18322-54-8Relevant academic research and scientific papers
Conjugate Addition Reactions Mediated by Samarium(II) Iodide
Molander, Gary A.,Harris, Christina R.
, p. 7418 - 7429 (1997)
Samarium(II) iodide in conjunction with a catalytic low-valent transition metal species has been employed to promote the conjugate addition reaction of primary and secondary alkyl halides onto α,β-unsaturated esters and amides. The method has been determined to be quite general and hence has been extended to the cyclization reactions of alkyl halides onto α,β-unsaturated lactones, lactams, and nitriles. The cyclization reactions described herein provide a very general approach to the synthesis of functionalized carbocycles from simple acyclic precursors with excellent diastereoselectivity and under very mild reaction conditions.
Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria
Abas, Siti Nurdiana,Aguiar, Anna Caroline Campos,Ang, Xiaoman,Angulo-Barturen, I?igo,Blaquiere, Nicole,Bodenreider, Christophe,Campbell, Simon,Campo, Brice,Chan, Katherine,Chan, Wai Ling,Chen, Yen-Liang,Cooper, Roland A.,Crespo-Fernandez, Benigno,Diagana, Thierry T.,Ding, Mei,Fang, Eric,Gamo, Francisco Javier,Guiguemde, Armand,Huang, Richard,Jain, Jay Prakash,Jiménez-Díaz, María Belén,Kirrane, Tom,Lakshminarayana, Suresh B.,Lanshoeft, Christian,Lim, Jessie,Liu, Yugang,Mata, Anne-Catherine,Pei, Luying,Qumber, Jafri,Rosenthal, Philip J.,Sarko, Christopher,Schulz, Hanna,Shu, Wei,Sim, Sandra,Simon, Oliver,Straimer, Judith,Taft, Benjamin R.,Thompson, Christopher,Tumwebaze, Patrick,Vankadara, Subramanyam,Wagner, Jürgen,Waldron, Grace,Yokokawa, Fumiaki,Zou, Bin
, p. 3798 - 3813 (2022/03/16)
A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves “artemisinin-like” kill kinetics in vitro with a parasite clearance time of 1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials.
Iron-Catalyzed Intermolecular Functionalization of Non-Activated Aliphatic C?H Bonds via Carbene Transfer
Rodríguez, Mònica,Font, Gemma,Nadal-Moradell, Joel,Hernán-Gómez, Alberto,Costas, Miquel
supporting information, p. 5116 - 5123 (2020/10/06)
The modification of strong Csp3?H bonds via iron carbene intermediates under mild reaction conditions has been an important challenge with attractive prospective in organic synthesis. In this work, we show the efficient combination of an electrophilic iron catalyst with a lithium Lewis acid for the functionalization of strong Csp3?H bonds of cyclic and linear alkanes by the activation of commercially available ethyl diazoacetate (EDA). The reaction proceeds with good yields, under mild reaction conditions (40 °C) and large excess of substrate is not needed. In addition, excellent activity is observed in the cyclopropanation of challenging aliphatic olefins. (Figure presented.).
Measuring the Relative Reactivity of the Carbon–Hydrogen Bonds of Alkanes as Nucleophiles
Olmos, Andrea,Gava, Riccardo,Noverges, Bárbara,Bellezza, Delia,Jacob, Kane,Besora, Maria,Sameera, W. M. Chamil,Etienne, Michel,Maseras, Feliu,Asensio, Gregorio,Caballero, Ana,Pérez, Pedro J.
supporting information, p. 13848 - 13852 (2018/09/06)
We report quantitative measurements of the relative reactivities of a series of C?H bonds of gaseous or liquid CnH2n+2 alkanes (n=1–8, 29 different C?H bonds) towards in situ generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C?C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C?H bonds.
Zinc(II)-Mediated Carbene Insertion into C-H Bonds in Alkanes
Kulkarni, Naveen V.,Dash, Chandrakanta,Jayaratna, Naleen B.,Ridlen, Shawn G.,Karbalaei Khani, Sarah,Das, Animesh,Kou, Xiaodi,Yousufuddin, Muhammed,Cundari, Thomas R.,Dias, H. V. Rasika
supporting information, p. 11043 - 11045 (2015/12/17)
The cationic zinc adduct {[HB(3,5-(CF3)2Pz)3]Zn(NCMe)2}ClO4 catalyzes the functionalization of tertiary, secondary, and primary C-H bonds of alkanes via carbene insertion. Ethyl diazoacetate serves as the:CHCO2Et carbene precursor. The counteranion, supporting ligand, and coordinating solvents affect the catalytic activity. An in situ generated {[HB(3,5-(CF3)2Pz)3]Zn}+ species containing a bulkier {B[3,5-(CF3)2C6H3]4}- anion gives the best results among the zinc catalysts used.
Catalytic, enantioselective, and highly chemoselective bromocyclization of olefinic dicarbonyl compounds
Zhao, Yi,Jiang, Xiaojian,Yeung, Ying-Yeung
, p. 8597 - 8601 (2013/09/12)
Overriding preferences: An amine-thiocarbamate catalyst can mediate the facile, efficient, and highly enantioselective bromocyclization of olefinic 1,3-dicarbonyl compounds. In the presence of the bifunctional catalyst, the bromination occurs chemoselectively at the olefinic moiety rather than at the carbon atom in the α-position to the carbonyl units. Copyright
COMPOUNDS FOR THE TREATMENT OF CNS DISORDERS
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Page/Page column 39, (2012/05/20)
The invention relates to novel cycloalkyl- or cycloalkenyl-substituted pyrazolopyrimidinones of formula (I), wherein ā is selected from the group A1 consisting of a C3-C8-cycloalkyl group or a C4-C8-cycloalkenyl group, whereby the members of C3-C8-cycloalkyl group being selected from the group of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl and cyclooctanyl; and the members of the C4-C8-cycloalkenyl group, being selected from cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cycloheptadienyl, cyclooctadienyl, cycloheptatrienyl, cyclooctathenyl, cyclooctatetraenyl. The new compounds shall be used for the manufacture of medicaments, in particular medicaments for improving perception, concentration, learning and/or memory in patients in need thereof. Chemically, the compounds are characterised as pyrazolopyrimidinones with a cycloalkyl-moiety directly bound to the 1 position of the pyrazolopyrimidinone and a second substituent in the 6 position which is bound via an optionally substituted methylene-bridge. Further aspects of the present invention refer to a process for the manufacture of the compounds and their use for producing medicaments.
Novel Biccyclic Compounds As GATA Modulators
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Page/Page column 19, (2010/06/19)
Novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided. Additionally, methods of forming novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided.
1-HETEROCYCLYL-1,5-DIHYDRO-PYRAZOLO[3,4-D] PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS PDE9A MODULATORS
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Page/Page column 163; 165, (2009/10/30)
The invention relates to novel 1,6-disubstituted pyrazolopyrimidinones, Formula (I) with Hc is a mono-, bi- or tricyclic heterocyclyl group, the ring members of which are carbon atoms and at least 1, preferably 1, 2 or 3, heteroatom(s), which are selected from the group of nitrogen, oxygen and sulphur, which is in the form of -S(O)r - with r being 0, 1 or 2, and - said heterocyclyl group is or comprises 1 non-aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member and - said heterocyclyl group is bound to the scaffold by said 1 non- aromatic, saturated, or partly unsaturated monocyclic ring which comprises at least 1 heteroatom as ring member. According to one aspect of the invention the new compounds are for the manufacture of medicaments, in particular medicaments for the treatment of conditions concerning deficits in perception, concentration, learning or memory. The new compounds are also for the manufacture of medicaments for the treatment of Alzheimer's disease.
Intermolecular copper-catalyzed carbon-hydrogen bond activation via carbene insertion
Diaz-Requejo, M. Mar,Belderrain, Tomas R.,Nicasio, M. Carmen,Trofimenko, Swiatoslaw,Perez, Pedro J.
, p. 896 - 897 (2007/10/03)
A series of catalysts of general formula TpXCu (TpX = homoscorpionate ligand) promote the insertion of :CHCO2Et (ethyl diazoacetate as the carbene source) into the C-H bonds of cycloalkanes and cyclic ethers in moderate to high yield. A correlation between the steric hindrance of these catalysts and the yield of the transformation has been observed. Copyright
