(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide

• ChemBase ID: 781
• Molecular Formular: C25H37NO4
• Molecular Mass: 415.56558
• Monoisotopic Mass: 415.27225867
• SMILES: O[C@@H]1[C@@H]([C@H]([C@H](O)C1)/C=C/[C@@H](O)CCc1ccccc1)C/C=C\CCCC(=O)NCC
• Canonical SMILES: CCNC(=O)CCC/C=C\C[C@H]1[C@@H](O)C[C@H]([C@@H]1/C=C/[C@H](CCc1ccccc1)O)O
• InChI: InChI=1S/C25H37NO4/c1-2-26-25(30)13-9-4-3-8-12-21-22(24(29)18-23(21)28)17-16-20(27)15-14-19-10-6-5-7-11-19/h3,5-8,10-11,16-17,20-24,27-29H,2,4,9,12-15,18H2,1H3,(H,26,30)/b8-3-,17-16+/t20-,21+,22+,23-,24+/m0/s1
• InChIKey: AQOKCDNYWBIDND-FTOWTWDKSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
• IUPAC Traditional name: bimatoprost
• Brand Name: Lumigan
• Synonyms: (5Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl]cyclopentyl]-N-ethyl-5-heptenamide; AGN-192024; Lumigan; Prostamide; AGN 192024; bimatoprost; Bimatoprost

Database IDs

• CAS Number: 155206-00-1
• PubChem SID: 160964244; 46505334
• PubChem CID: 5311027

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.34702
• H Acceptors: 4
• H Donor: 4
• LogD (pH = 5.5): 2.6292617
• LogD (pH = 7.4): 2.6292624
• Log P: 2.6292624
• Molar Refractivity: 122.8312 cm^3
• Polarizability: 47.097137 Å^3
• Polar Surface Area: 89.79 Å^2
• Rotatable Bonds: 12
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.41
• LOG S: -4.35
• Solubility (Water): 1.87e-02 g/l

PROPERTIES

Physical Property

• Solubility: Ethanol; Methanol; Slightly soluble
• Apperance: White Solid
• Melting Point: 66-68°C
• Hydrophobicity(logP): 3.2

Safety Information

• Storage Condition: Amber Vial, -20°C Freezer, Under Inert Atmosphere

DETAILS

DrugBank - DB00905

• Drug Groups: approved; investigational
• Description: Bimatoprost ophthalmic solution is a topical medication used for controlling the progression of glaucoma or ocular hypertension, by reducing intraocular pressure. It is a prostaglandin analogue that works by increasing the outflow of aqueous fluid from the eyes. It binds to the prostanoid FP receptor.
• Indication: For the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another intraocular pressure lowering medication.
• Pharmacology: Bimatoprost is a prostamide, a synthetic structural analog of prostaglandin with ocular hypotensive activity, that is chemically related to prostamide F. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost lowers intraocular pressure (IOP) in humans. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
• Toxicity: In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m^2 is at least 70 times higher than the accidental dose of one bottle of bimatoprost for a 10 kg child.
• Affected Organisms: Humans and other mammals
• Biotransformation: Bimatoprost undergoes oxidation, N-deethylation and glucuronidation to form a variety of metabolites.
• Absorption: Systemically absorbed when administered to the eye.
• Half Life: Elimination half-life is approximately 45 minutes.
• Protein Binding: Approximately 88% of bimatoprost is bound in human plasma.
• Elimination: Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.
• Distribution: * 0.67 L/kg
• Clearance: * 1.5 L/hr/kg [Healthy subjects receiving IV administration of 3.12 ug/kg]
• References: Chen MJ, Cheng CY, Chen YC, Chou CK, Hsu WM: Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma. J Ocul Pharmacol Ther. 2006 Jun;22(3):188-93. [Pubmed] ; Kruse P, Rieck P, Sherif Z, Liekfeld A: [Cystoid macular edema in a pseudophakic patient after several glaucoma procedures. Is local therapy with bimatoprost the reason?] Klin Monatsbl Augenheilkd. 2006 Jun;223(6):534-7. [Pubmed] ; Steinhauser SL: Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy. Optometry. 2006 Apr;77(4):177-9. [Pubmed] ; Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, Andrews SW, Shi L, Liang Y, Kedzie KM, Chen R, Gil DW, Kharlamb A, Archeampong A, Ling J, Madhu C, Ni J, Rix P, Usansky J, Usansky H, Weber A, Welty D, Yang W, Tang-Liu DD, Garst ME, Brar B, Wheeler LA, Kaplan LJ: The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S337-45. [Pubmed] ; Lim KS, Nau CB, O'Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. [Pubmed] ; Brubaker RF: Mechanism of action of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S347-51. [Pubmed] ; Christiansen GA, Nau CB, McLaren JW, Johnson DH: Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology. 2004 Sep;111(9):1658-62. [Pubmed] ; Easthope SE, Perry CM: Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension. Drugs Aging. 2002;19(3):231-48. [Pubmed] ; Patil AJ, Vajaranant TS, Edward DP: Bimatoprost - a review. Expert Opin Pharmacother. 2009 Nov;10(16):2759-68. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Toronto Research Chemicals - B386800

Bimatoprost is an antiglaucoma agent. Bimatoprost is an synthetic prostamide; structurally related to prostaglandin F2α.

REFERENCES

• Brubaker RF: Mechanism of action of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S347-51. Pubmed
• Christiansen GA, Nau CB, McLaren JW, Johnson DH: Mechanism of ocular hypotensive action of bimatoprost (Lumigan) in patients with ocular hypertension or glaucoma. Ophthalmology. 2004 Sep;111(9):1658-62. Pubmed
• Easthope SE, Perry CM: Topical bimatoprost: a review of its use in open-angle glaucoma and ocular hypertension. Drugs Aging. 2002;19(3):231-48. Pubmed
• Patil AJ, Vajaranant TS, Edward DP: Bimatoprost - a review. Expert Opin Pharmacother. 2009 Nov;10(16):2759-68. Pubmed
• Chen MJ, Cheng CY, Chen YC, Chou CK, Hsu WM: Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma. J Ocul Pharmacol Ther. 2006 Jun;22(3):188-93. Pubmed
• Kruse P, Rieck P, Sherif Z, Liekfeld A: [Cystoid macular edema in a pseudophakic patient after several glaucoma procedures. Is local therapy with bimatoprost the reason?] Klin Monatsbl Augenheilkd. 2006 Jun;223(6):534-7. Pubmed
• Steinhauser SL: Decreased high-density lipoprotein serum levels associated with topical bimatoprost therapy. Optometry. 2006 Apr;77(4):177-9. Pubmed
• Woodward DF, Krauss AH, Chen J, Lai RK, Spada CS, Burk RM, Andrews SW, Shi L, Liang Y, Kedzie KM, Chen R, Gil DW, Kharlamb A, Archeampong A, Ling J, Madhu C, Ni J, Rix P, Usansky J, Usansky H, Weber A, Welty D, Yang W, Tang-Liu DD, Garst ME, Brar B, Wheeler LA, Kaplan LJ: The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol. 2001 May;45 Suppl 4:S337-45. Pubmed
• Lim KS, Nau CB, O'Byrne MM, Hodge DO, Toris CB, McLaren JW, Johnson DH: Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008 May;115(5):790-795.e4. Pubmed
• Brandt, J.D., et al.: Ophthalmology, 108, 1023 (2001)
• Woodward, D.F., et al.: J. Pharmacol. Exp. Ther., 305, 772 (2001)
• Quinones, R., et al.: J. Ocul. Pharmacol. Ther., 20, 115 (2001)