METCALF, ANDREW T.,麦特卡菲 安德鲁 Ｔ,麥特卡菲 安德魯 Ｔ,FRY, DAVID,佛莱 大卫,佛萊 大衛,MCFADDIN, ELIZABETH A.,麦克法汀 伊丽莎贝斯 Ａ,麥克法汀 伊麗莎貝斯 Ａ,KOLAKOWSKI, GABRIELLE R.,科拉柯斯基 盖比尔 Ｒ,科拉柯斯基 蓋比爾 Ｒ,HAAS, JULIA,哈斯 茱莉亚,哈斯 茱莉亞,TANG, TONY P
申请号：
TW107135667
公开号：
TW201922741A
申请日:
2018.10.09
申请国别(地区):
TW
年份:
2019
代理人:
摘要：
Provided herein are compound of Formula I-IV and pharmaceutically acceptable salts thereof which exhibit rearranged during transfection (RET) kinase inhibition. In particular, provided herein are novel crystalline forms of 4-(6-(4-((6-methoxypyridin-3-yl)methyl)piperazin-1-yl)pyridin-3-yl)-6-(1-methyl-1H-pyrazol-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-carbonitrile (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 pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds, processes for making the compounds, and the use of the compounds in therapy. More particularly, the application relates to novel crystalline forms of Formula I-IV and pharmaceutically acceptable salts thereof useful in the treatment and prevention of diseases which can be treated with a RET kinase inhibitor, including RET-associated diseases and disorders.本文提供在轉染(RET)激酶抑制期間展現重排的式I-IV化合物及其醫藥學上可接受之鹽。特定言之，本文提供4-(6-(4-((6-甲氧基吡啶-3-基)甲基)哌嗪-1-基)吡啶-3-基)-6-(1-甲基-1H-吡唑-4-基)吡唑并[1,5-a]吡啶-3-甲腈(式I)、6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈(式II)、6-(2-羥基-2-甲基丙氧基)-4-(6-(6-(6-甲氧基菸鹼醯基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈(式III)、6-(2-羥基-2-甲基丙氧基)-4-(6-(4-羥基-4-(吡啶-2-基甲基)哌啶-1-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈(式IV)及其醫藥學上可接受之鹽的新穎結晶形式；包含該等化合物的醫藥組合物；製備該等化合物的方法；及該等化合物用於療法中的用途。更特定言之，本申請案係關於式I-IV及其醫藥學上可接受之鹽的新穎結晶形式，其適用於治療及預防能夠用RET激酶抑制劑治療的疾病，包括RET相關疾病及病症。
