메트칼프, 앤드류 티.,프라이, 데이비드,맥패딘, 엘리자베스 에이.,콜라코우스키, 가브리엘 알.,하스, 줄리아,탱, 토니 피.,지앙, 유통
申请号：
KR1020207010047
公开号：
KR1020200051744A
申请日:
2018.10.10
申请国别(地区):
KR
年份:
2020
代理人:
摘要：
Provided herein are compounds of Formula (I-IV) that exhibit inhibition of rearrangement (RET) kinase during transfection and pharmaceutically acceptable salts thereof. In particular, 4- (6- (4-((6-methoxypyridin-3-yl) methyl) piperazin-1-yl) pyridin-3-yl) -6- (1-methyl-1H-pyrazole- 4-yl) pyrazolo [1,5-a] pyridine-3-carbonitrile (Formula I), 6- (2-hydroxy-2-methylpropoxy) -4- (6- (6-((6 -Methoxypyridin-3-yl) methyl) -3,6-diazabicyclo [3.1.1] heptan-3-yl) pyridin-3-yl) pyrazolo [1,5-a] pyridine-3-carbonyl Tril (Formula II), 6- (2-hydroxy-2-methylpropoxy) -4- (6- (6- (6-methoxynicotinoyl) -3,6-diazabicyclo [3.1.1 ] Heptan-3-yl) pyridin-3-yl) pyrazolo [1,5-a] pyridine-3-carbonitrile (Formula III), 6- (2-hydroxy-2-methylpropoxy) -4- (6- (4-hydroxy-4- (pyridin-2-ylmethyl) piperidin-1-yl) pyridin-3-yl) pyrazolo [1,5-a] pyridine-3-carbonitrile (formula IV), and novel crystalline forms of pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds, methods of making the compounds, and use of the compounds in therapy are described herein It is provided. More particularly, this application relates to novel crystalline forms of Formula I-IV and its pharmaceutically acceptable salts useful for the treatment and prevention of diseases that can be treated with RET kinase inhibitors, including RET-associated diseases and disorders. .트랜스펙션 동안 재배열 (RET) 키나제 억제를 나타내는 화학식 I-IV의 화합물 및 그의 제약상 허용가능한 염이 본원에 제공된다. 특히, 4-(6-(4-((6-메톡시피리딘-3-일)메틸)피페라진-1-일)피리딘-3-일)-6-(1-메틸-1H-피라졸-4-일)피라졸로[1,5-a]피리딘-3-카르보니트릴 (화학식 I), 6-(2-히드록시-2-메틸프로폭시)-4-(6-(6-((6-메톡시피리딘-3-일)메틸)-3,6-디아자비시클로[3.1.1]헵탄-3-일)피리딘-3-일)피라졸로[1,5-a]피리딘-3-카르보니트릴 (화학식 II), 6-(2-히드록시-2-메틸프로폭시)-4-(6-(6-(6-메톡시니코티노일)-3,6-디아자비시클로[3.1.1]헵탄-3-일)피리딘-3-일)피라졸로[1,5-a]피리딘-3-카르보니트릴 (화학식 III), 6-(2-히드록시-2-메틸프로폭시)-4-(6-(4-히드록시-4-(피리딘-2-일메틸)피페리딘-1-일)피리딘-3-일)피라졸로[1,5-a]피리딘-3-카르보니트릴 (화학식 IV), 및 그의 제약상 허용가능한 염의 신규한 결정질 형태, 상기 화합물을 포함하는 제약 조성물, 상기 화합물의 제조 방법, 및 요법에서 상기 화합물의 용도가 본원에 제공된다. 더욱 특별하게는, 본 출원은 RET-연관된 질환 및 장애를
