630126-16-8

Usage

InChI:InChI=1/C12H8ClN3O/c13-11-6-12(16-7-15-11)17-9-1-2-10-8(5-9)3-4-14-10/h1-7,14H

Upstream product

• 1193-21-1 4,6-dichloropyrimidine 
• 1953-54-4 indol-5-ol 

Relevant academic research and scientific papers

Novel pazopanib derivatives and pharmaceutical composition comprising the same

The present invention relates to novel pazopanib derivatives or a salt thereof having inhibition activities of angiogenesis and epidermal growth factors at the same time, and to a pharmaceutical composition comprising the same as an active ingredient. The pazopanib derivatives have inhibition activities of angiogenesis and epidermal growth factors at the same time unlike pazopanib, thereby more effectively treating and preventing EGFR-related cancer diseases such as lung cancer, colon cancer or breast cancer through a multiple aim target, and effectively treating and preventing non-small-cell lung cancer which Iressa or Tarceva cannot have an effect on.COPYRIGHT KIPO 2017

Structure-activity relationship of indole-tethered pyrimidine derivatives that concurrently inhibit epidermal growth factor receptor and other angiokinases

Antiangiogenic agents have been widely investigated in combination with standard chemotherapy or targeted cancer agents for better management of advanced cancers. Therapeutic agents that concurrently inhibit epidermal growth factor receptor and other angiokinases could be useful alternatives to combination therapies for epidermal growth factor receptordependent cancers. Here, we report the synthesis of an indole derivative of pazopanib using a bioisosteric replacement strategy, which was designated MKP101. MKP101 inhibited not only the epidermal growth factor receptor with an IC50 value of 43 nM but also inhibited angiokinases as potently as pazopanib. In addition, MKP101 effectively inhibited vascular endothelial growth factor-induced endothelial proliferation, tube formation, migration of human umbilical vein endothelial cells and proliferation of HCC827, an epidermal growth factor receptor-addicted cancer cell line. A docking model of MKP101 and the kinase domain of the epidermal growth factor receptor was generated to predict its binding mode, and validated by synthesizing and evaluating MKP101 derivatives. Additionally, a study of structure-activity relationships of indolylamino or indolyloxy pyrimidine analogues derived from MKP101 demonstrated that selectivity for epidermal growth factor receptor and other angiokinases, especially vascular endothelial growth factor receptor 2 depends on the position of substituents on pyrimidine and the type of link between pyrimidine and the indole moiety. We believe that this study could provide a basis for developing angiokinase inhibitors having high affinity for the epidermal growth factor receptor, from the pyrimidine scaffold.

CYCLIC DIARLY UREAS SUITABLE AS TYROSINE KINASE INHIBITORS

The invention relates to novel compounds of Formula (I): wherein p is 1, 2 or 3; n is 0, 1, 2 or 3; mis0,1,2or3; A is CRc, S, NRc or O, where Rc is H or lower alkyl; X, Y and Z are each independently selected fro N or C-R

DIARYL UREA DERIVATIVES USEFUL FOR THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES

The invention relates to the use of diaryl urea derivatives in the treatment of protein kinase dependent diseases or for the manufacture of pharmaceutical compositions for use in the treatment of said diseases, methods of use of diaryl urea derivatives in the treatment of said diseases, pharmaceutical preparations comprising diaryl urea derivatives for the treatment of said diseases, diaryl urea derivatives for use in the treatment of said diseases, novel diaryl urea derivatives, pharmaceutical preparations comprising these novel diaryl urea derivatives, processes for the manufacture of the novel diaryl urea derivatives, the use or methods of use of the novel diaryl urea derivatives as mentioned above, and/or these novel diaryl urea derivatives for use in the treatment of the animal or human body.