LY-341495

LY-341495
LY-341495
LY-341,495.svg
임상 데이터
기타 이름(2S)-2-아미노-2-[(1S,2S)-2-카르복시클로프로프-1-일]-3-(크산트-9-일)프로판산
식별자
  • 2-[(1S, 2S)-2-카르복시클로프로필]-3-(9H-크산텐-9-일)-D-알라닌
CAS 번호
켐스파이더
CompTox 대시보드 (EPA )
화학 및 물리 데이터
공식C20H19NO5
몰 질량353.374 g/120−1
3D 모델(JSmol)
  • C1[C@@H]([C@H]1)[C@@](CC2C3=CC=CC=C3OC4=CC=CC=C24)(C(=O)O)N)C(=O)O
  • InChI=1S/C20H19NO5/c21-20(19)25,15-9-13(15)18(22)23)10-14)10-14-11-5-1-3-7-16(11)26-17-8-2-6-12(14)17/1-8,13-159,10,15,10)
  • 키: VLZBRVJVCCNPRJ-KPHUOKFYSA-N ☒N
☒NcheckY (이게 뭐죠?) (표준)

LY-341495는 제약회사 Eli Lilly에 의해 개발된 연구약으로, II 그룹 메타이트로픽 글루탐산 수용체(mGluR2/3)[1][2][3][4]에 대한 강력하고 선택적인 오르토스테릭 길항제 역할을 한다.

그것은 동물 [5][6][7][8]모델에서 항우울제 효과를 보여주고, 동물 [9][10][11][12]실험에서 환각 유발 약물의 행동 효과를 증가시키며, μ-오피오이드 작용제의 [13][14]진통제 효과를 증가시키며, 도파민 [15][16][17]수용체 기능을 조절하는 등 여러 다른 분야의 과학 연구에 사용된다.

1-플루오로시클로프로판 유사체는 우수한 약동학적 프로파일과 유사한 mGluR2/3 친화력을 가지며, 헵틸에스테르로 프로드러그를 생성하면 생체 가용성이 더욱 [18]높아진다.

1-플루오로-LY-341,495 헵틸에스테르

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레퍼런스

  1. ^ Ornstein PL, Bleisch TJ, Arnold MB, Kennedy JH, Wright RA, Johnson BG, Tizzano JP, Helton DR, Kallman MJ, Schoepp DD, Hérin M (January 1998). "2-substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioavailability". Journal of Medicinal Chemistry. 41 (3): 358–78. doi:10.1021/jm970498o. PMID 9464367.
  2. ^ Kingston AE, Ornstein PL, Wright RA, Johnson BG, Mayne NG, Burnett JP, Belagaje R, Wu S, Schoepp DD. "LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors". Neuropharmacology. 37 (1): 1–12. doi:10.1016/s0028-3908(97)00191-3. PMID 9680254.
  3. ^ Fitzjohn SM, Bortolotto ZA, Palmer MJ, Doherty AJ, Ornstein PL, Schoepp DD, Kingston AE, Lodge D, Collingridge GL (December 1998). "The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity". Neuropharmacology. 37 (12): 1445–58. doi:10.1016/s0028-3908(98)00145-2. PMID 9886667.
  4. ^ Johnson BG, Wright RA, Arnold MB, Wheeler WJ, Ornstein PL, Schoepp DD (October 1999). "[3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells". Neuropharmacology. 38 (10): 1519–29. doi:10.1016/s0028-3908(99)00053-2. PMID 10530814.
  5. ^ Pilc A, Chaki S, Nowak G, Witkin JM (March 2008). "Mood disorders: regulation by metabotropic glutamate receptors". Biochemical Pharmacology. 75 (5): 997–1006. doi:10.1016/j.bcp.2007.09.021. PMID 18164691.
  6. ^ Matrisciano F, Panaccione I, Zusso M, Giusti P, Tatarelli R, Iacovelli L, Mathé AA, Gruber SH, Nicoletti F, Girardi P (August 2007). "Group-II metabotropic glutamate receptor ligands as adjunctive drugs in the treatment of depression: a new strategy to shorten the latency of antidepressant medication?". Molecular Psychiatry. 12 (8): 704–6. doi:10.1038/sj.mp.4002005. PMID 17653204.
  7. ^ Koike H, Chaki S (September 2014). "Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats". Behavioural Brain Research. 271: 111–5. doi:10.1016/j.bbr.2014.05.065. PMID 24909673.
  8. ^ Lepack AE, Bang E, Lee B, Dwyer JM, Duman RS (December 2016). "Fast-acting antidepressants rapidly stimulate ERK signaling and BDNF release in primary neuronal cultures". Neuropharmacology. 111: 242–252. doi:10.1016/j.neuropharm.2016.09.011. PMC 5075989. PMID 27634096.
  9. ^ Gewirtz JC, Marek GJ (November 2000). "Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors". Neuropsychopharmacology. 23 (5): 569–76. doi:10.1016/S0893-133X(00)00136-6. PMID 11027922.
  10. ^ Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E (August 2007). "A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis". Molecular Pharmacology. 72 (2): 477–84. doi:10.1124/mol.107.035170. PMID 17526600.
  11. ^ Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB (January 2015). "The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice". Psychopharmacology. 232 (1): 275–84. doi:10.1007/s00213-014-3658-3. PMC 4282596. PMID 24985890.
  12. ^ Moreno JL, González-Maeso J. "Crosstalk Between 5-HT2A and mGlu2 Receptors: Implications in Schizophrenia and Its Treatment". 5-HT2A Receptors in the Central Nervous System. The Receptors. Vol. 32. pp. 147–189. doi:10.1007/978-3-319-70474-6_7. ISBN 978-3-319-70472-2.
  13. ^ Fischer BD, Miller LL, Henry FE, Picker MJ, Dykstra LA (June 2008). "Increased efficacy of micro-opioid agonist-induced antinociception by metabotropic glutamate receptor antagonists in C57BL/6 mice: comparison with (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959)". Psychopharmacology. 198 (2): 271–8. doi:10.1007/s00213-008-1130-y. PMID 18392754.
  14. ^ Fischer BD, Zimmerman EI, Picker MJ, Dykstra LA (February 2008). "Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception". The Journal of Pharmacology and Experimental Therapeutics. 324 (2): 732–9. doi:10.1124/jpet.107.131417. PMID 17982001.
  15. ^ O'Neill MF, Heron-Maxwell C, Conway MW, Monn JA, Ornstein P (October 2003). "Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice". Neuropharmacology. 45 (5): 565–74. doi:10.1016/S0028-3908(03)00232-6. PMID 12941370.
  16. ^ Chi H, Jang JK, Kim JH, Vezina P (October 2006). "Blockade of group II metabotropic glutamate receptors in the nucleus accumbens produces hyperlocomotion in rats previously exposed to amphetamine". Neuropharmacology. 51 (5): 986–92. doi:10.1016/j.neuropharm.2006.06.008. PMID 16901517.
  17. ^ Yoon HS, Jang JK, Kim JH (September 2008). "Blockade of group II metabotropic glutamate receptors produces hyper-locomotion in cocaine pre-exposed rats by interactions with dopamine receptors". Neuropharmacology. 55 (4): 555–9. doi:10.1016/j.neuropharm.2008.07.012. PMID 18675831.
  18. ^ Sakagami K, Yasuhara A, Chaki S, Yoshikawa R, Kawakita Y, Saito A, Taguchi T, Nakazato A (April 2008). "Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist". Bioorganic & Medicinal Chemistry. 16 (8): 4359–66. doi:10.1016/j.bmc.2008.02.066. PMID 18348906.