ARN19702 is a selective, orally bioactive, reversible, BBB (blood-brain barrier) permeable/penetrable N-acetylethanolamidase (NAAA) inhibitor (antagonist) with IC50 of 230 nM for human NAAA. ARN19702 has pain-relief properties.

Physicochemical Properties

Molecular Formula	C21H22FN3O3S2
Molecular Weight	447.5461
Exact Mass	447.11
Elemental Analysis	C, 56.36; H, 4.96; F, 4.25; N, 9.39; O, 10.72; S, 14.33
CAS #	1971937-18-4
PubChem CID	132145761
Appearance	Solid powder
LogP	3.9
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	732
Defined Atom Stereocenter Count	1
SMILES	CCS(=O)(=O)C1=CC=CC=C1C(=O)N2CCN(C[C@@H]2C)C3=NC4=C(S3)C=C(C=C4)F
InChi Key	UKQOLPNYRVPCBM-AWEZNQCLSA-N
InChi Code	InChI=1S/C21H22FN3O3S2/c1-3-30(27,28)19-7-5-4-6-16(19)20(26)25-11-10-24(13-14(25)2)21-23-17-9-8-15(22)12-18(17)29-21/h4-9,12,14H,3,10-11,13H2,1-2H3/t14-/m0/s1
Chemical Name	(S)-(2-(ethylsulfonyl)phenyl)(4-(6-fluorobenzo[d]thiazol-2-yl)-2-methylpiperazin-1-yl)methanone
Synonyms	ARN19702; ARN 19702; ARN-19702;
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	ARN19702 (3-10 mg/kg; oral; daily; for 7 days) reduces nociception associated with paclitaxel-induced neuropathy without inducing subacute antinociceptive tolerance in male rats [1] . In male mice, ARN19702 (0.1-30 mg/kg; p.o.) dose-dependently attenuates the spontaneous nociceptive response induced by intraplantar injection of formalin as well as intraplantar injection of carrageenan, paw incision, or sciatic nerve Hypersensitivity reaction caused by ligation[1]. ..ARN19702 (3-10 mg/kg; oral) exerts significant protective effects against multiple sclerosis in mice [2]. Pharmacokinetic properties of ARN19702 in mice 3 mg/kg, iv 3 mg/kg, po Cmax (ng/mL) 1660±166 613±68 Tmax (min) (5.0) 30 CL (mL/min/Kg ) 33.2±1.6 49 ±8 t1/2 (min) 73.9±3.7 104±16 AUC plasma (h×ng/mL) 1366.8±68.3 988±157 AUC brain (h×ng/mL) 404.3±109.1 181±28 F (%) - 72±11
Animal Protocol	Animal/Disease Models: SD (SD (Sprague-Dawley)) rats (200-220 g) injected with paclitaxel [1] Doses: 3 mg/kg and 10 mg/kg Route of Administration: Oral; injection. Daily; 7 days in a row (subchronic) Experimental Results: diminished nociception associated with paclitaxel-induced neuropathy.
References	[1]. Antinociceptive Profile of ARN19702, (2-Ethylsulfonylphenyl)-[(2S)-4-(6-fluoro-1,3-benzothiazol-2-yl)-2-methylpiperazin-1-yl]methanone, a Novel Orally Active N-Acylethanolamine Acid Amidase Inhibitor, in Animal Models. J Pharmacol Exp Ther. 2021 Aug;378(2):70-76. [2]. Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis. Angew Chem Int Ed Engl. 2016 Sep 5;55(37):11193-11197.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~223.44 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.59 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 (5.59 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 (5.59 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	2.2344 mL	11.1719 mL	22.3439 mL
	5 mM	0.4469 mL	2.2344 mL	4.4688 mL
	10 mM	0.2234 mL	1.1172 mL	2.2344 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.