Compounds > 3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol

3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol and Hypotension

3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol has been researched along with Hypotension* in 2 studies

Other Studies

2 other study(ies) available for 3-(2-hydroxy-4-(1-1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol and Hypotension

Article	Year
Bioisosteric replacements of the pyrazole moiety of rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists. Journal of medicinal chemistry, 2005, Mar-24, Volume: 48, Issue:6 Series of thiazoles, triazoles, and imidazoles were designed as bioisosteres, based on the 1,5-diarylpyrazole motif that is present in the potent CB(1) receptor antagonist rimonabant (SR141716A, 1). A number of target compounds was synthesized and evaluated in cannabinoid (hCB(1) and hCB(2)) receptor assays. The thiazoles, triazoles, and imidazoles elicited in vitro( )()CB(1) antagonistic activities and in general exhibited considerable CB(1) vs CB(2) receptor subtype selectivities, thereby demonstrating to be cannabinoid bioisosteres of the original diarylpyrazole class. Some key representatives in the imidazole series showed potent pharmacological in vivo activities after oral administration in both a CB agonist-induced hypotension model and a CB agonist-induced hypothermia model. Molecular modeling studies showed a close three-dimensional structural overlap between the key compound 62 and rimonabant. A structure-activity relationship (SAR) study revealed a close correlation between the biological results in the imidazole and pyrazole series. Topics: Administration, Oral; Animals; CHO Cells; Cricetinae; Cricetulus; Cyclohexanols; Hypotension; Hypothermia; Imidazoles; Mice; Models, Molecular; Molecular Conformation; Piperidines; Pyrazoles; Radioligand Assay; Rats; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Rimonabant; Stereoisomerism; Structure-Activity Relationship; Thiazoles; Triazoles	2005
The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression. Naunyn-Schmiedeberg's archives of pharmacology, 2003, Volume: 367, Issue:5 Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic outflow. In anaesthetised and artificially ventilated rats, i.v. injection of the cannabinoid agonists WIN55212-2 and CP55940 decreased mean arterial pressure, heart rate and the plasma noradrenaline concentration. These effects were antagonized by the CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia was abolished by the muscarinic acetylcholine receptor antagonist methylatropine. The decreases in mean arterial pressure and heart rate caused by cannabinoids in ventilated rats were much less pronounced than in spontaneously breathing rats. Microinjection of WIN55212-2 into the nucleus tractus solitarii had no effect. Microinjected into the rostral ventrolateral medulla oblongata, WIN55212-2 lowered mean arterial pressure slightly without changing other parameters. In pithed rats, WIN55212-2 inhibited the increases in mean arterial pressure, heart rate and the plasma noradrenaline concentration evoked by electrical stimulation of the sympathetic outflow. Our results show that activation of CB(1) cannabinoid receptors induces sympathoinhibition and enhancement of cardiac vagal tone, leading to hypotension and bradycardia. Presynaptic inhibition of noradrenaline release from terminals of postganglionic sympathetic neurons is the major component of the sympathoinhibition, but an effect in the rostral ventrolateral medulla oblongata may also contribute. The cannabinoid-evoked cardiovascular depression depends strongly on the respiratory state of the animals. Topics: Animals; Atropine Derivatives; Benzoxazines; Bradycardia; Cannabinoids; Cardiovascular System; Cyclohexanols; Disease Models, Animal; Dose-Response Relationship, Drug; Hypotension; Male; Medulla Oblongata; Microinjections; Morpholines; Naphthalenes; Norepinephrine; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System	2003

Article

Year

Bioisosteric replacements of the pyrazole moiety of rimonabant: synthesis, biological properties, and molecular modeling investigations of thiazoles, triazoles, and imidazoles as potent and selective CB1 cannabinoid receptor antagonists.

Journal of medicinal chemistry, 2005, Mar-24, Volume: 48, Issue:6

Series of thiazoles, triazoles, and imidazoles were designed as bioisosteres, based on the 1,5-diarylpyrazole motif that is present in the potent CB(1) receptor antagonist rimonabant (SR141716A, 1). A number of target compounds was synthesized and evaluated in cannabinoid (hCB(1) and hCB(2)) receptor assays. The thiazoles, triazoles, and imidazoles elicited in vitro( )()CB(1) antagonistic activities and in general exhibited considerable CB(1) vs CB(2) receptor subtype selectivities, thereby demonstrating to be cannabinoid bioisosteres of the original diarylpyrazole class. Some key representatives in the imidazole series showed potent pharmacological in vivo activities after oral administration in both a CB agonist-induced hypotension model and a CB agonist-induced hypothermia model. Molecular modeling studies showed a close three-dimensional structural overlap between the key compound 62 and rimonabant. A structure-activity relationship (SAR) study revealed a close correlation between the biological results in the imidazole and pyrazole series.

Topics: Administration, Oral; Animals; CHO Cells; Cricetinae; Cricetulus; Cyclohexanols; Hypotension; Hypothermia; Imidazoles; Mice; Models, Molecular; Molecular Conformation; Piperidines; Pyrazoles; Radioligand Assay; Rats; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Rimonabant; Stereoisomerism; Structure-Activity Relationship; Thiazoles; Triazoles

2005

The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression.

Naunyn-Schmiedeberg's archives of pharmacology, 2003, Volume: 367, Issue:5

Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic outflow. In anaesthetised and artificially ventilated rats, i.v. injection of the cannabinoid agonists WIN55212-2 and CP55940 decreased mean arterial pressure, heart rate and the plasma noradrenaline concentration. These effects were antagonized by the CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia was abolished by the muscarinic acetylcholine receptor antagonist methylatropine. The decreases in mean arterial pressure and heart rate caused by cannabinoids in ventilated rats were much less pronounced than in spontaneously breathing rats. Microinjection of WIN55212-2 into the nucleus tractus solitarii had no effect. Microinjected into the rostral ventrolateral medulla oblongata, WIN55212-2 lowered mean arterial pressure slightly without changing other parameters. In pithed rats, WIN55212-2 inhibited the increases in mean arterial pressure, heart rate and the plasma noradrenaline concentration evoked by electrical stimulation of the sympathetic outflow. Our results show that activation of CB(1) cannabinoid receptors induces sympathoinhibition and enhancement of cardiac vagal tone, leading to hypotension and bradycardia. Presynaptic inhibition of noradrenaline release from terminals of postganglionic sympathetic neurons is the major component of the sympathoinhibition, but an effect in the rostral ventrolateral medulla oblongata may also contribute. The cannabinoid-evoked cardiovascular depression depends strongly on the respiratory state of the animals.

Topics: Animals; Atropine Derivatives; Benzoxazines; Bradycardia; Cannabinoids; Cardiovascular System; Cyclohexanols; Disease Models, Animal; Dose-Response Relationship, Drug; Hypotension; Male; Medulla Oblongata; Microinjections; Morpholines; Naphthalenes; Norepinephrine; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System

2003