Википедија

L-733060

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.[1] Samo jedan enantiomer je aktivan. Nekoliko asimetričnih sintetičkih postupaka je razvijeno.[2][3][4]

L-733060
IUPAC ime
(2S,3S)-3[3,5-bis(trifluoromethyl)benzyl]oxy2-phenylpiperidine
Identifikatori
CAS broj148700-85-0 ДаY
ATC kodnone
PubChemCID 132846
Hemijski podaci
FormulaC20H19F6NO
Molarna masa403,361 g/mol
  • FC(F)(F)c(c2)cc(C(F)(F)F)cc2COC1CCCNC1c3ccccc3

L-733,060 ima antidepresivne[5][6] i anksiolitičke efekte u životinjskim studijama,[7] i umanjuje oslobađanje dopamina i neurotoksičnost proizvedenu metamfetaminom i kokainom.[8][9][10][11][12] On pokazuje antiinflamatorne i antihepatotoksične efekte kod životinja,[13][14] i sprečava razvoj hiperalgesija nakon povrede nerva.[15][16] On takođe ima antikancirogeno dejstvo u nizu in vitro modela.[17][18][19]

Reference

уреди
  1. ^ Seabrook, GR; Shepheard, SL; Williamson, DJ; Tyrer, P; Rigby, M; Cascieri, MA; Harrison, T; Hargreaves, RJ; Hill, RG (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. 
  2. ^ 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. PMID 15373484. doi:10.1021/jo049166z. 
  3. ^ 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. PMID 15730301. doi:10.1021/jo048073e. 
  4. ^ 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. PMID 18331063. doi:10.1021/jo8002979. 
  5. ^ 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. PMID 12576885. doi:10.1097/01.fbp.0000055962.09493.e9. 
  6. ^ 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. PMID 17912250. doi:10.1038/sj.npp.1301586. 
  7. ^ 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. PMID 12225694. doi:10.1016/S0893-133X(02)00313-5. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. PMID 12801594. doi:10.1016/S0024-3205(03)00393-X. 
  13. ^ 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. PMID 12649350. doi:10.1124/jpet.102.043539. 
  14. ^ 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. PMID 14617692. doi:10.1124/jpet.103.059329. 
  15. ^ 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. PMID 15082150. doi:10.1016/j.neulet.2004.02.043. 
  16. ^ 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. PMID 18043070. doi:10.1097/01.anes.0000291454.90754.de. 
  17. ^ 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. PMID 17525212. doi:10.1167/iovs.05-1591. 
  18. ^ 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. PMID 17906845. doi:10.1007/s10637-007-9087-y. 
  19. ^ 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. PMID 18781096. doi:10.1159/000152942. 

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