(5Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-N-methyl-5-heptenamide
[CAS# 155206-01-2]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: (5Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-N-methyl-5-heptenamide
• Synonyms: (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-methylhept-5-enamide
• Molecular Formula: C₂₄H₃₅NO₄
• Molecular Weight: 401.54
• CAS Registry Number: 155206-01-2
• SMILES: CNC(=O)CCC/C=CC[C@H]1[C@H](C[C@H]([C@@H]1/C=C/[C@H](CCC2=CC=CC=C2)O)O)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 621.5±55.0 °C 760 mmHg (Calc.)^*
• Flash point: 329.7±31.5 °C (Calc.)^*
• Solubility: Practically insoluble (0.08 g/L) (25 °C), Calc.
• Index of refraction: 1.597 (Calc.)^*

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

Discovery and Applications

(5Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-N-methyl-5-heptenamide, commonly known as bimatoprost, is a synthetic prostamide analog developed as a therapeutic agent to reduce intraocular pressure in patients with open-angle glaucoma and ocular hypertension. The discovery of bimatoprost emerged from research on prostaglandin analogs designed to optimize ocular hypotensive effects while minimizing systemic side effects. Unlike classical prostaglandins, bimatoprost is an amide derivative rather than a free acid, which confers unique pharmacological properties and allows it to act through prostamide-sensitive pathways in ocular tissues.

Bimatoprost was synthesized by modifying the prostaglandin F_2α framework to include an N-methyl amide group on the heptenamide side chain, a phenyl-substituted pentenyl omega-chain, and specific hydroxyl groups on the cyclopentane ring. These modifications, combined with strict stereochemical control at the chiral centers, were found to be critical for biological activity. Studies confirmed that the molecule’s configuration, particularly at positions 1R, 2R, 3R, 5S, and 3S on the omega-side chain, is essential for high-affinity interaction with prostamide-sensitive mechanisms in ocular tissues.

Pharmacologically, bimatoprost decreases intraocular pressure by enhancing both uveoscleral and trabecular outflow of aqueous humor. Unlike other prostaglandin F_2α analogs that are administered as isopropyl ester prodrugs and require enzymatic hydrolysis to release the active acid, bimatoprost acts directly as the pharmacologically active amide. This direct activity enables effective local action in the eye with minimal systemic absorption, which has been confirmed by pharmacokinetic studies showing low plasma levels following topical administration.

Bimatoprost’s therapeutic development involved extensive preclinical and clinical studies. In vitro and ex vivo investigations demonstrated increased outflow facility in trabecular meshwork and ciliary body tissues, consistent with the observed reduction in intraocular pressure. Clinical trials established the efficacy of bimatoprost ophthalmic solution in adults with open-angle glaucoma or ocular hypertension. Patients receiving bimatoprost showed significant reductions in intraocular pressure compared to baseline and to alternative prostaglandin analogs. The drug was generally well tolerated, with the most commonly reported adverse effect being conjunctival hyperemia. Other side effects, such as eye pruritus or increased eyelash growth, were documented and subsequently led to cosmetic applications for eyelash enhancement.

Bimatoprost has also been evaluated for non-ocular uses. Its ability to promote eyelash growth led to the development of formulations for hypotrichosis of the eyelashes, providing a treatment option supported by controlled clinical studies. Safety assessments confirmed that the compound remains largely localized when applied topically to the eyelashes, with minimal systemic exposure and a low incidence of serious adverse effects.

Structurally, bimatoprost exemplifies how modifications of the prostaglandin F_2α scaffold can yield compounds with unique pharmacological profiles. The molecule retains the cyclopentane ring and oxygenated side chains characteristic of prostaglandins while incorporating an amide moiety and precise stereochemistry to enhance ocular potency and selectivity. Its development represents a combination of medicinal chemistry, pharmacological testing, and clinical evaluation that has contributed to its status as a widely used ocular hypotensive agent and as a treatment for eyelash hypotrichosis.

References

Woodward DF, Krauss AH, Chen J, Liang Y (2008) Pharmacological characterization of prostaglandin analogs used in glaucoma therapy: prostamide-related activity of bimatoprost. Journal of Ocular Pharmacology and Therapeutics 24 475–482 DOI: 10.1124/jpet.102.047837

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