913723-61-2

Usage

Uses

Used in Inflammatory Disease Treatment:
Cl-Amidine is used as an anti-inflammatory agent for its capacity to inhibit the activity of peptidylarginine deiminases, thereby reducing inflammation associated with conditions such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.
Used in Oncology:
In the field of oncology, Cl-Amidine is utilized as an anticancer agent, exhibiting properties that inhibit cancer cell growth and prevent metastasis, making it a potential therapeutic for various cancer types.
Used in Neurodegenerative Disease Treatment:
Cl-Amidine is employed as a neuroprotective agent due to its potential to shield the nervous system from degeneration, offering a promising therapeutic approach for neurodegenerative diseases.
Used in Pharmaceutical Development:
Within the pharmaceutical industry, Cl-Amidine serves as a lead compound in the development of new drugs targeting PAD enzymes, aimed at treating a variety of inflammatory, autoimmune, and neurodegenerative disorders.

Upstream product

• 1043444-31-0 N-α-benzoyl-L-ornithine amide trifluoroacetate 
• 36743-66-5 ethyl chloroacetimidate hydrochloride 
• 184576-63-4 (R)-2-amino-5-(tert-butoxycarbonylamino)pentanoic acid 
• 98-88-4 benzoyl chloride 
• 1404060-34-9 C₁₂H₁₇N₃O₂ 
• 1404060-31-6 N¹-benzoyl-N⁴-Boc-D-ornithine amide 
• 1404060-28-1 N¹-benzoyl-N⁴-Boc-D-ornithine acid 

Relevant academic research and scientific papers

D-Amino acid-based protein arginine deiminase inhibitors: Synthesis, pharmacokinetics, and in cellulo efficacy

The protein arginine deiminases (PADs) are known to play a crucial role in the onset and progression of multiple inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and cancer. However, it is not known how each of the five PAD isozymes contributes to disease pathogenesis. As such, potent, selective, and bioavailable PAD inhibitors will be useful chemical probes to elucidate the specific roles of each isozyme. Because d-Amino amino acids often possess enhanced in cellulo stability, and perhaps unique selectivities, we synthesized a series of d-Amino acid analogues of our pan-PAD inhibitor Cl-Amidine, hypothesizing that this change would provide inhibitors with enhanced pharmacokinetic properties. Herein, we demonstrate that d-Cl-Amidine and d-o-F-Amidine are potent and highly selective inhibitors of PAD1. The pharmacokinetic properties of d-Cl-Amidine were moderately improved over those of l-Cl-Amidine, and this compound exhibited similar cell killing in a PAD1 expressing, triple-negative MDA-MB-231 breast cancer cell line. These inhibitors represent an important step in our efforts to develop stable, bioavailable, and highly selective inhibitors for all of the PAD isozymes.

An improved synthesis of haloacetamidine-based inactivators of protein arginine deiminase 4 (PAD4)

Protein arginine deiminase 4 (PAD4) is an enzyme that hydrolyzes peptidyl arginine residues to form citrulline and ammonia. This enzyme has been implicated in several disease states, for example, rheumatoid arthritis, and therefore represents a unique target for the development of a novel therapeutic. A solution-phase synthesis of Cl-amidine, the most potent PAD4 inactivator described to date, has been developed. This synthesis proceeds in 80% yield over four steps at a significantly (12-fold) lower cost.

SYNTHESIS AND USE OF NOVEL INHIBITORS AND INACTIVATORS OF PROTEIN ARGININE DEIMINASES

In one embodiment of the present disclosure, an inactivator of protein arginine deiminase 4 is disclosed. The inactivator includes: (I) and x includes F, Cl, and H, y includes OH and NH2, R includes H, an alkyl group, an alkenyl group, an alknyl group, and n is greater than 0.