BQCA

Last updated

BQCA
BQCA.svg
Identifiers
  • 1-[(4-methoxyphenyl)methyl]-4-oxoquinoline-3-carboxylic acid
CAS Number
PubChem CID
ChemSpider
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C18H15NO4
Molar mass 309.321 g·mol−1
3D model (JSmol)
  • COC1=CC=C(C=C1)CN2C=C(C(=O)C3=CC=CC=C32)C(=O)O
  • InChI=1S/C18H15NO4/c1-23-13-8-6-12(7-9-13)10-19-11-15(18(21)22)17(20)14-4-2-3-5-16(14)19/h2-9,11H,10H2,1H3,(H,21,22)
  • Key:BZBBTGCKPRSPGF-UHFFFAOYSA-N

BQCA (benzyl quinolone carboxylic acid) is an experimental drug that acts as a potent and selective positive allosteric modulator of the Muscarinic acetylcholine receptor M1. It was one of the first M1-selective positive allosteric modulators to be discovered, originally developed as a potential treatment agent for cognitive symptoms of schizophrenia, and while BQCA itself was not adopted for clinical use due to its poor side effect profile it is still used in research, and has led to the discovery of a wide range of structurally related M1 PAMs. [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]

References

  1. ↑ Ma L, Seager MA, Wittmann M, Jacobson M, Bickel D, Burno M, et al. (September 2009). "Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation". Proceedings of the National Academy of Sciences of the United States of America. 106 (37): 15950–15955. doi: 10.1073/pnas.0900903106 . PMC   2732705 . PMID   19717450.
  2. ↑ Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, et al. (November 2009). "A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning". The Journal of Neuroscience : The Official Journal of the Society for Neuroscience. 29 (45): 14271–14286. doi:10.1523/JNEUROSCI.3930-09.2009. PMC   2811323 . PMID   19906975.
  3. ↑ Thomsen M, Lindsley CW, Conn PJ, Wessell JE, Fulton BS, Wess J, et al. (April 2012). "Contribution of both M1 and M4 receptors to muscarinic agonist-mediated attenuation of the cocaine discriminative stimulus in mice". Psychopharmacology. 220 (4): 673–685. doi:10.1007/s00213-011-2516-9. PMC   3314162 . PMID   21964721.
  4. ↑ Chambon C, Jatzke C, Wegener N, Gravius A, Danysz W (December 2012). "Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication". European Journal of Pharmacology. 697 (1–3): 73–80. doi:10.1016/j.ejphar.2012.10.011. PMID   23085025.
  5. ↑ Mistry SN, Valant C, Sexton PM, Capuano B, Christopoulos A, Scammells PJ (June 2013). "Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor". Journal of Medicinal Chemistry. 56 (12): 5151–5172. doi:10.1021/jm400540b. PMID   23718562.
  6. ↑ Kuduk SD, Beshore DC (2014). "SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs)". Current Topics in Medicinal Chemistry. 14 (15): 1738–1754. doi:10.2174/1568026614666140826120224. PMID   25176125.
  7. ↑ Abdul-Ridha A, López L, Keov P, Thal DM, Mistry SN, Sexton PM, et al. (February 2014). "Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor". The Journal of Biological Chemistry. 289 (9): 6067–6079. doi: 10.1074/jbc.M113.539080 . PMC   3937673 . PMID   24443568.
  8. ↑ Choy KH, Shackleford DM, Malone DT, Mistry SN, Patil RT, Scammells PJ, et al. (November 2016). "Positive Allosteric Modulation of the Muscarinic M1 Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior". The Journal of Pharmacology and Experimental Therapeutics. 359 (2): 354–365. doi:10.1124/jpet.116.235788. PMID   27630144.
  9. ↑ Khajehali E, Valant C, Jörg M, Tobin AB, Conn PJ, Lindsley CW, et al. (August 2018). "Probing the binding site of novel selective positive allosteric modulators at the M1 muscarinic acetylcholine receptor". Biochemical Pharmacology. 154: 243–254. doi:10.1016/j.bcp.2018.05.009. PMC   6066355 . PMID   29777683.
  10. ↑ Lehner KR, Silverman HA, Addorisio ME, Roy A, Al-Onaizi MA, Levine Y, et al. (2019). "Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation". Frontiers in Immunology. 10: 585. doi: 10.3389/fimmu.2019.00585 . PMC   6455130 . PMID   31024522.
  11. ↑ Ishioh M, Nozu T, Miyagishi S, Igarashi S, Funayama T, Ohhira M, et al. (December 2022). "Activation of basal forebrain cholinergic neurons improves colonic hyperpermeability through the vagus nerve and adenosine A2B receptors in rats". Biochemical Pharmacology. 206: 115331. doi:10.1016/j.bcp.2022.115331. PMID   36330948.
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