Category: chlorides-buliding-blocks

Wilson, Jennifer M. published the artcileSynthesis of 5-deazaflavin derivatives and their activation of p53 in cells, Name: 2-Chloro-3-(trifluoromethyl)benzaldehyde, the main research area is structure deazaflavin derivative preparation p53 antitumor apoptosis E3 HMD2.

A family of 5-deazaflavin derivatives has been synthesized using a two-step convergent strategy. The biol. activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low mol. weight inhibitors of the E3 activity of HMD2 in tumors that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biol. activity.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 93118-03-7 belongs to class chlorides-buliding-blocks, name is 2-Chloro-3-(trifluoromethyl)benzaldehyde, and the molecular formula is C8H4ClF3O, Name: 2-Chloro-3-(trifluoromethyl)benzaldehyde.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Luecking, Ulrich published the artcileChanging for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for Once Weekly Intravenous Dosing for the Treatment of Cancer, Quality Control of 1214344-25-8, the main research area is CDK9 inhibitor VIP152 weekly intravenous dosing cancer; diffuse large B cell lymphoma.

Selective inhibition of exclusively transcription-regulating pos. transcription elongation factor b/CDK9 is a promising new approach in cancer therapy. Starting from atuveciclib, the first selective CDK9 inhibitor to enter clin. development, lead optimization efforts aimed at identifying i.v. (iv) applicable CDK9 inhibitors with an improved therapeutic index led to the discovery of the highly potent and selective clin. candidate VIP152 (I). The evaluation of various scaffold hops was instrumental in the identification of VIP152, which is characterized by the underexplored benzyl sulfoximine group. VIP152 exhibited the best preclin. overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats upon once weekly iv administration. VIP152 has entered clin. trials for the treatment of cancer with promising longterm, durable monotherapy activity in double-hit diffuse large B-cell lymphoma patients.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 1214344-25-8 belongs to class chlorides-buliding-blocks, name is 1-(Chloromethyl)-3-fluoro-5-nitrobenzene, and the molecular formula is C7H5ClFNO2, Quality Control of 1214344-25-8.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Yamada, Ken published the artcileDiscovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma, Formula: C8H5BrClF3, the main research area is CETP inhibition piperidine analog hypertriglyceridemic plasma activity; piperidine analog preparation hypertriglyceridemic plasma activity.

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead mol. with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound I (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclin. efficacy and safety profile, the compound was advanced into clin. trials.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 886496-91-9 belongs to class chlorides-buliding-blocks, name is 1-(Bromomethyl)-3-chloro-5-(trifluoromethyl)benzene, and the molecular formula is C8H5BrClF3, Formula: C8H5BrClF3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Ashraf-Uz-Zaman, Md. published the artcileDesign, synthesis and structure-activity relationship study of novel urea compounds as FGFR1 inhibitors to treat metastatic triple-negative breast cancer, COA of Formula: C13H9ClO2, the main research area is structure preparation urea compound FGFR1 inhibitor metastatic breast cancer; Blood-brain-barrier; FGFR1; In silico; Neurotoxicity; Synthesis; Triple-negative breast cancer.

Triple-neg. breast cancer (TNBC) is an aggressive type of cancer characterized by higher metastatic and reoccurrence rates, where approx. one-third of TNBC patients suffer from the metastasis in the brain. At the same time, TNBC shows good responses to chemotherapy, a feature that fuels the search for novel compounds with therapeutic potential in this area. Recently, we have identified novel urea-based compounds with cytotoxicity against selected cell lines and with the ability to cross the blood-brain barrier in vivo. We have synthesized and analyzed a library of more than 40 compounds to elucidate the key features responsible for the observed activity. We have also identified FGFR1 as a mol. target that is affected by the presence of these compounds, confirming our data using in silico model. Overall, we envision that these compounds can be further developed for the potential treatment of metastatic breast cancer.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 61343-99-5 belongs to class chlorides-buliding-blocks, name is 4-(4-Chlorophenoxy)benzaldehyde, and the molecular formula is C13H9ClO2, COA of Formula: C13H9ClO2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Ruchelman, Alexander L. published the artcileIsosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity, HPLC of Formula: 99585-12-3, the main research area is dioxopiperidinyl isoindolinone isoindoledione preparation antitumor antiinflammatory agent; structure dioxopiperidinyl isoindolinone isoindoledione inhibition TNF alpha; antitumor immunomodulation activity dioxopiperidinyl isoindolinone isoindoledione; bioavailability dioxopiperidinyl isoindolinone isoindoledione TNF alpha inhibitor.

Dioxopiperidinyl isoindolinones such as I (R = Cl, Me) and dioxopiperidinyl isoindolediones were prepared as analogs of the immunomodulary drugs lenalidomide and pomalidomide for potential use as antiinflammatory and antitumor agents. I (R = Me) and I (R = Cl), resp., displayed potent inhibition of tumor necrosis factor-α (TNF-α) in lipopolysaccharide-stimulated human peripheral blood mononuclear cells, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against Namalwa human lymphoma cells. I (R = Cl, Me) were orally bioavailable in rats.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 99585-12-3 belongs to class chlorides-buliding-blocks, name is Methyl 4-chloro-2-methylbenzoate, and the molecular formula is C9H9ClO2, HPLC of Formula: 99585-12-3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Lakhani, Kinjal published the artcileDesign, Syntheses, and Bioevaluations of Some Novel N2-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents, Related Products of chlorides-buliding-blocks, the main research area is acryloylbenzohydrazide chemostimulant cytotoxic agent colon breast cancer human; acryloylhydrazides; antineoplastic agents; chemosensitization; cytotoxins; mitochondrial membrane potential; reactive oxygen species.

A series of novel N2-acryloylhydrazides 1a-m and a related series of compounds 6a-c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the mol. features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.

Medicines published new progress about Antitumor agents. 35112-27-7 belongs to class chlorides-buliding-blocks, name is Ethyl 2,5-dichlorobenzoate, and the molecular formula is C9H8Cl2O2, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Czako, Barbara published the artcileDiscovery of IACS-9439, a Potent, Exquisitely Selective, and Orally Bioavailable Inhibitor of CSF1R, Related Products of chlorides-buliding-blocks, the main research area is discovery IACS 9439 preparation inhibitor CSF1R SAR anticancer.

Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Addnl., the high expression of CSF1R on tumor cells has been associated with poor survival in certain cancers, suggesting tumor dependency and therefore a potential therapeutic target. The CSF1-CSF1R signaling pathway modulates the production, differentiation, and function of TAMs; however, the discovery of selective CSF1R inhibitors devoid of type III kinase activity has proven to be challenging. We discovered a potent, highly selective, and orally bioavailable CSF1R inhibitor, IACS-9439 (I). Treatment with I led to a dose-dependent reduction in macrophages, promoted macrophage polarization toward the M1 phenotype, and led to tumor growth inhibition in MC38 and PANC02 syngeneic tumor models.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 100959-51-1 belongs to class chlorides-buliding-blocks, name is 2-Chloro-5-methoxy-4-nitrophenol, and the molecular formula is C7H6ClNO4, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Woo, L. W. Lawrence published the artcileDual Aromatase-Steroid Sulfatase Inhibitors, Name: 3-Chloro-4-hydroxy-5-methoxybenzoic acid, the main research area is YM511 sulfamate analog preparation structure aromatase steroid sulfatase inhibitor.

By introducing the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. Two best DASIs (I and II) in vitro (JEG-3 cells) had IC50(aromatase) = 0.82 nM; IC50(sulfatase) = 39 nM, and IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM, resp. X-ray crystallog. of I, and docking studies of selected compounds into an aromatase homol. model and the steroid sulfatase crystal structure are presented. Both I and II inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for I but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI I did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.

Journal of Medicinal Chemistry published new progress about Aromatase inhibitors. 62936-23-6 belongs to class chlorides-buliding-blocks, name is 3-Chloro-4-hydroxy-5-methoxybenzoic acid, and the molecular formula is C8H7ClO4, Name: 3-Chloro-4-hydroxy-5-methoxybenzoic acid.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Benniston, Andrew C. published the artcileIntramolecular excimer formation and delayed fluorescence in sterically constrained pyrene dimers, Safety of Pyrene-2-carboxylic acid, the main research area is intramol excimer delayed fluorescence sterically constrained pyrene dimer.

The synthesis is described for five mol. dyads comprising pyrene-based terminals covalently linked through a 1,3-disubstituted phenylene spacer. The extent of through-space communication between the pyrene units is modulated by steric interactions imposed by bulky moieties attached at the 6,8-positions of each pyrene unit. For the control compound, only hydrogen atoms occupy the 6,8 positions (DP1), whereas the remaining compounds incorporate ethynylene groups terminated with either triisopropylsilyl (DP2), 1-tert-butylbenzene (DP3), 2,6-di-tert-butylbenzene (DP4) or 1-tert-butyl-3,5-dimethylbenzene (DP5) units. Each compound shows a mixture of monomer and excimer fluorescence in fluid solution at room temperature, but only monomer emission in a glassy matrix at 77 K. The ratio of monomer to excimer fluorescence depends markedly on the mol. structure; DP1 is heavily biased in favor of the excimer and DP4 is enriched with monomer fluorescence. Photophys. properties, including laser induced and delayed fluorescence data, are reported for each compound Delayed fluorescence occurs by both intramol. and bimol. steps, but these events take place on different timescales. The possibility is raised for using intramol. triplet-triplet annihilation as a means of mol. imaging.

Chemistry – A European Journal published new progress about Correlation analysis. 36428-96-3 belongs to class chlorides-buliding-blocks, name is Pyrene-2-carboxylic acid, and the molecular formula is C17H10O2, Safety of Pyrene-2-carboxylic acid.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Deng, Guanghui published the artcileNovel complex crystal structure of prolyl hydroxylase domain-containing protein 2 (PHD2): 2,8-Diazaspiro[4.5]decan-1-ones as potent, orally bioavailable PHD2 inhibitors, Related Products of chlorides-buliding-blocks, the main research area is crystal structure prolyl hydroxylase domain protein diazaspirodecanone; 2,8-Diazaspiro[4.5]decan-1-one; Hypoxia inducible factor (HIF); PHD inhibitors; PHD2 crystal structure; Prolyl hydroxylase domain-containing protein 2 (PHD2); SAR study.

We have discovered a novel complex crystal structure of the PHD2 enzyme with its inhibitor, the 2,8-diazaspiro[4.5]decan-1-one analog 4b. The widely reported salt bridge between Arg383 of the enzyme and its inhibitors in all complex structures published thus far was not observed in our case. In our complex structure compound 4b forms several novel interactions with the enzyme, which include a hydrogen bond with Arg322, a π-cation interaction with Arg322, a π-π stacking with Trp389, and a π-π stacking with His313. Guided by the structural information, SAR studies were performed on the 2,8-diazaspiro[4.5]decan-1-one series leading to the discovery of compound 9p with high potency and good oral pharmacokinetic profile in mice.

Bioorganic & Medicinal Chemistry published new progress about Drug bioavailability. 6797-79-1 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-fluoroiodobenzene, and the molecular formula is C6H3ClFI, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics