biphenyl-indanone-a and Cocaine-Related-Disorders

biphenyl-indanone-a has been researched along with Cocaine-Related-Disorders* in 2 studies

Other Studies

2 other study(ies) available for biphenyl-indanone-a and Cocaine-Related-Disorders

Article	Year
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence. Journal of medicinal chemistry, 2014, May-22, Volume: 57, Issue:10 As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology. Topics: Allosteric Regulation; Animals; Cocaine-Related Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; HEK293 Cells; Humans; Male; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate	2014
Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats. Journal of medicinal chemistry, 2011, Jan-13, Volume: 54, Issue:1 The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties. These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes. They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration. The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence. Topics: Administration, Oral; Allosteric Regulation; Animals; Benzothiazoles; Biological Availability; Brain; Chlorobenzoates; Cocaine; Cocaine-Related Disorders; Drug Design; HEK293 Cells; Humans; Rats; Receptors, Metabotropic Glutamate; Self Administration; Structure-Activity Relationship; Tissue Distribution	2011

Article

Year

Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.

Journal of medicinal chemistry, 2014, May-22, Volume: 57, Issue:10

As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.

Topics: Allosteric Regulation; Animals; Cocaine-Related Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; HEK293 Cells; Humans; Male; Rats; Rats, Wistar; Receptors, Metabotropic Glutamate

2014

Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats.

Journal of medicinal chemistry, 2011, Jan-13, Volume: 54, Issue:1

The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties. These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes. They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration. The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence.

Topics: Administration, Oral; Allosteric Regulation; Animals; Benzothiazoles; Biological Availability; Brain; Chlorobenzoates; Cocaine; Cocaine-Related Disorders; Drug Design; HEK293 Cells; Humans; Rats; Receptors, Metabotropic Glutamate; Self Administration; Structure-Activity Relationship; Tissue Distribution

2011