- Heterocyclic compounds as FGFR4 inhibitors
-
The present invention provides heterocyclic compounds as selective inhibitors of fibroblast growth factor receptor 4 (FGFR4), pharmaceutical compositions containing the compounds, methods of preparingthe compounds, and methods of treating cell proliferative diseases, such as cancer, using the compounds of the invention.
- -
-
Paragraph 0498-0503
(2021/02/10)
-
- Fused tricyclic derivative as FGFR4 inhibitor
-
The present invention provides a fused tricyclic derivative that is the selective inhibitor of fibroblast growth factor receptor 4 (FGFR4), a pharmaceutical composition containing the compound, a method of making the compound and a method of treating cell proliferative diseases, such as cancer, using the compounds of the invention.
- -
-
Paragraph 0420-0425
(2021/05/12)
-
- Transition-metal-free mono- or dinitration of protected anilines
-
An amide-assisted arene nitration is presented, and both mono- and dinitration of protected anilines could be effected by using NaNO2 and NaNO3 as the mono- and bisnitrating agents, respectively. This divergent synthesis is transition-metal- and acid-free, and features a broad substrate scope, low cost, and ortho–para selectivity.
- Dai, Enrui,Dong, Ying,Dong, Yongrui,Kong, Rui,Liang, Deqiang,Liu, Guangzhang,Ma, Yinhai,Wu, Qiong
-
-
- PIII/PV=O Catalyzed Cascade Synthesis of N-Functionalized Azaheterocycles
-
An organocatalytic method for the modular synthesis of diverse N-aryl and N-alkyl azaheterocycles (indoles, oxindoles, benzimidazoles, and quinoxalinediones) is reported. The method employs a small-ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) and a hydrosilane reductant to drive the conversion of ortho-functionalized nitroarenes into azaheterocycles through sequential intermolecular reductive C?N cross coupling with boronic acids, followed by intramolecular cyclization. This method enables the rapid construction of azaheterocycles from readily available building blocks, including a regiospecific approach to N-substituted benzimidazoles and quinoxalinediones.
- Li, Gen,Luzung, Michael R.,Nykaza, Trevor V.,Radosevich, Alexander T.,Yang, Junyu
-
supporting information
p. 4505 - 4510
(2020/02/05)
-
- 3-(Ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium cation: A green alternative to tert-butyl nitrite for synthesis of nitro-group-containing arenes and drugs at room temperature
-
Due to their remarkable properties, task-specific ionic liquids have turned out to be progressively popular over the last few years in the field of green organic synthesis. Herein, for the first time, we report that a new task-specific nitrite-based ionic liquid such as 3-(ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium bis(trifluoromethanesulfonyl)imides (TS-N-IL) derived from biodegradable ethyl nicotinate indeed acted as an efficient and eco-friendly reagent for the synthesis of highly valuable nitroaromatic compounds and drugs including nitroxynil, tolcapone, niclofolan, flutamide, niclosamide and nitrazepam. The bridging of an ionic liquid with nitrite group not only increases the yield and rate of direct C[sbnd]N bond formation reaction but also allows easy product separation and recyclability of a byproduct. Nonvolatile nature, easy synthesis, merely stoichiometric need and mildness are a portion of the extra focal points of TS-N-IL while contrasted with tert-butyl nitrite an outstanding and highly-flammable reagent utilized largely in organic synthesis.
- Chaudhary, Renu,Natarajan, Palani,Rani, Neetu,Sakshi,Venugopalan, Paloth
-
supporting information
(2019/12/30)
-
- PYRIMIDINE DERIVATIVE, METHOD FOR PREPARING SAME AND USE THEREOF IN MEDICINE
-
The present invention relates to a pyrimidine derivative, a method for preparing same and use thereof in medicine. In particular, the present invention relates to a pyrimidine derivative represented by general formula (I), a method for preparing same and a pharmaceutically acceptable salt thereof as well as use thereof as a therapeutic agent, in particular as a FGFR4 kinase inhibitor, definitions of each substituent in the general formula (I) being the same as those defined in the description.
- -
-
Paragraph 0108; 0109
(2019/04/16)
-
- Regioselective nitration of anilines with Fe(NO3)3·9H2O as a promoter and a nitro source
-
An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2) intermediate, which is generated by the thermal decomposition of iron(iii) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.
- Gao, Yang,Mao, Yuanyou,Zhang, Biwei,Zhan, Yingying,Huo, Yanping
-
supporting information
p. 3881 - 3884
(2018/06/08)
-
- Heterocycle type derivative and preparing method and pharmaceutical application thereof
-
The invention relates to a novel heterocycle type derivative, a preparing method thereof, a medicine composition containing the derivative and application of the heterocycle type derivative as therapeutic agent, particularly an FGFR4 inhibitor. The preferable compound has a good inhibiting effect on FGFR4.
- -
-
Paragraph 0243; 0246-0249
(2018/07/30)
-
- Pyrimidine derivatives as well as preparation method and medical applications thereof
-
The invention relates to pyrimidine derivatives as well as a preparation method and medical applications thereof, in particular to pyrimidine derivatives shown as a general formula (I) in the description, a preparation method and medicinal salts thereof and applications of the pyrimidine derivatives and the medicinal salts as therapeutic agents, especially as FGFR4 (fibroblast growth factor receptor 4) kinase inhibitors. Definitions of substituent groups in the general formula (I) are the same as those in the description.
- -
-
Paragraph 0393; 0396-0399
(2017/12/27)
-
- Regioselective ortho-nitration of N-phenyl carboxamides and primary anilines using bismuth nitrate/acetic anhydride
-
An efficient and one-pot synthetic method for the regioselective ortho-nitration of the N-phenyl carboxamides and primary anilines has been developed by using bismuth nitrate and acetic anhydride as the nitrating reagents. Reaction proceeds at room temperature and results in corresponding ortho-nitrated products in moderate to excellent yields. This method provides an operationally simple, regioselective, and efficient access to synthesize o-nitro anilines under the mild conditions.
- Lu, Yang,Li, Yaming,Zhang, Rong,Jin, Kun,Duan, Chunying
-
supporting information
p. 9422 - 9427
(2013/10/08)
-
- Discovery and optimization of benzotriazine Di-N-oxides targeting replicating and nonreplicating mycobacterium tuberculosis
-
Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC 50) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.
- Chopra, Sidharth,Koolpe, Gary A.,Tambo-Ong, Arlyn A.,Matsuyama, Karen N.,Ryan, Kenneth J.,Tran, Tran B.,Doppalapudi, Rupa S.,Riccio, Edward S.,Iyer, Lalitha V.,Green, Carol E.,Wan, Baojie,Franzblau, Scott G.,Madrid, Peter B.
-
scheme or table
p. 6047 - 6060
(2012/09/05)
-
- Exploration of larger central ring linkers in furamidine analogues: Synthesis and evaluation of their DNA binding, antiparasitic and fluorescence properties
-
The effects of replacing the central furan ring of furamidine with indole and benzimidazole on their DNA binding affinity, antiparasitic activity and fluorescence are reported. The bis-cyanophenylindoles required to make the corresponding amidines were prepared by sequential Stille and/or Suzuki coupling reactions. The bis-cyanophenylbenzimidazoles were obtained by coupling 4-cyanobenzaldehydes with the appropriate cyano substituted phenylenediamine. The bis-nitriles were converted to the diamidines by reaction with LiN[Si(CH3)3]2 or by Pinner methodology. Specifically, we have prepared new series of 2,6- and 2,5-diaryl indoles (6a,b, 12 and 17a-d) and the related benzimidazoles (24, 30 and 35). The new compounds bind in the DNA minor groove in DNA AT base pair sequences and eight of the ten new analogues exhibit ΔTm values comparable to or higher than that of furamidine. Six of ten of the new compounds exhibit lower IC 50 values against Trypanosoma brucei rhodesiense (T. b. r.) and eight of ten exhibit lower IC50 values against Plasmodium falciparum (P. f.) than furamidine. Four of the ten show greater efficacy than furamidine in the rigorous T. b. r. STIB900 mouse model for African trypanosomiasis. Generally, the fluorescence properties of the new analogues are similar to that of DAPI.
- Farahat, Abdelbasset A.,Paliakov, Ekaterina,Kumar, Arvind,Barghash, Alaa-Eldin M.,Goda, Fatma E.,Eisa, Hassan M.,Wenzler, Tanja,Brun, Reto,Liu, Yang,Wilson, W. David,Boykin, David W.
-
p. 2156 - 2167
(2011/05/06)
-
- Synthesis and property studies of cyclotrisazobenzenes
-
Azobenzenophanes are fascinating macrocycles, which are of special interest due to their unique photochromic behavior. Cyclotrisazobenzenes 2 (R = H, Br, tBu) were prepared to probe how much strain the photoisomerization of the azobenzene motive can tolerate. The macrocycles were synthesized in an overall yield of 10-20% from oriho-phenylenediamine (6). Solid-state structures of cyclotrisazobenzenes 2a and 2b were obtained. Irradiation under various conditions did not induce any isomerization.
- Reuter, Raphael,Hostettler, Nik,Neuburger, Markus,Wegner, Hermann A.
-
supporting information; experimental part
p. 5647 - 5652
(2010/02/28)
-
- Synthesis of nitrile-terminated potential molecular electronic devices
-
Several potential molecular devices have been synthesized consisting of oligo(phenylene ethynylene) (OPE) backbones containing a terminal nitrile group alligator clip as a means of attachment to a metal surface. The synthesis of four new nitrile-containing OPEs is discussed, including an improved synthesis of an intermediate used in our prior production of OPEs containing acetate-protected thiol alligator clips.
- Dirk, Shawn M.,Tour, James M.
-
p. 287 - 293
(2007/10/03)
-
- Tetrazolyl-phenyl acetamide glucokinase activators
-
Tetrazolyl-phenyl acetamides are active as glucokinase activators, and are able to increase insulin secretion, which makes them useful for treating type II diabetes.
- -
-
-
- Tetrazolyl-phenyl acetamide glucokinase activators
-
Tetrazolyl-phenyl acetamides are active as glucokinase activators, and are able to increase insulin secretion, which makes them useful for treating type II diabetes.
- -
-
Page column 60
(2010/01/31)
-
- Ammonium nickel sulphate mediated nitration of aromatic compounds with nitric acid
-
Aromatic compounds were efficiently nitrated under mild conditions employing ammonium nickel sulphate and nitric acid as a reagent. This procedure works efficiently at room temperature yielding mononitro derivative in fair to good yield with high regioselectivity.
- Tasneem,Ali,Rajanna,Saiparakash
-
p. 1123 - 1127
(2007/10/03)
-
- Synthesis and progesterone receptor antagonist activities of 6-aryl benzimidazolones and benzothiazolones
-
Novel 6-aryl benzimidazolones and benzothiazolones were prepared and examined as bioisosteres of the recently reported 6-aryl dihydroquinolines (1) for progesterone receptor (PR) antagonist activities. PR antagonist activities increased when compounds 9c-f possessed a more lipophilic group at position-1 and pendent aryl moiety para to NH moiety. Furthermore, conversion of carbonyl moiety of 9e,f to the thio-carbonyl led to benzoimidazolethiones 15a,b with significantly improved potency and binding affinity.
- Zhang, Puwen,Terefenko, Eugene A.,Wrobel, Jay,Zhang, Zhiming,Zhu, Yuan,Cohen, Jeffrey,Marschke, Keith B.,Mais, Dale
-
p. 2747 - 2750
(2007/10/03)
-
- Reductive cyclization with baker's yeast of 4-alkyl-2-nitro-acetanilides to 6-alkylbenzimidazoles and 1-hydroxy-2-methyl-6-alkylbenzimidazoles
-
Reduction of 4-substituted 2-nitroacetanilides by baker's yeast in acid media effected cyclization, resulting in the formation of n-substituted 2-methylbenzimidazoles and 6-substituted 1-hydroxy-2-methylbenzimidazole via the chemo- and regioselective reduction of the 2-nitro aromatic group to amine or hydroxylamine.
- Navarro-Ocana,Olguin,Luna,Jimenez-Estrada,Barzana
-
p. 2754 - 2756
(2007/10/03)
-
- Mild, efficient and selective nitration of anilides, non-activated and moderately activated aromatic compounds with ammonium molybdate and nitric acid as a new nitrating agent
-
Ammonium molybdate [Mo(VI)] is operationally simple, environmentally safe and inexpensive reagent. Regioselective nitration of anilides, non-activated and moderately activated aromatic compounds could be afforded by employing ammonium molybdate and nitric acid as mild and effective nitrating agent. This procedure works efficiently under reflux conditions to prepare mononitroderivatives of anilides, non-activated and moderately activated aromatic compounds in good to excellent yield with high regioselectivity.
- Sana, Sariah,Rajanna,Ali, Mir Moazzam,Saiprakash
-
-
- Oxidative Bromination of Aromatic Amides using Sodium Perborate as Oxidant
-
Sodium perborate in glacial acetic acid-acetic anhydride with potassium bromide and sodium tungstate as a catalyst, provides a novel system for the bromination of aromatic amides.
- Hanson, James R.,Harpel, Simone,Medina, Inmaculada C. Rodriguez,Rose, Dorian
-
p. 432 - 433
(2007/10/03)
-
- Condensed Heteroaromatic Ring Systems. XII. Synthesis of Indole Derivatives from Ethyl 2-Bromocarbanilates
-
The palladium-catalyzed reaction of ethyl 2-bromocarbanilate with trimethylsilylacetylene yielded ethyl 2-(trimethylsilylethynyl)carbanilate, which was treated with sodium ethoxide to give indole.The carbanilates having a methyl or a bromo substituent were similarly transformed to corresponding indole derivatives.Furthermore, pyrrolo- and Pyrrolopyridines were synthesized by this method.Keywords---palladium-catalyzed reaction; trimethylsilylacetylene; ethyl 2-halocarbanilate; ethyl 2-halopyridinecarbamate; ethyl 2-(trimethylsilylethynyl)carbanylate; ethyl o-(trimethylsilylethynyl)pyridinecarbamate;indole;pyrrolopyridine
- Sakamoto, Takao,Kondo, Yoshinori,Iwashita, Shigeki,Yamanaka, Hiroshi
-
p. 1823 - 1828
(2007/10/02)
-