Bimatoprost isopropyl ester
[CAS# 130209-76-6]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: Bimatoprost isopropyl ester
• Synonyms: 7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-5-heptenoic acid 1-methylethyl ester
• Molecular Formula: C₂₆H₃₈O₅
• Molecular Weight: 430.58
• CAS Registry Number: 130209-76-6
• EC Number: 691-872-7
• SMILES: CC(C)OC(=O)CCC/C=C\C[C@H]1[C@H](C[C@H]([C@@H]1/C=C/[C@H](CCC2=CC=CC=C2)O)O)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 573.4±50.0 ºC 760 mmHg (Calc.)^*
• Flash point: 185.0±23.6 ºC (Calc.)^*
• Index of refraction: 1.579 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Hazard Statements: H302+H312+H332-H302-H312-H332-H360
• Precautionary Statements: P203-P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P318-P321-P330-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332

Discovory and Applicatios

Bimatoprost isopropyl ester is a member of the prostaglandin F-class structural family and is best understood in the context of two validated facts from the literature: the chemical strategy of isopropyl-ester prodrugs applied to PGF(2α)-type analogs, and the unique pharmacology of bimatoprost as a prostamide-related agent. The isopropyl-ester modification has been used repeatedly in the development of ocular hypotensive agents to increase lipophilicity and corneal penetration; once the ester crosses the corneal barrier it is hydrolyzed by ocular esterases to yield the active free acid or active metabolite. This prodrug approach is the established mechanism behind clinically used agents such as latanoprost and travoprost, where the isopropyl ester form enhances topical absorption and is subsequently converted in situ to the pharmacologically active species. Experimental pharmacology studies with FP-class analogues and their isopropyl esters have demonstrated that such ester derivatives can exhibit higher corneal permeability and, after hydrolysis, generate potent FP-receptor agonists in ocular tissues.

Bimatoprost itself is chemically distinct from classical PGF(2α) free acids because it is an amide (a prostamide analogue) rather than a carboxylic acid. The peer-reviewed literature documents that bimatoprost lowers intraocular pressure through actions consistent with prostamide pharmacology and that it can affect conventional aqueous outflow via interactions with receptors or pathways classed as prostamide-sensitive. Functional studies using human anterior segment models and trabecular meshwork preparations have shown that bimatoprost increases conventional outflow facility, and that selective antagonists of prostamide activity attenuate those effects. Reviews of prostamide pharmacology summarize that prostamide analogues such as bimatoprost have a pharmacological profile different from simple PGF(2α) free acids, supporting the view that bimatoprost acts through prostamide-related mechanisms in ocular tissues.

The compound named bimatoprost isopropyl ester has appeared in analytical and patent literature as an isopropyl-ester derivative related to the PGF-class structural series. From a mechanistic and chemical point of view, an isopropyl-ester derivative of a PGF-type scaffold would be expected to function as a prodrug: increased lipophilicity facilitates corneal penetration and subsequent esterase-mediated hydrolysis yields an active species in the eye. The broader literature on PGF(2α)-class isopropyl esters provides experimental evidence supporting that predictable prodrug behavior for this class. Analytical surveys and regulatory reviews have documented the occurrence of various prostaglandin analogues and related derivatives (including isopropyl-ester species) in unregulated topical products sold as eyelash serums; these surveys used validated LC-MS/MS methods to screen and quantify multiple PGF(2α)-type analogs in marketed preparations. Regulatory and safety assessments emphasize that prostaglandin-related molecules are pharmacologically active at low concentrations and therefore their presence in cosmetic products raises safety concerns and requires regulatory oversight.

In summary, the verified literature supports three core, non-speculative points: (1) isopropyl ester modification is an established prodrug strategy for PGF(2α)-class ocular agents that improves corneal penetration and relies on ocular esterases for conversion to active species, (2) bimatoprost is pharmacologically characterized as a prostamide-related agent that produces ocular hypotensive effects in part via conventional outflow mechanisms, and (3) isopropyl-ester derivatives related to PGF-type scaffolds have been described in patents and analytical studies and may be encountered in non-prescription topical products, which has prompted regulatory evaluation. The references below provide primary experimental studies and authoritative reviews that substantiate these points.

References

Wan Z, Woodward DF, Cornell CL, Fliri HG, Martos JL, Pettit SN et al. (2007) Bimatoprost, prostamide activity, and conventional drainage. Investigative Ophthalmology & Visual Science 48 4107–4115 DOI: 10.1167/iovs.07-0080

Sharif NA, Kelly CR, Crider JY (2002) Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor. Journal of Ocular Pharmacology and Therapeutics 18 313–324 DOI: 10.1089/10807680260218489

Rahman MS, Yoshida N, Hanafusa M, Matsuo A, Zhu S, Stub Y et al. (2022) Screening and quantification of undeclared PGF2α analogs in eyelash-enhancing cosmetic serums using LC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis 219 114940 DOI: 10.1016/j.jpba.2022.114940