Synthesis of 5-(arylmethylideneamino)-4-(1H-benzo[d]imidazol-1-yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of two intermediates and three final products.

A concise and versatile synthesis of 5-(arylmethylideneamino)-4-(1H-benzo[d]imidazol-1-yl)pyrimidines has been developed, starting from 4-(1H-benzo[d]imidazol-1-yl)pyrimidines, and we report here the synthesis and spectroscopic and structural characterization of three such products, along with those of two intermediates in the reaction pathway. The intermediates 4-[2-(4-chlorophenyl)-1H-benzo[d]imidazol-1-yl]-6-methoxypyrimidine-2,5-diamine, (II), and 4-[2-(4-bromophenyl)-1H-benzo[d]imidazol-1-yl]-6-methoxypyrimidine-2,5-diamine, (III), crystallize as the isostructural monohydrates CHClNO·HO and CHBrNO·HO, respectively, in which the components are linked into complex sheets by O-H..

A concise and efficient synthesis of amino-substituted (1H-benzo[d]imidazol-1-yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of six examples.

A concise and efficient synthesis of a series of amino-substituted benzimidazole-pyrimidine hybrids has been developed, starting from the readily available N-(2-aminophenyl)-6-methoxy-5-nitrosopyrimidine-2,4-diamine. In each of N-benzyl-6-methoxy-4-(2-phenyl-1H-benzo[d]imidazol-1-yl)pyrimidine-2,5-diamine, CHNO, (I), 6-methoxy-N-(4-methoxybenzyl)-4-[2-(4-methoxyphenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, CHNO, (III), 6-methoxy-N-(4-nitrobenzyl)-4-[2-(4-nitrophenyl)-1H-benzo[d]imidazol-1-yl]pyrimidine-2,5-diamine, CHNO, (IV), the molecules are linked into three-dimensional framework structures, using different combinations of N-H..

A concise synthesis of a highly substituted 6-(1H-benzimidazol-1-yl)-5-nitrosopyrimidin-2-amine: synthetic sequence and the molecular and supramolecular structures of one product and two intermediates.

A concise and efficient synthesis of 6-benzimidazolyl-5-nitrosopyrimidines has been developed using Schiff base-type intermediates derived from N-(2-aminophenyl)-6-methoxy-5-nitrosopyrimidine-2,4-diamine. 6-Methoxy-N-{2-[(4-methylbenzylidene)amino]phenyl}-5-nitrosopyrimidine-2,4-diamine, (I), and N-{2-[(ethoxymethylidene)amino]phenyl}-6-methoxy-5-nitrosopyrimidine-2,4-diamine, (III), both crystallize from dimethyl sulfoxide solution as the 1:1 solvates CHNO·CHOS, (Ia), and CHNO·CHOS, (IIIa), respectively. The interatomic distances in these intermediates indicate significant electronic polarization within the substituted pyrimidine system.

New substituted aminopyrimidine derivatives as BACE1 inhibitors: in silico design, synthesis and biological assays.

We report in this work new substituted aminopyrimidine derivatives acting as inhibitors of the catalytic site of BACE1. These compounds were obtained from a molecular modeling study. The theoretical and experimental study reported here was carried out in several steps: docking analysis, Molecular Dynamics (MD) simulations, Quantum Theory Atom in Molecules (QTAIM) calculations, synthesis and bioassays and has allowed us to propose some compounds of this series as new inhibitors of the catalytic site of BACE1.

Molecular modeling study of dihydrofolate reductase inhibitors. Molecular dynamics simulations, quantum mechanical calculations, and experimental corroboration.

A molecular modeling study on dihydrofolate reductase (DHFR) inhibitors was carried out. By combining molecular dynamics simulations with semiempirical (PM6), ab initio, and density functional theory (DFT) calculations, a simple and generally applicable procedure to evaluate the binding energies of DHFR inhibitors interacting with the human enzyme is reported here, providing a clear picture of the binding interactions of these ligands from both structural and energetic viewpoints. A reduced model for the binding pocket was used.

Hydrogen-bonded dimers in 3-amino-4-anilino-1H-isochromen-1-one and a hydrogen-bonded sheet in 3-amino-4-[methyl(phenyl)amino]-1H-isochromen-1-one.

The molecules of 3-amino-4-anilino-1H-isochromen-1-one, C15H12N2O2, (I), and 3-amino-4-[methyl(phenyl)amino]-1H-isochromen-1-one, C16H14N2O2, (II), adopt very similar conformations, with the substituted amino group PhNR, where R = H in (I) and R = Me in (II), almost orthogonal to the adjacent heterocyclic ring. The molecules of (I) are linked into cyclic centrosymmetric dimers by pairs of N-H···O hydrogen bonds, while those of (II) are linked into complex sheets by a combination of one three-centre N-H···(O)2 hydrogen bond, one two-centre C-H···O hydrogen bond and two C-H···π(arene) hydrogen bonds.

2-Amino-3-methyl-6-[methyl(phenyl)amino]-5-nitropyrimidin-4(3H)-one: polarized molecules within hydrogen-bonded sheets.

The pyrimidinone ring in the title compound, C(12)H(13)N(5)O(3), is effectively planar, despite the presence of five substituents. The bond distances provide evidence for significant polarization of the electronic structure, with charge separation, and the molecules are linked into sheets by a combination of N-H..

5-Nitro-N4,N6-diphenylpyrimidine-4,6-diamine: polarized molecules linked into pi-stacked chains via three-centre C-H...(O)2 hydrogen bonds.

Molecules of the title compound, C(16)H(13)N(5)O(2), have no internal symmetry despite the symmetric pattern of substitution in the pyrimidine ring. The intramolecular distances indicate polarization of the electronic structure. There are two intramolecular N-H.

Different hydrogen-bonded structures in the isomeric solvates 2-amino-6-anilino-4-methoxy-5-[(E)-4-nitrobenzylideneamino]pyrimidine dimethyl sulfoxide solvate and 2-amino-6-[methyl(phenyl)amino]-5-[(E)-4-nitrobenzylideneamino]pyrimidin-4(3H)-one dimethyl sulfoxide solvate.

The title solvates, (I) and (II), both C(18)H(16)N(6)O(3).C(2)H(6)OS, are isomeric. The conformations adopted by the 6-substituent are significantly different, with the 6-aminophenyl unit remote from the nitrophenyl ring in methoxypyrimidine (I) but adjacent to it in pyrimidinone (II).

Four 2-amino-6-aryl-4-methoxy-11H-pyrimido[4,5-b][1,4]benzodiazepines: similar molecular structures but different crystal structures.

2-Amino-4-methoxy-6-phenyl-11H-pyrimido[4,5-b][1,4]benzodiazepine, C(18)H(15)N(5)O, (I), and its 6-(2-fluorophenyl)-, 6-(3-nitrophenyl)- and 6-(4-methoxyphenyl)- analogues, viz. C(18)H(14)FN(5)O, (II), C(18)H(14)N(6)O(3), (III), and C(19)H(17)N(5)O(2), (IV), respectively, all adopt molecular conformations which are almost identical, containing boat-shaped seven-membered rings. In each structure, paired N-H.

4,6-Dimethoxy-2-phthalimidopyrimidine: sheets built from pi-stacked hydrogen-bonded chains.

The molecules of the title compound, C(14)H(11)N(3)O(4), have approximate but noncrystallographic twofold rotational symmetry. The molecules are linked into chains by a C-H..

2-Amino-4-chloro-6-[N-methyl-N-(4-methylphenyl)amino]pyrimidine: formation versus fragmentation of hydrogen-bonded chains of edge-fused R(2)2(8) rings in 4,6-disubstituted 2-aminopyrimidines.

Molecules of the title compound, C(12)H(13)ClN(4), are linked by two independent N-H...

A three-dimensional hydrogen-bonded framework in 2-amino-6-(N-methylanilino)pyrimidin-4(3H)-one and a ribbon of fused hydrogen-bonded rings in 2-amino-6-(N-methylanilino)-5-nitropyrimidin-4(3H)-one.

The molecular dimensions of both 2-amino-6-(N-methylanilino)pyrimidin-4(3H)-one, C11H12N4O, (I), and 2-amino-6-(N-methylanilino)-5-nitropyrimidin-4(3H)-one, C11H11N5O3, (II), are consistent with considerable polarization of the molecular-electronic structures. The molecules of (I) are linked into a three-dimensional framework by a combination of one N-H..

Hydrogen-bonded sheets of R2(2)(10) and R4(4)(24) rings in 1-deoxy-1-morpholino-D-fructopyranose.

In the title compound, C(10)H(19)NO(6), both rings adopt almost perfect chair conformations and their mutual orientation is influenced by an intramolecular O-H...