Basic information Safety Supplier Related
ChemicalBook >  Product Catalog >  Biochemical Engineering >  Inhibitors >  Stem Cells & Wnt >  Hedgehog / Smoothened inhibitor >  2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide

2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide

Basic information Safety Supplier Related

2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide Basic information

Product Name:
2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide
Synonyms:
  • 2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide
  • VisModegib (GDC-0449)
  • BenzaMide, 2-chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(Methylsulfonyl)-
  • Vismodegib
  • GDC-0449,Vismodegib
  • GDC-0449
  • 101098
  • CS-1913
CAS:
879085-55-9
MF:
C19H14Cl2N2O3S
MW:
421.3
EINECS:
806-752-3
Product Categories:
  • Inhibitors
  • Aromatics
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Inhibitor
  • API
Mol File:
879085-55-9.mol
More
Less

2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide Chemical Properties

Melting point:
179-181°C
Boiling point:
561.6±50.0 °C(Predicted)
Density 
1.440
storage temp. 
-20°
solubility 
Soluble in DMSO (up to 200 mg/ml) or in Ethanol (up to 10 mg/ml with warming)
form 
White solid.
pka
10.72±0.70(Predicted)
color 
Off-white or beige
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
More
Less

Safety Information

HS Code 
29333990
Hazardous Substances Data
879085-55-9(Hazardous Substances Data)
More
Less

2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamide Usage And Synthesis

Description

In January 2012, the US FDA approved vismodegib (also referred to as GDC-0449) for the treatment of adults with metastatic basal cell carcinoma (BCC), with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation. Vismodegib inhibits the Hh sig?naling pathway by functioning as an antagonist of SMO thereby inhibiting the activation of Hedgehog target genes, resulting in decreased downstream pro?duction of proliferation factors. The IC50 of vismodegib in a Hedgehog?responsive cell line derived from human embryonic palatal mesenchyme cells was 2.8 nM. In preclinical in vivostudies, vismodegib at 12.5 mg/kg (bid) caused complete regression of tumors in a Hh pathway dependent medulloblas?tomaallograft model generated from Ptch+/-mice. A synthesis of vismodegib starting from 2-chloro-5-nitro aniline and employing a Negishi coupling with 2-pyridyl zinc iodide as a key step has been reported.

Chemical Properties

White Solid

Originator

Curis/Genentech (United States)

Uses

Vismodegib targets the Hedgehog (Hh) pathway. Inhibition of the Hh signaling may be effective in the treatment and prevention of many types of human cancers. Potent Hedgehog inhibitor.

Uses

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM.

Definition

ChEBI: A benzamide obtained by formal condensation between the carboxy group of 2-chloro-4-(methylsulfonyl)benzoic acid and the anilino group of 4-chloro-3-(pyridin-2-yl)aniline. Used for the treatment metastatic basal cell carcinoma.

brand name

Erivedge

Clinical Use

Antineoplastic agent:
Treatment of basal cell carcinoma which is inappropriate for surgery or radiotherapy

Synthesis

The synthesis began with selective iodination of commercial carboxylic acid 179, affording trisubstituted arene 180 in 73% yield. A Curtius reaction then converted 180 to carbamate 181 in 84% 52 yield, and this was followed by a palladium(0)-catalyzed borylation of 181 which furnished Suzuki coupling partner 182 in 91% yield. Pinacol borane 182 was exposed to commercial 2-bromopyridine under conventional cross-coupling conditions to furnish biaryl 183, which underwent Boc-deprotection in quantitative conversion to generate 184. Amide bond formation with acid chloride 185 (readily available from the corresponding commercial acid) produced vismodegib (XXVIII) in 99% yield.

target

Hedgehog

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: concentration possibly reduced by rifampicin - avoid.
Antidepressants: concentration possibly reduced by St John’s wort - avoid.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - avoid.
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.

Metabolism

Vismodegib is hepatically metabolised by CYP2C9 and CYP3A4, however more than 98
% of total systemic vismodegib is not metabolised. Metabolic pathways of vismodegib include oxidation, glucuronidation, and pyridine ring cleavage. The two most abundant oxidative metabolites recovered in faeces are produced in vitro by recombinant CYP2C9 and CYP3A4/5.
Vismodegib is slowly eliminated by a combination of metabolism and excretion of parent drug, the majority is recovered in the faeces (82
%). Vismodegib and its metabolites are eliminated mainly by the hepatic route.

storage

Store at -20°C

References

1) Rominger et al. (2009), Evidence for allosteric interactions of antagonist binding to the smoothened receptor; J. Pharmacol. Exp. Therap., 329 995 2) Tian et al. (2012), The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+ homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells; Anticancer Res., 32 89 3) Zhang et al. (2009), Hedgehog pathway inhibitor HhAntag691 is a potent inhibitor of ABCG2/BCRP and ABCB1/Pgp; Neoplasia, 11 96 4) Cirrone and Harris (2012), Vismodegib anf the hedgehog pathway: a new treatment for basal cell carcinoma; Clin. Ther., 34 2039 5) Wu et al. (2017), Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines; Exp. Ther. Med., 13 2529 6)Singh et al. (2011) Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms; PLoS One 6?e27306 7) Rudin et al. (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449; N. Engl. J. Med., 361?1173 8) Von Hoff et al. (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma; N. Engl. J. Med., 361?1164

2-Chloro-N-[4-chloro-3-(2-pyridinyl)phenyl]-4-(methylsulfonyl)benzamideSupplier

Beijing Jingzi Pharmaceutical Technology Co., Ltd. Gold
Tel
15011485209
Email
17241816@qq.com
Shanghai Zhixin Chemical Technology Co., Ltd. Gold
Tel
021-60441077 18701958033
Email
shzxchem@163.com
ChangShu HengYao Advanced Material Co.,Ltd. Gold
Tel
0510-15312278075 15312278075
Email
xxl_hotmail@163.com
Wuhan Shanhai Zhihe Biotechnology Co., Ltd. Gold
Tel
17771424646
Email
shoubull@126.com
Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com