Amorolfine HCl (Ro 14-4767/002), a topically administered drug, is a potent and broad-spectrum antifungal agent with fungicidal effects against most fungi, dermatophytes and yeasts. Amorolfine blocks ergosterol biosynthesis by interfering with delta 14 reduction and the delta 7-8 isomerisation. Amorolfine is an antifungal showing activity against fungi pathogenic to plants, animals and humans. At 0.2, 2 and 5 micrograms/ml amorolfine did not have any significant inhibitory or enhancing effect on phagocytosis whether following simultaneous addition of blastospores and drug to the neutrophils, prior treatment of neutrophils for 2 h before addition of blastospores or prior treatment of blastospores for 2 h.

Physicochemical Properties

Molecular Formula	C21H35NO.HCL
Molecular Weight	353.97
Exact Mass	353.248
Elemental Analysis	C, 71.26; H, 10.25; Cl, 10.01; N, 3.96; O, 4.52
CAS #	78613-38-4
Related CAS #	67467-83-8;78613-35-1;78613-38-4 (HCl);
PubChem CID	54259
Appearance	White to off-white solid powder
Density	1.234
Boiling Point	78-82°C (9 Torr)
LogP	5.401
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	6
Heavy Atom Count	24
Complexity	336
Defined Atom Stereocenter Count	2
SMILES	Cl[H].O1[C@]([H])(C([H])([H])[H])C([H])([H])N(C([H])([H])[C@]1([H])C([H])([H])[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])[H]
InChi Key	XZKWIPVTHGWDCF-KUZYQSSXSA-N
InChi Code	InChI=1S/C21H35NO.ClH/c1-7-21(5,6)20-10-8-19(9-11-20)12-16(2)13-22-14-17(3)23-18(4)15-22;/h8-11,16-18H,7,12-15H2,1-6H3;1H/t16?,17-,18+;
Chemical Name	(2R,6S)-2,6-dimethyl-4-(2-methyl-3-(4-(tert-pentyl)phenyl)propyl)morpholine hydrochloride
Synonyms	Ro 14-4767/002; Amorolfin; Ro 14-4767-002; Ro-14-4767-002; Ro14-4767-002; Ro 14-4767; Ro-14-4767; Ro14-4767; Ro 144767; Ro-144767; Ro144767;
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, avoid exposure to moisture.
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 Vitro	Amorolfine hydrochloride has both fungistatic and fungicidal properties, and its primary mode of action is to inhibit the biosynthesis of ergosterol, a component of the fungal cell membrane. Amorolfine hydrochloride (0–128 mg/l) for 2–7 days exhibits antifungal activity against pathogenic yeasts, dimorphic fungi, dematiaceous fungi, and Dermatophyte fungi.With 90% killing corresponding concentrations of 3, 3, 10, and 100 mg/L for Trichophyton mentagrophytes, C. albicans, Histoplasma capsulatum, and Cryptococcus neoformans, respectively, amorolfine hydrochloride exhibits anti-fungal activity[1].
ln Vivo	In rats with vaginal candidiasis, amorolfine hydrochloride (0.01%–1%; intravaginal application; twice daily for three days) exhibits anti-fungal activity[1].
Animal Protocol	Animal Model: Rats (vaginal candidiasis)[1] Dosage: 0.01%-1% Administration: Intravaginal application; twice daily for 3 days Result: produced a dose-dependent log reduction in the number of cells; a 1% concentration totally removed C. albicans from the vagina.
References	[1]. Drugs. 1995 Jan;49(1):103-20. [2]. J Dermatolog Treat. 2016 Aug;27(4):359-63. [3]. Dermatology.1992;184 Suppl 1:3-7. [4]. Mycoses.1989 May;32(5):245-9.
Additional Infomation	Amorolfine hydrochloride is a hydrochloride resulting from the formal reacton of equimolar amounts of hydrogen chloride and amorolfine. An inhibitor of the action of squalene monooxygenase, Delta(14) reductase and D7-D8 isomerase and an antifungal agent, it is used for the topical treatment of fungal nail and skin infections. It has a role as an EC 1.14.13.132 (squalene monooxygenase) inhibitor, an EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor and an EC 1.3.1.70 (Delta(14)-sterol reductase) inhibitor. It is a hydrochloride and a morpholine antifungal drug. It contains an amorolfine(1+). Amorolfine Hydrochloride is the hyrochloride salt form of amorolfine, a morpholine antifungal agent. Amorolfine inhibits delta-14-reductase and delta-7,8-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membrane.

Solubility Data

Solubility (In Vitro)

Ethanol : ~71 mg/mL DMSO : 12.5~23 mg/mL ( 35.31 ~64.97 mM ) Water : 2~3.33 mg/mL(~9.41 mM )

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.53 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 12.5 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: ≥ 1.25 mg/mL (3.53 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 12.5 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: ≥ 1.25 mg/mL (3.53 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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 1.25 mg/mL (3.53 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8251 mL	14.1255 mL	28.2510 mL
	5 mM	0.5650 mL	2.8251 mL	5.6502 mL
	10 mM	0.2825 mL	1.4125 mL	2.8251 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.