Cligosiban (formerly known as PF-3274167) is a novel, potent, selective and high-affinity nonpeptide antagonist of oxytocin receptor (OTR) with Ki of 9.5 nM. PF-3274167 displayed promising in vivo pharmacokinetics and significantly improved aqueous solubility over related compounds containing a biaryl substituent. Oxytocin receptor is a G protein-coupled receptor/protein which functions as receptor for the hormone and neurotransmitter oxytocin. Oxytocin receptors are also present in the central nervous system. PF-3274167 is a high-affinity nonpeptide oxytocin receptor (OTR) antagonist, nM.

Physicochemical Properties

Molecular Formula	C19H19CLFN5O3
Molecular Weight	419.84
Exact Mass	419.116
CAS #	900510-03-4
Related CAS #	900510-03-4
PubChem CID	11683187
Appearance	Off-white to pink solid powder
Density	1.4±0.1 g/cm3
Boiling Point	584.0±60.0 °C at 760 mmHg
Flash Point	307.0±32.9 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.646
LogP	1.85
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	29
Complexity	532
Defined Atom Stereocenter Count	0
InChi Key	HNIFCPBQMKPRCX-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H19ClFN5O3/c1-27-11-17-23-24-19(26(17)13-4-6-18(28-2)22-8-13)25-9-14(10-25)29-16-5-3-12(21)7-15(16)20/h3-8,14H,9-11H2,1-2H3
Chemical Name	5-[3-[3-(2-chloro-4-fluorophenoxy)azetidin-1-yl]-5-(methoxymethyl)-1,2,4-triazol-4-yl]-2-methoxypyridine
Synonyms	cligosiban; PF-03274167; PF 03274167; PF03274167; PF-3274167; PF 3274167; PF3274167
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 vitro activity: PF-3274167 is a selective and high-affinity nonpeptide antagonist of oxytocin receptor (OTR) with Ki of 9.5nM. PF-3274167 displayed promising in vivo pharmacokinetics and significantly improved aqueous solubility over related compounds containing a biaryl substituent. Oxytocin receptor is a G protein-coupled receptor/protein which functions as receptor for the hormone and neurotransmitter oxytocin. Oxytocin receptors are also present in the central nervous system. Kinase Assay: PF-3274167 is a selective and high-affinity nonpeptide antagonist of oxytocin receptor (OTR) with Ki of 9.5nM. Cell Assay:
ln Vivo	PF-3274167 displayed promising in vivo pharmacokinetics and significantly improved aqueous solubility over related compounds containing a biaryl substituent. Oxytocin receptor is a G protein-coupled receptor/protein which functions as receptor for the hormone and neurotransmitter oxytocin. Oxytocin receptors are also present in the central nervous system.
Animal Protocol
References	Bioorg Med Chem Lett.2010 Jan 15;20(2):516-20.J Med Chem.2015 Mar 12;58(5):2547-52

Solubility Data

Solubility (In Vitro)

DMSO:10 mM in DMSO Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3 mg/mL (7.15 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 30.0 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: ≥ 3 mg/mL (7.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 3 mg/mL (7.15 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 30.0 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	2.3819 mL	11.9093 mL	23.8186 mL
	5 mM	0.4764 mL	2.3819 mL	4.7637 mL
	10 mM	0.2382 mL	1.1909 mL	2.3819 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.