US5025003A
Expired / Lapsed
US
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Isoprenoid phosphinylformic acid squalene synthetase inhibitors
Assignee: ER Squibb and Sons LLC
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Filing: 1989-09-18
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Granted: 1991-06-18
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Expires: 2009-09-18
Abstract
Abstract Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthetis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents, are provided which have the structure ##STR1## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m --O-- or R 1 --(CH 2 ) m --OCH 2 --, wherein n is 1 to 4 and m is 0 to 3, and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein R 5 , Q 1 , Q 2 and Q 3 are as defined herein. New intermediates, new methods of preparation and a method for using such compounds to inhibit cholesterol biosynthesis are also provided.
Inventors
- 👤 Scott A. Biller
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 01:28
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/28; C07F9/30; C07F9/307; A; A61; A61P; A61P3/00; A61P3/06; A61P43/00; A61P9/00; A61P9/10; C07F9/32; C07F9/3205; C07F9/3247; C07F9/3252; C07F9/38; C07F9/3804; C07F9/3886; C07F9/40; C07F9/4003; C07F9/4062
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
258 words
A compound having the formula ##STR79## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR80## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR81## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR82## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 2
Dependent Claim
258 words
A compound having the formula ##STR79## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR80## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR81## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR82## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 3
Dependent Claim
11 words
The compound as defined in claim 1 having the formula ##STR83##
Claim 4
Dependent Claim
11 words
The compound as defined in claim 1 having the formula ##STR84##
Claim 5
Dependent Claim
11 words
The compound as defined in claim 1 having the formula ##STR85##
Claim 6
Dependent Claim
12 words
The compound as defined in claim 1 wherein R 1 is ##STR86##
Claim 7
Dependent Claim
24 words
The compound as defined in claim 1 wherein R is R 1 --(CH 2 ) n -- and n is 1, 2 or 3.
Claim 8
Dependent Claim
23 words
The compound as defined in claim 1 wherein R is R 1 --(CH 2 ) m O-- and m is 1 or 2.
Claim 9
Dependent Claim
23 words
The compound as defined in claim 1 wherein R is R 1 --(CH 2 ) m OCH 2 -- wherein m is 1.
Claim 10
Dependent Claim
21 words
The compound as defined in claim 1 wherein R 2 is a metal ion and/or R 3 is a metal ion.
Claim 11
Dependent Claim
11 words
The compound as defined in claim 1 having the formula ##STR87##
Claim 12
Dependent Claim
63 words
The compound as defined in claim 1 having the name (E,E)-[ethoxy(5,9,13-trimethyl-4,8,12-tetradecatrienyl)phosphinyl]formic acid, ethyl ester, (E,E)-[hydroxy(5,9,13-trimethyl-4,8,12-tetradecatrienyl)phosphinyl]formic acid, disodium salt; (E,E)-[hydroxy(5,9,13-trimethyl-4,8,12-tetradecatrienyl)phosphinyl]formic acid, ethyl ester, monopotassium salt; (E,E)hydroxy-[hydroxy [(5,9,13-trimethyl-4,8,12-tetradecatrienyl)oxy]phosphinyl]formic acid, disodium salt; (E,E)-[ethoxy[(3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy]methyl]phosphinyl]formic acid, ethyl ester; (E,E)-[hydroxy[[(3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy]methyl]phosphinyl]formic acid, disodium salt; (E,E)-[ethoxy(6,10,14-trimethyl-5,9,13-pentadecatrienyl)phosphinyl]formic acid, ethyl ester; (E,E)-[hydroxy(6,10,14-trimethyl-5,9,13-pentadecatrienyl)phosphinyl]formic acid, disodium salt; (E,E)-[hydroxy[(4,8,12-trimethyl-3,7,11-tridecatrienyl)oxy]phosphinyl]formic acid, disodium salt; (E,E)-[hydroxy[(4,8,12-trimethyl-3,7,11-tridecatrienyl)oxy]phosphinyl]formic acid, ethyl ester, monosodium salt; (E,E)-[ethoxy(4,8,12-trimethyl-3,7,11-tridecatrienyl)[phosphinyl]formic acid, ethyl ester; (E,E)-[hydroxy(4,8,12-trimethyl-3,7,11-tridecatrienyl)phosphinyl]formic acid, disodium salt.
Claim 13
Dependent Claim
19 words
A hypocholesterolemic or hypolipemic composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable carrier therefor.
Claim 14
Independent Claim
282 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR88## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR89## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR90## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR91## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 15
Independent Claim
282 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR88## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR89## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR90## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR91## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 16
Dependent Claim
262 words
A combination comprising a compound having the formula ##STR92## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR93## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR94## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR95## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
Claim 17
Dependent Claim
262 words
A combination comprising a compound having the formula ##STR92## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 --Q 2 --Q 3 -- wherein Q 1 , Q 2 and Q 3 are independently: ##STR93## or a bond, at least one of Q 1 and/or Q 2 being other than a bond; if any of Q 1 , Q 2 and Q 3 is ##STR94## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR95## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
Claim 18
Dependent Claim
31 words
The combination as defined in claim 14 wherein said antihyperlipoproteinemic agent is probucol, gemfibrozil, a bile acid sequestrant, clofibrate, nicotinic acid, neomycin, p-aminosalicylic acid, bezafibrate, or an HMG CoA reductase inhibitor.
Claim 19
Dependent Claim
17 words
The combination as defined in claim 15 wherein the bile acid sequestrant is cholestyramine, colestipol or polidexide.
Claim 20
Dependent Claim
18 words
The combination as defined in claim 15 wherein the HMG CoA reductase inhibitor is lovastatin, pravastatin or simvastatin.
Claim 21
Dependent Claim
190 words
A compound having the formula ##STR96## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is ##STR97## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR98## including all stereoisomers thereof.
Claim 22
Dependent Claim
190 words
A compound having the formula ##STR96## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is ##STR97## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR98## including all stereoisomers thereof.
Claim 23
Independent Claim
213 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR99## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR100## including all stereoisomers thereof.
Claim 24
Independent Claim
213 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR99## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR100## including all stereoisomers thereof.
Claim 25
Dependent Claim
193 words
A combination comprising a compound having the formula ##STR101## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is ##STR102## (wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR103## including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
Claim 26
Dependent Claim
193 words
A combination comprising a compound having the formula ##STR101## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is ##STR102## (wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 5 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; with the proviso that R 10 and R 11 cannot both be H, when R 1 is ##STR103## including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
Claim 27
Dependent Claim
217 words
A compound having the formula ##STR104## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 -- wherein Q 1 is ##STR105## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsiyl or lower alkyl; R 9 is H, or lower alkyl; ##STR106## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 28
Dependent Claim
217 words
A compound having the formula ##STR104## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 -- wherein Q 1 is ##STR105## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsiyl or lower alkyl; R 9 is H, or lower alkyl; ##STR106## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 29
Independent Claim
240 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR107## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 wherein Q 1 is ##STR108## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR109## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 30
Independent Claim
240 words
A method of inhibiting cholesterol biosynthesis, which comprises administering to a patient in need of such treatment an effective cholesterol biosynthesis inhibiting amount of a compound having the formula ##STR107## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 wherein Q 1 is ##STR108## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is H, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR109## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl; R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof.
Claim 31
Dependent Claim
222 words
A combination comprising a compound having the formula ##STR110## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 wherein Q 1 is ##STR111## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR112## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
Claim 32
Dependent Claim
222 words
A combination comprising a compound having the formula ##STR110## wherein R 2 is a metal ion, lower alkyl or H; R 3 is a metal ion or lower alkyl; R is R 1 --(CH 2 ) n --, R 1 --(CH 2 ) m O-- which contains at least 12 carbons in the carbon chain, or R 1 --(CH 2 ) m OCH 2 --, wherein n is an integer from 1 to 4 and m is an integer from 0 to 3; and R 1 is R 5 --Q 1 wherein Q 1 is ##STR111## then R 6 is H, lower alkyl, fluoro or fluoroalkyl; R 7 is, fluoro, lower alkyl or alkylthio; R 8 is H, fluoro, trimethylsilyl or lower alkyl; R 9 is H, or lower alkyl; ##STR112## R 16 --C.tbd.C--CH 2 --(wherein R 16 is lower alkyl or H), or CH 3 (CH 2 ) p -- where p is 2 to 7; R 10 and R 11 are independently hydrogen, lower alkyl, fluoro, lower alkenyl or fluoroalkyl or R 10 and R 11 can be taken together to form (CH 2 ) s , where s is 2 to 7; R 12 is hydrogen, lower alkyl, fluoro or lower alkenyl R 13 and R 14 are independently lower alkyl; including all stereoisomers thereof, and an antihyperlipoproteinemic agent.
References Cited (Backward Citations)
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