INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDINGThe present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.A compound of Formula (I) or a pharmaceutically acceptable salt and/or solvate thereof:(I)wherein:R1 is a heterocycloalkyl that is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fiuoroalkyl, C3-iocycloalkyl, OR4, SR4, NR5R6, Ci-galkyleneOR4, Ci-6alkyleneSR4 and Ci-6alkyleneNR5R6, provided that R1 comprises at least one basic nitrogen atom;R2 is selected from C6-ioaryl and heteroaryl, and R2 is unsubstituted or substituted with one or more substituents selected from halo, Ci-6alkyl, Ci-6fluoroalkyl, =0, =S, OR7, SR7 and NR8R9;R3 is selected from Ce-io ryl, heteroaryl and heterocycloalkyl, and R3 is unsubstituted or substituted with one or more substituents selected from halo, CN, Ci-6alkyl, Ci_ efluoroalkyl, =0, =S, OR10, SR10, S02R10, NRnR12, R13, Ci-6alkyleneR13, Ci. salkenyleneR13, OCi-6alkyleneR13, SCi-6alkyleneR13, Ci. salkyleneOR10, Ci-6alkyleneSR10, OCi-6alkyleneNRnR12, SCi-6alkyleneNRnR12, OCi. salkyleneOR10, SCi-6alkyleneOR10, OCi-6alkyleneSR10, SCi-6alkyleneSR10, C(0)OR10, C(S)OR10, C(S)NRnR12 and C(0)NRnR12;R4 is selected from H, Ci-6alkyl Ci-6fluoroalkyl, C(0)Ci-6alkyl and C(0)d. 6fluoroalkyl;R5 and R6 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, heterocycloalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)OCi-6alkyl, C(0)NHCi_ 6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci-6alkyleneOCi-6alkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl, or R5 and R6 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, CN, OH, Ci-6alkyl OCi-6alkyl, Ci-6fiuoroalkyl, OCi- efluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(0)Ci-6alkyl, C(0)NHCi-6alkyl, S02Ci-6alkyl, S02HNCi-6alkyl, Ci.6alkyleneOCi-6alkyl, Ci-6alkyleneC6-ioaryl, Ci. 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl and Ci-6alkyleneC3-6cycloalkyl;R7 is selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci-6fluoroalkyl and C(0)Ci_ ealkyl;R8 and R9 are independently selected from H, Ci-6alkyl, Ci-6fluoroalkyl, C(0)Ci_ 6fluoroalkyl and C(0)Ci-6alkyl, or R8 and R9 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents selected from halo, OH, CN, Ci-6alkyl OCi- 6alkyl, Ci-6fluoroalkyl and OCi-6fluoroalkyl;R10 is selected from H, Ci-6alkyl, Ci.6fluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C3-iocycloalkyl, heterocycloalkyl, C6-ioaryl, heteroaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and is unsubstituted or substituted with one or more substituents selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-ioaryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6- loaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci_6alkyleneheterocycloalkyl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-6alkyleneSR14 and Ci-6alkyleneNR15R16;R11 and R12 are each independently selected from H, Ci-ioalkyl, Ci-iofluoroalkyl, C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(O)C3-i0cycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C(0)OCi-6alkyl, C(0)OCi-6fluoroalkyl, C(O)OC6-i0aryl, C(O)OC3-i0cycloalkyl, C(0)Oheteroaryl, C(0)Oheterocycloalkyl, C(0)NHCi-6alkyl, C(0)NHCi-6fluoroalkyl, C(0)NHC6-ioaryl, C(0)NHC3-locycloalkyl, C(0)NHheteroaryl, C(0)NHheterocycloalkyl, S02Ci-6alkyl, S02Ci_ 6fluoroalkyl, S02C6-ioaryl, S02C3-iocycloalkyl, S02heteroaryl, S02heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl, C6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneheteroaryl and Ci-6alkyleneheterocycloalkyl, and each of R11 and R12 are independently unsubstituted or substituted with one or more substituents selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-locycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci_ 6alkyleneheteroaryl, Ci-6alkyleneheterocycloalkyl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-galkyleneSR14 and Ci-6alkyleneNR15R16, orR11 and R12 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycle that is unsubstituted or substituted with one or more substituents independently selected from halo, CN, OR14, SR14, NR15R16, Ci-6alkyl, C(0)R14, C(0)OR14, C(0)NR15R16, S(0)Ci-6alkyl, S02Ci-6alkyl, C6-i0aryl, heteroaryl, C3-iocycloalkyl, heterocycloalkyl, Ci-6alkyleneC6-ioaryl, Ci-6alkyleneC3-iocycloalkyl, Ci-6alkyleneheteroaryl, Ci-6alkyleneR14, Ci-6alkyleneOR14, Ci-6alkyleneSR14 and Ci. 6alkyleneNR15R16;R13 is selected from C(0)Ci-6alkyl, C(0)Ci-6fluoroalkyl, C(O)C6-i0aryl, C(0)C3-locycloalkyl, C(0)heteroaryl, C(0)heterocycloalkyl, C3-iocycloalkyl, heterocycloalkyl, heteroaryl and C6-ioaryl, and R13...
WDR5 단백질-단백질 결합의 억제제본원은 식 I의 화합물: 이들 화합물을 포함하는 화합물, 및 예를 들어 WDR5 단백질과 그것의 결합 파트너 사이의 결합의 억제에 의해 매개되거나 치료가능한 질환, 장애 또는 병태의 치료용 약제로서의 그의 용도에 관한 것이다.식 (I)의 화합물 또는 이의 약제학적으로 허용가능한 염 및/또는 용매화물:식 중:R1은 헤테로사이클로알킬이고, 이는 비치환되거나 할로, C1-6알킬, C1-6플루오로알킬, C3-10사이클로알킬, OR4, SR4, NR5R6,C1-6알킬렌OR4, C1-6알킬렌R4 및 C1-6알킬렌NR5R6로부터 선택된 1개 이상의 치환체로 치환되고, 단, R1은 적어도 하나의 염기성 질소 원자를 포함하고;R2는 C6-10아릴 및 헤테로아릴로부터 선택되고, 그리고 R2는 비치환되거나 할로, C1-6알킬, C1-6플루오로알킬, =O, =S, OR7, SR7 및 NR8R9로부터 선택된 1개 이상의 치환체로 치환되고; R3은 C6-10아릴, 헤테로아릴 및 헤테로사이클로알킬로부터 선택되고, 그리고 R3은 비치환되거나 할로, CN, C1-6알킬, C1-6플루오로알킬, =O, =S, OR10, SR10, SO2R10, NR11R12,R13,C1-6알킬렌R13, C1-6알케닐렌R13,OC1-6알킬렌R13,SC1-6알킬렌R13, C1-6알킬렌NR11R12, C1-6알킬렌OR10, C1-6알킬렌R10, OC1-6알킬렌NR11R12, SC1-6알킬렌NR11R12, OC1-6알킬렌OR10, SC1-6알킬렌OR10,OC1-6알킬렌R10,SC1-6알킬렌R10,C(O)OR10, C(S)OR10, C(S)NR11R12 및 C(O)NR11R12로부터 선택된 1개 이상의 치환체로 치환되고;R4는 H, C1-6알킬 C1-6플루오로알킬, C(O)C1-6알킬 및 C(O)C1-6플루오로알킬로부터 선택되고; R5 및 R6은 H, C1-6알킬, C1-6플루오로알킬, 헤테로사이클로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)OC1-6알킬, C(O)NHC1-6알킬, SO2C1-6알킬, SO2HNC1-6알킬, C1-6알킬렌OC1-6알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬 및 C1-6알킬렌C3-6사이클로알킬로부터 독립적으로 선택되거나, 또는 R5 및 R6은, 이들이 부착된 질소 원자와 함께, 3-10 원 복소환을 형성하고, 이는 비치환되거나 할로, CN, OH, C1-6알킬 OC1-6알킬, C1-6플루오로알킬, OC1-6플루오로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)C1-6알킬, C(O)NHC1-6알킬, SO2C1-6알킬, SO2HNC1-6알킬, C1-6알킬렌OC1-6알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬 및 C1-6알킬렌C3-6사이클로알킬로부터 선택된 1개 이상의 치환체로 치환되고; R7은 H, C1-6알킬, C1-6플루오로알킬, C(O)C1-6플루오로알킬 및 C(O)C1-6알킬로부터 선택되고; R8 및 R9는 H, C1-6알킬, C1-6플루오로알킬, C(O)C1-6플루오로알킬 및 C(O)C1-6알킬로부터 독립적으로 선택되거나, 또는 R8 및 R9는, 이들이 부착된 질소 원자와 함께, 3-10 원 복소환을 형성하고, 이는 비치환되거나 할로, OH, CN, C1-6알킬 OC1-6알킬, C1-6플루오로알킬 및 OC1-6플루오로알킬로부터 선택된 1개 이상의 치환체로 치환되고;R10은 H, C1-6알킬, C1-6플루오로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C3-10사이클로알킬, 헤테로사이클로알킬, C6-10아릴, 헤테로아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌헤테로아릴 및 C1-6알킬렌헤테로사이클로알킬로부터 선택되고, 그리고 비치환되거나 할로, CN, OR14, SR14, NR15R16,C1-6알킬, C(O)R14, C(O)OR14, C(O)NR15R16, S(O)C1-6알킬, SO2C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬, C1-6알킬렌R14,C1-6알킬렌OR14, C1-6알킬렌R14 및 C1-6알킬렌NR15R16로부터 선택된 1개 이상의 치환체로 치환되고;R11 및 R12 각각은 H, C1-10알킬, C1-10플루오로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)C6-10아릴, C(O)C3-10사이클로알킬, C(O)헤테로아릴, C(O)헤테로사이클로알킬, C(O)OC1-6알킬, C(O)OC1-6플루오로알킬, C(O)OC6-10아릴, C(O)OC3-10사이클로알킬, C(O)O헤테로아릴, C(O)O헤테로사이클로알킬, C(O)NHC1-6알킬, C(O)NHC1-6플루오로알킬, C(O)NHC6-10아릴, C(O)NHC3-10사이클로알킬, C(O)NH헤테로아릴, C(O)NH헤테로사이클로알킬, SO2C1-6알킬, SO2C1-6플루오로알킬, SO2C6-10아릴, SO2C3-10사이클로알킬, SO2헤테로아릴, SO2헤테로사이클로알킬, C3-10사이클로알킬, 헤테로사이클로알킬, 헤테로아릴, C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌헤테로아릴 및 C1-6알킬렌헤테로사이클로알킬로부터 독립적으로 선택되고, 그리고 각각의 R11 및 R12는 독립적으로 비치환되거나 할로, CN, OR14, SR14, NR15R16,C1-6알킬, C(O)R14, C(O)OR14, C(O)NR15R16, S(O)C1-6알킬, SO2C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬, C1-6알킬렌R14,C1-6알킬렌OR14, C1-6알킬렌R14 및 C1-6알킬렌NR15R16로부터 선택된 1개 이상의 치환체로 치환되거나, 또는 R11 및 R12는, 이들이 부착된 질소 원자와 함께, 3-10 원 복소환을 형성하고, 이는 비치환되거나 할로, CN, OR14, SR14, NR15R16,C1-6알킬, C(O)R14, C(O)OR14, C(O)NR15R16, S(O)C1-6알킬, SO2C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌R14,C1-6알킬렌OR14, C1-6알킬렌R14 및 C1-6알킬렌NR15R16로부터 독립적으로 선택된 1개 이상의 치환체로 치환되고;R13은 C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)C6-10아릴, C(O)C3-10사이클로알킬, C(O)헤테로아릴, C(O)헤테로사이클로알킬, C3-10사이클로알킬, 헤테로사이클로알킬, 헤테로아릴 및 C6-10아릴로부터 선택되고, 그리고 R13은 비치환되거나 할로, CN, OR14, SR14, NR15R16,C1-6알킬, C(O)R14, C(O)OR14, C(O)NR15R16, S(O)C1-6알킬, SO2C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬, C1-6알킬렌R14,C1-6알킬렌OR14, C1-6알킬렌R14 및 C1-6알킬렌NR15R16로부터 독립적으로 선택된 1개 이상의 치환체로 치환되고,R14는 H, C1-6알킬, C1-6플루오로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C3-10사이클로알킬, 헤테로사이클로알킬, C6-10아릴, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬 및 C1-6알킬렌헤테로사이클로알킬로부터 선택되고, 그리고 R14는 비치환되거나 할로, CN, C1-6알킬, C1-6플루오로알킬, OH, SH, OC1-6알킬, OC1-6플루오로알킬, SC1-6알킬, SC1-6플루오로알킬, NH2, NHC1-6알킬, N(C1-6알킬)(C1-6알킬),C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)OH, C(O)OC1-6알킬, C(O)NH2, C(O)NHC1-6알킬, C(O)N(C1-6알킬)(C1-6알킬),SO2C1-6알킬, S(O)C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬, C1-6알킬렌OH, C1-6알킬렌OC1-6알킬, C1-6알킬렌H, C1-6알킬렌C1-6알킬, C1-6알킬렌NH2, C1-6알킬렌NHC1-6알킬 및 C1-6알킬렌N(C1-6알킬)(C1-6알킬)로부터 선택된 1개 이상의 치환체로 치환되고; R15 및 R16 각각은 H, C1-6알킬, C1-6플루오로알킬, C(O)C1-6알킬, C(O)C1-6플루오로알킬, C3-10사이클로알킬, 헤테로사이클로알킬, C6-10아릴, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬 및 C1-6알킬렌헤테로사이클로알킬로부터 독립적으로 선택되고, 그리고 각각의 R15 및 R16은 비치환되거나 할로, CN, C1-6알킬, C1-6플루오로알킬, OH, SH, OC1-6알킬, OC1-6플루오로알킬, SC1-6알킬, SC1-6플루오로알킬, NH2, NHC1-6알킬, N(C1-6알킬)(C1-6알킬),C(O)C1-6알킬, C(O)C1-6플루오로알킬, C(O)OH, C(O)OC1-6알킬, C(O)NH2, C(O)NHC1-6알킬, C(O)N(C1-6알킬)(C1-6알킬),SO2C1-6알킬, S(O)C1-6알킬, C6-10아릴, 헤테로아릴, C3-10사이클로알킬, 헤테로사이클로알킬, C1-6알킬렌C6-10아릴, C1-6알킬렌C3-10사이클로알킬, C1-6알킬렌헤테로아릴, C1-6알킬렌헤테로사이클로알킬, C1-6알킬렌OH, C1-6알킬렌OC1-6알킬, C1-6알킬렌H, C1-6알킬렌C1-6알킬, C1-6알킬렌NH2, C1-6알킬렌NHC1-6알킬 및 C1-6알킬렌N(C1-6알킬)(C1-6알킬)로부터 독립적으로 선택된 1개 이상의 치환체로 치환되거나, 또는 R15 및 R16은, 이들이 부착된 질소 원자와 함께, 3-10 원 복소환을 형성하고, 이는 비치환되거나 할로, CN, C1-6알킬, C1-6플루...