(1S,2S,3R,5S)-3-(7-(((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amino)-5-(propylsulfonyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

Manufacturer: Hangzhou Royalchem Co.,LTD.

Website:   www.cnroyalchem.com

【 Providing a complete set of intermediates and impurities for Ticagrelor 】

【 Providing a complete set of intermediates and impurities for Ticagrelor 】

【 Providing a complete set of intermediates and impurities for Ticagrelor 】

Chemical Identity:

CAS Registry Number:  274693-39-9

Systematic Name:  (1S,2S,3R,5S)-3-(7-(((1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylsulfonyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

Synonyms:  Osimertinib; AZD-9291; Tagrisso™ (brand name); Mereletinib.

Molecular Formula:  C 28 H 33 N 7 O 5 F 2 S

Molecular Weight:  617.67 g/mol

Structural Features & Mechanism of Action:

Core Scaffold:  Features a 3H-[1,2,3]triazolo[4,5-d]pyrimidine core, acting as an ATP-mimetic that binds to the EGFR kinase domain.

Acrylamide Warhead:  The cyclopropylamine group ((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)amine acts as a Michael acceptor, enabling  covalent, irreversible binding  to the cysteine-797 (C797) residue in the ATP-binding pocket of EGFR.

Specificity Elements:  The 3,4-difluorophenyl group and the propylsulfonyl group are critical for selectivity. They allow potent inhibition of mutant EGFR forms (especially T790M and exon 19 deletion/L858R) while sparing wild-type EGFR, reducing skin and GI toxicity common with 1st-gen TKIs.

Solubility/Properties:  The cyclopentane-1,2-diol moiety with the 2-hydroxyethoxy substituent contributes to solubility and overall physicochemical properties.

Pharmacology & Therapeutic Use:

Primary Indication:  Treatment of  non-small cell lung cancer (NSCLC) .

Key Mutations:  Specifically designed to target tumors harboring  EGFR T790M resistance mutations , which arise after treatment with 1st-generation (gefitinib, erlotinib) or 2nd-generation (afatinib) EGFR TKIs. Also highly active against classic EGFR activating mutations (exon 19 deletion, L858R).

Approved Uses (Examples):

First-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) mutations.

Treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC (confirmed by FDA-approved test) in patients who have progressed on or after prior EGFR TKI therapy.

Adjuvant treatment after tumor resection in NSCLC patients with EGFR exon 19 deletions or exon 21 (L858R) mutations.

Mechanism:  Irreversibly inhibits EGFR tyrosine kinase activity by covalently binding to C797, blocking downstream signaling pathways (e.g., PI3K/AKT, RAS/RAF/MEK/ERK) crucial for cancer cell proliferation and survival.

Key Properties:

Physical Form:  Typically supplied as a white to brown powder.

Solubility:  Low aqueous solubility. Formulated as a mesylate salt (Osimertinib mesylate) for oral dosage forms (tablets).

Brand Name:   Tagrisso™  (AstraZeneca).

Dosage Form:  Film-coated tablets (40 mg and 80 mg osimertinib base equivalent).