RESUMO
Indazole derivatives are currently drawing more and more attention in medicinal chemistry as kinase inhibitors. 1H-indazole-3-carboxaldehydes are key intermediates to access to a variety of polyfunctionalized 3-substituted indazoles. We report here a general access to this motif, based on the nitrosation of indoles in a slightly acidic environment. These very mild conditions allow the conversion of both electron-rich and electron-deficient indoles into 1H-indazole-3-carboxaldehydes.
RESUMO
A novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the Kabachnik-Fields reaction using I2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1) H NMR, (13) C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X-ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.
Assuntos
Antivirais/química , Organofosfonatos/química , Ribonucleosídeos/química , Triazóis/química , Animais , Antivirais/síntese química , Antivirais/farmacologia , Linhagem Celular , Cristalografia por Raios X , Vírus de DNA/efeitos dos fármacos , Humanos , Organofosfonatos/síntese química , Organofosfonatos/farmacologia , Vírus de RNA/efeitos dos fármacos , Ribonucleosídeos/síntese química , Ribonucleosídeos/farmacologia , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/farmacologiaRESUMO
In the title compound, C20H24N2O4, both peptide bonds adopt a trans configuration with respect to the -N-H and -C=O groups. The dihedral angle between the aromatic rings is 53.58â (4)°. The mol-ecular conformation is stabilized by an intra-molecular N-Hâ¯O hydrogen bond. The crystal packing is characterized by zigzag chains of N-Hâ¯O hydrogen-bonded mol-ecules running along the b-axis direction.
RESUMO
A novel series of hybrid molecules 4a-i and 5a-i were prepared by condensation of 4-(trimethylsilylethynyl)benzaldehyde 1 with substituted o-phenylenediamines. These in turn were reacted with 2-(azidomethoxy)ethyl acetate in a Cu alkyne-azide cycloaddition (CuAAC) to generate the 1,2,3-triazole pharmacophore under microwave assistance. The newly synthesized compounds were examined for their in vitro antimicrobial activities against Gram-positive and Gram-negative bacteria and the phytopathogenic fungi Verticillium dahliae and Fusarium oxysporum f. sp. albedinis. 2-((4-(4-(5-Trifluoromethyl benzimidazol-2-yl)phenyl)-1,2,3-triazol-1-yl)methoxy)ethanol 5e showed a moderate inhibition of 30% in the Foa sporulation test.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Desenho de Fármacos , Triazóis/síntese química , Triazóis/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Verticillium/efeitos dos fármacos , Verticillium/crescimento & desenvolvimentoRESUMO
In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro.
Assuntos
Nucleosídeos/síntese química , Quinazolinas/química , Triazóis/química , Antivirais/síntese química , Antivirais/farmacologia , Técnicas de Química Sintética , Reação de Cicloadição , Hepacivirus/efeitos dos fármacos , Humanos , Estrutura Molecular , Nucleosídeos/química , Nucleosídeos/farmacologiaRESUMO
Crystal structures are reported for four related diethyl [(arylamino)(4-ethynylphenyl)lmethyl]phosphonate derivatives, namely diethyl [(4-bromoanilino)(4-ethynylphenyl)methyl]phosphonate, C19H21BrNO3P, (I), diethyl ((4-chloro-2-methylanilino){4-[2-(trimethylsilyl)ethynyl]phenyl}methyl)phosphonate, C23H31ClNO3PSi, (II), diethyl ((4-fluoroanilino){4-[2-(trimethylsilyl)ethynyl]phenyl}methyl)phosphonate, C22H29FNO3PSi, (III), and diethyl [(4-ethynylphenyl)(naphthalen-2-ylamino)methyl]phosphonate, C23H24NO3P, (IV). The conformation of the anilinobenzyl group is very similar in all four compounds. The P-C bond has an approximately staggered conformation, with the aniline and ethynylphenyl groups in gauche positions with respect to the P=O double bond. The two six-membered rings are almost perpendicular. The sums of the valence angles about the N atoms vary from 344â (2) to 351â (2)°. In the crystal structures, molecules of (I), (III) and (IV) are arranged as centrosymmetric or pseudocentrosymmetric dimers connected by two N-H···O=P hydrogen bonds. The molecules of (II) are arranged as centrosymmetric dimers connected by C(methyl)-H···O=P hydrogen bonds. The N-H bond of (II) is not involved in hydrogen bonding.
Assuntos
Compostos de Anilina/química , Naftalenos/química , Organofosfonatos/química , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura MolecularRESUMO
In the title molecule, C(18)H(17)N(5)O(2), the dihedral angle between the benzene plane and the benzimidazole plane is 19.8â (1)° and the angle between the benzene plane and the triazole plane is 16.7â (1)°. In the crystal, mol-ecules are connected by O-Hâ¯N hydrogen bonds, forming zigzag chains along the c-axis direction. The chains are connected by bifurcated N-Hâ¯(N,N) hydrogen bonds into layers parallel to (100). These layers are connected along the a-axis direction by weak C-Hâ¯O contacts, forming a three-dimensional network.
RESUMO
In the mol-ecule of the title compound, C15H12ClNO3, the chloro-benzamide and benzoate units are almost co-planar, with a dihedral angle between the six-membered rings of 2.99â (10)°. An intra-molecular N-Hâ¯O hydrogen bond occurs. In the crystal, each mol-ecule is linked to a symmetry-equivalent counterpart across a twofold rotation axis by weak C-Hâ¯O and C-Hâ¯Cl hydrogen bonds, forming dimers. The packing is stabilized through weak π-π stacking along the b-axis direction, leading to π-stacked columns of inversion-related mol-ecules, with an inter-planar distance of 3.46â (2)â Å and a centroid-centroid vector of 3.897â (2)â Å.
RESUMO
In the compound, C(37)H(29)N(5)O(8), the quinazoline residue forms a dihedral angle of 72.90â (9)° with the triazole ring. The furan ring adopts a twist conformation. In the crystal, the mol-ecules are linked by non-classical C-Hâ¯N and C-Hâ¯O hydrogen bonds, building an infinite three-dimensional network.
RESUMO
In the heterocyclic title compound, C(17)H(19)N(5)O(3), the quinazolinone ring system forms a dihedral angle of 67.22â (7)° with the triazole ring. The butyl acetate group has a non-linear conformation, with an alternation of synclinal and anti-periplanar torsion angles [N-C-C-C = 58.5â (2)°, C-C-C-C = 170.72â (19)° and C-C-C-O = -65.9â (3)°]. The crystal structure features inter-molecular C-Hâ¯N and C-Hâ¯O non-classical hydrogen bonds, building an infinite one-dimensional network along the [100] direction.
RESUMO
The title compound, C(21)H(21)N(5)O(2)·0.5H(2)O, has two fused six-membered rings linked to a benzene ring and to a triazole ring, which is connected to a butanol group. The quinazoline ring forms a dihedral angle of 7.88â (8)° with the benzene ring, while the triazole ring is approximately perpendicular to the benzene ring and to the quinazoline system, making dihedral angles of 84.38â (10) and 76.55â (8)°, respectively. The stereochemical arrangement of the butanol chain, with a C-C-C-C torsion angle of 178.34â (19)°, corresponds to an anti-periplanar conformation. However the position of the -OH group is split into two very close [O-O = 0.810(3)â Å] positions of equal occupancy. The crystal structure features O-Hâ¯N and O-Hâ¯O hydrogen bonds, building an infinite three-dimensional network. The water molecule is located on a half-filled general position.