| 词条 | 5N-Bicalutamide |
| 释义 |
| Verifiedfields = | Watchedfields = | verifiedrevid = | drug_name = 5N-Bicalutamide | IUPAC_name = N-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methylpropanamide | image = 5-Azabicalutamide.svg | width = 250px | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number_Ref = | CAS_number = | CAS_supplemental = | class = Nonsteroidal antiandrogen | ATC_prefix = None | ATC_suffix = | ATC_supplemental = | PubChem = 118614933 | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = | ChemSpiderID_Ref = | ChemSpiderID = | UNII = | KEGG = | ChEBI = | ChEMBL = | synonyms = 5-Azabicalutamide | C=17 | H=13 | F=4 | N=3 | O=4 | S=1 | molecular_weight = 431.362 g/mol | SMILES = CC(CS(=O)(=O)C1=CC=C(C=C1)F)(C(=O)NC2=CN=C(C(=C2)C(F)(F)F)C#N)O | StdInChI_Ref = | StdInChI = 1S/C17H13F4N3O4S/c1-16(26,9-29(27,28)12-4-2-10(18)3-5-12)15(25)24-11-6-13(17(19,20)21)14(7-22)23-8-11/h2-6,8,26H,9H2,1H3,(H,24,25) | StdInChIKey_Ref = | StdInChIKey = JWQMHMGGGRQTSY-UHFFFAOYSA-N }}5N-Bicalutamide, or 5-azabicalutamide, is a highly potent nonsteroidal antiandrogen (NSAA) which was discovered in 2016.[1][2] It is a structural modification of bicalutamide differing it from it only by the replacement of a carbon atom with a nitrogen atom in one of its phenyl rings.[1] Similarly to bicalutamide, the drug acts as a selective antagonist of the androgen receptor (AR).[1] However, unlike bicalutamide, it is a reversible covalent antagonist and stays bound to the receptor for a far longer amount of time.[1] As a result of this difference, 5N-bicalutamide has markedly improved potency relative to bicalutamide, with approximately 150-fold higher affinity for the AR (Ki = 0.15 nM versus 22.3 nM) and about 20-fold greater functional inhibition ({{abbrlink|IC50|Half-maximal inhibitory concentration}} = 15 nM versus 310 nM) of the AR.[1] Future studies of 5N-bicalutamide in normal and mutated prostate cancer cells are planned or underway and it is anticipated that N-bicalutamide may be able to overcome resistance to current antiandrogens that are used in the treatment of prostate cancer.[1]Enzalutamide and related second-generation NSAAs like RD-162 and apalutamide were derived from bicalutamide and as a result are similar to it in chemical structure.[1] They have up to about 10-fold higher affinity for the AR than does bicalutamide and hence are comparatively more potent and efficacious antiandrogens.[1] However, their structures are rigidified such that the analogous structural modification that was done with bicalutamide to create 5N-bicalutamide could not be used to increase affinity or potency with them.[1] Enzalutamide was described in 2013 as "the emperor of all antiandrogens" and other second-generation NSAAs have similar potency to it,[3] so 5N-bicalutamide would appear to be the most potent AR antagonist to have been developed thus far.[1] See also
References1. ^1 2 3 4 5 6 7 8 9 {{cite journal | vauthors = de Jesus Cortez F, Nguyen P, Truillet C, Tian B, Kuchenbecker KM, Evans MJ, Webb P, Jacobson MP, Fletterick RJ, England PM | title = Development of 5N-Bicalutamide, a High-Affinity Reversible Covalent Antiandrogen | journal = ACS Chem. Biol. | volume = | issue = | pages = | year = 2017 | pmid = 28981251 | doi = 10.1021/acschembio.7b00702 | url = }} {{Androgen receptor modulators}}{{DEFAULTSORT:Bicalutamide, 5N-}}{{Antineoplastic-drug-stub}}{{Genito-urinary-drug-stub}}2. ^Pamela, M., Fletterick, R. J., Kuchenbecker, K., & de Jesus Cortez, F. (2016). U.S. Patent Application No. 15/382,942. https://www.google.com/patents/US20170101384 3. ^{{cite journal | vauthors = Antonarakis ES | title = Enzalutamide: The emperor of all anti-androgens | journal = Transl Androl Urol | volume = 2 | issue = 2 | pages = 119–120 | year = 2013 | pmid = 24076589 | pmc = 3785324 | doi = | url = }} 8 : Alcohols|Experimental cancer drugs|Hormonal antineoplastic drugs|Nitriles|Nonsteroidal antiandrogens|Pyridines|Sulfones|Trifluoromethyl compounds |
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