Compounds > 3-(3-pyridyl)-1-propyl-(2s)-1-(3-3-dimethyl-1-2-dioxopentyl)-2-pyrrolidinecarboxylate

3-(3-pyridyl)-1-propyl-(2s)-1-(3-3-dimethyl-1-2-dioxopentyl)-2-pyrrolidinecarboxylate and Parkinson-Disease--Secondary

3-(3-pyridyl)-1-propyl-(2s)-1-(3-3-dimethyl-1-2-dioxopentyl)-2-pyrrolidinecarboxylate has been researched along with Parkinson-Disease--Secondary* in 2 studies

Other Studies

2 other study(ies) available for 3-(3-pyridyl)-1-propyl-(2s)-1-(3-3-dimethyl-1-2-dioxopentyl)-2-pyrrolidinecarboxylate and Parkinson-Disease--Secondary

Article	Year
Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects. Journal of medicinal chemistry, 2002, Aug-01, Volume: 45, Issue:16 The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands. Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Administration, Oral; Amides; Animals; Corpus Striatum; Dopamine Agents; Immunohistochemistry; Ligands; Mice; Molecular Mimicry; Nerve Regeneration; Neurites; Neuroprotective Agents; Parkinson Disease, Secondary; Pipecolic Acids; Proline; Structure-Activity Relationship; Substantia Nigra; Sulfhydryl Compounds; Tacrolimus Binding Protein 1A; Tyrosine 3-Monooxygenase	2002
Synthesis of ketone analogues of prolyl and pipecolyl ester FKBP12 ligands. Journal of medicinal chemistry, 2002, Aug-01, Volume: 45, Issue:16 The recently discovered small-molecule ligands for the peptidyl and prolyl isomerases (PPIase) of FKBP12 have been shown to possess powerful neuroprotective and neuroregenerative effects. Ketone analogues of the prolyl and pipecolyl esters, which mimic only the FKBP binding domain portion of FK506, are proposed and an efficient synthetic strategy is presented in this report, along with the preliminary results of in vitro and in vivo biological studies. Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Dopamine Agents; Ketones; Ligands; Mice; Molecular Mimicry; Nerve Regeneration; Neurites; Neuroprotective Agents; Parkinson Disease, Secondary; Pipecolic Acids; Proline; Structure-Activity Relationship; Sulfhydryl Compounds; Tacrolimus Binding Protein 1A	2002

Article

Year

Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects.

Journal of medicinal chemistry, 2002, Aug-01, Volume: 45, Issue:16

The recent discovery that small molecule ligands for the peptidyl-prolyl isomerase (PPIase) FKBP12 possess powerful neuroprotective and neuroregenerative properties in vitro and in vivo suggests therapeutic utility for such compounds in neurodegenerative disease. The neurotrophic effects of these compounds are independent of the immunosuppressive pathways by which drugs such as FK506 and rapamycin operate. Previous work by ourselves and other groups exploring the structure-activity relationships (SAR) of small molecules that mimic only the FKBP binding domain portion of FK506 has focused on esters of proline and pipecolic acid. We have explored amide and thioester analogues of these earlier structures and found that they too are extremely potent in promoting recovery of lesioned dopaminergic pathways in a mouse model of Parkinson's disease. Several compounds were shown to be highly effective upon oral administration after lesioning of the dopaminergic pathway, providing further evidence of the potential clinical utility of a variety of structural classes of FKBP12 ligands.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Administration, Oral; Amides; Animals; Corpus Striatum; Dopamine Agents; Immunohistochemistry; Ligands; Mice; Molecular Mimicry; Nerve Regeneration; Neurites; Neuroprotective Agents; Parkinson Disease, Secondary; Pipecolic Acids; Proline; Structure-Activity Relationship; Substantia Nigra; Sulfhydryl Compounds; Tacrolimus Binding Protein 1A; Tyrosine 3-Monooxygenase

2002

Synthesis of ketone analogues of prolyl and pipecolyl ester FKBP12 ligands.

Journal of medicinal chemistry, 2002, Aug-01, Volume: 45, Issue:16

The recently discovered small-molecule ligands for the peptidyl and prolyl isomerases (PPIase) of FKBP12 have been shown to possess powerful neuroprotective and neuroregenerative effects. Ketone analogues of the prolyl and pipecolyl esters, which mimic only the FKBP binding domain portion of FK506, are proposed and an efficient synthetic strategy is presented in this report, along with the preliminary results of in vitro and in vivo biological studies.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Dopamine Agents; Ketones; Ligands; Mice; Molecular Mimicry; Nerve Regeneration; Neurites; Neuroprotective Agents; Parkinson Disease, Secondary; Pipecolic Acids; Proline; Structure-Activity Relationship; Sulfhydryl Compounds; Tacrolimus Binding Protein 1A

2002