Berotralstat
[CAS# 1809010-50-1]

Identification

• Classification: API >> Inhibitor drug
• Name: Berotralstat
• Synonyms: 2-[3-(aminomethyl)phenyl]-N-[5-[(R)-(3-cyanophenyl)-(cyclopropylmethylamino)methyl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide
• Molecular Formula: C₃₀H₂₆F₄N₆O
• Molecular Weight: 562.56
• CAS Registry Number: 1809010-50-1
• SMILES: C1CC1CN[C@@H](C2=CC(=C(C=C2)F)NC(=O)C3=CC(=NN3C4=CC=CC(=C4)CN)C(F)(F)F)C5=CC=CC(=C5)C#N

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.640, Calc.^*
• Boiling Point: 621.2±55.0 ºC (760 mmHg), Calc.^*
• Flash Point: 329.5±31.5 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

Berotralstat is a novel chemical compound that has garnered significant attention for its therapeutic potential in treating hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent episodes of severe swelling. This disorder is typically caused by a deficiency or dysfunction of C1 esterase inhibitor, a protein that helps regulate the complement system. The unique pharmacological profile of berotralstat, a selective oral inhibitor of plasma kallikrein, offers a new approach to managing HAE by preventing the uncontrolled activation of the complement system that leads to swelling.

The discovery of berotralstat was driven by the need for a more effective and convenient treatment for HAE patients. Traditional therapies, such as injectable C1 inhibitor concentrates or bradykinin receptor antagonists, provide relief but often require intravenous administration and can be cumbersome for patients. Berotralstat, however, is designed to be taken orally, providing a more accessible and patient-friendly option for long-term management. The development of berotralstat represents a significant advancement in the treatment of HAE, offering patients an effective oral alternative to intravenous therapies.

Berotralstat’s mechanism of action is centered around its ability to inhibit plasma kallikrein, an enzyme that plays a critical role in the generation of bradykinin, a key mediator of inflammation and vascular permeability. By inhibiting kallikrein, berotralstat reduces the production of bradykinin, thereby preventing the swelling episodes that are characteristic of HAE. This makes berotralstat an important tool in the prevention of attacks and the management of this debilitating condition.

The synthesis of berotralstat involves the use of advanced organic chemistry techniques, including the development of selective inhibitors that target plasma kallikrein with high specificity. Researchers have employed a combination of computational modeling and structure-activity relationship studies to optimize the drug's potency and selectivity, resulting in a compound that effectively inhibits kallikrein without significant off-target effects.

In clinical trials, berotralstat has demonstrated promising results, showing a significant reduction in the frequency of HAE attacks and improving patients’ quality of life. Its oral formulation has made it a highly preferred option for patients who require long-term prophylactic treatment. The success of berotralstat in clinical settings highlights its potential to become a standard treatment for HAE, providing a more convenient and effective alternative to existing therapies.

As research into berotralstat continues, it may also find applications in other areas where plasma kallikrein and bradykinin play a role in disease pathogenesis. This could include conditions such as acute pancreatitis, cardiovascular diseases, and other inflammatory disorders.