[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

3-(2,4,6-Trimethyl­benzo­yl)-2-naphthoic acid

The asymmetric unit of the title compound, C21H18O3, contains two crystallographically independent mol­ecules. The two mol­ecules are linked into cyclic centrosymmetric dimers R 2 2(8) by O—H⋯O hydrogen bonds. The dihedral angles between the naphthalene ring system and the benzene ring are 87.0 (8) and 84.4 (2)° in the two mol­ecules. The crystal packing is stabilized by O—H⋯O, C—H⋯π and π–π inter­actions [centroid–centroid distance = 3.664 (11) Å]. In one mol­ecule, the mesityl ring is disordered over two positions [occupancy ratio 0.690 (3):0.690 (3)]

Ethyl 2-acetoxy­methyl-1-phenyl­sulfonyl-1H-indole-3-carboxyl­ate

In the title compound, C20H19NO6S, the phenyl ring of the phenyl­sulfonyl group makes a dihedral angle of 83.35 (5)° with the indole ring system. The mol­ecular structure exhibits a number of short intramolecular C—H⋯O contacts

(4-Bromo­phen­yl)(1-phenyl­sulfonyl-1H-indol-2-yl)methanone

In the title compound, C21H14BrNO3S, the indole ring system forms dihedral angles of 65.64 (8) and 59.30 (8)°, respectively, with the phenyl and bromo­phenyl rings. In the crystal, mol­ecules are connected by a C—H⋯O hydrogen bond, forming a chain along [101]. The chains are further connected by weak inter­molecular C—H⋯π inter­actions, forming a layer parallel to the ac plane

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

In the title compound, C16H14ClNO2S, the phenyl ring makes a dihedral angle of 78.1 (1)° with the indole ring system. The mol­ecular structure is stabilized by weak intra­molecular C—H⋯O inter­actions. The crystal structure exhibits weak inter­molecular C—H⋯O, C—H⋯π and π–π [centroid–centroid distances = 3.620 (1)–3.794 (1) Å] inter­actions

Diethyl 3,4-bis(acetoxy­meth­yl)thieno[2,3-b]thio­phene-2,5-dicarboxyl­ate

In the title compound, C18H20O8S2, the dihedral angle between the two thio­phene rings is 2.33 (7)°. The methyl C atoms of the ester groups are disordered over two positions; the site-occupancy factors of the terminal methyl C atoms are 0.632 (18):0.368 (18) and 0.623 (17):0.377 (17). The mol­ecular structure is stabilized by weak intra­molecular C—H⋯O inter­actions and the crystal structure is stabilized through weak inter­molecular C—H⋯O inter­actions

N-(2-Formyl­phen­yl)benzene­sulfonamide

In the title compound, C13H11NO3S, the two aromatic rings are oriented at an angle of 88.18 (8)°. Intra­molecular N—H⋯O and C—H⋯O hydrogen bonds are observed, each of which generates an S(6) ring motif. In the crystal, mol­ecules are linked into C(7) chains along [010] by inter­molecular C—H⋯O hydrogen bonds. The structure is further stabilized by inter­molecular C—H⋯π inter­actions involving the sulfonyl-bound phenyl ring

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