Patent US5116870A successfully refreshed from Google Patents.
US5116870A
Expired / Lapsed
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HMG-CoA reductase inhibitors
Assignee: Merck and Co Inc
•
Filing: 1990-06-06
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Granted: 1992-05-26
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Expires: 2010-06-06
Abstract
Abstract Novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are useful as antihypercholesterolemic agents and are represented by the following general structural formula (II): ##STR1##
Inventors
- 👤 Robert L. Smith
- 👤 Wasyl Halczenko
- 👤 George D. Hartman
- 👤 Gerald E. Stokker
- 👤 Edward S. Inamine
- 👤 Otto D. Hensens
- 👤 David R. Houck
- 👤 Ta J. Lee
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:56
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C12; C12N; C12N1/00; C12N1/20; C12N1/205; C12P; C12P17/00; C12P17/02; C12P17/06; C12P7/00; C12P7/62; C12R; C12R2001/00; C12R2001/01; C12R2001/365
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
1070 words
A compound represented by the following structural formula II: ##STR49## wherein: R is ##STR50## R 1 and R 5 are independently: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O).sub. n, (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is: (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; (16) R 9 S in which R 9 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R 2 and R 6 are independently: (1) hydrogen; (2) C 1- 5 alkyl; (3) substituted C 1-5 alkyl in which the substituent is: (a) phenyl, (b) dimethylamino, and (c) acetylamino, and (4) 2,3-dihydroxypropyl; R 3 and R 4 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y. (i) C 1-10 alkylS(O) n , (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2-10 alkenyl; (5) substituted C 2-10 alkenyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n , (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (6) C 3-8 cycloalkyl; (7) substituted C 3-8 cycloalkyl in which one substituent is: (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; R 7 and R 8 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-10 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkyl S(O) n in which n is 0 to 2, (j) C 3-8 cycloalkyl S(O) n , (k) phenyl S(O) n ; (l) substituted phenyl S(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) aminocarbonyl; (7) substituted aminocarbonyl in which one or more substituent(s) is: (a) C 1-5 alkyl, (b) C 3-8 cycloalkyl, (c) phenyl, (d) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; (10) C 1-10 alkylcarbonyl; (11) C 3-8 cycloalkylcarbonyl; (12) phenylcarbonyl; (13) substituted phenylcarbonyl in which the substituents are X and Y; and X and Y independently are hydrogen, halogen, trifluoromethyl, C 1-3 alkyl, nitro, cyano or a group selected from: (1) R 10 O(CH 2 ) m in which m is 0 to 3 and R 10 is hydrogen, C 1-3 alkyl or hydroxy-C 2-3 alkyl; (2) ##STR51## in which R 11 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, phenyl, naphthyl, amino-C 1-3 alkyl, C 1-3 alkylamino C 1-3 alkyl, di(C 1-3 alkyl)amino-C 1-3 alkyl, hydroxy-C 2-3 -alkylamino-C 1-3 alkyl or di(hydroxy C 2-3 alkyl) amino-C 1-3 alkyl; (3) ##STR52## in which R 12 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, phenyl or naphthyl; (4) ##STR53## in which R 13 and R 14 independently are hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl; (5) R 15 S(O) n (CH 2 ) m in which R 15 is hydrogen, C 1-3 alkyl, amino, C 1-3 alkylamino or di(C 1-3 alkyl)amino; and a, b and c each represent single bonds or one of a, b and c represents a double bond or both a and c represent double bonds; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
1070 words
A compound represented by the following structural formula II: ##STR49## wherein: R is ##STR50## R 1 and R 5 are independently: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O).sub. n, (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is: (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; (16) R 9 S in which R 9 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R 2 and R 6 are independently: (1) hydrogen; (2) C 1- 5 alkyl; (3) substituted C 1-5 alkyl in which the substituent is: (a) phenyl, (b) dimethylamino, and (c) acetylamino, and (4) 2,3-dihydroxypropyl; R 3 and R 4 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y. (i) C 1-10 alkylS(O) n , (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2-10 alkenyl; (5) substituted C 2-10 alkenyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkylS(O) n , (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (l) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (6) C 3-8 cycloalkyl; (7) substituted C 3-8 cycloalkyl in which one substituent is: (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (l) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; R 7 and R 8 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-10 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, (i) C 1-10 alkyl S(O) n in which n is 0 to 2, (j) C 3-8 cycloalkyl S(O) n , (k) phenyl S(O) n ; (l) substituted phenyl S(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) aminocarbonyl; (7) substituted aminocarbonyl in which one or more substituent(s) is: (a) C 1-5 alkyl, (b) C 3-8 cycloalkyl, (c) phenyl, (d) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; (10) C 1-10 alkylcarbonyl; (11) C 3-8 cycloalkylcarbonyl; (12) phenylcarbonyl; (13) substituted phenylcarbonyl in which the substituents are X and Y; and X and Y independently are hydrogen, halogen, trifluoromethyl, C 1-3 alkyl, nitro, cyano or a group selected from: (1) R 10 O(CH 2 ) m in which m is 0 to 3 and R 10 is hydrogen, C 1-3 alkyl or hydroxy-C 2-3 alkyl; (2) ##STR51## in which R 11 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, phenyl, naphthyl, amino-C 1-3 alkyl, C 1-3 alkylamino C 1-3 alkyl, di(C 1-3 alkyl)amino-C 1-3 alkyl, hydroxy-C 2-3 -alkylamino-C 1-3 alkyl or di(hydroxy C 2-3 alkyl) amino-C 1-3 alkyl; (3) ##STR52## in which R 12 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, phenyl or naphthyl; (4) ##STR53## in which R 13 and R 14 independently are hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl; (5) R 15 S(O) n (CH 2 ) m in which R 15 is hydrogen, C 1-3 alkyl, amino, C 1-3 alkylamino or di(C 1-3 alkyl)amino; and a, b and c each represent single bonds or one of a, b and c represents a double bond or both a and c represent double bonds; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
187 words
A compound of claim 1 wherein: R 1 and R 5 are independently: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is: (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, and (i) oxo; (3) C 3-8 cycloalkyl; (4) substituted C 3-8 cycloalkyl in which one substituent is: (a) C 1-10 alkyl, (b) substituted C 1-10 alkyl in which the substituent is (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy (iv) C 1-5 acyloxy, (v) C 1-5 alkoxycarbonyl, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y, and (viii) oxo, (c) halogen, (d) hydroxy, (e) C 1-10 alkoxy, (f) C 1-5 alkoxycarbonyl, (g) C 1-5 acyloxy, (h) phenyl, (i) substituted phenyl in which the substituents are X and Y; (5) phenylamino; (6) substituted phenylamino in which the substituents are X and Y; (7) phenyl C 1-10 alkylamino; and (8) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y.
Claim 4
Dependent Claim
35 words
A compound of claim 2 wherein: R 1 and R 5 are independently: (1) C 1-10 alkyl; (2) C 3-8 cycloalkyl; (3) phenylamino; and (4) substituted phenylamino in which the substituents are X and Y.
Claim 5
Dependent Claim
26 words
A compound of claim 3 wherein: R 3 and R 4 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) C 3-8 cycloalkyl; and (4) phenyl.
Claim 6
Dependent Claim
56 words
A compound of claim 4 wherein: R 7 and R 8 are independently: (1) hydrogen; (2) C 1-10 alkyl; (3) C 3-8 cycloalkyl; (4) aminocarbonyl; (5) substituted aminocarbonyl in which one or more substituent(s) is: (a) C 1-5 alkyl, (b) C 3-8 cycloalkyl, (c) phenyl, (d) substituted phenyl in which the substituents are X and Y.
Claim 7
Dependent Claim
12 words
A compound of claim 5 wherein R 1 is 1,1-dimethylpropyl or sec-butyl.
Claim 8
Dependent Claim
24 words
A compound of claim 6 wherein R 3 and R 4 are independently selected from: (1) hydrogen; (2) C 1-5 alkyl; and (3) phenyl.
Claim 9
Dependent Claim
12 words
The compound of claim 7 wherein a and c represent double bonds.
Claim 10
Dependent Claim
9 words
The compound of claim 8 wherein R is ##STR54##
Claim 11
Dependent Claim
23 words
The compound of claim 9 selected from the group consisting of: (1) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-hydroxymethyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-hydroxymethyl-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(R)-hydroxymethyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-phenylaminocarbonyloxymethyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 12
Dependent Claim
14 words
The compound of claim 8 wherein R is CO 2 R 6 or ##STR55##
Claim 13
Dependent Claim
29 words
The compound of claim 11 selected from the group consisting of: (1) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-carboxy-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-carboxy-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(R)-carboxy-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-(N,N-dimethyl)aminocarbonyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (5) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(R)-aminocarbonyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (6) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-aminocarbonyl-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 14
Dependent Claim
23 words
The compound of claim 9 selected from the group consisting of: (1) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-(1-hydroxyethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(R)-(1-hydroxyethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(S)-(1-hydroxyethyl)-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,6,7,8,8a(R)-hexahydro-2(S)-methyl-6(R)-(1,hydroxyethyl)-8(S)-(2-methylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 15
Dependent Claim
13 words
The compound of claim 7 wherein a, b and c represent single bonds.
Claim 16
Dependent Claim
9 words
The compound of claim 13 wherein R is ##STR56##
Claim 17
Dependent Claim
26 words
The compound of claim 15 selected from the group consisting of: (1) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(1-hydroxymethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(2,2-dimethylbutyryloxymethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(R)-(1-hydroxyethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(1-hydroxyethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (5) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(1-hydroxyphenylmethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 18
Dependent Claim
14 words
The compound of claim 14 wherein R is CO 2 R 6 or ##STR57##
Claim 19
Dependent Claim
23 words
The compound of claim 17 selected from the group consisting of: (1) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-carboxy-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-ethoxycarbonyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-aminocarbonyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (4) 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(N-cyclohexylaminocarbonyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 20
Dependent Claim
9 words
The compound of claim 14 wherein R is ##STR58##
Claim 21
Dependent Claim
9 words
The compound of claim 19 which is: 7-[1,2,3,4,4a(S),5,6,7,8,8a(R)-decahydro-2(S)-methyl-6(S)-(1-oxoethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 22
Dependent Claim
16 words
The compound of claim 7 wherein one of a, b and c represents a double bond.
Claim 23
Dependent Claim
9 words
The compound of claim 21 wherein R is ##STR59##
Claim 24
Dependent Claim
20 words
The compound of claim 22 selected from the group consisting of: (1) 7-[1,2,3,4,6,7,8,8a(R)-octahydro-2(S)-methyl-6(R)-hydroxymethyl-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (2) 7-[1,2,3,4,6,7,8,8a(R)-octahydro-2(S)-methyl-6(R)-(2,2-dimethylbutyryloxymethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid; (3) 7-[1,2,3,4,6,7,8,8a(R)-octahydro-2(S)-methyl-6(R)-(1-hydroxyethyl)-8(S)-(2,2-dimethylbutyryloxy)-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid.
Claim 25
Dependent Claim
23 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a pharmaceutically acceptable carrier and a nontoxic effective amount of a compound as defined in claim 1.
Claim 26
Dependent Claim
28 words
A method of inhibiting cholesterol biosynthesis comprising the administration to a subject in need of such treatment a nontoxic therapeutically effective amount of a compound of claim 1.
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US4351844A
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-05-26 | 1995-11-25 | 1996-05-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-05-26 | 1999-11-25 | 2000-05-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-05-26 | 2003-11-25 | 2004-05-26 | $7700.00 | Window Closed / Lapsed |