# US 2013/0158031 A1 · Alkyne-bridged hetero-aromatics and uses thereof

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- Number: US 2013/0158031 A1
- Document ID: US20130158031A1
- Status: Published application
- Kind: A1
- Application number: 13/718,113
- Filed: 2012-12-18
- Published: 2013-06-20
- Earliest claimed: 2011-12-19
- Assignees: Su Zhou Jing Hong Biotech Co., Ltd.
- Inventors: Zhen-Wei CAI; Ding ZHOU; Yougang LIN; Ping CHEN
- Web page: https://patentgrep.com/patent/US20130158031A1

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to novel alkyne-bridged hetero-aromatics as described in the specification which are PDE10A inhibitors and useful for the treatment of neurological, psychiatric disorder, metabolic disorders, such as Schizophrenia, Parkinson's disease, Huntington's disease, Alzheimer's disease, learning memory disorder, drug addiction (abuse), sleeping disorder, depression, obesity, non-insulin dependent diabetes, bipolar disorder, obsessive compulsive disorder, or pain; to process for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.

## Claims

### Claim 1

A compound having the following Formulae, or a pharmaceutical acceptable salt thereof:
wherein X1 and X2 are each independently C or N;
Y1, Y2 and Y3 are each independently C or N;
each Het1 is independently aryl or 3-7-membered heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur, in which said aryl may be optionally substituted by one to three R1 and one R2, and said heterocycle may be optionally substituted by one to three R1;
each Het2 is independently 3-7-membered heterocycle containing at least one heteroatom selected from the group consisting of nitrogen, oxygen, and sulfur, in which said heterocycle may be optionally substituted by one R5 and one to three R6;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R2 is independently H, OH, CN, or NRaRb;
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 2 (depends on 1)

The compound of claim 1, wherein each Het1 is independently selected from Formulae A1-A5 below:
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R2 is independently H, OH, CN, or NRaRb;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
m is 1-3; and
q is 1-2.

### Claim 3 (depends on 1)

The compound of claim 1, wherein each Het2 is independently selected from Formulae B1-B23 below:
wherein X3 is O, or NR5;
each R3 and R4 is independently H, or (C1-C6)alkyl;
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
m is 1-3; and
q is 1-2.

### Claim 4 (depends on 1)

The compound of claim 1, having the structure of Formula (III):
wherein Y1, Y2 and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 5 (depends on 1)

The compound of claim 1, having the structure of Formula (IV):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 6 (depends on 1)

The compound of claim 1, having the structure of Formula (V):
wherein Y1, Y2 and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 7 (depends on 1)

The compound of claim 1, having the structure of Formula (VI):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 8 (depends on 1)

The compound of claim 1, having the structure of Formula (VII):
wherein Y1, Y2 and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6;
m is 1-3; and
q is 1-2.

### Claim 9 (depends on 1)

The compound of claim 1, having the structure of Formula (VIII):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 10 (depends on 1)

The compound of claim 1, having the structure of Formula (IX):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
m is 1-3.

### Claim 11 (depends on 1)

The compound of claim 1, having the structure of Formula (X):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 12 (depends on 1)

The compound of claim 1, having the structure of Formula (XI):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
q is 1-2; and m is 1-3.

### Claim 13 (depends on 1)

The compound of claim 1, having the structure of Formula (XII):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 14 (depends on 1)

The compound of claim 1, having the structure of Formula (XIII):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
q is 1-2; and m is 1-3.

### Claim 15 (depends on 1)

The compound of claim 1, having the structure of Formula (XIV):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 16 (depends on 1)

The compound of claim 1, having the structure of Formula (XV):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
q is 1-2; and m is 1-3.

### Claim 17 (depends on 1)

The compound of claim 1, having the structure of Formula (XVI):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 18 (depends on 1)

The compound of claim 1, having the structure of Formula (XVII):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
q is 1-2; and m is 1-3.

### Claim 19 (depends on 1)

The compound of claim 1, having the structure of Formula (XVIII):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R5 is independently H, (C1-C4)alkyl, (C3-C7)cycloalkyl, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, or (CH2)nNRaRb;
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 20 (depends on 1)

The compound of claim 1, having the structure of Formula (IXX):
wherein Y1, Y2, and Y3 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
q is 1-2; and m is 1-3.

### Claim 21 (depends on 1)

The compound of claim 1, having the structure of Formula (XX):
wherein Y1 and Y2 are each independently C or N;
Z1 and Z2 are each independently C or N;
each R1 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, or haloalkyl (e.g., CF3);
each R6 is independently H, halogen, OH, CN, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, (CH2)n(C1-C6)haloalkyl;
R7 and R8 are each independently H, halogen, OH, CN, OCF3, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)cycloalkyl, 3-7-membered heterocycle, (C1-C6)alkylthio, NRaRb, (C1-C6)haloalkyl (e.g., CF3), (CH2)n(C3-C7)cycloalkyl, (CH2)nORa, (CH2)nSRa, (CH2)nNRaRb, or (CH2)n(C1-C6)haloalkyl, in which said heterocycle contains at least one heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of halogen, OH, CN, (C1-C4)alkyl, (C1-C4)haloalkyl (e.g., CF3) and (C1-C4)alkoxy;
each occurrence of Ra and Rb is independently hydrogen or (C1-C6)alkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain another heteroatom selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of (C1-C4)alkyl, phenyl and benzyl;
n is 1-6; and
m is 1-3.

### Claim 22 (depends on 1)

A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically-acceptable carrier or diluent.

### Claim 23 (depends on 1)

A method for treating a psychotic disorder, an anxiety disorder, or a neurodegenerative disorder in a mammalian species in need thereof, the method comprising administering to the mammalian species a therapeutically effective amount of at least one compound according to claim 1.