N-(5-carbamimidamido-1-{2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl}-1-oxopentan-2-yl)-2-{2-[2-(3-hydroxy-2-{2-[3-(1H-imidazol-4-yl)-2-[(5-oxopyrrolidin-2-yl)formamido]propanamido]-3-(1H-indol-3-yl)propanamido}propanamido)-3-(4-hydroxyphenyl)propanamido]-3-(naphthalen-2-yl)propanamido}-4-methylpentanamide

• ChemBase ID: 548
• Molecular Formular: C66H83N17O13
• Molecular Mass: 1322.47132
• Monoisotopic Mass: 1321.6356258
• SMILES: O=C(N1C(CCC1)C(=O)NCC(=O)N)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C1NC(=O)CC1)Cc1nc[nH]c1)Cc1c2c([nH]c1)cccc2)CO)Cc1ccc(O)cc1)Cc1cc2c(cc1)cccc2)CC(C)C)CCCNC(=N)N
• Canonical SMILES: OCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1CCCC1C(=O)NCC(=O)N)CCCNC(=N)N)CC(C)C)Cc1ccc2c(c1)cccc2)Cc1ccc(cc1)O)NC(=O)C(Cc1c[nH]c2c1cccc2)NC(=O)C(NC(=O)C1CCC(=O)N1)Cc1nc[nH]c1
• InChI: InChI=1S/C66H83N17O13/c1-36(2)25-48(58(89)76-47(13-7-23-71-66(68)69)65(96)83-24-8-14-54(83)64(95)73-33-55(67)86)77-60(91)50(28-38-15-18-39-9-3-4-10-40(39)26-38)78-59(90)49(27-37-16-19-43(85)20-17-37)79-63(94)53(34-84)82-61(92)51(29-41-31-72-45-12-6-5-11-44(41)45)80-62(93)52(30-42-32-70-35-74-42)81-57(88)46-21-22-56(87)75-46/h3-6,9-12,15-20,26,31-32,35-36,46-54,72,84-85H,7-8,13-14,21-25,27-30,33-34H2,1-2H3,(H2,67,86)(H,70,74)(H,73,95)(H,75,87)(H,76,89)(H,77,91)(H,78,90)(H,79,94)(H,80,93)(H,81,88)(H,82,92)(H4,68,69,71)
• InChIKey: RWHUEXWOYVBUCI-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(5-carbamimidamido-1-{2-[(carbamoylmethyl)carbamoyl]pyrrolidin-1-yl}-1-oxopentan-2-yl)-2-{2-[2-(3-hydroxy-2-{2-[3-(1H-imidazol-4-yl)-2-[(5-oxopyrrolidin-2-yl)formamido]propanamido]-3-(1H-indol-3-yl)propanamido}propanamido)-3-(4-hydroxyphenyl)propanamido]-3-(naphthalen-2-yl)propanamido}-4-methylpentanamide
• IUPAC Traditional name: nafarelin
• Brand Name: Synarel
• Synonyms: Nafarelin acetate; Nafarelin

Database IDs

• CAS Number: 76932-56-4
• PubChem SID: 160964011; 46506496
• PubChem CID: 25077649

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.489206
• H Acceptors: 17
• H Donor: 17
• LogD (pH = 5.5): -5.395644
• LogD (pH = 7.4): -4.381258
• Log P: -2.695584
• Molar Refractivity: 357.7955 cm^3
• Polarizability: 136.63554 Å^3
• Polar Surface Area: 472.13 Å^2
• Rotatable Bonds: 33
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 1.21
• LOG S: -4.9
• Solubility (Water): 1.66e-02 g/l

DETAILS

DrugBank - DB00666

• Drug Groups: approved
• Description: A potent synthetic agonist of gonadotropin-releasing hormone with 3-(2-naphthyl)-D-alanine substitution at residue 6. Nafarelin has been used in the treatments of central precocious puberty and endometriosis. [PubChem]
• Indication: For treatment of central precocious puberty (true precocious puberty, GnRH-dependent precocious precocity, complete isosexual precocity) in children of both sexes and for the treatment of endometriosis.
• Pharmacology: Nafarelin is a potent agonistic analog of gonadotropin-releasing hormone (GnRH). At the onset of administration, nafarelin stimulates the release of the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting in a temporary increase of gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland. Twice daily administration leads to decreased secretion of gonadal steroids by about 4 weeks; consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent. After nafarelin therapy is discontinued, pituitary and ovarian function normalize and estradiol serum concentrations increase to pretreatment levels. Recurrences of endometriosis are frequent after cessation of any hormonal therapy, or surgery that leaves the ovaries and/or uterus intact.
• Toxicity: In experimental animals, a single subcutaneous administration of up to 60 times the recommended human dose (on a µg/kg basis, not adjusted for bioavailability) had no adverse effects. At present, there is no clinical evidence of adverse effects following overdosage of GnRH analogs.
• Affected Organisms: Humans and other mammals
• Biotransformation: Enzymatic hydrolysis.
• Absorption: Rapidly absorbed into the systemic circulation after intranasal administration. Bioavailability from a 400 µg dose averaged 2.8% (range 1.2 to 5.6%). Not absorbed after oral administration.
• Half Life: 3 hours
• Protein Binding: Approximately 80%.
• References: Hugues JN, Cedrin Durnerin IC: Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998 Jan-Feb;4(1):83-101. [Pubmed] ; Garner C: Uses of GnRH agonists. J Obstet Gynecol Neonatal Nurs. 1994 Sep;23(7):563-70. [Pubmed] ; Henzl MR: Gonadotropin-releasing hormone analogs: update on new findings. Am J Obstet Gynecol. 1992 Feb;166(2):757-61. [Pubmed] ; Burry KA: Nafarelin in the management of endometriosis: quality of life assessment. Am J Obstet Gynecol. 1992 Feb;166(2):735-9. [Pubmed] ; Saltiel E, Garabedian-Ruffalo SM: Pharmacologic management of endometriosis. Clin Pharm. 1991 Jul;10(7):518-31. [Pubmed] ; Chrisp P, Goa KL: Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs. 1990 Apr;39(4):523-51. [Pubmed] ; Letassy NA, Thompson DF, Britton ML, Suda RR Sr: Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990 Dec;24(12):1204-9. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Chrisp P, Goa KL: Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs. 1990 Apr;39(4):523-51. Pubmed
• Letassy NA, Thompson DF, Britton ML, Suda RR Sr: Nafarelin acetate: a gonadotropin-releasing hormone agonist for the treatment of endometriosis. DICP. 1990 Dec;24(12):1204-9. Pubmed
• Garner C: Uses of GnRH agonists. J Obstet Gynecol Neonatal Nurs. 1994 Sep;23(7):563-70. Pubmed
• Hugues JN, Cedrin Durnerin IC: Revisiting gonadotrophin-releasing hormone agonist protocols and management of poor ovarian responses to gonadotrophins. Hum Reprod Update. 1998 Jan-Feb;4(1):83-101. Pubmed
• Henzl MR: Gonadotropin-releasing hormone analogs: update on new findings. Am J Obstet Gynecol. 1992 Feb;166(2):757-61. Pubmed
• Burry KA: Nafarelin in the management of endometriosis: quality of life assessment. Am J Obstet Gynecol. 1992 Feb;166(2):735-9. Pubmed
• Saltiel E, Garabedian-Ruffalo SM: Pharmacologic management of endometriosis. Clin Pharm. 1991 Jul;10(7):518-31. Pubmed