Hydroxyethylamino sulfonamide derivatives

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• W is —O—, —CH2—, or —CD2—;
• each Y is independently selected from hydrogen or deuterium;
• R1 is hydrogen or —(C1-C11 alkylene)-R6, wherein, the C1-C11 alkylene is optionally substituted by one or more groups independently selected from halo, cyano, —OH, ═O, —SH, —PO3H, —PO3(C1-6 alkyl), ═N, —NH2, NH(C1-C4 alkyl), N(C1-C4 alkyl)2, —C1-C4 alkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, or a side group of a naturally occurring amino acid, and up to 4 methylene units in the C1-C11 alkylene are optionally and independently replaced with —O—, —S—, —S(O)—, S(O)2—, —P(O)2—, —P(O)(OH)—, —NH—, and —N(C1-C6 alkyl)-, provided that the terminal end of R1 bonded to the oxygen is not oxygen or nitrogen, wherein:
• R6 is selected from hydrogen, —N(R7)(R7), optionally substituted C1-C8 alkyl, C1-C8 alkoxy, a heteroaryl or cycloheteroalkyl wherein the heteroaryl or cycloheteroalkyl is optionally substituted with C1-C8 alkyl, and wherein each R7 is independently selected from hydrogen, C1-C8 alkyl, and C1-C8 alkoxy;
• R2a is hydrogen, —OH, —F, —O—Z—R10, or C1-4 alkyl optionally substituted with one or more —F, wherein
• Z is a C1-4 alkylene that is optionally substituted with deuterium;
• and
• R10 is selected from hydrogen, deuterium, phenyl, cyanophenyl, pyridyl, 3-cyanopyridyl, pyrazinyl, pyrazol-1-yl, 3,5-dimethylpyrazol-1-yl, isoxazol-3-yl, 5-methyl-isoxazol-3-yl, 2-methyl-thiazol-4-yl, 5-methyl-thiazol-4-yl, 2,5-dimethyl-thiazol-4-yl, 2-methyl-thiazol-5-yl, 4-methyl-thiazol-5-yl, 2,4-dimethyl-thiazol-5-yl, 2-thienyl, 4-morpholinyl, 4-methylpiperazin-1-yl, (C1-4 alkyl)aminocarbonyl, trifluoromethyl, hydroxymethyl, (C1 alkyl)sulfonylamino, (C1-4 alkoxy)methylcarbonylamino, (C1-4 alkyl)carbonylamino, phenylcarbonylamino, (C1-4 alkoxy)carbonylamino, 2-furanylcarbonylamino, 2-thienylcarbonylamino, (C1-4 alkyl)carbamyloxy, bis(methoxyethyl)amino, C6H5C(═N—CN)—NH—, 1H-pyrazol-5-ylamino, pyrimidin-2-ylamino, 1H-1,2,4-triazol-1-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, and 5-phenyl-1,2,4-oxadiazol-3-yl, wherein any methyl, alkyl or alkoxy moiety in R10 is optionally substituted with one or more deuterium;
• each of R2b and R2c is independently hydrogen or —F;
• R3 is a group that is optionally substituted with one or more deuterium and is selected from phenyl, C3-C6 cycloalkyl, C5-C6 cycloalkenyl, —CH2—CH(CH3)2, —CH(CH3)2, —CH(C2H5)2, —CH(CH3)—C2H5, —CH═CH2, and —C(CH3)2—(CH2)m—NH—R11, wherein:
• R11 is selected from hydrogen, —C(O)OCH3, —C(O)CH3, —C(O)NHCH3 and —S(O)2CH3;
• and
• m is 1, 2, 3, 4 or 5;
• and
• R4 is a group that is optionally substituted with one or more deuterium and is selected from 2,3-dihydrobenzofuran-5-yl, 3-oxo-2,3-dihydrobenzofuran-5-yl, chromanyl-6-yl, 4-oxo-chromanyl-6-yl, 4-oxo-4H-chromenyl-6-yl, 2,3-dihydrobenzo[b][1,4]dioxin-6-yl, 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl, 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl, 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl, 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl,
• wherein:
• each R5 is independently selected from hydrogen, —F, —NH2, —NHC(O)C1-6alkyl optionally substituted with one or more deuterium, such as —NHC(O)CH3 or —NHC(O)CD3, —NHC(O)C3-10 cycloalkyl optionally substituted with one or more deuterium, —OH, —OCH3, —OCD3, —OCF3, —OCHF2, —CH3, —CD3, —CF3, —CN, —CH2—OCD3, —CD2-OCD3, —CD2-OCH3, —CH2OH, —CD2OH, —OCH2CH3, —OCD2CD3, —OCH(CH3)2, —OCD(CH3)2, —OCD(CD3)2, and —OCH(CD3)2;
• each R12 is independently selected from hydrogen, deuterium, —CH3, and —CD3;
• R13 is selected from hydrogen, deuterium, —CH3, —CD3, —CH2—O—CH3, —CH2—O-CD3, —CD2-O-CD3, —CH2-(1-piperidinyl), —CH2-(4-morpholinyl), —(CH2)w-Q-C(O)-Q-R15, —(CD2)w-Q-C(O)-Q-R15, —CH2—NH—X—R15, and —CD2-NH—X—R15, wherein:
• X is selected from a bond, —C(O)—, —CO2— and —SO2—;
• R15 is selected from C1-6 alkyl, C3-6 cycloalkyl, or C4-10 (cycloalkyl)alkyl, wherein R15 is optionally substituted with one or more substituents independently selected from deuterium, —CF3, phenyl, —CH2-phenyl, —CD2-phenyl, 2-furanyl, —CH2-(2-furanyl), —CD2-(2-furanyl), —CH2-(2-benzofuranyl), —CD2-(2-benzofuranyl), 2-pyridyl, 3-pyridyl, —CH2-(2-pyridyl), —CD2-(2-pyridyl), —CH2-(3-pyridyl), —CD2-(3-pyridyl), 4-thiazolyl, —CH2-(4-thiazolyl), and —CD2-(4-thiazolyl);
• w is 1 or 2;
• and
• each Q is independently NH, O, CH2 or CD2;
• R14 is selected from hydrogen, deuterium, —CH3, —CD3, and —N(R16)2;
• each R16 is independently selected from C1-6 alkyl, C3-6 cycloalkyl, and C4-10 (cycloalkyl)alkyl, wherein R16 is optionally substituted with one or more substituents independently selected from deuterium, halo, hydroxyl, cyano, —N(R17)2, —C(O)—R17, —CO2R17, —C(O)—N(R17)2;
• each R17 is independently selected from C1-6 alkyl, C3-6 cycloalkyl, or C4-10 (cycloalkyl)alkyl, wherein R17 is optionally substituted with one or more deuterium:
• R18a is selected from hydrogen, deuterium, —CH3, —CD3,
• wherein n is 1 or 2, and wherein each of
• is optionally substituted on one or more carbon atoms with deuterium;
• and
• R18b is selected from hydrogen;
• deuterium;
• C1-6 alkyl optionally substituted with one or more of halo, aryl, or heteroaryl;
• cyano;
• —COOH;
• —OC1-6 alkyl;
• —NH2;
• —NH(C1-6 alkyl);
• N(C1-6alkyl)2;
• a 3- to 10-membered cycloheteroalkyl;
• C6-10 aryl, a 5- to 10-membered heteroaryl;
• —C(O)OC1-6 alkyl;
• —C(O)NHC1-6 alkyl;
• wherein n is 1 or 2, and wherein each of C1-6 alkyl, —OC1-6 alkyl, —NHC1-6 alkyl, N(C1-6alkyl)2, —C(O)OC1-6 alkyl, —C(O)NHC1-6
• is optionally substituted on one or more carbon atoms with deuterium;
• provided that when W is —O—, R2a is hydrogen and R3 is isopropyl optionally substituted with one or more deuterium, then R4 is other than
• and further provided that at least one Y is deuterium or at least one of R1, R2a, R3 or R4 comprises a deuterium atom.