Tìm theo
Nafarelin
Các tên gọi khác (4 ) :
  • Nafarelin
  • Nafarelina
  • Nafaréline
  • Nafarelinum
antiendometriotic agent, gonadotropin releasing hormone agonist
Thuốc Gốc
Small Molecule
CAS: 76932-56-4
ATC: H01CA02
ĐG : GD Searle LLC
CTHH: C66H83N17O13
PTK: 1322.4713
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]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C66H83N17O13
Phân tử khối
1322.4713
Monoisotopic mass
1321.635625827
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)
InChI Key
InChIKey=RWHUEXWOYVBUCI-UHFFFAOYSA-N
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
Traditional IUPAC Name
N-{5-carbamimidamido-1-[2-(carbamoylmethylcarbamoyl)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
SMILES
CC(C)CC(NC(=O)C(CC1=CC2=CC=CC=C2C=C1)NC(=O)C(CC1=CC=C(O)C=C1)NC(=O)C(CO)NC(=O)C(CC1=CNC2=CC=CC=C12)NC(=O)C(CC1=CNC=N1)NC(=O)C1CCC(=O)N1)C(=O)NC(CCCNC(N)=N)C(=O)N1CCCC1C(=O)NCC(N)=O
Độ hòa tan
1.66e-02 g/l
logP
-2.7
logS
-4.9
pKa (strongest acidic)
9.49
pKa (Strongest Basic)
11.92
PSA
472.13 Å2
Refractivity
357.8 m3·mol-1
Polarizability
137.29 Å3
Rotatable Bond Count
33
H Bond Acceptor Count
17
H Bond Donor Count
17
Physiological Charge
1
Number of Rings
8
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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] Like GnRH, initial or intermittent administration of nafarelin stimulates release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland, which in turn transiently increases production of estradiol in females and testosterone in both sexes. However, with continuous daily administration, nafarelin continuously occupies the GnRH receptor, leading to a reversible down-regulation of the GnRH receptors in the pituitary gland and desensitization of the pituitary gonadotropes. This causes a significant and sustained decline in the production of LH and FSH. A decline in gonadotropin production and release causes a dramatic reversible decrease in synthesis of estradiol, progesterone, and testosterone by the ovaries or testes. Like normal endometrium, endometriotic implants contain estrogen receptors. Estrogen stimulates the growth of endometrium. Use of nafarelin induces anovulation and amenorrhea and decreases serum concentrations of estradiol to the postmenopausal range, which induces atrophy of endometriotic implants. However, nafarelin does not abolish the underlying pathophysiology of endometriosis. In children with central precocious puberty receiving nafarelin, serum LH, testosterone, and estradiol concentrations return to prepubertal levels. This results in the supression of secondary sexual characteristics and decrased rate of linear growth and skeletal maturation. Following disconinuation of nafarelin, the effects of the drug is reversed, meaning FSH and LH concentrations usually return to pretreatment levels.
Dược Động Học :
▧ 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.
▧ Protein binding :
Approximately 80%.
▧ Metabolism :
Enzymatic hydrolysis.
▧ Half Life :
3 hours
Độc Tính : 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.
Chỉ Định : 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.
Liều Lượng & Cách Dùng : Aerosol, metered - Nasal
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Fuji Yakuhin
    Sản phẩm biệt dược : Nafarelil
  • Công ty : Pfizer
    Sản phẩm biệt dược : Nasanyl
  • Công ty : Pfizer
    Sản phẩm biệt dược : Synarel
  • Công ty : Pfizer
    Sản phẩm biệt dược : Synarela
  • Công ty : Pfizer
    Sản phẩm biệt dược : Synrelina
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00666
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=25077649
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506496
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07613
ChemSpider
http://www.chemspider.com/Chemical-Structure.10605761.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0025-0166-08
PharmGKB
http://www.pharmgkb.org/drug/PA164754805
Wikipedia
http://en.wikipedia.org/wiki/Nafarelin
RxList
http://www.rxlist.com/cgi/generic2/nafarelin.htm
Drugs.com
http://www.drugs.com/cdi/nafarelin.html
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