- NEW COMPOUND HAVING FGFR INHIBITORY ACTIVITY AND PREPARATION AND APPLICATION THEREOF
-
The present invention relates to a new compound having an FGFR inhibitory activity and preparation and application thereof. In particular, the compound according to the present invention has a structure as shown in formula I, wherein each group and substituent are as defined in the description. Also disclosed in the present invention are a preparation method for the compound and a use thereof in preparation of a drug for treating and/or preventing a tumor-related disease and/or an FGFR-related disease.
- -
-
Paragraph 0390; 0391
(2019/05/30)
-
- Development of matrix metalloproteinase-13 inhibitors – A structure-activity/structure-property relationship study
-
A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhi
- Fuerst, Rita,Yong Choi, Jun,Knapinska, Anna M.,Smith, Lyndsay,Cameron, Michael D.,Ruiz, Claudia,Fields, Gregg B.,Roush, William R.
-
supporting information
p. 4984 - 4995
(2018/09/27)
-
- Synthetic method of 4-chloropyrrolopyrimidine
-
The invention relates to a synthetic method of 4-chloropyrrolopyrimidine. The synthetic method takes ethyl cyanoacetate, bromoacetaldehyde diethyl acetal, thiourea, sodium ethoxide and hydrogen peroxide as raw materials and takes DMF, ethanol, water and phosphorous oxychloride as solvents to obtain the target product 4-chloropyrrolopyrimidine through four steps of reactions. The method improves amethod of removing a mercapto group in a third step. The mercapto group is first oxidized to sulfinic acid by using the hydrogen peroxide and then is removed under acidic conditions. The method is mild in reaction conditions, safe in operation and high in yield, is environmentally friendly, and is suitable for industrial production.
- -
-
Paragraph 0008; 0018
(2018/12/05)
-
- 6-methyl 7-position-denitrified purine nucleoside compounds and application thereof
-
The invention discloses6-methyl 7-position-denitrified purine nucleoside compounds and an application thereof and belongs to the field of medicinal chemistry. The 6-methyl 7-position-denitrified purine nucleoside compounds or pharmaceutically acceptable salts of the compounds having characteristics of a structure shown as formula I are a kind of novel-structured compounds designed and synthesized according to protein structure characteristics of RNA virus polymerase, and the compounds can inhibit RNA viruses, thereby being capable of serving as potential drugs for preventing and treating infection of RNA viruses such as HCV (hepatitis c virus), influenza virus, HRV (rhinovirus), RSV, Ebola virus, DENV (Dengue virus), enterovirus and the like.
- -
-
-
- Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase
-
Pre-steady state kinetic analysis was utilized for biochemical evaluation of a series of cyclobutyl adenosine nucleotide analogs with HIV-1 RT WT. The phosphonyl-diphosphate form of the cyclobutyl nucleotide, 5, was the most efficiently incorporated of the series. Nucleotide 5 was fourfold more efficiently incorporated than the FDA approved TFV-DP by RTWT. The kinetics of incorporation for 5 using the drug resistant mutant enzyme K65R was also determined. Compound 5 was threefold more efficiently incorporated compared to TFV-DP with RTK65R. These results demonstrate cyclobutyl adenosine analogs can act as substrates for incorporation by HIV-1 RT and be a potential scaffold for HIV inhibitors.
- Kim, Jiae,Wang, Ligong,Li, Yongfeng,Becnel, Kimberlynne D.,Frey, Kathleen M.,Garforth, Scott J.,Prasad, Vinayaka R.,Schinazi, Raymond F.,Liotta, Dennis C.,Anderson, Karen S.
-
p. 4064 - 4067
(2012/07/14)
-
- Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors
-
Thymidine phosphorylase (TP) is over-expressed in various tumour types and plays an important role in tumour angiogenesis, growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP, therefore, inhibitors of TP are of significant interest in cancer chemotherapy. A series of xanthine oxidase (XO) activated prodrugs of known inhibitors of TP have been designed and synthesized with the ultimate intent of improving tumour selectivity and pharmacokinetic characteristics. These prodrugs were not inhibitors of TP, but were selectively oxidized by XO at C-2 and/or C-4 of the uracil ring moiety to generate the desired TP inhibitor. Molecular modelling of both the TP inhibitors and XO-activated prodrugs rationalized their binding in the active site of the human TP crystal structure.
- Reigan, Philip,Gbaj, Abdul,Stratford, Ian J.,Bryce, Richard A.,Freeman, Sally
-
p. 1248 - 1260
(2008/09/21)
-
- Synthesis and enzymatic evaluation of xanthine oxidase-activated prodrugs based on inhibitors of thymidine phosphorylase
-
A series of xanthine oxidase-activated prodrugs of known inhibitors of thymidine phosphorylase are described. These prodrugs were oxidised by xanthine oxidase at C-2 and/or C-4 of the uracil ring to generate the desired TP inhibitor. The scheme shows the prodrug of TPI. A series of xanthine oxidase-activated prodrugs of known inhibitors of thymidine phosphorylase has been designed and synthesised to introduce tumour selectivity. These prodrugs were oxidised by xanthine oxidase at C-2 and/or C-4 of the uracil ring to generate the desired TP inhibitor.
- Reigan, Philip,Gbaj, Abdul,Chinje, Edwin,Stratford, Ian J.,Douglas, Kenneth T.,Freeman, Sally
-
p. 5247 - 5250
(2007/10/03)
-
