Ethylhydrocupreine HCl (Optochin HCl) is an antibacterial quinine analogue with activity against Streptococcus pneumoniae (S. pneumoniae). Ethylhydrocupreine HCl also has antimalarial activity against Plasmodium falciparum with IC50 of 25.75 nM. Ethylhydrocupreine HCl is a Gallus gallus 2 receptor (ggTas2r1, ggTas2r2 and ggTas2r7) agonist.

Physicochemical Properties

Molecular Formula	C21H29CLN2O2
Molecular Weight	376.92
Exact Mass	376.192
CAS #	3413-58-9
Related CAS #	Ethylhydrocupreine;522-60-1
PubChem CID	16219340
Appearance	Typically exists as solid at room temperature
Boiling Point	508.7ºC at 760 mmHg
Melting Point	121-123ºC
Flash Point	261.5ºC
LogP	4.527
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	446
Defined Atom Stereocenter Count	4
SMILES	CC[C@H]1CN2CC[C@H]1C[C@H]2[C@@H](C3=C4C=C(C=CC4=NC=C3)OCC)O.Cl
InChi Key	QNRATNLHPGXHMA-XZHTYLCXSA-N
InChi Code	InChI=1S/C21H28N2O2.ClH/c1-3-14-13-23-10-8-15(14)11-20(23)21(24)17-7-9-22-19-6-5-16(25-4-2)12-18(17)19;/h5-7,9,12,14-15,20-21,24H,3-4,8,10-11,13H2,1-2H3;1H/t14-,15-,20-,21+;/m0./s1
Chemical Name	(R)-(6-ethoxyquinolin-4-yl)-[(2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]methanol;hydrochloride
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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	S. pneumoniae[1] IC50: 25.75 nM (Plasmodium falciparum)[3] ggTas2r1, ggTas2r2 and ggTas2r7[4]
ln Vitro	Using fluctuation analysis, the mutation rate to ethylenedimine (optochin) resistance is calculated in three capsulated S. strains of pneumoniae (S. pneumoniae R6 ATCC BAA-255, S. pneumoniae D39 NCTC 7466, and S. pneumoniae ATCC 49619). For all three strains under investigation, exposure to subinhibitory amounts of penicillin elevated the mutation rate (measured as mutation per cell division) to ethylhydrocupreine (Optochin) resistance by 2.1–3.1 fold[2].
ln Vivo	Acute suppurative pleuritis on both sides is associated with suppurative pericarditis when 1 cc of a 24-hour dextrose blood broth culture of virulent Type I pneumococci is injected into the right pleural cavity of guinea pigs. One milliliter (1:500) of ethylhydrocupreine hydrochloride injections, given to each guinea pig's pleural cavity at different intervals for up to 24 hours following pleural infection, have typically demonstrated a significant curative effect. Dogs exhibit comparable outcomes [1].
References	[1]. J A Kolmer, et al. CHEMOTHERAPEUTIC STUDIES WITH ETHYLHYDROCUPREINE HYDROCHLORIDE IN EXPERIMENTAL PNEUMOCOCCUS PLEURITIS. J Exp Med. 1921 May 31;33(6):693-711. [2]. Paulo R Cortes, et al. Subinhibitory Concentrations of Penicillin Increase the Mutation Rate to Optochin Resistance in Streptococcus Pneumoniae. J Antimicrob Chemother. 2008 Nov;62(5):973-7. [3]. Nassira Mahmoudi, et al. Identification of New Antimalarial Drugs by Linear Discriminant Analysis and Topological Virtual Screening. J Antimicrob Chemother. 2006 Mar;57(3):489-97. [4]. Antonella Di Pizio, et al. Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors. Front Mol Biosci. 2018 Jan 31;5:6.

Solubility Data

Solubility (In Vitro)

DMSO : 125 mg/mL (331.64 mM) H2O : 50 mg/mL (132.65 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.52 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 20.8 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: ≥ 2.08 mg/mL (5.52 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 33.33 mg/mL (88.43 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6531 mL	13.2654 mL	26.5308 mL
	5 mM	0.5306 mL	2.6531 mL	5.3062 mL
	10 mM	0.2653 mL	1.3265 mL	2.6531 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.