- A convergent strategy towards febrifugine and related compounds
-
We report a modular five step synthetic route to the febrifugines that employs 2-(chloromethyl)allyl-trimethylsilane as a conjunctive reagent for the coupling of the piperidine and quinazolinone groups. We also demonstrate the application of a recent Rh-catalyzed quinazolinone synthesis for the facile generation of febrifugine analogs.
- Maiden,Mbelesi,Procopiou,Swanson,Harrity
-
p. 4159 - 4169
(2018/06/12)
-
- The drug intermediate halofuginone, fruits alkone parent nucleus synthesis method
-
The invention discloses a drug intermediate of halofuginone and a synthesis method of a halofuginone parent nucleus. The structural formula of the intermediate is disclosed in the specification. The synthesis method of the halofuginone parent nucleus is characterized by comprising the following steps: 1) in the presence of a catalyst, heating 3-bromo-4-chloroaniline and trimethyl orthoformate to sufficiently react, cooling, sufficiently reacting with NH3, separating, and carrying out primary purification to obtain a solid crude product; and 2) in the presence of a catalyst, sufficiently heating the obtained solid, acetic acid, CO and O2 to react, separating and purifying to obtain the end product. The synthesis method is a two-step process, and has the advantages of simple technique, environment friendliness, high yield and very low cost since the raw materials are accessible 3-bromo-4-chloroaniline and trimethyl orthoformate.
- -
-
Paragraph 0044; 0050; 0051
(2018/11/03)
-
- A novel synthesis of the efficient anti-coccidial drug halofuginone hydrobromide
-
Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods: First, 7-bromo-6-chloroquinazolin-4(3H)-one (2) was prepared from m-chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide (1) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3H)-one (4) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and 1H-NMR. Besides, the protective effect of compound 1-supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with E. tenella, by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. Results: Halofuginone hydrobromide (1) was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. Conclusions: The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production.
- Zhang, Junren,Yao, Qizheng,Liu, Zuliang
-
-
- COMBINATION THERAPIES FOR TREATMENT OF CANCER
-
Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.
- -
-
Page/Page column 291; 292
(2016/04/09)
-
- INHIBITORS OF KRAS G12C
-
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
- -
-
Page/Page column 239
(2015/04/28)
-
- A Mild and Regioselective Route to Functionalized Quinazolines
-
A Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4-aminoquinazolines in high yield. The method features a remarkably mild C(sp2)-H activation step and can be exploited to rapidly access compounds with established biological activity.
- Maiden, Tracy M. M.,Swanson, Stephen,Procopiou, Panayiotis A.,Harrity, Joseph P. A.
-
supporting information
p. 14342 - 14346
(2015/10/05)
-
- Facile synthesis of a 4-anilinoquinazoline dimer by Suzuki cross-coupling reaction
-
A novel 4-anilinoquinazoline dimer linked by a carbon-carbon bond in the C-7 position was synthesized via a one step Suzuki cross-coupling reaction. All structures of new compounds were characterized by 1H NMR, 13C NMR, and HRMS. The inhibition rate of the synthetic 4-anilinoquinazoline dimer 8 against epidermal growth factor receptor-tyrosine kinase enzymes (EGFR) in vitro was 44.4% at the concentration of 5.5 μmol/L.
- Chen, Shao Peng,Sun, Yue,Wan, Sheng Biao,Jiang, Tao
-
scheme or table
p. 1033 - 1035
(2012/06/18)
-
