1353550-13-6 Usage
Description
Different sources of media describe the Description of 1353550-13-6 differently. You can refer to the following data:
1. Olmutinib, codeveloped by
Boehringer Ingelheim and Hanmi Pharmaceutical Co., was
approved by the Korean Ministry of Food and Drug Safety
(MFDS) for treatment of locally advanced or metastatic EGFR
T790 M mutation-positive non-small cell lung cancer
(NSCLC). Olmutinib serves as a third-generation epidermal
growth factor receptor tyrosine kinase inhibitor (EGFR TKI),
which is being used as an oral therapy for patients who have
previously been treated with an alternate EGFR TKI. Firstand
second-generation EGFR TKIs, which bind reversibly and
irreversibly to the TK domain, respectively, are both generally
effective at onset of treatment but result in development of
resistance within the first year of treatment. Thirdgeneration
EGFR TKIs such as olmutinib have demonstrated
the ability to covalently bind to the kinase domain of EGFR
while sparing wild-type EGFR, leading to irreversible inhibition
of both EGFR mutations and the T790 M mutation, which is
linked to EGFR TKI resistance.
2. HM61713 is a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that inhibits both EGFR activating and T790M resistance mutations, while sparing wild-type EGFR. It has been investigated in Phase II clinical trials in patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC), who developed resistance to earlier generations of EGFR tyrosine kinase inhibitor therapy.
Uses
Olmutinib is an epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) against non-small cell lung cancer (NSCLC).
Synthesis
Synthetically, olmutinib can be accessed in two steps
beginning with 2,4-dichloro-thieno[3,2-d]pyrimidine (147), which is commercially available and can be
prepared in two steps from urea and 3-aminothiophene 2-
carboxylate. Nucleophilic addition of N-(3-hydroxyphenyl)-2-
propenamide (148) to 147 proceeded with complete
regioselectivity via treatment with K2CO3 in warm DMSO,
smoothly providing the desired diaryl ether 149 in 87% yield
after crystallization from isopropanol and water. From
149, substitution with commercially available piperazinyl aniline
150 under acidic heating conditions (DMA, IPA, TFA, 90 °C)
provided olmutinib in 82% yield. After recrystallization,
olmutinib (XVI) was obtained in 60% overall yield and
99.1% purity.
in vitro
olmutinib has been identified as an irreversible kinase inhibitor and could covalently bind to a cysteine residue near the kinase domain of mutant egfr. olmutinib had a half-life of over 24h for egfr inhibition. olmutinib was able to cause potent inhibition in cell lines h1975 (l858r and t790m) and hcc827 (exon 19 deletion). olmutinib showed a low potency for nsclc cell line h358 with wild-type egfr [1].
in vivo
the previous in vivo studies of xenograft models with grafts of h1975 and hcc827 showed that olmutinib was active against the tumors without dasplaying any side effects [1].
references
[1] wang s, cang s, liu d. third-generation inhibitors targeting egfr t790m mutation in advanced non-small cell lung cancer. j hematol oncol. 2016 apr 12;9:34.
Check Digit Verification of cas no
The CAS Registry Mumber 1353550-13-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,5,3,5,5 and 0 respectively; the second part has 2 digits, 1 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1353550-13:
(9*1)+(8*3)+(7*5)+(6*3)+(5*5)+(4*5)+(3*0)+(2*1)+(1*3)=136
136 % 10 = 6
So 1353550-13-6 is a valid CAS Registry Number.
1353550-13-6Relevant articles and documents
NOVEL METHOD FOR PREPARING THIENOPYRIMIDINE COMPOUND AND INTERMEDIATE
-
, (2019/11/11)
Provided are a novel method of preparing a thienopyrimidine compound having activity of selectively inhibiting tyrosine kinase, particularly, mutant epidermal growth factor receptor tyrosine kinase, and a novel intermediate used for the novel method. According to the method of the present disclosure, a compound of Formula 1 useful as a therapeutic agent for non-small cell lung cancer induced by mutant epidermal growth factor receptor tyrosine kinase can be industrially mass-produced more easily and efficiently than the prior art.
NOVEL METHOD FOR PREPARING THIENOPYRIMIDINE COMPOUND AND INTERMEDIATES USED THEREIN
-
, (2016/08/03)
The present invention provides a novel method for preparing a thienopyrimidine compound of Formula 1, which is a selective inhibitor of tyrosine kinase activity, in particular, of mutant epidermal growth factor receptor tyrosine kinase, and novel intermediates used in the method.[ 1 ]