132073-83-7Relevant articles and documents
Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER
Tamagnan, Gilles D.,Brenner, Eric,Alagille, David,Staley, Julie K.,Haile, Colin,Koren, Andrei,Early, Michelle,Baldwin, Ronald M.,Tarazi, Frank I.,Baldessarini, Ross J.,Jarkas, Nachwa,Goodman, Mark M.,Seibyl, John P.
, p. 533 - 537 (2007)
A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT im
Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands
Willmann, Michael,Ermert, Johannes,Prante, Olaf,Hübner, Harald,Gmeiner, Peter,Neumaier, Bernd
, p. 43 - 52 (2020/08/03)
Introduction: The dopamine D4 receptor (D4R) has attracted considerable attention as potential target for the treatment of a broad range of central nervous system disorders. Although many efforts have been made to improve the performance of putative radioligand candidates, there is still a lack of D4R selective tracers suitable for in vivo PET imaging. Thus, the objective of this work was to develop a D4-selective PET ligand for clinical applications. Methods: Four compounds based on previous and new lead structures were prepared and characterized with regard to their D4R subtype selectivity and predicted lipophilicity. From these, 3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine I and (S)-4-(3-fluoro-4-methoxybenzyl)-2-(phenoxymethyl)morpholine II were selected for labeling with fluorine-18 and subsequent evaluation by in vitro autoradiography to assess their suitability as D4 radioligand candidates for in vivo imaging. Results: The radiosynthesis of [18F]I and [18F]II was successfully achieved by copper-mediated radiofluorination with radiochemical yields of 7% and 66%, respectively. The radioligand [18F]II showed specific binding in areas where D4 expression is expected, whereas [18F]I did not show any uptake in distinct brain regions and exhibited an unacceptable degree of non-specific binding. Conclusions: The compounds studied exhibited high D4R subtype selectivity and logP values compatible with high brain uptake, but only ligand [18F]II showed low non-specific binding and is therefore a good candidate for further evaluation. Advances in knowledge: The discovery of new lead structures for high-affinity D4 ligands opens up new possibilities for the development of suitable PET-radioligands. Implications for patient: PET-imaging of dopamine D4-receptors could facilitate understanding, diagnosis and treatment of neuropsychiatric and neurodegenerative diseases.
Novel Hydrazinone-substituted Pyrimidine Derivatives and Use Thereof
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Paragraph 0114-0116, (2018/05/29)
The present invention relates to a pyrimidine derivative substituted with novel hydrazine or a pharmaceutically acceptable salt thereof, and to a pharmaceutical composition for inhibiting c-Met tyrosine kinase activity and to a pharmaceutical composition for preventing or treating hyperproliferative disorders, which comprise same as an active ingredient. The present invention can be effectively used as a treatment agent for various hyperproliferative disorders related to excessive cell proliferation and growth caused by abnormal kinase activity, such as cancer, psoriasis, rheumatoid arthritis, and diabetic retinopathy by efficiently inhibiting c-Met tyrosine kinase activity.
Discovery of substituted pyrazol-4-yl pyridazinone derivatives as novel c-Met kinase inhibitors
Kim, Eun-Young,Kang, Seung-Tae,Jung, Heejung,Park, Chi Hoon,Yun, Chang-Soo,Hwang, Jong Yeon,Byun, Byung Jin,Lee, Chong Ock,Kim, Hyoung Rae,Ha, Jae Du,Ryu, Do Hyun,Cho, Sung Yun
, p. 453 - 464 (2016/04/26)
A series of pyridazin-3-one substituted with morpholino-pyrimidine derivatives was synthesized and evaluated as tyrosine kinase inhibitors against c-Met enzyme, and anti-proliferative activities of Hs746T human gastric cancer cell line. Most of compounds exhibited good biological activity, while compound 10, 12a, 14a displayed excellent c-Met enzyme inhibitory activities and Hs746T cell-based activities.
Discovery of substituted 6-pheny-3H-pyridazin-3-one derivatives as novel c-Met kinase inhibitors
Kang, Seung-Tae,Kim, Eun-Young,Archary, Raghavendra,Jung, Heejung,Park, Chi Hoon,Yun, Chang-Soo,Hwang, Jong Yeon,Choi, Sang Un,Chae, Chonghak,Lee, Chong Ock,Kim, Hyoung Rae,Ha, Jae Du,Ryu, Dohyun,Cho, Sung Yun
supporting information, p. 5093 - 5097 (2014/12/11)
We report a series of phenyl substituted pyridazin-3-ones substituted with morpholino-pyrimidines. The SAR of the phenyl was explored and their c-Met kinase and cell-based inhibitory activity toward c-Met driven cell lines were evaluated. Described herein
MORPHOLINO COMPOUNDS, USES AND METHODS
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Paragraph 0172-0175, (2014/06/11)
The invention relates to morpholino-derivatives according to Formula (I) or stereoisomers or pharmaceutically acceptable salts or solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7/s
BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS
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Paragraph 0195, (2014/09/29)
The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.
MORPHOLINO COMPOUNDS, USES AND METHODS
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Page/Page column 48, (2012/12/13)
The invention relates to morpholino-derivatives according to Formula (I) or stereoisomers or pharmaceutically acceptable salts or solvate thereof, wherein R1, R2, R3, R4, R5, R6, R7/s
Sulfinamides as highly effective amine protecting groups and their use in the conversion of Amino alcohols into morpholines
Fritz, Sven P.,Mumtaz, Amara,Yar, Muhammad,McGarrigle, Eoghan M.,Aggarwal, Varinder K.
experimental part, p. 3156 - 3164 (2011/06/28)
1,2-Amino alcohols have been converted into morpholines by using sulfinamides as temporary protecting/activating groups on the amine. We have developed a procedure for the selective synthesis of monoprotected N-sulfinyl amino alcohols through a double sul
PYRAZIN-2-YL-PYRIDIN-2-YL-AMINE AND PYRAZIN-2-YL-PYRIMIDIN-4-YL-AMINE COMPOUNDS AND THEIR USE
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Page/Page column 258-259, (2009/05/29)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain biarylamine compounds (referred to herein as BAA compounds), and especially certain pyrazin- 2 - yl -pyridin- 2 -yl -amine and pyrazine - 2 - yl -pyrimidin- 4 - yl -amine compounds of formula (I), which, inter alia, inhibit Checkpoint Kinase 1 (CHK1 ) kinase function The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1. that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or Il inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionisiπq radiation. wherein: -X= is independently -CRA5= or -N=; and the rest of the substituents are as specified in the claims.