4-carbamoyloxy-piperidine-1-carboxylic acid esters: inhibitors o

Details 4-carbamoyloxy-piperidine-1-carboxylic acid esters: inhibitors o 4-carbamoyloxy-piperidine-1-carboxylic acid esters: inhibitors o

1994-06-13

1996-06-18

Chang, Ceila

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514255, 514269, 514316, 514317, 514318, 514319, 514320, 514321, 514322, 514323, 514324, 514326, 544298, 544302, 544408, 546 16, 546141, 546153, 546188, 546193, 546196, 546198, 546201, 546202, 546205, 546210, 546216, A61K 31445, C07D22120, C07D40110, C07D40112

Patent

active

055278043

ABSTRACT:
Compounds which inhibit the enzyme cholesterol ester hydrolase (CEH) thus inhibit the formation of esterified cholesterol. Esterified cholesterol is absorbed through the intestine and inhibition of the enzyme therefore results in inhibition of cholesterol absorption. The compounds of this invention inhibit cholesterol ester hydrolase and have the formula: ##STR1## wherein Z is --Ar.sup.1, --Ar.sup.1 --Ar.sup.2, --Ar.sup.1 --O--Ar.sup.2, --Ar.sup.1 --S--Ar.sup.2, ##STR2## --Ar.sup.1 --(CH.sub.2).sub.1-20 --Ar.sup.2, --Ar.sup.1 --(CH.sub.2).sub.1-20 --O--Ar.sup.2, --Ar.sup.1 --O--(CH.sub.2).sub.1-20 --Ar.sup.2, --Ar.sup.1 --(CR.sup.6 .dbd.CR.sup.6).sub.1-3 --Ar.sup.2 or --Ar.sup.1 --NR.sup.7 --Ar.sup.2 ; and

REFERENCES:
patent: 5112859 (1992-06-01), Commons
patent: 5169844 (1992-12-01), Commons
Lombardo "Catalytic properties of modified human pancreatic carboxylic ester hydrolase" Biochim. Biophys. Acra v. 700, 75-80 (1982).
Dipersio et al. "Site specific mutagenesis of an essential histidine residue in pancreatic cholesterol esterase" J. Bio. Chem. v. 266, 4033-4036 (1991).
Britt et al. "Identification of a cocaine esterase in a strain of Psseudomonas maltophilia" J. Bacteriology v. 174, 2087-2094 (1992).

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