Month: November 2022

Bodner, Ruth A. published the artcileNew directions for neurodegenerative disease therapy. Using chemical compounds to boost the formation of mutant protein inclusions, Application In Synthesis of 115687-05-3, the publication is Cell Cycle (2006), 5(14), 1477-1480, database is CAplus and MEDLINE.

A review. Neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s diseases are marked by neuronal accumulation of toxic misfolded protein. Developing therapies for these misfolding diseases requires finding chem. compounds that can either clear toxic misfolded protein, or can protect neurons from their impact. Such compounds could not only provide the starting points for potential drugs, but could also provide valuable research tools for untangling the complexities of the disease process. Until now, chem. screens for these diseases have focused on finding compounds that prevent aggregation of mutant protein. We recently published a compound, B2, which promotes the formation of large inclusions by mutant Huntingtin and α-synuclein, while rescuing some of the toxic effects of these proteins. As inclusions were long believed to be toxic to cells, this contradicts previous therapeutic approaches. At the same time, the results support growing evidence for the protective effects of inclusions. In this review, we discuss these results, and place them in the context of ongoing therapeutic discovery efforts for Huntington’s disease and other neurodegenerative diseases.

Cell Cycle published new progress about 115687-05-3. 115687-05-3 belongs to piperazines, auxiliary class Epigenetics,Sirtuin, name is (4-Chlorophenyl)(4-(8-nitroquinolin-5-yl)piperazin-1-yl)methanone, and the molecular formula is C20H17ClN4O3, Application In Synthesis of 115687-05-3.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Wollweber, H. published the artcile3-Amino-2H-1,2,4-benzothiadiazine-1,1-dioxides with antihypertensive and possibly diabetogenic activity, Synthetic Route of 71260-16-7, the publication is Arzneimittel-Forschung (1981), 31(2), 279-88, database is CAplus and MEDLINE.

Aminobenzothiadiazine dioxides I (R = Cl, OPh, SPh, CF₃; R¹ = amino) (74 compounds) were prepared by substitution in I (R¹ = Cl, SMe, SO₂Me). Some I have antihypertensive activity and are devoid of diuretic or antidiuretic activity, but some them inhibited insulin secretion.

Arzneimittel-Forschung published new progress about 71260-16-7. 71260-16-7 belongs to piperazines, auxiliary class Piperazine, name is 2-Methyl-1-(piperazin-1-yl)propan-1-one, and the molecular formula is C12H9N3O4, Synthetic Route of 71260-16-7.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Cheung, Peter K. published the artcileA Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing, Application In Synthesis of 55403-35-5, the publication is Journal of Medicinal Chemistry (2016), 59(5), 1869-1879, database is CAplus and MEDLINE.

A 256-compound library was evaluated in an anti-HIV screen to identify structural “mimics” of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1_IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC₅₀‘s of 0.6 and 0.9 μM, resp. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC₅₀‘s ranging from 0.9 to 1.5 μM. The CC₅₀ value obtained in a cytotoxicity assay for compound 9 was >100 μM, corresponding to a therapeutic index (CC₅₀/EC₅₀) of approx. 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent mol. 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Application In Synthesis of 55403-35-5.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Danneman, Michael W. published the artcileA Unified Approach to the Four Azaindoline Families by Inter-/Intramolecular Annulative Diamination of Vinylpyridines, Related Products of piperazines, the publication is Organic Letters (2015), 17(15), 3806-3809, database is CAplus and MEDLINE.

An operationally straightforward and metal-free inter-/intramol. oxidative diamination of vinyl aminopyridines is a common gateway to access all four azaindoline heterocycle families. 3-Amino azaindolines are formed by the reaction of ortho-vinyl N-tosyl anilines with electron-rich amines using phenyliododiacetate (PIDA) and an iodide additive.

Organic Letters published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Danneman, Michael W. published the artcileOxidative Inter-/Intermolecular Alkene Diamination of Hydroxy Styrenes with Electron-Rich Amines, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Organic Letters (2015), 17(10), 2558-2561, database is CAplus and MEDLINE.

Doubly intermol. alkene diamination is achieved with electron-rich, terminal alkenes through the use of a hypervalent iodine (PhI(OAc)₂) reagent, iodide, and electron-rich amines. Mono- and disubstituted amines combine with electron-rich alkenes, particularly o-hydroxystyrenes, to achieve the greatest level of generality. This operationally straightforward protocol, unreliant on conventional metal-based activation, is compatible with a broad range of functional groups.

Organic Letters published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Recommanded Product: (E)-1-Cinnamylpiperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Salama, Ismail published the artcileStructure-Selectivity Investigations of D₂-Like Receptor Ligands by CoMFA and CoMSIA Guiding the Discovery of D₃ Selective PET Radioligands, Product Details of C18H19ClN4, the publication is Journal of Medicinal Chemistry (2007), 50(3), 489-500, database is CAplus and MEDLINE.

Elucidation of the physiol. role of the D₃ receptor and its distribution in the brain using positron emission tomog. (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D₃ radioligands, we designed an integrative procedure involving the elucidation of structural features determining D₃ selectivity over both congeners D₂ and D₄ by comparative mol. anal. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinity differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q²_cv(D₃/D₂) = 0.86; q²_cv(D₃/D₄) = 0.92) and excellent predictions of a 16-ligand test set (r²_pred = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D₃ affinities and considerable selectivities over D₂ and D₄ and, subsequently, to the subtype selective PET tracers [¹⁸F]78 and [¹⁸F]79.

Journal of Medicinal Chemistry published new progress about 337972-47-1. 337972-47-1 belongs to piperazines, auxiliary class Inhibitor, name is 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, and the molecular formula is C18H19ClN4, Product Details of C18H19ClN4.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Tanoury, Gerald J. published the artcileTotal synthesis of (2R,4S,2’S,3’R)-hydroxyitraconazole: implementations of a recycle protocol and a mild and safe phase-transfer reagent for preparation of the key chiral units, Application of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Tetrahedron: Asymmetry (2003), 14(22), 3487-3493, database is CAplus.

A convergent total synthesis of enantiomerically-pure (2R,4S,2’S,3’R)-hydroxyitraconazole is described. The left dioxolane portion of the mol. was prepared in good yield by the conversion of (4S)-2,2-dimethyl-1,3-dioxolane-4-methanol to the corresponding enantiomerically and diastereomerically-pure acetonide (2R,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolane-4-methanol by a recycle protocol involving diastereoselective crystallization of the tosylate salt, followed by re-equilibration of the mother liquor and crystallization The right-hand triazolone moiety was generated by alkylation of a triazolone derivative with an enantiomerically pure cyclic sulfate [(4R,5R)-4,5-dimethyl-1,2,3-dioxathiolane 2,2-dioxide] under mild and essentially non-hazardous reaction conditions (TDA-1, K₂CO₃, acetonitrile).

Tetrahedron: Asymmetry published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C8H7NO4, Application of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Meuldermans, W. published the artcileExcretion and metabolism of flunarizine in rats and dogs, Synthetic Route of 87179-40-6, the publication is Arzneimittel-Forschung (1983), 33(8), 1142-51, database is CAplus and MEDLINE.

The excretion and metabolism of flunarizine (I) [52468-60-7] were studied after single oral doses in rats and dogs using tritium-labeled as well as ¹⁴C-labeled drug. I was well absorbed in both species. The mass balance for the unchanged drug and its major metabolites in urine, bile and feces allowed an explanation of the differences observed for the excretion pattern of the radioactivity in I [¹³C] and I [³H] dosed rats and in male and female rats. The main metabolic pathway in male rats was the oxidative N-dealkylation resulting in bis(4-fluorophenyl)methanol  [365-24-2] and a number of complementary metabolites of the cinnamylpiperazine moiety, of which hippuric acid  [495-69-2] was the main one. In female rats and male dogs, however, 4-hydroxyflunarizine  [87166-81-2] was the main metabolite, resulting from the aromatic hydroxylation of the Ph ring of the cinnamyl moiety. Enterohepatic circulation of bis(4-fluorophenyl)methanol and hydroxyflunarizine was proved by donor-acceptor coupling in rats; in bile and urine, these two metabolites were present mainly as glucuronides. The glucuronide of hydroxyflunarizine [87179-38-2] was also the main plasma metabolite in dogs.

Arzneimittel-Forschung published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Synthetic Route of 87179-40-6.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Xiao, Jichao published the artcileRemote sp³ C-H Amination of Alkenes with Nitroarenes, Product Details of C13H18N2, the publication is Chem (2018), 4(7), 1645-1657, database is CAplus.

Direct installation of a functional group at remote, unfunctionalized sites in an alkyl chain is a synthetically valuable but rarely reported process. The remote relay hydroarylamination of distal and proximal olefins, and of olefin isomeric mixtures, has been achieved through NiH-catalyzed alkene isomerization and sequential reductive hydroarylamination with nitroarenes. This provides an attractive approach to the direct installation of a distal arylamino group within alkyl chains. The single-step conversion of simple olefins and nitro(hetero)arenes to value-added arylamines is a practical strategy for amine synthesis as well as the remote activation of sp³ C-H bonds. The value of this transformation is further supported by the regioconvergent arylamination of isomeric mixtures of olefins.

Chem published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C6H12N2O, Product Details of C13H18N2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sajiki, Hironao published the artcileThe Formation of a Novel Pd/C-Ethylenediamine Complex Catalyst: Chemoselective Hydrogenation without Deprotection of the O-Benzyl and N-Cbz Groups, Recommanded Product: (E)-1-Cinnamylpiperazine, the publication is Journal of Organic Chemistry (1998), 63(22), 7990-7992, database is CAplus.

A Pd/C catalyst formed an isolable complex with ethylenediamine employed as the catalytic poison via one-to-one interaction between Pd metal and ethylenediamine, and this complex catalyst [Pd/C(en)] chemoselectively hydrogenated a variety of reducible functionalities such as olefin, acetylene, nitro, benzyl ester, and azido in the presence of an O-benzyl or N-Cbz protective group. These findings reinforce the versatility potential of O-benzyl and N-Cbz as protective groups in organic synthesis, and the Pd/C(en) catalyst has been identified as a novel and chemoselective catalyst for the hydrogenation.

Journal of Organic Chemistry published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Recommanded Product: (E)-1-Cinnamylpiperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics