L-745870 triHCl 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 960 nM). 2300 nM) receptor affinity is relatively weak, showing moderate affinity for 5-HT2 receptors, sigma sites and α-adrenergic receptors.

Physicochemical Properties

Molecular Formula	C18H19N4CL.3[HCL]
Molecular Weight	436.20608
Exact Mass	362.107
CAS #	866021-03-6
Related CAS #	L-745870;158985-00-3;L-745870 hydrochloride;1173023-36-3
PubChem CID	49759035
Appearance	Typically exists as solid at room temperature
LogP	4.343
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	377
Defined Atom Stereocenter Count	0
SMILES	Cl.ClC1C=CC(N2CCN(CC3C4C(=NC=CC=4)NC=3)CC2)=CC=1
InChi Key	KJSOYZLYCFYXFC-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H19ClN4.3ClH/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);3*1H
Chemical Name	3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine;trihydrochloride
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
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 rats and monkeys, with high brain-to-plasma ratio, great brain penetration, and oral bioavailability of 20–60% and plasma t1/2 of 2.1–2.8 hours[1]. 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 [1].
References	[1]. Bristow LJ, et al. Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist. Trends Pharmacol Sci. 1997 Jun;18(6):186-8. [2]. Patel S, et al. 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]. 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.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2925 mL	11.4624 mL	22.9247 mL
	5 mM	0.4585 mL	2.2925 mL	4.5849 mL
	10 mM	0.2292 mL	1.1462 mL	2.2925 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.