- Bi(OTf)3-catalyed One-pot Synthesis of α-Halo-β-amino Ketones and Acyl Aziridines from 3-Aryl Propargyl Alcohols
-
A Bi(OTf)3-catalyed reaction of 3-aryl propargyl alcohols with sulfonamide and halogen source was firstly investigated, which provided a facile route for the synthesis of a large variety of α-halo-β-amino ketones. The key intermediates, β-amino
- Zhang, Qinglin,Duan, Yongbin,Guo, Huifeng,Yang, Hong,Zhai, Jiulong,Li, Tiantian,Wang, Zhihai,Lu, Xiaolei,Wang, Yan,Yin, Yan
-
supporting information
p. 1832 - 1838
(2021/06/09)
-
- Synthesis of Azepino[1,2-a]indole-10-amines via [6+1] Annulation of Ynenitriles with Reformatsky Reagent
-
Lewis acid-catalyzed [6+1] annulation reactions of 2-cyano-1-propargyl- and 2-alkynyl-1-cyanomethyl-indoles with Reformatsky reagent are described. 8-Aryl, 8-alkyl-, 8-hetaryl-, 9-aryl, and 9-alkyl-azepino[1,2-a]indole amines were obtained through a 7-endo-mode cyclization of the β-aminoacrylate intermediates. The antiproliferative activity of the azepino[1,2-a]indoles analogs against the HCT-116 cells were also examined.
- Iioka, Ryoya,Yorozu, Kohei,Sakai, Yoko,Kawai, Rika,Hatae, Noriyuki,Takashima, Katsuki,Tanabe, Genzoh,Wasada, Hiroaki,Yoshimatsu, Mitsuhiro
-
supporting information
p. 1553 - 1558
(2021/02/26)
-
- Tricyclic Triazoles as σ1Receptor Antagonists for Treating Pain
-
The synthesis and pharmacological activity of a new series of 5a,7,8,8a-tetrahydro-4H,6H-pyrrolo[3,4-b][1,2,3]triazolo[1,5-d][1,4]oxazine derivatives as potent sigma-1 receptor (σ1R) ligands are reported. A lead optimization program aimed at improving the aqueous solubility of parent racemic nonpolar derivatives led to the identification of several σ1R antagonists with a good absorption, distribution, metabolism, and excretion in vitro profile, no off-target affinities, and characterized by a low basic pKa (around 5) that correlates with high exposure levels in rodents. Two compounds displaying a differential brain-to-plasma ratio distribution profile, 12lR and 12qS, exhibited a good analgesic profile and were selected as preclinical candidates for the treatment of pain.
- Díaz, José Luis,Cuevas, Félix,Oliva, Ana I.,Font, Daniel,Sarmentero, M. ángeles,álvarez-Bercedo, Paula,López-Valbuena, José M.,Pericàs, Miquel A.,Enrech, Raquel,Montero, Ana,Yeste, Sandra,Vidal-Torres, Alba,álvarez, Inés,Pérez, Pilar,Cendán, Cruz Miguel,Cobos, Enrique J.,Vela, José Miguel,Almansa, Carmen
-
p. 5157 - 5170
(2021/05/07)
-
- Copper-Catalyzed Cross-Nucleophile Coupling of β-Allenyl Silanes with Tertiary C-H Bonds: A Radical Approach to Branched 1,3-Dienes
-
Described herein is a distinctive approach to branched 1,3-dienes through oxidative coupling of two nucleophilic substrates, β-allenyl silanes, and hydrocarbons appending latent functionality by copper catalysis. Notably, C(sp3)-H dienylation proceeded in a regiospecific manner, even in the presence of competitive C-H bonds that are capable of occurring hydrogen atom transfer process, such as those located at benzylic and other tertiary sites, or adjacent to an oxygen atom. Control experiments support the intermediacy of functionalized alkyl radicals.
- Shan, Qi-Chao,Hu, Lu-Min,Qin, Wei,Hu, Xu-Hong
-
supporting information
p. 6041 - 6045
(2021/08/03)
-
- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
- -
-
Paragraph 00230; 00603
(2020/07/05)
-
- Metal-Free Regioselective Chloroazidation of Internal Alkynes
-
A metal-free, room temperature protocol for the regioselective chloroazidation of internal alkynes is disclosed. The reactions of internal alkynes with trimethylsilyl azide (TMSN3) in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) afforded the corresponding chloroazidoalkenes in good yields. This reaction has good functional group tolerance and is operationally simple.
- Huang, Bin,Liffert, Raphael,Linden, Anthony,Gademann, Karl
-
supporting information
p. 981 - 984
(2019/01/04)
-
- Applications of Thermal Activation, Ball-milling and Aqueous Medium in Stereoselective Michael Addition of Nitromethane to Enynones Catalyzed by Chiral Squaramides
-
Stereoselective addition of nitromethane to conjugated en-ynones was performed through the application of chiral squaramides. Three non-classical approaches to promote the addition reaction were tested, including activation of the nucleophile by inorganic base in a biphasic aqueous system, thermal activation, and ball-milling. Hydrogen-bonding catalysis was effective in all these methods, providing 1,4-addition products in high yields and stereoselectivities of up to 98% requiring 1–5 mol% of Cinchona alkaloid squaramide. (Figure presented.).
- Ignatiuk, ?aneta A.,Janicki, Miko?aj J.,Góra, Robert W.,Konieczny, Krzysztof,Kowalczyk, Rafa?
-
supporting information
p. 1108 - 1116
(2019/01/30)
-
- Synthesis and antiviral activity of novel spirocyclic nucleosides
-
The synthesis of a number of spirocyclic ribonucleosides containing either a triazolic or azetidinic system is described, along with two analogous phosphonate derivatives of the former. These systems were constructed from the same β-d-psicofuranose starti
- Cobb, Alexander J. A.,Dell'Isola, Antonio,Abdulsattar, Ban O.,McLachlan, Matthew M. W.,Neuman, Benjamin W.,Müller, Christin,Shankland, Kenneth,Al-Mulla, Hawaa M. N.,Binks, Alexander W. D.,Elvidge, Warren
-
p. 18363 - 18380
(2018/11/23)
-
- Synthesis and evaluation of (E)-2-(5-phenylpent-2-en-4-ynamido)cyclohex-1-ene-1-carboxylate derivatives as HCA2 receptor agonists
-
Novel series of compounds consisting of 2-amidocyclohex-1-ene carboxylate and phenyl parts which are connected by enyne (compounds 2a–f), but-1-yne (compounds 4a–j), and phenylethylene (compounds 5a–f) linkers as HCA2 full agonists were designed and their
- Bobileva, Olga,Ikaunieks, Martins,Duburs, Gunars,Mandrika, Ilona,Petrovska, Ramona,Klovins, Janis,Loza, Einars
-
p. 4314 - 4329
(2017/07/22)
-
- Ligand-Controlled Regiodivergence in the Copper-Catalyzed [2,3]- and [1,2]-Rearrangements of Iodonium Ylides
-
Despite the importance of allylic ylide rearrangements for the synthesis of complex molecules, the catalyst control of [2,3]- and [1,2]-rearrangements remains an unsolved problem. We developed the first regiodivergent [2,3]- and [1,2]-rearrangements of iodonium ylides that are controlled by copper catalysts bearing different ligands. In the presence of a 2,2′-dipyridyl ligand, diazoesters and allylic iodides react via a [2,3]-rearrangement pathway. Alternatively, a phosphine ligand favors the formation of the [1,2]-rearrangement product. A series of α-iodoesters containing a broad range of functional groups were obtained in high yields, regioselectivities, and diastereoselectivities. Deuterium-labeling studies suggest distinct mechanisms for the regioselective rearrangements.
- Xu, Bin,Tambar, Uttam K.
-
supporting information
p. 12073 - 12076
(2016/09/28)
-
- Palladium-catalyzed multicomponent reaction (MCR) of propargylic carbonates with isocyanides
-
A palladium-catalyzed multicomponent reaction (MCR) of propargylic carbonates with isocyanides is reported. Remarkably, the orderly insertion of isocyanides affords two types of valuable N-heterocyclic products (Z)-6-imino-4,6-dihydro-1H-furo[3,4-b]pyrrol-2-amines and (E)-5-iminopyrrolones in high yields. Systematic analysis of the reaction conditions indicates that the selectivity of these N-heterocyclic products can be controlled by ligands and temperature.
- Peng, Jianwen,Gao, Yang,Hu, Weigao,Gao, Yinglan,Hu, Miao,Wu, Wanqing,Ren, Yanwei,Jiang, Huanfeng
-
supporting information
p. 5924 - 5927
(2016/11/29)
-
- Synthesis and antiviral properties of spirocyclic [1,2,3]-Triazolooxazine nucleosides
-
An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromide
- Dell'Isola, Antonio,McLachlan, Matthew M. W.,Neuman, Benjamin W.,Al-Mullah, Hawaa M. N.,Binks, Alexander W. D.,Elvidge, Warren,Shankland, Kenneth,Cobb, Alexander J. A.
-
supporting information
p. 11685 - 11689
(2014/10/15)
-
- Oxathiolene oxide synthesis via chelation-controlled addition of organometallic reagents to alkynols followed by addition of sulfur electrophiles and evaluation of oxathiolene oxides as anticarcinogenic enzyme inducers
-
A number of alkynols have been prepared by Sonogashira coupling of propargyl alcohol to aromatic halides. Chelation-controlled addition of organometallic nucleophiles to these alkynols was then effected followed by the addition of the sulfur electrophiles
- Franks, Marion A.,Schrader, Edward A.,Pietsch, E. Christine,Pennella, Daniel R.,Torti, Suzy V.,Welker, Mark E.
-
p. 2221 - 2233
(2007/10/03)
-
- 5,5-Diaryl-2-amino-4-pentenoates as novel, potent, and selective glycine transporter type-2 reuptake inhibitors
-
A novel series of 5,5-diaryl-2-amino-4-pentenoates was synthesized and found to be potent and selective glycine transporter type-2 reuptake inhibitors.
- Isaac, Methvin,Slassi, Abdelmalik,Silva, Kathleen Da,Arora, Jalaj,MacLean, Neil,Hung, Bill,McCallum, Kirk
-
p. 1371 - 1373
(2007/10/03)
-
- Design and synthesis of m1-selective muscarinic agonists: (R)-(-)-(Z)- 1-azabicyclo[2.2.1]heptan-3-one, O-(3-(3'-methoxyphenyl)-2-propynyl)-oxime maleate (CI-1017), a functionally m1-selective muscarinic agonist
-
The synthesis and SAR of a series of (Z)-(±)-1- azabicyclo[2.2.1]heptan-3-one, O-(3-aryl-2-propynyl)oximes are described. The biochemistry and pharmacology of 24Z (PD 142505) and its enantiomers are highlighted. 24Z is functionally an m1-selective muscari
- Tecle, Halle,Barrett, Stephen D.,Lauffer, David J.,Augelli-Szafran, Corinne,Brann, Mark R.,Callahan, Michael J.,Caprathe, Bradley W.,Davis, Robert E.,Doyle, Patricia D.,Eubanks, David,Lipiniski, William,Mirzadegan, Tara,Moos, Walter H.,Moreland,Nelson, Carrie B.,Pavia, Michael R.,Raby, Charlotte,Schwarz, Roy D.,Spencer, Carolyn J.,Thomas, Anthony J.,Jaen, Juan C.
-
p. 2524 - 2536
(2007/10/03)
-