- β-nitroacrylates as useful building blocks for the synthesis of alkyl indole-2-carboxylates
-
Polyfunctionalized alkyl indole 2-carboxylates can be easily synthesized starting form β-nitroacrylates and o-bromoanilines through an addition-elimination process followed by an intramolecular palladium-catalyzed Heck reaction. Georg Thieme Verlag Stuttg
- Palmieri, Alessandro,Gabrielli, Serena,Maggi, Raimondo,Ballini, Roberto
-
-
Read Online
- Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore
-
We have previously reported the development of indole-based CNS-active antivirals for the treatment of neurotropic alphavirus infection, but further optimization is impeded by a lack of knowledge of the molecular target and binding site. Herein we describe the design, synthesis and evaluation of a series of conformationally restricted analogues with the dual objectives of improving potency/selectivity and identifying the most bioactive conformation. Although this campaign was only modestly successful at improving potency, the sharply defined SAR of the rigid analogs enabled the definition of a three-dimensional pharmacophore, which we believe will be of value in further analog design and virtual screening for alternative antiviral leads.
- Barraza, Scott J.,Sindac, Janice A.,Dobry, Craig J.,Delekta, Philip C.,Lee, Pil H.,Miller, David J.,Larsen, Scott D.
-
supporting information
(2021/06/18)
-
- 5-MEMBERED HETEROCYCLE FUSED WITH [3,4-D]PYRIDAZINONE, AND MANUFACTURING METHOD, PHARMACEUTICAL COMPOSITION, AND APPLICATION THEREOF
-
The present invention provides a compound comprising a 5-membered heterocycle fused with a pyridazinone, wherein the compound is used as an FGFR kinase inhibitor, and a manufacturing method and application thereof. The invention specifically provides a co
- -
-
Paragraph 0098; 0099
(2019/04/29)
-
- Inexpensive Radical Methylation and Related Alkylations of Heteroarenes
-
A simple method for the introduction of a methyl and higher aliphatic group to various heteroarenes using very inexpensive reagents is described. It is based on the radical addition of a carboxylic xanthate followed by decarboxylation. Depending on the heteroarene structure, the decarboxylation can be spontaneous or induced by heating in N,N-dimethylacetamide or N-methyl pyrrolidone in a microwave oven.
- Huang, Qi,Zard, Samir Z.
-
supporting information
p. 1413 - 1416
(2018/03/09)
-
- Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators
-
Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3?nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.
- Greig, Iain R.,Baillie, Gemma L.,Abdelrahman, Mostafa,Trembleau, Laurent,Ross, Ruth A.
-
p. 4403 - 4407
(2016/08/25)
-
- Visible-Light-Induced Direct Photocatalytic Carboxylation of Indoles with CBr4/MeOH
-
Photocatalysis enables the cascade reactions of indoles and CBr4 in MeOH through a C(sp2)-H functionalization/methanolysis sequence. The title reaction provides an efficient access to indole 2- and 3-carboxylates in a single operation (no preinstallation of protecting as well as directing groups was required) with good yields under mild reaction conditions. Shedding light on indole: The regioselective alkoxycarboxylation of indoles and heteroarenes using the CBr4/MeOH couple was accomplished through visible-light-induced photoredox catalysis. The described photocatalytic strategy features operational simplicity as well as high functional-group tolerance and represents a direct procedure to access indole carboxylates in generally moderate to good yields (see scheme).
- Yang, Qing-Qing,Marchini, Marianna,Xiao, Wen-Jing,Ceroni, Paola,Bandini, Marco
-
supporting information
p. 18052 - 18056
(2015/12/24)
-
- 2-Aroylindoles from o-bromochalcones via Cu(i)-catalyzed SNAr with an azide and intramolecular nitrene C-H insertion
-
A simple procedure for the synthesis of 2-aroylindole derivatives comprising a one-pot CuI-catalyzed SNAr reaction of o-bromochalcones with sodium azide and subsequent intramolecular cyclization through nitrene C-H insertion has been developed. This protocol is also applicable with the 2′-bromocinnamates giving the indole-2-carboxylates. This journal is the Partner Organisations 2014.
- Goriya, Yogesh,Ramana, Chepuri V.
-
supporting information
p. 7790 - 7792
(2014/07/08)
-
- Microwave-assisted synthesis of indole-2-carboxylic acid esters in ionic liquid
-
An improved procedure for the synthesis of indole-2-carboxylic acid esters in excellent yields has been achieved by the condensation of 2-halo aryl aldehydes or ketones and ethyl isocyanoacetate using ionic liquid under controlled microwave irradiation (100 W) at 50 °C. This method offers a number of advantages in terms of methodology, high-product yield, short period of conversion, mild reaction conditions and easy workup.
- Gu, Lijun,Li, Xiangguang
-
experimental part
p. 2036 - 2039
(2012/02/03)
-
- Assembly of indole-2-carboxylic acid esters through a ligand-free copper-catalysed cascade process
-
A straightforward synthesis of indole-2-carboxylic esters was developed through a ligand-free copper-catalysed condensation/coupling/deformylation cascade process from 2-halo aryl aldehydes or ketones with ethyl isocyanoacetate. The reactions proceeded we
- Cai, Qian,Li, Zhengqiu,Wei, Jiajia,Ha, Chengyong,Pei, Duanqing,Ding, Ke
-
supporting information; body text
p. 7581 - 7583
(2010/04/30)
-
- PYRROLO- AND THIAZOLO-PYRIDINE COMPOUNDS, AND METHODS OF USE THEREOF
-
The present invention relates to novel compounds capable of modulating the stability and/or activity of hypoxia inducible factor (HIF).
- -
-
Page/Page column 64
(2008/06/13)
-
- Dioxomolybdenum(VI)-catalyzed reductive cyclization of nitroaromatics. Synthesis of carbazoles and indoles
-
Reductive cyclization of nitrobiphenyls and nitrostyrenes to carbazoles and indoles, respectively, is carried out by triphenylphosphine under mild conditions catalyzed by a dichlorodioxomolybdenum(VI) complex. A one-pot procedure for the synthesis of regioselectively functionalized indoles has been developed from commercially available onitrobenzaldehydes and phosphoranes.
- Sanz, Roberto,Escribano, Jaime,Pedrosa, Maria R.,Aguado, Rafael,Arnaiz, Francisco J.
-
p. 713 - 718
(2008/02/09)
-
- Rearrangement of 3,3-disubstituted indolenines and synthesis of 2,3-substituted indoles
-
(Diagram presented) Synthesis of 2,3-substituted indoles from phenylhydrazine and α-branched aldehydes via rearrangement of 3,3-disubstituted indolenine intermediates is reported.
- Liu, Kevin G.,Robichaud, Albert J.,Lo, Jennifer R.,Mattes, James F.,Cai, Yanxuan
-
p. 5769 - 5771
(2007/10/03)
-
- Analogs of indole-3-carbinol metabolites as chemotherapeutic and chemopreventive agents
-
Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of indole-3-carbinol metabolites wherein the structures and substituents of the compounds are selected to enhance the compounds' overall efficacy, particularly with respect to therapeutic activity, oral bioavailability, long-term safety, patient tolerability, and therapeutic window. The compounds are useful not only in treatment of cancer but also in prevention of cancer. One preferred class of the novel compounds have the structure of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 are defined herein. Pharmaceutical compositions are provided as well, as are methods of synthesis and use.
- -
-
Page/Page column 21-22
(2008/06/13)
-
- Construction of heterocyclic compounds by use of α-diazophosphonates: New one-pot syntheses of indoles and isocoumarins
-
(Matrix Presented) α-Diazophosphonates, which have extremely useful properties from a synthetic point of view, are disclosed as 1,1-ambiphilic one-carbon building blocks for one-pot construction of various heterocyclic compounds. They are easily prepared and have higher stability by the effect of the phosphoryl group than corresponding α-diazocarbonyl compounds. Using this synthon, we have developed a novel, mild, and efficient synthetic method of 2,3-disubstituted indoles and 3,4-disubstituted isocoumarins.
- Nakamura, Yoshinori,Ukita, Tatsuzo
-
p. 2317 - 2320
(2007/10/03)
-
- Tripeptidylpeptidase inhibitors
-
A compound of formula wherein the substituents are defined as in the specification and salts or hydrates thereof is disclosed as well as a method of treating disorders associated with the inactivation or excessive degradation of cholecystokinin.
- -
-
-
- 3-(Arylamino)quinolin-2(1H)- and -4(1H)-ones: Reinvestigation of the reaction between ethyl 2-chloro-3-(phenylamino)but-2-enoate and arylamines
-
The reaction between ethyl 2-chloro-3-(phenylamino)but-2-enoate (5) and aniline gave 4-methyl-3-(phenylamino)quinolin-2(1H)-one (6) and not, as reported earlier in the literature, the isomeric 2-methyl-3- (phenylamino)quinolin-4(1H)-one (1). The latter co
- Fretz, Heinz,Gaugler, Markus,Schneider, Joseph
-
p. 1145 - 1150
(2007/10/03)
-
- Synthesis and biological activity of N-(aminoiminomethyl)-1H-indole carboxamide derivatives as Na+/H+ exchanger inhibitors
-
A series of N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7- position of the indole ring system showed that a substitution at the 2- position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series of N- (aminoiminomethyl)-1H-indole-2-carboxamide derivatives. Derivatives having an alkyl or substituted alkyl group at the 1-position of the indole ring system showed higher levels of in vitro activities. N-(aminoiminomethyl)-1-(2- phenylethyl)-1H-indole-2-carboxamide (49) had the strongest activity.
- Kitano, Masafumi,Kojima, Atsuyuki,Nakano, Kazuhiro,Miyagishi, Akira,Noguchi, Tsuyoshi,Ohashi, Naohito
-
p. 1538 - 1548
(2007/10/03)
-
- New findings on the hemetsberger-knittel reaction (synthetic studies on indoles and related compounds. XLIII(1))
-
In the Hemetsberger-Knittel reaction for indole synthesis, the intermediate ethyl 2-azido-3-hydroxy-3-aryl-propionate (4) was found to be formed in the reaction of arylaldehyde 1 with ethyl azidoacetate at a lower temperature (-30°C) as the main product,
- Murakami, Yasuoki,Watanabe, Toshiko,Suzuki, Hideharu,Kotake, Nobuyo,Takahashi, Tomoko,Toyonari, Kiyono,Ohno, Masami,Takase, Kyoko,Suzuki, Takayuki,Kondo, Kazuhiro
-
p. 1739 - 1744
(2007/10/03)
-
- Facile Syntheses of Ethyl 2-Alkylindole-3-carboxylates: Reinvestigation of an Earlier Synthesis of Ethyl 3-Methylindole-2-carboxylates
-
A convenient, general synthesis of ethyl 2-alkylindole-3-carboxylates has been described from the easily accesible o-nitroarylaldehydes.In an alternate approach the same o-nitroarylaldehydes have been converted to ethyl 3-alkylindole-2-carboxylates.
- Wadia, M. S.,Mali, R. S.,Tilve, S. G.,Yadav, V. J.
-
p. 401 - 404
(2007/10/02)
-