84348-39-0

Usage

Uses

Used in Pharmaceutical Industry:
N-Boc-4-Methylene-L-proline Methyl Ester is used as a key intermediate in the synthesis of novel peptide deformylase inhibitors for the development of new antibiotics. Peptide deformylase is an essential enzyme in bacterial protein synthesis, and its inhibition can lead to the disruption of bacterial growth and survival.
Additionally, N-Boc-4-Methylene-L-proline Methyl Ester exhibits antibacterial activity, making it a potential candidate for the development of new antimicrobial agents to combat drug-resistant bacterial infections.
Used in Organic Synthesis:
N-Boc-4-Methylene-L-proline Methyl Ester is used as a versatile building block in organic synthesis for the preparation of various complex organic molecules, including natural products, pharmaceuticals, and agrochemicals. Its unique structural features allow for the formation of diverse chemical entities through various synthetic routes.

Upstream product

• 186581-53-3 diazomethane 
• 84348-38-9 (S)-1-(tert-butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid 
• 27200-84-6 methyl triphenylphosphonium bromide 
• 102195-80-2 (S)-1-tert-butyl 2-methyl 4-oxopyrrolidine-1,2-dicarboxylate 
• 1779-49-3 Methyltriphenylphosphonium bromide 
• 19493-09-5 Methylenetriphenylphosphorane 
• 74-88-4 methyl iodide 
• 24424-99-5 di-tert-butyl dicarbonate 
• 40216-83-9 L-4-hydroxyproline methyl ester hydrochloride 
• 75-24-1 trimethylaluminum 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 51-35-4 4R-4-hydroxyproline 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 593-71-5 Chloroiodomethane 

Downstream Products

• 84348-38-9 (S)-1-(tert-butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid 
• 84348-40-3 methyl 4-methylene-L-proline 
• 109606-56-6 1-tert-butyl 2-methyl (2S)-4-methylpyrrolidine-1,2-dicarboxylate 
• 1268819-47-1 C₂₂H₂₉N₃O₄ 
• 1268819-48-2 C₂₂H₂₈FN₃O₄ 
• 1256162-56-7 C₂₃H₃₂N₂O₆ 
• 1256162-57-8 C₂₂H₃₀N₂O₆ 
• 1268819-53-9 C₂₄H₃₂N₂O₆ 
• 1256162-68-1 C₂₆H₃₇N₃O₆ 
• 1256162-64-7 C₂₈H₃₅N₃O₅ 
• 1256162-66-9 C₂₈H₃₄FN₃O₅ 
• 1268819-36-8 C₂₈H₃₅N₃O₆ 
• 1256162-58-9 C₂₇H₃₃FN₄O₅ 
• 1256162-65-8 (S)-1-((R)-2-((N-hydroxyformamido)methyl)hexanoyl)-4-methylene-N-phenylpyrrolidine-2-carboxamide 

Relevant academic research and scientific papers

NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG

PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT

VISUAL DETECTION OF PBD INDUCED DNA CROSSLINKS

The present invention relates to the field of oncology, laboratory tools and methods, and especially anti-tumor DNA crosslinking agents. Most patients with advanced solid tumors develop resistance to chemotherapy due to the ability of cancer cells to repair or tolerate sustained DNA damages. The inventors showed that the compounds according to the present invention allow the detection and visualization of alkylated DNA damages induced by PBDs without altering their DNA crosslinking ability. This enables the study of the effect and properties of PBDs. In particular, the present invention relates new derivates of PBD molecules and their synthesis. The present invention also relates to a method for visualizing DNA crosslinking; to a method for assessing the resistance of a tumor to a crosslinking agent and to a method for identifying a molecule or treatment for improving the efficiency of a crosslinking agent.

BACTERIAL EFFLUX PUMP INHIBITORS

Disclosed herein are compounds of formula I: (formula I) and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.

MASP INHIBITORY COMPOUNDS AND USES THEREOF

The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.

CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES

A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP

Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

Design and synthesis of a folate-receptor targeted diazepine-ring-opened pyrrolobenzodiazepine prodrug conjugate

Pyrrolobenzodiazepines (PBDs) and their dimers (bis-PBDs) have emerged as some of the most potent chemotherapeutic compounds and are currently under development as novel payloads in antibody-drug conjugates (ADCs). However, when used as stand-alone therapeutics or as warheads for small molecule drug conjugates (SMDCs), dose-limiting toxicities are often observed. As an elegant solution to this inherent problem, we designed and synthesized a diazepine-ring-opened bis-PBD prodrug (pro-PBD-PBD) folate conjugate lacking the one of the two imine moieties found in the corresponding free bis-PBD. Upon entering a targeted cell, cleavage of the linker system, including the hydrolysis of an oxazolidine moiety, results in the formation of a reactive intermediate which possesses a newly formed aldehyde as well as an aromatic amine. A fast and spontaneous intramolecular ring-closing reaction subsequently takes place as the aromatic amine adds to the aldehyde with the loss of water to give the imine, and as a result, the diazepine ring, thereby delivering the bis-PBD to the targeted cell. The in vitro and in vivo activity of this conjugate has been evaluated on folate receptor positive KB cells. Sub-nanomolar activity with good specificity and high cure rates with minimal toxicity have been observed.

Ni-Catalyzed Arylboration of Unactivated Alkenes: Scope and Mechanistic Studies

A method for the Ni-catalyzed arylboration of unactivated monosubstituted, 1,1-disubstituted, and trisubstituted alkenes is disclosed. The reaction is notable in that it converts highly substituted alkenes, aryl bromides, and diboron reagents to products that contain a quaternary carbon and a synthetically versatile carbon-boron bond with control of stereoselectivity and regioselectivity. In addition, the method is demonstrated to be useful for the synthesis of saturated nitrogen heterocycles, which are important motifs in pharmaceutical compounds. Finally, due to the unusual reactivity demonstrated, the mechanistic details of the reaction were studied with both computational and experimental techniques.

PYRROLOBENZODIAZEPINE CONJUGATES

A compound of formula (I) : (I) and its conjugates.

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF

Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.