[2-(4-Methylbenzoyl)phenyl](4-methylphenyl)methanone

The asymmetric unit of the title compound, C22H18O2, contains one half-mol­ecule, the complete mol­ecule being generated by the operation of a crystallographic twofold rotation axis. The carbonyl group and the two C atoms attached to it forms inter­planar angles of 23.67 (7)° with the methyl-substituted phenyl ring and 50.74 (8)° with the central ring. In the crystal, mol­ecules are linked into infinite chains along the b-axis direction by inter­molecular C—H⋯O inter­actions, generating R 2 2(10) graph-set motifs

(2-Benzoyl­phen­yl)(3,4-dimethyl­phen­yl)methanone

In the title compound, C22H18O2, the central benzene ring forms dihedral angles of 76.0 (1) and 73.1 (1)° with the phenyl ring and dimethyl-substituted benzene ring, respectively. The carbonyl-group O atoms deviate significantly from the phenyl ring and the dimethyl-substituted benzene ring [−0.582 (12) and 0.546 (12) Å, respectively]. The crystal packing is stabilized by C—H⋯π inter­actions

4-[(Dieth­oxy­phosphino­yl)meth­yl]benzoic acid

In the title compound, C12H17N2O5P, the phospho­nate group is almost orthogonal to both the ethyl groups, with a dihedral angle of 83.75 (11)°. In the crystal, mol­ecules are linked into centrosymmetric dimers via pairs of O—H⋯O hydrogen bonds with an R 2 2(20) graph-set motif. The crystal structure is further consolidated by weak C—H⋯π inter­actions

Design, crystal structure determination, molecular dynamic simulation and MMGBSA calculations of novel p38-alpha MAPK inhibitors for combating Alzheimer's disease

The hallmark of the Alzheimer's disease (AD) is the accumulation of aggregated, misfolded proteins. The cause for this accumulation is increased production of misfolded proteins and impaired clearance of them. Amyloid aggregation and tau hyperphosphorylation are the two proteinopathies which accomplish deprivation of cell and tissue hemostasis during neuropathological process of the AD, as a result of which progressive neuronal degeneration and the loss of cognitive functions. p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in both the events associated with AD: tau protein phosphorylation and inflammation. p38 alpha MAPK pathway is activated by a dual phosphorylation at Thr180 and Tyr182 residues. Clinical and preclinical evidence implicates the stress related kinase p38 alpha MAPK as a potential neurotherapeutic target. Drug design of p38 alpha MAPK inhibitors is mainly focused on small molecules that compete for Adenosine triphosphate in the catalytic site. Here we have carried out the synthesis of phenyl sulfonamide derivatives Sulfo (I) and Sulfo (II). Crystal structures of Sulfo (I) and Sulfo (II) were solved by direct methods using SHELXS-97. Sulfo (I) and Sulfo (II) have R(int)values of 0.0283 and 0.0660, respectively, indicating good quality of crystals and investigated their ability against p38 alpha MAPK. Docking studies revealed that the Sulfo (I) had better binding affinity (-62.24 kcal/mol) as compared to Sulfo (II) and cocrystal having binding affinity of -54.61 kcal/mol and -59.84 kcal/mol, respectively. Molecular dynamics simulation studies of Sulfo (I) and cocrystal of p38 alpha MAPK suggest that during the course of 30 ns simulation run, compound Sulfo (I) attained stability, substantiating the consistency of its binding to p38 alpha MAPK compared to cocrystal. Binding free energy analysis suggests that the compound Sulfo (I) is better than the cocrystal. Thus, this study corroborates the therapeutic potential of synthesized Sulfo (I) in combatting AD

(2-Benzoyl­phen­yl)(2-meth­oxy-1-naphth­yl)methanone

In the title compound C25H18O3, the central benzene ring forms dihedral angles of 87.4 (5) and 85.4 (4)° with the phenyl ring and the naphthalene ring system, respectively. The carbonyl O atoms deviate significantly from the phenyl ring and the meth­oxy-substituted naphthalene ring system [by 0.508 (1) and 0.821 (1) Å, respectively]. The crystal packing is stabilized by C—H⋯O hydrogen bonds, which generate C(6) chains, and C—H⋯π inter­actions

Ethyl 1,3,10,12-tetra­phenyl-19,20-dioxa­hexa­cyclo­[10.6.1.13,10.02,11.04,9.013,18]icosa-4(9),5,7,13(18),14,16-hexa­ene-2-carboxyl­ate

The title compound, C45H34O4, is the product of a tandem ‘pincer’ Diels–Alder reaction consisting of two consecutive [4 + 2] cyclo­additions between two 2-benzofuran units and ethyl propiolate. The mol­ecule comprises a fused hexa­cyclic system containing four five-membered rings, which are in the usual envelope conformation, and two six-membered rings. In addition, four phenyl rings are attached to the hexa­cyclic system. The packing is stabilized by C—H⋯π inter­actions

[3-Hy­droxy­methyl-1,4-bis­(4-methyl­phen­yl)naphthalen-2-yl]methanol

In the title compound, C26H24O2, the crowded naphthalene ring system is essentially planar [maximum deviation of 0.027 (2) Å for one of the C atoms of the unsubstituted ring]. In the crystal, mol­ecules are connected by O—H⋯O hydrogen bonds into chains along the a axis. Pairs of the oppositely oriented chains are further cross-linked by O—H⋯O hydrogen bonds, forming infinte bands of alternating R 4 4(8) dimers and R 2 2(14) motifs

[2-(2-Meth­oxy-1-naphtho­yl)phen­yl](1-naphth­yl)methanone

The title compound, C29H20O3, adopts an ‘S’ conformation with a dihedral angle of 68.5 (2)° beween the two acetone planes. The central phenyl ring forms dihedral angles of 83.8 (4) and 84.5 (4)° with the naphthalene and meth­oxy-substituted naphthalene mean planes, respectively. Both carbonyl-group O atoms deviate significantly from the naphthalene moiety and the meth­oxy-substituted naphthalene moiety [0.574 (1) and −1.053 (1) Å, respectively]. The crystal packing is stabilized by C—H⋯O inter­molecular inter­actions, generating C(7) chain and R 2 2(10) graph-set motifs

3,4-Dibromo-2,5-bis­[(dieth­oxy­phosphor­yl)meth­yl]-1-phenyl­sulfonyl-1H-pyrrole

In the title compound, C20H29Br2NO8P2S, the pyrrole ring is essentially planar, with a maximum deviation of 0.013 (3) Å for a C atom. The pyrrole ring is almost orthogonal to the sulfonyl-bound phenyl ring, with a dihedral angle 88.5 (2)°. Both P atoms exhibit distorted tetra­hedral configurations with O—P—O angles widened and O—P—C angles narrowed from the ideal tetra­hedral value. In the crystal, mol­ecules are linked into centrosymmetric dimers via C—H⋯O inter­actions, resulting in R 2 2(10) graph-set motifs which are further consolidated by R 2 2(13) graph-set ring motifs via C—H⋯O inter­actions, further resulting in chains of mol­ecules running parallel to the c axis; a phosphono O atom is involved in bifurcated hydrogen bonding. All the eth­oxy groups are disordered over two positions each with unequal site-occupancy factors

2-Azido­methyl-3-methyl-1-phenyl­sulfonyl-1H-indole

In the title compound, C16H14N4O2S, the plane of the indole ring is twisted by 70.4 (2)° with respect to the plane of the azidomethyl­ substituent. As a result of the electron-withdrawing character of the phenyl­sulfonyl groups, the N—C bond lengths are slightly longer than the anti­cipated value of approximately 1.355 Å for an N atom with a planar configuration. The indole ring is essentially planar, with a maximum deviation of 0.0296 Å. The azide group is almost linear, the N—N—N angle being 171.4 (3)°. The methyl group on the azide-substituted C atom is in a flagpole position. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 87.07 (10)° with the best plane of the indole moiety. The crystal packing is stabilized by inter­molecular C—H⋯O inter­actions, which link the mol­ecules into infinite chains running parallel to the b axis. The crystal packing is further stabilized by C—H⋯π inter­actions