244059-08-3Relevant articles and documents
Copper-catalyzed asymmetric reductions of aryl/heteroaryl ketones under mild aqueous micellar conditions
Etemadi-Davan, Elham,Fialho, David M.,Gadakh, Amol,Langner, Olivia C.,Lipshutz, Bruce H.,Sambasivam, Ganesh,Takale, Balaram S.
supporting information, p. 3282 - 3286 (2021/05/29)
Enantioselective syntheses of nonracemic secondary alcohols have been achieved in an aqueous micellar medium via copper-catalyzed (Cu(OAc)2·H2O/(R)-3,4,5-MeO-MeO-BIPHEP) reduction of aryl/heteroaryl ketones. This methodology serves as a green protocol to access enantio-enriched alcohols under mild conditions (0-22 °C) using a base metal catalyst, together with an inexpensive, innocuous, and convenient stoichiometric hydride source (PMHS). The secondary alcohol products are formed in good to excellent yields with ee values greater than 90%.
Reductive Arylation of Amides via a Nickel-Catalyzed Suzuki–Miyaura-Coupling and Transfer-Hydrogenation Cascade
Boit, Timothy B.,Mehta, Milauni M.,Kim, Junyong,Baker, Emma L.,Garg, Neil K.
, p. 2472 - 2477 (2020/12/03)
We report a means to achieve the addition of two disparate nucleophiles to the amide carbonyl carbon in a single operational step. Our method takes advantage of non-precious-metal catalysis and allows for the facile conversion of amides to chiral alcohols via a one-pot Suzuki–Miyaura cross-coupling/transfer-hydrogenation process. This study is anticipated to promote the development of new transformations that allow for the conversion of carboxylic acid derivatives to functional groups bearing stereogenic centers via cascade processes.
Tuning the activity of known drugs via the introduction of halogen atoms, a case study of SERT ligands – Fluoxetine and fluvoxamine
Staroń, Jakub,Pietru?, Wojciech,Bugno, Ryszard,Kurczab, Rafa?,Sata?a, Grzegorz,Warszycki, Dawid,Lenda, Tomasz,Wantuch, Anna,Hogendorf, Adam S.,Hogendorf, Agata,Duszyńska, Beata,Bojarski, Andrzej J.
supporting information, (2021/06/02)
The selective serotonin reuptake inhibitors (SSRIs), acting at the serotonin transporter (SERT), are one of the most widely prescribed antidepressant medications. All five approved SSRIs possess either fluorine or chlorine atoms, and there is a limited number of reports describing their analogs with heavier halogens, i.e., bromine and iodine. To elucidate the role of halogen atoms in the binding of SSRIs to SERT, we designed a series of 22 fluoxetine and fluvoxamine analogs substituted with fluorine, chlorine, bromine, and iodine atoms, differently arranged on the phenyl ring. The obtained biological activity data, supported by a thorough in silico binding mode analysis, allowed the identification of two partners for halogen bond interactions: the backbone carbonyl oxygen atoms of E493 and T497. Additionally, compounds with heavier halogen atoms were found to bind with the SERT via a distinctly different binding mode, a result not presented elsewhere. The subsequent analysis of the prepared XSAR sets showed that E493 and T497 participated in the largest number of formed halogen bonds. The XSAR library analysis led to the synthesis of two of the most active compounds (3,4-diCl-fluoxetine 42, SERT Ki = 5 nM and 3,4-diCl-fluvoxamine 46, SERT Ki = 9 nM, fluoxetine SERT Ki = 31 nM, fluvoxamine SERT Ki = 458 nM). We present an example of the successful use of a rational methodology to analyze binding and design more active compounds by halogen atom introduction. ‘XSAR library analysis’, a new tool in medicinal chemistry, was instrumental in identifying optimal halogen atom substitution.
COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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Page/Page column 58, (2019/01/17)
The present invention relates to a compound of formula (I): wherein the meanings for the various substituents are as disclosed in the description, having dual pharmacological activity towards both the α2δ subunit, in particular the α2δ- 1 subunit, of the voltage-gated calcium channel and the NET receptor, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
IDO inhibitors
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Page/Page column 344, (2018/09/02)
Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.
TCDA: Practical Synthesis and Application in the Trifluoromethylation of Arenes and Heteroarenes
Wang, Jian,Zhang, Xiaomin,Wan, Zehong,Ren, Feng
supporting information, p. 836 - 839 (2016/05/19)
A practical synthesis of the reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported on 50 g scale. The trifluoromethylation with TCDA was optimized, and the reaction shows very broad scope with respect to electron-deficient, -neutral, -rich aryl/heteroaryl iodides, as well as excellent functional group tolerability, such as ester, amide, aldehyde, hydroxyl, and carboxylic acid. The reagent was also applied to the late-stage trifluoromethylation of three medicinally relevant compounds. Additionally, the building block trifluoromethylpyridine and one drug related molecule Boc-Fluoxetin were synthesized in 10 g scale by this method, demonstrating its practical applications in process chemistry.
HYDROXY ALIPHATIC SUBSTITUTED PHENYL AMINOALKYL ETHER DERIVATIVES
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Paragraph 0292-0293, (2015/12/24)
New hydroxy aliphatic substituted phenyl aminoalkyl ether compounds of formula (I), compositions thereof and their use as a medicament in the treatment of nervous system diseases and/or the treatment of developmental, behavioral and/or mental disorders associated with cognitive deficits.
SUBSTITUTED 3-HETEROARYLOXY-3-(HETERO)ARYL-PROPYLAMINES AS SEROTONIN TRANSPORTER AND SEROTONIN HT2C RECEPTOR MODULATORS
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, (2014/04/04)
The present invention relates to compounds compound according to Formula (1): and pharmaceutically acceptable salts, hydrates and solvates thereof. These compounds have serotonin (5-HT) transporter inhibitory effects and 5-HT 2C receptor antagonist or inverse agonist effects. The present invention also relates to pharmaceutical compositions comprising these compounds, and methods of using them for application in the prophylaxis or treatment of CNS disorders.
Catalytic decarboxylative fluorination for the synthesis of Tri- and difluoromethyl arenes
Mizuta, Satoshi,Stenhagen, Ida S.R.,O'Duill, Miriam,Wolstenhulme, Jamie,Kirjavainen, Anna K.,Forsback, Sarita J.,Tredwell, Matthew,Sandford, Graham,Moore, Peter R.,Huiban, Mickael,Luthra, Sajinder K.,Passchier, Jan,Solin, Olof,Gouverneur, Véronique
, p. 2648 - 2651 (2013/07/11)
Treatment of readily available α,α-difluoro- and α-fluoroarylacetic acids with Selectfluor under Ag(I) catalysis led to decarboxylative fluorination. This operationally simple reaction gave access to tri- and difluoromethylarenes applying a late-stage fluorination strategy. Translation to [18F]labeling is demonstrated using [ 18F]Selectfluor bis(triflate), a reagent affording [ 18F]tri- and [18F]difluoromethylarenes not within reach with [18F]F2.
MULTITARGET SUBSTITUTED BIPHENYL DIOL DERIVATIVES
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Page/Page column 36-37, (2012/02/13)
Biphenyl diol compounds of formula (I) and their use as a medicament to suppress tumor growth and/or prevent recurrence or metastasis or to treat a cancer selected from the group consisting of brain, bone, colon, ovary, pancreas, prostate, skin, lung, and
