Sulfonamide compounds and uses as TNAP inhibitors

A method for treating pathological calcification or vascular calcification in a mammal comprising administering to the mammal with pathological calcification or vascular calcification a tissue-nonspecific alkaline phosphatase (TNAP) inhibitor compound of Formula I, or a pharmaceutically acceptable salt, polymorph, solvate, tautomer, or N-oxide thereof:

• wherein:
• Y1 is a bond, and Y2 is —N(R6)—;
• L1 and L2 are each a bond;
• X1 is ═N— or ═C(R2)—;
• X2 is ═N— or ═C(R3)—;
• R1 and R4 are independently selected from the group consisting of halogen, —CN, —C(O)—N(R7)—R8, —C(O)—O—R9, —OMe, —OCF3, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;
• R2, R3, and R5 are hydrogen;
• R6 is hydrogen;
• R7 and R8 are independently hydrogen, optionally substituted alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted phenyl,
• or R7 and R8 together with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino;
• R9 is selected from the group consisting of hydrogen, optionally substituted alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, and optionally substituted phenyl;
• and
• A is —C(O)—N(R7)—R8, or —C(O)—O—R9, or A is an optionally substituted phenyl or optionally substituted 5- or 6-membered heteroaryl, wherein A is selected from:
• R12 and R13 are independently selected from the group consisting of hydrogen, halogen, —CN, —OH, —C(O)—O—R19, alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted alkoxy, haloalkyl, haloalkoxy, optionally substituted phenyl, and optionally substituted 5- or 6-membered heteroaryl;
• R19 is selected from the group consisting of hydrogen, optionally substituted alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, and optionally substituted phenyl;
• and
• R15 is hydrogen or optionally substituted alkyl.