- Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety
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The reported toxicities of current antitrypanosomal drugs and the emergence of drug resistant trypanosomes underscore the need for the development of new antitrypanosomal agents. We report herein the synthesis and antitrypanosomal activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted benzenesulphonamide. Nine of the new derivatives showed comparable antitrypanosomal activities at IC50 range of 1–6 nM (melarsoprol 5 nM). Compound 11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the rest of the reported derivatives. The novel compounds showed satisfactory predicted physico-chemical properties including oral bioavailability, permeability and transport properties.
- Ugwu, David Izuchukwu,Okoro, Uchechukwu Chris,Mishra, Narendra Kumar
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- Synthesis, characterization, molecular docking and in?vitro antimalarial properties of new carboxamides bearing sulphonamide
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Sulphonamides and carboxamides have shown large number of pharmacological properties against different types of diseases among which is malaria. Twenty four new carboxamide derivatives bearing benzenesulphonamoyl alkanamides were synthesized and investigated for their in silico and in?vitro antimalarial and antioxidant properties. The substituted benzenesulphonyl chlorides (1a-c) were treated with various amino acids (2a-h) to obtain the benzenesulphonamoyl alkanamides (3a-x) which were subsequently treated with benzoyl chloride to obtain the N-benzoylated derivatives (5a-f, i-n and q-v). Further reactions of the N-benzoylated derivatives or proline derivatives with 4-aminoacetophenone (6) using boric acid as a catalyst gave the sulphonamide carboxamide derivatives (7a-x) in excellent yields. The in?vitro antimalarial studies showed that all synthesized compounds had antimalarial property. Compound 7k, 7c, 7l, 7s, and 7j had mean MIC value of 0.02, 0.03, 0.05, 0.06 and 0.08?μM respectively comparable with chloroquine 0.06?μM. Compound 7c was the most potent antioxidant agent with IC50 value of 0.045?mM comparable with 0.34?mM for ascorbic acid. In addition to the successful synthesis of the target molecules using boric acid catalysis, the compounds were found to have antimalarial and antioxidant activities comparable with known antimalarial and antioxidant drugs. The class of compounds reported herein have the potential of reducing oxidative stress arising from malaria parasite and chemotherapeutic agent used in the treatment of malaria.
- Ugwu,Okoro,Ukoha,Okafor,Ibezim,Kumar
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p. 349 - 369
(2017/05/04)
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- Evaluation of Antibacterial and Antifungal Effects of Novel Hydroxamic Acids Linked-natural Amino Acids
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A SERIES of new derivatives containing hydroxamic acids linked-amino acids has been synthesized and fully characterized by spectroscopic techniques including; 1H, 13C, DEPT 135 and HRMS.These new compounds were tested for their antib
- Albalawi, Marzough Aziz
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p. 613 - 618
(2019/12/24)
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- Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
- Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 9067 - 9089
(2017/11/14)
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- HIV protease inhibitors based on amino acid derivatives
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A compound selected from the group consisting of a compound of formula I 1a compound of formula II 2and when the compound of formula I and II comprises an amino group pharmaceutically acceptable ammonium salts thereof, wherein R1, R2, Cx, n, R3, R4, R5, Y are as defined in the specification.
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- PIPERIDINE AND HEXAHYDROPYRIDAZINE THROMBIN INHIBITORS
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Compounds of the invention have the following structure: STR1
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- PYRROLIDINE THROMBIN INHIBITORS
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Compounds of the invention have the following structure: STR1 for example STR2 These compounds inhibit thrombin and associated thrombosis.
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- N-Acylated α-Amino Acids as Novel Oral Delivery Agents for Proteins
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A series of N-acylated α-amino acids were synthesized and shown to improve the oral delivery of two protein drugs, salmon calcitonin (sCT) and interferon-α.Forty-five compounds in this series were tested in vivo in rats and primates.A significant positive
- Leone-Bay, Andrea,Santiago, Noemi,Achan, Douglas,Chaudhary, Kiran,DeMorin, Frenel,et al.
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p. 4263 - 4269
(2007/10/03)
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