2-(2-amino-3-benzoylphenyl)acetamide

• ChemBase ID: 4479
• Molecular Formular: C15H14N2O2
• Molecular Mass: 254.28386
• Monoisotopic Mass: 254.1055277
• SMILES: c1ccc(cc1)C(=O)c1c(c(ccc1)CC(=O)N)N
• Canonical SMILES: NC(=O)Cc1cccc(c1N)C(=O)c1ccccc1
• InChI: InChI=1S/C15H14N2O2/c16-13(18)9-11-7-4-8-12(14(11)17)15(19)10-5-2-1-3-6-10/h1-8H,9,17H2,(H2,16,18)
• InChIKey: QEFAQIPZVLVERP-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-(2-amino-3-benzoylphenyl)acetamide
• IUPAC Traditional name: nepafenac
• Brand Name: Nevanac
• Synonyms: Amfenac amide; Nepafenac; 2-Amino-3-benzoylbenzeneacetamide; AHR 9434; AL 6515; Nevanac

Database IDs

• CAS Number: 78281-72-8
• PubChem SID: 160967911; 99443294
• PubChem CID: 151075

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.818239
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 2.0843859
• LogD (pH = 7.4): 2.0844774
• Log P: 2.0844786
• Molar Refractivity: 74.4637 cm^3
• Polarizability: 28.004637 Å^3
• Polar Surface Area: 86.18 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.53
• LOG S: -4.11
• Solubility (Water): 1.97e-02 g/l

PROPERTIES

Physical Property

• Solubility: DMSO; Methanol
• Apperance: Light Yellow Solid
• Melting Point: 177-181°C

Safety Information

• Storage Condition: -20°C; Refrigerator, Under Inert Atmosphere

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB06802

• Drug Groups: approved
• Description: Nepafenac is a non-steroidal anti-inflammatory prodrug (NSAID) usually sold as a prescription eye drop. It is used to treat pain and inflammation associated with cataract surgery.
• Indication: For the treatment of pain and inflammation associated with cataract surgery.
• Pharmacology: Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration.
• Toxicity: Ocularly applied non-steroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
• Biotransformation: Nepafenac (prodrug) is deaminated to amfenac (active compound) in the ciliary body epithelium, retina, and choroid by intraocular hydrolases. Subsequently, amfenac undergoes extensive metabolism to more polar metabolites involving hydroxylation of the aromatic ring leading to glucuronide conjugate formation.
• Absorption: Nepafenac rapidly cross the cornea (6 times faster than diclofenac in vitro).
• Protein Binding: Amfenac has high affinity toward serum albumin proteins. In vitro, the percent bound to human albumin and human serum was 95.4% and 99.1% respectively.
• Elimination: After oral administration of 14C-nepafenac to healthy volunteers, urinary excretion was found to be the major route of radioactivity elimination, accounting for approximately 85% of the dose, while fecal excretion represented approximately 6% of the dose. Nepafenac (prodrug) and amfenac (active compound) were not quantifiable in the urine.
• References: Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. [Pubmed] ; Ke TL, Graff G, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers. Inflammation. 2000 Aug;24(4):371-84. [Pubmed] ; Lane SS, Modi SS, Lehmann RP, Holland EJ: Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007 Jan;33(1):53-8. [Pubmed] ; Walters T, Raizman M, Ernest P, Gayton J, Lehmann R: In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2007 Sep;33(9):1539-45. [Pubmed] ; Bucci FA Jr, Waterbury LD: Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2008 Aug;34(8):1226; author reply 1226-7. [Pubmed] ; Summary Basis of Decision (SBD): NEVANAC. [Health Canada]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1255

Research Area: Retinal oedema
Biological Activity:
Nepafenac is a non-steroidal anti-inflammatory drug (NSAID), usually sold as a prescription eye drop. It reduces pain and inflammation in the eyes. Nepafenac ophthalmic is used to reduce pain and swelling after cataract surgery. Its side effects may include decreased visual acuity, a feeling that something is in the eye, increased eye pressure or a sticky sensation, as well as other effects.

Toronto Research Chemicals - N390080

A non-steroidal anti-inflammatory with analgesic activity; selective COX-2 inhibitor. Prodrug of Amfenac.

REFERENCES

• Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Inflammation. 2000 Aug;24(4):357-70. Pubmed
• Ke TL, Graff G, Spellman JM, Yanni JM: Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers. Inflammation. 2000 Aug;24(4):371-84. Pubmed
• Lane SS, Modi SS, Lehmann RP, Holland EJ: Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007 Jan;33(1):53-8. Pubmed
• Walters T, Raizman M, Ernest P, Gayton J, Lehmann R: In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2007 Sep;33(9):1539-45. Pubmed
• Bucci FA Jr, Waterbury LD: Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg. 2008 Aug;34(8):1226; author reply 1226-7. Pubmed
• Summary Basis of Decision (SBD): NEVANAC. Health Canada
• http://en.wikipedia.org/wiki/Nepafenac
• Walsh, D.A., et al.: J. Med. Chem., 33, 2296 (1990)
• Gamache, D.A., et al.: Inflammation, 24, 357 (1990)
• Lindstrom, R., et al.: Curr. Med. Res. Opin., 22, 397 (1990)