US 7,442,693 B2Granted

Diazepine compounds as ligands of the melanocortin 1 and/or 4 receptors

AssigneeSmithKline Beecham Corporation

InventorsJerzy Ryszard Szewczyk, Jason Daniel Speake, Douglas McCord Sammond, Ronald George Sherrill

Life of this patent

Estimating the term…

Abstract

There is provided novel diazepines that function as agonists at the melanocortin 4 receptor and as agonists at the melanocortin 1 receptor, pharmaceutical compositions containing them, methods for their use in treatment, and processes for their preparation.

Claims3

Dependent claims

A compound selected from the group consisting of

Example #
Structure
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Example #
Name
2
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methoxyphenyl)acetamide
3
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
chlorophenyl)-N-isopropylacetamide
4
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(2-methyl-4-trifluoromethoxy)phenyl)
acetamide
5
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-3-methoxy-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-(4-fluorophenyl) N-isopropylacetamide
6
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-(trifluoromethoxyphenyl)acetamide
7
3-(1H-indazol-3-ylmethylene)-1-[2-(6-
methoxy-2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)-2-oxoethyl]-5-phenyl-
1H-1,5-diazepine-2,4-dione
8
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
ethylphenyl)-N-isopropylacetamide
9
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-propylphenyl)acetamide
10
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
iodophenyl)-N-isopropylacetamide
11
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-trifluoromethylphenyl)acetamide
12
2-[2,4-dioxo-3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-
methylene-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-isopropyl-N-(4-methoxyphenyl)acetamide
13
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
ethoxyphenyl)-N-isopropylacetamide
14
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methylphenyl)acetamide
15
3-(6-fluoro-1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
16
3-(1H-indazol-3-ylmethylene)-1-[2-oxoethyl-2-(2,3,4,5-tetra-
hydro-1H-1-benzazepin-1-yl)]-5-phenyl-1H-1,5-
diazepine-2,4-dione
17
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-phenyl-
2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methoxyphenyl)acetamide
18
(Chiral) 3-(1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
19
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
fluorophenyl)-N-isopropylacetamide
20
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
21
(Chiral) 2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-
5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
22
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
fluorophenyl)-N-isopropylacetamide
23
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
methoxyphenyl)-N-propylacetamide
24
(Chiral) 3-(1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
25
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-ethyl-
N-(4-methoxyphenyl)acetamide
26
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
isopropoxyphenyl)-N-isopropylacetamide
27
2-[2,4-dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-
ylmethylene)-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-isopropyl-N-(4-methoxyphenyl)acetamide
28
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
hydroxyphenyl)-N-isopropylacetamide
29
2-[2,4-dioxo-3-(1H-benzimidazol-1-ylmethylene)-5-phenyl-
2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-
methoxyphenyl)acetamide
30
1-[2-(3,4-dihydro-2H-2-methylquinolin-1-yl)-2-
oxoethyl]-3-(1H-indazol-3-ylmethylene)-5-phenyl-1H-1,5-
diazepine-2,4-dione
31
2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-isopropylphenyl)acetamide
32
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-
5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
and salts thereof.

162 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/569,257Filed 27 May 2005 · us provisional application
Priority: 28 May 2004
Published: US 2007/0270411 A122 Nov 2007
Granted: 28 Oct 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 25/00
Drugs for disorders of the nervous system

Family

Application60/575,644Us provisional application · filed 28 May 2004
US 2007/0270411 A1Pre-grant publication · published 22 Nov 2007
US 7,442,693 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound selected from the group consisting of

Example #
Structure
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Example #
Name
2
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methoxyphenyl)acetamide
3
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
chlorophenyl)-N-isopropylacetamide
4
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(2-methyl-4-trifluoromethoxy)phenyl)
acetamide
5
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-3-methoxy-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-(4-fluorophenyl) N-isopropylacetamide
6
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-(trifluoromethoxyphenyl)acetamide
7
3-(1H-indazol-3-ylmethylene)-1-[2-(6-
methoxy-2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)-2-oxoethyl]-5-phenyl-
1H-1,5-diazepine-2,4-dione
8
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
ethylphenyl)-N-isopropylacetamide
9
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-propylphenyl)acetamide
10
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
iodophenyl)-N-isopropylacetamide
11
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-trifluoromethylphenyl)acetamide
12
2-[2,4-dioxo-3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-
methylene-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-isopropyl-N-(4-methoxyphenyl)acetamide
13
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
ethoxyphenyl)-N-isopropylacetamide
14
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methylphenyl)acetamide
15
3-(6-fluoro-1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
16
3-(1H-indazol-3-ylmethylene)-1-[2-oxoethyl-2-(2,3,4,5-tetra-
hydro-1H-1-benzazepin-1-yl)]-5-phenyl-1H-1,5-
diazepine-2,4-dione
17
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-phenyl-
2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-methoxyphenyl)acetamide
18
(Chiral) 3-(1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
19
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
fluorophenyl)-N-isopropylacetamide
20
2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-5-
phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
21
(Chiral) 2-[2,4-dioxo-3-(6-fluoro-1H-indazol-3-ylmethylene)-
5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
22
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
fluorophenyl)-N-isopropylacetamide
23
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
methoxyphenyl)-N-propylacetamide
24
(Chiral) 3-(1H-indazol-3-ylmethylene)-1-
[2-oxoethyl-2-(2,3,4,5-tetrahydro-1H-1-
benzazepin-1-yl)]-5-phenyl-1H-1,5-diazepine-2,4-dione
25
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-ethyl-
N-(4-methoxyphenyl)acetamide
26
2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
isopropoxyphenyl)-N-isopropylacetamide
27
2-[2,4-dioxo-5-phenyl-3-(4,5,6,7-tetrahydro-1H-indazol-3-
ylmethylene)-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-
N-isopropyl-N-(4-methoxyphenyl)acetamide
28
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-(4-
hydroxyphenyl)-N-isopropylacetamide
29
2-[2,4-dioxo-3-(1H-benzimidazol-1-ylmethylene)-5-phenyl-
2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-
methoxyphenyl)acetamide
30
1-[2-(3,4-dihydro-2H-2-methylquinolin-1-yl)-2-
oxoethyl]-3-(1H-indazol-3-ylmethylene)-5-phenyl-1H-1,5-
diazepine-2,4-dione
31
2-[2,4-dioxo-3-(1H-indazol-3-
ylmethylene)-5-phenyl-2,3,4,5-
tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-(4-isopropylphenyl)acetamide
32
(Chiral) 2-[2,4-dioxo-3-(1H-indazol-3-ylmethylene)-
5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-
isopropyl-N-phenylacetamide
and salts thereof.

162 more elements

Facts

Application

11/569,257Filed 27 May 2005 · us provisional application

Priority

28 May 2004

Published

US 2007/0270411 A122 Nov 2007

Granted

28 Oct 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 25/00
Drugs for disorders of the nervous system