Talnetant (formerly also known as SB 223412) is a potent and selective NK3 receptor antagonist with ki value of 1.4 nM (hNK-3-CHO); Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that Talnetant is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 microM. Talnetant has been shown in vitro to be a potent functional antagonist of the hNK-3 receptor (reversing senktide-induced contractions in isolated rabbit iris sphincter muscles and reversing NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor). In vivo, however, this compound has been shown to exhibit oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced behavioral responses in rabbits). Talnetant may be used as a pharmacological tool in animal models of disease to evaluate the pathophysiological and functional role of the NK-3 receptor and to determine the appropriate use of non-peptide NK-3 receptor antagonists for therapeutic purposes, according to the biological data gathered thus far.

Physicochemical Properties

Molecular Formula	C25H22N2O2
Molecular Weight	382.4544
Exact Mass	382.168
Elemental Analysis	C, 78.51; H, 5.80; N, 7.32; O, 8.37
CAS #	174636-32-9
Related CAS #	Talnetant hydrochloride; 204519-66-4
PubChem CID	5311424
Appearance	White to off-white solid powder
Density	1.212g/cm3
Boiling Point	580.4ºC at 760mmHg
Flash Point	304.8ºC
Vapour Pressure	4.51E-14mmHg at 25°C
Index of Refraction	1.657
LogP	6.063
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	527
Defined Atom Stereocenter Count	1
SMILES	O([H])C1C(C2C([H])=C([H])C([H])=C([H])C=2[H])=NC2=C([H])C([H])=C([H])C([H])=C2C=1C(N([H])[C@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C([H])([H])C([H])([H])[H])=O
InChi Key	BIAVGWDGIJKWRM-FQEVSTJZSA-N
InChi Code	InChI=1S/C25H22N2O2/c1-2-20(17-11-5-3-6-12-17)27-25(29)22-19-15-9-10-16-21(19)26-23(24(22)28)18-13-7-4-8-14-18/h3-16,20,28H,2H2,1H3,(H,27,29)/t20-/m0/s1
Chemical Name	3-hydroxy-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide
Synonyms	SB223412; SB-223412; SB 223412; Talnetant
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	Talnetant (SB 223412) (0.1–1 μM) has the ability to decrease the build-up of NKB-induced IP in human NK3 receptor-expressing U-2OS cells[3].
ln Vivo	Talnetant (SB 223412) (0.5-2 mg/kg iv, 2min pretreatment) can inhibit the miosis caused by senktide (25µg, iv) in a dose-dependent manner with an ED50 of 0.44mg/kg in conscious rabbits[1]. Talnetant (SB 223412) (i.p., 1-100 mg/kg, 1 h) can decrease haloperidol-induced increases in dopamine levels in the vomeronasal nucleus of freely moving guinea pigs, significantly increase extracellular dopamine and norepinephrine in the medial prefrontal cortex, and significantly attenuate "wet dog wagging" behavior induced by senktide in a dose-dependent manner[3].
Animal Protocol	Male Dunkin-Hartley guinea pig 1, 3, 10, 30 or 100 mg/kg Intraperitoneal injection; 1 h
References	[1]. Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (SB 223412). J Med Chem . 1999 Mar 25;42(6):1053-65. [2]. Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. Neurogastroenterol Motil. 2007 Sep;19(9):732-43. [3]. In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia. Neuropsychopharmacology. 2008 Jun;33(7):1642-52.
Additional Infomation	Talnetant (SB-223,412) is a neurokinin 3 receptor antagonist developed by GlaxoSmithKline, which is being researched for several different functions, primarily for irritable bowel syndrome and as a potential antipsychotic drug for the treatment of schizophrenia. Drug Indication Investigated for use/treatment in schizophrenia and schizoaffective disorders, irritable bowel syndrome (IBS), and chronic obstructive pulmonary disease (COPD).

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 100 mg/mL (~261.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6147 mL	13.0736 mL	26.1472 mL
	5 mM	0.5229 mL	2.6147 mL	5.2294 mL
	10 mM	0.2615 mL	1.3074 mL	2.6147 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.