Biphenyl-pyrazolecarboxamide compounds
The present invention relates to biphenyl-pyrazole compounds and in particular biphenyl-pyrazolecarboxamides. The invention further provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by antagonism or inverse agonism of the CB 1 receptor, such as obesity, smoking cessation, and normalization of blood lipid composition.
1. A compound selected from a compound of Formula II:
or a pharmaceutically acceptable salt thereof; wherein:
each Y 1 , each Y 2 , and each Z is deuterium; and
each Y 3 is independently selected from deuterium or hydrogen.
2. The compound according to claim 1 , wherein Y 3a , Y 3b , and Y 3c are simultaneously deuterium.
3. The compound according to claim 1 , wherein said compound is selected from a compound class set forth in the table below, wherein D is deuterium; any undesignated Y or Z is hydrogen; and any hydrogen that is not Y or Z is optionally replaced by deuterium;
Compound Class
Y 1a
Y 1b
Y 2a
Y 2b
Y 3a
Y 3b
Y 3c
Z 1a
Z 1b
Z 2a
Z 2b
Z 3a
Z 3b
Y 4a
Y 4b
Formula
4
9
D
D
D
D
D
D
D
D
D
D
II
10
D
D
D
D
D
D
D
D
D
D
D
D
D
II
4. The compound according to claim 3 , wherein each hydrogen atom that is not Y or Z is present at its naturally occurring isotopic abundance.
5. A mixture consisting of:
a. a compound of Formula II according to claim 1 wherein each Y 1 , each Y 2 and each Z is deuterium; and each Y 3 is independently selected from the group consisting of deuterium and hydrogen; and
b. lighter isotopologues of said compound of Formula II, wherein at least 50% of said mixture is said compound of Formula II.
6. A mixture consisting of:
c. a compound of Formula II according to claim 1 wherein each Y 1 , each Y 2 and each Z is deuterium; and each Y 3 is independently selected from the group consisting of deuterium and hydrogen; and
d. lighter isotopologues of said compound of Formula II, wherein at least 50% of the compounds in said mixture comprise an isotope at each position indicated as being occupied by an isotope in a chemical formula of said compound of Formula II.
7. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt of said compound; and an acceptable carrier.
8. The pharmaceutical composition according to claim 7 , further comprising an effective amount of a second therapeutic agent, wherein said second therapeutic agent is useful for treating a condition in a patient selected from obesity, diabetes, and coronary artery disease.
9. The composition according to claim 8 , wherein said second therapeutic agent is selected from a norepinephrine transporter inhibitor, a ghrelin antagonist, a H3 antagonist/inverse agonist, a melanin-concentrating hormone 1 receptor antagonist, a melanin-concentrating hormone 2 receptor agonist/antagonist, a neuropeptide Y1 antagonist, a neuropeptide Y2 agonist, a neuropeptide Y4 agonist, a neuropeptide Y5 antagonist, a metabotropic glutamate subtype 5 receptor antagonist, leptin, a leptin agonist/modulator, a leptin derivative, an opioid antagonist, an orexin antagonist, a cholecystokinin-A agonist, a serotonin reuptake inhibitor, ciliary neurotrophic factor (CNTF), a CNTF agonist/modulator, a CNTF derivative, a 5-hydroxytryptamine 2c agonist, a melanocortin 4 receptor agonist, a monoamine reuptake inhibitor, a serotonin reuptake inhibitor, a glucagon-like-peptide-1 agonist, topiramate, phytopharm compound 57, a COX-2 inhibitor, a PPARα agonist, an aldosterone antagonist; a lipase inhibitor; or a pharmaceutically acceptable salt of any of the foregoing agents.