Publications (12) View all
-
Article: 4-(3-Fluoro-anilino)thieno[2,3-b]pyridine-6-carb-oxy-lic acid.
[show abstract] [hide abstract]
ABSTRACT: In the title compound, C(14)H(9)FN(2)O(2)S, the thieno[2,3-b]pyridine residue is almost planar (r.m.s. deviation = 0.0194 Å), with the carb-oxy-lic acid group [dihedral angle = 11.9 (3)°] and the benzene ring [71.1 (4)°] being twisted out of this plane to different extents. An intra-molecular N-H⋯O(carbon-yl) hydrogen bond closes an S(6) ring. Supra-molecular chains along [01-1] mediated by O-H⋯N(pyridine) hydrogen bonds feature in the crystal. A three-dimensional architecture is completed by π-π inter-actions occurring between the benzene ring and the two rings of the thieno[2,3-b]pyridine residue [centroid-centroid distances = 3.6963 (13) and 3.3812 (13) Å]. The F atom is disordered over the two meta sites in a near statistical ratio [0.545 (5):0.455 (5)].Acta Crystallographica Section E Structure Reports Online 07/2012; 68(Pt 7):o2217-8. · 0.35 Impact Factor -
Article: N-(4-Chloro-phen-yl)-5-(4,5-dihydro-1H-imidazol-2-yl)thieno[2,3-b]pyridin-4-amine.
[show abstract] [hide abstract]
ABSTRACT: In the title compound, C(16)H(13)ClN(4)S, the thienopyridine fused-ring system is nearly planar (r.m.s. deviation = 0.0333 Å) and forms a dihedral angle of 4.4 (3)° with the attached dihydro-imidazole ring (r.m.s. deviation = 0.0429 Å) allowing for the formation of an intra-molecular (exocyclic amine)N-H⋯N(imine) hydrogen bond. The benzene rings of the disordered (50:50) -N(H)-C(6)H(4)Cl residue form dihedral angles of 59.1 (3) and 50.59 (15)° with the fused ring system. In the crystal, (imidazole amine)N-H⋯N(pyridine) hydrogen bonds lead to a supra-molecular helical chain along the b axis. The chains assemble into layers (ab plane) with inter-digitation of the chloro-benzene rings which results in weak C-H⋯Cl inter-actions in the c-axis direction.Acta Crystallographica Section E Structure Reports Online 07/2012; 68(Pt 7):o2135-6. · 0.35 Impact Factor -
Article: Synthesis and antiviral activity of new 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids derivatives
[show abstract] [hide abstract]
ABSTRACT: The synthesis of new 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3a-l) derivatives and the new 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (5a–c) derivatives was achieved with an efficient synthetic route. Ethyl 4-chloro-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (1) on fusion with appropriate substituted anilines or aminopicolines gave the required new ethyl 4-(phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (2a–l) (52–82%) or new ethyl 4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylates (4a–c) (50–60%), respectively. Subsequent hydrolysis of the esters afforded the corresponding carboxylic acids (3a–l) (86–93%) and (5a–c) in high yield (80–93%). Inhibitory effects of 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids. Derivatives on Herpes simplex virus type 1 (HSV-1), Mayaro virus (MAY) and vesicular stomatitis virus (VSV) were investigated. Compounds 2d, 3f, 3a, and 3c exhibited antiviral activity against HSV-1, MAY, and VSV virus with EC50 values of 6.8, 2.2, 4.8, 0.52, 2.5, and 1.0. None of these compounds showed toxicity for Vero cells.Medicinal Chemistry Research 04/2012; 16(7):352-369. · 1.27 Impact Factor -
Article: Searching for new antileishmanial lead drug candidates: Synthesis, biological and theoretical evaluations of promising thieno[2,3-b]pyridine derivatives
[show abstract] [hide abstract]
ABSTRACT: Cutaneous leishmaniasis is a parasitic disease associated with high morbidity and mortality rates. This work reports the synthesis, biological and theoretical evaluations of a new antileishmanial series of 5-(4,5-dihydro-1H-imidazol-2-yl)-4-(arylamino)thieno[2,3-b]pyridine derivatives -3 (H), 3a (m-CH 3), 3b (m-OCH 3), 3c (m-NO 2), 3d (m-F), 3e (m-Br), 3f (p-CH 3), 3g (p-OCH 3), 3h (p-NO 2), 3i (p-F), 3j (p-Br). Interestingly 3f and 3g showed a better profile against Leishmania amazonensis (EC 50 =29.49 and 32.23 μM, respectively) than glucantime, the current drug on the market (EC 50 =163.7 μM). The theoretical analysis pointed a correlation among the antileishmanial profile and the conformational and electrostatic features of these new molecules. ADMET and "Lipinski´s rule of 5" revealed higher theoretical biodisponibility, druglikeness and drugscore values for these derivatives compared to known antileishmanial drugs. Our results pointed these thieno[2,3-b]pyridine derivatives as lead compounds for designing new agents for treatment of cutaneous leishmaniasis.Journal of Microbiology and Antimicrobials. 02/2012; 4:32-39. -
Article: New trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents.
[show abstract] [hide abstract]
ABSTRACT: According to the World Health Organization, half of the World's population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF₃ group substituted at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC₅₀ values ranging from 0.023 to 20 μM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.Molecules 01/2012; 17(7):8285-302. · 2.39 Impact Factor
