Small molecule inhibitors of the ribosome biogenesis factor NVL2

A compound of formula (I):

• wherein:
• R1 is selected from:
• R3;
• —C(O)R3;
• —C(S)R3;
• —C(O)NHR3;
• —C(S)NHR3;
• —C(O)NR5R6;
• —C(S)NR5R6;
• R2 is selected from:
• C1-C8alkyl;
• C2-C8alkenyl;
• C2-C8alkynyl including all isomers thereof and all optionally substituted with one or more of:
• D, F, OH, C(O)NHR4 and all optionally having one or more methylene units replaced with O, S, NH, NR4, C(O);
• R3 is selected from:
• C1-C7alkyl, C3-C7cycloalkyl optionally bridged with CH2 or CH2CH2, CH2-linked or CHMe-linked C3-C7cycloalkyl optionally bridged with CH2 or CH2CH2, C2-C7alkenyl, C5-C7cycloalkenyl optionally bridged with CH2 or CH2CH2, CH2-linked or CHMe-linked C5-C7cycloalkenyl optionally bridged with CH2 or CH2CH2, C2-C7alkynyl, bridged or fused C5-C9cycloalkyl, CH2-linked or CHMe-linked bridged or fused C5-C9cycloalkyl C5-C10spiroalkanes, CH2-linked or CHMe-linked C5-C10spiroalkanes, all including all possible isomers thereof and all optionally substituted with one or more of:
• D, F, CN, R4, OR4, OH, NHC(O)H, NHC(O)R4, NHSO2R4, CO2H, CO2R4, C(O)NH2, C(O)NHR4, C(O)NR4R4 and all optionally having one or more methylene units replaced with O, S, SO2, S(O), NH, NR4, NC(O)H, NC(O)R4, NSO2R4, C(O), C═NOH, C═NOR4 or C═NR4, phenyl or naphtyl (optionally substituted at one or more of each position with R7), 5- and 6-membered heteroaryls and fused heteroaryls including but not limited to oxazoles, isoxazoles, thiazoles, isothiazoles, furans, thiophenes, pyrazoles, imidazoles, triazoles, tetrazoles, pyridines, pyrimidines, pyrazines, pyridazines, quinolines, isoquinolines, quinazolines, quinoxalines, cinnolines, phtalazines, naphthyridines, pyridopyrazines, pyrazolopyridines, pyridopyrimidines, pyridopyridazines, benzoxazoles, benzoisoxazoles, benzothiazoles, benzoisothiazoles, indoles, indazoles, benzimidazoles, dioxolopyridines, dioxolopyridazines, dioxolopyrimidines, dioxolopyrazines, benzofurans, benzothiophenes, imidazopyridines, benzodioxoles, benzoxazolones, benzoisoxazolones, benzothiazolones, benzoisothiazolones, 1,3-dihydro-2H-benzimidazoles, benzo[d]imidazol-2-ones, benzodioxolones, dioxolopyridines, dioxolopyridazines, dioxolopyrimidines, dioxolopyrazines, coumarins, isocoumarins, and including all possible isomers thereof, and all optionally substituted at one or more of each position with R7;
• R4 is selected from:
• Me;
• Et;
• Pr;
• iPr;
• cPr;
• cBu optionally substituted with one or more of:
• D, F, CN, OH, OCD3, OCHnF(3-n) (n=0-3);
• NR5R6 completes a 4- to 7-membered azacycle or a bridged or fused 6- to 9-membered azacycle or 5- to 9-membered azaspiroalkane including all possible isomers thereof and all optionally substituted with one or more of:
• D, F, CN, R4, OR4, OH, NHC(O)H, NHC(O)R4, NHSO2R4, CO2H, CO2R4, C(O)NH2, C(O)NHR4, C(O)NR4R4 and all optionally having one or more methylene units replaced with O, S, SO2, NH, NR4, NC(O)H, NC(O)R4, NSO2R4, C(O), C═NOH, C═NR4;
• R7 is selected from:
• D, F, Cl, Br, CN, N3, OH, OR4, R4, oxetanyl, NHC(O)H, NHC(O)R4, CO2H, CO2R4, C(O)NH2, C(O)NHR4, C(O)NR4R4, SO2NH2, SO2NHR4, SO2NR4R4, C2-C6alkenyl or C2-C6alkynyl including all isomers thereof and all optionally substituted with one or more of:
• D, F, CN, OH and all optionally having one or more methylene units replaced with O, S, S(O), SO2, NH, NR4, NC(O)H, NC(O)R4, NSO2R4, C(O), C═NOH, C═NR4;
• aryl or 5- or 6-membered heteroaryl or heterocyclyl all optionally substituted with one or more of:
• D, F, Cl, CN, R4, OH, OR4);
• Z is selected from:
• S, CH2, CD2, CHR4, CDR4, CR4R4, CHOH, CDOH, CHOR4, CDOR4, CR4OH, CR4OR4, CHCN, CDCN, CHF, CDF, CF2, NH, NR4, NC(O)H, NC(O)R4, NSO2R4;
• X is selected from:
• CH, CD, CF, CCl, CCN;
• Y is selected from:
• CH, CD, CF, CCl;
• U and W are independently selected from:
• CH, CD, N;
• excluding R1=C(O) furan-3-yl, X, Y, U, W=CH, Z=S, R2=(CH2)2OMe (MM017), or a salt, hydrate or stereoisomer thereof.