39180-84-2Relevant articles and documents
Selective synthesis of mono- and di-methylated amines using methanol and sodium azide as C1 and N1 sources
Chakrabarti, Kaushik,Mishra, Anju,Panja, Dibyajyoti,Paul, Bhaskar,Kundu, Sabuj
supporting information, p. 3339 - 3345 (2018/07/29)
A Ru(ii) complex mediated synthesis of various N,N-dimethyl and N-monomethyl amines from organic azides using methanol as a methylating agent is reported. This methodology was successfully applied for a one-pot reaction of bromide derivatives and sodium azide in methanol. Notably, by controlling the reaction time several N-monomethylated and N,N-dimethylated amines were synthesized selectively. The practical applicability of this tandem process was revealed by preparative scale reactions with different organic azides and synthesis of an anti-vertigo drug betahistine. Several kinetic experiments and DFT studies were carried out to understand the mechanism of this transformation.
Selective Monomethylation of Amines with Methanol as the C1 Source
Choi, Geunho,Hong, Soon Hyeok
supporting information, p. 6166 - 6170 (2018/04/30)
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
Design, synthesis, and biological evaluation of a series of resorcinol-based N-benzyl benzamide derivatives as potent Hsp90 inhibitors
Park, Sun You,Oh, Yong Jin,Lho, Yunmee,Jeong, Ju Hui,Liu, Kwang-Hyeon,Song, Jaeyoung,Kim, Soong-Hyun,Ha, Eunyoung,Seo, Young Ho
, p. 390 - 401 (2017/12/07)
Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. Therefore, Hsp90 has emerged as an attractive target in the field of cancer chemotherapy. In this study, we report the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors. In particular, compound 30f shows a significant Hsp90α inhibitory activity with IC50 value of 5.3 nM and an excellent growth inhibition with GI50 value of 0.42 μM against non-small cell lung cancer cells, H1975. Compound 30f effectively reduces the expression levels of Hsp90 client proteins including Her2, EGFR, Met, Akt, and c-Raf. Consequently, compound 30f promotes substantial cleavages of PARP, Caspase 3, and Caspase 8, indicating that 30f induces cancer cell death via apoptotic pathway. Moreover, cytochrome P450 assay indicates that compound 30f has weak inhibitory effect on the activities of five major P450 isoforms (IC50 > 5 μM for 1A2, 2C9, 2C19, 2D6, and 3A), suggesting that clinical interactions between 30f and the substrate drugs of the five major P450 isoforms are not expected. Compound 30f also inhibits the tumor growth in a mouse xenograft model bearing subcutaneous H1975 without noticeable abnormal behavior and body weight changes. The immunostaining and western immunoblot analysis of EGFR, Met, Akt in xenograft tissue sections of tumor further demonstrate a good agreement with the in vitro results.
4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors
Pechulis, Anthony D.,Beck, James P.,Curry, Matt A.,Wolf, Mark A.,Harms, Arthur E.,Xi, Ning,Opalka, Chet,Sweet, Mark P.,Yang, Zhicai,Vellekoop, A. Samuel,Klos, Andrew M.,Crocker, Peter J.,Hassler, Carla,Laws, Mia,Kitchen, Douglas B.,Smith, Mark A.,Olson, Richard E.,Liu, Shuang,Molino, Bruce F.
, p. 7219 - 7222 (2013/01/15)
Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.
Highly enantioselective synthesis of tetrahydroquinolines via cobalt(II)-catalyzed tandem 1,5-hydride transfer/cyclization
Cao, Weidi,Liu, Xiaohua,Wang, Wentao,Lin, Lili,Feng, Xiaoming
, p. 600 - 603 (2011/04/15)
A chiral catalyst prepared from N,N′-dioxide and Co(BF 4)2·6H2O was applied in the asymmetric hydride transfer initiated cyclization reaction, giving optically active tetrahydroquinolines in good yields with high enantioselectivities under mild reaction conditions. Meanwhile, in light of the absolute configuration of the product, a possible working model was proposed to explain the origin of the activation and asymmetric induction.
A novel construction of 2-benzazepine scaffold based on TiCl 4-mediated tandem Mannich reaction - Aromatic electrophilic substitution
Li, Liangxi,Li, Zhiming,Wang, Quanrui
experimental part, p. 2754 - 2761 (2010/04/02)
A novel construction of 2-benzazepine derivatives based on TiCl 4-mediated tandem Mannich reaction of electron-rich benzyl iminium ions with alkenyl ethers and Friedel - Crafts-type alkylation is described. The protocol is amenable to provide the tricyclic furo[3,2-d][2]benzazepine and pyrano[3,2-d][2]benzazepine derivatives, respectively, with 2,3-dihydrofuran or 3,4-dihydro-2H-pyran as the substrates.
Formation of benzylamines from triazene compounds via a 1,2-proton shift
Nishiwaki, Keiji,Ogawa, Takashi,Shigeta, Kazumi,Takahashi, Koichi,Matsuo, Keizo
, p. 7034 - 7042 (2007/10/03)
A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group. The reaction contains the following steps: intramolecular carbon-carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that the reaction proceeds through a 1,2-proton shift.
Aryl- and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
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Page/Page column 106-107, (2008/06/13)
The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14; with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.
TACHYKININ RECEPTOR ANTAGONISTS
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Page 28, (2010/02/10)
The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.
α-lithiation of 1-Aryl-3,3-dialkyltriazenes and intramolecular conversion to benzylamine and tetrahydrobenzotriazine derivatives
Nishiwaki, Keiji,Ogawa, Takashi,Matsuo, Keizo
, p. 484 - 486 (2007/10/03)
An alternative route to benzylamine derivatives is provided by the lithiation of aryltriazenes followed by treatment with an electrophile [Eq. (1)]. The regioselectivity of the reaction can be controlled by means of the substituents X. When the 2- and 6-p
