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Z3517967757

From Wikipedia, the free encyclopedia
Chemical compound

Pharmaceutical compound
Z3517967757
Clinical data
Other namesZ7757
Identifiers
  • 4-[1-(1-pyrimidin-2-ylethyl)piperidin-3-yl]phenol
CAS Number
PubChemCID
Chemical and physical data
FormulaC17H21N3O
Molar mass283.375 g·mol−1
3D model (JSmol)
  • CC(C1=NC=CC=N1)N2CCCC(C2)C3=CC=C(C=C3)O
  • InChI=1S/C17H21N3O/c1-13(17-18-9-3-10-19-17)20-11-2-4-15(12-20)14-5-7-16(21)8-6-14/h3,5-10,13,15,21H,2,4,11-12H2,1H3
  • Key:JDCMEPNJYDYSCB-UHFFFAOYSA-N

Z3517967757, or simplyZ7757, is a3-phenylpiperidinederivative which acts as anagonist at the5-HT2 family ofserotoninreceptors, first reported in 2024. It can also be viewed as aring-restrainedphenethylamine.[1] It has strongestactivity at the5-HT2A receptor and loweraffinity at the5-HT2B and5-HT2C receptors. However, it has been reported to have excellentselectivity for the 5-HT2A receptor, with no agonistic activity at the 5-HT2B and 5-HT2C receptors.[1] The drug was developed usingin silico modelling todock a largelibrary of compounds against a 5-HT2A receptor model generated by theartificial intelligence programAlphaFold, and thensynthesised and tested in the laboratory to confirm activity. It has twostereogenic centers and four possibleisomers, but has only been tested as aracemic mixture.[2][3][4]

See also

[edit]

References

[edit]
  1. ^abGumpper RH, Nichols DE (23 August 2024),Chemistry/structural biology of psychedelic drugs and their receptor(s), Authorea, Inc.,doi:10.22541/au.172441788.88647620/v1,Another compound to come out of a large-scale docking screen is the recently reported Z7757 (Figure 5B) (Lyu et al., 2024). This compound was discovered from a 1.6 billion molecule docking screen against the AlphaFold model of the 5-HT2A receptor. Similar to the recent report of LPH-5, Z7757 is a ring-restrained phenethylamine. However, it has a pyrimidine ring substituent coming off the tertiary nitrogen. Remarkably, Z7757 shows excellent selectivity for 5-HT2A with no activity being detected for 5-HT2B or 5-HT2C in calcium mobilization assays, but further optimization to increase potency and in vivo testing is needed.
  2. ^Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, et al. (December 2023)."AlphaFold2 structures template ligand discovery".bioRxiv.doi:10.1101/2023.12.20.572662.PMC 10769324.PMID 38187536.
  3. ^Callaway E (18 January 2024). "AlphaFold found thousands of possible psychedelics. Will its predictions help drug discovery?".Nature News.doi:10.1038/d41586-024-00130-8.PMID 38238624.
  4. ^Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, et al. (May 2024)."AlphaFold2 structures guide prospective ligand discovery".Science eadn6354. New York, N.Y.doi:10.1126/science.adn6354.PMC 11253030.PMID 38753765.
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Phenethylamines
Amphetamines
Phentermines
Cathinones
Phenylisobutylamines
(and further-extended)
Catecholamines
(and close relatives)
Cyclized
phenethylamines
Phenylalkylpyrrolidines
2-Benzylpiperidines
(phenidates)
Phenylmorpholines
(phenmetrazines)
Phenyloxazolamines
(aminorexes)
Isoquinolines and
tetrahydroisoquinolines
2-Aminoindanes
2-Aminotetralins
Others / unsorted
Related compounds


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