Month: November 2022

Yan, Luping published the artcileStructure-Activity Relationships for the Marine Natural Product Sintokamides: Androgen Receptor N-Terminus Antagonists of Interest for Treatment of Metastatic Castration-Resistant Prostate Cancer, Application of Methyl 4,4,4-trichlorobutanoate, the main research area is marine sintokamide androgen receptor antagonist prostate cancer antitumor preparation.

Synthetic analogs of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogs. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogs missing the nonchlorinated Me groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogs with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the Me ether on the tetramic acid fragment are essential for activity. The SAR optimized analog 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.

Journal of Natural Products published new progress about Antitumor agents. 19376-57-9 belongs to class chlorides-buliding-blocks, name is Methyl 4,4,4-trichlorobutanoate, and the molecular formula is C5H7Cl3O2, Application of Methyl 4,4,4-trichlorobutanoate.

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

Di Matteo, Mauro published the artcileSynthesis and biological characterization of 3-(imidazol-1-ylmethyl)piperidine sulfonamides as aromatase inhibitors, Category: chlorides-buliding-blocks, the main research area is imidazolylmethylpiperidine sulfonamide preparation aromatase inhibitor; Anticancer agents; Aromatase inhibitor; Imidazole; Sulfonamide; Synthesis.

The most frequently used treatment for hormone receptor pos. breast cancer in post-menopausal women are aromatase inhibitors. In order to develop new aromatase inhibitors, we designed and synthesized new imidazolylmethylpiperidine sulfonamides using the structure of the previously identified aromatase inhibitor SYN 20028567 as starting lead. By this approach, three new aromatase inhibitors with IC50 values that are similar to that of letrozole and SYN 20028567 were identified.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 7079-48-3 belongs to class chlorides-buliding-blocks, name is 4-Fluoro-2-methylbenzene-1-sulfonyl chloride, and the molecular formula is C7H6ClFO2S, Category: chlorides-buliding-blocks.

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

Nam, Nguyen-Hai published the artcileSynthesis, bioevaluation and docking study of 5-substituted phenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents, Quality Control of 89978-31-4, the main research area is thiadiazole hydroxamic acid preparation histone deacetylase inhibitor antitumor; 5-phenyl-1,3,4-thiadiazole; cytotoxicity; heterocycle; histone deacetylase (HDAC) inhibitors.

Since the first histone deacetylase (HDAC) inhibitor (Zolinza, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of the ongoing research in this area, the authors designed and synthesized a series of thiadiazole-based hydroxamic acids I [R = H, 2-Cl, 4-Me, etc.] as analogs of SAHA and evaluated their biol. activities. A number of compounds in this series, e.g. I [R = H], I [R = 2-Cl], I [R = 4-MeO], were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. These compounds were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 89978-31-4 belongs to class chlorides-buliding-blocks, name is 5-(2,6-Dichlorophenyl)-1,3,4-thiadiazol-2-amine, and the molecular formula is C8H5Cl2N3S, Quality Control of 89978-31-4.

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

Kohlmann, Anna published the artcileFragment Growing and Linking Lead to Novel Nanomolar Lactate Dehydrogenase Inhibitors, Formula: C7H6ClNO4, the main research area is preparation lactate dehydrogenase A inhibitor cancer.

Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small mols. is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (Kd) and enzyme inhibition (IC50) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, resp. The binding modes of selected fragments were investigated by X-ray crystallog. Fragment growing and linking, followed by chem. optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected mols. inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.

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, Formula: C7H6ClNO4.

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

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

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

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

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

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