- Busch, Brett B.,Stevens Jr., William C.,Martin, Richard,Ordentlich, Peter,Zhou, Sihong,Sapp, Douglas W.,Horlick, Robert A.,Mohan, Raju
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p. 5593 - 5596
(2007/10/03)
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