CHIRAL SPIROCYCLIC BENZOPYRAN POTASSIUM CHANNEL OPENERS - EVIDENCE FOR THE ACTIVE CONFORMATION OF LEVCROMAKALIM

被引：9

作者：

GADWOOD, RC

THOMASCO, LM

GROPPI, VE

BURNETT, BA

HUMPHREY, SJ

SMITH, MP

WATT, W

机构：

[1] UPJOHN CO,UPJOHN LABS,DEPT CELL BIOL & INFLAMMAT RES,KALAMAZOO,MI 49001

[2] UPJOHN CO,UPJOHN LABS,DEPT CARDIOVASC PHARMACOL,KALAMAZOO,MI 49001

[3] UPJOHN CO,UPJOHN LABS,DEPT PHYS & ANALYT CHEM,KALAMAZOO,MI 49001

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 18期

关键词：

D O I：

10.1016/0960-894X(95)00356-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Both enantiomers of a spirocyclic benzopyran imidazolone were prepared in high enantiomeric purity. The S-isomer was found to be a potent potassium channel opener while the R-isomer was completely inactive. Comparison of this structurally rigid compound with levcromakalim suggests that the biologically active conformation of levcromakalim is the same as its preferred conformation in solution and solid state.

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页码：2101 / 2104

页数：4

相关论文

共 12 条

[1] CONFORMATIONAL-ANALYSIS OF THE NOVEL ANTIHYPERTENSIVE AGENT CROMAKALIM (BRL34915) [J].

CASSIDY, F ;

EVANS, JM ;

SMITH, DM ;

STEMP, G ;

EDGE, C ;

WILLIAMS, DJ .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1989, (06) :377-378

[2]

EDWARDS G, 1993, ANNU REV PHARMACOL, V33, P597, DOI 10.1146/annurev.pharmtox.33.1.597

[3] CHARACTERIZATION OF THE STEADY-STATE AND DYNAMIC FLUORESCENCE PROPERTIES OF THE POTENTIAL-SENSITIVE DYE BIS-(1,3-DIBUTYLBARBITURIC ACID)TRIMETHINE OXONOL (DIBAC(4)(3)) IN MODEL SYSTEMS AND CELLS [J].

EPPS, DE ;

WOLFE, ML ;

GROPPI, V .

CHEMISTRY AND PHYSICS OF LIPIDS, 1994, 69 (02) :137-150

[4] SYNTHESIS AND BIOLOGICAL-ACTIVITY OF SPIROCYCLIC BENZOPYRAN IMIDAZOLONE POTASSIUM CHANNEL OPENERS [J].

GADWOOD, RC ;

KAMDAR, BV ;

DUBRAY, LAC ;

WOLFE, ML ;

SMITH, MP ;

WATT, W ;

MIZSAK, SA ;

GROPPI, VE .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (10) :1480-1487

[5] 3-METHYL-2H-1-BENZOPYRAN POTASSIUM CHANNEL ACTIVATORS [J].

GERICKE, R ;

HARTING, J ;

LUES, I ;

SCHITTENHELM, C .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (10) :3074-3085

[6] POTASSIUM CHANNEL ACTIVATOR DRUGS - MECHANISM OF ACTION, PHARMACOLOGICAL PROPERTIES, AND THERAPEUTIC POTENTIAL [J].

LONGMAN, SD ;

HAMILTON, TC .

MEDICINAL RESEARCH REVIEWS, 1992, 12 (02) :73-148

[7] PREPARATION OF ALPHA-SUBSTITUTED ALPHA-AMINO-ACIDS OF HIGH ENANTIOMERIC PURITY [J].

PIRKLE, WH ;

HEIRE, R ;

HYUN, MH .

CHIRALITY, 1992, 4 (05) :302-307

[8] SPIRO HYDANTOIN ALDOSE REDUCTASE INHIBITORS DERIVED FROM 8-AZA-4-CHROMANONES [J].

SARGES, R ;

GOLDSTEIN, SW ;

WELCH, WM ;

SWINDELL, AC ;

SIEGEL, TW ;

BEYER, TA .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (07) :1859-1865

[9] SYNTHESIS, ABSOLUTE-CONFIGURATION, AND CONFORMATION OF THE ALDOSE REDUCTASE INHIBITOR SORBINIL [J].

SARGES, R ;

BORDNER, J ;

DOMINY, BW ;

PETERSON, MJ ;

WHIPPLE, EB .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (11) :1716-1720

[10] SYNTHESIS OF OPTICALLY-ACTIVE SPIROHYDANTOINS BY ASYMMETRIC INDUCTION - HYDANTOIN FORMATION FROM AMINO NITRILES AND CHLOROSULFONYL ISOCYANATE [J].

SARGES, R ;

HOWARD, HR ;

KELBAUGH, PR .

JOURNAL OF ORGANIC CHEMISTRY, 1982, 47 (21) :4081-4085