CS 476 (NSC-302998), an orally bioavailable sulphonylurea analog, has been shown to be a potent hypoglycaemic agent. In normal fasting dogs, rabbits, rats and mice the maximal hypoglycaemia produced by intravenous administration of CS 476 was comparable on a weight basis to that produced by glibenclamide. Randomized Latin square experiments in dogs showed that 0.03 mg/kg orally of CS 476 and of glibenclamide caused the same maximal decrease of blood glucose and that CS 476 had the shorter duration of action. CS 476 had no hypoglycaemic effect in totally pancreatectomized dogs nor in streptozotocin diabetic dogs and rats. The insulin releasing activity was studied in dogs after intravenous and oral administration of equipotent doses of CS 476, tolbutamide and glibenclamide. It was found that the insulin curves after CS 476 tended to have a plateau-like maximum like those after glibenclamide although the duration of effect was shorter.

Physicochemical Properties

Molecular Formula	C24H29N3O5S
Molecular Weight	471.5692
Exact Mass	471.183
CAS #	41177-35-9
PubChem CID	100459
Appearance	Typically exists as solid at room temperature
Density	1.35g/cm3
Index of Refraction	1.633
LogP	5.168
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	33
Complexity	770
Defined Atom Stereocenter Count	0
SMILES	S(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])N([H])C(C1=C([H])C([H])=C([H])C2=C1OC([H])([H])C2([H])[H])=O)(N([H])C(N([H])C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O)(=O)=O
InChi Key	RNQMWIVFHOCVMM-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H29N3O5S/c28-23(21-8-4-5-18-14-16-32-22(18)21)25-15-13-17-9-11-20(12-10-17)33(30,31)27-24(29)26-19-6-2-1-3-7-19/h4-5,8-12,19H,1-3,6-7,13-16H2,(H,25,28)(H2,26,27,29)
Chemical Name	N-(4-(2-(2,3-Dihydrobenzo(b)furan-7-carboxamido)ethyl)benzenesulfonyl)-N'-cyclohexylurea
Synonyms	CS 476; CS-476; CS476; NOVO CS 476; NSC-302998; NSC302998; NSC 302998.
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 Vivo

Intravenous CS476 produced maximal hypoglycemia comparable to that produced by glyburide in rabbits, rats, mice, and fully pancreatectomized dogs; oral administration of CS476 and glyburide at 0.03 mg/kg caused the same maximum reduction in blood glucose and that CS476 had a shorter duration of action; CS476 had no hypoglycemic effects in streptozotocin diabetic dogs and rats; and the insulin-releasing activity of dogs was examined after intravenous and oral administration of equal doses of CS476, tolbutamide, and glibenclamide [1].

References

[1]. Jorgensen KD. The pharmacology of a new hypoglycaemic agent N-[4-(2-(2,3-dihydrobenzo(b)furan-m-carboxamido)-ethyl)-benzenesulphonyl]-N'-cyclohexylurea (NOVO CS 476). I. Pharmacological studies on the hypoglycaemic effect. Acta Pharmacol Toxicol (Copenh).

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	2.1206 mL	10.6029 mL	21.2058 mL
	5 mM	0.4241 mL	2.1206 mL	4.2412 mL
	10 mM	0.2121 mL	1.0603 mL	2.1206 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.