1. Basic Information
· CAS Number: 1563540-10-2
· Chemical Name:
· (1R,2S,5S)-N-((S)-1-cyano-2-((S)-2-oxopyrrolidine-3-yl)ethyl)-6,6-dimethyl-3-aza-bicyclo[3.1.0]hexane-2-carboxamide
· This lengthy name describes the precise stereochemical structure and atomic connection mode of the compound.
· Common Name/Code: It is a specific fragment of narametivir, but in chemical synthesis, it is often referred to as N1-fragment or N1-pyrrolidine fragment. It is sometimes also directly labeled as Narametivir intermediate.
2. Chemical structure characteristics
· Core structure: This molecule contains three key stereocenters (chiral centers):
1. 3-aza-bicyclo[3.1.0]hexane: This is a rigid bicyclic structure that provides a specific three-dimensional spatial orientation, which is crucial for the efficient binding with the target (the main protease of the coronavirus).
2. Pyrrolidone ring: A five-membered amide ring, which is a key part for mimicking the amino acids in the protein substrate.
3. Nitrile group: A very important pharmacophore that can form reversible covalent bonds with the cysteine residue at the active site of the viral main protease, thereby inhibiting the enzyme's activity.
· Stereodynamics: All the chiral centers of this molecule are specific and fixed ((1R,2S,5S) and (S) configurations). This precise stereoscopic configuration is the decisive factor for its highly effective antiviral activity. Any error in the configuration will result in a significant reduction or complete loss of activity.
3. Main Uses and Importance
The primary application of this compound is as a key intermediate for synthesizing the antiviral drug nirmatrelvir.
· Namatvet: It is one of the two components of Paxlovid (Paxlovid is an oral COVID-19 treatment drug developed by Pfizer, used to treat mild to moderate COVID-19 patients with a risk of progressing to severe conditions).
· Role in synthesis: In the multi-step synthesis route of namatvet, CAS 1563540-10-2 acts as a pre-prepared complex fragment with the correct stereoconfiguration, and is coupled with another key fragment (such as the N2-fragment, with the CAS number 1563540-99-8, a carboxylic acid) through an amide bond, ultimately forming the namatvet molecule.
· Importance: Due to the complexity of its structure, especially the presence of multiple chiral centers, the efficient and high-purity synthesis of this intermediate is one of the technical cores and difficulties in the large-scale production of Paxlovid. Developing an economic and environmentally friendly process for asymmetric synthesis of this fragment is a research focus for many chemists and pharmaceutical companies worldwide.
4. Physical Properties (Overview)
· Appearance: Usually a white to off-white solid powder.
· Solubility: Soluble in common organic solvents such as dimethyl sulfoxide (DMSO), methanol, ethanol, dichloromethane, ethyl acetate, etc. The solubility in water may be limited.
· Stability: Should be stored at low temperatures (such as -20°C), in a dry environment, and protected from light to maintain its chemical stability and stereoisomer purity. It may be sensitive to air and humidity.
5. Market and Supply Chain
Since Paxlovid was granted emergency use authorization and formal approval, the demand for this intermediate has risen sharply. Its supply chain involves:
· Patent holder: Pfizer holds the core patent for nemonutiv.
· Raw material producer: Some authorized generic drug producers (through the MPP agreement) and contract manufacturing organizations (CMOs) providing services to Pfizer need to purchase or produce large quantities of this intermediate.
· Chemical synthesis company: Many fine chemical companies are dedicated to developing and optimizing the synthesis process of this intermediate to reduce costs and increase production.
Summary
CAS 1563540-10-2 is not merely an ordinary chemical; it is a key weapon in the global fight against the COVID-19 pandemic - the core component of the oral medication Paxlovid. It represents a model of chiral synthesis and rational drug design in modern drug chemistry, and its efficient and precise industrial production is of great significance for ensuring global public health security.
