SB-271046

SB-271046
SB-271046
SB-271,046 structure.png
식별자
  • 5-클로로-N-(4-메톡시-3-피페라진-1-ylphenyl)-3-메틸-1-벤조티오페네-2-술포나미드
CAS 번호
펍켐 CID
IUPHAR/BPS
켐스파이더
유니
켐벨
화학 및 물리적 데이터
공식C20H22CLN3O3S2
어금질량451.98 g·190−1
3D 모델(JSmol)
  • C4CNCCN4c3cc(ccc3OC)NS(=O)c1sc2cc(Cl)cc2c1C
  • InChI=1S/C20H22ClN3O3S2/c1-13-16-11-14(21)3-6-19(16)28-20(13)29(25,26)23-15-4-5-18(27-2)17(12-15)24-9-7-22-8-10-24/h3-6,11-12,22-23H,7-10H2,1-2H3 ☒N
  • 키:LOCQRDBFWS신방신기-UHFFFAOYSA-N
☒NcheckY (이게 뭐야?) (iii)

SB-271046은 과학 연구에 사용되는 약물이다. 최초로 발견된 선택적 5-HT6 수용체 길항제 중 하나였으며, 복제된 5-HT6 수용체를 대상으로 스미스클라인 비첨 복합은행의 고투과 선별을 통해 발견되었으며, 초기 납 화합물은 SAR(구조-활동 관계) 연구를 통해 SB-271046으로 개발되었다.[1] SB-271046은 체외에서 강력하고 선택적 생체이용률이 높았으나 혈액-뇌장벽에 걸쳐 침투력이 좋지 않아 SB-357,134,SB-399,885와 같은 5-HT6 길항자를 개선한 것으로 조사되었다.[2]

SB-271046은 흥분성 아미노산 신경전달물질 글루탐산염과 아스파테이트뿐만 아니라 [3]쥐의 전두피질과 해마에서 도파민, 노르아드레날린[4] 등의 수치를 증가시키는 것으로 밝혀졌으며,[5] 5-HT6 길항제들은 다양한 동물 연구에서 비등방성 효과를 내는 것으로 밝혀졌다.[6][7][8] 이러한 약물들의 제안된 적용은 정신분열증 치료와 다른 정신질환을 포함한다.[9][10][11][12]

참조

  1. ^ Bromidge SM, Brown AM, Clarke SE, Dodgson K, Gager T, Grassam HL, et al. (January 1999). "5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor antagonist". Journal of Medicinal Chemistry. 42 (2): 202–5. doi:10.1021/jm980532e. PMID 9925723.
  2. ^ Ahmed M, Briggs MA, Bromidge SM, Buck T, Campbell L, Deeks NJ, et al. (November 2005). "Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 15 (21): 4867–71. doi:10.1016/j.bmcl.2005.06.107. PMID 16143522.
  3. ^ Dawson LA, Nguyen HQ, Li P (May 2000). "In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate". British Journal of Pharmacology. 130 (1): 23–6. doi:10.1038/sj.bjp.0703288. PMC 1572041. PMID 10780993.
  4. ^ Lacroix LP, Dawson LA, Hagan JJ, Heidbreder CA (February 2004). "5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex". Synapse. 51 (2): 158–64. doi:10.1002/syn.10288. PMID 14618683. S2CID 6539467.
  5. ^ Dawson LA, Nguyen HQ, Li P (November 2001). "The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus". Neuropsychopharmacology. 25 (5): 662–8. doi:10.1016/S0893-133X(01)00265-2. PMID 11682249.
  6. ^ Rogers DC, Hagan JJ (November 2001). "5-HT6 receptor antagonists enhance retention of a water maze task in the rat". Psychopharmacology. 158 (2): 114–9. doi:10.1007/s002130100840. PMID 11702084. S2CID 29472459.
  7. ^ Foley AG, Murphy KJ, Hirst WD, Gallagher HC, Hagan JJ, Upton N, et al. (January 2004). "The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats". Neuropsychopharmacology. 29 (1): 93–100. doi:10.1038/sj.npp.1300332. PMID 14571256.
  8. ^ Marcos B, Chuang TT, Gil-Bea FJ, Ramirez MJ (October 2008). "Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat". British Journal of Pharmacology. 155 (3): 434–40. doi:10.1038/bjp.2008.281. PMC 2567877. PMID 18622410.
  9. ^ Minabe Y, Shirayama Y, Hashimoto K, Routledge C, Hagan JJ, Ashby CR (April 2004). "Effect of the acute and chronic administration of the selective 5-HT6 receptor antagonist SB-271046 on the activity of midbrain dopamine neurons in rats: an in vivo electrophysiological study". Synapse. 52 (1): 20–8. doi:10.1002/syn.20002. PMID 14755629. S2CID 25687099.
  10. ^ de Foubert G, O'Neill MJ, Zetterström TS (July 2007). "Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression". Neuroscience. 147 (3): 778–85. doi:10.1016/j.neuroscience.2007.04.045. PMID 17560041. S2CID 37184427.
  11. ^ Marcos B, Aisa B, Ramírez MJ (March 2008). "Functional interaction between 5-HT(6) receptors and hypothalamic-pituitary-adrenal axis: cognitive implications". Neuropharmacology. 54 (4): 708–14. doi:10.1016/j.neuropharm.2007.11.019. PMID 18206183. S2CID 21417069.
  12. ^ Loiseau F, Dekeyne A, Millan MJ (January 2008). "Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex". Psychopharmacology. 196 (1): 93–104. doi:10.1007/s00213-007-0934-5. PMID 17922111. S2CID 35795618.
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신경계통에 관한 이 약물 기사는 단조롭다. 위키피디아를 확장하여 도울 수 있다.