Month: November 2022

Boutard, Nicolas published the artcileDiscovery and structure-activity relationships of N-aryl 6-aminoquinoxalines as potent PFKFB3 kinase inhibitors, Recommanded Product: 4-Bromo-2-chloro-6-nitroaniline, the main research area is crystal structure neoplasm antitumor PFKFB3 kinase inhibitor aminoquinoxaline; cancer; enzymes; glycolysis; inhibitors; metabolism.

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biol. evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported. X-ray crystallog. and docking were instrumental in the design and optimization of a series of N-aryl 6-aminoquinoxalines. The most potent representative, N-(4-methanesulfonylpyridin-3-yl)-8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-amine, displayed an IC50 of 14 nM for the target and an IC50 of 0.49 μM for fructose-2,6-biphosphate production in human colon carcinoma HCT116 cells. This work provides a new entry in the field of PFKFB3 inhibitors with potential for development in oncol.

ChemMedChem published new progress about Antitumor agents. 34033-41-5 belongs to class bromides-buliding-blocks, name is 4-Bromo-2-chloro-6-nitroaniline, and the molecular formula is C6H4BrClN2O2, Recommanded Product: 4-Bromo-2-chloro-6-nitroaniline.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Henry, James R. published the artcileDiscovery of 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF Inhibitor with Minimal Paradoxical Activation and Activity against BRAF or RAS Mutant Tumor Cells, Name: 1-Bromo-4-fluoro-2-methylbenzene, the main research area is antitumor RAF inhibitor LY3009120 preparation structure activity cancer.

The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation typically mediated through cell surface receptors. The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown significant clin. efficacy in melanoma patients harboring this mutation. Because of paradoxical pathway activation, both agents were demonstrated to promote growth and metastasis of tumor cells with RAS mutations in preclin. models and are contraindicated for treatment of cancer patients with BRAF WT background, including patients with KRAS or NRAS mutations. To eliminate the issues associated with paradoxical MAPK pathway activation and to provide therapeutic benefit to patients with RAS mutant cancers, we sought to identify a compound not only active against BRAF V600E but also wild type BRAF and CRAF. On the basis of its superior in vitro and in vivo profile, compound 13 was selected for further development and is currently being evaluated in phase I clin. studies.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 452-63-1 belongs to class bromides-buliding-blocks, name is 1-Bromo-4-fluoro-2-methylbenzene, and the molecular formula is C7H6BrF, Name: 1-Bromo-4-fluoro-2-methylbenzene.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Kuo, Gee-Hong published the artcileSynthesis and structure-activity relationships of pyrazine-pyridine biheteroaryls as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors, Computed Properties of 41668-13-7, the main research area is pyridinyltin dichloropyrazine Stille coupling; chloropyrazine pyridine preparation; pyrazine pyridine derivative preparation VEGFR2 ligand; pyridine pyrazine derivative preparation anticancer.

There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, I [R = NH(CH2)4OH, NH(CH2)2NMe2] exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of I were demonstrated in the A375 human melanoma xenograft nude mice model. Mol. modeling (QSAR anal.) was conducted in an attempt to rationalize the observed structure-activity relationship.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 41668-13-7 belongs to class bromides-buliding-blocks, name is 5-Bromo-6-hydroxynicotinic acid, and the molecular formula is C6H4BrNO3, Computed Properties of 41668-13-7.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Ghalib, Raza Murad published the artcilePhytochemical analysis, cytotoxic activity and constituents-activity relationships of the leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae), Related Products of bromides-buliding-blocks, the main research area is Cinnamomum antitumor leaf tumor.

The leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae) have been refluxed successively with chloroform and alc. to get chloroform extract and alc. extract Both the extracts have been assayed for cytotoxicity against human colorectal tumor cells. The chloroform extract exhibited significant cytotoxicity with IC50 31 μg mL-1 (p < 0.01). However, ethanol extract was found to be much less cytotoxic with IC50 > 200 μg mL-1. The chloroform extract has been further proceeded for chem. anal. by GC-TOFMS and 178 components were identified including acids, amines, amides, aldehydes, alcs., esters, benzene derivatives, bicyclic compounds, terpenes, hydrocarbons, naphthalene derivatives, furan derivatives, azulenes, etc. Nine components representing 51.73% of the total chloroform extract were detected as major components. Caryophyllene (14.41%) and Eicosanoic acid Et ester (12.17%) are the most prominent components of the chloroform extract Components of the chloroform extract β-Caryophyllene (14.41%) as most abundant compound supports potent cytotoxicity as shown by chloroform extract

Natural Product Research published new progress about Antitumor agents. 55099-31-5 belongs to class bromides-buliding-blocks, name is Ethyl 10-bromodecanoate, and the molecular formula is C12H23BrO2, Related Products of bromides-buliding-blocks.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Melin, Lea published the artcileDevelopment of LM98, a Small-Molecule TEAD Inhibitor Derived from Flufenamic Acid, Quality Control of 647020-71-1, the main research area is anticancer agent cell migration TEAD LM98 flufenamic acid; Flufenamic acid; Hippo pathway; SAR; TEAD; palmitic acid.

The YAP-TEAD transcriptional complex is responsible for the expression of genes that regulate cancer cell growth and proliferation. Dysregulation of the Hippo pathway due to overexpression of TEAD has been reported in a wide range of cancers. Inhibition of TEAD represses the expression of associated genes, demonstrating the value of this transcription factor for the development of novel anti-cancer therapies. We report herein the design, synthesis and biol. evaluation of LM98, a flufenamic acid analog. LM98 shows strong affinity to TEAD, inhibits its autopalmitoylation and reduces the YAP-TEAD transcriptional activity. Binding of LM98 to TEAD was supported by 19F-NMR studies while co-crystallization experiments confirmed that LM98 is anchored within the palmitic acid pocket of TEAD. LM98 reduces the expression of CTGF and Cyr61, inhibits MDA-MB-231 breast cancer cell migration and arrests cell cycling in the S phase during cell division.

ChemMedChem published new progress about Antitumor agents. 647020-71-1 belongs to class bromides-buliding-blocks, name is Methyl 2-bromo-3-fluorobenzoate, and the molecular formula is C8H6BrFO2, Quality Control of 647020-71-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Tria, George S. published the artcileDiscovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer, Synthetic Route of 452-63-1, the main research area is benzothiophene preparation selective estrogen receptor degrader breast cancer treatment.

In breast cancer, estrogen receptor alpha (ERα) pos. cancer accounts for approx. 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα pos. breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant, the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochem. properties. THe authors describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclin. activity as SERDs. This article culminates in the identification of LSZ102 (I), a compound in clin. development for the treatment of ERα pos. breast cancer.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 452-63-1 belongs to class bromides-buliding-blocks, name is 1-Bromo-4-fluoro-2-methylbenzene, and the molecular formula is C7H6BrF, Synthetic Route of 452-63-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Cacheux, Fanny published the artcileThe Piancatelli rearrangement of non-symmetrical furan-2,5-dicarbinols for the synthesis of highly functionalized cyclopentenones, Computed Properties of 452-63-1, the main research area is hydroxymethyl hydroxycyclopentenone preparation regioselective diastereoselective antitumor activity microwave irradiation; furan dicarbinol preparation Piancatelli rearrangement dysprosium chloride catalyst; aminocyclopentenone preparation regioselective diastereoselective microwave irradiation; aniline furan dicarbinol Aza Piancatelli rearrangement.

Substituted and non-sym. furan-2,5-dicarbinols I (R = Ph, 4-fluoro-2-methylphenyl, phenanthren-9-yl, 1,3-benzodioxol-5-yl, etc.) were readily prepared from 5-(hydroxymethyl)furfural (HMF), a renewable raw material from biomass. The Piancatelli rearrangement of these furan-2,5-dicarbinols I, catalyzed by DyCl3and under microwave activation, affords 5-substituted-4-hydroxymethyl-4-hydroxycyclopentenones (4S,5R)/(4S,5S)-II in a regio- and diastereoselective manner. This methodol. can be extended to aza-Piancatelli type reactions by using nitrogen nucleophiles, to furnish the corresponding aminocyclopentenone derivatives III (R1 = I, Br). Some of these synthesized bis-hydroxylated cyclopentenone derivatives exhibited significant cytotoxicity against eight human tumor cell lines.

Organic Chemistry Frontiers published new progress about Antitumor agents. 452-63-1 belongs to class bromides-buliding-blocks, name is 1-Bromo-4-fluoro-2-methylbenzene, and the molecular formula is C7H6BrF, Computed Properties of 452-63-1.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Cui, Pei H. published the artcileAntiproliferative and Antimigratory Actions of Synthetic Long Chain n-3 Monounsaturated Fatty Acids in Breast Cancer Cells That Overexpress Cyclooxygenase-2, Application In Synthesis of 55099-31-5, the main research area is antitumor antimetastatic monounsaturated fatty acid preparation breast cancer; structure activity antitumor monounsaturated fatty acid preparation breast cancer.

Cyclooxygenase-2 (COX-2) is overexpressed in many human cancers and converts the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid to prostaglandin E2 (PGE2), which drives tumorigenesis; in contrast, n-3 PUFA inhibit tumorigenesis. We tested the hypothesis that these antitumor actions of n-3 PUFA may involve the n-3 olefinic bond. n-3 Monounsaturated fatty acids (MUFAs) of chain length C16-C22 were synthesized and evaluated in MDA-MB-468 breast cancer cells that stably overexpressed COX-2 (MDA-COX-2 cells). Longer chain (C19-C22) n-3 MUFAs inhibited proliferation, activated apoptosis, decreased PGE2 formation, and decreased cell invasion; C16-C18 analogs were less active. Mol. modeling showed that interactions of Arg120, Tyr355, and several hydrophobic amino acid residues in the COX-2 active site with C19-C22 MUFA analogs were favored. Thus, longer-chain n-3 MUFAs may be prototypes of novel anticancer agents that decrease the formation of PGE2 in tumor cells that contain high levels of COX-2.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 55099-31-5 belongs to class bromides-buliding-blocks, name is Ethyl 10-bromodecanoate, and the molecular formula is C12H23BrO2, Application In Synthesis of 55099-31-5.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Hu, Quan-Fang published the artcileDesign, synthesis and biological evaluation of novel 1-phenyl phenanthridin-6(5H)-one derivatives as anti-tumor agents targeting TOPK, Synthetic Route of 211315-53-6, the main research area is OTS964 phenanthridin synthesis antitumor apoptosis TOPK colorectal cancer; 1-Phenyl phenanthridin-6(5H)-one; Colorectal cancer; Pharmacokinetics; Structure activity relationship; TOPK inhibitor.

T-lymphokine-activated killer cell-originated protein kinase (TOPK) is a serine-threonine mitogen-activated protein kinase that is highly expressed in many types of human cancer. Due to its important role in cancer progression, TOPK is becoming an attractive target in chemotherapeutic drug design. In this study, a series of 1-Ph phenanthridin-6(5H)-one derivatives have been identified as a novel chem. class of TOPK inhibitors. Some of them displayed very potent anti-cancer activity with IC50s less than 100 nM, superior than reference compound OTS964. The most potent compound, 9g suppressed the growth of cancer cells by apoptosis and specifically inhibited the activities of TOPK. Oral administration of 9g effectively suppressed tumor growth with TGI >79.7% in colorectal cancer xenograft models, demonstrating superior efficacy compared to OTS964. Pharmacokinetic studies reveal its good oral bioavailability. Our findings therefore show that 9g is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic agent against colorectal cancer.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 211315-53-6 belongs to class bromides-buliding-blocks, name is (R)-tert-Butyl (2-(4-bromophenyl)propyl)carbamate, and the molecular formula is C14H20BrNO2, Synthetic Route of 211315-53-6.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Hu, De-Xuan published the artcileSynthesis of Methoxy-, Methylenedioxy-, Hydroxy-, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer, Quality Control of 74317-85-4, the main research area is benzophenanthridinone preparation TOP1 TDP1 enzyme inhibitor antitumor SAR.

Herein, the synthesis of benzophenanthridinone derivatives I [R = 1-MeO, 2-Br, 8-OH, etc], II [R1 = R2 = 2,3-OCH2O, 8,9-Meo, 8,9-F], III [R3 = 8-F, 8-Br, 9-MeO; R4 = R5 = 2,3-OCH2O, 2,3-MeO, etc] as TOP1 and TDP1 inhibitors was reported. Seven compounds III [R3 = 8-F, 8-NO2, 8-MeO, 9-Cl, 7,8-OH, 8,9-F; R4 = R5 = 2,3-OCH2O] showed a robust TOP1 inhibitory activity (+++ or ++++), and four compounds I [R = 12-MeO] and III [R3 = 7,8-OH, 8-MeO, 8,9-MeO; R4 = R5 = 2,3-OCH2O, 8,9-MeO] showed a TDP1 inhibition (half-maximal inhibitory concentration values of 15 or 19μM). Also the dual TOP1 and TDP1 inhibitor III [R = 2,3-OCH2O, 7,8-OH] induces both cellular TOP1cc, TDP1cc formation and DNA damage was showed ,resulting in cancer cell apoptosis at a sub-micromolar concentration In addition, III [R = 2,3-OCH2O, 7,8-OH] showed an enhanced activity in drug-resistant MCF-7/TDP1 cancer cells and was synergistic with topotecan in both MCF-7 and MCF-7/TDP1 cells.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 74317-85-4 belongs to class bromides-buliding-blocks, name is 2-Bromo-4-methoxybenzoic acid, and the molecular formula is C8H7BrO3, Quality Control of 74317-85-4.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary