CO-1686 | 1374640-70-6

CO-1686 Properties

Melting point	202 - 205°C (dec.)
Density	1.372±0.06 g/cm3(Predicted)
storage temp.	Amber Vial, -20°C Freezer, Under inert atmosphere
solubility	DMSO (Slightly), Methanol (Slightly)
form	Solid
pka	13.23±0.70(Predicted)
color	Off-White
CAS DataBase Reference	1374640-70-6
FDA UNII	72AH61702G
NCI Drug Dictionary	rociletinib
ATC code	L01EB05

SAFETY

Risk and Safety Statements

Symbol(GHS)

GHS07

Signal word

Warning

Hazard statements

H302-H315-H319-H335

Precautionary statements

P261-P264-P270-P271-P280-P301+P312-P330-P302+P352-P321-P304+P340-P305+P351+P338-P332+P313-P362+P364-P337+P313-P403+P233-P405-P501

Risk Statements

23-25-36

Safety Statements

24

HS Code

29335990

NFPA 704

	0
2		0

CO-1686 price More Price(29)

Manufacturer	Product number	Product description	CAS number	Packaging	Price	Updated	Buy
Cayman Chemical	16244	CO-1686 ≥98%	1374640-70-6	1mg	$68	2024-03-01	Buy
Cayman Chemical	16244	CO-1686 ≥98%	1374640-70-6	5mg	$201	2024-03-01	Buy
Cayman Chemical	16244	CO-1686 ≥98%	1374640-70-6	10mg	$335	2024-03-01	Buy
TRC	C633000	CO1686	1374640-70-6	100mg	$275	2021-12-16	Buy
ChemScene	CS-1631	Rociletinib 99.59%	1374640-70-6	100mg	$250	2021-12-16	Buy

Product number	Packaging	Price	Buy
16244	1mg	$68	Buy
16244	5mg	$201	Buy
16244	10mg	$335	Buy
C633000	100mg	$275	Buy
CS-1631	100mg	$250	Buy

CO-1686 Chemical Properties,Uses,Production

Anti-cancer drugs

On May 20, 2014, Clovis Oncology announced that the US FDA had granted its test drug CO-1686 for breakthrough treatment drug qualification, as a second line, single administrated drug for the treatment of EFGR mutation non-small cell lung cancer (NSCLC) of the T790M mutation patients. The awarding for this breakthrough therapeutic drug eligibility was based on the efficacy and safety results of Co-1686 in an ongoing Phase 1/2 study. Data of related study have shown that CO-1686 is a third-generation EGFR inhibitor, being used for the treatment of non-small cell lung cancer, overcoming the drug resistance generated from the EGFR T790M mutations, and has excellent efficacy and tolerability on NSCLC with T790M + EGFR mutations. Its major market competitor, the third-generation EGFR inhibitor, AZD9291 (AstraZeneca) has also gained FDA's groundbreaking drug eligibility.
CO-1686 is a novel, oral-administrated, targeted covalent (irreversible) inhibitor of the epidermal growth factor receptor (EGFR) mutations, being able to suppress key activation mutations and T790 drug-resistant mutations, leaving the wild-type EGFR signal unused. This drug was developed for the treatment of NSCLC patients carrying initially activated EGFR mutations and major resistant mutant T790M.
The above information is compiled and edited by Xiao Nan of Chemicalbook.

Biological activity

Rociletinib (CO-1686, AVL-301) is an irreversible, mutation-selective EGFR inhibitor that targets EGFRL858R/T790M and EGFRWT with a Ki of 21.5 nM and 303.3 nM, respectively. Phase 2.
Target: EGFR (L858R/T790M) EGFR (wt)
IC50: 21.5 nM (Ki) 303.3 nM (Ki)

In vitro study

CO-1686 inhibited the p-EGFR in EGFR-expressing cells with an IC50 ranging from 62 to 187 nM while inhibiting EGFR phosphorylation. In three WT EGFR-expressing cells, the IC50 is larger than 2,000 nM. CO-1686 can selectively inhibit the growth of mutant EGFR expressing NSCLC cells with a GI50 ranging from 7 to 32 nM while inducing apoptosis. The CO-1686-resistant NSCLC cell line exhibited a signal for epithelial-mesenchymal transition and increased susceptibility to AKT inhibitors.

In vivo studies

In all EGFR mutant models, as well as in transgenic mice expressing human EGFRL858R-and EGFRL858R/T790M, CO-1686 caused significant tumor growth inhibition in a dose-dependent manner.

Synthesis method

5-fluoro-2-nitroanisole was condensed with piperazine, acetylated and reduced to give 1-(3-methoxy-4-aminophenyl)-4-acetylpiperazine (4) In addition, use 2, 4-dichloro-5-trifluoro methyl pyrimidine to undergo condensation with 3-nitroaniline, reduction and amidation to obtain N-[3-(2-Chloro-5-trifluoromethyl-pyrimidin-4-amino) phenyl] acrylamide (7). 4 and 7 were condensed to give the EGFR inhibitor, the anticancer drug CO-1686 with a total yield of about 71% (based on 2, 4-dichloro-5-trifluoromethyl pyrimidine).
Reference: Synthesis of CO-1686 [J]. Chinese Pharmaceutical Industry, 2014, 45 (8): 710-713.
OF: (1) Lai Yisheng, male, professor, doctoral supervisor, engaged in anti-inflammatory and anti-tumor drugs studied. (2) Zhang Shan, female, graduate students, professional direction: medicinal chemistry.

Description

CO-1686 is an irreversible kinase inhibitor that specifically targets mutant forms of the epidermal growth factor receptor (EGFR) including T790M (K_i = 21.5 nM) with significantly reduced activity at the wild-type form of the receptor (K_i = 303.3 nM). CO-1686 has been shown to inhibit the proliferation of non-small cell lung cancer (NSCLC) cells expressing mutant EGFR with GI₅₀ values ranging from 7-32 nM in vitro, inducing apoptosis. It also demonstrates anti-tumor activity in NSCLC EGFR mutant xenograft and transgenic models dosed orally at 100 mg/kg/day.

Uses

CO 1686 is seen as an irreversible epidermal growth factor receptor (EFGR1) kinase inhibitor.

target

L858R/T790M mutant EGFR

References

[1] walter a o, tjin r, haringsma h, et al. co-1686, an orally available, mutant-selective inhibitor of the epidermal growth factor receptor (egfr), causes tumor shrinkage in non-small cell lung cancer (nsclc) with t790m resistance mutations. mol cancer ther, 2011, 10(11 suppl).
[2] walter a o, sjin r t t, haringsma h j. discovery of a mutant-selective covalent inhibitor of egfr that overcomes t790m-mediated resistance in nsclc.

CO-1686 synthesis

Synthesis of CO-1686 from 2,4-Dichloro-5-trifluoromethylpyrimidine

CO-1686 Preparation Products And Raw materials

Raw materials

N-[2-chloro-5-(trifluoroMethyl)-4-pyriMidinyl]-1,3-benzenediaMine N-BOC-M-PHENYLENEDIAMINE 2,4-Dichloro-5-trifluoromethylpyrimidine CO-1686 intermediate 1 tert-butyl (3-((2-chloro-5-(trifluoroMethyl)pyriMidin-4-yl)aMino)phenyl)carbaMate

N-(4-aminophenyl)acrylamide 1-(4-(3-Methoxy-4-nitrophenyl)piperazin-1-yl)ethanone 1-(4-(4-aMino-3-Methoxyphenyl)piperazin-1-yl)ethanone 5-Fluoro-2-nitroanisole 3-Chloropropionyl chloride

Acryloyl chloride

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Preparation Products

CO-1686 Suppliers

Global( 199)Suppliers

Supplier	Tel	Email	Country	ProdList	Advantage
Capot Chemical Co.,Ltd.	571-85586718 +8613336195806	sales@capotchem.com	China	29797	60
Shanghai Yingrui Biopharma Co., Ltd.	+86-21-33585366 - 03@	sales03@shyrchem.com	CHINA	738	60
Nanjing Finetech Chemical Co., Ltd.	025-85710122 17714198479	sales@fine-chemtech.com	CHINA	885	55
ATK CHEMICAL COMPANY LIMITED	+undefined-21-51877795	ivan@atkchemical.com	China	32480	60
career henan chemical co	+86-0371-86658258	sales@coreychem.com	China	29914	58
Biochempartner	0086-13720134139	candy@biochempartner.com	CHINA	967	58
Hubei Jusheng Technology Co.,Ltd.	18871490254	linda@hubeijusheng.com	CHINA	28180	58
BOC Sciences	+1-631-485-4226	inquiry@bocsci.com	United States	19553	58
Chongqing Chemdad Co., Ltd	+86-023-61398051 +8613650506873	sales@chemdad.com	China	39916	58
Jurong Coupling Biotechnology Co., Ltd.	13656108824	coupling278191416@hotmail.com	CHINA	184	58

Supplier	Advantage
Capot Chemical Co.,Ltd.	60
Shanghai Yingrui Biopharma Co., Ltd.	60
Nanjing Finetech Chemical Co., Ltd.	55
ATK CHEMICAL COMPANY LIMITED	60
career henan chemical co	58
Biochempartner	58
Hubei Jusheng Technology Co.,Ltd.	58
BOC Sciences	58
Chongqing Chemdad Co., Ltd	58
Jurong Coupling Biotechnology Co., Ltd.	58

View Lastest Price from CO-1686 manufacturers

Image	Update time	Product	Price	Min. Order	Purity	Supply Ability	Manufacturer
	2019-07-06	CO-1686 1374640-70-6	US $1.00 / KG	1KG	99%	1000KG	Career Henan Chemical Co
	2019-07-06	CO-1686 1374640-70-6	US $7.00 / KG	1KG	99%	1000KG	Career Henan Chemical Co

CO-1686
1374640-70-6
US $1.00 / KG
99%
Career Henan Chemical Co

CO-1686
1374640-70-6
US $7.00 / KG
99%
Career Henan Chemical Co

CO-1686 Spectrum

CO-1686(1374640-70-6)¹HNMR

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CO-1686 AVL-301 CNX-419 CO-1686 (AVL-301) CO-1686/CO1686 N-[3-[[2-[[4-(4-Acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]phenyl]-2-propenamide Clovis CO-1686 CO-1686(free base) Rociletinib(AVL-301,CNX-419,CO-1686) N-(3-(2-(4-(4-acetylpiperazin-1-yl)-2-methoxyphenylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)phenyl)acrylamide CO-1686, >=98% N-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide ROCILETINIB Rociletinib(CO1686) 2-Propenamide, N-[3-[[2-[[4-(4-acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]phenyl]- Rociletinib (CO-1686, AVL-301) Co 1686 N-[3-[[2-[[4-(4-Acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]phenyl]-2-propenamide N-[3-[[2-[[4-(4-Acetyl-1-piperazinyl)-2-methoxyphenyl]amino]-5-(trifluoromethyl)-4-pyrimidinyl]amino]phenyl]-2-propenamide Co 1686 CO-1686(ROCILETINIB) Pyridostadin N-(3-((2-((4-(4-Acetylpiperazin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl CO1686; CO-1686; CO 1686; AVL301; AVL 301; AVL-301; CNX419; CNX 419; CNX-419; ROCILETINIB. Rociletinib (CO1686,CNX419) CS-851 ROCILETINIB; AVL-301; CNX-419;CO 1686;CO1686 N-(3-((2-((4-(4-Acetylpiperazin-1-yl)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)phenyl)prop-2-enamide CO-1686 (Rociletinib, AVL-301) Pyridostadin 3TFA CO-1686 USP/EP/BP Rociletinib (CO-1686, AVL-301, CNX-419) Rociletinib(free base) Pazufloxacin Monomer 1374640-70-6 C27H28F3N7O3 Inhibitors API