Phenylsulfonyl Ring Research Articles

Crystal structure and Hirshfeld surface analysis of 3-(bromo-meth-yl)-2-[1,2-di-bromo-2-(6-nitro-benzo[d][1,3]dioxol-5-yl)eth-yl]-1-(phenyl-sulfon-yl)-1H-indole chloro-form 0.585-solvate.

The title indole derivative, C24H17Br3N2O6S, crystallizes with a partial occupancy [0.585 (4)] CHCl3 solvent mol-ecule. The dihedral angles between the indole ring system and pendant nitro-benzodioxolane rings system and phenyl-sulfonyl ring are 4.81 (14) and 72.24 (19)°, respectively. In the crystal, the indole mol-ecules are linked to each other and to the chloro-form mol-ecule by weak C-H⋯O, C-H⋯Cl, C-H⋯π, C-Br⋯π and C-Cl⋯π and aromatic π-π stacking inter-actions. A Hirshfeld surface analysis was carried out and the inter-molecular contacts with the most significant contributions are H⋯O/O⋯H (24.3%), H⋯H (18.4%), Br⋯H/H⋯Br (16.8%) and C⋯H/H⋯C (8.4%).

Crystal structures of two new carbazole derivatives: 12-(4-nitro-phen-yl)-7-phenyl-sulfonyl-7H-benzofuro[2,3-b]carbazole and 2-methyl-4-(4-nitro-phen-yl)-9-phenyl-sulfonyl-9H-thieno[2,3-b]carbazole.

The title compounds, C30H18N2O5S, (I), and C27H18N2O4S2, (II), are carbazole derivatives with a phenyl-sulfonyl group and a nitro-phenyl group attached to the carbazole moiety in identical positions in both mol-ecules. A benzo-furan ring system in (I) and a methyl-thio-phene ring in (II) are fused with the respective carbazole moieties on the same sides. The mean plane of the carbazole ring system makes a dihedral angle of 3.17 (7)° with the benzo-furan ring system in (I) and a dihedral angle of 3.39 (11)° with the methyl-thio-phene ring in (II), implying that both fused units are essentially planar. The mean planes of the carbazole ring systems in both the compounds are almost orthogonal to the respective nitro-substituted phenyl rings, making dihedral angles of 75.64 (10) and 77.63 (12)° in compounds (I) and (II), respectively. In (I), the phenyl-sulfonyl ring system is positionally disordered with a refined occupancy ratio of 0.63 (2):0.37 (2). In both compounds, the mol-ecular structures are stabilized by intra-molecular C-H⋯O hydrogen bonds, generating S(6) ring motifs with the sulfone group O atoms. In the crystal of compound (I), mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, which generate R22(18) inversion dimers, and inter-connected by C(14) chains running along the c-axis direction, whereas in compound (II), the C-H⋯O hydrogen bonds generate R43(37) ring motifs. In the crystals of both compounds, C-H⋯O hydrogen-bonded sheets are formed lying parallel to (10-1). In addition, C-H⋯π and offset π-π inter-actions [inter-centroid distance = 3.7158 (14) Å in (I) and 3.9040 (15) Å in (II)] are also present in the crystals of both compounds.

Crystal structures of three indole derivatives: 3-ethnyl-2-methyl-1-phenyl-sulfonyl-1H-indole, 4-phenyl-sulfonyl-3H,4H-cyclo-penta-[b]indol-1(2H)-one and 1-{2-[(E)-2-(5-chloro-2-nitro-phen-yl)ethen-yl]-1-phenyl-sulfonyl-1H-indol-3-yl}ethan-1-one chloro-form monosolvate.

The title compounds, C17H13NO2S, (I), C17H13NO3S, (II), and C24H17ClN2O5S·CHCl3, (III), are indole derivatives. Compounds (I) and (II) crystalize with two independent mol-ecules in the asymmetric unit. The indole ring systems in all three structures deviate only slightly from planarity, with dihedral angles between the planes of the pyrrole and benzene rings spanning the tight range 0.20 (9)-1.65 (9)°. These indole ring systems, in turn, are almost orthogonal to the phenyl-sulfonyl rings [range of dihedral angles between mean planes = 77.21 (8)-89.26 (8)°]. In the three compounds, the mol-ecular structure is stabilized by intra-molecular C-H⋯O hydrogen bonds, generating S(6) ring motifs with the sulfone O atom. In compounds (I) and (II), the two independent mol-ecules are linked by C-H⋯O hydrogen bonds and C-H⋯π inter-actions, while in compound (III), the mol-ecules are linked by C-H⋯O hydrogen bonds, generating R 2 (2)(22) inversion dimers.

Modeling Study of Phenylsulfonylfuroxan Derivatives as P-gp Inhibitors: A Combined Approach of CoMFA, CoMSIA and HQSAR

Multidrug resistance (MDR) is a phenomenon whereby cancer cells experience intrinsic or acquired resistance to a broad spectrum of structurally and functionally distinct chemotherapeutic agents. Permeability glycoprotein (P-gp) is the key protein responsible for the development of MDR in cancer cells, as it exports chemotherapeutic agents from cells. In the present study, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram quantitative structure activity relationship (HQSAR) techniques were used to derive predictive models for phenylsulfonylfuroxan derivatives as P-gp inhibitors. Cross-validated correlation coefficients (q(2)) of 0.811, 0.855, and 0.907 and non-cross-validated correlation coefficients (r(2)) of 0.87, 0.985, and 0.973 were obtained for CoMFA, CoMSIA, and HQSAR derived models, respectively. The predictive power of the models were assessed using an external test set of five compounds and showed reasonable external predictabilities (r(2) pred) of 0.704, 0.517, and 0.713, respectively. Contour and atomic contribution maps were generated to investigate physicochemical requirements of ligands for better receptor binding affinity. 3D Contour maps suggested molecular interactions such as steric and electrostatic effects and hydrogen bond formation. However, atomic contribution maps indicated that ortho and para positions of the R(1) phenylsulfonyl ring are the most desirable regions to modulate P-gp antagonism. The 3(rd) and 4(th) positions of the central five-membered ring were also found to be important. Our results are in line with previous reports. Information obtained from the contour and atomic contribution maps were utilized to design more potent compounds containing different R(1) fragments. In addition, the activities of these more potent compounds were predicted using derived models.

(1-Phenylsulfonyl-1H-indol-2-yl)(thiophen-2-yl)methanone

The crystal studied of the title compound, C19H13NO3S2, was found to be a non-merohedral twin with a domain ratio of 0.877 (3):0.123 (3). There are two independent mol­ecules in the asymmetric unit. The dihedral angles between the mean plane of the indole ring system and the phenyl­sulfonyl ring are 71.67 (13) and 71.95 (13)° in the two mol­ecules while the indole unit and the thiophene ring make dihedral angles of 54.91 (12) and 56.92 (13)° in the two molecules. The crystal packing is stabilized by weak C—H⋯π inter­actions.

N-[(3-Phenylsulfanyl-1-phenylsulfonyl-1H-indol-2-yl)methyl]acetamide.

In the title compound, C23H20N2O3S2, the phenylsulfonyl ring and phenylthio ring make dihedral angles of 66.5 (7) and 81.2 (6)°, respectively, with the indole unit. In the crystal, mol­ecules are linked into centrosymmetric dimers via pairs of N—H⋯O hydrogen bonds with graph-set motif R 2 2(14). The crystal structure is further stabilized by weak inter­molecular C—H⋯O and very weak C—H⋯π inter­actions.

1-Methyl-3-phenylsulfonyl-2-piperidone

The piperidone ring in the title compound, C12H15NO3S, has a slightly distorted half-chair conformation with the methyl, carbonyl and phenyl­sulfonyl ring substituents occupying equatorial, equatorial and axial positions, respectively. Mol­ecules are connected into centrosymmetric dimers via C—H⋯O inter­actions and these associate into layers via C—H⋯O—S contacts. Further C—H⋯O inter­actions involving both the carbonyl and sulfonyl O atoms consolidate the crystal packing by providing connections between the layers.

9-(Phenylsulfonyl)-9H-carbazol-2-ol

The crystal structure of the title mol­ecule, C19H13NO3S, confirms the structure of this compound formed from a Diels–Alder reaction between 3-nitro-1-(phenyl­sulfon­yl)indole and 1-meth­oxy-3-(trimethyl­siloxy)-1,3-butadiene (Danishefsky's diene). The angle between planes of tthe carbazole ring system and the phenylsulfonyl ring is 89.97 (17)°.

The indirect mechanism of action of the trifluoroacetyl peptides on elastase. Enzymatic and 19F NMR studies.

Trifluoroacetyl (CF3CO) dipeptide anilides are potent reversible inhibitors of elastase. Their 19F NMR spectra in the presence of the enzyme correspond therefore to slow chemical exchange. Their characteristics are very similar to those previously reported for other CF3CO-peptides. This should correspond to a single binding mode, in which the CF3CO group lies in a specific site in close contact with protein protons. Elastase, irreversibly inhibited by alkylation of Ser-195 with phenylsulfonyl fluoride derivatives, binds the CF3CO-Ala-containing dipeptide anilides still more tightly than the native enzyme. It no longer binds the dipeptide anilides containing a bulky CF3CO-Lys group, suggesting a location of the CF3CO site near the S1 subsite. On the other hand, the chemical shift of the CF3CO 19F resonance in the complex is the only NMR property affected by the enzyme sulfonylation, the T1 and nuclear Overhauser effect values being unmodified as compared to those in the complexes with the native enzyme. The observation of the NMR characteristics of elastases inhibited by phenylsulfonyl groups substituted with fluorine shows that complexation with CF3CO-peptides induces a change of conformation of the catalytic site which should correspond to a displacement of His-57 toward the ortho position of the phenylsulfonyl ring. Such a transconformation is not observed with corresponding acetylated peptides. The phenylsulfonyl fluoride derivatives are still able to react with elastase in the presence of a large excess of CF3CO-peptides. In such conditions the rate of inactivation is much slower but still at least 5% of that measured in the absence of the reversible inhibitors. This residual activity is hardly compatible with the presence of two exclusive modes of interaction of the CF3CO-peptides with native elastase. On the contrary, these observations are better interpreted by a single and identical mode of binding of the peptide to the native and sulfonylated enzymes. According to this mode of binding, the reversible inhibition of elastase by CF3CO-peptides should correspond to an indirect mechanism by which a change of conformation at the active site results in a reduced catalytic activity.

1-(Phenylsulfonyl)-2-[1-(phenylsulfonyl)-2-(3,4,5-trimethoxyphenyl)ethyl]indole

The title compound contains an indole ring system with two phenylsulfonyl groups and one 3,4,5-trimethoxyphenyl group as exocyclic substituents. The methoxy groups in the 3,4,5-trimethoxyphenyl moiety are twisted with respect to the plane of the ring. One of the phenylsulfonyl ring systems and the ring of the 3,4,5-trimethoxyphenyl group are nearly perpendicular to the indole ring system, while the other phenylsulfonyl ring system is inclined at an angle of 30° to it

2-[2-(4-Methoxyphenyl)-1-(phenylsulfonyl)vinyl]-3-(phenylthio)indole

In the title compound, C 29 H 23 NO 3 S 2 , the phenylthio, phenylsulfonyl and anisole rings are inclined at 76.4 (1), 60.0 (1) and 102.6 (1) o , respectively, to the indole ring. The phenylthio and phenylsulfonyl rings are nearly parallel to each other, the dihedral angle between them being 17.6 (1) o