Tetrahydropyridinyl and Dihydropyrrolyl Compounds and the Use Thereof

Abstract

The invention relates to tetrahydropyridinyl and dihydropyrrolyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X, Y, Z, R 1 , R 2 , m, and n are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

1 .- 66 . (canceled) 
     
     
         67 . A method of modulating calcium channels in a mammal, comprising administering to the mammal at least one compound having the Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Hy is, a 6-membered heteroaromatic ring, a 5-membered heteroaromatic ring, or a 5-membered heterocyclic ring, wherein said Hy has at least one nitrogen atom, and wherein said Hy is attached to the tetrahydropyridinyl or dihydropyrrolyl ring by a carbon atom; 
 R 1  is attached to a carbon atom of said Hy ring and is selected from the group consisting of
 a) —(═W)NR 3 R 4 ; 
 b) —C(═O)OR 5 ; 
 c) —NR 6 —C(═O)R 7 ; 
 d) cyano; 
 e) hydroxyalkyl; and 
 f) a 5-membered, N-containing heteroaryl or a 5-membered, partially unsaturated, N-containing heterocyclo each of which is optionally substituted with one or two substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino; wherein 
 
 W is O or NR 14 , wherein 
 R 14  is hydrogen or alkyl; 
 R 3 , R 4 , and R 7  are each independently selected from the group consisting of hydrogen alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 R 5  and R 6  are hydrogen or alkyl; 
 R 2  is selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxyalkyl, hydroxy, alkoxy, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, nitro, cyano, amino, alkylamino, and dialkylamino; 
 m is 0, 1, 2, or 3; 
 n is 0 or 1; 
 X is —CHR 8 — or —C(═O)—; 
 R 8  and R 9  are both hydrogen or together form a bridge —(CH 2 ) p —, wherein 
 p is 2, 3, or 4; 
 Z is Z 1  or Z 2 , wherein 
 Z 1  is —SO 2 —R 10 , wherein 
 R 10  is selected from the group consisting of C 3-12  alkyl, halo(C 3-12 )alkyl, C 5-12  cycloalkyl, (C 3-12  cycloalkyl)alkyl, C 5-12  cycloalkenyl, (C 3-12  cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, aryalkyl, heteroaryl, heteroaryalkyl, arylamino, and aryl(alkyl)amino, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 Z 2  is —C(R 11 R 12 )R 13 , wherein 
 R 11  and R 12  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, halogen, hydroxy, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, cyano, amino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl; and 
 R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting, of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino: 
 with the following provisos when X is —CHR 8 —, and R 8  is hydrogen: 
 1) when R 11  and R 12  are both hydrogen and R 13  is arylalkyl, then the aryl portion of R 13  is substituted with at least one of haloalkyl or haloalkoxy or 
 2) when Hy is a pyridin-2-yl ring, then R 1  is other than optionally substituted 2-aminophenylaminocarbonyl or 2-hydroxyphenylaminocarbonyl. 
 
     
     
         68 . The method of  claim 67 , wherein the N-type calcium channel is modulated. 
     
     
         69 .- 73 . (canceled) 
     
     
         74 . The method of  claim 67 , wherein n is 1. 
     
     
         75 . The method of  claim 74 , wherein X is —CHR 8 — and R 8  and R 9  are both hydrogen, the compound having the Formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, provided that when Hy is a pyridin-2-yl ring, then R 1  is other than optionally substituted 2-aminophenylaminocarbonyl or 2-hydroxyphenylaminocarbonyl. 
       
     
     
         76 . The method of  claim 74 , wherein X is —CHR 8 —, R 8  and R 9  together form a bridge —(C 1-12 ) p —, and p is 2, 3, or 4, the compound having the Formula III: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         77 . The method of  claim 76 , wherein p is 2, the compound having the Formula IV: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         78 . The method of  claim 74 , wherein X is —C(═O)— and R 9  is hydrogen, the compound having the Formula V: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         79 . The method of  claim 67 , wherein n is 0. 
     
     
         80 . The method of  claim 79 , wherein X is —CHR 8 — and R 8  and R 9  are both hydrogen, the compound having the Formula VI: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, provided that when Hy is a pyridin-2-yl ring, then R 1  is other than optionally substituted 2-aminophenylaminocarbonyl or 2-hydroxyphenylaminocarbonyl. 
       
     
     
         81 . The method of  claim 79 , wherein X is —CHR 8 —, R 8  and R 9  together form a bridge —(CH 2 ) p —, and p is 2, 3, or 4, the compound having the Formula VII: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         82 . The method of  claim 81 , wherein p is 2, the compound having the Formula VIII: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         83 . The method of  claim 79 , wherein X is —C(═O)— and R 9  is hydrogen, the compound having the Formula IX: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         84 . The method of  claim 67 , wherein Hy is selected from the group consisting of pyridyl, pyrimidinyl, pyrazinyl, pyrrolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, and 1,2,4-oxadiazolyl. 
     
     
         85 . The method of  claim 84 , wherein Hy is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-2-yl, imidazol-2-yl, imidazol-4-yl, and oxazol-2-yl. 
     
     
         86 . The method of  claim 85 , wherein Hy is pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, or oxazol-2-yl. 
     
     
         87 . The method of  claim 67 , wherein R 1  is attached to a carbon atom adjacent to a nitrogen atom of said Hy ring. 
     
     
         88 . The method of  claim 67 , the compound having the Formula X: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein one of Q 1 , Q 2 , or Q 3  is N and the remaining two are each CH; or 
         Q 1 , Q 2 , and Q 3  each are CH; and 
         X, Z, R 1 , R 2 , R 9  and m are as defined in  claim 67 . 
       
     
     
         89 . The method of  claim 88 , the compound having the Formula XI: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         90 . The method of  claim 67 , the compound having the Formula XII: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein X, R 1 , R 2 , and R 9  and m are as defined in  claim 67 . 
       
     
     
         91 . The method of  claim 88 , wherein X is —CHR 8 — and R 8  and R 9  both are hydrogen. 
     
     
         92 . The method of  claim 88 , wherein X is —CHR 8 — and R 8  and R 9  together form a bridge —(CH 2 ) p — and p is 2, 3, or 4. 
     
     
         93 . The method of  claim 92 , wherein p is 2. 
     
     
         94 . The method of  claim 88 , wherein X is —C(═O)— and R 9  is hydrogen. 
     
     
         95 . The method of  claim 67 , wherein R 1  is —C(═W)NR 3 R 4 , wherein W is O or NR 14 , R 14  is hydrogen or alkyl, and R 3  and R 4  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         96 . The method of  claim 95 , wherein R 14  is hydrogen, R 3  is hydrogen or alkyl and R 4  is as defined in  claim 95 . 
     
     
         97 . The method of  claim 96 , wherein R 3  is hydrogen and R 4  is selected from the group consisting of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, halo(C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  Cycloalkenyl(C 1-4 )alkyl, 5- or 6-membered heterocyclo, 5- or 6-membered heterocyclo(C 1-4 )alkyl, C 6-10  aryl, C 6-10  aryl(C 1-4 )alkyl, 5- or 6-membered heteroaryl, and 5- or 6-membered heteroaryl(C 1-4 )alkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl, and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         98 . The method of  claim 97 , wherein R 4  is selected from the group consisting of C 1-6  alkyl, C 2-6  alkenyl, halo(C 1-6 )alkyl, monohydroxy(C 1-6 )alkyl, dihydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  cycloalkenyl(C 1-4 )alkyl, phenyl, and benzyl, wherein said phenyl or phenyl portion of said benzyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-6  alkyl, C 1-6  alkoxy, halogen, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy, hydroxy, hydroxy(C 1-6 )alkyl, cyano, amino, amino(C 1-6 )alkyl, C 1-6  alkylamino, di(C 1-6 )alkylamino, and hydroxy(C 1-6 )alkylamino. 
     
     
         99 . The method of  claim 95 , wherein W is O. 
     
     
         100 . The method of  claim 95 , wherein R 1  is —C(═O)—NH-cyclopropyl, —C(═O)—NH 2  or —C(═O)—NH—CH 2 -cyclopropyl. 
     
     
         101 . The method of  claim 95 , wherein W is NH. 
     
     
         102 . The method of  claim 95 , wherein R 1  is —C(═NH)—NH—CH 2 -cyclopropyl. 
     
     
         103 . The method of  claim 67 , wherein R 1  is —C(═O)OR 5  wherein R 5  is hydrogen or alkyl. 
     
     
         104 . The method of  claim 67 , wherein R 1  is —NR 6 —C(═O)R 7 , wherein R 6  is hydrogen or alkyl, and R 7  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         105 . The method of  claim 104 , wherein R 7  is selected from the group consisting of C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, halo(C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  cycloalkenyl(C 1-4 )alkyl, 5- or 6-membered heterocyclo, 5- or 6-membered heterocyclo(C 1-4 )alkyl, C 6-10  aryl, C 6-10  aryl(C 1-4 )alkyl, 5- or 6-membered heteroaryl, and 5- or 6-membered heteroaryl(C 1-4 )alkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl, and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         106 . The method of  claim 105 , wherein R 7  is selected from the group consisting of C 1-6  alkyl, C 2-6  alkenyl, halo(C 1-6 )alkyl, monohydroxy(C 1-6 )alkyl, dihydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  cycloalkenyl(C 1-4 )alkyl, phenyl, and benzyl, wherein said phenyl or phenyl portion of said benzyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-6  alkyl, C 1-6  alkoxy, halogen, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy, hydroxy, hydroxy(C 1-6 )alkyl, cyano, amino, amino(C 1-6 )alkyl, C 1-6  alkylamino, di(C 1-6 )alkylamino, and hydroxy(C 1-6 )alkylamino. 
     
     
         107 . The method of  claim 104 , wherein R 1  is —NH—C(═O)-cyclopropyl. 
     
     
         108 . The method of  claim 67 , wherein R 1  is cyano. 
     
     
         109 . The method of  claim 67 , wherein R 1  is hydroxyalkyl. 
     
     
         110 . The method of  claim 67 , wherein R 1  is a 5-membered, N-containing heteroaryl or a 5-membered, partially unsaturated, N-containing heterocyclo each of which is optionally substituted with one or two substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino. 
     
     
         111 . The method of  claim 110 , wherein R 1  is selected from the group consisting of oxazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, and thiazolyl, any of which is optionally substituted with one or two substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino. 
     
     
         112 . The method of  claim 111 , wherein R 1  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       wherein
 R 101  is selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino, A is O or S, and ---- is an optional bond forming a double bond. 
 
     
     
         113 . The method of  claim 67 , wherein R 2  is selected from the group consisting of C 1-4  alkyl, halo(C 1-4 )alkyl, halogen, hydroxy(C 1-4 )alkyl, hydroxy, C 1-4  alkoxy, C 1-4  alkoxy(C 1-4 )alkyl, halo(C 1-4 )alkoxy, halo(C 1-4 )alkoxy(C 1-4 )alkyl, nitro, cyano, amino, C 1-4  alkylamino, and di(C 1-4 )alkylamino. 
     
     
         114 . The method of  claim 67 , wherein m is 0 or 1. 
     
     
         115 . The method of  claim 67 , wherein Z is Z 1 . 
     
     
         116 . The method of  claim 115 , wherein R 10  is C 4-8  alkyl, halo(C 3-6 )alkyl, C 5-12  cycloalkyl, (C 3-12  cycloalkyl)alkyl, C 5-12  cycloalkenyl, (C 3-12  cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylamino, and aryl(alkyl)amino, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         117 . The method of  claim 116 , wherein R 10  is selected from the group consisting of C 4-6  alkyl, monohalo(C 3-6 )alkyl, dihalo(C 3-6 )alkyl, trihalo(C 3-6 )alkyl, C 5-8  cycloalkyl, C 3-8  cycloalkyl(C 1-2 )alkyl, C 5-8  cycloalkenyl, C 3-8  cycloalkenyl(C 1-2 )alkyl, 5- or 6-membered heterocyclo, 5- or 6-membered heterocyclo(C 1-2 )alkyl, C 6-14  aryl, C 6-14  aryl(C 1-2 )alkyl, 5- or 6-membered heteroaryl, and 5- or 6-membered heteroaryl(C 1-2 )alkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino. 
     
     
         118 . The method of  claim 117  wherein R 10  is selected from the group consisting of
 a) cyclohexyl; 
 b) cycloheptyl; 
 c) cyclohexylmethyl; 
 d) cycloheptylmethyl; 
 e) phenyl, unsubstituted or substituted with 1, 2 or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, ino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino; 
 f) benzyl, unsubstituted or substituted with 1, 2 or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino; 
 g) phenylethyl, unsubstituted or substituted with 1, 2 or 3 substituents each independently selected from the group consisting of C 1-4  alkyl C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino; 
 h) pyridin-1-yl, pyridin-2-yl, or pyridin-3-yl, unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, and cyano; 
 i) thiophen-2-yl or thiophen-3-yl, unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, and cyano; 
 j) isoxazol-3-yl, isoxazol-4-yl, or isoxazol-5-yl, unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, and cyano; 
 k) oxazol-2-yl, oxazol-4-yl, or oxazol-5-yl, unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, and cyano; and 
 l) isoxazol-3-ylmethyl, isoxazol-4-ylmethyl, or isoxazol-5-ylmethyl, unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, and cyano. 
 
     
     
         119 . The method of  claim 118 , wherein R 10  is e) phenyl, unsubstituted or substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino. 
     
     
         120 . The method of  claim 67 , wherein Z is Z 2 . 
     
     
         121 . The method of  claim 120 , wherein R 11  and R 12  are both hydrogen, and R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino, provided that when X is —CHR 8 — and R 8  is hydrogen, and R 13  is aryl or arylalkyl, then the aryl portions are substituted by at least one of trifluoromethyl or trifluoromethoxy. 
     
     
         122 . The method of  claim 121 , wherein R 13  is phenyl, benzyl, phenylethyl, pyrrolyl, pyridyl, pyrimidyl, isoxazolyl, oxazolyl, thienyl, pyrrolyl(C 1-2 )alkyl, pyridyl(C 1-2 )alkyl, pyrimidyl(C 1-2 )alkyl, isoxazolyl(C 1-2 )alkyl, oxazolyl(C 1-2 )alkyl, or thienyl(C 1-2 )alkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino. 
     
     
         123 . The method of  claim 120 , wherein R 11  is hydrogen, R 12  is selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, halogen, hydroxy, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, cyano, amino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl, and R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         124 . The method of  claim 123 , wherein R 12  is selected from the group consisting of C 1-4  alkyl, halo(C 1-4 )alkyl, hydroxy(C 1-4 )alkyl, halogen, hydroxy, halo(C 1-4 )alkoxy, and halo(C 1-4 )alkoxy(C 1-4 )alkyl, and R 13  is phenyl, benzyl, phenylethyl, pyrrolyl, pyridyl, pyrimidyl, isoxazolyl, oxazolyl, thienyl, pyrrolyl(C 1-2 )alkyl, pyridyl(C 1-2 )alkyl, pyrimidyl(C 1-2 )alkyl, isoxazolyl(C 1-2 )alkyl, oxazolyl(C 1-2 )alkyl, or thienyl(C 1-2 )alkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino. 
     
     
         125 . The method of  claim 120 , wherein R 11  and R 12  are each independently selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, halogen, hydroxy, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, cyano, amino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl, and R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino. 
     
     
         126 . The method of  claim 125 , wherein R 11  and R 12  are each independently selected from the group consisting of C 1-4  alkyl, halo(C 1-4 )alkyl, hydroxy(C 1-4 )alkyl, halogen, hydroxy, halo(C 1-4 )alkoxy, and halo(C 1-4 )alkoxy(C 1-4 )alkyl, and R 13  is phenyl, benzyl, phenylethyl, pyrrolyl, pyridyl, pyrimidyl, isoxazolyl, oxazolyl, thienyl, pyrrolyl(C 1-2 )alkyl, pyridyl(C 1-2 )alkyl, pyrimidyl(C 1-2 )alkyl, isoxazolyl(C 1-2 )alkyl, oxazolyl(C 1-2 )alkyl, or thienyl(C 1-2 )alkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino. 
     
     
         127 . The method of  claim 89 , wherein
 R 1  is —C(═W)NR 3 R 4 , wherein   W is O;   R 3  is hydrogen; and   R 4  is C 1-6  alkyl, C 2-6  alkenyl, halo(C 1-6 )alkyl, monohydroxy(C 1-6 )alkyl, dihydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  cycloalkenyl(C 1-4 )alkyl, phenyl, or benzyl, wherein the cycloalkyl, cycloalkenyl, and phenyl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino;   R 2  is fluoro, chloro or bromo;   m is 0 or 1;   X is —CHR 8 —;   R 8  and R 9  are both hydrogen or together form a bridge —(CH 2 ) p —, wherein   p is 2, 3, or 4; and   R 10  is phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino.   
     
     
         128 . The method of  claim 127 , wherein R 8  and R 9  are both hydrogen. 
     
     
         129 . The method of  claim 127 , wherein R 8  and R 9  together form a bridge —(CH 2 ) p —. 
     
     
         130 . The method of  claim 89 , wherein
 R 1  is —C(═W)NR 3 R 4 , wherein   W is O;   R 3  is hydrogen; and   R 4  is C 1-6  alkyl, C 2-6  alkenyl, halo(C 1-6 )alkyl, monohydroxy(C 1-6 )alkyl, dihydroxy(C 1-6 )alkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl(C 1-4 )alkyl, C 3-7  cycloalkenyl, C 3-7  cycloalkenyl(C 1-4 )alkyl, phenyl, or benzyl, wherein the cycloalkyl, cycloalkenyl, and phenyl portions thereof are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino;   R 2  is fluoro, chloro or bromo;   m is 0 or 1;   X is —C(═O)—;   R 9  is hydrogen; and   R 10  is phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of C 1-4  alkyl, C 1-4  alkoxy, halogen, halo(C 1-4 )alkyl, halo(C 1-4 )alkoxy, hydroxy, hydroxy(C 1-4 )alkyl, cyano, amino, amino(C 1-4 )alkyl, C 1-4  alkylamino, di(C 1-4 )alkylamino, and hydroxy(C 1-4 )alkylamino.   
     
     
         131 . The method of  claim 67 , wherein said compound is
 1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3-chlorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(2-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(4-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(4-fluorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3-cyanobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-dimethylsulfamoyl-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3,3,3-trifluoropropylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-cyclohexylsulfonyl-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(2,4-dichlorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3-cyano-4-fluorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(pyridin-2-ylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(pyridin-3-ylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3-trifluoromethylbenzylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(3,5-dichlorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(2,4,6-trifluorobenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(2-methylprop-1-ylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-cyclopentylsulfonyl-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(thiophen-3-ylsulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-(4-trifluoromethoxybenzyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   2-[1-(4-trifluoromethoxybenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-pyrimidine-4-carboxylic acid amide;   2-[1-(3-trifluoromethylbenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]pyrimidine-4-carboxylic acid amide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4]bipyridinyl-2-carboxylic acid methyl ester;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4]bipyridinyl-2-carboxylic acid cyclopropylmethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4′]bipyridinyl-2-carboxylic acid 2,2,2-trifluoroethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4′]bipyridinyl-2-carboxylic acid 3,3,3-trifluoropropylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4′]bipyridinyl-2-carboxylic acid 2,2,2-trifluoroethylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4′]bipyridinyl-2-carboxylic acid 3,3,3-trifluoropropylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[3,4′]bipyridinyl-2-carboxylic acid cyclopropylmethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylmethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]-bipyridinyl-6-carboxylic acid 2,2,2-trifluoroethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]-bipyridinyl-6-carboxylic acid 3,3,3-trifluoropropylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid 2,2,2-trifluoroethylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]-bipyridinyl-6-carboxylic acid 3,3,3-trifluoropropylamide;   1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]-bipyridinyl-6-carboxylic acid 4-fluorophenylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid amide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid 2-hydroxyethylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid 1,3-dihydroxyprop-2-ylamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carbonitrile;   N-cyclopropylmethyl-1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxamidine;   2-[1-(3-trifluoromethylbenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]pyrimidine-4-carboxylic acid cyclopropylamide;   2-[1-(3-trifluoromethylbenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]pyrimidine-4-carboxylic acid cyclopropylmethylamide;   2-[1-(4-trifluoromethoxybenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]pyrimidine-4-carboxylic acid cyclopropylamide;   5-chloro-1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   5-chloro-1′-(4-trifluoromethoxybenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   6′-oxo-1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   6-[8-(3-trifluoromethylbenzenesulfonyl)-8-aza-bicyclo[3.2.1]oct-2-en-3-yl]pyridine-2-carboxylic acid cyclopropylamide;   2-[1-(4-trifluoromethoxybenzenesulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]oxazole-4-carboxylic acid cyclopropylamide;   1′-[2,2,2-trifluoro-1-(4-trifluoromethoxyphenyl)-ethyl]-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   1′-[2,2,2-trifluoro-1-(4-hydroxymethylphenyl)-ethyl]-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid cyclopropylamide;   N-cyclopropyl-6-{1-[(3-trifluoromethylisoxazol-5-yl)methyl]-1,2,3,6-tetrahydropyridin-4-yl}picolinamide;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid methyl ester;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-carboxylic acid;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro-[2,4′]bipyridinyl-6-yl]methanol;   1′-(3-trifluoromethylbenzenesulfonyl)-1′,2′,3′,6′-tetrahydro[2,4′]bipyridinyl-6-cyclopropanoylamine;   1′-[(3-trifluoromethylbenzene)aminosulfonyl]-1′,2′,3′,6′-tetrahydro-[2,4]bipyridinyl-6-carboxylic acid cyclopropylamide;   
       or a pharmaceutically acceptable salt thereof. 
     
     
         132 . A method of treating a disorder responsive to the blockade of calcium channels in a mammal suffering from said disorder, comprising administering to a mammal in need of such treatment an effective amount of a compound having the Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Hy is a 6-membered heteroaromatic ring, a 5-membered heteroaromatic ring, or a 5-membered heterocyclic ring, wherein said Hy has at least one nitrogen atom, and wherein said Hy is attached to the tetrahydropyridinyl or dihydropyri olyl ring by a carbon atom; 
 R 1  is attached to a carbon atom of said Hy ring and is selected from the group consisting of
 a) —C(═W)NR 3 R 4 ; 
 b) —C(═O)OR 5 ; 
 c) —NR 6 —C(═O)R 7 ; 
 d) cyano; 
 e) hydroxyalkyl; and 
 a 5-membered, N-containing heteroaryl or a 5-membered, partially unsaturated, N-containing heterocyclo each of which is optionally substituted with one or two substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino; wherein 
 
 W is O or NR 14 , wherein 
 R 14  is hydrogen or alkyl; 
 R 3 , R 4 , and R 7  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 R 5  and R 6  are hydrogen or alkyl; 
 R 2  is selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxyalkyl, hydroxy, alkoxy, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, nitro, cyano, amino, alkylamino, and dialkylamino; 
 m is 0, 1, 2, or 3; 
 n is 0 or 1; 
 X is —CHR 8 — or —C(═O)—; 
 R 8  and R 9  are both hydrogen or together form a bridge —(CH 2 ) p —, wherein 
 p is 2, 3, or 4; 
 Z is Z 1  or Z 2 , wherein 
 Z 1  is —SO 2 —R 10 , wherein 
 R 10  is selected from the group consisting of C 3-12  alkyl, halo(C 3-12 )alkyl, C 5-12  cycloalkyl, (C 3-12  cycloalkyl)alkyl, C 5-12  cycloalkenyl, (C 3-12  cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylamino, and aryl(alkyl)amino, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 Z 2  is —C(R 11 R 12 )R 13 , wherein 
 R 11  and R 12  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, halogen, hydroxy, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, cyano, amino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl; and 
 R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; 
 with the following provisos when X is —CHR 8 — and R 8  is hydrogen: 
 1) when R 11  and R 12  are both hydrogen and R 13  is aryl or arylalkyl, then the aryl portion of R 13  is substituted with at least one of haloalkyl or haloalkoxy; or 
 2) when Hy is a pyridin-2-yl ring, then R 1  is other than optionally substituted 2-aminophenylaminocarbonyl or 2-hydroxyphenylaminocarbonyl. 
 
     
     
         133 . The method of  claim 132 , wherein a disorder responsive to the blockade of N-type calcium channels is treated. 
     
     
         134 . A method for treating stroke, neuronal damage resulting from head trauma, epilepsy, migraine, a mood disorder, schizophrenia, a neurodegenerative disorder, depression, anxiety, a psychosis, or cardiac arrhythmia in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound having the Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 Hy is a 6-membered heteroaromatic ring, a 5-membered heteroaromatic ring, or a 5-membered heterocyclic ring, wherein said Hy has at least one nitrogen atom, and 
 
       wherein said Hy is attached to the tetrahydropyridinyl or dihydropyrrolyl ring by a carbon atom;
 R 1  is attached to a carbon atom of said Hy ring and is selected from the group consisting of 
 a) —C(═W)NR 3 R 4 ; 
 b) —C(═O)OR 5 ; 
 c) —NR 6 —C(═O)R 7 ; 
 d) cyano; 
 e) hydroxyalkyl; and 
 f) a 5-membered, N-containing heteroaryl or a 5-membered, partially unsaturated, N-containing heterocyclo each of which is optionally substituted with one or two substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino; wherein 
 W is O or NR 14 , wherein 
 R 14  is hydrogen or alkyl; 
 R 3 , R 4 , and R 7  are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 R 5  and R 6  are hydrogen or alkyl; 
 R 2  is selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, hydroxyalkyl, hydroxy, alkoxy, alkoxyalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, nitro, cyano, amino, alkylamino, and dialkylamino; 
 m is 0, 1, 2, or 3; 
 n is 0 or 1; 
 X is —CHR 8 — or —C(═O)— 
 R 8  and R 9  are both hydrogen or together form a bridge —(CH 2 ) p —, wherein 
 p is 2, 3, or 4; 
 Z is Z 1  or Z 2 , wherein 
 Z 1  is —SO 2 —R 10 , wherein 
 R 10  is selected from the group consisting of C 3-12  alkyl, halo(C 3-12 )alkyl, C 5-12  cycloalkyl, (C 3-12  cycloalkyl)alkyl, C 5-12  cycloalkenyl, (C 3-12  cycloalkenyl)alkyl, heterocyclo, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylamino, and aryl(alkyl)amino, wherein the cycloalkyl, cycloalkenyl, heterocyclo, aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; and 
 Z 2  is —C(R 11 R 12 )R 13 , wherein 
 R 11  and R 12  are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, halogen, hydroxy, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, cyano, amino, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl; and 
 R 13  is selected from the group consisting of aryl, arylalkyl, heteroaryl, and heteroarylalkyl, wherein the aryl and heteroaryl portions thereof are optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, dialkylamino, and hydroxyalkylamino; 
 with the following provisos when X is —CHR 8 — and R 8  is hydrogen: 
 1) when R 11  and R 12  are both hydrogen and R 13  is aryl or arylalkyl, then the aryl portion of R 13  is substituted with at least one of haloalkyl or haloalkoxy; or 
 2) when Hy is a pyridin-2-yl ring, then R 1  is other than optionally substituted 2-aminophenylaminocarbonyl or 2-hydroxyphenylaminocarbonyl.