Isotopically enriched arylsulfonamide CCR3 antagonists

A compound having the structure of Formula II:

• or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, a tautomer, or a mixture of two or more tautomers thereof;
• or a pharmaceutically acceptable salt thereof;
• wherein:
• X is O or S;
• R1, R3, and R5 are each independently hydrogen or deuterium;
• R2, R4, and R8 are each independently halo, C1-6 alkyl, cyano, or nitro;
• R6, R7, and R9 are each independently hydrogen or deuterium;
• R12 is (a) hydrogen;
• or (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
• R13 is (a) hydrogen, deuterium, halo, cyano, nitro, oxo, or guanidine;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-5 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more substituents Q;
• or (c) —C(O)R1a, —C(O)OR1a, —C(O)NR1bR1c, —C(NR1a)NR1bR1c, —OS(O)R1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(═NR1a)NR1bR1c, —OS(O)R1a, —OS(O)2R1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1a—C(O)R1d, —NR1a—C(O)OR1d, —NR1a—C(O)NR1bR1c, —NR1a—C(═NR1d)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
• wherein each R1a , R1b , R1c and R1d is independently hydrogen, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, heteroaryl, or heterocyclyl;
• or each pair of R1b and R1c together with the N atom to which they are attached independently form heteroaryl or heterocyclyl;
• wherein the compound is isotopically enriched;
• wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclyl, and heteroaryl in R1,R2, R3, R4, R5, R8, R12, R1a, R1b, R1c, , or R1d, is optionally substituted with one or more substituents Q, where each Q is independently selected from (a) deuterium, cyano, halo, and nitro;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one, two, three, or four, substituents Qa;
• and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc,—C(NRa)NRbRc, —ORa, —OC(O)Ra, ——OC(O)OR a, —OC(O)NR bRc, —OC(═NRa)NRbRc, —OS(O)Ra —OS(O)2Ra, —OS(O)NRbRc, —OS(O)2NR bRc, —NRbRc, —NRa—C(O)Rd, —NRa—C(O)ORd, —NRa—C(O)NRbRc, —NRa—C(═NRd)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium;
• (ii) Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7 -15 aralkyl, heteroaryl, or heterocyclyl, each optionally substituted with one, two, three, or four, substituents Qa;
• or (iii) each pair of Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted with one, two, three, or four, substituents Qa;
• wherein each Qa is independently selected from the group consisting of (a) deuterium, cyano, halo, and nitro;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl;
• and (c) -—C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(NRe)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(═NRe)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NRe—C(O)Rh, —NRe—C(O)ORf, —NRe—C(O)NRfRg, —NRe—C(═NRh)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —SRe, —S(O)Re, —(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
• wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium;
• (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
• or (iii) each pair of Rf and Rg together with the N atom to which they are attached form heterocyclyl;
• m is 1;
• n is 1;
• and
• p is an integer of 1, 2, 3, 4, 5, 6, 7, or 8.