Oligomer-calcimimetic conjugates and related compounds

1. A compound, of the formula

wherein:

is selected from the group consisting of 3-methoxyphenyl, 3-chlorophenyl and 1-naphthyl;

each R 4 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, phenyl, —CF 3 , —CF 2 H, —CFH 2 , lower alkyl, —O-lower alkyl, —OCH 2 CF 3 , —OH, —CN, —NO 2 , —C(O)-lower alkyl, —C(O)O-lower alkyl, —C(O)NH-lower alkyl, —C(O)N-lower alkyl 2 , —OC(O)-lower alkyl, and —NH—C(O)-lower alkyl;

(a) is an integer from 1 to 5;

R 5 is lower alkyl;

n is an integer from 10 to about 2000;

X is a spacer moiety of the formula —(CR x R y ) a —K w —(CR x R y ) b —(CH 2 CH 2 O) c —(CR x R y ) d —K z —,

wherein

each R x and R y , in each occurrence, is independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and substituted aryl;

a is an integer from 0 to 5;

b is an integer from 0 to 5;

each of K w , and K z , is independently selected from —NH—, —C(O)—, —C(O)NH—, —NH—C(O)—, —O—, —S—, O—C(O)—, C(O)—O—, —O—C(O)—O—, O—C(O)—NH—, —NH—C(O)— —O—;

c is an integer from 0 to 10, and

d is an integer from 0 to 5; and

AA is a single amino acid residue chosen from alanine, valine, leucine, isoleucine, glycine, threonine, serine, cysteine, methionine, tyrosine, phenylalanine, tryptophan, aspartic acid, glutamic acid, lysine, arginine, histidine, and proline, or a pharmaceutically acceptable salt or solvate thereof.

2. A composition comprising a compound of claim 1 , and optionally, a pharmaceutically acceptable excipient.

3. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.

4. The compound of claim 1 , wherein R 4 is —CF 3 ; (a) is 1; R 5 is methyl;

is 1-naphthyl; and n is an integer from 10 to about 400.

5. The compound of claim 1 , wherein the compound of Formula VI is a compound of Formula VII:

wherein:

n is an integer from 10 to about 2000;

X is a spacer moiety of the formula —(CR x R y ) a —K w —(CR x R y ) b —(CH 2 CH 2 O) c —(CR x R y ) d —K z —,

wherein

each R x and R y , in each occurrence, is independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and substituted aryl;

a is an integer from 0 to 5;

b is an integer from 0 to 5;

each of and K w and K z is independently selected from —NH—, —C(O)—, —C(O)NH—, —NH—C(O)—, —O—, —S—, O—C(O)—, C(O)—O—, —O—C(O)—O—, O—C(O)—NH—, —NH—C(O)— —O—;

c is an integer from 0 to 10, and

d is an integer from 0 to 5; and

AA is a single amino acid residue chosen from alanine, valine, leucine, isoleucine, glycine, threonine, serine, cysteine, methionine, tyrosine, phenylalanine, tryptophan, aspartic acid, glutamic acid, lysine, arginine, histidine, and proline, or a pharmaceutically acceptable salt or solvate thereof.

6. The compound of claim 5 , wherein the compound of Formula VII is a compound of Formula VIII:

wherein:

n is an integer from 10 to about 2000; and

AA is a single amino acid residue chosen from alanine, valine, leucine, isoleucine, glycine, threonine, serine, cysteine, methionine, tyrosine, phenylalanine, tryptophan, aspartic acid, glutamic acid, lysine, arginine, histidine, and proline, or

a pharmaceutically acceptable salt or solvate thereof.

7. The compound of claim 6 , wherein n is an integer from about 10 to about 950.

8. The compound of claim 7 , wherein n is an integer from about 200 to about 800.

9. The compound of claim 7 , wherein the amino acid residue is chosen from glycine, leucine, valine, and isoleucine.

10. The compound of claim 1 , selected from a compound of the formula:

wherein mPEG-10k is a methoxy capped poly(ethylene glycol) having a weight average molecular weight of about 10,000 Daltons and mPEG-20k is a methoxy capped poly(ethylene glycol) having a weight average molecular weight of about 20,000 Daltons.

11. The compound of claim 5 , wherein each R x and R y , in each occurrence, are independently selected from H or lower alkyl.

12. The compound of claim 11 , wherein a is 0; b is 1, K w is C(O)—O—; R x and R y , in each occurrence are independently H or lower alkyl; c is 0; d is 0; and K z is —O—.

13. The compound of claim 12 , wherein the amino acid residue is chosen from glycine, leucine, valine, and isoleucine.

14. The compound of claim 6 , wherein the amino acid residue is chosen from glycine, leucine, valine, and isoleucine.

15. The compound of claim 14 , wherein the amino acid residue is selected from D-leucine, D-valine, and D-isoleucine.

16. The compound of claim 14 , wherein the amino acid residue is selected from L-leucine, L-valine, and L-isoleucine.

17. A compound selected from

or a pharmaceutically acceptable salt or solvate thereof;

wherein mPEG-10k is a methoxy capped poly(ethylene glycol) having a weight average molecular weight of about 10,000 Daltons and mPEG-20k is a methoxy capped poly(ethylene glycol) having a weight average molecular weight of about 20,000 Daltons.

18. A composition comprising a compound of claim 17 , and optionally, a pharmaceutically acceptable excipient.

19. A composition of matter comprising a compound of claim 17 , wherein the compound is present in a dosage form.

20. The compound of claim 16 , the amino acid residue is leucine.