Month: November 2022

Parallel Solid-Phase Synthesis using a New Diethylsilylacetylenic Linker and Leading to Mestranol Derivatives with Potent Antiproliferative Activities on Multiple Cancer Cell Lines was written by Dutour, Raphael;Maltais, Rene;Perreault, Martin;Roy, Jenny;Poirier, Donald. And the article was included in Anti-Cancer Agents in Medicinal Chemistry in 2018.Product Details of 86069-86-5 The following contents are mentioned in the article:

However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to the development of the mestranol derivative RM-581. Methods: Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilylacetylenic linker. To establish structure-activity relationships, we then investigated their antiproliferative potency on a panel of cancer cell lines from various cancers (breast, prostate, ovarian and pancreatic). Results: Some of the mestranol derivatives have shown in vitro anticancer activities that are close to, or better than, those observed for RM-581. Compound 23, a mestranol derivative having a ((3,5-dimethylbenzoyl)- L-prolyl)piperazine side chain at position C2, was found to be active as an antiproliferative agent (IC50 = 0.38 ± 0.34 to 3.17 ± 0.10 μM) and to be twice as active as RM-581 on LNCaP, PC-3, MCF-7, PANC-1 and OVCAR-3 cancer cells (IC50 = 0.56 ± 0.30, 0.89 ± 0.63, 1.36 ± 0.31, 2.47 ± 0.91 and 3.17 ± 0.10 μM, resp.). Conclusion: Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chem., promising compound 23 could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Product Details of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Piperidine prefers a chair conformation, similar to cyclohexane. Unlike cyclohexane, piperidine has two distinguishable chair conformations: one with the N–H bond in an axial position, and the other in an equatorial position.Product Details of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Parallel Solid-Phase Synthesis using a New Diethylsilylacetylenic Linker and Leading to Mestranol Derivatives with Potent Antiproliferative Activities on Multiple Cancer Cell Lines was written by Dutour, Raphael;Maltais, Rene;Perreault, Martin;Roy, Jenny;Poirier, Donald. And the article was included in Anti-Cancer Agents in Medicinal Chemistry in 2018.Product Details of 86069-86-5 The following contents are mentioned in the article:

However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to the development of the mestranol derivative RM-581. Methods: Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilylacetylenic linker. To establish structure-activity relationships, we then investigated their antiproliferative potency on a panel of cancer cell lines from various cancers (breast, prostate, ovarian and pancreatic). Results: Some of the mestranol derivatives have shown in vitro anticancer activities that are close to, or better than, those observed for RM-581. Compound 23, a mestranol derivative having a ((3,5-dimethylbenzoyl)- L-prolyl)piperazine side chain at position C2, was found to be active as an antiproliferative agent (IC50 = 0.38 ± 0.34 to 3.17 ± 0.10 μM) and to be twice as active as RM-581 on LNCaP, PC-3, MCF-7, PANC-1 and OVCAR-3 cancer cells (IC50 = 0.56 ± 0.30, 0.89 ± 0.63, 1.36 ± 0.31, 2.47 ± 0.91 and 3.17 ± 0.10 μM, resp.). Conclusion: Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chem., promising compound 23 could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Product Details of 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives.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. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Product Details of 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Multigenerational effects of a complex urban contaminant mixture on the behavior of larval and adult fish in multiple fitness contexts was written by Swank, Ally;Wang, Lina;Ward, Jessica;Schoenfuss, Heiko. And the article was included in Science of the Total Environment in 2021.Reference of 83799-24-0 The following contents are mentioned in the article:

Agricultural and urban storm water runoffs can introduce chems. of emerging concern (CECs) into waterways. These chems. can be continually released, persist, or even accumulate over time, with adverse effects on the physiol. and behavior of aquatic species. Most studies aimed at evaluating the intergenerational effects of CECs have focused exclusively on single chems. By comparison, little is known about the effects of complex CEC mixtures on the behavior of organisms, or how these effects might manifest in subsequent generations. In this study, we exposed three generations of fathead minnows (Pimephales promelas) to environmentally relevant concentrations of a complex CEC mixture representative of urban-impacted waterways and assessed the growth and behavior of larval and adult fish in life-stage-relevant fitness contexts (foraging, boldness, courtship). We found that (i) multigenerational exposure to a complex mixture of CECs altered the behavior of both larvae and adults in different fitness contexts; (ii) concentration-dependent patterns of behavioral impairment were consistent across fitness contexts and life stages; and (iii) the effects of exposure were magnified in the F1 and F2 generations. These results highlight the need for long-term, multigenerational assessments of CECs in affected waterways to robustly inform conservation practices aimed at managing aquatic systems. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Reference of 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives.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. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Reference of 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pharmacokinetic screening of soluble epoxide hydrolase inhibitors in dogs was written by Tsai, Hsing-Ju;Hwang, Sung Hee;Morisseau, Christophe;Yang, Jun;Jones, Paul D.;Kasagami, Takeo;Kim, In-Hae;Hammock, Bruce D.. And the article was included in European Journal of Pharmaceutical Sciences in 2010.Formula: C16H20F3N3O3 The following contents are mentioned in the article:

Epoxyeicosatrienoic acids that have anti-hypertensive and anti-inflammatory properties are mainly metabolized by soluble epoxide hydrolase (sEH, EC 3.3.2.3). Therefore, sEH has emerged as a therapeutic target for treating various cardiovascular diseases and inflammatory pain. N,N’-Disubstituted ureas are potent sEH inhibitors in vitro. However, in vivo usage of early sEH inhibitors has been limited by their low bioavailability and poor physiochem. properties. Therefore, a group of highly potent compounds with more drug-like physiochem. properties were evaluated by monitoring their plasma profiles in dogs treated orally with sEH inhibitors. Urea compounds with an adamantyl or a 4-trifluoromethoxyphenyl group on one side and a piperidyl or a cyclohexyl ether group on the other side of the urea function showed pharmacokinetic profiles with high plasma concentrations and long half lives. In particular, the inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB) not only is very potent with good physiochem. properties, but also shows high oral bioavailability for doses ranging from 0.01 to 1 mg/kg. This compound is also very potent against the sEH of several mammals, suggesting that t-AUCB will be an excellent tool to evaluate the biol. of sEH in multiple animal models. Such compounds may also be a valuable lead for the development of veterinary therapeutics. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Formula: C16H20F3N3O3).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives.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. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Formula: C16H20F3N3O3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression was written by Huerta-Yepez, Sara;Tirado-Rodriguez, Ana;Montecillo-Aguado, Mayra R.;Yang, Jun;Hammock, Bruce D.;Hankinson, Oliver. And the article was included in Scientific Reports in 2020.Quality Control of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea The following contents are mentioned in the article:

Abstract: The Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can metabolize PUFA to epoxides. Mice fed ω3-rich or ω6-rich diets were treated with TCDD and injected s.c. with AHR-competent Hepa1-GFP hepatoma cells or AHR-deficient LLC lung cancer cells. TCDD reduced the growth rates of the resulting tumors in ω3-fed mice and inhibited their metastasis to the liver and/or lung, but had the opposite effects in mice fed ω6 PUFA. These responses were likely attributable to the corresponding PUFA epoxides generated in tumor cells and/or host, since many depended upon co-administration of a soluble epoxide hydrolase (EPHX2) inhibitor in males, and/or were associated with increases in epoxide levels in tumors and sites of metastasis. Equivalent effects occurred in females in the absence of EPHX2 inhibition, probably because this sex expressed reduced levels of EPHX2. The responses elicited by TCDD were associated with effects on tumor vascularity, tumor cell proliferation and/or apoptosis. Thus environmental AHR agonists, and potentially also endogenous, nutritional, and microbiome-derived agonists, may reduce or enhance cancer progression depending on the composition of dietary PUFA, particularly in females. This study involved multiple reactions and reactants, such as 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7Quality Control of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea).

1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (cas: 1222780-33-7) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.Quality Control of 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Effect of human plasma on hepatic uptake of organic anion-transporting polypeptide 1B substrates: studies using transfected cells and primary human hepatocytes was written by Bi, Yi-an;Ryu, Sangwoo;Tess, David A.;Rodrigues, A. David;Varma, Manthena V. S.. And the article was included in Drug Metabolism & Disposition in 2021.SDS of cas: 83799-24-0 The following contents are mentioned in the article:

Current challenges with the in vitro-in vivo extrapolation (IVIVE) of hepatic uptake clearance involving organic anion-transporting polypeptide (OATP) 1B1/1B3 hinder drug design strategies. Here we evaluated the effect of 100% human plasma on the uptake clearance using transfected human embryonic kidney (HEK) 293 cells and primary human hepatocytes and assessed IVIVE. Apparent unbound uptake clearance (PS_inf,_u) increased significantly (P <0.05) in the presence of plasma (vs. buffer incubations) for about 50% of compounds in both OATP1B1-transfected and wild-type HEK cells. Thus, plasma showed a minimal effect on the uptake ratios. With cultured human hepatocytes, plasma significantly (P < 0.05) increased PSinf,u for 11 of 19 OATP1B substrates (median change of 2.1-fold). Cell accumulation in HEK cells and hepatocytes was also increased for tolbutamide, which is not an OATP substrate. Plasma-to-buffer ratio of P_Sinf,u obtained in hepatocytes showed a good correlation with unbound fraction in plasma, and the relationship was best described by a “facilitated-dissocn” model. IVIVE was evaluated for the 19 OATP1B substrates using hepatocyte data in the presence of buffer and plasma. PS_inf,u from buffer incubations markedly underpredicted hepatic intrinsic clearance (calculated via well stirred and parallel tube models) with an estimated bias of 0.10-0.13. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0SDS of cas: 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Several piperidine alkaloids isolated from natural herbs, were found to exhibit antiproliferation and antimetastatic effects on various types of cancers both in vitro and in vivo for example Piperine, Evodiamine, Matrine, Berberine and Tetrandine.SDS of cas: 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis and biological activity of oxytocin analogues containing conformationally-restricted residues in position 7 was written by Fragiadaki, Maria;Magafa, Vassiliki;Borovickova, Lenka;Slaninova, Jirina;Cordopatis, Paul. And the article was included in European Journal of Medicinal Chemistry in 2007.Name: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid The following contents are mentioned in the article:

The authors report the solid-phase synthesis and some pharmacol. properties of twenty oxytocin [OT; H-cyclo(Cys¹-Tyr²-Ile³-Gln⁴-Asn⁵-Cys⁶)-Pro⁷-Leu⁸-Gly⁹-NH₂] analogs. Basic modifications at position 7 [introduction of α-aminoisobutyric acid (Aib), L– or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (L/D-Tic), L-α-t-butylglycine [Gly(Bu-t)] and pipecolic acid (Pip)] were combined with D-Tyr(Et)², L/D-(pEt)Phe², D-Tic², and Mpa¹ modifications and their various combinations in a total of 14 analogs. Addnl., two analogs having one more modification in position 3, i.e., Gly(Bu-t), and three analogs having glycine in position 9 substituted by D-Tic or Aib, were prepared The analogs were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OT receptor. The analog having the highest antioxytocic activity was [Mpa¹, D-Tyr(Et)², D-Tic⁷, Aib⁹]OT having pA₂ = 8.31 ± 0.19; this analog was also selective. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5Name: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.Name: (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthesis and biological activity of oxytocin analogues containing conformationally-restricted residues in position 7 was written by Fragiadaki, Maria;Magafa, Vassiliki;Borovickova, Lenka;Slaninova, Jirina;Cordopatis, Paul. And the article was included in European Journal of Medicinal Chemistry in 2007.SDS of cas: 86069-86-5 The following contents are mentioned in the article:

The authors report the solid-phase synthesis and some pharmacol. properties of twenty oxytocin [OT; H-cyclo(Cys¹-Tyr²-Ile³-Gln⁴-Asn⁵-Cys⁶)-Pro⁷-Leu⁸-Gly⁹-NH₂] analogs. Basic modifications at position 7 [introduction of α-aminoisobutyric acid (Aib), L– or D-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (L/D-Tic), L-α-t-butylglycine [Gly(Bu-t)] and pipecolic acid (Pip)] were combined with D-Tyr(Et)², L/D-(pEt)Phe², D-Tic², and Mpa¹ modifications and their various combinations in a total of 14 analogs. Addnl., two analogs having one more modification in position 3, i.e., Gly(Bu-t), and three analogs having glycine in position 9 substituted by D-Tic or Aib, were prepared The analogs were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OT receptor. The analog having the highest antioxytocic activity was [Mpa¹, D-Tyr(Et)², D-Tic⁷, Aib⁹]OT having pA₂ = 8.31 ± 0.19; this analog was also selective. This study involved multiple reactions and reactants, such as (S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5SDS of cas: 86069-86-5).

(S)-1-(((9H-Fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (cas: 86069-86-5) belongs to piperidine derivatives.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. Industrially, piperidine is produced by the hydrogenation of pyridine, usually over a molybdenum disulfide catalyst. Pyridine can also be reduced to piperidine via a modified Birch reduction using sodium in ethanol.SDS of cas: 86069-86-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Comprehensive two-dimensional liquid chromatography as a biomimetic screening platform for pharmacokinetic profiling of compound libraries in early drug development was written by Russo, Giacomo;Grumetto, Lucia;Baert, Mathijs;Lynen, Frederic. And the article was included in Analytica Chimica Acta in 2021.Reference of 83799-24-0 The following contents are mentioned in the article:

A comprehensive two-dimensional liquid chromatog.-based biomimetic platform (LCxLC) has been developed and validated for drug diffusion studies. Human serum albumin (HSA) and immobilized artificial membrane (IAM) were thereby used in the first (1D) and second (2D) separation dimension, resp. While the former was meant to emulate the blood, the latter was instead intended to mimic the intestinal mucosa epithelium. Therefore, the exptl. conditions, i.e. pH, temperature and buffer composition, were modulated to reflect faithfully in vivo conditions. 30 compounds, whose effective intestinal permeability (Peff) assayed in situ on humans by a validated technique was known from the literature, were used as model drugs. A good and orthogonal separation was achieved for the whole dataset, although for a better distribution of the most polar compounds in the elution window a segmented gradient elution program had to be employed. Interestingly, the passively uptaken compounds having the most favorable Peff populated a specific area of the 2D plots, implying that the affinity for HSA and IAM has to lie in specific ranges in order for a compound to be satisfactorily absorbed from the intestinal lumen. Although these results should be regarded as preliminary, this work paves an entirely new and unprecedented way to profile pharmaceutically relevant compounds for their in vivo absorption and distribution potential. This study involved multiple reactions and reactants, such as 2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0Reference of 83799-24-0).

2-(4-(1-Hydroxy-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butyl)phenyl)-2-methylpropanoic acid (cas: 83799-24-0) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.Reference of 83799-24-0

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem