TREATMENT OF ALZHEIMER'S DISEASE AND MILD COGNITIVE IMPAIRMENT USING GNRH-I ANALOGS AND ONE OR MORE OF ACETYLCHOLINESTERASE INHIBITORS AND NMDA RECEPTOR ANTAGONISTS

1 . A method of treating, mitigating, slowing the progression of, or preventing a condition selected from the group consisting of Alzheimer's disease and Mild Cognitive Impairment (MCI), comprising the step of:

administering a therapeutically effective combination of a gonadotropin-releasing hormone analog with an acetylcholinesterase inhibitor or an N-methyl-D-aspartate receptor antagonist.

2 - 3 . (canceled)

4 . A method of treating, mitigating, slowing the progression of, or preventing Alzheimer's disease, comprising the step of:

administering a therapeutically effective synergistic combination of a gonadotropin-releasing hormone analog with an acetylcholinesterase inhibitor or an N-methyl-D-aspartate receptor antagonist.

5 . The method of claim 1 , wherein the gonadotropin releasing hormone is leuprolide acetate, and the acetylcholinesterase inhibitor is a selected from the group consisting of donepezil, rivastigimine, galantamine and tacrine.

6 . (canceled)

7 . The method of claim 1 , wherein the gonadotropin releasing hormone is leuprolide acetate, and the N-methyl-D-aspartate receptor antagonist is memantine.

8 . The method of claim 1 , wherein the gonadotropin releasing hormone is leuprolide acetate, and the N-methyl-D-aspartate receptor antagonist is memantine.

9 . The method of claim 4 , wherein the therapeutically effective synergistic combination comprises a therapeutically effective amount of an acetylcholinestarase inhibitor selected from the group consisting of donepezil, rivastigimine, galantamine and tacrine and a therapeutically effective amount of an N-methyl-D-aspartate receptor antagonist.

10 . The method of claim 9 , wherein the N-methyl-D-aspartate receptor antagonist is memantine.

11 . The method of claim 4 , wherein the therapeutically effective synergistic combination is a therapeutically effective synergistic combination of leuprolide acetate and an acetylcholinestarase inhibitor selected from the group consisting of donepezil, rivastigimine, galantamine and tacrine.

12 . The method of claim 4 , wherein the therapeutically effective synergistic combination is a therapeutically effective synergistic combination of leuprolide acetate and memantine.

13 . The method of claim 1 , wherein the gonadotropin-releasing hormone analog comprises leuprolide and is administered approximately once every 60 days in combination with a stable dose of an acetylcholinesterase inhibitor.

14 . The method of claim 1 , wherein the combination comprises approximately 22.5 mg of leuprolide acetate.

15 . The method of claim 14 , wherein the leuprolide acetate is administered in a controlled-release formulation.

16 . A combination comprising:

a gonadotropin-releasing hormone analog and at least one of an acetylcholinesterase inhibitor and an N-methyl-D-aspartate receptor antagonist.

17 . The combination of claim 16 , wherein the gonadotropin-releasing hormone comprises leuprolide acetate and the acetylcholinesterase inhibitor is selected from the group consisting of donepezil, rivastigimine, galantamine and tacrine.

18 . The combination of claim 16 , wherein the gonadotropin-releasing hormone comprises leuprolide acetate and the N-methyl-D-aspartate receptor antagonist comprises memantine.

19 . The combination of claim 16 , wherein the gonadotropin-releasing hormone analog has the following structural formula:

or a pharmaceutically acceptable salt thereof; wherein:

A is an amino acyl residue selected from the group consisting of:

L-pyroglutamyl, D-pyroglutamyl, N-acetyl-L-prolyl, N-acetyl-D-prolyl, N-acetyl-L-delta 3,4 -prolyl, N-acetyl-D-delta 3,4 -prolyl, N-acetyl-L phenylalanyl, N-acetyl-D-phenylalanyl, N-acetyl-L-3-(2-thienyl)alanyl, N-acetyl-D-3-(2-thienyl)alanyl, N-acetyl-L-3-(4-chlorophenyl)alanyl, N-acetyl-D-3-(4-chlorophenyl)alanyl, N-acetyl-L-3-(4-fluorophenyl)alanyl, N-acetyl-D-3-(4-fluorophenyl)alanyl, N-acetyl-L-3-(4-bromophenyl)alanyl, N-acetyl-D-3-(4-bromophenyl)alanyl, N-acetyl-L-3-(4-methylphenyl)alanyl, N-acetyl-D-3-(4-methylphenyl)alanyl, N-acetyl-L-3-(pentamethylphenyl)alanyl, N-acetyl-D-3-(pentamethylphenyl)alanyl, N-acetyl-L-3-(3,4,5-trimethylphenyl)alanyl, N-acetyl-D-3-(3,4,5-trimethylphenyl)alanyl, N-acetyl-L-3-tryptyl(N-indole-methyl), N-acetyl-D-3-tryptyl(N-indole-methyl), N-acetyl-L-tryptyl(N-indole-formyl), N-acetyl-D-tryptyl-(N-indole-formyl), N-acetyl-L-3-(1-adamantyl)alanyl, N-acetyl-D-3-(1-adamantyl)alanyl, N-acetyl-L-5-fluorotryptyl(N-indole-formyl), N-acetyl-D-5-fluorotryptyl(N-indole-formyl), N-acetyl-L-3-(2-naphthyl)alanyl, N-acetyl-D-3-(2-naphthyl)alanyl, N-acetyl-L-3-(3-benzothienyl)alanyl, N-acetyl-D-3-(3-benzothienyl)alanyl, N-acetyl-L-3-(3-benzoxazolyl)alanyl, N-acetyl-D-3-(3-benzoxazolyl)alanyl, N-acetyl-alpha-methyl-L-3-(4-chlorophenyl)alanyl, N-acetyl-alpha-methyl-D-3-(4-chlorophenyl)alanyl, N-acetyl-L-3-(4-trifluoromethylphenyl)alanyl, N-acetyl-D-3-(4-trifluoromethylphenyl)alanyl, N-acetyl-L-tyrosyl, N-acetyl-D-tyrosyl, N-acetyl-L-O-methyl-tyrosyl, N-acetyl-D-O-methyl-tyrosyl, N-acetyl-D-3-(2-naphthyl)alanyl, N-acetyl-L-3-(1-naphthyl)alanyl, N-acetyl-D-3-(1-naphthyl)alanyl, N-acetylsarcosyl, N-acetyl-L-3-(cyclohexyl)alanyl, N-acetyl-D-3-(cyclohexyl)alanyl, N-acetylglycyl, L-N-acetyl-N-methylalanyl, N-acetyl-N-methyl-D-alanyl, N-acetyl-alpha-methyl-L-phenylalanyl, N-acetyl-alpha-methyl-D-phenylalanyl, N-acetyl-D-phenylalanyl, N-acetyl-L-phenylalanyl, N-formylsarcosyl, N-formyl-N-methyl-L-alanyl, N-formyl-N-methylalanyl, 2-N-beta-(ethylaminocarbonyl)-N-epsilon-(ethylamido)glutamyl, N-delta-ethyl-glutamyl, L-prolyl, D-prolyl, L-delta 3,4 -prolyl, D-delta 3,4 -prolyl, L-phenylalanyl, D-phenylalanyl, L-3-(4-methylphenyl)alanyl), D-3-(4-methylphenyl)alanyl, L-3-(4-nitrophenyl)alanyl, D-3-(4-nitrophenyl)alanyl, L-3-(4-acetylaminophenyl)alanyl, D-3-(4-acetylaminophenyl)alanyl, L-3-(4-chlorophenyl)alanyl, D-3-(4-chlorophenyl)alanyl, L-3-(4-fluorophenyl)alanyl, D-3-(4-fluorophenyl)alanyl, alpha-methyl-L-3-(4-chlorophenyl)alanyl, alpha-methyl-D-3-(4-chlorophenyl)alanyl, L-3-(4-trifluoromethylphenyl)alanyl, D-3-(4-trifluoromethylphenyl)alanyl, L-tyrosyl, D-tyrosyl, L-O-methyl-tyrosyl, D-O-methyl-tyrosyl, sarcosyl, glycyl, L-N-methylalanyl, N-methyl-D-alanyl, N-methyl-L-pyroglutamyl, N-methyl-D-pyroglutamyl, alpha-methyl-L-phenylalanyl, alpha-methyl-D-phenylalanyl, N-acetyl-alpha-aza-3-(4-chlorophenyl)alanyl, N-acetyl-alpha-aza-3-(4-fluorophenyl)alanyl, N-acetyl-alpha-aza-3-(2-naphthyl)alanyl, N-acetyl-alpha-aza-3-(1-naphthyl)alanyl, N-acetyl-alpha-aza-alanyl, N-acetyl-alpha-aza-glycyl, N-acetyl-alpha-aza-sarcosyl, N-acetyl-alpha-aza-3-(4-methylphenyl)alanyl, N-acetyl-alpha-aza-cyclohexylalanyl, N-acetyl-alpha-aza-3-(1-adamantyl)alanyl, N-acetyl-alpha-aza-tyrosyl(O-methyl), N-acetyl-alpha-aza-3-(3-benzothienyl)alanyl, N-acetyl-alpha-aza-phenylalanyl, N-methyl-alpha-aza-pyroglutamyl, N-acetyl-alpha-aza-3-(2-thienyl)alanyl, N-acetyl-alpha-aza-3-(3-benzoxazolyl)alanyl, N-acetyl-alpha-aza-3-(3,4,5-trimethylphenyl)alanyl, N-acetyl-alpha-aza-3-(pentamethylphenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(2-naphthyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(1-naphthyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(4-chlorophenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(4-fluorophenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(4-methylphenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(4-methoxyphenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza (1-adamantyl)alanyl, N-acetyl-N-alpha-methyl alpha-aza-3-(phenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-alanyl, N-acetyl-N-alpha-methyl alpha-aza-3-(cyclohexyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(benzothienyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(benzoxazolyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(3,4,5-trimethylphenyl)alanyl, N-acetyl-N-alpha-methyl-alpha-aza-3-(pentamethylphenyl)alanyl and N-acetyl-N-alpha-methyl-alpha-aza-3-(2-thienyl)alanyl;

B is absent or is an amino acyl residue selected from the group consisting of L-histidyl, D-histidyl, L-tryptyl, D-tryptyl, L-tryptyl(N-indole-methyl), D-tryptyl(N-indole-methyl), L-phenylalanyl, D-phenylalanyl, L-3-(2-naphthyl)-alanyl, D-3-(2-naphthyl)-alanyl, L-3-(1-naphthyl)-alanyl, D-3-(1-naphthyl)-alanyl, L-3-(3-benzoxazolyl)alanyl, D-3-(3-benzoxazolyl)alanyl, L-3-(3-pyridyl)-alanyl, L-3-(2-pyridyl)-alanyl, D-3-(3-pyridyl)-alanyl, D-3-(2-pyridyl)-alanyl, L-3-(2-thiazolyl)alanyl, D-3-(2-thiazolyl)-alanyl, L-3-(3-benzothienyl)alanyl, D-3-(3-benzothienyl)alanyl, L-3-(2-benzothienyl)alanyl, D-3-(2-benzothienyl)alanyl, L-3-(2-thienyl)-alanyl, D-3-(2-thienyl)-alanyl, L-cyclohexylalanyl, D-cyclohexylalanyl, L-3-(3-pyrazolyl)alanyl, D-3-(3-pyrazolyl)alanyl, L-3-(4-chlorophenyl)alanyl, D-3-(4-chlorophenyl)alanyl, L-3-(4-fluorophenyl)alanyl, D-3-(4-fluorophenyl)alanyl, L-3-(4-bromophenyl)alanyl, D-3-(4-bromophenyl)alanyl, L-3-(4-trifluoromethylphenyl)alanyl, D-3-(4-trifluoromethylphenyl)alanyl, L-3-(4-aminophenyl)alanyl, D-3-(4-aminophenyl)alanyl, L-3-(4-nitrophenyl)alanyl, D-3-(4-nitrophenyl)alanyl, L-3-(4-cyanophenyl)alanyl, D-3-(4-cyanophenyl)alanyl, L-tyrosyl-(O-methyl), D-tyrosyl(O-methyl), L-3-(4-methylphenyl)alanyl, D-3-(4-methylphenyl)alanyl, L-3-(4-nitrophenyl)alanyl, D-3-(4-nitrophenyl)alanyl, L-3-(4-acetylaminophenyl)alanyl, D-3-(4-acetylaminophenyl)alanyl, L-methionyl, D-methionyl, L-alpha-methyl-3-(4-chlorophenyl)alanyl, D-alpha-methyl-3-(4-chlorophenyl)alanyl, (3S)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl, (3R)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl, (2)-N-(ethylaminocarbonyl)-(5)-N-(ethylamido)glutamyl, alpha-aza-3-(3,4,5-trimethylphenyl)alanyl, alpha-aza-3-(4-bromophenyl)alanyl, alpha-aza-3-(4-methylphenyl)alanyl, alpha-aza-3-(1-naphthyl)alanyl, alpha-aza-3-(1-adamantyl)alanyl, L-3-(3-quinolyl)-alanyl, D-3-(3-quinolyl)-alanyl, alpha-aza-3-(4-chlorophenyl)alanyl, alpha-aza-3-(4-fluorophenyl)alanyl, alpha-aza-3-(2-naphthyl)alanyl, alpha-aza-3-(3-quinolyl)alanyl, alpha-aza-phenylalanyl, alpha-aza-tyrosyl(O-methyl), alpha-aza-3-(2-thienyl)alanyl, alpha-aza-3-(3-benzthienyl)alanyl, alpha-aza-cyclohexylalanyl, alpha-aza-tryptyl, alpha-aza-tryptyl(N-indole-methyl), alpha-aza-tryptyl(N-indole-formyl), N—(R 31 )-L-phenylalanyl, N—(R 31 )-D-phenylalanyl, N—(R 31 )-D-3-(4-chlorophenyl)alanyl, N—(R 31 )-L-3-(4-chlorophenyl)alanyl, N—(R 31 )-D-3-(4-fluorophenyl)alanyl, N—(R 31 )-L-3-(4-fluorophenyl)alanyl, N—(R 31 )-L-3-(4-trifluoromethylphenyl)alanyl, N—(R 31 )-D-3-(4-trifluoromethylphenyl)alanyl, N—(R 31 )-L-3-(cyclohexyl)alanyl, N—(R 31 )-D-3-(cyclohexyl)alanyl, N—(R 31 )-L-3-(4-bromophenyl)alanyl, N—(R 31 )-D-3-(4-bromophenyl)alanyl, N—(R 31 )-L-3-(4-nitrophenyl)alanyl, N—(R 31 )-D-3-(4-nitrophenyl)alanyl, L-prolyl, D-prolyl, N—(R 31 )-L-O-methyltyrosyl, N—(R 31 )-L-tyrosyl, N—(R 31 )-D-O-methyl-tyrosyl, N—(R 31 )-D-tyrosyl, N—(R 31 )-L-histidyl, N—(R 31 )-D-histidyl, N—(R 31 )-L-3-(2-thienyl)alanyl, N—(R 31 )-D-3-(2-thienyl)alanyl, N—(R 31 )-L-3-(2-thiazolyl)alanyl, N—(R 31 )-D-3-(2-thiazolyl)alanyl, N—(R 31 )-L-3-(2-pyridyl)alanyl, N—(R 31 )-D-3-(2-pyridyl)alanyl, N—(R 31 )-D-3-(2-naphthyl)alanyl, N—(R 31 )-L-3-(2-naphthyl)alanyl, N—(R 31 )-L-3-(3-benzothienyl)alanyl, N—(R 31 )-D-3-(3-benzothienyl)alanyl, N—(R 31 )-L-3-(2-benzothienyl)alanyl, N—(R 31 )-D-3-(2-benzothienyl)alanyl, N—(R 31 )-L-3-(3-benzoxazolyl)alanyl, N—(R 31 )-D-3-(3-benzoxazolyl)alanyl, N—(R 31 )-L-3-(3-pyridyl)alanyl, N—(R 31 )-D-3-(3-pyridyl)alanyl, N—(R 31 )-L-tryptyl, N—(R 31 )-D-tryptyl, N—(R 31 )-L-tryptyl(N-indole-methyl), N—(R 31 )-D-tryptyl(N-indole-methyl), N—(R 31 )-D-methionyl, N—(R 31 )-L-methionyl, N—(R 31 )-D-3-(1-naphthyl)alanyl, and N—(R 31 )-L-3-(1-naphthyl)alanyl, wherein R 31 — is methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, propyl or isopropyl;

C is an amino acyl residue selected from the group consisting of L-tryptyl, D-tryptyl, L-tryptyl(N-indole-formyl), D-tryptyl(N-indole-formyl), L-tryptyl(N-indole-methyl), D-tryptyl(N-indole-methyl), 5-fluoro-L-tryptyl, 5-fluoro-D-tryptyl, L-phenylalanyl, L-prolyl, D-prolyl, L-tyrosyl, D-tyrosyl, D-phenylalanyl, D-3-(3-pyridyl)alanyl, L-3-(3-pyridyl)alanyl, D-3-(3-pyridyl-N-oxide)alanyl, L-3-(3-pyridyl-N′-oxide)alanyl, D-3-(3-quinolyl)alanyl, L-3-(3-quinolyl)alanyl, D-3-(3-quinolyl-N′-oxide)alanyl, L-3-(3-quinolyl-N′-oxide)alanyl, D-3-(1-adamantyl)alanyl, L-3-(1-adamantyl)alanyl, L-3-(1-naphthyl)alanyl, D-3-(1-naphthyl)alanyl, L-3-(3-benzothienyl)alanyl, D-3-(3-benzothienyl)alanyl, L-3-(2-benzothienyl)alanyl, D-3-(2-benzothienyl)alanyl, L-3-(3-benzoxazolyl)alanyl, D-3-(3-benzoxazolyl)alanyl, L-cyclohexylalanyl, D-cyclohexylalanyl, L-3-(3-indazolyl)alanyl, D-3-(3-indazolyl)alanyl, alpha-methyl-L-phenylalanyl, alpha-methyl-D-phenylalanyl, L-3-(2-naphthyl)alanyl, D-3-(2-naphthyl)alanyl, L-O-methyltyrosyl, D-O-methyltyrosyl, L-3-(4-methylphenyl)alanyl, D-3-(4-methylphenyl)alanyl, L-3-(pentamethylphenyl)alanyl, D-3-(pentamethylphenyl)alanyl, L-3-(3,4,5-trimethylphenyl)alanyl, D-3-(3,4,5-trimethylphenyl)alanyl, L-3-(4-chlorophenyl)alanyl, D-3-(4-chlorophenyl)alanyl, alpha-methyl-L-3-(4-chlorophenyl)alanyl, alpha-methyl-D-3-(4-chlorophenyl)alanyl, L-3-(4-trifluoromethylphenyl)alanyl, D-3-(4-trifluoromethylphenyl)alanyl, L-3-(4-fluorophenyl)alanyl, D-3-(4-fluorophenyl)alanyl, L-3-(2-thienyl)-alanyl, D-3-(2-thienyl)-alanyl, N—(R 32 )-L-3-(3-pyridyl)alanyl, N—(R 32 )-D-3-(3-pyridyl)alanyl, N—(R 32 )-L-3-(3-pyridyl-N′-oxide)alanyl, N—(R 32 )-D-3-(3-pyridyl-N′-oxide)alanyl, L-3-(2-thiazolyl)-alanyl, D-3-(2-thiazolyl)alanyl, alpha-aza-3-(1-naphthyl)alanyl, alpha-aza-tryptyl, alpha-aza-phenylalanyl, alpha-aza-3-(2-thienyl)alanyl, alpha-aza-3-4-methylphenyl)alanyl, alpha-aza-3-(pentamethylphenyl)alanyl, alpha-aza-3-(2-naphthyl)alanyl, alpha-aza-3-(3-benzothienyl)alanyl, alpha-aza-3-(3-benzoxazolyl)alanyl, alpha-aza-3-(cyclohexyl)alanyl, alpha-aza-3-(1-adamantyl)alanyl, alpha-aza-3-(4-methoxyphenyl)alanyl, alpha-aza-3-(4-chlorophenyl)alanyl, alpha-aza-3-(4 bromophenyl)alanyl, alpha-aza-tryptyl(N-indole-methyl), alpha-aza-3-(3-pyridyl)alanyl, alpha-aza-3-(3-quinolyl)alanyl, alpha-aza-3-(2-thiazolyl)alanyl, N—(R 32 )-L-3-(2-thienyl)alanyl, N—(R 32 )-D-3-(2-thienyl)alanyl, L-3-(3-quinolyl)alanyl, D-3-(3-quinolyl)alanyl, L-3-(2-naphthyl)alanyl, D-3-(2-naphthyl)alanyl, N—(R 32 )-D-phenylalanyl, N—(R 32 )-L-phenylalanyl, N—(R 32 )-D-tryptyl, N—(R 32 )-L-tryptyl, N—(R 32 )-L-tryptyl(N-indole-formyl), N—(R 32 )-D-tryptyl(N-indole-formyl), N—(R 32 )-L-tryptyl(N-indole-methyl), N—(R 32 )-D-tryptyl(N-indole-methyl), N—(R 32 )-L-3-(2-thiazolyl)alanyl, N—(R 32 )-D-3-(2-thiazolyl)alanyl, N—(R 32 )-L-3-(3-pyridyl)alanyl, N—(R 32 )-D-3-(3-pyridyl)alanyl, N—(R 32 )-D-3-(3-quinolyl)alanyl, N—(R 32 )-L-3-(3-quinolyl)alanyl, N—(R 32 )-D-3-(1-adamantyl)alanyl, N—(R 32 )-L-3-(1-adamantyl)alanyl, N—(R 32 )-D-3-(4-fluorophenyl)alanyl, N—(R 32 )-L-3-(4-fluorophenyl)alanyl, N—(R 32 )-D-3-(4-chlorophenyl)alanyl, N—(R 32 )-L-3-(4-chlorophenyl)alanyl, N—(R 32 )-L-3-(4-trifluoromethylphenyl)alanyl, N—(R 32 )-D-3-(4-trifluoromethylphenyl)alanyl, N—(R 32 )-D-3-(2-naphthyl)alanyl, N—(R 32 )-L-3-(2-naphthyl)alanyl, N—(R 32 )-D-3-(1-naphthyl)alanyl, N—(R 32 )-L-3-(1-naphthyl)alanyl, N—(R 32 )-L-3-(3-benzothienyl)alanyl, N—(R 32 )-D-3-(3-benzothienyl)alanyl, N—(R 32 )-L-3-(2-benzothienyl)alanyl, N—(R 32 )-D-3-(2-benzothienyl)alanyl, N—(R 32 )-L-3-(3-benzoxazolyl)alanyl, N—(R 32 )-D-3-(3-benzoxazolyl)alanyl, N—(R 32 )-L-tyrosyl, N—(R 32 )-D-tyrosyl, N—(R 32 )-L-3-(3,4,5-trimethylphenyl)alanyl, N—(R 32 )-D-3-(3,4,5-trimethylphenyl)alanyl, N—(R 32 )-L-3-(4-methylphenyl)alanyl, N—(R 32 )-D-3-(4-methylphenyl)alanyl, N—(R 32 )-L-3-(pentamethylphenyl)alanyl, N—(R 32 )-D-3-(pentamethylphenyl)alanyl, N—(R 32 )-L-3-(4-bromophenyl)alanyl, N—(R 32 )-D-3-(4-bromophenyl)alanyl, N—(R 32 )-L-cyclohexylalanyl, N—(R 32 )-D-cyclohexylalanyl, N—(R 32 )-L-3-(3-indazolyl)alanyl, N—(R 32 )-D-3-(3-indazolyl)alanyl, N-alpha-N—(R 32 )-alpha-aza-3-(1-naphthyl)alanyl, N-alpha-(R 32 )-alpha-aza-3-(3-pyridyl)alanyl, N-alpha-(R 32 )-alpha-aza-phenylalanyl, N-alpha-(R 32 )-alpha-aza-3-(3-benzothienyl)alanyl, N-alpha-(R 32 )-alpha-aza-3-(2-benzothienyl)alanyl, N-alpha-(R 32 )-alpha-aza-3-(4-methylphenyl)alanyl, N-alpha-(R 32 )-alpha-aza-3-(4-methylphenyl)alanyl, N-alpha-(R 32 )-alpha-aza-3-(4-chlorophenyl)alanyl, N—(R 32 )—O-methyl-D-tyrosyl and N—(R 32 )—O-methyl-L-tyrosyl, wherein R 32 is methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, propyl or isopropyl;

D is an amino acyl residue selected from the group consisting of prolyl, 4-hydroxyproline, L-seryl, L-seryl(O-benzyl), L-seryl(O—PO 3 H 2 ), L-seryl(O—PO 3 Me 2 ), D-seryl, D-seryl(O-benzyl), D-seryl(O—PO 3 H 2 ), D-seryl(O—PO 3 Me 2 ), L-glutamine, D-3-(3-pyridyl)alanyl, L-3-(3-pyridyl)alanyl, D-3-(3-pyridyl-N′-oxide)alanyl, L-3-(3-pyridyl-N′-oxide)alanyl, D-3-(3-quinolyl)alanyl, L-3-(3-quinolyl)alanyl, D-3-(3-quinolyl-N′-oxide)alanyl, L-3-(3-quinolyl-N′-oxide)alanyl, L-alpha,beta-diaminopropionyl, L-alanyl, L-threonyl, 2,3-diaminopropionyl, 2-amino-3-guanidinopropionyl, 2,3-diaminopropionyl (wherein the 3-amino group is substituted with lower alkyl, 3-pyridinecarbonyl, 2-pyrazinecarbonyl or 2-indolecarbonyl), N-alpha-aza-glycyl, N-alpha-aza-alanyl, N-alpha-(R 0 )-alpha-aza-glycyl, N-alpha-(R 0 )-alpha-aza-alanyl, N-alpha-(R 0 )-L-seryl, N-alpha-(R 0 )-L-seryl(O-benzyl), N N-alpha-(R 0 )-L-glutamine, N-alpha-(R 0 )-L-alanyl, N-alpha-(R 0 )-beta-aminopropionyl, N-alpha-(R 0 )—N-beta-ethylaminopropionyl, N—(R 0 )-L-seryl(O—PO 3 H 2 ), N—(R 0 )-L-seryl(O—PO 3 Me 2 ), and N—(R 0 )-L-threonyl, wherein R 0 is lower alkyl or allyl;

or D is a glycosyl derivative of D- or L-serine or D- or L-threonine;

or D is a C 1 -C 12 ether derivative of D- or L-serine or D- or L-threonine;

or D is a polyethyleneglycol ether derivative of D- or L-serine or D- or L-threonine; wherein the ethyleneglycol ether portion is selected from 1, 2, 3, 4 or up to 100 (O—C 2 H 4 —) units; and is preferably selected from 1, 2, 3, or 4 to 50 (O—C 2 H 4 —) units; or from 1 to 20 (O—C 2 H 4 —) units; or from 2 to 20 (O—C 2 H 4 —) units; or from 3 to 20 (O—C 2 H 4 —) units; or from 4 to 20 (O—C 2 H 4 —) units; or from 1 to 10 (O—C 2 H 4 —) units; or from 2 to 10 (O—C 2 H 4 —) units; or from 3 to 10 (O—C 2 H 4 —) units; or from 4 to 10 (O—C 2 H 4 —) units; and wherein said polyether terminates in a group selected from the group consisting of: alkyl, aryl, —OH, —OR, —O(C(O))R, —O(C(O))NHR, —O(C(O))NRR, —O—C 2 H 4 —CO 2 H, —O—CH 2 —CO 2 H, —NH 2 , —NHR, —NR 2 , or —NH(C(O))R, —O(C(O))NHR, or —O(C(O))NRR; wherein R is selected independently from lower alkyl, cycloalkyl, benzyl or aryl;

E is an amino acyl residue selected from the group consisting of L-tyrosyl, L-tyrosyl(O-methyl), L-tyrosyl(O-ethyl), L-tyrosyl(O—PO 3 H 2 ), L-tyrosyl(O—PO 3 Me 2 ), D-alanyl, L-phenylalanyl, N—(R 33 )-L-tyrosyl, N—(R 33 )-L-tyrosyl(O-methyl), N—(R 33 )-L-tyrosyl(O—PO 3 H 2 ), N—(R 33 )-L-tyrosyl(O—PO 3 Me 2 ), 3-(2-thienyl)alanyl, 3-(3-benzothienyl)alanyl, 3-(1-naphthyl)alanyl, 3-(2-naphthyl)alanyl, N—(R 33 )-L-phenylalanyl, L-3-(4-chlorophenyl)alanyl, L-3-(4-fluorophenyl)alanyl, L-histidyl, L-3-(cyclohexyl)alanyl, L-3-(4-aminophenyl)alanyl, 1-3-(4 acetylaminophenyl)alanyl, N—(R 33 )-L-3-(4-aminophenyl)alanyl, N—(R 33 )-L-3-(4-acetylaminophenyl)alanyl, N—(R 33 )-L-3-(4-fluorophenyl)alanyl, N—(R 33 )-L-3-(4-chlorophenyl)alanyl, N—(R 33 )-L-histidyl, N—(R 33 )-L-3-(cyclohexyl)alanyl, N—(R 33 )-3-(2-thienyl)alanyl, N—(R 33 )-3-(3-benzothienyl)alanyl, N—(R 33 )-3-(1-naphthyl)alanyl, N—(R 33 )-3-(2-naphthyl)alanyl, and N—(R 33 )-L-tyrosyl(O-ethyl), wherein (R 33 ) is methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, propyl or isopropyl;

or E is

—N(R 30 )—C((CH 2 ) n R 1 )H—(CO)—

wherein n is 1 to 5; R 30 is hydrogen, methyl, ethyl, propyl or isopropyl; and R 1 is amino, alkylamino, cycloalkylamino or alkanoylamino; or R 1 is —N(R 3 )—C(O)(CH 2 ) ff R 60 or —NHC(N(R 3 ) 2 )═NR 4 wherein R 3 is hydrogen, lower alkyl or cycloalkyl; R 4 is hydrogen, lower alkyl, cycloalkyl, amino or cyano; ff is 0 to 6; and R 60 is loweralkyl, dialkylamino, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl or —NHR 120 wherein R 120 is hydrogen, loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl, amino, alkanoylamino or —NHR 62 wherein R 62 is loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl or —C(O)R 63 wherein R 63 is loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic or (heterocyclic)alkyl;

or R 1 is —C(O)R** wherein R** is hydroxy, alkoxy, amino, phenoxy or -methoxyphenyl;

F is a D-aminoacyl residue derived from any of the naturally-occurring alpha amino acids, or from synthetic, non-natural alpha amino acids including (t-Bu)-D-glycyl-, D-seryl(O-tBu), D-3-(2-naphthyl)alanyl, Nt-benzyl-D-histidyl-, and including but not limited to those listed for group B; or

F is a D-amino acyl residue having the formula:

—N(R 34 )—C((CH 2 ) z (CO)R 37 )H—(CO)—

wherein z is 0 to 3 and R 37 is hydroxy, alkoxy, phenoxy, amino or p-methoxyphenyl and R 34 is hydrogen, methyl, ethyl, propyl or isopropyl;

or F is a D-lysine residue or D-homolysine residue substituted with a polyethyleneglycol group (PEG) on the distal nitrogen wherein the PEG unit is attached via acylation to give an amide derivative of a structure selected from the group consisting of:

—NH—C((CH 2 ) y -NH—(CO)(CH 2 ) x -(O—C 2 H 4 —) n -OH))H—(CO)—; or

—NH—C((CH 2 ) y -NH—(CO)(CH 2 )) x -(O—C 2 H 4 —) n -OR))H—(CO)—;

wherein y is 4 or 5; x is an integer selected from 1-10 inclusive; n is an integer selected from 1-100 inclusive; preferably selected from 1-50, more preferably selected from 1-20; and R is a group selected from lower alkyl, aryl, heteroaryl, benzyl, acyl, aroyl, or heteroaroyl; or

or F is a D-lysine residue or D-homolysine residue substituted with a polyethyleneglycol group (PEG) on the distal nitrogen wherein the PEG unit is attached via alkylation to give an amine derivative of a structure such as:

—NH—C((CH 2 )y-NH—(CH 2 )xCH 2 —(O—C 2 H 4 —)n-OR))H—(CO)—; wherein y is 4 or 5; x is an integer selected from 1-10 inclusive; n is an integer from 1-100 inclusive; preferably selected from 1-50, more preferably selected from 1-20; and R is a group selected from lower alkyl, aryl, heteroaryl, benzyl, acyl, aroyl, or heteroaroyl;

or F is a D-citrullinyl residue, D-ornithinyl residue, D-lysyl residue or D-homolysyl residue; or

is a D-ornithinyl residue, D-lysyl residue or D-homolysyl residue substituted on the distal nitrogen with one or two groups selected independently from the group consisting of: H, lower alkyl, aryl, heteroaryl, cycloalkyl, ureido, guanidinyl, —(C(O))R, —(C(O))NHR, —(C(O))NRR, —C 2 H 4 —CO 2 H, —CH 2 —CO 2 H, —NH 2 , —NHR, —NR 2 , —NH(C(O))R, (C(O))NHR, and —(C(O))NRR; and wherein R is selected independently from lower alkyl, cycloalkyl, benzyl or aryl;

or F is a glycosyl derivative of D- or L-serine or D- or L-threonine;

or F is a polyethyleneglycol ether derivative of D- or L-serine or D- or L-threonine; wherein the ethyleneglycol ether portion is selected from the group consisting of from 1-100 (O—C 2 H 4 —) units; or

alternatively is selected from 1-50 (O—C 2 H 4 —) units; or

alternatively is selected from 1 to 20 (O—C 2 H 4 —) units; or

alternatively is selected from 2 to 20 (O—C 2 H 4 —) units; or from 3 to 20 (O—C 2 H 4 —) units; or from 4 to 20 (O—C 2 H 4 —) units; or from 1 to 10 (O—C 2 H 4 —) units; or from 2 to 10 (O—C 2 H 4 —) units; or from 3 to 10 (O—C 2 H 4 —) units; or from 4 to 10 (O—C 2 H 4 —) units; and

wherein said polyether unit terminates in a group selected from the group consisting of: alkyl, aryl, —OH, —OR, —O(C(O))R, —O(C(O))NHR, —O(C(O))NRR, —O—C 2 H 4 —CO 2 H, —O—CH 2 —CO 2 H, —NH 2 , —NHR, —NR 2 , —NH(C(O))R, —O(C(O))NHR, and —O(C(O))NRR; and

wherein R is selected independently from lower alkyl, cycloalkyl, benzyl or aryl;

provided that if D is a glycosyl derivative or a polyethyleneglycol ether derivative of a serine or threonine, then F can not be a glycosyl derivative or a polyethyleneglycol ether derivative of a serine or threonine or lysine;

G is an amino acyl residue selected from the group consisting of L-arginyl, L-leucyl, D-leucyl, (t-Bu)-D-glycyl-, (t-Bu)-L-glycyl-, L-isoleucyl, norleucyl, alloisoleucyl, valyl, norvalyl, seryl(O-t-Bu), tyrosyl, tryptyl, 2-aminobutyryl, L-(cyclohexyl)alanyl, phenylalanyl, D-tryptyl, tyrosyl, seryl(O-alkyl), prolyl, pipecolyl, L-(β-nicotinoyl)lysyl, seryl and D-seryl;

H is an amino acyl residue selected from L-prolyl, L-arginyl, L-leucyl, L-(O-nicotinoyl)lysyl; or

H is of the formula:

—N(R 30 )—C((CH 2 ) n R 1 )H—(CO)—

wherein n is 1 to 5; R 30 is hydrogen, methyl, ethyl, propyl or isopropyl; and R 1 is amino, alkylamino, cycloalkylamino or alkanoylamino; or R 1 is —N(R 3 )—C(O)(CH 2 ) ff R 60 or —NHC(N(R 3 ) 2 )═NR 4 wherein R 3 is hydrogen, lower alkyl or cycloalkyl; R 4 is hydrogen, lower alkyl, cycloalkyl, amino or cyano; ff is 0 to 6; and R 60 is loweralkyl, dialkylamino, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl or —NHR 120 wherein R 120 is hydrogen, loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl, amino, alkanoylamino or —NHR 62 wherein R 62 is loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic, (heterocyclic)alkyl or —C(O)R 63 wherein R 63 is loweralkyl, cycloalkyl, aryl, arylalkyl, heterocyclic or (heterocyclic)alkyl;

I is an NH 2 or NHR group wherein R is selected from lower alkyl such as methyl, ethyl, propyl, hydroxyethyl, fluoroethyl, difluoroethyl, or trifluoroethyl; or

I is imino acyl or aliphatic amino acyl residue selected from the group consisting of L-prolyl, L-pipecolyl, alpha-aza-prolyl, trans-beta-aminocyclopentanecarbonyl, cis-beta-aminocyclopentanecarbonyl, 3-(lower alkyl)-prolyl, N-methyl-L-alanyl, N-methyl-norvalyl, 1-dihydroisoindole-2-L-carbonyl and thiazolidine-5-L-carbonyl; or

I is L-(β-isopropyl)lysyl;

and J is nothing if I is an NH 2 or NHR group; or

J is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, or an amino acyl residue selected from D-alanylamide, L-alanylamide, glycylamide, sarcosylamide, N—(R 40 )-D-alanylamide, N—(R 40 )-L-alanyl amide, N—(R 40 )-beta-L-alanylamide, N—(R 40 )-beta-D-alanylamide, L-2-aminobutyrylamide, D-2-aminobutyrylamide, N—(R 40 )-L-2-aminobutyrylamide, N—(R 40 )-D-2-aminobutyrylamide, L-serylamide, D-serylamide, N—(R 40 )-L-serylamide, N—(R 40 )-D-serylamide, N—(R 40 )-L-norvalylamide, N—(R 40 )-D-norvalylamide, L-norvalylamide, D-norvalylamide, alpha-aza-glycylamide or alpha-aza-alanylamide, wherein R 40 is H, methyl, ethyl, propyl or isopropyl.