Movatterモバイル変換

[0]ホーム
URL:

Jump to content
WikipediaThe Free Encyclopedia
Search

LY-178210

From Wikipedia, the free encyclopedia

Pharmaceutical compound
LY-178210
Clinical data
Other namesLY178210; LY-228729; LY228729
Drug classSerotonin5-HT1A receptorpartial agonist
Identifiers
  • 4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indole-6-carboxamide
CAS Number
PubChemCID
ChemSpider
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC18H25N3O
Molar mass299.418 g·mol−1
3D model (JSmol)
  • CCCN(CCC)C1CC2=CNC3=C2C(=C(C=C3)C(=O)N)C1
  • InChI=1S/C18H25N3O/c1-3-7-21(8-4-2)13-9-12-11-20-16-6-5-14(18(19)22)15(10-13)17(12)16/h5-6,11,13,20H,3-4,7-10H2,1-2H3,(H2,19,22)
  • Key:YTOJFUORFUYGSV-UHFFFAOYSA-N

LY-178210 is aselective and highlypotentserotonin5-HT1A receptorpartial agonist.[1][2][3][4] It has anaffinity (Ki) of 0.67 nM for the serotonin 5-HT1A receptor.[1][3] The drug has high selectivity for this receptor over 12 other assessedtargets, including theserotonin5-HT1D,5-HT2A,5-HT2C, and5-HT3 receptors among others (Ki = ≥380–4,000 nM).[4][2][5] LY-178210 is atricyclicsimplified or partial ergoline and isstructurally related toLSD.[2][1][6] It was described as a potentialclinical development candidate but was not further developed and was never marketed.[5] The drug was first reported in thescientific literature by 1990.[4]

See also

[edit]

References

[edit]
  1. ^abcGlennon RA (1992). "Concepts for the design of 5-HT 1A serotonin agonists and antagonists".Drug Development Research.26 (3):251–274.doi:10.1002/ddr.430260306.ISSN 0272-4391.Fig. 1. Structures of some indolealkylamines: 5-HT 5-CAT (2), RU 24969 (3), (+)LSD (4), RU 28306 (5), BAY R 1531 (6), and LY 178210 (7). [...] Partial ergolines have also been examined [Flaugh et al., 1988]. For example, RU 28306 (5) binds at 5-HT1, sites with relatively low affinity (Ki = 329 nM) [Taylor et al., 1987]; however, the corresponding N,N-dipropyl-6-substituted analogs BAY R 1531 (6) [Glaser et al., 1987] and LY 178210 (7) [Slaughter et al., 1990] bind with significantly higher affinity (Ki <1 nM). These latter two agents, as with O-methyl DiPS [Glennon et al., 1988a] and N,N-dipropyl-5-carboxamidotryptamine [Hibert et al., 1987], possess 5-HT1, agonist activity. The hydroxy analog of compound 6 is apparently a full agonist [Seiler et al., 1990] whereas LY 178210 (7) acts as a partial agonist in an adenylate cyclase assay [Slaughter et al., 1990].
  2. ^abcAudia JE, Cohen ML (1991). "Chapter 11. Serotonin Modulators and Cardiovascular/Gastrointestinal Diseases".Annual Reports in Medicinal Chemistry. Vol. 26. Elsevier. pp. 103–112.doi:10.1016/s0065-7743(08)61198-7.ISBN 978-0-12-040526-8.Ergolines and Partial Ergolines - Although primarily investigated as 5-HT2 receptor ligands, several ergolines, including lisuride and lysergic acid diethylamide (LSD), show high affinity for 5-HT1A receptors, although they lack selectivity (47). Some partial ergolines, including LY 178210 (8) and LY 197206 (9), show surprising selectivity as 5-HT1A agonists relative to related ergolines (65). This specificity, however, can be more readily rationalized by recognizing the similarities to the 5-HT1A-selective aminotetralins [...] From an SAR perspective, a partial ergoline such as LY 178210 (Q) does not retain this high affinity for the 5-HT1C receptor (65). [...] Miscellaneous Structures - Many ergolines, particularly metergoline and methysergide have high affinity for the 5-HT1D receptor, while other ergolines such as mesulergine and the partial ergoline LY 178210 (9) lack significant affinity at this receptor subtype (65).
  3. ^abNelson DL (December 1991). "Structure-activity relationships at 5-HT1A receptors: binding profiles and intrinsic activity".Pharmacology, Biochemistry, and Behavior.40 (4):1041–1051.doi:10.1016/0091-3057(91)90124-k.PMID 1816558.Table 3 Effect on 5-HT1A Affinity by Substitutions at the C6 Position of a Series of Tricyclic Partial Ergolines [...]
  4. ^abcSlaughter JL, Harrington MA, Peroutka SJ (1990)."6-substituted tricyclic partial ergoline compounds are selective and potent 5-hydroxytryptamine1A receptor agents".Life Sciences.47 (15):1331–1337.doi:10.1016/0024-3205(90)90197-y.PMID 2172684.
  5. ^abPerregaard J, Sánchez C, Arnt J (1993). "Overview: Recent Developments in Anxiolytics".Current Opinion on Therapeutic Patents.3 (1):101–128.doi:10.1517/13543776.3.1.101.ISSN 0962-2594.Many of the Lilly compounds (25) were shown to have nanomolar affinity for 5-HT1D, as well as for 5-HT1A, receptors. An exception is the clinical development candidate LY 178210, which has 500-fold less affinity for 5-HT1D receptors than for 5-HT1A receptors [88].
  6. ^Vangveravong S (1994).Synthesis of trans-2-(indol-3-yl)cyclopropylamines: Rigid tryptamine analogues (Ph.D. thesis). Purdue University.ProQuest 304131663. Retrieved22 March 2025.Figure 5. Rigid Serotonin Receptor Ligands [...]
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Stub icon

Thispsychoactive drug-related article is astub. You can help Wikipedia byexpanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=LY-178210&oldid=1284379713"
Categories:
Hidden categories:
[8]ページ先頭
©2009-2025 Movatter.jp