Tag: M.W=350-400

Yang, Shyh-Ming published the artcile4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: Urea-based analogs, SDS of cas: 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(24), 6773-6776, database is CAplus and MEDLINE.

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C14H14, SDS of cas: 1032229-33-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Koltun, Dmitry O. published the artcileNovel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(7), 2048-2052, database is CAplus and MEDLINE.

We identified a series of structurally novel SCD (Δ9 desaturase) inhibitors via high-throughput screening and follow-up SAR studies. Modification of the central bicyclic scaffold has proven key to our potency optimization effort. The most potent analog (8g) had IC₅₀ value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Δ5 and Δ6 desaturases.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Imberdis, Thibaut published the artcileCell models of lipid-rich α-synuclein aggregation validate known modifiers of α-synuclein biology and identify stearoyl-CoA desaturase, Safety of 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is Proceedings of the National Academy of Sciences of the United States of America (2019), 116(41), 20760-20769, database is CAplus and MEDLINE.

Microscopy of Lewy bodies in Parkinson’s disease (PD) suggests they are not solely filamentous deposits of α-synuclein (αS) but also contain vesicles and other membranous material. We previously reported the existence of native αS tetramers/multimers and described engineered mutations of the αS KTKEGV repeat motifs that abrogate the multimers. The resultant excess monomers accumulate in lipid membrane-rich inclusions associated with neurotoxicity exceeding that of natural familial PD mutants, such as E46K. Here, we use the αS “3K” (E35K+E46K+E61K) engineered mutation to probe the mechanisms of reported small-mol. modifiers of αS biochem. and then identify compounds via a medium-throughput automated screen. αS 3K, which forms round, vesicle-rich inclusions in cultured neurons and causes a PD-like, L-DOPA-responsive motor phenotype in transgenic mice, was fused to YFP, and fluorescent inclusions were quantified. Live-cell microscopy revealed the highly dynamic nature of the αS inclusions: for example, their rapid clearance by certain known modulators of αS toxicity, including tacrolimus (FK506), isradipine, nilotinib, nortriptyline, and trifluoperazine. Our automated 3K cellular screen identified inhibitors of stearoyl-CoA desaturase (SCD) that robustly prevent the αS inclusions, reduce αS 3K neurotoxicity, and prevent abnormal phosphorylation and insolubility of αS E46K. SCD inhibition restores the E46K αS multimer:monomer ratio in human neurons, and it actually increases this ratio for overexpressed wild-type αS. In accord, conditioning 3K cells in saturated fatty acids rescued, whereas unsaturated fatty acids worsened, the αS phenotypes. Our cellular screen allows probing the mechanisms of synucleinopathy and refining drug candidates, including SCD inhibitors and other lipid modulators.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Safety of 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Xin, Zhili published the artcileDiscovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors, Quality Control of 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(15), 4298-4302, database is CAplus and MEDLINE.

A series of structurally novel stearoyl-Co-A desaturase 1 (SCD1) inhibitors has been identified via mol. scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(Me carbamoyl)phenyl]piperidine-1-carboxamide (I) exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C9H21NO3, Quality Control of 1032229-33-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Deng, Yongqi published the artcileDiscovery of liver-targeted inhibitors of stearoyl-CoA desaturase (SCD1), Computed Properties of 1032229-33-6, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(3), 791-796, database is CAplus and MEDLINE.

Inhibitors based on a benzo-fused spirocyclic oxazepine scaffold were discovered for stearoyl-CoA (CoA) desaturase 1 (SCD1) and subsequently optimized to potent compounds with favorable pharmacokinetic profiles and in vivo efficacy in reducing the desaturation index in a mouse model. Initial optimization revealed potency preferences for the oxazepine core and benzylic positions, while substituents on the piperidine portions were more tolerant and allowed for tuning of potency and PK properties. After preparation and testing of a range of functional groups on the piperidine nitrogen, three classes of analogs were identified with single digit nanomolar potency: glycine amides, heterocycle-linked amides, and thiazoles. Responding to concerns about target localization and potential mechanism-based side effects, an initial effort was also made to improve liver concentration in an available rat PK model. An advanced compound 17m with a 5-carboxy-2-thiazole substructure appended to the spirocyclic piperidine scaffold was developed which satisfied the in vitro and in vivo requirements for more detailed studies.

Bioorganic & Medicinal Chemistry Letters published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Computed Properties of 1032229-33-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Dai, Shuang published the artcileSCD1 confers temozolomide resistance to human glioma cells via the Akt/GSK3β/β-catenin signaling axis, Quality Control of 1032229-33-6, the publication is Frontiers in Pharmacology (2017), 960/1-960/12, database is CAplus and MEDLINE.

Resistance to temozolomide (TMZ), the standard chemotherapy agent for glioblastoma (GBM), poses a major clin. challenge to GBM prognosis. Understanding the mechanisms of TMZ resistance can help to identify novel drug targets and more effective therapies. Recent studies suggest that bioenergetic alterations of cancer cells play important roles in drug resistance. In our study, the altered metabolism of cancer cells was observed using a metabolic PCR array. We found that stearoyl-CoA desaturase 1 (SCD1), a key rate-limiting enzyme for synthesis of monounsaturated fatty acids, was significantly upregulated in TMZ-resistant GBM cells compared to their parental counterparts. Overexpression of SCD1 promoted resistance to TMZ in parental GBM cells, whereas SCD1 downregulation by siRNA could re-sensitize TMZ-resistant cells in vitro. Combinational treatment of TMZ and an SCD1-specific inhibitor showed a combined inhibitory effect on TMZ-resistant glioma cells. We also observed that overexpression of SCD1 promoted Akt/GSK3β/β-catenin signaling, while silencing of SCD1 inhibited the signaling. The combination of an Akt activator with exogenous SCD1 or the combined inhibition of Akt and enforced expression of SCD1 resulted in the most significant changes of Akt signaling. Functionally, significantly lower viability and mobility rates were observed in TMZ-resistant cells when treated with Akt inhibitors and an SCD1 inhibitor simultaneously compared to when treated individually. In conclusion, our study identified SCD1 along with its functional pathway as a novel target in the development of TMZ resistance. SCD1 inhibition used alone or in combination with Akt inhibition could effectively overcome TMZ resistance in gliomas.

Frontiers in Pharmacology published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Quality Control of 1032229-33-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Zhang, Hua published the artcileQuantification and molecular imaging of fatty acid isomers from complex biological samples by mass spectrometry, COA of Formula: C20H22ClN3O3, the publication is Chemical Science (2021), 12(23), 8115-8122, database is CAplus and MEDLINE.

Elucidating the isomeric structure of free fatty acids (FAs) in biol. samples is essential to comprehend their biol. functions in various physiol. and pathol. processes. Herein, we report a novel approach of using peracetic acid (PAA) induced epoxidation coupled with mass spectrometry (MS) for localization of the C-C bond in unsaturated FAs, which enables both quantification and spatial visualization of FA isomers from biol. samples. Abundant diagnostic fragment ions indicative of the C-C positions were produced upon fragmentation of the FA epoxides derived from either in-solution or on-tissue PAA epoxidation of free FAs. The performance of the proposed approach was evaluated by anal. of FAs in human cell lines as well as mapping the FA isomers from cancer tissue samples with MALDI-TOF/TOF-MS. Merits of the newly developed method include high sensitivity, simplicity, high reaction efficiency, and capability of spatial characterization of FA isomers in tissue samples.

Chemical Science published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C9H21NO3, COA of Formula: C20H22ClN3O3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Lien, Evan C. published the artcileLow glycaemic diets alter lipid metabolism to influence tumour growth, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, the publication is Nature (London, United Kingdom) (2021), 599(7884), 302-307, database is CAplus and MEDLINE.

Dietary interventions can change metabolite levels in the tumor microenvironment, which might then affect cancer cell metabolism to alter tumor growth1-5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumor progression by lowering blood glucose and insulin levels6-8, we found that only CR inhibits the growth of select tumor allografts in mice, suggesting that other mechanisms contribute to tumor growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumors. Upregulation of stearoyl-CoA desaturase (SCD), which synthesizes monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumor SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumor growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumor SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumors, and changing the KD fat composition to increase tumor saturated fatty acid levels cooperates with decreased tumor SCD activity to slow tumor growth. These data suggest that diet-induced mismatches between tumor fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycemic diets impair tumor growth.

Nature (London, United Kingdom) published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C20H22ClN3O3, Recommanded Product: 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

von Roemeling, Christina A. published the artcileStearoyl-CoA Desaturase 1 Is a Novel Molecular Therapeutic Target for Clear Cell Renal Cell Carcinoma, COA of Formula: C20H22ClN3O3, the publication is Clinical Cancer Research (2013), 19(9), 2368-2380, database is CAplus and MEDLINE.

Purpose: We set out to identify Stearoyl-CoA desaturase 1 (SCD1) as a novel mol. target in clear cell renal cell carcinoma (ccRCC) and examine its role in tumor cell growth and viability in vitro and in vivo independently as well as in combination with current U.S. Food and Drug Administration (FDA)-approved regimens. Exptl. Design: Patient normal and ccRCC tissue samples and cell lines were examined for SCD1 expression. Genetic knockdown models and targeted inhibition of SCD1 through use of a small mol. inhibitor, A939572, were analyzed for growth, apoptosis, and alterations in gene expression using gene array anal. Therapeutic models of synergy were evaluated utilizing pharmacol. inhibition of SCD1 with the tyrosine kinase inhibitors (TKI) sunitinib and pazopanib, and the mTOR inhibitor temsirolimus. Results: Our studies identify increased SCD1 expression in all stages of ccRCC. Both genetic knockdown and pharmacol. inhibition of SCD1 decreased tumor cell proliferation and induced apoptosis in vitro and in vivo. Upon gene array, quant. real-time PCR, and protein anal. of A939572-treated or SCD1 lentiviral knockdown samples, induction of endoplasmic reticulum stress response signaling was observed, providing mechanistic insight for SCD1 activity in ccRCC. Furthermore, combinatorial application of A939572 with temsirolimus synergistically inhibited tumor growth in vitro and in vivo. Conclusions: Increased SCD1 expression supports ccRCC viability and therefore we propose it as a novel mol. target for therapy either independently or in combination with an mTOR inhibitor for patients whose disease cannot be remedied with surgical intervention, such as in cases of advanced or metastatic disease. Clin Cancer Res; 19(9); 2368-80. ©2013 AACR.

Clinical Cancer Research published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C15H12O8, COA of Formula: C20H22ClN3O3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Sutherland, Mathew published the artcileRational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics, SDS of cas: 2757618-86-1, the publication is ChemMedChem (2021), 16(7), 1116-1125, database is CAplus and MEDLINE.

Protein arginine N-Me transferase 4 (PRMT4) asym. dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers had stimulated interest in the discovery of inhibitors as biol. tools and, potentially, therapeutics. Although several PRMT4 inhibitors had reported, most display poor selectivity against other members of the PRMT family of Me transferases. Herein, the structure-based design of a new class of alanine-containing 3-arylindoles such as I [R = Me, i-Pr, NMe₂, etc.] as potent and selective PRMT4 inhibitors was reported, and described key structure-activity relationships for this class of compounds

ChemMedChem published new progress about 2757618-86-1. 2757618-86-1 belongs to piperidines, auxiliary class Boronic acid and ester, name is 1-((3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperidine, and the molecular formula is C6H12Br2, SDS of cas: 2757618-86-1.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem