139290-70-3Relevant articles and documents
Heteroaromatic and aniline derivatives of piperidines as potent ligands for vesicular acetylcholine transporter
Li, Junfeng,Zhang, Xiang,Zhang, Zhanbin,Padakanti, Prashanth K.,Jin, Hongjun,Cui, Jinquan,Li, Aixiao,Zeng, Dexing,Rath, Nigam P.,Flores, Hubert,Perlmutter, Joel S.,Parsons, Stanley M.,Tu, Zhude
, p. 6216 - 6233 (2013)
To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over σ1 and σ2 receptors (Ki = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[11C]24b (Ki = 0.78 nM for VAChT, 1200-fold over σ receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[11C]24b has highest binding in striatum and has favorable pharmacokinetics in the brain.
Iodonium ylides for one-step, no-carrier-added radiofluorination of electron rich arenes, exemplified with 4-(([18F]fluorophenoxy)- phenylmethyl)piperidine NET and SERT ligands
Cardinale, Jens,Ermert, Johannes,Humpert, Sven,Coenen, Heinz H.
, p. 17293 - 17299 (2014)
Iodonium ylide precursors of electron rich arenes, i.e. the NET and SERT ligands 4-((3- and 4-fluorophenoxy)phenylmethyl)piperidine, served as model compounds for the direct substitution with n.c.a. [18F]fluoride. Good radiochemical yields of a
Discovery of benzimidazole pyrrolidinyl amides as prolylcarboxypeptidase inhibitors
Shen, Hong C.,Ding, Fa-Xiang,Zhou, Changyou,Xiong, Yusheng,Verras, Andreas,Chabin, Renee M.,Xu, Suoyu,Tong, Xinchun,Xie, Dan,Lassman, Michael E.,Bhatt, Urmi R.,Garcia-Calvo, Margarita M.,Geissler, Wayne,Shen, Zhu,Chen, Dunlu,Sinharoy, Ranabir,Hale, Jeffery J.,Tata, James R.,Pinto, Shirly,Shen, Dong-Ming,Colletti, Steven L.
, p. 1299 - 1305 (2011)
A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC50's were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH)
Cai, Qijun,Chen, Jiahui,Chen, Zhen,Fowler, Christopher J.,Gan, Jiefeng,Hou, Lu,Li, Guocong,Liang, Steven H.,Tan, Zhiqiang,Wang, Lu,Xu, Hao,Ye, Weijian,Zheng, Chao
, (2020)
Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC50 value 11 nM at a substrate concentration of 0.5 μM), and without showing time-dependency. The PET tracer [11C]8 (also called [11C]FAAH-1906) was successfully radiolabeled with [11C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [11C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [11C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
1,2,3,4-Tetrahydroquinoline-containing αVβ 3 integrin antagonists with enhanced oral bioavailability
Ghosh, Shyamali,Santulli, Rosemary J.,Kinney, William A.,DeCorte, Bart L.,Liu, Li,Lewis, Joan M.,Proost, Jef C.,Leo, Gregory C.,Masucci, John,Hageman, William E.,Thompson, Andrew S.,Chen, Ian,Kawahama, Reiko,Tuman, Robert W.,Galemmo Jr., Robert A.,Johnson, Dana L.,Damiano, Bruce P.,Maryanoff, Bruce E.
, p. 5937 - 5941 (2004)
Selective reduction of the quinoline yielded potent α vβ53 antagonists with improved oral bioavailability relative to the corresponding quinoline derivatives. Reduction of the quinoline ring in an αvβ3 antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant αVβ3 antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.
ALIPHATIC ACID AMIDE DERIVATIVE
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, (2022/03/19)
The present invention relates to a compound represented by formula (1): the compound having antagonist activity against serotonin 5-HT2A receptors and serotonin 5-HT7 receptors; or a pharmaceutically acceptable salt of the compound. (In the formula, Z is a nitrogen atom and the like; Y is carbonyl and the like; m and n are 1 and the like; R1a through R1d, R2a through R2d, and R4a through R4d are a hydrogen atom and the like; R3 is alkyl and the like; and Q is a specific bicyclic group.)
METHODS AND COMPOSITIONS FOR TARGETING TREGS USING CCR8 INHIBITORS
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Paragraph 0317-0318, (2022/01/12)
Provided herein are compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.
TRPML MODULATORS
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, (2021/06/26)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
AZETIDINE AND SPIROAZETIDINE COMPOUNDS AND USES THEREOF
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Page/Page column 45-46, (2021/12/30)
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
Knez, Damijan,Colettis, Natalia,Iacovino, Luca G.,Sova, Matej,Pi?lar, Anja,Konc, Janez,Le?nik, Samo,Higgs, Josefina,Kamecki, Fabiola,Mangialavori, Irene,Dol?ak, Ana,?akelj, Simon,Trontelj, Jurij,Kos, Janko,Binda, Claudia,Marder, Mariel,Gobec, Stanislav
, p. 1361 - 1387 (2020/03/10)
The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.
