Inhibitors of the Renal Outer Medullary Potassium Channel

A compound having structural Formula I

• or a pharmaceutically acceptable salt thereof wherein:
• R1 is
• wherein one of Ra and Rb is —CN, tetrazolyl,
• and the other is —H, halo, —C1-6alkyl optionally substituted with one to three of —F, or —OC1-6alkyl optionally substituted with one to three of —F;
• and Rc is —H, halo, —C1-6alkyl optionally substituted with one to three of —F, or —OC1-6alkyl optionally substituted with one to three of —F;
• wherein one of Rd and Re is —CN or tetrazolyl and the other is —H, halo, —C1-3alkyl optionally substituted with one to three of —F or —OC1-3alkyl optionally substituted with one to three of —F;
• wherein
• Rf is —H, —C1-6 alkyl, halo, —CN or tetrazolyl,
• Rg is —H, —C1-6 alkyl, halo, —CN or tetrazolyl, and
• Rh is —H, —C1-6 alkyl, halo, —CN or tetrazolyl,
• provided that only one of Rf, Rg or Rh may be —CN or tetrazolyl;
• (e) a 5 membered unsaturated heterocyclic ring containing carbon atoms and one to three heteroatoms independently selected at each occurrence from N, S or O, wherein the heterocyclic ring is
• (1) optionally substituted on an available ring carbon with —C1-6alkyl, —OC1-6alkyl, —C3-6cycloalkyl, —OC3-6cycloalkyl or —CN, and (2) optionally substituted on an available ring nitrogen with phenyl optionally substituted with one or more of —C1-3alkyl and halo;
• or
• (f) a 5 membered unsaturated heterocyclic ring containing carbon atoms and one to three heteroatoms independently selected at each occurrence from N, S or O, which is fused to a pyridyl ring via two adjacent carbon atoms shared between the heterocyclic ring and the pyridyl ring, to form a 9 member hetero-bicyclic ring system;
• R2 is —H or —C1-6alkyl;
• or R1 is a 6-membered ring, and R2 is —(CH2)n— and is joined together with R1 and the nitrogen to which they are both attached to form
• wherein Ra, Rb and Rc are as defined above;
• one of X1, X2 or X3 is N and the others are CH;
• n is an integer selected from 1 or 2;
• R3 is —H, —OH, —F or —NH2;
• R4 is —H, —OH, oxo, —F or —C1-6alkyl;
• R5 is —H, halo or —C1-3alkyl optionally substituted with one to three of —F;
• R5a is —H, halo or —C1-3alkyl optionally substituted with one to three of —F;
• R6 is —H, halo, —O—C1-3alkyl, —C(O)OC1-3alkyl or —C1-3alkyl optionally substituted with one to three of —F;
• R6a is —H, halo, —O—C1-3alkyl, —C(O)OC1-3alkyl or —C1-3alkyl optionally substituted with one to three of —F;
• and
• the dashed line “- - -” represents the presence or absence of a bond.