Inhibitors of cholesterol ester transfer protein

Patent metadata

Field	Value
Publication number	US-9708277-B2
Application number	US-201514981088-A
Country	US
Kind code	B2
Filing date	Dec 28, 2015
Priority date	Mar 16, 2007
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The invention relates to novel oxazolidinones their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering cholesterol ester transfer protein inhibitors.

First claim

What is claimed is:

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Each of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 , Y 7 and Y 8 is independently selected from hydrogen and deuterium;
R 1 is CD 3 ;
each of R 2 and R 3 is independently selected from CH 3 , CH 2 D, CHD 2 , and CD 3 ;
R 4 is selected from H, CH 3 , CH 2 D, CHD 2 , and CD 3 ;
R 5 is selected from H and F;
the stereochemistry at * is either (R) or (S); and wherein any atom not designated as deuterium is present at its natural isotopic abundance, and the deuterium incorporation at each designated deuterium atom is at least 90%.

2. The compound of claim 1 , wherein
R 4 is selected from H and CH 3 ;
—CY 3 (R 2 )(R 3 ) is selected from —CH(CH 3 ) 2 , —CD(CD 3 ) 2 , and —CD(CH 2 D)CH 3 ; and
Y 4 , Y 5 , Y 6 , Y 7 and Y 8 are simultaneously hydrogen.

3. The compound of claim 2 , wherein R 4 is (S)—CH 3 ; R 5 is F; Y 1 and Y 2 are the same; the stereochemistry at * is (R); and the compound is selected from any one of the compounds set forth in the table below:

Cmpd #
Y 1 and Y 2
Y 3
R 2
R 3

101
H
H
CH 3
CH 3

110
D
H
CH 3
CH 3

117
H
D
CH 2 D
CH 3

125
H
D
CD 3
CD 3

158
H
D
CH 3
CH 3

159
D
D
CH 3
CH 3

160
D
D
CD 3
CD 3

161
H
H
CD 3
CD 3 and

162
D
H
CD 3
CD 3

or a pharmaceutically acceptable salt thereof.

4. A compound of Formula II:

 or a pharmaceutically acceptable salt thereof, wherein:
Y 1 and Y 2 are the same and are hydrogen or deuterium;
each of Y 3 , Y 4 , Y 5 , Y 6 , Y 7 and Y 8 is independently selected from hydrogen and deuterium;
R 1 is CD 3 ;
each of R 2 , R 3 and R 4a is independently selected from CH 3 and CD 3 ; and wherein any atom not designated as deuterium is present at its natural isotopic abundance, and the deuterium incorporation at each designated deuterium atom is at least 90%.

5. The compound of claim 4 , wherein R 4a is CH 3 .

6. The compound of claim 4 , wherein Y 6 , Y 7 , and Y 8 are the same.

7. The compound of claim 6 , wherein R 2 and R 3 are the same; Y 4 and Y 5 are the same; Y 6 , Y 7 , and Y 8 are simultaneously hydrogen; and the compound is selected from any one of the compounds set forth in the table below:

Cmpd
Y 1 and Y 2
Y 3
Y 4 and Y 5
R 1
R 2 and R 3
R 4a

178
H
H
H
CD 3
CD 3
CD 3

179
H
D
H
CD 3
CD 3
CD 3

180
D
H
H
CD 3
CD 3
CD 3

181
D
D
H
CD 3
CD 3
CD 3

182
H
H
H
CD 3
CH 3
CD 3

183
H
D
H
CD 3
CH 3
CD 3

184
D
H
H
CD 3
CH 3
CD 3

185
D
D
H
CD 3
CH 3
CD 3

201
H
H
D
CD 3
CD 3
CD 3

202
H
D
D
CD 3
CD 3
CD 3

203
D
H
D
CD 3
CD 3
CD 3

204
D
D
D
CD 3
CD 3
CD 3

205
H
H
D
CD 3
CH 3
CD 3

206
H
D
D
CD 3
CH 3
CD 3

207
D
H
D
CD 3
CH 3
CD 3 and

208
D
D
D
CD 3
CH 3
CD 3

Assignees

• Concert Pharmaceuticals Inc

Inventors

• Tung Roger D

Classifications

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K31/421

  1,3-Oxazoles, e.g. pemoline, trimethadione · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07D263/20 Primary

  attached in position 2 · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title