Acyl benzo[d]thiazol-2-amine and their methods of use

A compound having a structure according to formula (I):

• including pharmaceutically acceptable salts thereof, wherein:
• R1, R2, and R4 are each independently selected from the group consisting of hydrogen, halogen, C1-C6 linear alkyl, C1-C6 linear alkenyl, C3-C7 branched alkyl, C3-C7 branched alkenyl, C3-C7 cycloalkyl, C1-C6 linear alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, —S—C1-C6 linear alkyl, —S—C3-C7 branched alkyl, —S—C3-C7 cycloalkyl, —SO2—C1-C6 linear alkyl, —SO2—C3-C7 branched alkyl, —SO2—C3-C7 cycloalkyl, OCF3, OCHF2, OCH2F, SCF3, SCHF2, SCH2F, NO2, NH2, N(R29)2, NHCOR29, NHSO2R29, NHSO2NH2, CO2R29, and CON(R29)2;
• R3 is selected from the group consisting of hydrogen, halogen, C1-C6 linear alkyl, C1-C6 linear alkenyl, C3-C7 branched alkyl, C3-C7 branched alkenyl, C3-C7 cycloalkyl, C1-C6 linear alkoxy, C3-C7 branched alkoxy, C3-C7 cycloalkoxy, —S—C1-C6 linear alkyl, —S—C3-C7 branched alkyl, —S—C3-C7 cycloalkyl, —SO2—C1-C6 linear alkyl, —SO2—C3-C7 branched alkyl, —SO2—C3-C7 cycloalkyl, OCHF2, OCH2F, SCF3, SCHF2, SCH2F, NO2, NH2, N(R29)2, NHCOR29, NHSO2R29, NHSO2NH2, CO2R29, and CON(R29)2;
• R1 and R2 are taken together with the atoms to which they are bound to form a ring consisting of 5 to 6 atoms, optionally containing up to two members selected from the group consisting of nitrogen, oxygen, and sulfur;
• R2 and R3 are taken together with the atoms to which they are bound to form a ring consisting of 5 to 6 atoms, optionally containing up to two members selected from the group consisting of nitrogen, oxygen, and sulfur;
• R3 and R4 are taken together with the atoms to which they are bound to form a ring consisting of 5 to 6 atoms, optionally containing up to two members selected from the group consisting of nitrogen, oxygen, and sulfur;
• R5 is selected from the group consisting of C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C1-C6 fluoroalkyl, OR6, (CR10aR10b)mNHR11, CR14aR14bNR15R16,
• R6 is selected from the group consisting of CH2(CH2)nNR7aR7b,
• R7a and R7b are independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and CO2R8;
• R7a and R7b are taken together with the atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring consisting of two to five carbon atoms and a member selected from the group consisting of O, NR9, S, and SO2;
• n is 1 or 2;
• R8 is selected from the group consisting of C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, optionally substituted phenyl, and optionally substituted benzyl;
• R9 is selected from the group consisting of C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R10a and R10b are at each occurrence independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 branched alkyl, optionally substituted C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R10a and R10b are taken together with the atom to which they are bound to form an optionally substituted 6 membered ring;
• m is 1, 2, or 3;
• R11 is selected from the group consisting of COCR12aR12b(NHR3),
• R12a and R12b are at each occurrence independently selected from the group consisting of hydrogen, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2OH, CH(OH)CH3, CH2Ph, CH2(4-OH-Ph), (CH2)4NH2, (CH2)3NHC(NH2)NH, CH2(3-indole), CH2(5-imidazole), CH2CO2H, CH2CH2CO2H, CH2CONH2, and CH2CH2CONH2;
• R13 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• Y is at each occurrence independently selected from the group consisting of H2 and O;
• R14a and R14b are at each occurrence independently selected from the group consisting of hydrogen, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2OH, CH2OCH2Ph, CH(OH)CH3, CH2Ph, CH2(4-OH-Ph), (CH2)4NH2, (CH2)3NHC(NH2)NH, CH2(3-indole), CH2(5-imidazole), CH2(CCH), CH2(cyclohexyl), CH2CO2H, CH2CH2CO2H, CH2CONH2, and CH2CH2CONH2;
• R14a and R14b are taken together with the atom to which they are bound to form an optionally substituted three to six membered saturated carbocyclic ring;
• R15 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C1-C6 haloalkyl, and C2-C6 alkynyl;
• R14a and R15 are taken together with the atoms to which they are bound to form an optionally substituted four to six membered ring containing one nitrogen atom;
• R14b and R15 are taken together with the atoms to which they are bound to form an optionally substituted four to six membered ring containing one nitrogen atom;
• R16 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, COCR17aR17bNR19aR19b, COCR17aR17bOR18, SO2CR17aR17bNR19aR19b, COCR17aR17bNHSO2R19a,
• and (CR23aR23b)qNHR24;
• R15 and R16 are taken together with the atom to which they are bound to form an optionally substituted four to six membered saturated heterocyclic ring containing a nitrogen atom and optionally containing an additional heteroatom from the group consisting of N and O;
• R17a and R17b are at each occurrence independently selected from the group consisting of hydrogen, CH3, CH2CH3, CH2CH2CH3, CH2CCH, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2OH, CH2OCH2Ph, CH2CH2OCH2Ph, CH(OH)CH3, CH2Ph, CH2(cyclohexyl), CH2(4-OH-Ph), (CH2)4NH2, (CH2)3NHC(NH2)NH, CH2(3-indole), CH2(5-imidazole), CH2CO2H, CH2CH2CO2H, CH2CONH2, and CH2CH2CONH2;
• R17a and R17b are taken together with the atom to which they are bound to form an optionally substituted three to six membered saturated carbocyclic ring;
• R17a and R17b are taken together with the atom to which they are bound to form an optionally substituted six membered saturated heterocyclic ring with one 0 atom within the ring;
• R17a and R18 are taken together with the atoms to which they are bound to form an optionally substituted four to six membered ring containing one nitrogen atom;
• R17a and R19a are taken together with the atoms to which they are bound to form an optionally substituted four to six membered ring containing one nitrogen atom;
• Y1 is at each occurrence independently selected from the group consisting of H2, O, and —H/—OCH2Ph;
• R18 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R19a and R19b are at each occurrence independently selected from the group consisting of H, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl C1-C6 fluoroalkyl, COR25, CH2R25, SO2R26, an optionally substituted four to six membered saturated heterocyclic ring containing a heteroatom selected from the group consisting of NR28 and O, COCHR27NH2
• R19a and R19b are taken together with the atom to which they are bound to form an optionally substituted three to six membered saturated heterocyclic ring consisting of two to five carbon atoms and a member selected from the group consisting of O, NR9, S, and SO2;
• R20 is at each occurrence independently selected from the group consisting of CH2, O, C═O, and NH;
• R21 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R22 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• R21 and R22 are taken together with the atoms to which they are bound to form an optionally substituted five or six membered ring containing two nitrogen atoms;
• R23a and R23b are at each occurrence independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C7 branched alkyl, optionally substituted C3-C7 cycloalkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C2-C6 alkynyl;
• R23a and R23b are taken together with the atom to which they are bound to form an optionally substituted 3 to 6 membered carbocyclic ring;
• R24 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• q is 1, or 2;
• R25 is at each occurrence independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 fluoroalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• R26 is at each occurrence independently selected from the group consisting of C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, optionally substituted aryl, optionally substituted heteroaryl;
• R27 is selected from the group consisting of H, CH3, CH2CH3, CH2CH2CH3, CH2CCH, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2OH, CH2OCH2Ph, CH2CH2OCH2Ph, CH(OH)CH3, CH2Ph, CH2(cyclohexyl), CH2(4-OH-Ph), (CH2)4NH2, (CH2)3NHC(NH2)NH, CH2(3-indole), CH2(5-imidazole), CH2CO2H, CH2CH2CO2H, CH2CONH2, and CH2CH2CONH2;
• R28 is at each occurrence independently selected from the group consisting of H, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, optionally substituted aryl, optionally substituted heteroaryl, COR29, and SO2—C1-6alkyl;
• and R29 is at each occurrence independently selected from the group consisting of H, C1-C6 alkyl, C3-C7 branched alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, optionally substituted aryl, optionally substituted heteroaryl, C1-C6 alkoxy, and C1-C6 alkylamino.