Organic compounds

Patent metadata

Field	Value
Publication number	US-10105349-B2
Application number	US-201515533525-A
Country	US
Kind code	B2
Filing date	Dec 7, 2015
Priority date	Dec 6, 2014
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

The present invention relates to certain PDE2 inhibitory compounds, in free or salt form, pharmaceutical compositions containing such compounds and methods for the treatment of PDE2 mediated disorders.

First claim

What is claimed is:

1. A Compound of Formula I

wherein
(i) R 1 is C 1-4 alkyl
(ii) R 2 is selected from the group consisting of:
H,
—OH,
halo,
C 1-4 alkyl,
C 1-4 alkoxy,
—N(R f )(R g ),
—C(O)N(R h )(R i ),
—C(O)OR j ,
—CN,
C 1-4 alkylthio,
heteroaryl,
heteroC 3-7 cycloalkyl or pyrrolidinyl, and
aryloxy wherein said aryl is optionally substituted with one or more halo;

(iii) R 3 is H or C 1-4 alkyl;
(iv) R a , R b , R c , R d and R e are independently H, halo, —O—C 1-6 alkyl;
(v) R f and R g are independently H, C 1-4 alkyl or heteroaryl;
(vi) R h and R i are independently H or C 1-4 alkyl;
(vii) R j is H or C 1-4 alkyl;

in free or salt form.

2. The compound according to claim 1 , wherein the compound is Formula I(i):

in free or salt form.

3. The compound according to claim 1 , wherein:
(i) R 1 is C 1-4 alkyl;
(ii) R 2 is C 1-4 alkoxy;
(iii) R 3 is H;
(iv) R b , R c and R e are H; R a is halo and R d is —O—C 1-6 alkyl;

in free or salt form.

4. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
1-(5-Butoxy-2-fluorophenyl)-8-(4-fluorophenoxy)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-8-(dimethylamino)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-8-(pyrrolidin-1-yl)-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-8-(1H-pyrazol-1-yl)-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-8-(pyridin-2-ylamino)-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-8-(ethylthio)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c][1,5]naphthyridine-8-carbonitrile;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c][1,5]naphthyridine-8-carboxylic acid;
Ethyl 1-(5-butoxy-2-fluorophenyl)-3-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c][1,5]naphthyridine-8-carboxylate;
1-(5-Butoxy-2-fluorophenyl)-N-ethyl-3-methyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c][1,5]naphthyridine-8-carboxamide;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-4-oxo-3a,4-dihydro-1H-pyrazolo[4,3-c][1,5]naphthyridine-8-carboxamide;
8-Chloro-1-(2-chloro-5-(cyclopropylmethoxy)phenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(2,5-Dichlorophenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(2-Chlorophenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(2-Chlorophenyl)-3,5-dimethyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(2,5-Dichlorophenyl)-3,5-dimethyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-chlorophenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-fluorophenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
8-Chloro-1-(2,5-dichlorophenyl)-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-chlorophenyl)-8-chloro-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;
1-(5-Butoxy-2-chlorophenyl)-8-methoxy-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one; and
1-(2-Chloro-5-(cyclobutylmethoxy)phenyl)-8-methoxy-3-methyl-1H-pyrazolo[4,3-c][1,5]naphthyridin-4(5H)-one;

in free or salt form.

5. A pharmaceutical composition comprising a compound according to claim 1 , in combination or association with pharmaceutically acceptable diluents or carrier.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Li Peng
• Zheng Hailin
• Snyder Gretchen
• Wennogle Lawrence P
• Hendrick Joseph

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title