- Radiosynthesis and evaluation of 18F-labeled dopamine D4-receptor ligands
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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.
- Willmann, Michael,Ermert, Johannes,Prante, Olaf,Hübner, Harald,Gmeiner, Peter,Neumaier, Bernd
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- COMPOUNDS
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The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).
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Page/Page column 123
(2015/09/23)
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- CXCR4 Receptor Antagonists
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Disclosed are compounds that are antagonists of the CXCR4 receptor.
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Paragraph 0368; 0369
(2013/11/06)
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- Sulfinamides as highly effective amine protecting groups and their use in the conversion of Amino alcohols into morpholines
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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
- Fritz, Sven P.,Mumtaz, Amara,Yar, Muhammad,McGarrigle, Eoghan M.,Aggarwal, Varinder K.
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experimental part
p. 3156 - 3164
(2011/06/28)
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- BENZAMIDE DERIVATIVES, THEIR PREPARATION AND USES IN MEDICINE THEREOF
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The present invention discloses novel benzamide derivatives represented by general formula (I), their preparation, pharmaceutical compositions containing the derivatives and their use as medicament, especially as a 5-HT4 stimulator, wherein the
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Page/Page column 14
(2010/06/15)
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- BENZAMIDE DERIVATIVES, THEIR PREPARATION AND USES IN MEDICINE THEREOF
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The present invention discloses novel benzamide derivatives represented by general formula (I), their preparation, pharmaceutical compositions containing the derivatives and their use as medicament, especially as a 5-HT4 stimulator, wherein the
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Page/Page column 13
(2010/08/22)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present application relates to cannabinoid receptor ligands of formula (I) wherein X1, A1, Rx, R2, R3, R4, and z are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions.
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Page/Page column 37
(2010/04/23)
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- PYRAZIN-2-YL-PYRIDIN-2-YL-AMINE AND PYRAZIN-2-YL-PYRIMIDIN-4-YL-AMINE COMPOUNDS AND THEIR USE
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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.
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Page/Page column 259
(2009/05/29)
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- PIPERAZINES AS ANTI-OBESITY AGENTS
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The present invention relates to new compounds of formula (I), to pharmaceutical compositions comprising these compounds, to processes for their preparation, and to the use of these compounds as leptin receptor modulator mimetics in the preparation of medicaments against conditions associated with weight gain, type 2 diabetes and dyslipidemias.
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Page/Page column 30-31
(2009/07/17)
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- Concise synthesis of (S)-N-BOC-2-hydroxymethylmorpholine and (S)-N-BOC-morpholine-2-carboxylic acid
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(Chemical Equation Presented) An operationally simple synthesis of N-BOC-2-hydroxymethylmorpholine (1) and N-BOC-morpholine-2-carboxylic acid (2) from epichlorohydrin has been developed. No chromatography is required in the processing, which allows high p
- Henegar, Kevin E.
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p. 3662 - 3665
(2008/09/20)
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- METHODS OF USE FOR INHIBITORS OF AKT ACTIVITY
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Invented is the use of 1 H-imidazo[4,5-c]pyridin-2-yl compounds in the treatment of specified cancers.
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Page/Page column 44
(2008/12/04)
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- CYSTEINE PROTEASE INHIBITORS
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Stereoisomers of the formula (III) wherein R is H or C1-C3 optionally halo-substituted alkyl; or pharmaceutically acceptable salts, hydrates or N-oxides thereof have utility in the treatment of disorders mediated by inappropriate exp
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Page/Page column 38-39
(2008/06/13)
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- NOREPINEPHRINE TRANSPORTER RADIOTRACERS AND METHODS OF SYNTHESES THEREOF
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The present invention provides compounds and radiotracers thereof for locating, diagnosing, identifying, evaluating, detecting or quantitating NET by in vivo imaging. The invention also provides methods for locating, diagnosing, identifying, evaluating, detecting or quantitating NET, using radiotracers of high-affinity or labeled compounds of the invention, which exhibit low toxicity, can cross the blood-brain barrier and, preferably, distinguish among normal and abnormal brains. For example, a radiotracer of the invention can be administered to a patient in an amount suitable for in vivo imaging thereof. Preferably, radiotracers of the invention can also be used to locate, diagnosis, identify, evaluate, detect and quantitate NET in such diseases, disorders, conditions or maladies as, without limitation, depression, anxiety, ADHD and drug dependency.
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Page/Page column 52
(2008/06/13)
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- Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER
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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
- 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.
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p. 533 - 537
(2007/10/03)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 50
(2008/06/13)
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- HETEROARYL UREA DERIVATIVES USEFUL FOR INHIBITING CHKl
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Substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division, also are disclosed.
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- Therapeutic pyrazolo[3,4-B]pyridines and indazoles
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The present invention provides for compounds of Formula I: wherein R2, R3, R4, R5, R6, R7, X, and L have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of central nervous disorders and conditions including attention deficit hyperactivity disorder, neuropathic pain, urinary incontinence, anxiety, depression, and schizophrenia and fibromyalgia. Also provided are pharmaceutical compositions comprising one or more compounds of Formula I.
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Page/Page column 13
(2008/06/13)
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- Asymmetric synthesis of (+)-(S,S)-reboxetine via a new (S)-2- (hydroxymethyl)morpholine preparation
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(Chemical Equation Presented) (S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99% ee in eight steps. Key steps were selective oxidation of an N-protected hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic substitution.
- Brenner, Eric,Baldwin, Ronald M.,Tamagnan, Gilles
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p. 937 - 939
(2007/10/03)
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- FACILE SYNTHESIS OF OPTICALLY ACTIVE SULFONATES OF 4-tert-BUTOXYCARBONYL-2-HYDROXYMETHYLMORPHOLINE
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Optically active sulfonates of 4-tert-butoxycarbonyl-2-hydroxymethylmorpholine were prepared from 1,2:5,6-di-O-D-mannitol by practical procedures.These compounds are versatile intermediates for optically active isomers of a number of neuropharmacologicall
- Yanagisawa, Hiroaki,Kanazaki, Takuro
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p. 105 - 109
(2007/10/02)
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