IP Library › Granted Patent US 7,491,835

Granted Patent B2

US 7,491,835 · App. 10/946,540 · Granted Feb 17, 2009

Prodrugs of amino acids with affinity for the α2δ-protein

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Quick Facts

Patent No.: US 7,491,835
App. No.: 10/946,540
Granted: Feb 17, 2009
Kind: B2

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Abstract

This invention relates to prodrugs of certain amino acids that bind to the alpha-2-delta (α2δ) subunit of a calcium channel. These compounds and their pharmaceutically acceptable salts are useful in the treatment of a variety of psychiatric, pain and other disorders.

Claims (351)

1. A compound selected from the group consisting of the following compounds and their pharmaceutically acceptable salts:

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-octanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-octanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-octanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2-Amino-propionylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-propionylamino)-methyl]-5-methyl-octanoic acid;

3-[(2-Amino-propionylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2-Amino-propionylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2-Amino-propionylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2-Amino-propionylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2-Amino-propionylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2-Amino-propionylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2-Amino-acetylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-acetylamino)-methyl]-5-methyl-octanoic acid;

3-[(2-Amino-acetylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2-Amino-acetylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2-Amino-acetylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2-Amino-acetylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2-Amino-acetylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2-Amino-acetylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-(2-Amino-acetylamino)-5-methyl-heptanoic acid;

3-(2-Amino-acetylamino)-5-methyl-octanoic acid;

3-(2-Amino-acetylamino)-5-methyl-nonanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-propionylamino)-5-methyl-heptanoic acid;

3-(2-Amino-propionylamino)-5-methyl-octanoic acid;

3-(2-Amino-propionylamino)-5-methyl-nonanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-heptanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-octanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-nonanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2-Amino4-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2-Amino4-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino4-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid; and

3-(2-Amino4-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid.

2. A compound selected from the group consisting of the following compounds and their pharmaceutically acceptable salts:

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-octanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-octanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-octanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-5-methyl-octanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-5-methyl-nonanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2S-Amino-propionylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-5-methyl-octanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-5-methyl-heptanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-4,5-dimethyl-heptanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-4,5-dimethyl-octanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-4,5-dimethyl-nonanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-5-methyl-hexanoic acid;

3-[(2S-Amino-acetylamino)-methyl]-4,5-dimethyl-hexanoic acid;

3-(2S-Amino-acetylamino)-5-methyl-heptanoic acid;

3-(2S-Amino-acetylamino)-5-methyl-octanoic acid;

3-(2S-Amino-acetylamino)-5-methyl-nonanoic acid;

3-(2S-Amino-acetylamino)-4,5-dimethyl-heptanoic acid;

3-(2S-Amino-acetylamino)-4,5-dimethyl-octanoic acid;

3-(2S-Amino-acetylamino)-4,5-dimethyl-nonanoic acid;

3-(2S-Amino-propionylamino)-5-methyl-heptanoic acid;

3-(2S-Amino-propionylamino)-5-methyl-octanoic acid;

3-(2S-Amino-propionylamino)-5-methyl-nonanoic acid;

3-(2S-Amino-propionylamino)-4,5-dimethyl-heptanoic acid;

3-(2S-Amino-propionylamino)-4,5-dimethyl-octanoic acid;

3-(2S-Amino-propionylamino)-4,5-dimethyl-nonanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-5-methyl-heptanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-5-methyl-octanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-5-methyl-nonanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-4,5-dimethyl-heptanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-4,5-dimethyl-octanoic acid;

3-(2S-Amino-3-methyl-butyrylamino)-4,5-dimethyl-nonanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid;

3-(2S-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid;

3-(2S-Amino-4-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2S-Amino-4-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2S-Amino-4-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2S-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2S-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid; and

3-(2S-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid.

3. A compound selected from the group consisting of the following compounds and their pharmaceutically acceptable salts:

3S-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5R-methyl-octanoic acid;

3S-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5R-methyl-heptanoic acid;

3S-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5R-methyl-nonanoic acid;

3R-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-heptanoic acid;

3R-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-octanoic acid;

3R-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-nonanoic acid;

3S-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-5R-methyl-hexanoic acid;

3R-[(2S-Amino-4-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-hexanoic acid;

3S-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5R-methyl-heptanoic acid;

3S-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5R-methyl-octanoic acid;

3S-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5R-methyl-nonanoic acid;

3R-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-heptanoic acid;

3R-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-octanoic acid;

3R-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4R,R5-dimethyl-nonanoic acid;

3S-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-5R-methyl-hexanoic acid;

3R-[(2S-Amino-3-methyl-pentanoylamino)-methyl]-4R,5R-dimethyl-hexanoic acid;

3S-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5R-methyl-heptanoic acid;

3S-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5R-methyl-octanoic acid

3S-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5R-methyl-nonanoic acid;

3R-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4R,5R-dimethyl-heptanoic acid;

3R-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4R,5R-dimethyl-octanoic acid;

3R-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4R,5R-dimethyl-nonanoic acid;

3S-[(2S-Amino-3-methyl-butyrylamino)-methyl]-5R-methyl-hexanoic acid;

3R-[(2S-Amino-3-methyl-butyrylamino)-methyl]-4R,5R-dimethyl-hexanoic acid;

3S-[(2S-Amino-propionylamino)-methyl]-5R-methyl-heptanoic acid;

3S-[(2S-Amino-propionylamino)-methyl]-5R-methyl-octanoic acid;

3S-[(2S-Amino-propionylamino)-methyl]-5R-methyl-nonanoic acid;

3R-[(2S-Amino-propionylamino)-methyl]-4R,5R-dimethyl-heptanoic acid;

3R-[(2S-Amino-propionylamino)-methyl]-4R,5R-dimethyl-octanoic acid;

3R-[(2S-Amino-propionylamino)-methyl]-4R,5R-dimethyl-nonanoic acid;

3S-[(2S-Amino-propionylamino)-methyl]-5R-methyl-hexanoic acid;

3R-[(2S-Amino-propionylamino)-methyl]-4R,5R-dimethyl-hexanoic acid;

3S-[(2S-Amino-acetylamino)-methyl]-5R-methyl-heptanoic acid;

3S-[(2S-Amino-acetylamino)-methyl]-5R-methyl-octanoic acid;

3S-[(2S-Amino-acetylamino)-methyl]-5R-methyl-heptanoic acid;

3R-[(2S-Amino-acetylamino)-methyl]-4R,5R-dimethyl-heptanoic acid;

3R-[(2S-Amino-acetylamino)-methyl]-4R,5R-dimethyl-octanoic acid;

3R-[(2S-Amino-acetylamino)-methyl]-4R,5R-dimethyl-nonanoic acid;

3S-[(2S-Amino-acetylamino)-methyl]-5R-methyl-hexanoic acid;

3R-[(2S-Amino-acetylamino)-methyl]-4R,5R-dimethyl-hexanoic acid;

3S-(2S-Amino-acetylamino)-5R-methyl-heptanoic acid;

3S-(2S-Amino-acetylamino)-5R-methyl-octanoic acid;

3S-(2S-Amino-acetylamino)-5R-methyl-nonanoic acid;

3R-(2S-Amino-acetylamino)-4R,5R-dimethyl-heptanoic acid;

3R-(2S-Amino-acetylamino)-4R,5R-dimethyl-octanoic acid;

3R-(2S-Amino-acetylamino)-4R,5R-dimethyl-nonanoic acid;

3R-(2S-Amino-propionylamino)-5R-methyl-heptanoic acid;

3S-(2S-Amino-propionylamino)-5R-methyl-octanoic acid;

3S-(2S-Amino-propionylamino)-5R-methyl-nonanoic acid;

3R-(2S-Amino-propionylamino)-4R,5R-dimethyl-heptanoic acid;

3R-(2S-Amino-propionylamino)-4R,5R-dimethyl-octanoic acid;

3R-(2S-Amino-propionylamino)-4R,5R-dimethyl-nonanoic acid;

3S-(2S-Amino-3-methyl-butyrylamino)-5R-methyl-heptanoic acid;

3S-(2S-Amino-3-methyl-butyrylamino)-5R-methyl-octanoic acid;

3S-(2S-Amino-3-methyl-butyrylamino)-5R-methyl-nonanoic acid;

3R-(2S-Amino-3-methyl-butyrylamino)-4R,5R-dimethyl-heptanoic acid;

3R-(2S-Amino-3-methyl-butyrylamino)-4R,5R-dimethyl-octanoic acid;

3R-(2S-Amino-3-methyl-butyrylamino)-4R,5R-dimethyl-nonanoic acid;

3S-(2S-Amino-3-methyl-pentanoylamino)-5R-methyl-heptanoic acid;

3S-(2S-Amino-3-methyl-pentanoylamino)-5R-methyl-octanoic acid;

3S-(2S-Amino-3-methyl-pentanoylamino)-5R-methyl-nonanoic acid;

3R-(2S-Amino-3-methyl-pentanoylamino)-4R,5R-dimethyl-heptanoic acid;

3R-(2S-Amino-3-methyl-pentanoylamino)-4R,5R-dimethyl-octanoic acid;

3R-(2S-Amino-3-methyl-pentanoylamino)-4R,5R-dimethyl-nonanoic acid;

3S-(2S-Amino-4-methyl-pentanoylamino)-5R-methyl-heptanoic acid;

3S-(2S-Amino-4-methyl-pentanoylamino)-5R-methyl-octanoic acid;

3S-(2S-Amino-4-methyl-pentanoylamino)-5R-methyl-nonanoic acid;

3R-(2S-Amino-4-methyl-pentanoylamino)-4R,5R-dimethyl-heptanoic acid;

3R-(2S-Amino-4-methyl-pentanoylamino)-4R,5R-dimethyl-octanoic acid; and

3R-(2S-Amino-4-methyl-pentanoylamino)-4R,5R-dimethyl-nonanoic acid.

4. A compound having the formula IV

wherein R 1 is hydrogen or (C 1 -C 10 )alkyl optionally substituted with from one to five fluorine atoms;

R 2 is hydrogen or (C 1 -C 6 )alkyl;

R 1 and R 2 , together with the carbon to which they are attached, may form a three to six membered cycloalkyl ring;

R 3 is selected from the group consisiting of hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, and pyridyl-(C 1 -C 3 )alkyl, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;

R 4 is hydrogen or (C 1 -C 6 )alkyl optionally substituted with from one to five fluorine atoms;

R 5 is hydrogen or (C 1 -C 6 )alkyl optionally substituted with from one to five fluorine atoms;

R 4 and R 5 , together with the carbon to which they are attached, may form a three to six membered cycloalkyl ring; and

R 6 is a side chain derived from an α-amino acid or other (C 1 -C 8 )alkyl;

or a pharmaceutically acceptable salt of such a compound.

5. A compound according to claim 4 selected from the group consisting of the following compounds and their pharmaceutically acceptable salts:

3-(2-Amino-acetylamino)-5-methyl-heptanoic acid;

3-(2-Amino-acetylamino)-5-methyl-octanoic acid;

3-(2-Amino-acetylamino)-5-methyl-nonanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-acetylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-propionylamino)-5-methyl-heptanoic acid;

3-(2-Amino-propionylamino)-5-methyl-octanoic acid;

3-(2-Amino-propionylamino)-5-methyl-nonanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-propionylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-heptanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-octanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-5-methyl-nonanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-3-methyl-butyrylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid;

3-(2-Amino-3-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-5-methyl-heptanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-5-methyl-octanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-5-methyl-nonanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-heptanoic acid;

3-(2-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-octanoic acid; and

3-(2-Amino-4-methyl-pentanoylamino)-4,5-dimethyl-nonanoic acid.

6. A compound having the formula V

wherein R 1 is hydrogen or (C 1 -C 10 )alkyl optionally substituted with from one to five fluorine atoms;

R 2 is hydrogen or (C 1 -C 6 )alkyl;

R 1 and R 2 , together with the carbon to which they are attached, may form a three to six membered cycloalkyl ring;

R 3 is selected from the group consisting of hydrogen, (C 1 -C 8 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl-(C 1 -C 6 )alkyl, phenyl, phenyl-(C 1 -C 3 )alkyl, pyridyl, and pyridyl-(C 1 -C 3 )alkyl, wherein each of the foregoing alkyl moieties can be optionally substituted with from one to five fluorine atoms, preferably with from zero to three fluorine atoms, and wherein said phenyl and said pyridyl and the phenyl and pyridyl moieties of said phenyl-(C 1 -C 3 )alkyl and said pyridyl-(C 1 -C 3 )alkyl, respectively, can be optionally substituted with from one to three substituents, preferably with from zero to two substituents, independently selected from chloro, fluoro, amino, nitro, cyano, (C 1 -C 3 )alkylamino, (C 1 -C 3 )alkyl optionally substituted with from one to three fluorine atoms and (C 1 -C 3 )alkoxy optionally substituted with from one to three fluorine atoms;

R 4 is hydrogen or (C 1 -C 6 )alkyl optionally substituted with from one to five fluorine atoms;

R 5 is hydrogen or (C 1 -C 6 )alkyl optionally substituted with from one to five fluorine atoms;

R 4 and R 5 , together with the carbon to which they are attached, may form a three to six membered cycloalkyl ring; and

R 6 is a side chain derived from an α-amino acid or other (C 1 -C 8 )alkyl;

or a pharmaceutically acceptable salt of such a compound.

7. A compound according to claim 6 selected from the group consisting of the following compounds and their pharmaceutically acceptable salts: