Chemically modified quinoline and quinolone derivatives useful as CB-1 inverse agonists

Patent metadata

Field	Value
Publication number	US-9815790-B2
Application number	US-201615239476-A
Country	US
Kind code	B2
Filing date	Aug 17, 2016
Priority date	Aug 27, 2015
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the CB1 receptor. Such compounds are represented by Formula (I)

wherein R 1 , R 2 , R 3 , L 1 , n, v, r, w, and g are defined herein.

and further represented by Formula (II)

wherein the group “X═Y”, ring A, R 10 , R 11 , R 30 , W, and t are defined herein.

First claim

The invention claimed is:

1. A compound of Formula (I)

wherein
R 1 and R 2 are selected from the group consisting of

i) hydrogen,

such that one of R 1 and R 2 is hydrogen in every instance;
R 3 is a substituent selected from the group consisting of methyl, C 1-4 alkoxycarbonylamino-ethyl, C 1-4 alkoxycarbonyl-ethyl, carboxyethyl, aminoethyl, hydrogen, 4-hydroxymethylphenyl, or a substituent selected from the group consisting of

wherein L 1 is selected from

n is an integer from 2 to 36;
v is an integer from 1 to 12;
r is an integer from 2 to 7;
w is an integer from 1 to 24;
g is an integer from 1 to 24;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

2. The compound of claim 1 wherein R 1 and R 2 are selected from the group consisting of
i) hydrogen,

r is an integer from 2 to 5;

such that one of R 1 and R 2 is hydrogen in every instance.

3. The compound of claim 2 wherein r is an integer from 5 to 7.

4. The compound of claim 1 wherein R 1 and R 2 are selected from the group consisting of
i) hydrogen,

wherein n is an integer selected from the group consisting of
ii) 3, 4, 6, 7, and 11;

wherein r is 5;

5. The compound of claim 1 wherein R 3 is a substituent selected from the group consisting of hydrogen, methyl, t-butoxycarbonylamino-ethyl, t-butoxycarbonyl-ethyl, aminoethyl, carboxyethyl, 4-hydroxymethylphenyl, or a substituent selected from the group consisting of

wherein v is 9 or 12;

wherein L 1 is

and w is 12;

wherein g is 12.

6. The compound of claim 1 wherein R 3 is a substituent selected from the group consisting of hydrogen, methyl, t-butoxycarbonylamino-ethyl, t-butoxycarbonyl-ethyl, aminoethyl, carboxyethyl, 4-hydroxymethylphenyl, or a substituent selected from the group consisting of

wherein v is 9 or 12;

wherein L 1 is

and w is 12;

wherein g is 12.

7. The compound of claim 1 wherein n is an integer from 3 to 12.

8. The compound of claim 6 wherein v is an integer from 5 to 12.

9. A compound of Formula (I)

wherein
R 1 and R 2 are selected from the group consisting of

i) hydrogen,

such that one of R 1 and R 2 is hydrogen in every instance;
R 3 is a substituent selected from the group consisting of methyl, carboxyethyl, aminoethyl, hydrogen, 4-hydroxymethylphenyl, or a substituent selected from the group consisting of

wherein L 1 is

and
n is an integer from 3 to 12;
v is an integer from 5 to 12;
r is an integer from 2 to 5;
w is an integer from 1 to 12;
g is an integer from 1 to 12;

or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

10. A compound of Formula (I)

wherein
R 1 and R 2 are selected from the group consisting of

i) hydrogen,

R 3 is a substituent selected from the group consisting of hydrogen, methyl, t-butoxycarbonylamino-ethyl, t-butoxycarbonyl-ethyl, aminoethyl, carboxyethyl, 4-hydroxymethylphenyl, and a substituent selected from the group consisting of

 wherein L 1 is

n is an integer selected from the group consisting of 3, 4, 6, 7, and 11;
v is 9 or 12;
r is 5;
w is 12;
g is 12;

or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

11. A compound of Formula (II)

wherein
the group “X═Y” is

such that when X═Y is

 R 11 is

ring A is selected from

R 10 and R 11 are selected from the group consisting of hydrogen or

 wherein W is O or absent; such that one of R 10 and R 11 is hydrogen in every instance where both R 10 and R 11 are present;
R 30 is a substituent selected from the group consisting of hydrogen, methyl, C 1-4 alkoxycarbonylamino-ethyl, C 1-4 alkoxycarbonyl-ethyl, carboxyethyl, aminoethyl, and 4-hydroxymethylphenyl;
t is an integer from 2 to 14;

or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

12. The compound of claim 11 wherein the group “X═Y” is

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Macielag Mark J
• Zhang Yue-Mei
• Greco Michael N
• Springer Barry A
• Murray William V

Classifications

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D215/44 Primary

  with aryl radicals attached to said nitrogen atoms · CPC title

• C09B11/02

  derived from diarylmethanes · CPC title

• C09B69/103

  containing a diaryl- or triarylmethane dye · CPC title