Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

Serving 500+ biopharmaceutical companies globally:

Daiichi Sankyo
Accenture
Healthtrust
Cipla
Mallinckrodt
Baxter
Harvard Business School
Chubb
Federal Trade Commission
Queensland Health

Generated: August 17, 2017

DrugPatentWatch Database Preview

Details for Patent: ► Subscribe

« Back to Dashboard

Details for Patent: ► Subscribe

Title: Quinoline type mevalonolactones useful for treating hyperlipidemia, hyperlipoproteinemia or atherosclerosis
Abstract:A compound of the formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are independently hydrogen, C.sub.1-6 alkyl, C.sub.1-6 cycloalkyl, C.sub.1-3 alkoxy, n-butoxy, i-butoxy, sec-butoxy, R.sup.7 R.sup.8 N-- (wherein R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.19 (wherein R.sup.19 is hydrogen or C.sub.1-3 alkyl, and l is 1,2 or 3); or when located at the ortho position to each other, R.sup.1 and R.sup.2, or R.sup.3 and R.sup.4 together form --CH.dbd.CH--CH.dbd.CH--; or when located at the ortho position to each other, R.sup.1 and R.sup.2 together form --OC(R.sup.15 l) (R.sup.16)O-- (wherein R.sup.15 and R.sup.16 are independently hydrogen or C.sub.1-3 alkyl); Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH-- or -- CH.dbd.CH--CH.sub.2 --; and Z is --Q--CH.sub.2 WCH.sub.2 --CO.sub.2 R.sup.12, ##STR2## (wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--; W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11) (OH)--; R.sup.11 is hydrogen atom or C.sub.1-3 alkyl; R.sup.12 is hydrogen or R.sup.14 (wherein R.sup.14 is physiologically hydrolyzable alkyl or M (wherein M is NH.sub.4, sodium, potassium, 1/2 calcium or a hydrate of lower alkyl amine, di-lower alkyl amine or tri-lower alkyl amine)); two R.sup.13 are independently primary or secondary C.sub.1-6 alkyl; or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 ; R.sup.17 and R.sup.18 are independently hydrogen or C.sub.1-3 alkyl; and R.sup.5 is hydrogen, C.sub.1-6 alkyl, C.sub.2-3 alkenyl, C.sub.3-6 cycloalkyl, ##STR3## wherein R.sup.9 is a hydrogen atom, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, fluoro, chloro, bromo or trifluoromethyl), phenyl--(CH.sub.2).sub.m -- (wherein m is 1,2 or 3), --(CH.sub.2).sub.n CH(CH.sub.3)--phenyl or phenyl--(CH.sub.2).sub.n CH(CH.sub.3)-- (wherein n is 0,1 or 2).
Inventor(s): Fukikawa; Yoshihiro (Funabashi, JP), Suzuki; Mikio (Funabashi, JP), Iwasaki; Hiroshi (Funabashi, JP), Sakashita; Mitsuaki (Shiraoka, JP), Kitahara; Masaki (Shiraoka, JP)
Assignee: Nissan Chemical Industries Ltd. (Tokyo, JP)
Filing Date:Feb 23, 1990
Application Number:07/483,829
Claims:1. A compound of the formula: ##STR17## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6 are independently hydrogen C.sub.1-6 alkyl, C.sub.1-3 alkoxy, n-butoxy, i-butoxy, sec-butoxy, R.sup.7 R.sup.8 N-- (wherein R.sup.7 and R.sup.8 are independently hydrogen or C.sub.1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy diphenyl-t-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.19 (wherein R.sup.19 is hydrogen or C.sub.1-3 alkyl, and l is 1, 2 or; Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH-- or --CH.dbd.CH--CH.sub.2 --; and Z is ##STR18## (wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--; W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11)(OH)--; R.sup.11 is hydrogen or C.sub.1-3 alkyl; R.sup.12 is hydrogen or R.sup.14 (wherein R.sup.14 is physiologically hydrolyzable alkyl or M (wherein M is NH.sub.4, sodium, potassium, 1/2 calcium or a hydrate of lower alkylamine, di-lower alkylamine or tri-lower alkylamine)); two R.sup.13 are independently primary or secondary C.sub.1-6 alkyl; or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 --; R.sup.17 and R.sup.18 are independently hydrogen or C.sub.1-3 alkyl; and R.sup.5 is hydrogen, C.sub.1-6 alkyl, C.sub.2-3 alkenyl, C.sub.3-6 cycloalkyl, ##STR19## (wherein R.sup.9 is hydrogen, C.sub.1-4 alkyl, C.sub.1-3 alkoxy, fluoro, chloro, bromo or trifluoromethyl), phenyl-(CH.sub.2).sub.m -- (wherein m is 1, 2 or 3), --(CH.sub.2).sub.n CH(CH.sub.3)-phenyl or phenyl-(CH.sub.2).sub.n CH(CH.sub.3)-- (wherein n provided that at least one of R.sup.1, R.sup.2 and R.sup.6 is trimethylsilyloxy or diphenyl-t-butylsilyloxy.

2. The compound according to claim 1, wherein in the formula I, R.sup.1, R.sup.2 and R.sup.6 are independently hydrogen, fluoro, chloro, bromo, C.sub.1-3 alkyl, C.sub.1-3 alkoxy, dimethylamino, hydroxy, hydroxymethyl, hydroxyethyl, trifluoromethyl, trifluoromethoxy, difluoromethoxy, phenoxy or benzyloxy; trimethylsilyloxy or diphenyl-t-butylsilyloxy; when R.sup.4 is hydrogen, R.sup.3 is hydrogen, 3'-fluoro, 3'-chloro, R.sup.11 is hydrogen or C.sub.1-3 alkyl 3'-methyl, 4'-methyl, 4'-chloro or 4'-fluoro; or R.sup.3 and R.sup.4 together represent 3'-methyl-4'-chloro, 3',5'-dichloro, 3',5'-difluoro, 3',5'-dimethyl or 3'-methyl-4'-fluoro; R.sup.5 is primary or secondary C.sub.1-6 alkyl or C.sub.3-6 cycloalkyl; and Y is --CH.sub.2 --CH.sub.2 or --CH.dbd.CH--; and Z is ##STR20## provided that at least one of R.sup.1, R.sup.2 and R.sup.6 is trimethylsilyloxy or diphenyl-t-butylsilyloxy.

3. Compound according to claim 2, wherein R.sup.1, R.sup.2 and R.sup.6 are independently trimethylsilyloxy or diphenyl-t-butylsilyloxy; when R.sup.3 is hydrogen, R.sup.4 is hydrogen, 4'-methyl, 4'-chloro or 4'-fluoro; or when both R.sup.3 and R.sup.4 are not hydrogen, they represent 3',5'-dimethyl or 3'-methyl-4'-fluoro; and Y is --CH.sub.2 --CH.sub.2 -- or (E)----CH.dbd.CH--.

4. The compound according to claim 3, wherein R.sup.3 is hydrogen, R.sup.4 is hydrogen, 4'-fluoro or 4'-chloro; or R.sup.3 and R.sup.4 together represent 3'-methyl-4'-fluoro; R.sup.5 is ethyl, n-propyl, i-propyl or cyclopropyl; and Y is (E)----CH.dbd.CH--.

5. The compound according to claim 3, wherein when both R.sup.2 and R.sup.6 are hydrogen, R.sup.1 is trimethylsilyloxy or diphenyl-t-butylsilyloxy; when R.sup.3 is hydrogen, R.sup.4 is hydrogen, 4'-chloro or 4'-fluoro; R.sup.5 is i-propyl or cyclopropyl; and Y is (E)----CH.dbd.CH--.

6. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-[4'-(4"-fluorophenyl)-2'-(1"-methylethyl)6'-trimethyls ilyloxy-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

7. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-[4'-(4"-fluorophenyl)-2'-(1"-methylethyl)7'-trimethyls ilyloxy-6'-chloro-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

8. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-[4'-(4"-fluorophenyl)-2'-(1"-methylethyl)8'-trimethyls ilyloxy-6'-methyl-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

9. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-2'-cyclopropyl[4'-(4"-fluorophenyl)6'-trimethylsilylox y-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

10. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-[2-cyclopropyl4'-(4"-fluorophenyl)7'-trimethylsilyloxy -2'-cyclopropyl-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

11. The compound according to claim 1, which is (E)-3,5-dihydroxy-7-[2'-cyclopropyl4'-(4"-fluorophenyl)7'-trimethylsilylox y-2'-cyclopropyl-6'-chloro-quinolin-3'-yl]-hept-6-enoic acid, a lactone formed by the condensation of the carboxylic acid with hydroxy at the 5-position, or a sodium salt or C.sub.1-3 alkyl ester of the carboxylic acid.

12. A method for treating hyperlipidemia, which comprises administering an effective amount of the compound of the formula I as defined in claim 1 to a host in need of treatment for hyperlipidemia.

13. A method for treating hyperlipoproteinemia which comprises administering an effective amount of the compound of the formula I as defined in claim 1 to a host in need of treatment for hyperlipoproteinemia.

14. A method for treating atherosclerosis which comprises administering an effective amount of the compound of the formula I as defined in claim 1 to a host in need of treatment for atherosclerosis.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Serving 500+ biopharmaceutical companies globally:

Argus Health
Mallinckrodt
Healthtrust
McKesson
Colorcon
QuintilesIMS
Dow
Merck
US Department of Justice
Fuji

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

Copyright 2002-2017 thinkBiotech LLC
ISSN: 2162-2639

Secure SSL Encrypted Heap | Mobile and Web Analytics
Privacy and Cookies
Terms & Conditions

Follow DrugPatentWatch:



Google
Twitter
Google Plus
botpot