IRREVERSIBLE ENZYME INHIBITORS .145. PROTEOLYTIC ENZYMES .8. ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF ALPHA-CHYMOTRYPSIN DERIVED FROM ALPHA-(2-CARBOXY-4-CHLOROPHENOXY)ACETAMIDE BEARING A TERMINAL SULFONYL FLUORIDE

被引：15

作者：

BAKER, BR

HURLBUT, JA

机构：

[1] Department of Chemistry, University of California at Santa Barbara, Santa Barbara

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1969年 / 12卷 / 01期

关键词：

D O I：

10.1021/jm00301a030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thirteen candidate irreversible inhibitors derived from N-benzyl- or N-phenyl-α-(2-carboxy-4-chlorophenoxy)-acetamide with a terminal SO2F group on the N substituent were synthesized and evaluated. A number of these at a Ki concentration gave essentially complete inactivation of α-chymotrypsin in 60 min at 37°. The best compound was α-(2-carboxy-4-chlorophenoxy)-N-[m-(m-fluorosulfonylphenyluieido)benzyl] acetamide (7) which showed a half-life of inactivation of 2 min when a Ki = 81 μM concentration was incubated with 1 μM chymotrypsin. © 1969, American Chemical Society. All rights reserved.

引用

页码：118 / &

共 17 条

[1] IRREVERSIBLE ENZYME INHIBITORS . 144 . PROTEOLYTIC ENZYMES .7. ADDITIONAL ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF TRYPSIN DERIVED FROM M- AND P-(PHENOXYALKOXY)BENZAMIDINES WITH A TERMINAL SULFONYL FLUORIDE
BAKER, BR
ERICKSON, EH
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1969, 12 (01) : 112 - &
[2] IRREVERSIBLE ENZYME INHIBITORS .114. PROTEOLYTIC ENZYMES .4. ADDITIONAL ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF ALPHA-CHYMOTRYPSIN DERIVED FROM PHENOXYACETAMIDES BEARING A TERMINAL SULFONYL FLUORIDE
BAKER, BR
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[3] IRREVERSIBLE ENZYME INHIBITORS .113. PROTEOLYTIC ENZYMES .3. ACTIVE-SITE-DIRECTED IRREVERSIBLE INHIBITORS OF ALPHA-CHYMOTRYPSIN DERIVED FROM PHENOXYACETAMIDES WITH AN N-FLUOROSULFONYLPHENYL SUBSTITUENT
BAKER, BR
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[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1968, 11 (02) : 233 - &
[4] IRREVERSIBLE ENZYME INHIBITORS .107. PROTEOLYTIC ENZYMES .2. BULK TOLERANCE WITHIN CHYMOTRYPSIN-INHIBITOR COMPLEXES
BAKER, BR
HURLBUT, JA
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1967, 10 (06) : 1129 - &
[5] IRREVERSIBLE ENZYME INHIBITORS .91. CANDIDATE ACTIVE-SITE DIRECTED IRREVERSIBLE INHIBITORS OF THYMIDYLATE SYNTHETASE .2. 2-AMINO-6-METHYL-5-(P-TOLYLSULFONAMIDOPROPYL)-4-PYRIMIDINOLS WITH N-SUBSTITUENTS ON SULFONAMIDO MOIETY (1,2)
BAKER, BR
COWARD, JK
[J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1967, 4 (02) : 202 - &
[6] BAKER BR, 1969, J MED CHEM, V12, P74, DOI 10.1021/jm00301a019
[7] IRREVERSIBLE ENZYME INHIBITORS .132. PROTEOLYTIC ENZYMES .6. TOLERANCE FOR POLAR GROUPS ON PHENOXYACETANILIDE TYPE OF INHIBITOR OF ALPHA-CHYMOTRYPSIN
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[8] IRREVERSIBLE ENZYME INHIBITORS .106. PROTEOLYTIC ENZYMES .I. BULK TOLERANCES IN TRYPSIN-INHIBITOR COMPLEXES
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[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1967, 10 (06) : 1123 - +
[9] ANALOGS OF TETRAHYDROFOLIC ACID .39(1,2). SELECTIVE BROMOACYLATION OF POLYFUNCTIONAL MOLECULES FOR SYNTHESIS OF ACTIVE-SITE-DIRECTED IRREVERSIBLE ENZYME INHIBITORS
BAKER, BR
SANTI, DV
COWARD, JK
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[J]. JOURNAL OF HETEROCYCLIC CHEMISTRY, 1966, 3 (04) : 425 - &
[10] BAKER BR, 1967, DESIGN ACTIVESITEDIR, pCH9

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