# US 10,501,452 B2 · Lactam compound derivative and application thereof

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- Number: US 10,501,452 B2
- Document ID: US10501452B2
- Status: Granted
- Kind: B2
- Application number: 15/776,645
- Filed: 2016-11-21
- Published: 2018-11-15
- Granted: 2019-12-10
- Earliest claimed: 2015-11-20
- Assignees: Nhwa Pharma. Corporation
- Applicants: Nhwa Pharma. Corporation
- Inventors: Yin Chen; Fei Dou; Yinli Qiu; Minquan Yu; Guisen Zhang
- Web page: https://patentgrep.com/patent/US10501452B2

## CPC

- C07D 413/14: containing three or more hetero rings
- A61K 31/4725: containing further heterocyclic rings
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- C07D 217/24: Oxygen atoms
- C07D 221/04: Ortho- or peri-condensed ring systems
- C07D 239/88: Oxygen atoms
- C07D 239/90: with acyclic radicals attached in position 2 or 3
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to a lactam compound derivative, a medicine composition comprising the lactam compound derivative, and uses of the composition and the lactam compound derivative in preparation of a medicine for preventing or treating schizophrenia, the lactam compound derivative having a structure as shown in Formula I.

## Claims

### Claim 1

A compound of Formula I or a pharmaceutically acceptable salt or prodrug thereof:
wherein,
X is C, O, N or NH;
Z is-(CH2)n—, which is unsubstituted or substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy and halogen, n is an integer of 2˜7;
R1 and R2 are each independently hydrogen, linear or branched alkyl containing 1˜5 carbon atoms, wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy and halogen;
R3 is hydrogen, halogen or linear or branched alkyl containing 1˜5 carbon atoms, wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy and halogen;
P is CH or N;
Ar is a group selected from the group consisting of formula II-VII:
L and M are independently CH or N;
Q is O or S;
R6, R7 and R8 are each independently hydrogen, halogen, linear or branched alkyl containing 1˜5 carbon atoms, or alkoxyl containing 1˜5 carbon atoms, wherein the alkyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy and halogen, and wherein the alkoxyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy and halogen;
R4, R5 are each independently hydrogen, halogenated C1-5 alkyl, methoxyl, ethoxyl or propoxy.

### Claim 2 (depends on 1)

The compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, wherein,
R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, n-butyl, iso-butyl, trifluoromethyl, trifluoroethyl or trifluoropropyl.

### Claim 3 (depends on 1)

The compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, wherein,
R3 is hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, n-butyl or iso-butyl.

### Claim 4 (depends on 1)

The compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, wherein,
R8 is hydrogen, halogenated C1-5 alkyl, methoxyl, ethoxyl, propoxy, chlorine, fluorine or bromine.

### Claim 5 (depends on 4)

The compound according to claim 4 or the pharmaceutically acceptable salt or prodrug thereof, wherein, the halogenated C1-5 alkyl is trifluoromethyl, trifluoroethyl, trifluoropropyl or trifluorobutyl.

### Claim 6 (depends on 1)

The compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, wherein,
the halogen is independently fluorine, chlorine, bromine or iodine.

### Claim 7 (depends on 1)

The compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, wherein,
X is C, O, N or NH;
Z is-(CH2)n—, which is unsubstituted or substituted by one or more hydroxy, n is an integer of 2˜5;
R1 is hydrogen, methyl or ethyl;
R2 is hydrogen, methyl or ethyl;
R3 is hydrogen, methyl or fluorine.

### Claim 8

A compound or the pharmaceutically acceptable salt or prodrug thereof, wherein,
the compound is selected from

### Claim 9 (depends on 1)

A pharmaceutical composition, comprising the compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable excipient, carrier, adjuvant, solvent or the combination thereof.

### Claim 10 (depends on 1)

A method for the treatment of schizophrenia comprising administering to a subject having said disease the compound according to claim 1 or the pharmaceutically acceptable salt or prodrug thereof in an effective amount.

### Claim 11 (depends on 9)

A method for the treatment of schizophrenia comprising administering to a subject having said disease the pharmaceutical composition according to claim 9 in an effective amount.

### Claim 12 (depends on 8)

A pharmaceutical composition comprising the compound according to claim 8 or the pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable excipient, carrier, adjuvant, solvent or the combination thereof.

### Claim 13 (depends on 8)

A method for the treatment of schizophrenia comprising administering to a subject having said disease an effective amount the compound according to claim 8 or the pharmaceutically acceptable salt or prodrug thereof.

### Claim 14 (depends on 12)

A method for the treatment of schizophrenia comprising administering to a subject having said disease an effective amount of the pharmaceutical composition according to claim 12.