L-745870 is a potent, selective, BBB (blood-brain barrier) permeable/penetrable and orally bioactive dopamine D4 receptor blocker (antagonist) with Ki of 0.43 nM and is effective against D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors have relatively weak affinity, exhibiting moderate affinities for 5-HT2 receptors, sigma sites, and α-adrenergic receptors.

Physicochemical Properties

Molecular Formula	C18H19CLN4
Molecular Weight	326.82300
Exact Mass	326.13
CAS #	158985-00-3
Related CAS #	L-745870 hydrochloride;1173023-36-3;L-745870 trihydrochloride;866021-03-6
PubChem CID	5311200
Appearance	White to off-white solid powder
Boiling Point	590.8ºC at 760mmHg
Flash Point	311.1ºC
Vapour Pressure	3.05E-14mmHg at 25°C
LogP	3.541
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	23
Complexity	377
Defined Atom Stereocenter Count	0
InChi Key	OGJGQVFWEPNYSB-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H19ClN4/c19-15-3-5-16(6-4-15)23-10-8-22(9-11-23)13-14-12-21-18-17(14)2-1-7-20-18/h1-7,12H,8-11,13H2,(H,20,21)
Chemical Name	3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells, L-745870 inhibits the capacity of D4 receptors to suppress agonist-induced stimulation of [35S]-GTPgS binding. It also prevents forskolin-stimulated glandular stimulation. Glycolate cyclase activity inhibition, blocking dopamine-induced suppression of the Ca2+ current in transfected GH4C1 pituitary cells, blocking D4 activation of clonal G protein-coupled inward rectifier K+ channels, and counteracting the stimulation of extracellular acidification of transfected cells caused by dopamine[1].
ln Vivo	L-745870 exhibits favorable pharmacokinetic characteristics in both rats and monkeys, with great brain penetration in rats and a high brain-to-plasma ratio (oral bioavailability of 20–60% and plasma t1/2 of 2.1–2.8 hours)[2]. Squirrel monkeys were given 10 mg/kg p.o. of L745870 orally, which resulted in mild sedation and extrapyramidal motor symptoms, including bradykinesia, which became noticeable at 30 mg/kg. In monkeys, lower doses of L-745870 did not cause any behavioral changes [2].
References	[1]. Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist. Trends Pharmacol Sci. 1997 Jun;18(6):186-8. [2]. Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):636-47. [3]. 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.
Additional Infomation	3-[[4-(4-chlorophenyl)-1-piperazinyl]methyl]-1H-pyrrolo[2,3-b]pyridine is a member of piperazines.

Solubility Data

Solubility (In Vitro)

DMSO : ~25 mg/mL (~76.49 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0598 mL	15.2989 mL	30.5979 mL
	5 mM	0.6120 mL	3.0598 mL	6.1196 mL
	10 mM	0.3060 mL	1.5299 mL	3.0598 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.