# US 12,180,210 B2 · Compounds

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- Number: US 12,180,210 B2
- Document ID: US12180210B2
- Status: Granted
- Kind: B2
- Application number: 17/288,225
- Filed: 2019-10-23
- Published: 2022-03-03
- Granted: 2024-12-31
- Earliest claimed: 2018-10-23
- Assignees: Intra-Cellular Therapies, Inc.
- Applicants: Intra-Cellular Therapies, Inc.
- Inventors: Peng Li; Hailin Zheng
- Web page: https://patentgrep.com/patent/US12180210B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 25/00: Drugs for disorders of the nervous system
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to novel PDE2 inhibitory compounds of Formula I as described herein, their use as pharmaceuticals and pharmaceutical compositions comprising them.

## Claims

### Claim 1

A Compound of Formula I
wherein
(i) R1 and R2 together with the nitrogen atom form an unsubstituted heteroC3-7cycloalkyl;
(ii) R3 is H or C1-4alkyl;
(iii) R4 is heteroaryl, halo, cyano or aryl optionally substituted with one or more groups selected from C1-4alkyl, C3-7cycloalkyl, C1-4alkoxy and haloC1-4alkyl;
(iv) R5 is H or C1-4alkyl;
(v) R6 is H or C1-4alkyl;
in free or salt form.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein R1 and R2 together with the nitrogen atom form an azetidin-1-yl.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein R3 is C1-4alkyl.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein R4 is aryl substituted with one or more groups selected from C1-4alkyl, C3-7cycloalkyl, C1-4alkoxy and haloC1-4alkyl.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein R4 is aryl substituted with C1-4alkyl.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein R4 is aryl substituted with C3-7cycloalkyl.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein R4 is aryl substituted with C1-4alkoxy.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein R4 is aryl substituted with haloC1-4alkyl.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein R5 and R6 are H.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein the compound is selected from the group consisting of:
8-(azetidin-1-yl)-3-methyl-1-(1-methyl-5-(p-tolyl)-1H-pyrazol-4-yl) imidazo[1,5-a]pyrazine,
8-(azetidin-1-yl)-3-methyl-1-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl) imidazo[1,5-a]pyrazine,
8-(azetidin-1-yl)-3,5-dimethyl-1-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl) imidazo[1,5-a]pyrazine,
8-(azetidin-1-yl)-1-(5-(4-isopropylphenyl)-1-methyl-1H-pyrazol-4-yl)-3-methyl-imidazo[1,5-a]pyrazine,
8-(azetidin-1-yl)-1-(5-(4-ethylphenyl)-1-methyl-1H-pyrazol-4-yl)-3-methylimidazo[1,5-a]pyrazine, and
8-(azetidin-1-yl)-1-(5-(4-cyclopropylphenyl)-1-methyl-1H-pyrazol-4-yl)-3-methyl-imidazo[1,5-a]pyrazine;
in free or salt form.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 11)

A method for the treatment of a PDE2 mediated disorder comprising administering to a subject in need thereof the pharmaceutical composition according to claim 11.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disorder is selected from the group consisting of neurological disorders epilepsy; Alzheimer's disease; Parkinson's disease; brain injury; stroke; cerebrovascular diseases; spinal muscular atrophy; lateral sclerosis; multiple sclerosis; cognitive disorders; cognitive dysfunction associated with Parkinson's disease and depression; mental deficiency; sleep disorders; psychiatric disorders; factitious disorder; impulse control disorders; mood disorders; psychomotor disorders; psychotic disorders; drug dependence; eating disorders; pediatric psychiatric disorders; mental and behavioral disorders due to psychoactive substance use; cardiovascular disorder; and pain.

### Claim 14 (depends on 12)

The method of claim 12 wherein the disorder is selected from the following: anxiety, depression, autism spectrum disorder, schizophrenia, anxiety and/or depression in autistic and/or schizophrenic patients, and cognitive impairment associated with schizophrenia or dementia.

### Claim 15 (depends on 1)

The compound according to claim 1, wherein R3 is methyl.

### Claim 16 (depends on 1)

The compound according to claim 1, wherein R6 is methyl.

### Claim 17 (depends on 1)

The compound according to claim 1, wherein R4 is phenyl optionally substituted with methyl, ethyl, or isopropyl.

### Claim 18 (depends on 1)

The compound according to claim 1, wherein R4 is phenyl optionally substituted with cyclopropyl.

### Claim 19 (depends on 1)

The compound according to claim 1, wherein R4 is phenyl optionally substituted with methoxy.

### Claim 20 (depends on 1)

The compound according to claim 1, wherein R4 is phenyl optionally substituted with trifluoromethyl.