scholarly journals Design, synthesis, and in vitro and in vivo characterization of 1-{4-[4-(substituted)piperazin-1-yl]butyl}guanidines and their piperidine analogues as histamine H3 receptor antagonists

MedChemComm ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 234-251 ◽  
Author(s):  
Marek Staszewski ◽  
Anna Stasiak ◽  
Tadeusz Karcz ◽  
Daniel McNaught Flores ◽  
Wiesława Agnieszka Fogel ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Design Synthesis ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
In Vivo Characterization ◽  
Histamine H3

The prominent members of 1-{4-[4-(substituted)piperazin-1-yl]butyl}guanidines as histamine H3 receptor antagonists.

ChemInform Abstract: Substituted N-Phenylcarbamates as Histamine H3 Receptor Antagonists with Improved in vivo Potency.

ChemInform ◽  
2010 ◽  
Vol 31 (24) ◽  
pp. no-no
Author(s):  
S. Reidemeister ◽  
H. Stark ◽  
X. Ligneau ◽  
C. R. Ganellin ◽  
J.-C. Schwartz ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

scholarly journals A Novel Potent and Selective Histamine H3 Receptor Antagonist Enerisant: In Vitro Profiles, In Vivo Receptor Occupancy, and Wake-Promoting and Procognitive Effects in Rodents

2020 ◽  
Vol 375 (2) ◽  
pp. 276-285
Author(s):  
Noriko Hino ◽  
Toshiyuki Marumo ◽  
Makiko Kotani ◽  
Toshiharu Shimazaki ◽  
Ayaka Kaku-Fukumoto ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Receptor Occupancy ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

0155 SUVN-G3031, A Potent and Selective Histamine H3 Receptor Inverse Agonist - Differentiating Features Over Current Treatments of Narcolepsy

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A61-A61
Author(s):  
A Shinde ◽  
R Subramanian ◽  
R Palacharla ◽  
S Pandey ◽  
V Benade ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Abuse Liability ◽  
Species Variation ◽  
Pharmacological Agents ◽  
Histamine H3 Receptor ◽  
Inverse Agonists ◽  
H3 Receptor ◽  
Histamine H3

Abstract Introduction Majority of pharmacological agents used in the treatment of narcolepsy have several limitations. Both nonclinical and clinical evidences suggest usefulness of the histamine H3 receptor (H3R) inverse agonists for the treatment of narcolepsy and addressing several of the current limitations. Methods Extensive nonclinical studies were carried out for SUVN-G3031 and other pharmacological agents that are currently being used for the treatment of narcolepsy. Nonclinical parameters like inter-species binding affinity, selectivity profile, in vivo and in vitro ADME features, nonclinical efficacy, neurochemistry and safety were compared. Results SUVN-G3031 has no inter-species variation in binding affinity at H3R with less than 50% inhibition at 1 µM against 70 other targets. Unlike pitolisant, SUVN-G3031 has no significant binding affinity at sigma 1 and 2 receptor. SUVN-G3031 has no inhibition and induction liability towards major CYP enzymes and transporters. Pitolisant is reported to be a CYP3A4, CYP2B6, and CYP1A2 inducer and a CYP2D6 and OCT1 inhibitor. SUVN-G3031 has robust wake promoting effects. SUVN-G3031 showed negligible affinity towards hERG channel with IC50 > 10 µM and had no effects on any ECG parameters in dog telemetry study. SUVN-G3031 did not show convulsion in rats up to the tested dose of 100 mg/kg, p.o. Most of the pharmacological agents used for the treatment of narcolepsy have abuse liability; SUVN-G3031 produced no change in the striatal and accumbal dopamine levels in rats suggesting no propensity to induce abuse liability. Unlike competing H3R inverse agonists, SUVN-G3031 has no effects on fertility and embryo-fetal development up to the highest tested doses. Conclusion Nonclinical studies demonstrate superiority of SUVN-G3031 over pharmacological agents currently used in the treatment of narcolepsy. SUVN-G3031 is being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support None

Design, Synthesis, In Vitro, and In Vivo Characterization of Phenylpiperazines and Pyridinylpiperazines as Potent and Selective Antagonists of the Melanocortin-4 Receptor

2007 ◽  
Vol 50 (25) ◽  
pp. 6356-6366 ◽  
Author(s):  
Joe A. Tran ◽  
Wanlong Jiang ◽  
Fabio C. Tucci ◽  
Beth A. Fleck ◽  
Jenny Wen ◽  
...  
Keyword(s):  
Design Synthesis ◽  
Selective Antagonists ◽  
Melanocortin 4 Receptor ◽  
In Vivo Characterization

scholarly journals In vitro and in vivo characterization of NK3 receptors in the rabbit eye by use of selective non-peptide NK3 receptor antagonists

1997 ◽  
Vol 122 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Andrew D. Medhurst ◽  
Douglas W. P. Hay ◽  
Andrew A. Parsons ◽  
Lenox D. Martin ◽  
Don E. Griswold
Keyword(s):  
Receptor Antagonists ◽  
Rabbit Eye ◽  
Nk3 Receptor ◽  
In Vivo Characterization

Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: Identification of candidates for clinical development

2010 ◽  
Vol 20 (14) ◽  
pp. 4210-4214 ◽  
Author(s):  
Michael A. Letavic ◽  
Leah Aluisio ◽  
John R. Atack ◽  
Pascal Bonaventure ◽  
Nicholas I. Carruthers ◽  
...  
Keyword(s):  
Clinical Development ◽  
Receptor Antagonists ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

In vitro and in vivo characterization of novel nonsteroidal progesterone receptor antagonists derived from the fungal metabolite PF1092C

2002 ◽  
Vol 82 (2-3) ◽  
pp. 217-223 ◽  
Author(s):  
Yuji Tabata ◽  
Yumiko Iizuka ◽  
Naomi Takei Masuda ◽  
Rie Shinei ◽  
Ken-ichi Kurihara ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Fungal Metabolite ◽  
Receptor Antagonists ◽  
In Vivo Characterization

ChemInform Abstract: Diphenylmethyl Ethers: Synthesis and Histamine H3-Receptor Antagonist in vitro and in vivo Activity.

ChemInform ◽  
2010 ◽  
Vol 27 (52) ◽  
pp. no-no
Author(s):  
A. HUELS ◽  
K. PURAND ◽  
H. STARK ◽  
X. LIGNEAU ◽  
J.-M. ARRANG ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3

Novel heterocyclic-substituted benzofuran histamine H3 receptor antagonists: In vitro properties, drug-likeness, and behavioral activity

2007 ◽  
Vol 73 (8) ◽  
pp. 1243-1255 ◽  
Author(s):  
Marlon Cowart ◽  
Gregory A. Gfesser ◽  
Kaitlin E. Browman ◽  
Ramin Faghih ◽  
Thomas R. Miller ◽  
...  
Keyword(s):  
Behavioral Activity ◽  
Receptor Antagonists ◽  
Histamine H3 Receptor ◽  
H3 Receptor ◽  
Histamine H3
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