- Synthesis and nicotinic acetylcholine receptor in vitro and in vivo pharmacological properties of 2′-fluoro-3′-(substituted phenyl)deschloroepibatidine analogues of 2′-fluoro-3′-(4- nitrophenyl)deschloroepibatidine
-
Herein, we report the synthesis and nicotinic acetylcholine receptor (nAChR) in vitro and in vivo pharmacological properties of 2′-fluoro- 3′-(substituted phenyl)deschloroepibatidines 5b-g, analogues of 3′-(4-nitrophenyl) compound 5a. All compounds had hi
- Ondachi, Pauline,Castro, Ana,Luetje, Charles W.,Damaj, M. Imad,Mascarella, S. Wayne,Navarro, Hernán A.,Carroll, F. Ivy
-
-
Read Online
- Practical and efficient synthesis of aryl trifluoromethyl sulfones from arylsulfonyl chlorides with Umemoto's reagent II
-
A practical and efficient method for the synthesis of aryl trifluoromethyl sulfones has been developed by a tandem reaction of arylsulfonyl chlorides with Umemoto's reagent II. The advantageous features of this method are simple operation, mild reaction conditions, wide scope of substrates, high yield of products, and easy scalability.
- Zhou, Xiaocong,Hu, Dufen,He, Xinyi,Li, Yuanqiang,Chu, Youqun,She, Yuanbin
-
supporting information
(2019/12/24)
-
- Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
-
SuFEx is a new-generation click chemistry transformation that exploits the unique properties of S?F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx-based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S?F exchange with trifluoromethyltrimethylsilane (TMSCF3) upon activation by potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative mechanism is proposed involving nucleophilic displacement of S?F by the trifluoromethyl anion via a five-coordinate intermediate. The utility of late-stage SuFEx trifluoromethylation is demonstrated through the synthesis and selective anticancer properties of a bis(trifluoromethyl)sulfur oxyimine.
- Smedley, Christopher J.,Zheng, Qinheng,Gao, Bing,Li, Suhua,Molino, Andrew,Duivenvoorden, Hendrika M.,Parker, Belinda S.,Wilson, David J. D.,Sharpless, K. Barry,Moses, John E.
-
supporting information
p. 4552 - 4556
(2019/03/07)
-
- Synthesis of Aryl Triflones through the Trifluoromethanesulfonylation of Benzynes
-
The direct synthesis of aryl triflones, that is, trifluoromethanesulfonyl arenes, was achieved through the trifluoromethanesulfonylation of benzynes. The trifluoromethanesulfonyl group, one of the fluorinated functional groups, is a highly electron-negative and mild lipophilic substituent. Aryl triflones have high potential in the synthesis of bioactive compounds and specialty materials. The treatment of 2-(trimethylsilyl)aryl trifluoromethanesulfonates with cesium fluoride in the presence of 15-crown-5 generated benzynes, which reacted with sodium trifluoromethanesulfinate followed by protonation with tBuOH under heating conditions, provided aryl triflones in moderated to good yields. Both symmetrical and unsymmetrical triflones were nicely accessed under the same reaction conditions. Interestingly, the trifluoromethanesulfonylation of unsymmetrical benzyne precursors proceeded smoothly to furnish corresponding aryl triflones in good yields with good to high regioselectivities. The balance of polarization of electric charge as well as steric hindrance of the benzyne intermediates are central factors to control the outcome of regioselectivity.
- Sumii, Yuji,Sugita, Yutaka,Tokunaga, Etsuko,Shibata, Norio
-
p. 204 - 211
(2018/03/02)
-
- Enantioselective, Catalytic Vicinal Difluorination of Alkenes
-
The enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2-symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Br?nsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).
- Scheidt, Felix,Sch?fer, Michael,Sarie, Jér?me C.,Daniliuc, Constantin G.,Molloy, John J.,Gilmour, Ryan
-
supporting information
p. 16431 - 16435
(2018/11/23)
-
- Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs
-
Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18–56 nm). Seven co-crystal structures with P. vivax (Pv) SHMT were solved at 2.2–2.6 ? resolution. We observed an unprecedented influence of the torsion angle of ortho-substituted biphenyl moieties on cell-based efficacy. The peculiar lipophilic character of the sulfonyl moiety was highlighted in the complexes with aryl sulfonamide analogues, which bind in their preferred staggered orientation. The results are discussed within the context of conformational preferences in the ligands.
- Schwertz, Geoffrey,Frei, Michelle S.,Witschel, Matthias C.,Rottmann, Matthias,Leartsakulpanich, Ubolsree,Chitnumsub, Penchit,Jaruwat, Aritsara,Ittarat, Wanwipa,Sch?fer, Anja,Aponte, Raphael A.,Trapp, Nils,Mark, Kerstin,Chaiyen, Pimchai,Diederich, Fran?ois
-
supporting information
p. 14345 - 14357
(2017/10/09)
-
- A method of manufacturing a benzene derivative (trifluoromethylsulfonyl)
-
PROBLEM TO BE SOLVED: To provide a method for producing a (trifluoromethylsulfonyl)benzene derivative which is useful as a medicine, an agricultural chemical, a functional material and a production intermediate thereof. SOLUTION: In this method, a (trifluoromethylsulfonyl)benzene derivative is produced by reacting diaryliodonium salt represented by general formula (1) with trifluoromethanesulfinic acid salt in the presence of a copper (I) salt. (In the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9and R10each independently represents a hydrogen atom, a 1-6C alkyl group, a 1-6C haloalkyl group, a 1-6C alkoxy group, a 2-6C acyl group, (1-5C alkoxy)carbonyl group, a nitro group, a cyano group, a chlorine atom or a bromine atom). COPYRIGHT: (C)2013,JPOandINPIT
- -
-
Paragraph 0059; 0060
(2016/10/08)
-
- METHOD FOR PRODUCING TRIFLUOROMETHYLSULFONYL COMPOUND DERIVATIVE
-
PROBLEM TO BE SOLVED: To provide a method for producing a trifluoromethylsulfonyl compound derivative useful as synthetic intermediates for medicines and agrochemicals. SOLUTION: The method for producing a trifluoromethylsulfonyl compound derivative repre
- -
-
Paragraph 0019-0020;0021-0023
(2017/05/12)
-
- Organocatalyzed Trifluoromethylation of Ketones and Sulfonyl Fluorides by Fluoroform under a Superbase System
-
Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). Despite its attractive properties, taming HCF3 for trifluoromethylation is quite problematic owing to its low acidity and the labilit
- Okusu, Satoshi,Hirano, Kazuki,Tokunaga, Etsuko,Shibata, Norio
-
p. 581 - 585
(2015/10/20)
-
- Cu-catalyzed couplings of aryl iodonium salts with sodium trifluoromethanesulfinate
-
A convenient method for the preparation of aryl trifluoromethylsulfones from the reactions of diaryliodonium salts with sodium trifluoromethanesulfinate in the presence of copper catalysts is described. Cuprous oxide in DMF was found to be the optimal catalyst for the reaction. The reaction conditions are tolerant of various functional groups as well as of various counteranions of the iodonium salt. The synthetic utility of the process is demonstrated by performing the reaction on a preparative scale (88 g).
- Cullen, Steven C.,Shekhar, Shashank,Nere, Nandkishor K.
-
p. 12194 - 12201
(2014/01/06)
-
- NICOTINIC RECEPTOR COMPOUNDS
-
Compounds and compositions for promoting smoking cessation or descreasing tobacco use or nicotine addiction are provided. The compounds are 2'-fluoro-3'-(substituted phenyl) deschloroepibatidine analogs. The compounds have been found to modulate neuronal nicotine acetylcholine receptors and are useful in methods for the treatment of conditions or disorders influenced by the modulation of neuronal nicotinic acetylcholine receptors.
- -
-
Paragraph 0070; 0071; 0080; 0081
(2013/07/19)
-
- COLD MENTHOL RECEPTOR-1 ANTAGONISTS
-
The invention is directed to TRPM8 antagonists of Formula (I). More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating TRPM8-mediated disorders. Pharmaceutical and veterinary compositions and methods of treating pain and various other disease states or conditions using compounds of the invention are also described.
- -
-
Page/Page column 73
(2012/03/12)
-
- COLD MENTHOL RECEPTOR-1 ANTAGONISTS
-
The invention is directed to TRPM8 antagonists of Formula (I). More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating TRPM8-mediated disorders. Pharmaceutical and veterinary compositions and methods of treating pain and various other disease states or conditions using compounds of the invention are also described.
- -
-
Page/Page column 73
(2012/07/28)
-
- SUBSTITUTED BIPHENYL DERIVATIVE
-
The present invention relates to a biaryl derivative or a pharmacologically acceptable salt thereof having an excellent collagen-synthesis inhibition activity. A biaryl derivative having a structure represented by the following General Formula (I) or a pharmacologically acceptable salt thereof: wherein R1 represents a C6-C10 aryl group which is substituted with one to three group(s) each independently selected from the group consisting of a group defined by formula R-L-, a di-(C1-C6 alkyl)amino group, a di-(C1-C6 alkyl)aminosulfonyl group, a hydroxyaminocarbonyl group, and a halogen atom, and so on; R represents a C1-C6 alkyl group, and so on; L represents a sulfonyl group, an aminosulfonyl group, or a sulfonylamino group, and so on; R2 represents a hydrogen atom, and so on; A represents a group defined by formula (II), (III), or (IV); R3 represents a C1-C6 alkyl group, and so on; and R4 represents a C1-C6 alkyl group, and so on.
- -
-
Page/Page column 154
(2010/11/27)
-
- Synthesis, fluorescence, and two-photon absorption of a series of elongated rodlike and banana-shaped quadrupolar fluorophores: A comprehensive study of structure-property relationships
-
An extensive series of push-push and pull-pull derivatives was prepared from the symmetrical functionalization of an ambivalent core with conjugated rods made from arylene-vinylene or arylene-ethynylene building blocks, bearing different acceptor or donor
- Mongin, Olivier,Porres, Laurent,Charlot, Marina,Katan, Claudine,Blanchard-Desce, Mireille
-
p. 1481 - 1498
(2008/02/04)
-
- HYDANTOIN DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISORDERS
-
This invention relates to compounds of the Formula: (I); or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, aggrecanase, TNF-α or combinations thereof.
- -
-
Page/Page column 150
(2008/06/13)
-
- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
-
The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).
- -
-
Page/Page column 149-150
(2008/06/13)
-
- SELECTIVE ESTROGEN RECEPTOR MODULATORS CONTAINING A PHENYLSULFONYL GROUP
-
The present invention relates to a selective estrogen receptor modulator of formula I or a pharmaceutical acid addition salt thereof; useful, e.g., for treating endometriosis and/or uterine leiomyoma/leiomyomata.
- -
-
Page/Page column 24-25
(2008/06/13)
-
- Nonlinear Optical Epoxy Polymers with Polar Tolan Chromophores
-
A variety of optically nonlinear tolan chromophores and epoxy based polymers containing them have been prepared and studied.The molecular hyperpolarizabilities of the dye chromophores have been measured by the EFISH technique while the polymers containing
- Twieg, R.,Ebert, M.,Jungbauer, D.,Lux, M.,Reck, B.,et al.
-
-