- Pyrazole derivative for FGFR inhibitor and preparation method of pyrazole derivative
-
The invention provides a pyrazole derivative for an FGFR inhibitor and a preparation method of the pyrazole derivative. The invention specifically relates to an amide pyrazole compound serving as an FGFR irreversible inhibitor, and a preparation method and application thereof. The present invention provides a compound as shown in Formula I, or a pharmaceutically acceptable salt, or solvate, isotope substitute, prodrug, or metabolite thereof. The compound as shown in general formula I have FGFR inhibitory activity, and is capable of preventing or treating disorders associated with FGFR activityor expression, preferably such as cancer.
- -
-
Paragraph 0324-0328
(2021/03/06)
-
- Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAFV600E/p38α inhibitors
-
The synergistic effect of dual inhibition of serine/threonine protein kinases that are involved in the same signalling pathway of the diseases can exert superior biological benefits for treatment of these diseases. In the present work, a new series of (imidazol-5-yl)pyrimidine was designed and synthesized as dual inhibitors of BRAFV600E and p38α kinases which are considered as key regulators in mitogen-activated protein kinase (MAPK) signalling pathway. The target compounds were evaluated for dual kinase inhibitory activity. The tested compounds exhibited nanomolar scale IC50 values against BRAFV600E and low to sub-micromolar IC50 range against p38α. Compound 20h was identified as the most potent dual BRAFV600E/p38α inhibitor with IC50 values of 2.49 and 85 nM, respectively. Further deep investigation revealed that compound 20h possesses inhibitory activity of TNF-α production in lipopolysaccharide-induced RAW 264.7 macrophages with IC50 value of 96.3 nM. Additionally, the target compounds efficiently frustrated the proliferation of LOX-IMVI melanoma cell line. Compound 20h showed a satisfactory antiproliferative activity with IC50 value of 13 μM, while, compound 18f exhibited the highest cytotoxicity potency with IC50 value of 0.9 μM. Compound 18f is 11.11-fold more selective toward LOX-IMVI melanoma cells than IOSE-80PC normal cells. The newly reported compounds represent therapeutically promising candidates for further development of BRAFV600E/p38α inhibitors in an attempt to overcome the acquired resistance of BRAF mutant melanoma.
- Ali, Eslam M.H.,El-Telbany, Rania Farag A.,Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,Mersal, Karim I.,Zaraei, Seyed-Omar,El-Gamal, Mohammed I.,Choi, Se-In,Lee, Kyung-Tae,Kim, Hee-Kwon,Lee, Kwan Hyi,Oh, Chang-Hyun
-
-
- BICYCLIC ETHER O-GLYCOPROTEIN-2-ACETAMIDO-2-DEOXY-3-D-GLUCOPYRANOSIDASE INHIBITORS
-
Described herein are compounds represented by formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of preparing and using the same. The variables Ar, X, R1, R3, R 4, Y1, Y2, n and p are as defined herein.
- -
-
Paragraph 00259
(2020/08/22)
-
- A 1 substituted benzimidazole derivatives and the preparation method
-
The invention discloses a 1 substituted benzimidazole derivatives (4 - (1 H - benzo [d] imidazol - 1 - yl) - 3 - methoxyphenyl) preparation of method, in order to 4 - fluoro - 3 - methoxybenzoic acid as the starting material, through esterification, conde
- -
-
Paragraph 0021; 0022
(2018/03/13)
-
- Pyrazolo [3,4 - the b] pyridine and [...] composition preparation method and use of (by machine translation)
-
The present invention provides a pyrazolo [3,4 - the b] pyridine and [...] compound of preparation and use, in particular, the present invention provides a following formula (I) compounds are shown, wherein the definition of each group as described in the specification. The compounds of the invention has excellent tyrosine kinase inhibiting activity, so can be used for preparing a series of treating diseases associated with the tyrosine kinase activity of the drug. (by machine translation)
- -
-
Paragraph 0548; 0549; 0550; 0551
(2017/07/22)
-
- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
-
Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
- -
-
Paragraph 0175
(2014/05/24)
-
- HETEROCYCLIC COMPOUND AND USE THEREOF
-
The present invention provides a heterocycle derivative having a superior amyloid β production inhibitory activity and/or a superior γ-secretase modulation activity, and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the present specification, or a salt thereof.
- -
-
Page/Page column 69
(2012/03/26)
-
- A scalable synthesis of MN-447, an antagonist for integrins αvβ3 and αIIbβ 3
-
(2S)-Benzeneslfonylamino-3-[3-methoxy-4-{4-(1,4,5,6-tetrahydropyrimidin-2- ylamino)piperidin-1-yl}benzoylamino]propionic acid, MN-447, is a potent antagonist of the integrins αvβ33 and αIIbβ3 Herein, we report a novel synthetic protocol that produces MN-447 in an overall yield of 45%. This protocol, when compared with the original synthetic route for MN-447, is more cost-effective, requires fewer steps, does not require chromatographic purification of intermediates and MN-447, and increases the overall yield by 35%. This report focuses on the synthetic strategies that were developed for this protocol. Now, the large quantities of MN-447 that are needed for preclinical and toxicological studies can be readily obtained.
- Ishikawa, Minoru,Tsushima, Masaki,Kubota, Dai,Yanagisawa, Yumiko,Hiraiwa, Yukiko,Kojima, Yasuo,Ajito, Keiichi,Anzai, Naomichi
-
p. 596 - 602
(2013/01/03)
-
- Facile synthesis of 7-amino anilinoquinazolines via direct amination of the quinazoline core
-
The facile preparation of 4-(3-chloro-4-fluoroanilino)-6-alkoxy-7- aminoquinazolines from their corresponding 7-triflate and 7-fluoro precursors are highlighted.
- Harris, Craig S.,Kettle, Jason G.,Williams, Emma J.
-
p. 7381 - 7384
(2007/10/03)
-
- Pyrimido compounds having antiproliferative activity
-
Disclosed are novel pyrimido compounds that are selective inhibitors of both KDR and FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular breast, colon, lung and prostate tumors. Also disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer.
- -
-
Page/Page column 42
(2010/02/08)
-
- Aminopiperidine derivates as integrin αvβ3 antagonists
-
An objective of the present invention is to provide compounds having integrin αvβ3antagonistic activity, cell adhesion inhibitory activity, GP IIb/IIIa antagonistic activity, and/or human platelet aggregation inhibitory activity, and, therapeutic agents for treating cardiovascular diseases, angiogenesis-related diseases, cerebrovascular diseases and the like and for inhibiting platelet aggregation. The derivatives according to the present invention are compounds represented by formula (I) or pharmaceutically acceptable salts or solvates thereof: wherein A represents a five- to seven-membered heterocyclic group containing two nitrogen atoms or the like; D represents >NH2, >CH2or the like; X and Z represent CH or a nitrogen atom; R7and R8represent alkyl, halogen or the like; Q represents >C═O, >CH2or the like; R9represents H, alkyl, aralkyl or the like; R10represents H, alkynyl or the like; R11represents H, substituted amino or the like; R12represents H or alkyl; m is 0 to 5; n is 0 to 4; p and q are each 1 to 3; and r is 0 or 1.
- -
-
-
- Antiestrogens. Synthesis and Evaluation of Mammary Tumor Inhibiting Activity of 1,1,2,2-Tetraalkyl-1,2-diphenylethanes
-
Among the newly synthesized 1,1,2,2-tetraalkyl-1,2-diphenylethanes, 1,1,2,2-tetramethyl-1,2-bis(4'-hydroxyphenyl)ethane (23) and 1,1,2,2-tetramethyl-1,2-bis(3'-hydroxyphenyl)ethane (26) were the most active compounds regarding estradiol receptor affinity, exhibiting Ka values of 0.73*108 and 0.67*108 M-1, respectively.In vivo, 23 and 26 showed only very small uterotrophic activity in the mouse.They strongly inhibited (73percent) the estrone-stimulated mouse uterine growth.Tested on the 9,10-dimethyl-1,2-benzanthracene induced hormone-dependent mammary adenocarcinoma of the Sprague-Dawley rat, compounds 23 and 26 exhibited a dose-dependent inhibition of the tumor growth, having a strong effect at a dose of 20 (mg/kg)/day (compound 23).
- Hartmann, Rolf W.,Kranzfelder, Gerhard,Angerer, Erwin, v.,Schoenenberger, Helmut
-
p. 841 - 848
(2007/10/02)
-