| 摘要 |
1. A compound, selected from: (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-hydroxymethylpyrrolidine; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinetetrazole; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinecarbonytryl; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-aminocarbonylpiperidine; [1-(3,3-dimethyl-2-oxopentanoil)pirrolidine-2-yl]-N-(2-thienylcarbonyl-amino)formamide; 3,3-dimethyl-1-{2-[(4-notrophenoxy)methyl]pyrrolidinyl}pentane-1,2-dione; 2-[1-(3,3-dimethyl-2-oxopentanoy)pyrrilidine-2-yl]ethannitryl]; 1-[2-(3-ethyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 1-[2-[3-(4-fluorophenyl)(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 3,3-dimethyl-1-[2-(3-methyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-[(methylsulfonyl)-amino]formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-methylphenyl)-sulfonyl]-amino}formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-fluorophenyl)-sulfonyl]-amino}formamide; (2S)-3,3-dimethyl-1-[2-(5-sulfanyl(4H-1,2,4-triazole-3-yl))pyrrolodinyl]-pentane-1,2-dione; (2S)-3,3-dimethyl-1-[2-(pyrrolidinylmethyl)pyrrolidinyl]pentane-1,2-dione; (2S)-N-[(aminothioxomethyl)amino][1-3,3-dimethyl-2-oxopentanoil)-pyrrolidine-2-yl]formamide; (2S)-1-[2-[benzotriazole-1-ylcarbonyl) pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; N-amino-2-[2-(N-aminocarbamoyl) pyrrolidinyl]-2-oxoethanamide; 2-[1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidyl]acetic acid; 1-(2-{[4-(2H-benzo[3,4-d]1,3-dioxolene-5-ylmethyl)piperazinyl]carbonyl}-pyrrolidinyl)-3,3-dimethylpentane-1,2-dione; and 1-(2-{[4-[bis(4-fluorophenyl)methyl}piperazinyl}carbonyl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione. 2. Pharmaceutical composition, comprising: (a) effective quantity of compound, selected from: (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-hydroxymethylpyrrolidine; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinetetrazole; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinecarbonytryl; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-aminocarbonylpiperidine; [1-(3,3-dimethyl-2-oxopentanoil)pirrolidine-2-yl]-N-(2-thienylcarbonyl-amino)formamide; 3,3-dimethyl-1-{2-[(4-notrophenoxy)methyl]pyrrolidinyl}pentane-1,2-dione; 2-[1-(3,3-dimethyl-2-oxopentanoy)pyrrilidine-2-yl]ethannitryl]; 1-[2-(3-ethyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 1-[2-[3-(4-fluorophenyl)(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 3,3-dimethyl-1-[2-(3-methyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-[(methylsulfonyl)-amino]formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-methylphenyl)-sulfonyl]-amino}formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-fluorophenyl)-sulfonyl]-amino}formamide; (2S)-3,3-dimethyl-1-[2-(5-sulfanyl(4H-1,2,4-triazole-3-yl))pyrrolodinyl]-pentane-1,2-dione; (2S)-3,3-dimethyl-1-[2-(pyrrolidinylmethyl)pyrrolidinyl]pentane-1,2-dione; (2S)-N-[(aminothioxomethyl)amino][1-3,3-dimethyl-2-oxopentanoil)-pyrrolidine-2-yl]formamide; (2S)-1-[2-[benzotriazole-1-ylcarbonyl) pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; N-amino-2-[2-(N-aminocarbamoyl) pyrrolidinyl]-2-oxoethanamide; 2-[1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidyl]acetic acid; 1-(2-{[4-(2H-benzo[3,4-d]1,3-dioxolene-5-ylmethyl)piperazinyl]carbonyl}-pyrrolidinyl)-3,3-dimethylpentane-1,2-dione; and 1-(2-{[4-[bis(4-fluorophenyl)methyl}piperazinyl}carbonyl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; (b) pharmaceutically acceptable carrier. 3. Pharmaceutical composition according to Claim 2, further comprising an additional neurotrophic factor. 4. The pharmaceutical composition of claim 3, wherein said additional neurotrophic factor is selected from neurotrophic growth factor, brain derived growth factor, glial derived growth factor, cilial neurotrophic factor, insulin growth factor and active truncated derivatives thereof, acidic fibroblast growth factor, basic fibroblast growth factor, platelet-derived growth factors, neurotropin-3 and neurotropin 4/5. 5. A method of treating a disorder in an animal, comprising: administering to the animal an effective amount of compound selected from: (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-hydroxymethylpyrrolidine; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinetetrazole; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinecarbonytryl; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-aminocarbonylpiperidine; [1-(3,3-dimethyl-2-oxopentanoil)pirrolidine-2-yl]-N-(2-thienylcarbonyl-amino)formamide; 3,3-dimethyl-1-{2-[(4-notrophenoxy)methyl]pyrrolidinyl}pentane-1,2-dione; 2-[1-(3,3-dimethyl-2-oxopentanoy)pyrrilidine-2-yl]ethannitryl]; 1-[2-(3-ethyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 1-[2-[3-(4-fluorophenyl)(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 3,3-dimethyl-1-[2-(3-methyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-[(methylsulfonyl)-amino]formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-methylphenyl)-sulfonyl]-amino}formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-fluorophenyl)-sulfonyl]-amino}formamide; (2S)-3,3-dimethyl-1-[2-(5-sulfanyl(4H-1,2,4-triazole-3-yl))pyrrolodinyl]-pentane-1,2-dione; (2S)-3,3-dimethyl-1-[2-(pyrrolidinylmethyl)pyrrolidinyl]pentane-1,2-dione; (2S)-N-[(aminothioxomethyl)amino][1-3,3-dimethyl-2-oxopentanoil)-pyrrolidine-2-yl]formamide; (2S)-1-[2-[benzotriazole-1-ylcarbonyl) pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; N-amino-2-[2-(N-aminocarbamoyl)pyrrolidinyl]-2-oxoethanamide; 2-[1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidyl]acetic acid; 1-(2-{[4-(2H-benzo[3,4-d]1,3-dioxolene-5-ylmethyl)piperazinyl]carbonyl}-pyrrolidinyl)-3,3-dimethylpentane-1,2-dione; and 1-(2-{[4-[bis(4-fluorophenyl)methyl}piperazinyl}carbonyl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione. 6. A method of treating of neurological disorder in animal for stimulating growth of damaged peripheral nerves, for activation of regeneration of neurons or preventing neurodegeneration, comprising: administering to the animal an effective amount of compound selected from: (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-hydroxymethylpyrrolidine; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinetetrazole; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidinecarbonytryl; (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-aminocarbonylpiperidine; [1-(3,3-dimethyl-2-oxopentanoil)pirrolidine-2-yl]-N-(2-thienylcarbonyl-amino)formamide; 3,3-dimethyl-1-{2-[(4-notrophenoxy)methyl]pyrrolidinyl}pentane-1,2-dione; 2-[1-(3,3-dimethyl-2-oxopentanoy)pyrrilidine-2-yl]ethannitryl]; 1-[2-(3-ethyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 1-[2-[3-(4-fluorophenyl)(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; 3,3-dimethyl-1-[2-(3-methyl(1,2,4-oxadiazole-5-yl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-[(methylsulfonyl)-amino]formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-methylphenyl)-sulfonyl]-amino}formamide; [1-(3,3-dimethyl-2-oxopentanoyl)pyrrolodine-2-yl]-N-{[(4-fluorophenyl)-sulfonyl]-amino}formamide; (2S)-3,3-dimethyl-1-[2-(5-sulfanyl(4H-1,2,4-triazole-3-yl))pyrrolodinyl]-pentane-1,2-dione; (2S)-3,3-dimethyl-1-[2-(pyrrolidinylmethyl)pyrrolidinyl]pentane-1,2-dione; (2S)-N-[(aminothioxomethyl)amino][1-3,3-dimethyl-2-oxopentanoil)-pyrrolidine-2-yl]formamide; (2S)-1-[2-[benzotriazole-1-ylcarbonyl) pyrrolidinyl]-3,3-dimethylpentane-1,2-dione; N-amino-2-[2-(N-aminocarbamoyl) pyrrolidinyl]-2-oxoethanamide; 2-[1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidyl]acetic acid; 1-(2-{[4-(2H-benzo[3,4-d]1,3-dioxolene-5-ylmethyl)piperazinyl]carbonyl}-pyrrolidinyl)-3,3-dimethylpentane-1,2-dione; and 1-(2-{[4-[bis(4-fluorophenyl)methyl}piperazinyl}carbonyl)pyrrolidinyl]-3,3-dimethylpentane-1,2-dione. 7. The method of claim 6, wherein the neurological disorder is selected from the group consisting of peripheral neuropathies cause by physical injury or disease state, physical damage to the brain, physical damage to the spinal cord, stroke associated with brain damage, and neurological disorders relating to neurodegeneration. 8. The method of claim 6, wherein the neurological disorder is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, amyotrophic lateral sclerosis, prosopalgia, glossopharyngeal neuralgia, Bell's palsy, serious pseudoparalytic myasthenia, muscular dystrophy, progressive muscular atrophy, progressive heritable bulbar muscular atrophy, hernia syndrome, intervertebral disk rupture, cervical spondylosis, plexus diseases, clavicular artery, fixed by muscles of first rib and clavicle area, syndrome Guione-Barre-Schtroll and sciatic nerve damages. 9. The method of claim 6, wherein the neurological disorder is Alzheimer's disease. 10. The method of claim 6, wherein the neurological disorder is Parkinson's disease. 11. The method of claim 6, wherein the neurological disorder is amyotrophic lateral sclerosis. 12. The method of treating of Huntington's disease, comprising: administering to the animal an effective amount of compound of formula (I) wherein n is 1-3; X is O or S; R1 is selected from the group consisting of C1-C9 straight or branched chain alkyl or alkenyl, C2-C9 straight or branched chain alkenyl, aryl, heteroaryl, carbocycle, or heterocycle; D is a bond, or a C2-C10 straight or branched chain alkyl, C2-C10 alkenyl or C2-C10 alkynyl; R2 is selected from -COOH; -SO3H; -SO2HNR3; -PO2(R3)2; -CN; -PO3(R3)2; -OR3; -SR3; -NHCOR3; -N(R3)2; -CON(R3)2; -CONH(O)R3; -CONHNHSO2R3; -COHNSO2R3; and -CONR3CN; wherein said alkyl, alkenyl, alkenyl, alkylene, aryl, heteroaryl, carbocycle, heterocycle or a group R2 is possibly substituted with one or more than deputy, selected from R3, wherein R3 is hydrogen, hydroxy, halo, haloalkyl, thio
|
