L-741,626

Names

[ Name ]:
L-741,626

[Synonym ]:
4-(4-Chlorophenyl)-1-(1H-indol-3-ylmethyl)-4-piperidinol
L 741,626
1-(indol-3-ylmethyl)-4-hydroxy-4-(p-chlorophenyl)piperidine
4-Piperidinol,4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)
3-(4-(4-Chlorophenyl-4-hydroxypiperidino)methyl)indole

Biological Activity

[Description]:

L-741626 is a selective D2 dopamine receptor antagonist, with the Ki values of 2.4, 100 and 220 nM for human D2, D3 and D4 receptors respectively[1].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

[Target]

Ki: 2.4 nM (human D2 receptor), 100 nM (human D3 receptor), 220 nM (human D4 receptor)[1]

[In Vitro]

Intrinsic activities in a functional assay using inhibition of quinpirole stimulation of mitogenesis in human dopamine D2 or D3 receptors transfected into Chinese hamster ovary (CHO) cells, L-741626 is prepared by literature methods (Ki (D2)=11.2 nM) and displays a D3/D2 and D4/D2 selectivity ratio of 15-fold and 136-fold, respectively. In the functional assay L-741626 is a potent antagonist (EC50 (D2)=4.46 nM) with some D2 selectivity (EC50 (D3)=90.4 nM)[2].

[In Vivo]

L-741626 (1.0 mg/kg; i.h.) is effective at shifting to the right the pramipexole dose-response curve in pramipexole-trained male Sprague Dawley rats[3]. Coadministrating Cocaine with the D2 antagonist L-741626 (3 mg/kg; i.p.; 15 min before Cocaine) for 5 days reduces the Cocaine-induced increase in microglial TNF-α production in adult mice[4].

[References]

[1]. Lewitus GM, et al. Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization. Neuron. 2016 May 4;90(3):483-91.

[2]. Grundt P, et al. Analogues of the dopamine D2 receptor antagonist L741,626: Binding, function, and SAR. Bioorg Med Chem Lett. 2007 Feb 1;17(3):745-9.

[3]. Koffarnus MN, et al. The discriminative stimulus effects of dopamine D2- and D3-preferring agonists in rats. Psychopharmacology (Berl). 2009 Apr;203(2):317-27.

[4]. Kulagowski JJ, et al. 3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor. J Med Chem. 1996 May 10;39(10):1941-2.

Chemical & Physical Properties

[ Density]:
1.311g/cm3

[ Boiling Point ]:
548.8ºC at 760 mmHg

[ Molecular Formula ]:
C₂₀H₂₁ClN₂O

[ Molecular Weight ]:
340.84700

[ Flash Point ]:
285.7ºC

[ Exact Mass ]:
340.13400

[ PSA ]:
39.26000

[ LogP ]:
4.24280

[ Index of Refraction ]:
1.686

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma.

Oncotarget 5(4) , 882-93, (2014)

Glioblastoma remains one of the deadliest of human cancers, with most patients succumbing to the disease within two years of diagnosis. The available data suggest that simultaneous inactivation of cri...

3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor.

J. Med. Chem. 39 , 1941, (1996)

The role of the dopamine D2 receptor in descending control of pain induced by motor cortex stimulation in the neuropathic rat.

Brain Res. Bull. 89(3-4) , 133-43, (2012)

We studied in rats with a spinal nerve ligation-induced neuropathy whether dopamine D2 receptors (D2Rs) play a role in descending control of pain induced by stimulation of the primary motor cortex (M1...

Related Compounds

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