Tag: 200-300

On January 27, 2015, Sozio, Piera; Fiorito, Jole; Di Giacomo, Viviana; Di Stefano, Antonio; Marinelli, Lisa; Cacciatore, Ivana; Cataldi, Amelia; Pacella, Stephanie; Turkez, Hasan; Parenti, Carmela; Rescifina, Antonio; Marrazzo, Agostino published an article.Computed Properties of 39512-49-7 The title of the article was Haloperidol metabolite II prodrug: Asymmetric synthesis and biological evaluation on rat C6 glioma cells. And the article contained the following:

In a previous work the authors reported the antiproliferative effects of (±)-MRJF4, a novel haloperidol metabolite II (HP-mII) (a sigma-1 antagonist and sigma-2 agonist) prodrug, obtained through conjugation to 4-phenylbutyric acid (PhBA) [a histone deacetylase inhibitor (HDACi)] by an ester bond. As a continuation of this work, here the authors report the asym. synthesis of compounds Benzenebutanoic acid 4-[(1R)-4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)butyl ester [(R)-(+)-MRJF4] and 4-[(1R)-4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)butyl ester [(S)-(-)-MRJF4] and the evaluation of their biol. activity on rat C6 glioma cells, derived from glioblastoma multiforme (GBM), which is the most common and deadliest central nervous system (CNS) invasive malignancy. Favorable physicochem. properties, high permeability in the parallel artificial membrane permeability assay (PAMPA), good enzymic and chem. stability, in vivo anticancer activity, associated with the capacity to reduce cell viability and to increase cell death by apoptosis, render compound (R)-(+)-MRJF4 a promising candidate for the development of a useful therapeutic for glioma therapy. The synthesis of the target compounds was achieved by a reaction of (αS)-4-(4-chlorophenyl)-α-(4-fluorophenyl)-4-hydroxy-1-piperidienbutanol or (αR)-4-(4-chlorophenyl)-α-(4-fluorophenyl)-4-hydroxy-1-piperidienbutanol with benzenebutanoyl chloride. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Computed Properties of 39512-49-7

The Article related to haloperidol metabolite prodrug anticancer antitumor glioma, benzenebutanoic acid hydroxypiperidine preparation anticancer agent cns glioma, glioma, hdac, inhibitors, medicinal chemistry, sigma receptors and other aspects.Computed Properties of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 15, 2004, Duan, Jingwu; King, Bryan W.; Decicco, Carl; Maduskuie, Thomas P.; Voss, Mathew E. published a patent.Electric Literature of 362703-57-9 The title of the patent was Preparation of β-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-α. And the patent contained the following:

Novel β-amino acid derivatives A-CR3R4aCR2R4NR1CO-X-Z-Ua-Xa-Ya-Za [A = CO2H, SH, CH2SH, S(O)Ra:NH (Ra = H, alkyl), P(O)(OH)2, etc.; X, Xa is absent or alkylene, alkenylene or alkynylene; Z is absent or substituted C3-13 carbocycle or 5-14 membered heterocycle; Ua is absent or O, NRa1 [Ra1 = H, (un)substituted alkyl, alkenyl or alkynyl; Ra and Ra1 may form a ring], CO, CO2, O2C, CONRa1, S(O)p (p = 0-2), etc.; Ya is absent or O, NRa1, S(O)p or CO; Za is H, substituted C3-13 carbocycle or 5-14 membered heterocycle; R1 is H, alkyl, Ph, benzyl; R2 is Q (Q is H, substituted carbocycle or heterocycle), alkylene-Q, (CRaRa1)r1O(CRaRa1)r-Q (r, r1 = 0-4), (CRaRa1)r1NRa(CRaRa1)r-Q, etc.; R3 = Q1 (Q1 is any group given for Q), alkylene-Q1, (CRaRa1)r1O(CRaRa1)r-Q1, (CRaRa1)r1NRa(CRaRa1)r-Q1, etc.; R4, R4a = H, substituted alkyl, alkenyl or alkynyl; alternatively R1 and R2, R1 and R3, R3 and R4a may form rings (with provisos)] or a stereoisomer or pharmaceutically acceptable salt were prepared as metalloprotease and TNF-α inhibitors. Thus, N-hydroxy-1-[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]acetyl]-3-azetidinecarboxamide was prepared by a multistep procedure involving reactions of Me 4-hydroxyphenylacetate, 2-methyl-4-quinolinylmethanol, and 3-azetidinecarboxylic acid Me ester. The experimental process involved the reaction of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate(cas: 362703-57-9).Electric Literature of 362703-57-9

The Article related to amino acid beta preparation inhibitor metalloprotease tnf, heterocyclyl beta amino acid preparation inhibitor metalloprotease tnf, cycloalkyl beta amino acid preparation inhibitor metalloprotease tnf and other aspects.Electric Literature of 362703-57-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On September 27, 2001, Duan, Jingwu; King, Bryan W.; Decicco, Carl; Maduskuie, Thomas P., Jr.; Voss, Matthew E. published a patent.Electric Literature of 362703-57-9 The title of the patent was Preparation of β-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-α. And the patent contained the following:

Novel β-amino acid derivatives A-CR3R4aCR2R4NR1CO-X-Z-Ua-Xa-Ya-Za [A = CO2H, SH, CH2SH, S(O)Ra:NH (Ra = H, alkyl), P(O)(OH)2, etc.; X, Xa is absent or alkylene, alkenylene or alkynylene; Z is absent or substituted C3-13 carbocycle or 5-14 membered heterocycle; Ua is absent or O, NRa1 [Ra1 = H, (un)substituted alkyl, alkenyl or alkynyl; Ra and Ra1 may form a ring], CO, CO2, O2C, CONRa1, S(O)p (p = 0-2), etc.; Ya is absent or O, NRa1, S(O)p or CO; Za is H, substituted C3-13 carbocycle or 5-14 membered heterocycle; R1 is H, alkyl, Ph, benzyl; R2 is Q (Q is H, substituted carbocycle or heterocycle), alkylene-Q, (CRaRa1)r1O(CRaRa1)r-Q (r, r1 = 0-4), (CRaRa1)r1NRa(CRaRa1)r-Q, etc.; R3 = Q1 (Q1 is any group given for Q), alkylene-Q1, (CRaRa1)r1O(CRaRa1)r-Q1, (CRaRa1)r1NRa(CRaRa1)r-Q1, etc.; R4, R4a = H, substituted alkyl, alkenyl or alkynyl; alternatively R1 and R2, R1 and R3, R3 and R4a may form rings (with provisos)] or a stereoisomer or pharmaceutically acceptable salt were prepared as metalloprotease and TNF-α inhibitors. Thus, N-hydroxy-1-[[4-[(2-methyl-4-quinolinyl)methoxy]phenyl]acetyl]-3-azetidinecarboxamide was prepared by a multistep procedure involving reactions of Me 4-hydroxyphenylacetate, 2-methyl-4-quinolinylmethanol, and 3-azetidinecarboxylic acid Me ester. The experimental process involved the reaction of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate(cas: 362703-57-9).Electric Literature of 362703-57-9

The Article related to amino acid beta preparation inhibitor metalloprotease tnf, heterocyclyl beta amino acid preparation inhibitor metalloprotease tnf, cycloalkyl beta amino acid preparation inhibitor metalloprotease tnf and other aspects.Electric Literature of 362703-57-9

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Application In Synthesis of (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylateOn June 10, 1996, Machetti, Fabrizio; Cordero, Franca M.; De Sarlo, Francesco; Guarna, Antonio; Brandi, Alberto published an article in Tetrahedron Letters. The article was 《Rearrangement of isoxazolidine 5-spiro derivates. 13. A new synthesis of (2S)-4-oxopipecolic acid by thermal rearrangement of enantiopure spirocyclopropaneisoxazolidine》. The article mentions the following:

A novel synthesis of (2S)-4-oxopipecolic acid is reported. The synthetic route employs as a key step the diastereoselective cycloaddition of the N-glycosylnitrone I to methylenecyclopropane followed by thermal rearrangement of the spirocyclopropaneisoxazolidine II. Stereoselective reduction of the N-Boc 4-oxopipecolic acid Et ester by L-selectride gives the protected cis-4-hydroxypipecolic acid III. The experimental part of the paper was very detailed, including the reaction process of (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate(cas: 180854-44-8Application In Synthesis of (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate)

(S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate(cas: 180854-44-8) 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.Application In Synthesis of (S)-1-tert-Butyl 2-ethyl 4-oxopiperidine-1,2-dicarboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2019,Organic Chemistry Frontiers included an article by Xu, Yuliang; Xu, Ze-Jun; Liu, Zhao-Peng; Lou, Hongxiang. Formula: C10H20N2O2. The article was titled 《Visible-light-mediated de-aminative alkylation of N-arylamines with alkyl Katritzky salts》. The information in the text is summarized as follows:

A visible-light-mediated de-aminative alkylation of N-arylamines was developed, providing direct access to α-amino C-H functionalization of N-arylamines from readily available Katritzky salts under mild conditions to get tetrahydroisoquinolines, e.g., I, and alkyl-N-aryl-aminoesters, e.g., II. In some cases, this operationally simple protocol could be performed in the absence of a photocatalyst. A wide range of substrates and functional groups were tolerated. The utility of this approach was highlighted by its application to the late-state modification of drug mols., natural products and peptides. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Formula: C10H20N2O2)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Formula: C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2019,ACS Central Science included an article by Lee, Kin Sing Stephen; Yang, Jun; Niu, Jun; Ng, Connie J.; Wagner, Karen M.; Dong, Hua; Kodani, Sean D.; Wan, Debin; Morisseau, Christophe; Hammock, Bruce D.. Electric Literature of C10H20N2O2. The article was titled 《Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways》. The information in the text is summarized as follows:

The drug discovery and development process is greatly hampered by difficulties in translating in vitro potency to in vivo efficacy. Recent studies suggest that the long-neglected drug-target residence time parameter complements classical drug affinity parameters (KI, Kd, IC50, or EC50) and is a better predictor of in vivo efficacy. Compounds with a long drug-target residence time are often more efficacious in vivo. The impact, however, of the drug-target residence time on in vivo efficacy remains controversial due to difficulties in exptl. determining the in vivo target occupancy during drug treatment. To tackle this problem, an in vivo displacement assay was developed using soluble epoxide hydrolase as a biol. model. In this report, we exptl. demonstrated that drug-target residence time affects the duration of in vivo drug-target binding. In addition, the drug-target residence time plays an important role in modulating the rate of drug metabolism which also affects the efficacy of the drug. In the experimental materials used by the author, we found tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Electric Literature of C10H20N2O2)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Electric Literature of C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Xue, Ding; Xu, Yibin; Kyani, Armita; Roy, Joyeeta; Dai, Lipeng; Sun, Duxin; Neamati, Nouri published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery and Lead Optimization of Benzene-1,4-disulfonamides as Oxidative Phosphorylation Inhibitors》.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Inhibition of oxidative phosphorylation (OXPHOS) is a promising therapeutic strategy for select cancers that are dependent on aerobic metabolism Here, we report the discovery, optimization, and structure-activity relationship (SAR) study of a series of novel OXPHOS inhibitors. The hit compound, benzene-1,4-disulfonamide 1 (I), was discovered in a phenotypic screen selective for cytotoxicity in a galactose-containing medium. Our multi-parameter optimization campaign led to the discovery of 65 (DX3-235)(II), showing nanomolar inhibition of complex I function and ATP production in a galactose-containing medium resulting in significant cytotoxicity. Importantly, 64 (DX3-234)(III), a close analog of 65, is well tolerated in mice and shows significant single agent efficacy in a Pan02 syngeneic pancreatic cancer model, suggesting that highly potent and selective OXPHOS inhibitors can be useful for the treatment of pancreatic cancer. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Li, Zilu; Zhang, Min; Teuscher, Kevin B.; Ji, Haitao published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of 1-Benzoyl 4-Phenoxypiperidines as Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction》.Synthetic Route of C10H19NO3 The article contains the following contents:

Structure-based design and optimization were performed to develop small-mol. β-catenin/B-cell lymphoma 9 (BCL9) inhibitors and improve their inhibitory activities. Compound ZL3138 with a novel 1-benzoyl 4-phenoxypiperidine scaffold was discovered to disrupt the β-catenin/BCL9 protein-protein interaction (PPI) with a Ki of 0.96μM in AlphaScreen competitive inhibition assays and displayed good selectivity for β-catenin/BCL9 over β-catenin/E-cadherin PPIs. The binding mode of new inhibitors was characterized by structure-activity relationship and site-directed mutagenesis studies. Protein pull-down assays indicate that this series of compounds directly binds with β-catenin. Cellular target engagement and co-immunoprecipitation experiments demonstrate that ZL3138 binds with β-catenin and disrupts the β-catenin/BCL9 interaction without affecting the β-catenin/E-cadherin interaction in living cells. Further cell-based studies show that ZL3138 selectively suppresses transactivation of Wnt/β-catenin signaling, regulates transcription and expression of Wnt target genes, and inhibits the growth of Wnt/β-catenin-dependent cancer cells. After reading the article, we found that the author used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Synthetic Route of 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.Synthetic Route of C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Recommanded Product: 136624-42-5On June 13, 2016, Stotani, Silvia; Lorenz, Christoph; Winkler, Matthias; Medda, Federico; Picazo, Edwige; Ortega Martinez, Raquel; Karawajczyk, Anna; Sanchez-Quesada, Jorge; Giordanetto, Fabrizio published an article in ACS Combinatorial Science. The article was 《Design and Synthesis of Fsp3-Rich, Bis-Spirocyclic-Based Compound Libraries for Biological Screening》. The article mentions the following:

The exploration of innovative chem. space is a critical step in the early phases of drug discovery. Bis-spirocyclic frameworks occur in natural products and other biol. relevant metabolites and show attractive features, such as mol. compactness, structural complexity, and three-dimensional character. A concise approach to the synthesis of bis-spirocyclic-based compound libraries starting from readily available com. reagents and robust chem. transformations has been developed. A number of novel bis-spirocyclic scaffold examples, as implemented in the European Lead Factory project, is presented. The experimental process involved the reaction of 4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5Recommanded Product: 136624-42-5)

4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5) belongs to anime. Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aromatic amines have the nitrogen atom connected to an aromatic ring.Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine (NClH2).Recommanded Product: 136624-42-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Optical resolution of amino acid derivatives by high-performance liquid chromatography on tris(phenylcarbamate)s of cellulose and amylose》 was written by Okamoto, Yoshio; Kaida, Yuriko; Aburatani, Ryo; Hatada, Koichi. Formula: C16H21NO4 And the article was included in Journal of Chromatography on August 30 ,1989. The article conveys some information:

The optical resolution of 10 N-protected alanine esters was examined by HPLC using 6 cellulose and 5 amylose tris(phenylcarbamate) derivatives as chiral stationary phases. Tris(3,5-dimethylphenylcarbamate)s of both cellulose and amylose showed high resolving power for these racemates. The resolution of 23 N-benzyloxycarbonyl α-amino acid ester was also tested on tris(3,5-dimethylphenylcarbamate)s of cellulose and amylose. All but 2 amino acid derivatives were completely resolved at least by one of the columns. On cellulose tris(3,5-dimethylphenylcarbamate), all L-amino acids (except threonine) eluted first. In the experiment, the researchers used 1-Benzyl 2-ethyl piperidine-1,2-dicarboxylate(cas: 126401-22-7Formula: C16H21NO4)

1-Benzyl 2-ethyl piperidine-1,2-dicarboxylate(cas: 126401-22-7) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Formula: C16H21NO4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem