- COMPOSITIONS OF TROFINETIDE
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This disclosure describes compounds of Formula (I), stereoisomers, side compounds thereof, pharmaceutical compositions and methods of manufacturing such compounds, using silylation reagents and producing compositions and products made using such methods. More particularly, this disclosure describes manufacture of trofinetide and side products, compositions and products containing such compounds, for pharmaceutical uses to treat neurodegenerative or neurodevelopmental disorders.
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Page/Page column 38-40
(2021/02/12)
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- Development of glycine-α-methyl-proline-containing tripeptides with neuroprotective properties
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Herein is described the synthesis of novel glycine-α-methyl-proline-containing tripeptides (GPMeX tripeptides namely GPMeR, GPMeK, and GPMeH) with the aim of obtaining derivatives highly stable in human plasma and able to counteract neuroinflammatory processes that are distinctive of neurodegenerative pathologies. The syntheses of GPMeR, GPMeK, and GPMeH were all achieved both by introducing the ProMe residue into the Gly-Pro-Arg (GPR) sequence in place of the native Pro in P2 position and replacing the basic amino acid Arg in P3 position by Lys or His. Results showed that all novel GPMeX tripeptides are stable in human plasma (t1/2 > 51 h) and that GPMeH - generating stable intramolecular H-bond in a C11-turn by interaction of His imidazole ring and Gly carbonyl group - restored physiological levels of nitric oxide deriving from neuronal NOS (nNOS) activity, thus preventing the inflammatory response by suppression of the NF-kB activity and, consequently, the expression of inflammatory genes such as inducibile NOS (iNOS). Therefore, GPMeH could be a lead compound for further development of peptidomimetics able to contrast neuroinflammatory processes.
- Cacciatore, Ivana,Fornasari, Erika,Di Stefano, Antonio,Marinelli, Lisa,Cerasa, Laura Serafina,Turkez, Hasan,Aydin, Elanur,Moretto, Alessandro,Ferrone, Alessio,Pesce, Mirko,Di Giacomo, Viviana,Reale, Marcella,Costantini, Erica,Di Giovanni, Pamela,Speranza, Lorenza,Felaco, Mario,Patruno, Antonia
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p. 553 - 563
(2015/12/30)
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- TREATMENT OF AUTISM SPECTRUM DISORDERS USING GLYCYL-L-2-METHYLPROLYL-L-GLUTAMIC ACID
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This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methyIprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder, Asperger Syndro
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- TREATMENT OF AUTISM SPECTRUM DISORDERES USING GLYCYL-L-2-METHYLPROLYL-L-GLUTAMIC ACID
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This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder, Asperger Syndro
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- ANALOGS OF GLYCYL-PROLYL-GLUTAMATE
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Embodiments of this invention include novel analogs of Glycyl-Prolyl-Glutamate (GPE) and compositions containing such analogs of GPE. Of these, certain analogs have modified proline residues. Other embodiments of this invention include uses of analogs of GPE to protect neural cells from degeneration and/or death in response to injury or disease. Disorders treatable with compounds and compositions of this invention include hypoxia/ischemia, toxic injury, and chronic neurodegenerative disorders including Parkinson''s disease.
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- Synthesis of proline-modified analogues of the neuroprotective agent glycyl-L-prolyl-glutamic acid (GPE)
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The synthesis of ten proline-modified analogues of the neuroprotective tripeptide GPE is described. Five of the analogues incorporate a proline residue with a hydrophobic group at C-2 and two further analogues have this side chain locked into a spirolactam ring system. The pyrrolidine ring was also modified by replacing the γ-CH2 group with sulfur and/or incorporation of two methyl groups at C-5.
- Harris, Paul W.R.,Brimble, Margaret A.,Muir, Victoria J.,Lai, Michelle Y.H.,Trotter, Nicholas S.,Callis, David J.
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p. 10018 - 10035
(2007/10/03)
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