CGS-20625 is an anti-anxiety drug for scientific research. It has similar effects to benzodiazepines but has a different structure and is therefore classified as a non-benzodiazepine anxiolytic. It produces anxiolytic and anticonvulsant (antiepileptic/antiseizure) effects, but has no sedative effects and no significant muscle relaxant effects even at high doses. It is orally bioactive in humans but has relatively low bioavailability. CGS-20625 is a PAM (positive allosteric modulator) of multiple GABAA receptor types. Due to the potency of the alicyclic portion of its γ1 subunit, CGS-20625 contains a more distinct receptor type than benzodiazepines. The γ1 subunit is expressed at higher levels in the central amygdala.

Physicochemical Properties

Molecular Formula	C18H19N3O2
Molecular Weight	309.37
Exact Mass	309.148
Elemental Analysis	C, 69.88; H, 6.19; N, 13.58; O, 10.34
CAS #	111205-55-1
PubChem CID	163844
Appearance	Solid powder
Density	1.246g/cm3
Boiling Point	503.8ºC at 760mmHg
Flash Point	258.5ºC
Vapour Pressure	2.82E-10mmHg at 25°C
Index of Refraction	1.617
LogP	2.991
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	23
Complexity	436
Defined Atom Stereocenter Count	0
SMILES	COC1C=CC(N2NC3=C4CCCCCC4=NC=C3C2=O)=CC=1
InChi Key	XRUUVUYJUULCBQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H19N3O2/c1-23-13-9-7-12(8-10-13)21-18(22)15-11-19-16-6-4-2-3-5-14(16)17(15)20-21/h7-11,19H,2-6H2,1H3
Chemical Name	Cyclohepta(b)pyrazolo(3,4-d)pyridin-3(2H)-one, 5,6,7,8,9,10-hexahydro-2-(4-methoxyphenyl)-
Synonyms	CGS20625; CGS-20625; CGS 20625;
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

References

1: Hirschberg Y, Oberle RL, Ortiz M, Lau H, Markowska M. Oral absorption of CGS-20625, an insoluble drug, in dogs and man. J Pharmacokinet Biopharm. 1995 Feb;23(1):11-23. doi: 10.1007/BF02353783. PMID: 8576841. 2: Williams M, Bennett DA, Loo PS, Braunwalder AF, Amrick CL, Wilson DE, Thompson TN, Schmutz M, Yokoyoma N, Wasley JW. CGS 20625, a novel pyrazolopyridine anxiolytic. J Pharmacol Exp Ther. 1989 Jan;248(1):89-96. PMID: 2563294. 3: Khom S, Baburin I, Timin EN, Hohaus A, Sieghart W, Hering S. Pharmacological properties of GABAA receptors containing gamma1 subunits. Mol Pharmacol. 2006 Feb;69(2):640-9. doi: 10.1124/mol.105.017236. Epub 2005 Nov 4. PMID: 16272224. 4: Jarvis MF, Bennett DA, Loo PA, Braunwalder AF, Thompson TN, Schmutz M, Yokoyoma N, Wasley JW, Williams M. CGS 20625, a novel pyrazolopyridine with selective anxiolytic activity. Prog Clin Biol Res. 1990;361:477-82. PMID: 1981266. 5: Tang AH, Franklin SR. The discriminative stimulus effects of diazepam in rats at two training doses. J Pharmacol Exp Ther. 1991 Sep;258(3):926-31. PMID: 1679851. 6: Brunner LA, Luders RC. Determination of a potential anxiolytic drug (CGS 20625) in human plasma by high-performance liquid chromatography. J Chromatogr. 1991 Aug 23;568(2):487-93. doi: 10.1016/0378-4347(91)80188-i. PMID: 1686029. 7: Bennett DA. Pharmacology of the pyrazolo-type compounds: agonist, antagonist and inverse agonist actions. Physiol Behav. 1987;41(3):241-5. doi: 10.1016/0031-9384(87)90360-x. PMID: 2893398. 8: Ogris W, Pöltl A, Hauer B, Ernst M, Oberto A, Wulff P, Höger H, Wisden W, Sieghart W. Affinity of various benzodiazepine site ligands in mice with a point mutation in the GABA(A) receptor gamma2 subunit. Biochem Pharmacol. 2004 Oct 15;68(8):1621-9. doi: 10.1016/j.bcp.2004.07.020. PMID: 15451405.

Additional Infomation

LSM-3520 is a member of pyrazoles and a ring assembly.

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	3.2324 mL	16.1619 mL	32.3238 mL
	5 mM	0.6465 mL	3.2324 mL	6.4648 mL
	10 mM	0.3232 mL	1.6162 mL	3.2324 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.