Carbonic anhydrase inhibitors. Part 61. Quantum chemical QSAR of a group of benzenedisulfonamides

被引：74

作者：

Clare, BW ^{[1
]}

Supuran, CT

机构：

[1] Murdoch Univ, Div Sci, Murdoch, WA 6150, Australia

[2] Univ Western Australia, Dept Chem, Nedlands, WA 6009, Australia

[3] Univ Florence, Lab Chim Inorgan & Bioinorgan, I-50121 Florence, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1999年 / 34卷 / 06期

关键词：

carbonic anhydrase inhibition; QSAR; quantum chemical; synthesis; charge; benzenedisulfonamide;

D O I：

10.1016/S0223-5234(99)80096-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis of a large group of benzenesulfonamides containing both a primary and secondary sulfonamide moiety is described. These compounds are powerful inhibitors of several isozymes of the enzyme carbonic anhydrase. Separate QSAR's are given for inhibition of three of these isozymes, using descriptors mainly derived from molecular orbital calculations by the semiempirical AM1 method. Activity was found to depend on electrostatic potential-based charges on the atoms of both sulfonamide groups, HOMO and LUMO energies, dipole moments, and lipophilicities. These results are compared with those from other studies. (C) Elsevier, Paris.

引用

收藏

页码：463 / 474

页数：12

相关论文

共 52 条

[1] Catalysis and inhibition of human carbonic anhydrase IV [J].

Baird, TT ;

Waheed, A ;

Okuyama, T ;

Sly, WS ;

Fierke, CA .

BIOCHEMISTRY, 1997, 36 (09) :2669-2678

[2] STRUCTURAL AND FUNCTIONAL DIFFERENCES BETWEEN CARBONIC-ANHYDRASE ISOENZYME-I AND ISOENZYME-II AS STUDIED BY SITE-DIRECTED MUTAGENESIS [J].

BEHRAVAN, G ;

JONASSON, P ;

JONSSON, BH ;

LINDSKOG, S .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1991, 198 (03) :589-592

[3] Homosulfandamides [J].

Bergeim, FH ;

Braker, W .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1944, 66 :1459-1460

[4] ATOMIC CHARGES DERIVED FROM SEMIEMPIRICAL METHODS [J].

BESLER, BH ;

MERZ, KM ;

KOLLMAN, PA .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1990, 11 (04) :431-439

[5]

*BMDP, BMDP DYN REL 7

[6] A PARADIGM FOR DRUG DISCOVERY EMPLOYING ENCODED COMBINATORIAL LIBRARIES [J].

BURBAUM, JJ ;

OHLMEYER, MHJ ;

READER, JC ;

HENDERSON, I ;

DILLARD, LW ;

LI, G ;

RANDLE, TL ;

SIGAL, NH ;

CHELSKY, D ;

BALDWIN, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (13) :6027-6031

[7] Studying how different terminal groups change the motion of H2NSO2C6H4CONH(EG)3R when bound to the active site of human carbonic anhydrase II [J].

Chin, DN ;

Lau, AY ;

Whitesides, GM .

JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (04) :938-945

[8] THE RELATIONSHIP OF CHARGE-TRANSFER COMPLEXES TO FRONTIER ORBITAL ENERGIES IN QSAR [J].

CLARE, BW .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 1995, 331 (1-2) :63-78

[9] Carbonic anhydrase inhibitors .41. Quantitative structure-activity correlations involving kinetic rate constants of 20 sulfonamide inhibitors from a non-congeneric series [J].

Clare, BW ;

Supuran, CT .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1997, 32 (04) :311-319

[10] CHARGE-TRANSFER COMPLEXES AND FRONTIER ORBITAL ENERGIES IN QSAR - A CONGENERIC SERIES OF ELECTRON-ACCEPTORS [J].

CLARE, BW .

JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 1995, 337 (02) :139-150

← 1 2 3 4 5 6 →