Tag: 200-300

《Novel colchicine conjugate with unusual effect on the microtubules of cancer cells》 was published in Pure and Applied Chemistry in 2020. These research results belong to Zefirova, Olga N.; Nurieva, Evgenia V.; Wobith, Birgit; Schulz, Svetlana; Zefirov, Nikolay A.; Kuznetsov, Sergei A.. Synthetic Route of C10H19NO3 The article mentions the following:

Colchicine derivative bearing substituted bispidine moiety, namely N-{7-(3,7-Di-(tert-butoxycarbonyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-yl)-oxy-7-oxoheptanoyl}-N-deacetylcolchicine, was synthesized and tested for its effect on the net of microtubules (MT) in lung cancer cells A549. The compound induced not only MT depolymerization but stimulated the formation of small tubulin aggregates and long tubulin fibrils localized mainly around nuclei. The assemblies were morphol. different from tubulin clusters induced by structurally related anticancer agent tubuloclustin. The biotests data demonstrate that the depolymerization takes place for both pure tubulin and tubulin in cellulo, while fibrils are formed only in the cells. The research data of structure-activity relationship for several similar colchicine derivatives synthesized in the work give evidence for the proposition that the initial conjugate may interact not only with tubulin and MT in the cells, but also with MT-associated proteins, involved in the process of tubulin polymerization The ability to affect simultaneously MAP – tubulin interactions opens attractive prospects in the design of novel anticancer agents. The experimental process involved the reaction of 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

Sasakura, Kazuyuki; Adachi, Makoto; Sugasawa, Tsutomu published their research in Synthetic Communications on February 29 ,1988. The article was titled 《Simple synthesis of 1-(azacycloalkyl)indoles using exclusive ortho α-chloroacetylation of N-(azacycloalkyl)anilines》.Recommanded Product: 1-(Piperidin-4-yl)-1H-indole The article contains the following contents:

Indoles I (n = 1,2; R1 = H, F; R2 = H, halo, OMe) were prepared from the resp. 2-amino-2-chloroacetophenones II (R3 = Me, PhCH2) by sequential hydride reduction, cyclization, dealkylation-acylation with ClCO2Et, and deacylation. In the part of experimental materials, we found many familiar compounds, such as 1-(Piperidin-4-yl)-1H-indole(cas: 118511-81-2Recommanded Product: 1-(Piperidin-4-yl)-1H-indole)

1-(Piperidin-4-yl)-1H-indole(cas: 118511-81-2) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Recommanded Product: 1-(Piperidin-4-yl)-1H-indole

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Structure-Based Bioisosterism Yields HIV-1 NNRTIs with Improved Drug-Resistance Profiles and Favorable Pharmacokinetic Properties》 was written by Kang, Dongwei; Feng, Da; Sun, Yanying; Fang, Zengjun; Wei, Fenju; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng. Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylateThis research focused onthiophenepyrimidine piperidine substituted preparation antiHIV activity. The article conveys some information:

The development of efficacious NNRTIs for AIDS therapy commonly encountered the rapid generation of drug-resistant mutations, which becomes a major impediment to effective anti-HIV treatment. Using a structure-based bioisosterism strategy, a series of piperidine-substituted thiophene[2,3-d]pyrimidine derivatives were designed and synthesized. Compound I yielded the greatest potency, exhibiting significantly better anti-HIV-1 activity than ETR against all of the tested NNRTI-resistant HIV-1 strains. In addition, the phenotypic (cross)resistance of I and other NRTIs to the different selected HIV-1 strains was evaluated. As expected, no phenotypic cross-resistance against the NRTIs (AZT and PMPA) was observed with the mutant Ires strain. Furthermore, I was identified with improved solubility, lower CYP liability, and hERG inhibition. Remarkably, I exhibited optimal pharmacokinetic properties in rats (F = 37.06%) and safety in mice (LD50 > 2000 mg/kg), which highlights I as a promising anti-HIV-1 drug candidate. After reading the article, we found that the author used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Quality Control 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.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Zhuming; Connolly, Peter J.; Lim, Heng Keang; Pande, Vineet; Meerpoel, Lieven; Teleha, Christopher; Branch, Jonathan R.; Ondrus, Janine; Hickson, Ian; Bush, Tammy; Luistro, Leopoldo; Packman, Kathryn; Bischoff, James R.; Ibrahim, Salam; Parrett, Christopher; Chong, Yolanda; Gottardis, Marco M.; Bignan, Gilles published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of JNJ-63576253: A Clinical Stage Androgen Receptor Antagonist for F877L Mutant and Wild-Type Castration-Resistant Prostate Cancer (mCRPC)》.Related Products of 109384-19-2 The article contains the following contents:

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clin. relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clin. stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC). The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Related Products of 109384-19-2)

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.Related Products of 109384-19-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Schade, Markus; Merla, Beatrix; Lesch, Bernhard; Wagener, Markus; Timmermanns, Simone; Pletinckx, Katrien; Hertrampf, Torsten. Computed Properties of C10H19NO3 The article mentions the following:

Pharmacol. inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization. In addition to this study using tert-Butyl 4-hydroxypiperidine-1-carboxylate, there are many other studies that have used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Computed Properties of C10H19NO3) was used in this study.

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.Computed Properties of C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Catalytic Transfer Hydrogenation of Arenes and Heteroarenes》 was published in Chemistry – A European Journal in 2020. These research results belong to Gelis, Coralie; Heusler, Arne; Nairoukh, Zackaria; Glorius, Frank. Category: piperidines The article mentions the following:

Transfer hydrogenation reactions are of great interest to reduce diverse mols. under mild reaction conditions. To date, this type of reaction has only been successfully applied to alkenes, alkynes and polarized unsaturated compounds such as ketones, imines, pyridines, etc. The reduction of benzene derivatives by transfer hydrogenation has never been described, which is likely due to the high energy barrier required to dearomatize these compounds In this context, a catalytic transfer hydrogenation reaction for the reduction of benzene derivatives and heteroarenes to form complex 3-dimensional scaffolds bearing various functional groups at room temperature without needing compressed hydrogen gas has been developed. In the experiment, the researchers used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Category: piperidines)

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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity》 was published in Journal of Medicinal Chemistry in 2020. These research results belong to Leger, Paul R.; Hu, Dennis X.; Biannic, Berenger; Bui, Minna; Han, Xinping; Karbarz, Emily; Maung, Jack; Okano, Akinori; Osipov, Maksim; Shibuya, Grant M.; Young, Kyle; Higgs, Christopher; Abraham, Betty; Bradford, Delia; Cho, Cynthia; Colas, Christophe; Jacobson, Scott; Ohol, Yamini M.; Pookot, Deepa; Rana, Payal; Sanchez, Jerick; Shah, Niket; Sun, Michael; Wong, Steve; Brockstedt, Dirk G.; Kassner, Paul D.; Schwarz, Jacob B.; Wustrow, David J.. Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylate The article mentions the following:

USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochem. and cellular assays and extremely selective for USP7 over other deubiquitinases. The succinimide was identified as a key potency-driving motif, forming two strong hydrogen bonds to the allosteric pocket of USP7. Redesign of an initial benzofuran-amide scaffold yielded a simplified ether series of inhibitors, utilizing acyclic conformational control to achieve proper amine placement. Further improvements were realized upon replacing the ether-linked amines with carbon-linked morpholines, a modification motivated by free energy perturbation (FEP+) calculations This led to the discovery of compound 41(I), a highly potent, selective, and orally bioavailable USP7 inhibitor. In xenograft studies, compound 41 demonstrated tumor growth inhibition in both p53 wildtype and p53 mutant cancer cell lines, demonstrating that USP7 inhibitors can suppress tumor growth through multiple different pathways.tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylate) was used in this study.

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.Safety of tert-Butyl 4-hydroxypiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The author of 《Structure overhaul affords a potent purine PI3Kδ inhibitor with improved tolerability》 were Methot, Joey L.; Zhou, Hua; Kattar, Sam D.; McGowan, Meredeth A.; Wilson, Kevin; Garcia, Yudith; Deng, Yongi; Altman, Michael; Fradera, Xavier; Lesburg, Charles; Fischmann, Thierry; Li, Chaomin; Alves, Steve; Shah, Sanjiv; Fernandez, Rafael; Goldenblatt, Peter; Hill, Armetta; Shaffer, Lynsey; Chen, Dapeng; Tong, Vince; McLeod, Robbie L.; Yu, Hongshi; Bass, Alan; Kemper, Ray; Gatto, Nicholas T.; LaFranco-Scheuch, Lisa; Trotter, Benjamin Wesley; Guzi, Timothy; Katz, Jason D.. And the article was published in Journal of Medicinal Chemistry in 2019. Product Details of 87120-72-7 The author mentioned the following in the article:

PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematol. malignancies in which the AKT pathway is overactive. A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury. Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif. Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacol. profile. A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathol. evidence of vascular injury. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Product Details of 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Product Details of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2019,Nature (London, United Kingdom) included an article by Xiang, Jinbao; Shang, Ming; Kawamata, Yu; Lundberg, Helena; Reisberg, Solomon H.; Chen, Miao; Mykhailiuk, Pavel; Beutner, Gregory; Collins, Michael R.; Davies, Alyn; Del Bel, Matthew; Gallego, Gary M.; Spangler, Jillian E.; Starr, Jeremy; Yang, Shouliang; Blackmond, Donna G.; Baran, Phil S.. Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate. The article was titled 《Hindered dialkyl ether synthesis with electrogenerated carbocations》. The information in the text is summarized as follows:

Hindered ethers are of high value for various applications; however, they remain an underexplored area of chem. space because they are difficult to synthesize via conventional reactions. Such motifs are highly coveted in medicinal chem., because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochem. oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochem. potentials, capture an alc. donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcs. and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chem. scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labor required to prepare them. The use of mol. probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined The reaction manifold that we report here demonstrates the power of electrochem. to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible 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

The author of 《4-Substituted piperidines. III. Reduction of 1-benzyl-4-cyano-4-tert-aminopiperidines with lithium aluminum hydride》 were Hermans, Bert; van Daele, Paul; van de Westeringh, Cornelis; van der Eycken, Cyriel; Boey, Jozef; Janssen, Paul A. J.. And the article was published in Journal of Medicinal Chemistry in 1966. Safety of 4-Amino-1-benzylpiperidine-4-carbonitrile The author mentioned the following in the article:

cf. CA 63, 16298f. The reduction of 1-benzyl-4-cyano-4-tert-aminopiperidines with LiAlH4 is described; this reduction results in dentrilation, whereas the same reduction of the corresponding primary carboxamides yields the expected primary amines, which can easily be acylated. The obtained compounds are debenzylated, after which other substituents are introduced. These new compounds are virtually devoid of hypotensive or central nervous system depressant activity. In the part of experimental materials, we found many familiar compounds, such as 4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5Safety of 4-Amino-1-benzylpiperidine-4-carbonitrile)

4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Safety of 4-Amino-1-benzylpiperidine-4-carbonitrile

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem