Heterocyclic Spiro bicyclic Heterocyclic derivatives or bridged bicyclic, of pyrazolo 1,5-a pyrimidines as inhibitors of RAF Kinase and Methods for their Preparation

摘要

Referring to a Heterocyclic Compound Derivative of pyrazolo [1,5-a] pyrimidine of formula (a), where R1 is a Heterocyclic Ring of 5 to 7 members optionally replaced with Cho, CN -, N3, among others; R2 is a bicyclic Ring 9 to 14 members, a heteroaryl Ring 5 to 7 members Anil, a The bicyclic heteroaryl 9 to 14 members, among others; R3, R4 and R5 are CN, c1-c6 alkyl, or7, C (o)Among others; R7 is H, alkyl of C1 - C6 Ring heteroaryl 5 to 10 members, among others. Preferred compounds are: 3 - (7 - [6 - [(1-azabicyclo [2.2.2] oct - 4 - methyl) amino] pyridin-3-yl) - pyridin - 2 - 4 - ilpirazolo [1,5-a] pyrimidine - 3 - il) phenol, 2 - (6 - [7 - {(3S) - 1-azabicyclo [2.2.2] Oct - 3 - ilamino] pyridin-3-yl) - pyridin - 2 - 4 - ilpirazolo [1,5-a] pyrimidin-2-yl) - 3 - il phenol, among others.It also relates to a Pharmaceutical Composition and a preparation method. These compounds inhibit Tyrosine Kinases, K - Raf and RAF Kinases and are useful in the treatment of cancer cells