Inhibitors of the Renal Outer Medullary Potassium Channel

A compound having structural Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• B1—ZB— is B1—CHR1CH2—, B1—CHR1C(O)—, B1—C(O)—, B1—CHR1CH2C(O)—, B1—OCH2C(O)—, or B1—CH(CH2OH)—;
• —ZA-A1 is CHR21CR2R22-A1, —CH═CR2-A1, C≡C-A1, —S-A1, —CH2O-A1, —C(O)CHR2-A1, —O-A1, —NHCHR2-A1, —CH2N(CH3)CH2CH(OH)-A1, —CH2N(CH3)CH(CH2OH)-A1, —CH2N(CH3)-A1, —CH2S-A1, —CH2O-A1, CH2S(O)-A1, —CH2S(O2)-A1, or —NH-A1;
• A1 is
• B1 is
• X is O or S;
• R1 is —H, —C1-6 alkyl, —C3-6 cycloalkyl, CF3, —OH, F, —CH2OH, —C(O)OH, —C(O)OC1-6 alkyl, or
• R1 may be joined with R13b by 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring;
• R2 is —H, —C1-6 alkyl, —C3-6 cycloalkyl, CF3, —OH, F, —CH2OH, —C(O)OH, —C(O)OC1-6 alkyl, or
• R2 may be joined with R13a by 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring;
• R4 is H, —OH, F, —O—C1-6 alkyl, or —C1-6 alkyl, or may be joined with R5 by a bond, or by 1-4 carbon atoms, to form a ring;
• R5 is H, —OH, F, —O—C1-6 alkyl, or —C1-6 alkyl, or may be joined with R4 by a bond, or by 1-4 carbon atoms to form a ring;
• R6 is H, —C1-6 alkyl, —C(O)OC1-6 alkyl, —OH, halogen, —OC(O)C1-6 alkyl, —CH2OH, —CHF2, —N(C1-6 alkyl)2, C6H5, CF3, or a 5 or 6 membered heteroaryl ring having 1, 2, 3, or 4 heteroatoms;
• R13a is —H, —C1-6 alkyl, —C3-6 cycloalkyl, -halogen, CF3, —CH2OH, —CO2R16a, —OR16a, —SR16a, —CN, -aryl, -heterocycle, —NR16aR18a, or R13a may be joined with R2 by 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring, or R13a may be joined with R14a by 3-4 carbon atoms or 2-3 carbon atoms and one heteroatom to form a ring;
• R13b is —H, —C1-6 alkyl, —C3-6 cycloalkyl, -halogen, CF3, —CH2OH, —CO2R16b, —OR16b, —SR16b, —CN, -aryl, -heterocycle, —NR16bR18b, or R13b may be joined to R1 by 2-3 carbon atoms or 1-2 carbon atoms and one heteroatom to form a ring, or R13b may be joined to R14b by 3-4 carbon atoms or 2-3 carbon atoms and one heteroatom to form a ring;
• R14a is —H, —C1-6 alkyl, —C3-6 cycloalkyl, -halogen, CF3, —CH2OH, —CO2R17a, —OR17a, —SR17a, CN, -aryl, -heterocycle, or R14a may be joined to R13a by 3-4 carbon atoms or 2-3 carbon atoms and one heteroatom to form a ring;
• R14b is —H, —C1-6 alkyl, —C3-6 cycloalkyl, -halogen, CF3, —CH2OH, —CO2R17b, —OR17b, —SR17b, —CN, -aryl, -heterocycle, or R14b may be joined to R13b by 3-4 carbon atoms or 2-3 carbon atoms and one heteratom to form a ring;
• R15a is H, halogen, —C1-6 alkyl, C3-6 cycloalkyl, —OC1-6 alkyl, or —CF3;
• R15b is H, halogen, —C1-6 alkyl, C3-6 cycloalkyl, —OC1-6 alkyl, or —CF3;
• R16a, R16b, R17a, R17b, R18a, and R18b are independently —H, —C1-6 alkyl, or —C3-6 cycloalkyl;
• R19 and R20 are H, or may be joined by a bond or 1-2 carbon atoms, to form a 4-5-membered ring;
• and
• R21 and R22 are H, or, together with carbon atom to which they are attached, form —C3-6 cycloalkyl.