Day: October 18, 2022

The author of 《Preclinical efficacy of a novel dual PI3K/mTOR inhibitor, CMG002, alone and in combination with sorafenib in hepatocellular carcinoma》 were Kim, Mi Na; Lee, Seung Min; Kim, Jin Sung; Hwang, Seong Gyu. And the article was published in Cancer Chemotherapy and Pharmacology in 2019. Synthetic Route of C10H20N2O2 The author mentioned the following in the article:

Sorafenib has been the only first systemic drug that improves survival of patients with advanced hepatocellular carcinoma (HCC). However, because the response rate of sorafenib is relatively low, novel therapeutic strategies are needed to improve survival in patients with HCC. This study investigated the effect of CMG002 alone and in combination with sorafenib on HCC in vitro and vivo. The effect of a newly developed dual PI3K/mTOR inhibitor, CMG002, on the proliferation of Huh-7 and HepG2 HCC cells was investigated using the MTT assay. Western blotting was performed to assess phosphorylation of the key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. HepG2 cells were inoculated into mice, which were treated with vehicle, sorafenib, CMG002, and their combinations. Tumor cell proliferation and tumor angiogenesis were evaluated by immunohistochem. anal. of Ki-67 and CD31, resp. Tumor cell apoptosis was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Levels of key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways were evaluated by western blot anal. The combination of sorafenib and CMG002 additively inhibited Huh-7 and HepG2 cell proliferation compared to single-agent treatment. Sorafenib and CMG002 as single agents differentially inhibited or activated key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. The combination of sorafenib and CMG002 inhibited all key enzymes in the two pathways. Treatment with CMG002 for 4 wk alone and in combination with sorafenib strongly inhibited tumor growth. CMG002 inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Furthermore, these effects were enhanced when CMG002 was combined with sorafenib. The combination of CMG002 and sorafenib significantly inhibited HCC cell proliferation and tumorigenesis by inhibiting the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. These findings suggest that CMG002 to be a potential novel candidate treatment for HCC. After reading the article, we found that the author used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Synthetic Route of C10H20N2O2)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Synthetic Route of C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Novel pleuromutilin derivatives with substituted 6-methylpyrimidine: Design, synthesis and antibacterial evaluation》 was written by Fan, Yuan; Liu, Yu; Wang, Hao; Shi, Tao; Cheng, Feng; Hao, Baocheng; Yi, Yunpeng; Shang, Ruofeng. SDS of cas: 622-26-4 And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

A series of novel pleuromutilin derivatives with substituted 6-methylpyrimidine moieties was designed, synthesized, and evaluated for their antibacterial activities. Most of the tested compounds exhibited potent antibacterial activities against Staphylococcus aureus ATCC 25923 (S. aureus-25923), methicillin-resistant Staphylococcus epidermidis ATCC 51625 (MRSE-51625), methicillin-resistant Staphylococcus aureus BNCC 337371 (MRSA-337371), Streptococcus dysgalactiae (S. dysgalactiae) and Streptococcus agalactiae (S. agalactiae). Compounds I (NR1R2 = pyrrolidino, morpholino) were the most active and displayed bacteriostatic activities against MRSA. In vivo mouse systemic infection experiment showed that I (NR1R2 = pyrrolidino) significantly improved the survival rate of mice (ED50 = 18.02 mg/kg), reduced the bacterial load and alleviated the pathol. changes in the lungs of the affected mice. In the part of experimental materials, we found many familiar compounds, such as 2-(Piperidin-4-yl)ethanol(cas: 622-26-4SDS of cas: 622-26-4)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKSDS of cas: 622-26-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Zhuming; Connolly, Peter J.; Trabalon Escolar, Luis; Rocaboy, Christian; Pande, Vineet; Meerpoel, Lieven; Lim, Heng-Keang; Branch, Jonathan R.; Ondrus, Janine; Hickson, Ian; Bush, Tammy L.; Bischoff, James R.; Bignan, Gilles published their research in ACS Medicinal Chemistry Letters in 2021. The article was titled 《Spirocyclic Thiohydantoin Antagonists of F877L and Wild-Type Androgen Receptor for Castration-Resistant Prostate Cancer》.Formula: C10H19NO3 The article contains the following contents:

Androgen receptor (AR) transcriptional reactivation plays a key role in the development and progression of lethal castration-resistant prostate cancer (CRPC). Recurrent alterations in the AR enable persistent AR pathway signaling and drive resistance to the treatment of second-generation antiandrogens. AR F877L, a point mutation in the ligand binding domain of the AR, was identified in patients who acquired resistance to enzalutamide or apalutamide. In parallel to our previous structure-activity relationship (SAR) studies of compound 4 (JNJ-pan-AR) and clin. stage compound 5 (JNJ-63576253), we discovered addnl. AR antagonists that provide opportunities for future development. Here we report a highly potent series of spirocyclic thiohydantoins as AR antagonists for the treatment of the F877L mutant and wild-type CRPC. A chirally pure enantiomer,(R)-29 (I) is a full antagonist against AR F877L. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Formula: C10H19NO3)

tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Formula: C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Huang, Mingming; Hu, Jiefeng; Krummenacher, Ivo; Friedrich, Alexandra; Braunschweig, Holger; Westcott, Stephen A.; Radius, Udo; Marder, Todd B. published an article in Chemistry – A European Journal. The title of the article was 《Base-Mediated Radical Borylation of Alkyl Sulfones》.Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate The author mentioned the following in the article:

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal-free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2neop2), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late-stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates. In the experiment, the researchers used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate)

tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Cao, Yu; Tu, Yutong; Fu, Liping; Yu, Qian; Gao, Lixin; Zhang, Mengmeng; Zeng, Linghui; Zhang, Chong; Shao, Jiaan; Zhu, Huajian; Zhou, Yubo; Li, Jia; Zhang, Jiankang published an article in European Journal of Medicinal Chemistry. The title of the article was 《Metabolism guided optimization of peptidomimetics as non-covalent proteasome inhibitors for cancer treatment》.Name: tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

A series of novel non-covalent peptidomimetic proteasome inhibitors possessing bulky group at the C-terminus and N-alkylation at the N-terminus were designed with the aim to increase metabolic stabilities in vivo. All the target compounds were screened for their inhibitory activities against human 20S proteasome, and most analogs exhibited notable potency compared with the pos. control bortezomib with IC50 values lower than 10 nM, which also displayed potent cytotoxic activities against multiple myeloma (MM) cell lines and human acute myeloid leukemia (AML) cells. Furthermore, whole blood stability and in vivo proteasome inhibitory activity experiments of selected compounds were conducted for further evaluation, and the representative compound 43 (IC50 = 8.39 ± 2.32 nM, RPMI-8226: IC50 = 15.290 ± 2.281 nM, MM-1S: IC50 = 9.067 ± 3.103 nM, MV-4-11: IC50 = 2.464 ± 0.713 nM) revealed a half-life extension of greater than 9-fold (329.21 min VS 36.79 min) and potent proteasome inhibitory activity in vivo. The pos. results confirmed the reliability of the metabolism guided optimization strategy, and the analogs discovered are potential leads for exploring new anti-MM drugs. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Name: tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Name: tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Safety of 2-(Piperidin-4-yl)ethanolIn 2014 ,《Synthesis and in vitro evaluation of tetrahydroisoquinolines with pendent aromatics as sigma-2 (σ2) selective ligands》 was published in Organic & Biomolecular Chemistry. The article was written by Ashford, Mark E.; Nguyen, Vu H.; Greguric, Ivan; Pham, Tien Q.; Keller, Paul A.; Katsifis, Andrew. The article contains the following contents:

5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl]-2,3-dimethoxybenzamide 1 is a potent and selective σ2 receptor ligand suitable for further development. A series of new analogs, incorporating a variety of isoquinoline and carboxylic acid moieties,e.g. I [R = 2-indolyl, styryl, 1-naphthyl, etc.], linked together with either a linear or cyclic amine spacer have been synthesized and assessed for their σ1/σ2 binding affinity and selectivity. Compounds with a rigid piperidine spacer gave Ki values for the σ2 receptor between 8.7-845 nM. Changing the configuration of the methoxy groups on the isoquinoline moiety resulted in mols. with σ2Ki values of 4.4-133 nM whereas varying the length and flexibility of the carbon spaces gave σ2Ki values 0.88-15.0 nM, some of the most active, selective σ2 ligands to date. Thus, the flexibility and length of the carbon linker and the carboxylic acid moiety are confirmed to be key to the exceptional binding affinity and selectivity for this active series. Addnl., the incorporation of a halogen on selected carboxylic acid moieties provided a convenient strategy for the introduction of a radiohalogen for applications in pharmacol. and imaging studies. In the experiment, the researchers used 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Safety of 2-(Piperidin-4-yl)ethanol)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKSafety of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Design, synthesis and biological evaluation of imidazo[1,5-a]pyrazin-8(7H)-one derivatives as BRD9 inhibitors》 was written by Zheng, Peiyuan; Zhang, Jian; Ma, Hui; Yuan, Xinrui; Chen, Pan; Zhou, Jinpei; Zhang, Huibin. HPLC of Formula: 39546-32-2 And the article was included in Bioorganic & Medicinal Chemistry on April 1 ,2019. The article conveys some information:

BRD9 is the subunit of mammalian SWI/SNF chromatin remodeling complex (BAF). SWI/SNF complex mutations were found in nearly 20% of human cancers. The biol. role played by BRD9 bromodomain remains poorly understood, and it is therefore imperative to identify potent and highly selective inhibitors to effectively explore the biol. of individual bromodomain proteins. In this paper, we synthesized a series of imidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD9 inhibitors and evaluated their BRD9 inhibitory activity in vitro and anti-proliferation effects against tumor cells. Gratifyingly, compound 27(I) and 29(II) exhibited robust potency of BRD9 inhibition with IC50 values of 35 and 103 nM resp. Docking studies were performed to explain the structure-activity relationship. Furthermore, I potently inhibited cell proliferation in cell lines A549 and EOL-1 with an IC50 value of 6.12 μM and 1.76 μM resp. The chem. probe, I, was identified that should prove to be useful in further exploring BRD9 bromodomain biol. in both in vitro and in vivo settings. In the experimental materials used by the author, we found Piperidine-4-carboxamide(cas: 39546-32-2HPLC of Formula: 39546-32-2)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Examples of direct uses of amines and their salts are as corrosion inhibitors in boilers and in lubricating oils (morpholine), as antioxidants for rubber and roofing asphalt (diarylamines), as stabilizers for cellulose nitrate explosives (diphenylamine), as protectants against damage from gamma radiation (diarylamines), as developers in photography (aromatic diamines), as flotation agents in mining, as anticling and waterproofing agents for textiles, as fabric softeners, in paper coating, and for solubilizing herbicides.HPLC of Formula: 39546-32-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Category: piperidinesOn November 30, 2007 ,《Development and validation of TLC-densitometric method for resolution and determination of enantiomeric purity of ropivacaine, using different cyclodextrins as chiral selector》 appeared in Current Pharmaceutical Analysis. The author of the article were Taha, Elham A.. The article conveys some information:

A novel economic procedure for stereoselective separation and determination of R(+)- and S(-)- ropivacaine was described using different thin layer chromatog. plates and different cyclodextrins at different temperatures The spots were detected either with iodine vapors or UV lamp 254 nm, followed by densitometric measurements at 262 nm. Comparative study was achieved using different cyclodextrins namely, hydroxypropyl-β-cyclodextrin (HP-β-CD), methyl-β-cyclodextrin (M-β-CD), and dimethyl-β-cyclodextrin (DM-β-CD) as chiral selectors. The mobile phase enabling successful resolution of (±) ropivacaine was acetonitrile: water (17:3 volume/volume) containing 1 mM of DM-β-CD at ambient temperature 25 ± 2°. All variables affecting the resolution, such as concentration of different chiral selectors, temperature, and pH were investigated and the conditions were optimized. The procedure provided a linear response over the concentration range of 1.25-35 μg/spot for determination of R(+)- and S(-)- enantiomers (r = 0.9998, n = 8), (r = 0.9998, n = 6) with acceptable precision (% RSD <1.5) and accuracy (% RE = -1.18 to 2.00). Limits of detection and quantification were found to be 0.29 μg/spot and 0.96 μg/spot for (R) and 0.26 μg/spot and 0.86 μg/spot for (S) resp. The developed method was validated and proved to be robust. Ropivacaine sample solution was found to be stable for one weak in methanol. The proposed method was found to be selective and accurate for identification and quant. determination of enantiomeric purity of ropivacaine in bulk powder and pharmaceutical dosage form. In the experiment, the researchers used (R)-N-(2,6-Dimethylphenyl)-1-propylpiperidine-2-carboxamide hydrochloride(cas: 112773-90-7Category: piperidines)

(R)-N-(2,6-Dimethylphenyl)-1-propylpiperidine-2-carboxamide hydrochloride(cas: 112773-90-7) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Related Products of 1690-72-8On October 31, 1990 ,《Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors》 appeared in Journal of Medicinal Chemistry. The author of the article were Street, Leslie J.; Baker, Raymond; Book, Tracey; Kneen, Clare O.; MacLeod, Angus M.; Merchant, Kevin J.; Showell, Graham A.; Saunders, John; Herbert, Richard H.. The article conveys some information:

The synthesis and biochem. evaluation of novel 1,2,4-oxadiazole-based muscarinic agonists which can readily penetrate into the CNS is reported. Efficacy and binding of these compounds are markedly influenced by the structure and physicochem. properties of the cationic head group. In a series of azabicyclic ligands efficacy and affinity are influenced by the size of the surface area presented to the receptor at the active site, and the degree of conformational flexibility. The exo-1-azanorbornane I represents the optimum arrangement, and this compound is one of the most efficacious and potent muscarinic agonists known. In a series of isoquinuclidine-based muscarinic agonists efficacy and affinity are influenced by the geometry between the cationic head group and H-bond acceptor pharmacophore and steric bulk in the vicinity of the base. The anti configuration represented by II is optimal for muscarinic activity. Ligands with pKa <6.5 show poor binding to the muscarinic receptor as exemplified by the diazabicyclic derivative III. In the experiment, the researchers used Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8Related Products of 1690-72-8)

Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Related Products of 1690-72-8

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

HPLC of Formula: 39546-32-2On March 1, 2021, Mizukawa, Yuki; Ikegami-Kawai, Mayumi; Horiuchi, Masako; Kaiser, Marcel; Kojima, Masayoshi; Sakanoue, Seiki; Miyagi, Seiya; Nanga Chick, Christian; Togashi, Hiroyuki; Tsubuki, Masayoshi; Ihara, Masataka; Usuki, Toyonobu; Itoh, Isamu published an article in Bioorganic & Medicinal Chemistry. The article was 《Quest for a potent antimalarial drug lead: Synthesis and evaluation of 6,7-dimethoxyquinazoline-2,4-diamines》. The article mentions the following:

Quinazolines have long been known to exert varied pharmacol. activities that make them suitable for use in treating hypertension, viral infections, tumors, and malaria. Since 2014, author’s have synthesized approx. 150 different 6,7-dimethoxyquinazoline-2,4-diamines and evaluated their antimalarial activity via structure-activity relationship studies. Here, author’s summarize the results and report the discovery of 6,7-dimethoxy-N4-(1-phenylethyl)-2-(pyrrolidin-1-yl)quinazolin-4-amine, which exhibits high antimalarial activity as a promising antimalarial drug lead. The results came from multiple reactions, including the reaction of Piperidine-4-carboxamide(cas: 39546-32-2HPLC of Formula: 39546-32-2)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).HPLC of Formula: 39546-32-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem