192703-06-3

Basic information

• Product Name: SR 144528
• Synonyms: SR 144528
• CAS NO: 192703-06-3
• Molecular Formula: C29H34ClN3O
• Molecular Weight: 476.05276
• Mol File: 192703-06-3.mol

Chemical Properties

• Boiling Point: 627.699 °C at 760 mmHg
• Flash Point: 333.42 °C
• Appearance: /
• Density: 1.222 g/cm³
• Vapor Pressure: 1.14E-15mmHg at 25°C
• Refractive Index: 1.632
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 20 mg/ml, with warming).
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: SR 144528(CAS DataBase Reference)
• NIST Chemistry Reference: SR 144528(192703-06-3)
• EPA Substance Registry System: SR 144528(192703-06-3)

Safety Data

• RTECS: UQ6276700
• Hazardous Substances Data: 192703-06-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
SR 144528 is used as a cannabinoid CB2 receptor antagonist for studying its blocking effect on the anti-dyskinetic functionality of HU-308, its effects on spontaneous excitatory postsynaptic currents (sEPSCs) from the globus pallidus neurons, and analyzing its effect on the gastric emptying in rats.
Used in Cancer Research:
SR 144528 acts as a selective peripheral cannabinoid (CB2) receptor inverse agonist. It is used in studies involving the application of cannabis and anticancer drugs and multi-drug resistance (MDR) of the patient, providing insights into the role of CB2 receptors in cancer treatment and resistance mechanisms.
Used in Neuroscience Research:
SR 144528 is utilized in neuroscience research to explore the role of CB2 receptors in modulating neuronal activity and their potential therapeutic implications in neurological disorders and conditions.

Biochem/physiol Actions

SR144528 is a potent and highly selective cannabinoid CB2 receptor inverse agonist. SR144528 exhibited a Ki of 0.6 nM at CB2 compared to 400 nM at the related CB1 receptor.

in vitro

sr 144528 displayed subnanomolar affinity for both the rat spleen and cloned human cb2 receptors and had a 700-fold lower affinity for both the rat brain and cloned human cb1 receptors. moreover, sr 144528 showed no affinity for more than 70 receptors, ion channels or enzymes tested. sr 144528 could antagonize the inhibitory effects of the cannabinoid receptor agonist cp 55,940 on forskolin-stimulated adenylyl cyclase activity in cell lines expressing the human cb2 receptor but not in cells expressing the human cb1. in addition, sr 144528 could selectively block the mitogen-activated protein kinase activity that was induced by cp 55,940 in cell lines expressing human cb2 while an ic50 value of more than 1 μm was observed in cells expressing human cb1 [1].

in vivo

animal study showed that oral administration of sr 144528 could totally displace the ex vivo [3h]-cp 55,940 binding to mouse spleen membranes with a long action duration. whereas, after the oral route sr 144528 did not interact with the cannabinoid receptor expressed in the mouse brain cb1 [1].

References

1) Rinaldi-Carmona et al. (1998), SR-144528, the first potent and selective antagonist of the CB2 cannabinoid receptor; J. Pharmacol. Exp. Ther., 284 644 2) Portier et al. (1999), SR-144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist; J. Pharmacol. Exp. Ther., 288 582

InChI:InChI=1/C29H34ClN3O/c1-18-6-8-20(9-7-18)17-33-25(21-10-11-23(30)19(2)14-21)15-24(32-33)26(34)31-27-28(3,4)22-12-13-29(27,5)16-22/h6-11,14-15,22,27H,12-13,16-17H2,1-5H3,(H,31,34)/t22-,27-,29+/m1/s1

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Relevant articles and documents

Tritiation of the cannabinoid receptor antagonist SR144528 involving lithium aluminum tritide reduction; assessment of the kinetic isotope effect by 3H-NMR

The cannabinoid receptor antagonist SR144528 was synthesized by an approach that enabled the incorporation of high specific activity tritium label while circumventing the lability of the target compound to catalytic hydrogenation. Lithium aluminum tritide

3-pyrazolecarboxamide derivatives having cannabinoid receptor affinity

The present invention relates to compounds of the formula STR1 in which: X 1 is a group --NR 1 R 2 or a group --OR 2 ;g 2, g 3, g 4, g 5, g 6 and w 2, w 3, w 4, w 5, w 6 are identical or different and are each independently hydrogen, a halogen atom, a (C 1 -C 4)alkyl, a (C 1 -C 4)alkoxy, a trifluoromethyl, a nitro or a (C 1 -C 4)alkylthio, with the proviso that at least one of the substituents g 2, g 3, g 4, g 5, g 6 and at least one of the substituents w 2, w 3, w 4, w 5, w 6 are other than hydrogen;R 1 is hydrogen or a (C 1 -C 4)alkyl;R 2 is a non-aromatic (C 3 -C 15)carbocyclic radical which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from a halogen atom, a (C 1 -C 4)alkyl and a (C 1 -C 4)alkoxy;R 3 is hydrogen or a group --CH 2 R 6 ; andR 4 and R 5 are each independently a hydrogen, a (C 1 -C 4)alkyl or a trifluoromethyl;or else R 4 is hydrogen and R 5 and w 6 together constitute an ethylene or trimethylene radical; andR 6 is hydrogen, a (C 1 -C 4)alkyl, a fluorine, a hydroxyl, a (C 1 -C 5)alkoxy, a (C 1 -C 5)alkylthio, a hydroxy(C 1 -C 5)alkoxy, a cyano, a (C 1 -C 5)alkylsulfinyl or a (C 1 -C 5)alkylsulfonyl with the proviso that when the substituents g 2, g 3, g 4, g 5 and/or g 6 are a (C 1 -C 4)alkyl R 6 is only hydrogen;to a process for their preparation and to the pharmaceutical compositions in which they are present.These compounds have a good affinity for the peripheral cannabinoid receptors.