- NBS-mediated synthesis of β-keto sulfones from benzyl alcohols and sodium arenesulfinates
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An efficient synthetic route towards the synthesis of β-keto sulfones has been developed from secondary benzyl alcohols using N-bromosuccinimide (NBS). The present protocol utilizes NBS as oxidant as well as brominating agent, readily accessible benzyl alcohols and sodium arenesulfinates as the sulfonylating reagent under mild conditions. The control experiments revealed that the reaction proceeds via oxidation of alcohol to ketone, α-bromination of ketone and nucleophilic substitution by sodium arenesulfinate. Furthermore, the efficiency of the methodology was tested with a gram scale reaction and also shown the synthetic utility.
- Muneeswara, Madithedu,Sundaravelu, Nallappan,Sekar, Govindasamy
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p. 3479 - 3484
(2019/05/21)
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- Synthesis and antidepressant activity of arylalkanol-piperidine derivatives as triple reuptake inhibitors
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A series of arylalkanol-piperidine derivatives was synthesized, and their triple reuptake inhibition and in vivo activities have been evaluated. Among them, compounds 2a, 2j, 2k, 2m and 2n exhibited high potency for 5-HT, NA and DA transporters. Optimized compounds 2j and 2m showed significant reduction of immobility time compared to that of vehicle in the mouse tail suspension test (TST) test at doses ranging from 10 to 50 mg/kg po, and were not generally motor stimulants at 50 mg/kg dose. In addition, compounds 2j and 2m displayed desirable pharmacokinetic properties in SD rats.
- Zheng, Yong-Yong,Guo, Lin,Zhen, Xue-Chu,Li, Jian-Qi
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p. 123 - 136
(2012/09/08)
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- 3,8-DIAZA-BICYCLO[4.2.0]OCT-3-YL AMIDES
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The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-3-yl amide derivatives of formula (I), wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
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Page/Page column 71
(2012/07/13)
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- 3,8-DIAZA-BICYCLO[4.2.0]OCT-8-YL AMIDES
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The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-8-yl amide derivatives of formula (I) Formula (I) wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar 2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
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Page/Page column 62
(2012/07/13)
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- Novel Imidazole Derivatives Useful for the Treatment of Arthritis
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The present invention provides compounds of the formula below: where A, X and R1-R6 are as described herein, a pharmaceutical salt thereof, and a pharmaceutical composition containing this compound; methods of treating pain associated with osteoarthritis using one of the compounds or a pharmaceutically acceptable salt thereof, and processes for preparing the compounds.
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Page/Page column 14
(2012/12/13)
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- PHENYLMORPHOLINES AND ANALOGUES THEREOF
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Provided herein are compounds and prodrugs and methods of preparation of compounds and prodrugs that are capable of functioning as releasers and/or uptake inhibitors of one or more monoamine neurotransmitters, including dopamine, serotonin, and norepinephrine. Also provided are pharmaceutical compositions comprising one or more of these compounds or prodrugs, which may further comprise one or more additional therapeutic agents. Also provided are methods of treatment of various conditions that may be responsive to modification of monoamine neutrotransmitter levels, such as pre-obesity, obesity, addiction, and depression.
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Page/Page column 52
(2011/12/04)
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- MONOAM1NE REUPTAKE INHIBITORS
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The invention provides bupropion analogue compounds capable of inhibiting the reuptake of one or more monoamines. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine,and serotonin. Such compounds may be used to treat conditions that are responsive to inhibition of the reuptake of monoamines, including addiction, depression, and obesity
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Page/Page column 63-64
(2010/11/04)
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- Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation
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Bupropion (2a) analogues were synthesized and tested for their ability to inhibit monoamine uptake and to antagonize the effects of human α3β4*, α4β2, α4β4, and α1 * nAChRs. The analogues were evaluated for their ability to block nicotine-induced effects in four tests in mice. Nine analogues showed increased monoamine uptake inhibition. Similar to 2a, all but one analogue show inhibition of nAChR function selective for human α3β4*-nAChR. Nine analogues have higher affinity at α3β4*-nAChRs than 2a. Four analogues also had higher affinity for α4β2 nAChR. Analogues 2r, 2m, and 2n with AD50 values of 0.014,0.015, and 0.028 mg/kg were 87,81, and 43 times more potent than 2a in blocking nicotine-induced antinociception in the tail-flick test. Analogue 2x with IC50 values of 31 and 180 nM for DA and NE, respectively, and with IC50 of 0.62 and 9.8 μm for antagonism of α3β4 and α4β2 nAChRs had the best overall in vitro profile relative to 2a.
- Carroll, F. Ivy,Blough, Bruce E.,Mascarella, S. Wayne,Navarro, Hernán A.,Eaton, J. Brek,Lukas, Ronald J.,Damaj, M. Imad
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experimental part
p. 2204 - 2214
(2010/09/05)
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- Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction
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A series of bupropion (1a) analogues (1b-1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a 1a analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [3H] dopamine ([3H]DA), [3H]serotonin ([3H]5HT), and [3H]norepinephrine ([3H]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [125I]RTI-55 in cloned transporters. Several analogues showed increased [3H]DAuptake inhibition with reduced or little change in [3H]5HT and [3H]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a time course cocaine discrimination study using oral administration. 2-(N-Cyclopropylamino)-3- chloropropiophenone (1x) had the most favorable in vitro efficacy and in vivo pharmacological profile for an indirect dopamine agonist pharmacotherapy for treating cocaine, methamphetamine, nicotine, and other drugs of abuse addiction. 2009 American Chemical Society.
- Carroll, F. Ivy,Blough, Bruce E.,Abraham, Philip,Mills, Andrew C.,Holleman, J. Ashley,Wolckenhauer, Scott A.,Decker, Ann M.,Landavazo, Antonio,McElroy, K. Timothy,Navarro, Hernán A.,Gatch, Michael B.,Forster, Michael J.
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supporting information; experimental part
p. 6768 - 6781
(2010/04/06)
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- P70 S6 KINASE INHIBITORS
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The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.
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Page/Page column 16
(2009/01/20)
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- Arylmorpholine, preparation and use
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A method for the treatment of depression in a human being, the method comprising administering to the human being an antidepressant effective amount of a compound of the following formula STR1 or a pharmaceutically acceptable salt thereof, wherein R and R
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