(5Z)-7-[(1R,2R,3R,5S)-2-[(1E)-3,3-Difluoro-4-phenoxy-1-buten-1-yl]-3,5-dihydroxycyclopentyl]-N-ethyl-5-heptenamide
[CAS# 1185851-52-8]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: (5Z)-7-[(1R,2R,3R,5S)-2-[(1E)-3,3-Difluoro-4-phenoxy-1-buten-1-yl]-3,5-dihydroxycyclopentyl]-N-ethyl-5-heptenamide
• Molecular Formula: C₂₄H₃₃F₂NO₄
• Molecular Weight: 437.52
• CAS Registry Number: 1185851-52-8
• EC Number: 867-521-0
• SMILES: CCNC(=O)CCC/C=C\C[C@H]1[C@H](C[C@H]([C@@H]1/C=C/C(COC2=CC=CC=C2)(F)F)O)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 609.3±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 322.3±31.5 ºC (Calc.)^*
• Solubility: Practically insoluble (0.053 g/L) (25 ºC), Calc.
• Index of refraction: 1.559 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Hazard Statements: H302-H319-H336-H360
• Precautionary Statements: P203-P261-P264-P264+P265-P270-P271-P280-P301+P317-P304+P340-P305+P351+P338-P318-P319-P330-P337+P317-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H302

Discovory and Applicatios

(5Z)-7-[(1R,2R,3R,5S)-2-[(1E)-3,3-difluoro-4-phenoxy-1-buten-1-yl]-3,5-dihydroxycyclopentyl]-N-ethyl-5-heptenamide is the systematic name for tafluprost ethyl amide, a difluorinated prostanoid analogue closely related to the clinically used ocular prodrug tafluprost. The molecule has the empirical formula C₂₄H₃₃F₂NO₄ and incorporates the characteristic prostanoid cyclopentane core bearing vicinal diol substituents, a conjugated heptenamide side chain, and a 3,3-difluoro-4-phenoxy butenyl fragment that confers improved metabolic stability and receptor interactions relative to non-fluorinated analogues.

Compounds of this structural family were developed in medicinal chemistry programmes targeting the prostanoid FP receptor (the prostaglandin F receptor), which modulates aqueous humour outflow and intraocular pressure. Fluorination at strategic positions was introduced to enhance potency, selectivity and metabolic resistance; such chemical design principles underlie tafluprost and its close analogues. Tafluprost itself is an isopropyl ester prodrug (the isopropyl ester of the 5-heptenoic acid derivative) that is hydrolysed in ocular tissues to the active free acid. Ethyl-amide derivatives, including the ethyl amide named above, have been described in the literature and in supplier/product monographs as related derivatives used in pharmacological studies, as synthetic intermediates, and in exploratory formulations for effects on eyelash or hair follicles in topical applications. These derivatives retain the prostanoid pharmacophore that engages the FP receptor family.

From a pharmacological standpoint, molecules bearing the 3,3-difluoro-4-phenoxybutenyl side chain and the 3,5-dihydroxycyclopentyl core display potent FP-receptor agonism in in vitro assays and give rise to ocular-hypotensive effects in animal models and humans when formulated for ocular delivery. The mechanism involves activation of FP receptors on ocular tissues, increasing uveoscleral outflow and thereby lowering intraocular pressure, which is the therapeutic mechanism exploited by tafluprost ophthalmic preparations. The ethyl amide derivative itself is primarily described in the chemical and toxicological literature as a close structural analogue and research compound rather than a marketed ophthalmic drug; information on its systemic pharmacokinetics or clinical efficacy is limited in primary clinical reports.

Synthetic access to such prostanoid analogues typically uses convergent prostaglandin-type assembly strategies: construction of the substituted cyclopentyl core with defined stereochemistry, installation of the difluorobutenyl side chain (often via Wittig/olefination or transition-metal–mediated coupling), and final introduction of the amide or ester functionality at the acidic side chain position. The stereochemical pattern (1R,2R,3R,5S in the name above) is crucial for FP-receptor activity and is controlled using enantioselective synthesis or chiral pool approaches; fluorination steps are carried out with electrophilic or nucleophilic fluorinating reagents under conditions that preserve adjacent stereocentres.

In practical laboratory handling, tafluprost ethyl amide and related prostanoid analogues are managed as light- and temperature-sensitive small molecules; they are typically stored under inert atmosphere at low temperature and characterised by NMR (including 19F NMR for the difluoro fragment), mass spectrometry and chiral chromatography. When employed in formulation work or preclinical assays, attention is paid to stereochemical purity and to the propensity of prostanoid compounds to isomerise about conjugated double bonds, which can affect potency.

Regulatory and clinical literature on tafluprost (the commercial analogue) documents its approval and clinical use as a preservative-free topical prostaglandin analogue for lowering intraocular pressure; that body of work provides the pharmacological and safety context for structural relatives such as the ethyl amide. Where ethyl-amide derivatives appear in product or supplier literature, they are most often presented as research standards, synthetic intermediates, or components of non-therapeutic cosmetic formulations rather than as independently approved medicinal products.

References


Ota T, Nonaka H, Ochi T, Fujita T, Yoshida K, Noguchi Y, Kobayashi K & Matsuo M (2003) New fluoroprostaglandin F&sub>2α derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents. Biological and Pharmaceutical Bulletin 26(12) 1691–1695. DOI: 10.1248/bpb.26.1691

Sutton A, Gilvarry A & Ropo A (2007) A comparative, placebo-controlled study of prostanoid fluoroprostaglandin-receptor agonists tafluprost and latanoprost in healthy males. Journal of Ocular Pharmacology and Therapeutics 23(4) 359–365. DOI: 10.1089/jop.2006.0061

Pantcheva MB, Seibold LK, Awadallah NS & Kahook MY (2011) Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Advances in Therapy 28(9) 707–715. DOI: 10.1007/s12325-011-0055-8