Urea derivatives as calcium channel blockers

1. A compound of the formula:

or a salt thereof,

wherein A is H;

B is piperidine;

R 1 is H or alkyl (1-8C), alkenyl (2-8C) or alkynyl (2-8C);

Z is N;

each R 3 is independently a substituent selected from the group consisting of ═O, alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), acyl, aryl, alkylaryl, halo, CHF 2 , CF 3 , OCF 3 , OCHF 2 , OCOR, CN, NO 2 , NR 2 , OR, SR, COR, COOR, CONR 2 , SOR, SO 2 R, SO 3 R, NRCOR, NRCOOR, OCONR 2 , SONR, SO 2 NR, OOCR, NRSOR and NRSO 2 R, wherein R is H or alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), aryl, or alkylaryl, wherein two R on the same nitrogen may form a 5-7 membered ring, and wherein two substituents on adjacent carbons may form a 5-7 membered ring;

wherein each R 4 is independently H or alkyl (1-4C);

m is 0-3;

n is 0-2;

each Ar is phenyl; and

wherein each B and each Ar moiety in formula (1) may be substituted by one or more substituents selected from the group consisting of ═O (in nonaromatic cyclic moieties), alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), acyl, aryl, alkylaryl, halo, CHF 2 , CF 3 , OCF 3 , OCHF 2 , OCOR, CN, NO 2 , NR 2 , OR, SR, COR, COOR, CONR 2 , SOR, SO 2 R, SO 3 R, NRCOR, NRCOOR, OCONR 2 , SONR, SO 2 NR, OOCR, NRSOR and NRSO 2 R, wherein R is H or alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), aryl, or alkylaryl, wherein two R on the same nitrogen may form a 5-7 membered ring, and wherein two substituents on adjacent carbons may form a 5-7 membered ring, and

wherein any alkyl, alkenyl, alkynyl or aryl set forth above may further be substituted by ═O, alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), acyl, aryl, alkylaryl, halo, CHF 2 , CF 3 , OCF 3 , OCHF 2 , OCOR, CN, NO 2 , NR 2 , OR, SR, COR, COOR, CONR 2 , SOR, SO 2 R, SO 3 R, NRCOR, NROR, NRCOOR, OCONR 2 , SONR, SO 2 NR, OOCR, NRSOR and NRSO 2 R, wherein R is H or alkyl (1-8C), alkenyl (2-8C), alkynyl (2-8C), aryl, or alkylaryl, wherein two R on the same nitrogen may form a 5-7 membered ring, and wherein two substituents on adjacent carbons may form a 5-7 membered.

2. The compound of claim 1 , wherein R 1 is H.

3. The compound of claim 1 , wherein n is 0.

4. The compound of claim 1 , wherein m is 0.

5. The compound of claim 1 , wherein n is 2 and R 3 is ═O or COOH.

6. The compound of claim 1 , wherein each R 4 is H.

7. The compound of claim 1 , wherein the compound is

4-(1-methyl-piperidin-4-ylmethyl)-piperazine-1-carboxylic acid benzhydryl-amide;

4-(1-methyl-piperidin-3-ylmethyl)-piperazine-1-carboxylic acid benzhydryl-amide;

4-[(1-phenyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

4-cyclopropylmethyl-piperazine-1-carboxylic acid benzhydryl-amide;

4-[(1-benzyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

4-[(1-methyl-piperidin-2-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

2,6-dimethyl-4-[(1-benzyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

3-methyl-4-[(1-benzyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

4-[(1-methyl-4-phenyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

2,6-dimethyl-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxylic acid benzhydryl-amide;

N-[bis(4-methylphenyl)methyl]-2,6-dimethyl-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide;

N-[bis(4-fluorophenyl)methyl]-2,6-dimethyl-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide;

N-[bis(3-fluorophenyl)methyl]-2,6-dimethyl-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide;

N-[bis(4-chlorophenyl)methyl]-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide;

N-[bis(4-methylphenyl)methyl]-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide;

N-[bis(4-fluorophenyl)methyl]-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide; or

N-[bis(3-fluorophenyl)methyl]-4-[(1-methyl-piperidin-4-yl)-methyl]-piperazine-1-carboxamide,

or the salt or conjugate thereof.

8. The compound of claim 1 which is

4-(1-methyl-piperidin-4-ylmethyl)-piperazine-1-carboxylic acid benzhydryl-amide, or a salt thereof.

9. The compound of claim 1 , which is coupled to polyethylene glycol.

10. The compound of claim 7 , which is coupled to polyethylene glycol.