L-371,257

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L-371,257
L-371,257 structure.png
Systematic (IUPAC) name
1-[4-[(1-Acetyl-4-piperidinyl)oxy]-2-methoxybenzoyl]-4-(2-oxo-2H-3,1-benzoxazin-1(4H)-yl)piperidine
Clinical data
Legal status
?
Identifiers
CAS number 162042-44-6 YesY
ATC code ?
PubChem CID 6918320
ChEMBL CHEMBL24781 N
Chemical data
Formula C28H33N3O6 
Mol. mass 507.577 g/mol
 N (what is this?)  (verify)

L-371,257 is a compound used in scientific research which acts as a selective antagonist of the oxytocin receptor with over 800x selectivity over the related vasopressin receptors.[1] It was one of the first non-peptide oxytocin antagonists developed,[2][3][4][5] and has good oral bioavailability, but poor penetration of the blood–brain barrier which gives it good peripheral selectivity with few central side effects.[6] Potential applications are likely to be in the treatment of premature labour.[7]

References[edit]

  1. ^ Williams, PD, Clineschmidt, BV, Erb, JM, Freidinger, RM, Guidotti, MT, Lis, EV, Pawluczyk, JM, Pettibone, DJ et al. (1995). "1-(1-4-(N-acetyl-4-piperidinyl)oxy-2-methoxybenzoylpiperidin-4- yl)-4H-3,1-benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist". Journal of Medical Chemistry 38 (23): 4634–6. doi:10.1021/jm00023a002. PMID 7473590. 
  2. ^ Bell, IM, Erb, JM, Freidinger, RM, Gallicchio, SN, Guare, JP, Guidotti, MT, Halpin, RA, Hobbs, DW et al. (1998). "Development of orally active oxytocin antagonists: studies on 1-(1-4-1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy-2- methoxybenzoylpiperidin-4-yl)-1,4-dihydrobenzd1,3oxazin-2-one (L-372,662) and related pyridines". Journal of Medical Chemistry 41 (12): 2146–63. doi:10.1021/jm9800797. PMID 9622556. 
  3. ^ Kuo, MS, Bock, MG, Freidinger, RM, Guidotti, MT, Lis, EV, Pawluczyk, JM, Perlow, DS, Pettibone, DJ et al. (1998). "Nonpeptide oxytocin antagonists: potent, orally bioavailable analogs of L-371,257 containing a 1-R-(pyridyl)ethyl ether terminus". Bioorganic & Medicinal Chemistry Letters 8 (21): 3081–6. doi:10.1016/S0960-894X(98)00568-X. PMID 9873680. 
  4. ^ Williams, PD, Bock, MG, Evans, BE, Freidinger, RM, Gallicchio, SN, Guidotti, MT, Jacobson, MA, Kuo, MS et al. (1999). "Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency". Bioorganic & Medicinal Chemistry Letters 9 (9): 1311–6. doi:10.1016/S0960-894X(99)00181-X. PMID 10340620. 
  5. ^ Wyatt, PG, Allen, MJ, Chilcott, J, Foster, A, Livermore, DG, Mordaunt, JE, Scicinski, J, Woollard, PM (2002). "Identification of potent and selective oxytocin antagonists. Part 1: indole and benzofuran derivatives". Bioorganic & Medicinal Chemistry Letters 12 (10): 1399–404. doi:10.1016/S0960-894X(02)00159-2. PMID 11992786. 
  6. ^ Ring, RH, Malberg, JE, Potestio, L, Ping, J, Boikess, S, Luo, B, Schechter, LE, Rizzo, S et al. (2006). "Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications". Psychopharmacology 185 (2): 218–25. doi:10.1007/s00213-005-0293-z. PMID 16418825. 
  7. ^ Hawtin, SR, Ha, SN, Pettibone, DJ, Wheatley, M (2005). "A Gly/Ala switch contributes to high affinity binding of benzoxazinone-based non-peptide oxytocin receptor antagonists". FEBS Letters 579 (2): 349–56. doi:10.1016/j.febslet.2004.10.108. PMID 15642343.