L-733060

L-733060
(IUPAC) ime
(2S,3S)-3[3,5-bis(trifluoromethyl)benzyl]oxy2-phenylpiperidine
Klinički podaci
Identifikatori
CAS broj 148700-85-0
ATC kod nije dodeljen
PubChem[1][2] 132846
Hemijski podaci
Formula C20H19F6NO 
Mol. masa 403,361 g/mol
SMILES eMolekuli & PubHem
Farmakoinformacioni podaci
Trudnoća ?
Pravni status

L-733,060 je lek koji je razvio Merck, Sharpe & Dohme. On deluje kao oralno aktivni, ne-peptidni, selektivni antagonist NK1 receptora, za koji se vezuje sa Ki od 0.08 nM.[3] Samo jedan enantiomer je aktivan. Nekoliko asimetričnih sintetičkih postupaka je razvijeno.[4][5][6]

L-733,060 ima antidepresivne[7][8] i anksiolitičke efekte u životinjskim studijama,[9] i umanjuje oslobađanje dopamina i neurotoksičnost proizvedenu metamfetaminom i kokainom.[10][11][12][13][14] On pokazuje antiinflamatorne i antihepatotoksične efekte kod životinja,[15][16] i sprečava razvoj hiperalgesija nakon povrede nerva.[17][18] On takođe ima antikancirogeno dejstvo u nizu in vitro modela.[19][20][21]

Reference

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  1. ↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519.  edit
  2. ↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1. 
  3. ↑ Seabrook GR, Shepheard SL, Williamson DJ, Tyrer P, Rigby M, Cascieri MA, Harrison T, Hargreaves RJ i dr.. (1996). „L-733,060, a novel tachykinin NK1 receptor antagonist; effects in Ca2+i mobilisation, cardiovascular and dural extravasation assays”. European journal of pharmacology 317 (1): 129–35. PMID 8982729. 
  4. ↑ Liu LX, Ruan YP, Guo ZQ, Huang PQ (2004). „A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones: application to the asymmetric syntheses of neurokinin substance P receptor antagonist (-)-L-733,061 and (-)-deoxocassine”. The Journal of organic chemistry 69 (18): 6001–9. DOI:10.1021/jo049166z. PMID 15373484. 
  5. ↑ Tsai MR, Chen BF, Cheng CC, Chang NC (2005). „A novel and highly regioselective approach to 5-methoxy-6-substituted-3-sulfonyl-delta-enlactams from 5-methoxy-3-sulfonyl glutarimide: synthesis of cis-2-substituted-3-piperidinols”. The Journal of organic chemistry 70 (5): 1780–5. DOI:10.1021/jo048073e. PMID 15730301. 
  6. ↑ Liu RH, Fang K, Wang B, Xu MH, Lin GQ (2008). „Concise asymmetric synthesis of (+)-CP-99,994 and (+)-L-733,060 via efficient construction of homochiral syn-1,2-diamines and syn-1,2-amino alcohols”. The Journal of organic chemistry 73 (8): 3307–10. DOI:10.1021/jo8002979. PMID 18331063. 
  7. ↑ Varty GB, Cohen-Williams ME, Hunter JC (2003). „The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension test”. Behavioural pharmacology 14 (1): 87–95. DOI:10.1097/01.fbp.0000055962.09493.e9. PMID 12576885. 
  8. ↑ Wallace-Boone TL, Newton AE, Wright RN, Lodge NJ, McElroy JF (2008). „Behavioral and pharmacological validation of the gerbil forced-swim test: effects of neurokinin-1 receptor antagonists”. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33 (8): 1919–28. DOI:10.1038/sj.npp.1301586. PMID 17912250. 
  9. ↑ Varty GB, Cohen-Williams ME, Morgan CA, Pylak U, Duffy RA, Lachowicz JE, Carey GJ, Coffin VL (2002). „The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists”. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 27 (3): 371–9. DOI:10.1016/S0893-133X(02)00313-5. PMID 12225694. 
  10. ↑ Kraft M, Noailles P, Angulo JA (2001). „Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat brain”. Annals of the New York Academy of Sciences 937: 121–31. PMID 11458533. 
  11. ↑ Yu J, Allison S, Ibrahim D, Cadet JL, Angulo JA (2002). „Ontogeny of neurokinin-1 receptor mediation of methamphetamine neurotoxicity in the striatum of the mouse brain”. Annals of the New York Academy of Sciences 965: 247–53. PMID 12105100. 
  12. ↑ Noailles PA, Angulo JA (2002). „Neurokinin receptors modulate the neurochemical actions of cocaine”. Annals of the New York Academy of Sciences 965: 267–73. PMID 12105102. 
  13. ↑ Yu J, Cadet JL, Angulo JA (2002). „Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain”. Journal of neurochemistry 83 (3): 613–22. PMID 12390523. 
  14. ↑ Loonam TM, Noailles PA, Yu J, Zhu JP, Angulo JA (2003). „Substance P and cholecystokinin regulate neurochemical responses to cocaine and methamphetamine in the striatum”. Life sciences 73 (6): 727–39. DOI:10.1016/S0024-3205(03)00393-X. PMID 12801594. 
  15. ↑ Bang R, Sass G, Kiemer AK, Vollmar AM, Neuhuber WL, Tiegs G (2003). „Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury”. The Journal of pharmacology and experimental therapeutics 305 (1): 31–9. DOI:10.1124/jpet.102.043539. PMID 12649350. 
  16. ↑ Bang R, Biburger M, Neuhuber WL, Tiegs G (2004). „Neurokinin-1 receptor antagonists protect mice from CD95- and tumor necrosis factor-alpha-mediated apoptotic liver damage”. The Journal of pharmacology and experimental therapeutics 308 (3): 1174–80. DOI:10.1124/jpet.103.059329. PMID 14617692. 
  17. ↑ Jang JH, Nam TS, Paik KS, Leem JW (2004). „Involvement of peripherally released substance P and calcitonin gene-related peptide in mediating mechanical hyperalgesia in a traumatic neuropathy model of the rat”. Neuroscience letters 360 (3): 129–32. DOI:10.1016/j.neulet.2004.02.043. PMID 15082150. 
  18. ↑ Rittner HL, Lux C, Labuz D, Mousa SA, Schäfer M, Stein C, Brack A (2007). „Neurokinin-1 receptor antagonists inhibit the recruitment of opioid-containing leukocytes and impair peripheral antinociception”. Anesthesiology 107 (6): 1009–17. DOI:10.1097/01.anes.0000291454.90754.de. PMID 18043070. 
  19. ↑ Muñoz M, Rosso M, Coveñas R, Montero I, González-Moles MA, Robles MJ (2007). „Neurokinin-1 receptors located in human retinoblastoma cell lines: antitumor action of its antagonist, L-732,138”. Investigative ophthalmology & visual science 48 (6): 2775–81. DOI:10.1167/iovs.05-1591. PMID 17525212. 
  20. ↑ Muñoz M, Rosso M, Aguilar FJ, González-Moles MA, Redondo M, Esteban F (2008). „NK-1 receptor antagonists induce apoptosis and counteract substance P-related mitogenesis in human laryngeal cancer cell line HEp-2”. Investigational new drugs 26 (2): 111–8. DOI:10.1007/s10637-007-9087-y. PMID 17906845. 
  21. ↑ Rosso M, Robles-Frías MJ, Coveñas R, Salinas-Martín MV, Muñoz M (2008). „The NK-1 receptor is expressed in human primary gastric and colon adenocarcinomas and is involved in the antitumor action of L-733,060 and the mitogenic action of substance P on human gastrointestinal cancer cell lines”. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 (4): 245–54. DOI:10.1159/000152942. PMID 18781096. 

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Šablon:Neuropeptidni ligandi