Month: November 2022

Burger, Matthew T. published the artcileSynthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors, Product Details of C4HBr3N2, the main research area is morpholino heterocyclic pyrimidine preparation phosphoinositide kinase inhibitor; PI3K/AKT pathway; phosphoinositide 3-kinase alpha.

Phosphoinositide-3-kinases (PI3K) are important oncol. targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties. A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered. Within this series a compound (I) was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKTSer473 phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Product Details of C4HBr3N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Axten, Jeffrey M. published the artcileDiscovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), COA of Formula: C7H5BrClN3, the main research area is methyltrifluoromethylphenylacetyldihydroindolylpyrrolopyrimidinamine preparation SAR PERK inhibitory antitumor.

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small mol. inhibitors. Through screening and lead optimization using the human PERK crystal structure, we discovered compound I (GSK2606414), an orally available, potent, and selective PERK inhibitor. Compound I inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1266343-30-9 belongs to class pyrimidines, name is 5-Bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, and the molecular formula is C7H5BrClN3, COA of Formula: C7H5BrClN3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Horiuchi, Takao published the artcileDiscovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2, Recommanded Product: Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, the main research area is cyclin dependent kinase 4 CDK4 inhibitor cancer; hydrazone derivative SAR preparation.

The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogs as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted Ph groups, 4-[(methylamino)methyl]benzaldehyde (22)(I) and 5-isoindolinecarbaldehyde (24)(II) (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone derivatives have been identified. In this paper, the potency, selectivity profile and structure-activity relationships of our synthetic compounds are discussed.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 439692-55-4 belongs to class pyrimidines, name is Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, and the molecular formula is C10H11ClN2S, Recommanded Product: Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Lefranc, Julien published the artcileDiscovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor, SDS of cas: 3122-84-7, the main research area is BAY985 TBK1 IKK epsilon inhibitor antitumor activity antiproliferative melanoma.

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homolog IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 3122-84-7 belongs to class pyrimidines, name is 4-Chloro-6-(methoxymethyl)pyrimidine, and the molecular formula is C6H7ClN2O, SDS of cas: 3122-84-7.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Miura, Takaaki published the artcileLead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design, Recommanded Product: 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, the main research area is HSP90 inhibitor virtual screening antitumor structure drug design cancer; anticancer CH5015765 preparation 3D Xray HSP90 complex crystal structure; aminotriazine aminopyrimidine derivative mol structure HSP90 target antitumor design.

Heat shock protein 90 (Hsp90) is a mol. chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 66373-25-9 belongs to class pyrimidines, name is 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, and the molecular formula is C7H9N3O, Recommanded Product: 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Burger, Matthew T. published the artcileIdentification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer, Formula: C4HBr3N2, the main research area is morpholino heterocyclic pyrimidine preparation oral PI3 kinase inhibitor cancer; NVP-BKM120; PI3K/AKT3 pathway; phosphoinositide-3-kinase.

Phosphoinositide-3-kinases (PI3Ks) are important oncol. targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clin. trials for the treatment of cancer.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Formula: C4HBr3N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kala, Pruthu published the artcileDesign, Synthesis, and Anticancer Activity of Substituted Styryl Incorporated Quinazoline Derivatives, Application In Synthesis of 5472-46-8, the main research area is styryl pyrimidopyrimidine preparation diastereoselective human anticancer.

A novel series of substituted aryl ethynyl incorporated quinazolines has been synthesized. The products have been tested for their preliminary anticancer activity against human cancer cell lines like MCF-7 (human breast cancer), A549 (human lung cancer), DU-145 (human prostate cancer), and MDA MB-231 (human breast cancer). All the synthesized compounds showed good to excellent activity against tested cell lines.

Russian Journal of General Chemistry published new progress about Antitumor agents. 5472-46-8 belongs to class pyrimidines, name is Ethyl 4-amino-2-methylpyrimidine-5-carboxylate, and the molecular formula is C8H11N3O2, Application In Synthesis of 5472-46-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Tseng, Chih-Hua published the artcileSynthesis and antiproliferative evaluation of 3-phenylquinolinylchalcone derivatives against non-small cell lung cancers and breast cancers, Category: pyrimidines, the main research area is methoxyphenylquinolinyl aryl propenone stereoselective preparation antitumor activity; structure methoxyphenylquinolinyl aryl propenone inhibition human cancer normal cell; breast non small cell lung cancer inhibition methoxyphenylquinolinyl arylpropenone; cell cycle progression cellular administration methoxyphenylquinolinyl aryl propenone; cleavage apoptotic protein cellular administration methoxyphenylquinolinyl aryl propenone; methoxyphenyl methoxyphenylquinolinyl propenone mol crystal structure.

3-(4-Methoxyphenyl)quinolinyl aryl propenones I [R = Ph, 4-FC6H4, 4-HOC6H4, 4-MeOC6H4, 2,4-(MeO)2C6H3, 2,6-(MeO)2C6H3, 3,4-(MeO)2C6H3, 3,5-(MeO)2C6H3, 4-H2NC6H4, 4-O2NC6H4, 2-furyl, 2-thienyl, 2-pyridinyl, 5-Br-2-thienyl, 3-thienyl, 2-pyrrolyl, 3-amino-2-thienyl, 2-amino-4-methyl-5-pyrimidinyl, 3-indolyl] were prepared as potential antitumor agents. I (R = Ph) inhibited the growth of H1299 non-small cell lung cancer and SKBR-3 breast cancer cells with IC50 values of 1.41 and 0.70 μM, resp., while the standard topotecan inhibited their growth with IC50 values of 6.02 and 8.91 μM, resp. I (R = 5-Br-2-thienyl) inhibited the growth of MDA-MB-231 breast cancer cells with an IC50 value of less than 0.10 μM, while inhibiting the growth of noncancerous mammary epithelial cells at an IC50 value of 9.38 μM. I (R = 5-Br-2-thienyl) induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and cell death. The structure of I [R = 2,4-(MeO)2C6H3] was determined by X-ray crystallog.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 66373-25-9 belongs to class pyrimidines, name is 1-(2-Amino-4-methylpyrimidin-5-yl)ethanone, and the molecular formula is C7H9N3O, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Easmon, Johnny published the artcileSynthesis, Cytotoxicity, and Antitumor Activity of Copper(II) and Iron(II) Complexes of 4N-Azabicyclo[3.2.2]nonane Thiosemicarbazones Derived from Acyl Diazines, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone, the main research area is antitumor copper iron thiosemicarbazone complex synthesis Burkitt lymphoma.

A series of thiosemicarbazones (TSCs) (bearing a 4N-azabicyclo[3.2.2]nonane moiety) derived from 3-acylpyridazines, 4-acetylpyrimidines, and 2-acetylpyrazines were synthesized as potential antitumor agents. TSCs exhibited potent cytotoxic activity against human acute lymphoblastic leukemia CCRF-CEM cells (IC = 0.05-0.77 M) and colon adenocarcinoma HT-29 cells (IC = 0.011-2.22 M). Copper II complexes of TSCs showed significant improvement in cytotoxic activity against HT-29 cells (IC50 = 0.004-1.51 μM) by a factor of 3. However, complexation of some TSC ligands with Fe(II) results in lowering of cytotoxic activity by a factor of 7. In clonogenic assays involving human tumor cells of different tumor origins, three of the TSCs and their copper complexes exhibited remarkable cytotoxic activities with mean IC50 values of 6, 0.18, 1, 1, 0.37, and 0.37 nM, resp. In particular, the compounds were highly effective against human colon carcinoma and large and small cell lung carcinoma cells. One of the TSC derivative was evaluated in vivo in nude mice bearing LXFL 529 human large cell lung carcinoma cells. With respect to antitumor activity, application of 30 mg/kg/d resulted in moderate inhibition (42%) of tumor growth. No effect on tumor growth was observed at a dose of 10 mg/kg/d. However, a dose of 40 or 60 mg/kg/d resulted in 50 and 75% death, resp., in the treated mice, indicating the high toxicity of these compounds Using human liver microsomes, one of the TSC compound was rapidly and highly metabolized in vitro. In actual fact, only 2% of the unmetabolized compound could be detected in the incubation medium after 5 min. The IC50 for cell proliferation (0.006-0.022 μM) elicited by these compounds is much lower than that of the inhibition of [14C]cytidine incorporation into DNA (0.18-3.32 μM). These compounds are also non-cell cycle specific agents. Interestingly, three of these compounds were potent inducers of apoptosis in Burkitt’s lymphoma cells.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 67073-96-5 belongs to class pyrimidines, name is 1-(6-Methylpyrimidin-4-yl)ethanone, and the molecular formula is C7H8N2O, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Schinazi, Raymond F. published the artcileSynthesis of 5-(dihydroxyboryl)-2′-deoxyuridine and related boron-containing pyrimidines, Recommanded Product: 2,4,6-Tribromopyrimidine, the main research area is boryldeoxyuridine dihydroxy; uridine deoxy dihydroxyboryl; uracil dihydroxyboryl; virucide dihydroxyboryldeoxyuridine; neoplasm inhibitor dihydroxyboryldeoxyuridine.

Organoboron derivatives of pyrimidines and of 2′-deoxyribonucleosides were prepared as potential antiviral and anticancer agents. The title nucleoside (I) was prepared via a metal-halogen exchange at -50° in THF on 5-bromo-3′,5′-bis-O-(trimethylsilyl)-2′-deoxyuridine using BuLi followed by boronation at -65° with B(OBu)3 in the presence of HMPT. After hydrolysis, I was purified by column chromatog. and repeated fractional crystallization I was hydrolytically stable and showed no activity against Sarcoma 180 but inhibited herpes simplex virus type 1 at a nontoxic concentration I sensitized hamster V-79 cells to neutrons and could be of potential use in B neutron capture therapy. 5-(Dihydroxyboryl)uracil and 6-(dihydroxyboryl)uracil were similarly prepared The phys. characteristics of these analogs, as well as those of their iminodiethanol esters, are described.

Journal of Organic Chemistry published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Recommanded Product: 2,4,6-Tribromopyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia