- Deadly KCN and pricey metal free track for accessing β-ketonitriles employing mild reaction conditions
-
A one pot synthesis of β-ketonitriles from readily accessible 3-chloropropenals using economically benign iodine, aqueous ammonia and sodium hydroxide solution, employing mild reaction conditions have been described. This report presents a convenient, inexpensive, highly toxic-matter-free and eco-friendly approach for β-ketonitriles.
- Sharma, Pawan K.,Kumar, Rajiv,Ram, Sita,Chandak, Navneet
-
supporting information
p. 1847 - 1856
(2021/04/26)
-
- 3,5-Diaryl-1H-pyrazolo[3,4-b]pyridines as potent tubulin polymerization inhibitors: Rational design, synthesis and biological evaluation
-
A series of novel 3,5-diaryl-1H-pyrazolo[3,4-b]pyridines as tubulin polymerization inhibitors targeting the colchicine site were designed via ring tethering strategy, which was supported by conformational analysis. The general, chemically unstable and rot
- Zhai, Min'an,Liu, Shiyuan,Gao, Meiqi,Wang, Long,Sun, Jun,Du, Jianan,Guan, Qi,Bao, Kai,Zuo, Daiying,Wu, Yingliang,Zhang, Weige
-
p. 426 - 435
(2019/03/05)
-
- Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model
-
FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.
- Heng, Hao,Wang, Zhijie,Li, Hongmei,Huang, Yatian,Lan, Qingyuan,Guo, Xiaoxing,Zhang, Liang,Zhi, Yanle,Cai, Jiongheng,Qin, Tianren,Xiang, Li,Wang, Shuxian,Chen, Yadong,Lu, Tao,Lu, Shuai
-
p. 248 - 267
(2019/05/21)
-
- Palladium-Catalyzed Carbonylative α-Arylation of tert -Butyl Cyanoacetate with (Hetero)aryl Bromides
-
A three-component coupling protocol has been developed for the generation of 3-oxo-3-(hetero)arylpropanenitriles via a carbonylative palladium-catalyzed α-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of 13C-labeled carbon monoxide generated from 13COgen, the corresponding 13C-isotopically labeled β-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific 13C-isotope labeling. (Chemical Equation Presented).
- Jensen, Mikkel T.,Juhl, Martin,Nielsen, Dennis U.,Jacobsen, Mikkel F.,Lindhardt, Anders T.,Skrydstrup, Troels
-
p. 1358 - 1366
(2016/03/01)
-
- Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors
-
Described herein is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological effects of these compounds on the target enzyme were evaluated by using in vitro assays, leading to the potent and selective PDE-4 inhibitor (IC50 10 nM).
- Kim, Ikyon,Song, Jong Hwan,Park, Chang Min,Jeong, Joon Won,Kim, Hyung Rae,Ha, Jin Ryul,No, Zaesung,Hyun, Young-Lan,Cho, Young Sik,Sook Kang, Nam,Jeon, Dong Ju
-
scheme or table
p. 922 - 926
(2010/06/22)
-
- Stereoselective synthesis of 3,3-diarylacrylonitriles as tubulin polymerization inhibitors
-
(Chemical Equation Presented) A series of 3,3-diarylacrylonitriles were synthesized stereo-selectively as tubulin polymerization inhibitors for potential use in cancer chemotherapy. This synthetic route features stannylcupration and palladium-catalyzed St
- Fang, Zhenglai,Song, Yunlong,Sarkar, Taradas,Hamel, Ernest,Fogler, William E.,Agoston, Gregory E.,Fanwick, Phillip E.,Cushman, Mark
-
p. 4241 - 4244
(2008/09/20)
-
- Thienodipyridine derivatives, production and use thereof
-
A compound of the formula (I): wherein R is hydrogen or C2-6alkanoyl; X is halogen; and ring A is benzene ring which is optionally substituted by 1 to 4 substituents selected from {circle around (1)} halogen, {circle around (2)} hydroxy, {circl
- -
-
-
- Aminopyrazole derivatives
-
The present invention relates to a compound represented by the general formula [I]: wherein Ar1 represents an aryl or heteroaryl group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl, lower alke
- -
-
-
- Urea derivatives
-
The present invention relates to a compound represented by the general formula [I]: STR1 wherein A represents a nitrogen atom or a group represented by C--R5 ; Ar1 represents an aryl group which may have a substituent selected from t
- -
-
-
- Pyrazole derivatives
-
The present invention relates to a compound represented by the general formula [I]: wherein A and B rings are ortho-condensed to each other, A ring represents an aromatic carbocyclic or heterocyclic ring and B ring represents an aliphatic four- to seven-m
- -
-
-
- Thienopyridine derivatives and their use
-
PCT No. PCT/JP97/01413 Sec. 371 Date Jun. 26, 1997 Sec. 102(e) Date Jun. 26, 1997 PCT Filed Apr. 23, 1997 PCT Pub. No. WO97/40050 PCT Pub. Date Oct. 30, 1997There is disclosed a compound of the formula (A): wherein W is C-G or C-G' (G is optionally esterified carboxyl; and G' is halogen); X is oxygen, optionally oxidized sulfur or -(CH2)q- (q is 0 to 5); R is optionally substituted amino or heterocyclic group; the ring B is optionally substituted nitrogen-containing 5- to 7-membered ring; L is hydrogen, optionally substituted hydrocarbon residue, optionally substituted acyl, optionally substituted carbamoyl, optionally substituted thiocarbamoyl or optionally substituted sulfonyl provided that, when W is C-G, L is hydrogen, optionally substituted acyl, optionally substituted carbamoyl, optionally substituted alkoxycarbonyl, optionally substituted thiocarbamoyl or optionally substituted sulfonyl; n is 0 or 1; the ring A may have a substituent. A process for producing the compound (A) and a pharmaceutical composition containing the compound (A) are also disclosed. The pharmaceutical composition is useful for an anti-inflammatory drug, particularly, a drug for preventing or treating arthritis, a drug for inhibiting bone resorption, immunosuppressant or the like.
- -
-
-
- Thienopyridine or thienopyrimidine derivatives and their use
-
This invention provides an anti-inflammatory agent, particularly an agent for treating arthritis, and a bone resorption inhibiting agent, containing a thienopyridine or thienopyrimidine derivative or a salt thereof. This invention also provides a novel th
- -
-
-