Compounds with mutant IDH inhibiting activity, and preparation method and application thereofThe invention provides compounds capable of preventing and treating IDH mutation related diseases, and a preparation method and application thereof. Particularly, the invention provides compounds disclosed as Formula I and stereomers, racemes or pharmaceutically acceptable salts thereof, and also provides application of the compounds in preparing drugs for preventing and treating IDH mutation related diseases.The compound shown in a kind of formulas i, its stereoisomer, racemic modification or its pharmaceutically acceptable salt：wherein,for singly-bound or double bond；x1for c or s；work as x1during for c, r1with r2merge into=o；work as x1during for s, r1and r2respectively=o；x2for-cr12、-cr12r13, o, s or-nr12；wherein, x is worked as2for-cr12when,for double bond；work as x2for-cr12r13、o、s or-nr12when,for singly-bound；r12and r13it is each independently：h, substituted or unsubstituted c1-4alkyl, substituted or unsubstituted-c (o) c1-4alkyl, take generation or unsubstituted-c (o) c1-4alkenyl or substituted or unsubstituted c1-4alkyl cyano group；r3it is selected from：h, substituted or unsubstituted c1-4alkyl, substituted or unsubstituted c6-10aryl, substituted or unsubstituted c5-10it is miscellaneous aryl；r4it is selected from：nothing, h, substituted or unsubstituted c1-4alkyl, substituted or unsubstituted c6-10it is aryl, substituted or unsubstituted c5-10heteroaryl；or r3with r4merge into=o, or r3with r4substituted or unsubstituted c is collectively forming with the c atoms being attached thereto3-6cycloalkyl, or r3with r4substituted or unsubstituted 3-8 circle heterocycles are collectively forming with the c atoms being attached thereto and described heterocycle has 1-3 hetero atom selected from s, o, n；r5it is selected from：h, substituted or unsubstituted c1-4alkyl, substituted or unsubstituted c6-10aryl, substituted or unsubstituted c5-10it is miscellaneous aryl, substituted or unsubstituted c3-6cycloalkyl, substituted or unsubstituted 3-8 circle heterocycles base；r6it is selected from：h, substituted or unsubstituted c1-4alkyl, substituted or unsubstituted c6-10aryl, substituted or unsubstituted c5-10it is miscellaneous aryl, substituted or unsubstituted c3-6cycloalkyl, substituted or unsubstituted 3-8 circle heterocycles base；or r5with r6merge into=o, or r5with r6substituted or unsubstituted c is collectively forming with the c atoms being attached thereto3-6cycloalkyl, or r5with r6substituted or unsubstituted 3-8 circle heterocycles are collectively forming with the c atoms being attached thereto and described heterocycle has 1-3 hetero atom selected from s, o, n；r7、r8it is independently each：h, halogen, substituted or unsubstituted c1-4alkyl；r9it is selected from：h, substituted or unsubstituted c1-4alkyl；r10it is selected from：substituted or unsubstituted c1-4alkyl；or r9with r10with the c-shaped being attached thereto into substituted or unsubstituted c3-6cycloalkyl, substituted or unsubstituted 3-8 circle heterocycles base and described heterocyclic radical have the 1-3 hetero atoms for being selected from s, o, n；r11it is selected from：substituted or unsubstituted c6-20aryl, substituted or unsubstituted c5-15heteroaryl, substituted or unsubstituted c3-15 heterocyclic radical, substituted or unsubstituted c3-15cycloalkyl；wherein, described c5-15heteroaryl, c3-15heterocyclic radical contains independently of one another the 1-4 hetero atoms selected from n, o or s；and described ' substitution ' refers to one or more (such as 1,2,3 or 4 selected from a groups it is individual) substituent：a group substituents are selected from the group：h, halogen, substituted or unsubstituted c1-6alkyl, substituted or unsubstituted c3-8cycloalkyl, take generation or unsubstituted c1-4alkoxy, substituted or unsubstituted c6-10aryl, substituted or unsubstituted c5-10heteroaryl, substitution or not substituted c6-10aryloxy ,-c (o) nhra ',wherein, ra ' is selected from：it is substituted or unsubstituted c1-6alkyl, substituted or unsubstituted c3-8cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-8 unit's heteroaryls, with substituted or unsubstituted 3-8 circle heterocycles base；each rb is independently selected from h, halogen, substituted or unsubstituted c1-4alkyl, c1-4halogen substituted alkyl, substituted or unsubstituted c1-4alkoxy, substituted or unsubstituted c1-4halogenated alkoxy；and m is 0,1 or 2；for r1-r10, described ' substitution ' refer to one or more substituents selected from b groups；b group substituents are selected from the group：h, halogen, substituted or unsubstituted c1-6alkyl, c1-3haloalkyl, c1-3alkyl hydroxy ,- oh, substituted or unsubstituted c1-4alkoxy, substituted or unsubstituted c1-3alkylamino radical, 3-8 membered cyclic alkyls, 3-8 circle heterocycles base, ammonia base, nitro；also, in the a groups and b group substituents, ' substitution ' is selected from the group：halogen, c1-4alkyl, trifluoromethyl, ammonia base, nitro ,-oh.
돌연변이형 IDH 억제 활성을 지닌 화합물, 이의 제조 방법 및 용도본 발명은 IDH 돌연변이와 관련된 질환을 예방 및 치료하는 화합물, 이의 제조 방법 및 용도를 제공한다. 구체적으로, 본 발명은 식I의 화합물, 이의 입체 이성질체, 라세미체, 또는 이의 약학적으로 허용 가능한 염을 제공하고, IDH 돌연변이와 관련된 질환을 예방 및 치료하기 위한 약물의 제조에서의 응용을 제공한다. [이미지](I)식I로 표시되는 화합물, 이의 입체 이성질체, 라세미체(Racemate) 또는 이의 약학적으로 허용 가능한 염에 있어서,[이미지] (I), 상기 식에서, R3, R4는 각각 독립적으로 H, D, 치환 또는 비치환된 C1-4알킬기(Alkyl group)로부터 선택되고; 또는 R3 및 R4는 이에 연결된 C원자와 함께 치환 또는 비치환된 C3-6시클로알킬기(Cycloalkyl group)를 형성하거나, R3과 R4는 이에 연결된 C원자와 함께 치환 또는 비치환된 C3-6에폭시알킬기(Epoxy alkyl group)를 형성하며;R5, R6은 각각 독립적으로으로 H, 치환 또는 비치환된 C1-4알킬기, 치환 또는 비치환된 C6-10아릴기(Aryl group), 치환 또는 비치환된 C3-6시클로알킬기로부터 선택되고;또는 R5 및 R6은 이에 연결된 C원자와 함께 치환 또는 비치환된 C3-6시클로알킬기를 형성하며;R7과 R8은 각각 독립적으로 H, 할로겐(halogen), 치환 또는 비치환된 C1-4알킬기로부터 선택되고;R9는 H, 치환 또는 비치환된 C1-4알킬기로부터 선택되며;R10은 치환 또는 비치환된 C1-4알킬기로부터 선택되고;또는 R9 및 R10은 이에 연결된 C와 치환 또는 비치환된 C3-6시클로알킬기를 형성하며;R11은 치환 또는 비치환된 C6-10아릴기, 치환 또는 비치환된 C5-10헤테로아릴기(Heteroaryl group)로부터 선택되고; 상기 C5-10헤테로아릴기는 N, O 또는 S로부터 선택되는 1 ~ 4개의 헤테로 원자를 함유하며; 상기 “치환”은 A그룹으로부터 선택되는 하나 또는 다수개(예를 들어 1개, 2개, 3개 또는 4개)의 치환기를 구비하는 것을 지칭하고; A그룹 치환기는 H, D, 할로겐, 치환 또는 비치환된 C1-6알킬기, 치환 또는 비치환된 C3-8시클로알킬기, 치환 또는 비치환된 C1-4알콕시기(Alkoxy group), 치환 또는 비치환된 C6-10아릴기, 치환 또는 비치환된 C5-10헤테로아릴기, 치환 또는 비치환된 C6-10아릴옥시기(Aryloxy group), -C(O)NHRa’로부터 선택되며; Ra’는 치환 또는 비치환된 C1-6알킬기, 치환 또는 비치환된 C3-8시클로알킬기로부터 선택되고;R12는 H, D, 치환 또는 비치환된 C1-4알킬기, 치환 또는 비치환된 3-6원 고리로부터 선택되며; R3-R12에 관하여, 상기 “치환”은 B그룹으로부터 선택되는 하나 또는 다수개의 치환기를 구비하는 것을 지칭하고;B그룹 치환기는 H, D, 할로겐, 치환 또는 비치환된 C1-6알킬기, -OH, 치환 또는 비치환된 C1-4알콕시기3-8원 시클로탄화수소기(Cyclohydrocarbon group), 아미노기(Amino group), 니트로기(Nitro group)로부터 선택되며;또한, 상기 A그룹과 B그룹 치환기에서, 상기 “치환”은 D, 할로겐, C1-4알킬기, 트리플루오로메틸기(Trifluoromethyl group), 아미노기, 니트로기, -OH로부터 선택되는 하나 또는 다수개(예를 들어 1/2/3/4 또는 5)의 치환기 구비하는 것을 지칭하는 식I로 표시되는 화합물, 이의 입체 이성질체, 라세미체 또는 이의 약학적으로 허용 가능한 염.