14296-92-5

Usage

Chemical Properties

White to off-white powder

InChI:InChI=1/C12H20N2O5/c1-12(2,3)19-11(18)13-7-9(15)14-6-4-5-8(14)10(16)17/h8H,4-7H2,1-3H3,(H,13,18)(H,16,17)

Upstream product

• 43041-12-9 methyl pyrrolidine-2-carboxylate 
• 4530-20-5 BOC-glycine 
• 29776-78-1 (S)-1-(2-tert-butoxycarbonylaminoacetyl)pyrrolidine-2-carboxylic acid benzyl ester 
• 3392-07-2 tert-butyl N-{2-[(2,5-dioxopyrrolidin-1-yl)oxy]-2-oxoethyl}carbamate 
• 147-85-3 L-proline 
• 95104-84-0 Boc-Gly-OCOOEt 
• 41863-49-4 t-butyloxycarbonyl-glycyl-proline methyl ester 
• 3655-05-8 tert-butoxycarbonylglycine p-nitrophenylester 
• 7757-82-6 sodium sulfate 
• 609-36-9 rac-Pro-OH 
• 24424-99-5 di-tert-butyl dicarbonate 
• 704-15-4 H-Gly-Pro-OH 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 67084-40-6 1-(N-tert-butoxycarbonyl-glycyloxy)-1H-benzotriazole 

Downstream Products

• 124169-15-9 Boc-Gly-Pro-Leu-Ala-NHOBzl 
• 108305-00-6 Boc-Gly-Pro-Hyp-OBzl 
• 124169-17-1 Boc-Gly-Pro-Phe-Gly-NHOBzl 
• 137022-77-6 Boc-Gly-Pro-Leu-β-Ala-NHOBzl 
• 124169-15-9 Boc-Gly-Pro-Leu-D-Ala-NHOBzl 
• 137022-75-4 Boc-Gly-Pro-D-Leu-Gly-NHOBzl 
• 55301-08-1 N-Boc-glycyl-L-prolyl-glycyl-L-proline benzyl ester 
• 73870-87-8 Boc-Gly-Pro-Gly-Ala-Gly-Gly-OBzl 
• 87543-97-3 Boc-Gly-L-Pro-Gly-Gly-pNA 
• 87543-96-2 Boc-Gly-L-Pro-L-Asn-Gly-pNA 
• 87543-99-5 Boc-Gly-L-Pro-L-Gln-Gly-pNA 
• 87543-98-4 Boc-Gly-L-Pro-L-Ala-Gly-pNA 
• 87544-00-1 Boc-Gly-L-Pro-D-Ala-Gly-pNA 
• 361541-79-9 Boc-Gly-Pro-Pro-Phe-OMe 

Relevant academic research and scientific papers

Bioinspired design for the assembly of Glypromate neuropeptide conjugates with active pharmaceutical ingredients

Neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, are a class of heterogeneous pathologies of the central nervous system (CNS) affecting millions of people worldwide. CNS-related pathologies represent a global health burden in developed and developing countries with no curative treatments currently available. Thus, the development of novel multitarget neuroprotective drugs is a health priority. In this work, a bioinspired methodology in solution-phase for the assembly and regioselective conjugation of Glypromate neuropeptide with active pharmaceutical ingredients (APIs) is described. The main purpose is to design new hybrid molecules which may offer increased systemic resistance of Glypromate towards proteases and/or allow the controlled release of both APIs and the neuroprotective peptide within CNS. For the synthesis of such peptide-hybrid compounds (R)-1-aminoindane, amantadine, and memantine were selected as APIs for conjugation with Glypromate. Furthermore, capping strategies are explored to prepare Glypromate conjugates with more favorable pharmacodynamic profiles by masking polar exposed groups. Overall, this synthetic approach led to the development of a small library of 12 conjugates with improved drug-like properties in comparison with Glypromate, paving the way for the discovery of novel CNS multitarget drugs. Additionally, by exploring the bis-functionalization of glutamate, the formation of chiral glutarimides is disclosed for the first time employing TBTU as the coupling reagent. This unusual reactivity of TBTU with glutamate offers a new synthetic approach for the preparation of chiral glutarimide alkaloids.

Structural-functional study of glycine-and-proline-containing peptides (Glyprolines) as potential neuroprotectors

A synthetic scheme for preparation of (Gly-Pro) n, (Pro-Gly) n (n = 2, 3), and (Pro-Gly-Pro) n (n = 1, 2) peptides was elaborated. The effect of the synthesized peptides and the Gly-Pro and Pro-Gly dipeptides on survival of cultured cells of PC12 rat pheochromocytoma was studied under the conditions of oxidative stress induced by brief incubation of the cells with hydrogen peroxide. Peptides of the general formula (Gly-Pro) n and the Pro-Gly-Pro peptide at a concentration of 0.2-100 μM were shown to decrease the number of damaged cells. The Gly-Pro peptide was the most active and decreased the number of damaged cells by 49% on average at a concentration of 100 μM.

Ferrocene tripeptide Gly-Pro-Arg conjugates: Synthesis and inhibitory effects on Alzheimer's Aβ1-42 fibrillogenesis and Aβ-induced cytotoxicity in vitro

Alzheimer's disease (AD) is the most common cause of dementia, and currently there is no clinical treatment to cure it or to halt its progression. Aggregation and fibril formation of β-amyloid peptides (Aβ) are central events in the pathogenesis of AD. Ma

Two-Dimensional Barriers for Probing Conformational Shifts in Macrocycles

We describe the development and use of composite two-dimensional barriers in macrocyclic backbones. These tunable constructs derive their mode of action from heterocyclic rearrangements. The Boulton-Katritzky reaction has been identified as a particularly versatile means to effect a composite barrier, allowing the examination of the influence of heterocycle translocation on conformation. Kinetic studies using 1H NMR have revealed that the in-plane atom movement is fast in 17, 18, 19-membered rings but slows down in 16-membered rings. The analysis by NMR and MD simulation experiments is consistent with the maintenance of rare cis-amide motifs during conformational interconversion. Taken together, our investigation demonstrates that heterocyclic rearrangement reactions can be used to control macrocyclic backbones and provides fundamental insights that may be applicable to the development of a wide range of other conformational control elements.

STAT DEGRADERS AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

5,5-FUSED ARYLENE OR HETEROARYLENE HEPATITIS C VIRUS INHIBITORS

Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

Iridium-Catalyzed Reductive Strecker Reaction for Late-Stage Amide and Lactam Cyanation

A new iridium-catalyzed reductive Strecker reaction for the direct and efficient formation of α-amino nitrile products from a broad range of (hetero)aromatic and aliphatic tertiary amides, and N-alkyl lactams is reported. The protocol exploits the mild and highly chemoselective reduction of the amide and lactam functionalities using IrCl(CO)[P(C6H5)3]2 (Vaska's complex) in the presence of tetramethyldisiloxane, as a reductant, to directly generate hemiaminal species able to undergo substitution by cyanide upon treatment with TMSCN (TMS=trimethylsilyl). The protocol is simple to perform, broad in scope, efficient (up to 99 % yield), and has been successfully applied to the late-stage functionalization of amide- and lactam-containing drugs, and naturally occurring alkaloids, as well as for the selective cyanation of the carbonyl carbon atom linked to the N atom of proline residues within di- and tripeptides.

Synthesis, characterization and biological screening of diandrine A

Synthesis of a proline-rich cyclic hexapeptide - diandrine A [VI] was accomplished by coupling of tetrapeptide unit Boc-Gly-Pro-Trp-Pro-OH with dipeptide unit Tyr-Phe-OMe followed by cyclization of linear peptide unit [V] under alkaline condition. Structu

High penetration prodrug compositions of peptides and peptide-related compounds

The invention provides compositions of novel high penetration compositions (HPC) or high penetration prodrugs (HPP) of peptides and peptide-related compounds, which are capable of crossing biological barriers with higher penetration efficiency comparing t

Zinc(II) complexes of Pro-Gly and Pro-Leu dipeptides: Synthesis, characterization, in vitro DNA binding and cleavage studies

Dipeptide (Pro-Gly and Pro-Leu) Zinc(II) complexes 1 and 2 were designed and synthesized for potential use as cancer chemotherapeutic agents. In order to augment the DNA recognition of metallonuclease activity, zinc metal ion was tethered to peptide motif to carry out DNA site specific hydrolytic cleavage. The structural formulation of the complexes 1 and 2 was done by elemental analysis, spectroscopic methods (IR, NMR, electronic) and molar conductance measurements. Their in vitro DNA binding profile was investigated by UV-vis titrations, fluorescence titrations and circular dichroism which revealed that these complexes bind to CT DNA by electrostatic interactions via groove binding mode. Zn(II) Pro-Gly complex 1 showed greater binding affinity to CT DNA as compared to the Zn(II) Pro-Leu complex 2 due to steric constraints in the latter. The supercoiled pBR322 DNA cleavage activity of complex 1, ascertained by gel electrophoresis demonstrated efficient DNA cleaving ability via hydrolytic mechanistic pathway. Further, the molecular docking studies confirmed that complex 1 bind to the minor groove of DNA having AT-rich sequences with relative binding energy of -196.72 kJ mol-1.