# US 9,102,656 B2 · Use of rosuvastatin lactols as medicaments

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- Number: US 9,102,656 B2
- Document ID: US9102656B2
- Status: Granted
- Kind: B2
- Application number: 14/029,056
- Filed: 2013-09-17
- Published: 2014-01-16
- Granted: 2015-08-11
- Earliest claimed: 2009-03-10
- Assignees: Redx Pharma PLC
- Applicants: RedX Pharma Limited
- Inventors: Derek Lindsay; Peter Jackson
- Web page: https://patentgrep.com/patent/US9102656B2

## CPC

- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/12: for cataracts
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 405/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to the discovery of novel rosuvastatin analogs. More specifically, the invention relates to novel rosuvastatin analogs which have utility in treating conditions treatable by the inhibition of HMG-CoA reductase.

## Claims

### Claim 1

A method of treating a condition comprising: administering an effective amount of a compound of Formula I
or pharmaceutically acceptable salts or solvates thereof to inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase),
wherein the condition is selected from the group consisting of: hypercholesterolemia, atherosclerosis, hyperlipidemia, coronary heart disease, myocardial infarction, stroke, and peripheral artery disease,
further wherein:
R1 and R4 are independently selected from the group consisting of: hydrogen, halo, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, aryl, C1-4 alkyl aryl, heterocyclyl, and C1-4 alkyl heteroaryl;
R2 is —S(O)2R9 wherein R9 is C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkyl aryl or aryl;
R3 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl or aryl;
R5 and R6 are independently selected from the group consisting of: hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-6 cycloalkyl, aryl, C1-6 alkyl aryl, C1-6 alkanoyl aryl, heteroaryl, C1-6 alkanoyl heteroaryl and C1-6 alkyl heteroaryl; provided always that both R5 and R6 are not hydrogen;
R7 and R8 are independently selected from the group consisting of: H, C1-4 alkyl and halo;
X is —(CRaRb)m(CRa═CRb)n(CRaRb)o where Ra and Rb are independently selected from the group consisting of: H, methyl, ethyl and halo and m, n, and o are independently 0, 1, 2, or 3 provided that m+n+o is not more than 3; and wherein each of the above groups R1 to R9 may, where chemically possible, be independently optionally substituted by from 1 to 5 groups chosen independently at each occurrence from the group consisting of: halo, C1-3 alkyl, halo C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkoxy, hydroxy, and cyano.

### Claim 2 (depends on 1)

The method of claim 1 wherein the condition is selected from the group consisting of: hypercholesterolemia, atherosclerosis, hyperlipidemia, coronary heart disease, myocardial infarction, and peripheral artery disease.

### Claim 3 (depends on 1)

The method of claim 1 wherein the condition is selected from the group consisting of: hypercholesterolemia, atherosclerosis and hyperlipidemia.

### Claim 4 (depends on 1)

The method of claim 1, wherein R1 is C1-6 alkyl.

### Claim 5 (depends on 1)

The method of claim 1, wherein R9 is C1-6 alkyl.

### Claim 6 (depends on 1)

The method of claim 1, wherein R3 is hydrogen or C1-6 alkyl.

### Claim 7 (depends on 1)

The method of claim 1, wherein R4 is optionally substituted aryl.

### Claim 8 (depends on 1)

The method of claim 1, wherein R1 is i-propyl, R2 is —S(O)2Me, R3 is methyl and R4 is 4-fluorophenyl.

### Claim 9 (depends on 1)

The method of claim 1, wherein R5 is selected from the group consisting of: hydrogen, C1-6 alkyl, aryl, C1-6 alkyl aryl, C1-6 alkanoyl aryl, heteroaryl, C1-6 alkanoyl heteroaryl and C1-6 alkyl heteroaryl.

### Claim 10 (depends on 9)

The method of claim 9, wherein R5 is hydrogen.

### Claim 11 (depends on 9)

The method of claim 9, wherein R5 is selected from the group consisting of: —C1 alkyl-Ph, —C2 alkyl-Ph, —C3 alkyl-Ph, and —C4 alkyl-Ph.

### Claim 12 (depends on 11)

The method of claim 11, wherein R5 is benzyl.

### Claim 13 (depends on 9)

The method of claim 9, wherein R5 is C1-6 alkanoyl pyridine.

### Claim 14 (depends on 13)

The method of claim 13, wherein R5 is 3-methanoyl pyridine.

### Claim 15 (depends on 1)

The method claim 1, wherein R6 is selected from the group consisting of: hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-6 cycloalkyl, aryl, C1-6 alkyl aryl, heteroaryl and C1-6 alkyl heteroaryl.

### Claim 16 (depends on 15)

The method of claim 15, wherein R6 is selected from the group consisting of: C1-6 alkyl, C1-6 halo alkyl and C2-6 alkenyl.

### Claim 17 (depends on 16)

The method of claim 16 wherein R6 is selected from the group consisting of: methyl, ethyl, propyl, butyl, chloromethyl, chloroethyl, chloropropyl, chlorobutyl and propylene.

### Claim 18 (depends on 15)

The method of claim 15, wherein R6 is optionally substituted aryl.

### Claim 19 (depends on 18)

The method of claim 18, wherein R6 is selected from the group consisting of: C1-6 alkoxy substituted phenyl and halo substituted phenyl.

### Claim 20 (depends on 19)

The method of claim 19, wherein R6 is selected from the group consisting of: 2,4,6-trifluorophenyl and 2,4-dimethoxyphenyl.

### Claim 21 (depends on 1)

The method of claim 1, wherein R5 is hydrogen and R6 is an optionally substituted aryl group.

### Claim 22 (depends on 1)

The method of claim 1, wherein R5 is an optionally substituted benzyl and R6 is an optionally substituted C1-6 alkyl, an optionally substituted C2-6 alkenyl or a C1-6 haloalkyl.

### Claim 23 (depends on 1)

The method of claim 1, wherein R5 is a C1-6 alkanoyl heteroaryl and R6 is an optionally substituted C1-6 alkyl.

### Claim 24 (depends on 1)

The method of claim 1, wherein R7 is H and R8 is H.

### Claim 25 (depends on 1)

The method of claim 1, wherein Ra is H, Rb is H and m=0, n=1 and o=0.

### Claim 26 (depends on 1)

The method of claim 1 wherein in the step of administering the compound has a structure selected from: