4 research outputs found
Search for a 5-CT alternative. In vitro and in vivo evaluation of novel pharmacological tools: 3-(1-alkyl-1H-imidazol-5-yl)-1H-indole-5-carboxamides, low-basicity 5-HT7 receptor agonists
- Author
- Publication venue
- 'Royal Society of Chemistry (RSC)'
- Publication date
- 01/01/2018
- Field of study
Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol
- Author
- Publication venue
- Publication date
- 01/01/2017
- Field of study
A series of 5-aryl-1-alkylimidazole derivatives was synthesized using the van Leusen multicomponent
reaction. The chemotype is the first example of low-basicity scaffolds exhibiting high affinity for 5-HT7
receptor together with agonist function. The chosen lead compounds 3-(1-ethyl-1H-imidazol-5-yl)-5-
iodo-1H-indole (AGH-107, 1o, Ki 5-HT7=6nM, EC50=19nM, 176-fold selectivity over 5-HT1AR) and 1e
(5-methoxy analogue, Ki 5-HT7=30nM, EC50=60nM) exhibited high selectivity over related CNS targets,
high metabolic stability and low toxicity in HEK-293 and HepG2 cell cultures. A rapid absorption to the
blood, high blood-brain barrier permeation and a very high peak concentration in the brain (Cmax=2723
ng/g) were found for 1o after i.p. (5mg/kg) administration in mice. The compound was found active
in novel object recognition test in mice, at 0.5, 1 and 5mg/kg. Docking to 5-HT7R homology models
indicated a plausible binding mode which explain the unusually high selectivity over the related CNS
targets. Halogen bond formation between the most potent derivatives and the receptor is consistent
with both the docking results and SAR. 5-Chlorine, bromine and iodine substitution resulted in a 13, 27
and 89-fold increase in binding affinities, respectively, and in enhanced 5-HT1AR selectivity
Radiolabeling and in vivo evaluation of [11C]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor
- Author
- A Matthys
- Adam S. Hogendorf
- Agata Hogendorf
- AJ Schwarz
- Andreas Kjær
- Andrzej J. Bojarski
- AS Hogendorf
- DV Garcia
- Elina T. L’Estrade
- Gitte M. Knudsen
- HD Hansen
- HD Hansen
- Ida N. Petersen
- J Andries
- Jesper L. Kristensen
- L Lemoine
- M Guscott
- M Herth
- M Piel
- M Ruat
- Maria Erlandsson
- Matthias M. Herth
- Mengfei Xiong
- MM Herth
- MM Herth
- MM Herth
- N Gillings
- PB Hedlund
- R Kallem
- S Syvänen
- Tomas Ohlsson
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries
- Author
- ?tinas A
- Aalem HAA
- Ababneh H
- Abbas A
- Abbas A
- Abbas H
- Abbasi A
- Abbassi F
- Abbasy J
- Abbood AH
- Abboud K
- Abdallah A
- Abdalsalam SJA
- Abdelaal A
- Abdelalemm M
- Abdelhafez MHZ
- Abdelhalim K
- Abdeljalil M
- Abdelkarem M
- Abdelmageed A
- Abdelmageed A
- Abdelmaksoud M
- Abdelmawgoud S
- Abdelmawla M
- Abdelmawla MOMK
- Abdelmoneim N
- Abdelnoor A
- Abdelrahman F
- Abdelrazek HA
- Abdelrhman R
- Abdelzaher A
- Abdelzaher AT
- Abdou K
- Abdoun M
- Abdualqader M
- Abdualqader MYM
- Abdulhaq A
- Abduljawad H
- Abdullaev A
- Abdullah NAN
- Abdulmonem A
- Abdulwahed E
- Abebrese J
- Abiyere H
- Abobakr AM
- Aboelfath S
- Abosamak NE
- Abu Harb Z
- Abu Hilal M
- Abu Hilal M
- Abu Jayyab M
- Abu-Elfatth AM
- Abu-Ghazal S
- Abu-Ghazal SY
- Abuali ASAME
- Abuelazm M
- Abuelnaga Y
- Abuelnaga Y
- Abughazal SY
- Abuleil A
- Abusannuga M
- Abuzaina K
- Adam I
- Aday U
- Adeyeye A
- Adeyeye NA
- Adham M
- Adhikari KM
- Affary AA
- Afzal A
- Afzal I
- Aghdassi A
- Ahmadi BE
- Ahmed EA
- Ahmed MBE
- Ahmed R
- Ahmeed
- Ajayi P
- Akahoshi K
- Akbar A
- Akhtar N
- Al-Abdi R
- Al-Abed O
- Al-Ameri S
- Al-Ameri SAAS
- Al-Asadi MAMM
- Al-Dowsh NA
- Al-Eryani F
- Al-Faiq S
- Al-Haj A
- Al-Hyari A
- Al-Isawi A
- Al-juaifari MA
- Al-Khawlani Q
- Al-Kubati W
- Al-Maadani B
- Al-Mallah R
- Al-Markiz E
- Al-Mekhlafi A
- Al-Melhani W
- Al-Naggar H
- Al-Naggar H
- Al-Ogaili M
- Al-Qasrawi S
- Al-Saban R
- Al-saban RAM
- Al-Sader MA-J
- Al-Samawi A
- Al-Samawi H
- Al-Sarireh B
- Al-Shami K
- Al-shami M
- Al-sharabi EAE
- Al-Shehari M
- Al-Tekreeti S
- Alahmed F
- Alahmed H
- Alaimo L
- Alali MB
- Alannaz O
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- Alatise O
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- Albaba S
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- Albar A
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- Albishti A
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- Alegria CR
- Alfano MS
- Alfatah MA
- Alfonso C
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- Alhashemi M
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- Ali AYM
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- Aliwy MA
- Aljaber A
- Aljamal S
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- Alkhadem MA
- Alkhaleel W
- Alkhateb H
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- Allam A
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- Alsoudani A
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- Amina H
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- Štironja I
- Publication venue
- Publication date
- 18/01/2024
- Field of study