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Acetothiolutamide

January 01, 1970

Acetothiolutamide is a selective androgen receptor modulator (SARM) derived from the nonsteroidal antiandrogen bicalutamide that was described in 2002 and was one of the first SARMs to be discovered and developed.[1][2][3][4] It is a high-affinity, selective ligand of the androgen receptor (AR) (Ki = 2.1–4.9 nM), where it acts as a full agonist in vitro, and has in vitro potency comparable to that of testosterone.[2][4][5] However, in vivo, acetothiolutamide displayed overall negligible androgenic effects, though significant (albeit very low) anabolic effects were observed at high doses.[2] In addition, notable antiandrogen effects were observed in castrated male rats treated with testosterone propionate.[2] The discrepancy between the in vitro and in vivo actions of acetothiolutamide was determined to be related to rapid plasma clearance and extensive hepatic metabolism into a variety of metabolites with differing pharmacological activity, including AR partial agonism and antagonism.[2][4][6] In accordance with its poor metabolic stability, acetothiolutamide is not orally bioavailable, and shows activity only via injected routes such as subcutaneous and intravenous.[2]

Acetothiolutamide
Clinical data
Other namesThioacetolutamide
Identifiers
  • (2R)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-acetamidophenyl)sulfanyl]-2-hydroxy-2-methylpropanamide
CAS Number
  • 216665-38-2
PubChem CID
  • 10873814
ChemSpider
  • 9049091
UNII
  • SW1TF3RGAH
ChEMBL
  • ChEMBL121940
CompTox Dashboard (EPA)
  • DTXSID8040806
Chemical and physical data
FormulaC20H18F3N3O3S
Molar mass437.44 g·mol−1
3D model (JSmol)
  • Interactive image
  • CC(=O)NC1=CC=C(C=C1)SCC(C)(C(=O)NC2=CC(=C(C=C2)C#N)C(F)(F)F)O
  • InChI=1S/C20H18F3N3O3S/c1-12(27)25-14-5-7-16(8-6-14)30-11-19(2,29)18(28)26-15-4-3-13(10-24)17(9-15)20(21,22)23/h3-9,29H,11H2,1-2H3,(H,25,27)(H,26,28)/t19-/m0/s1
  • Key:FEDHYHIWSREKGN-IBGZPJMESA-N

See also edit

References edit

  1. ^ Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD (March 1998). "Discovery of nonsteroidal androgens". Biochemical and Biophysical Research Communications. 244 (1): 1–4. doi:10.1006/bbrc.1998.8209. PMID 9514878.
  2. ^ a b c d e f Yin D, Xu H, He Y, Kirkovsky LI, Miller DD, Dalton JT (March 2003). "Pharmacology, pharmacokinetics, and metabolism of acetothiolutamide, a novel nonsteroidal agonist for the androgen receptor". The Journal of Pharmacology and Experimental Therapeutics. 304 (3): 1323–33. doi:10.1124/jpet.102.040832. PMID 12604713. S2CID 6816508.
  3. ^ Kearbey JD (2004), Preclinical Pharmacokinetics and Skeletal Pharmacology of a Selective Androgen Receptor Modulator
  4. ^ a b c Perera MA, Yin D, Wu D, Chan KK, Miller DD, Dalton J (October 2006). "In vivo metabolism and final disposition of a novel nonsteroidal androgen in rats and dogs". Drug Metabolism and Disposition. 34 (10): 1713–21. doi:10.1124/dmd.106.009985. PMID 16815963. S2CID 14708913.
  5. ^ Kim J, Wu D, Hwang DJ, Miller DD, Dalton JT (October 2005). "The para substituent of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides is a major structural determinant of in vivo disposition and activity of selective androgen receptor modulators". The Journal of Pharmacology and Experimental Therapeutics. 315 (1): 230–9. doi:10.1124/jpet.105.088344. PMID 15987833. S2CID 30799845.
  6. ^ Yin D, Gao W, Kearbey JD, Xu H, Chung K, He Y, Marhefka CA, Veverka KA, Miller DD, Dalton JT (March 2003). "Pharmacodynamics of selective androgen receptor modulators". The Journal of Pharmacology and Experimental Therapeutics. 304 (3): 1334–40. doi:10.1124/jpet.102.040840. PMC 2040238. PMID 12604714.



 

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January 01, 1970
acetothiolutamide, selective, androgen, receptor, modulator, sarm, derived, from, nonsteroidal, antiandrogen, bicalutamide, that, described, 2002, first, sarms, discovered, developed, high, affinity, selective, ligand, androgen, receptor, where, acts, full, ag. Acetothiolutamide is a selective androgen receptor modulator SARM derived from the nonsteroidal antiandrogen bicalutamide that was described in 2002 and was one of the first SARMs to be discovered and developed 1 2 3 4 It is a high affinity selective ligand of the androgen receptor AR Ki 2 1 4 9 nM where it acts as a full agonist in vitro and has in vitro potency comparable to that of testosterone 2 4 5 However in vivo acetothiolutamide displayed overall negligible androgenic effects though significant albeit very low anabolic effects were observed at high doses 2 In addition notable antiandrogen effects were observed in castrated male rats treated with testosterone propionate 2 The discrepancy between the in vitro and in vivo actions of acetothiolutamide was determined to be related to rapid plasma clearance and extensive hepatic metabolism into a variety of metabolites with differing pharmacological activity including AR partial agonism and antagonism 2 4 6 In accordance with its poor metabolic stability acetothiolutamide is not orally bioavailable and shows activity only via injected routes such as subcutaneous and intravenous 2 AcetothiolutamideClinical dataOther namesThioacetolutamideIdentifiersIUPAC name 2R N 4 cyano 3 trifluoromethyl phenyl 3 4 acetamidophenyl sulfanyl 2 hydroxy 2 methylpropanamideCAS Number216665 38 2PubChem CID10873814ChemSpider9049091UNIISW1TF3RGAHChEMBLChEMBL121940CompTox Dashboard EPA DTXSID8040806Chemical and physical dataFormulaC 20H 18F 3N 3O 3SMolar mass437 44 g mol 13D model JSmol Interactive imageSMILES CC O NC1 CC C C C1 SCC C C O NC2 CC C C C2 C N C F F F OInChI InChI 1S C20H18F3N3O3S c1 12 27 25 14 5 7 16 8 6 14 30 11 19 2 29 18 28 26 15 4 3 13 10 24 17 9 15 20 21 22 23 h3 9 29H 11H2 1 2H3 H 25 27 H 26 28 t19 m0 s1Key FEDHYHIWSREKGN IBGZPJMESA NSee also editAndarine Enobosarm LG 121071References edit Dalton JT Mukherjee A Zhu Z Kirkovsky L Miller DD March 1998 Discovery of nonsteroidal androgens Biochemical and Biophysical Research Communications 244 1 1 4 doi 10 1006 bbrc 1998 8209 PMID 9514878 a b c d e f Yin D Xu H He Y Kirkovsky LI Miller DD Dalton JT March 2003 Pharmacology pharmacokinetics and metabolism of acetothiolutamide a novel nonsteroidal agonist for the androgen receptor The Journal of Pharmacology and Experimental Therapeutics 304 3 1323 33 doi 10 1124 jpet 102 040832 PMID 12604713 S2CID 6816508 Kearbey JD 2004 Preclinical Pharmacokinetics and Skeletal Pharmacology of a Selective Androgen Receptor Modulator a b c Perera MA Yin D Wu D Chan KK Miller DD Dalton J October 2006 In vivo metabolism and final disposition of a novel nonsteroidal androgen in rats and dogs Drug Metabolism and Disposition 34 10 1713 21 doi 10 1124 dmd 106 009985 PMID 16815963 S2CID 14708913 Kim J Wu D Hwang DJ Miller DD Dalton JT October 2005 The para substituent of S 3 phenoxy 2 hydroxy 2 methyl N 4 nitro 3 trifluoromethyl phenyl propionamides is a major structural determinant of in vivo disposition and activity of selective androgen receptor modulators The Journal of Pharmacology and Experimental Therapeutics 315 1 230 9 doi 10 1124 jpet 105 088344 PMID 15987833 S2CID 30799845 Yin D Gao W Kearbey JD Xu H Chung K He Y Marhefka CA Veverka KA Miller DD Dalton JT March 2003 Pharmacodynamics of selective androgen receptor modulators The Journal of Pharmacology and Experimental Therapeutics 304 3 1334 40 doi 10 1124 jpet 102 040840 PMC 2040238 PMID 12604714 nbsp This antineoplastic or immunomodulatory drug article is a stub You can help Wikipedia by expanding it vte nbsp This drug article relating to the genito urinary system is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Acetothiolutamide amp oldid 1135223329, wikipedia, wiki, book, books, library,

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