TWI752098B - 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 - Google Patents
作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 Download PDFInfo
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- TWI752098B TWI752098B TW106134612A TW106134612A TWI752098B TW I752098 B TWI752098 B TW I752098B TW 106134612 A TW106134612 A TW 106134612A TW 106134612 A TW106134612 A TW 106134612A TW I752098 B TWI752098 B TW I752098B
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- hetcyc
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