Day: December 30, 2022

Identification of 1-(3-(6,7-Dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea Hydrochloride (CEP-32496), a Highly Potent and Orally Efficacious Inhibitor of V-RAF Murine Sarcoma Viral Oncogene Homologue B1 (BRAF) V600E was written by Rowbottom, Martin W.;Faraoni, Raffaella;Chao, Qi;Campbell, Brian T.;Lai, Andiliy G.;Setti, Eduardo;Ezawa, Maiko;Sprankle, Kelly G.;Abraham, Sunny;Tran, Lan;Struss, Brian;Gibney, Michael;Armstrong, Robert C.;Gunawardane, Ruwanthi N.;Nepomuceno, Ronald R.;Valenta, Ianina;Hua, Helen;Gardner, Michael F.;Cramer, Merryl D.;Gitnick, Dana;Insko, Darren E.;Apuy, Julius L.;Jones-Bolin, Susan;Ghose, Arup K.;Herbertz, Torsten;Ator, Mark A.;Dorsey, Bruce D.;Ruggeri, Bruce;Williams, Michael;Bhagwat, Shripad;James, Joyce;Holladay, Mark W.. And the article was included in Journal of Medicinal Chemistry in 2012.Name: 3-(tert-Butyl)isoxazol-5-amine This article mentions the following:

The Ras/RAF/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway plays a central role in the regulation of cell growth, differentiation, and survival. Expression of mutant BRAF^V600E results in constitutive activation of the MAPK pathway, which can lead to uncontrolled cellular growth. Herein, we describe an SAR optimization campaign around a series of quinazoline derived BRAF^V600E inhibitors. In particular, the bioisosteric replacement of a metabolically sensitive tert-Bu group with fluorinated alkyl moieties is described. This effort led directly to the identification of a clin. candidate 1-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-yl)urea hydrochloride (CEP-32496, I). CEP-32496 exhibits high potency against several BRAF^V600E-dependent cell lines and selective cytotoxicity for tumor cell lines expressing mutant BRAF^V600E vs. those containing wild-type BRAF. It also exhibits an excellent PK profile across multiple preclin. species. In addition, significant oral efficacy was observed in a 14-day BRAF^V600E-dependent human Colo-205 tumor xenograft mouse model, upon dosing at 30 and 100 mg/kg BID. In the experiment, the researchers used many compounds, for example, 3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9Name: 3-(tert-Butyl)isoxazol-5-amine).

3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9) belongs to isoxazole derivatives. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib (Bextra) and a neurotransmitter agonist AMPA. Fe(CO)5 efficiently cleaves the N–O bond of fused isoxazolo-1,4-quinones to give the corresponding imines.All the common reducing reagents failed to open the isoxazole ring.Name: 3-(tert-Butyl)isoxazol-5-amine

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Identification of pyrazine-based TrkA inhibitors: design, synthesis, evaluation, and computational modeling studies was written by Frett, Brendan;McConnell, Nick;Wang, Yuanxiang;Xu, Zhigang;Ambrose, Andrew;Li, Hong-yu. And the article was included in MedChemComm in 2014.Product Details of 59669-59-9 This article mentions the following:

Trk receptors play a key role in the development and maintenance of neuronal networks. Recent evidence suggests that the Trk family, specifically TrkA, is an important driver for tumor growth, inflammatory and neuropathic pain, and chemoresistance. Through a computational screen, a novel Trk active pharmacophore was identified and a series of pyrazine-based inhibitors were developed, which potently inhibited TrkA. Inhibitors displayed the highest activity on TrkA when screened against a small, tyrosine kinase panel and also exhibited a non-linear SAR. Predicted binding modes of the inhibitors were examined, which identified exploitable regions for future development of more advanced inhibitors. In the experiment, the researchers used many compounds, for example, 3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9Product Details of 59669-59-9).

3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9) belongs to isoxazole derivatives. Isoxazoles present in various natural products and synthetic compounds of biological importance like antibacterial, antagonists, antiinflammatory, analgesics, and also show the applications in functional materials. The electrophilic cyclization of various 2-alkynone O-methyl oximes with a wide range of substrates such as ICl, I2, Br2, PhSeBr, etc. provides a variety of 3,4,5-trisubstituted isoxazoles in good to excellent yields.Product Details of 59669-59-9

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

An efficient synthesis of fused 3-formylpyridines and 5-formylpyrimidines was written by Mityuk, Andrey P.;Kolodych, Sergey E.;Mytnyk, Sergey A.;Dmytriv, Yuri V.;Volochnyuk, Dmitriy M.;Mykhailiuk, Pavel K.;Tolmachev, Andrey A.. And the article was included in Synthesis in 2010.Recommanded Product: 59669-59-9 This article mentions the following:

Cyclization of 2-[(dimethylamino)methylene]-1,3-bis(dimethylimonio)propane diperchlorate, Me₂NCH:C(CH:N⁺Me₂)₂.2ClO₄^–, with various amino heterocycles led to the formation of a series of fused heterocyclic systems containing a 3-formylpyridine or 5-formylpyrimidine unit. In the experiment, the researchers used many compounds, for example, 3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9Recommanded Product: 59669-59-9).

3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9) belongs to isoxazole derivatives. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib (Bextra) and a neurotransmitter agonist AMPA. Isoxazole can be synthesised via a variety of methods. Examples include via a 1,3-dipolar cycloaddition of nitrile oxides with alkynes.Recommanded Product: 59669-59-9

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem