mGluR2 antagonist 1 is an orally bioactive, BBB (blood-brain barrier) permeable/penetrable, selective negative allosteric modulator (NAM) of mGluR2 (IC50 is 9 nM).

Physicochemical Properties

Molecular Formula	C21H16FN3O3
Molecular Weight	377.3684
Exact Mass	377.117
CAS #	1432728-49-8
PubChem CID	71566598
Appearance	White to off-white solid powder
LogP	1.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	618
Defined Atom Stereocenter Count	0
SMILES	FC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(C(N([H])[H])=O)=NC2C([H])=C(C([H])=C([H])C=21)C([H])([H])N1C(C([H])([H])C([H])([H])C1=O)=O
InChi Key	XSTBUOHORFUCIB-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H16FN3O3/c22-14-4-2-13(3-5-14)16-10-18(21(23)28)24-17-9-12(1-6-15(16)17)11-25-19(26)7-8-20(25)27/h1-6,9-10H,7-8,11H2,(H2,23,28)
Chemical Name	7-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carboxamide
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

Targets	mGluR2 9 nM (IC50)
ln Vivo	mGluR2 antagonist 1 (Compound 25) has good efficacy at 10 mg/kg in the mouse delayed non-match to position experiment and reverses the effects of mGluR2 agonist LY379268 in amphetamine-induced hyperlocomotion in vivo.
References	[1]. Discovery of 4-arylquinoline-2-carboxamides, Highly Potent and Selective Class of mGluR2 Negative Allosteric Modulators: From HTS to Activity in Animal Models. Bioorg Med Chem Lett. 2020 May 1;30(9):127066.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (264.99 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 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 (6.62 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 25.0 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: ≥ 2.5 mg/mL (6.62 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	2.6499 mL	13.2496 mL	26.4992 mL
	5 mM	0.5300 mL	2.6499 mL	5.2998 mL
	10 mM	0.2650 mL	1.3250 mL	2.6499 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.