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

Physicochemical Properties

Molecular Formula	C21H28N2O2
Exact Mass	340.215
CAS #	522-60-1
Related CAS #	Ethylhydrocupreine hydrochloride;3413-58-9
PubChem CID	87880
Appearance	Typically exists as solid at room temperature
Density	1.18g/cm3
Boiling Point	508.7ºC at 760mmHg
Melting Point	123-128° when solvent-free
Flash Point	261.5ºC
Index of Refraction	1.618
LogP	3.725
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	446
Defined Atom Stereocenter Count	4
SMILES	CCOC1C=CC2=C(C([C@H]([C@@]3(C[C@]4([H])CCN3C[C@H]4CC)[H])O)=CC=N2)C=1
InChi Key	SUWZHLCNFQWNPE-LATRNWQMSA-N
InChi Code	InChI=1S/C21H28N2O2/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/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
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	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.
Additional Infomation	Optochin is a cinchona alkaloid consisting of 10,11-dihydrocinchonan bearing hydroxy and ethoxy substituents at positions 9 and 6' respectively. It has a role as an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor. It is a cinchona alkaloid and an aromatic ether. It is functionally related to a cinchonan.

Solubility Data

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.)