Tag: M.W=200-250

Bordner, Jon published the artcile1,3-Diamino-6,7-dimethoxyisoquinoline derivatives as potential α₁-adrenoceptor antagonists, COA of Formula: C10H17N3O2, the publication is Journal of Medicinal Chemistry (1988), 31(5), 1036-9, database is CAplus and MEDLINE.

Treatment of 2,4,5-Me(MeO)₂C₆H₂CN (I) with LiN(CHMe₂)₂ followed by reaction with R₂NCN [R = Me, R₂ = (CH₂)₅] provided 1,3-diamino-6,7-dimethoxyisoquinolines II (R = as above), which were evaluated for α-adrenoceptor binding affinity and antihypertensive activity. II (R = Me) showed no significant affinity for α₁-adrenoceptors, while the 3-(2-furoyl-1-piperazinyl) analog III, prepared from I and 1-cyano-4-(tert-butoxycarbonyl)piperazine in 3 steps, was 1000-fold less potent than prazosin. PK_a data showed that 34% N(2) protonation of II (R = Me) (pK_a = 7.1) would occur at physiol. pH, in agreement with x-ray crystallog. anal. of III.HCl. Comparison of pos. charge distribution following protonation of II (R = Me) with the corresponding quinoline and quinazoline cations confirmed that N(1) protonation is required for these heterocyclic nuclei to bind efficiently to the α₁-adrenoceptor. Computer-assisted comparison of the x-ray structures of III.HCl and prazosin suggested that the 4.0 kcal/mol difference in α₁-adrenoceptor binding energies was largely due to salt-bridge formation (ca. 3.0 kcal/mol) between the protonated quinazoline and the receptor protein. Neither II nor III were effective antihypertensive agents in rats even when administered at relatively high doses (10 mg/kg). These results support the hypothesis that the antihypertensive activity of prazosin, doxazosin, and related compounds derives solely from α₁-adrenoceptor blocking.

Journal of Medicinal Chemistry published new progress about 113534-02-4. 113534-02-4 belongs to piperazines, auxiliary class Piperazine,Nitrile,Amide, name is tert-Butyl 4-cyanopiperazine-1-carboxylate, and the molecular formula is C10H17N3O2, COA of Formula: C10H17N3O2.

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

Pagano, Mafalda published the artcileThe Fight against the Influenza A Virus H1N1: Synthesis, Molecular Modeling, and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors, Application In Synthesis of 67914-60-7, the publication is ChemMedChem (2014), 9(1), 129-150, database is CAplus and MEDLINE.

The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biol. data and lays the foundation for the rational development of more effective PA-PB1 inhibitors.

ChemMedChem 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 C12H16N2O2, Application In Synthesis of 67914-60-7.

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

El Kihel, Laila published the artcileNew lithocholic and chenodeoxycholic piperazinylcarboxamides with antiproliferative and pro-apoptotic effects on human cancer cell lines, Category: piperazines, the publication is Bioorganic & Medicinal Chemistry (2008), 16(18), 8737-8744, database is CAplus and MEDLINE.

Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116)) cell lines. The best activity was obtained with compound (I) on multiple myeloma cells (LD₅₀: 8.5±0.5 μM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFκB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.

Bioorganic & Medicinal 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, Category: piperazines.

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

Dei, Silvia published the artcileDesign and synthesis of new potent N,N-bis(arylalkyl)piperazine derivatives as multidrug resistance (MDR) reversing agents, Computed Properties of 87179-40-6, the publication is European Journal of Medicinal Chemistry (2018), 7-20, database is CAplus and MEDLINE.

A series of 1,4-substituted arylalkyl piperazine derivatives I (Ar = 2-phenoxyethyl, 4,4-diphenylbutyl, 9-anthracenylmethyl, etc.; Ar¹ = cinnamyl, 4,4-bis(4-fluorophenyl)butyl, 4,4-bis(4-methoxyphenyl)butyl, etc.) were synthesized and studied with the aim to obtain potent P-gp-dependent multidrug-resistant (MDR) reversers. The new compounds were designed on the basis of the structures of previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity. All new compounds were active in the pirarubicin uptake assay on the doxorubicin-resistant erythroleukemia K562cells (K562/DOX). In particular, compounds bearing methoxy aromatic moieties showed fairly high reversal activities. The most potent compounds, I (Ar = (3,4,5-trimethoxyphenoxy)ethyl, 3,4,5-trimethoxycinnamyl, 3,4,5-trimethoxybenzyl; Ar¹ = 4,4-bis-(4-methoxyphenyl)butyl, 9-anthracenylmethyl) were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) and the inhibition of P-gp-mediated rhodamine-123 (Rhd 123) efflux on the K562/DOX cell line. The results of all pharmacol. assays indicated that the combination of a basic piperazine scaffold with arylalkyl residues allowed us to obtain very interesting P-gp modulating compounds Overall compound I (Ar = (3,4,5-trimethoxyphenyl)allyl; Ar¹ = 4,4-bis-(4-methoxyphenyl)butyl) appeared the most promising compound being a potent and long-lasting P-gp-dependent MDR modulator.

European Journal of Medicinal 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, Computed Properties of 87179-40-6.

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

Capuano, Ben published the artcileSynthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogs of Clozapine. III. Replacement of the Tricyclic Nucleus with a Bicyclic Template, SDS of cas: 87179-40-6, the publication is Australian Journal of Chemistry (2007), 60(12), 928-933, database is CAplus.

As a continuing part of our research program in search of novel compounds for the treatment of schizophrenia, we report the synthesis and preliminary receptor binding affinity for a series of bicyclic analogs of clozapine [I; Y = CH₂, Z = H, 3,4-OCH₂O, 3-OMe, 4-OMe; Y = CH₂CH₂, (CH₂)₃, (E)-CH:CHCH₂, Z = H] derived from a selection of promising tricyclic candidates published previously. These bicyclic compounds investigate some substituent effects and the length and nature of the linker between an ionizable nitrogen atom at physiol. pH and the introduced aryl moiety. The chem., structural characterization, and in vitro evaluation are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and selected substituents coupled to the bicyclic nucleus are discussed in relation to affinity for dopamine D₄ and serotonin 5-HT_2A receptors.

Australian Journal of 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, SDS of cas: 87179-40-6.

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

Capuano, Ben published the artcileSynthesis and Preliminary Pharmacological Evaluation of 4′-Arylalkyl Analogues of Clozapine. II. Effect of the Nature and Length of the Linker, Computed Properties of 87179-40-6, the publication is Australian Journal of Chemistry (2003), 56(9), 875-886, database is CAplus.

We report the synthesis of a second generation of tricyclic analogs of clozapine, investigating the length and nature of the chain between an ionizable nitrogen atom at physiol. pH and the introduced aryl moiety. The chem., structural characterization, and pharmacol. evaluation of this series of 4′-arylalkyl analogs of clozapine are described. Preliminary findings on the effects on activity of the nature and length of the linker, degree of unsaturation, and type of aryl moiety on blockade of dopamine D₄ and serotonin 5-HT_2A receptors are discussed and animal behavioral data for key compounds presented.

Australian Journal of 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, Computed Properties of 87179-40-6.

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

Cremonesi, Giuseppe published the artcileLewis acid-catalyzed formylation reaction of 4-(piperazin-1-yl)phenols, SDS of cas: 67914-60-7, the publication is Heterocycles (2014), 88(1), 603-606, database is CAplus.

The Lewis acid-catalyzed reaction of 4-(piperazin-1-yl)phenols I (R¹ = Ac, CHO, Boc, PhCH₂; R² = H) with paraformaldehyde in aprotic solvents afforded salicylaldehydes I (R² = CHO) in good yields.

Heterocycles 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 C12H16N2O2, SDS of cas: 67914-60-7.

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

Crespo, Roberto A. published the artcileStructure-Guided Drug Design of 6-Substituted Adenosine Analogues as Potent Inhibitors of Mycobacterium tuberculosis Adenosine Kinase, SDS of cas: 180698-19-5, the publication is Journal of Medicinal Chemistry (2019), 62(9), 4483-4499, database is CAplus and MEDLINE.

Mycobacterium tuberculosis adenosine kinase (MtbAdoK) is an essential enzyme of Mtb and forms part of the purine salvage pathway within mycobacteria. Evidence suggests that the purine salvage pathway might play a crucial role in Mtb survival and persistence during its latent phase of infection. In these studies, we adopted a structural approach to the discovery, structure-guided design, and synthesis of a series of adenosine analogs that displayed inhibition constants ranging from 5 to 120 nM against the enzyme. Two of these compounds exhibited low micromolar activity against Mtb with half maximal effective inhibitory concentrations of 1.7 and 4.0 μM. Our selectivity and preliminary pharmacokinetic studies showed that the compounds possess a higher degree of specificity against MtbAdoK when compared with the human counterpart and are well tolerated in rodents, resp. Finally, crystallog. studies showed the mol. basis of inhibition, potency, and selectivity and revealed the presence of a potentially therapeutically relevant cavity unique to the MtbAdoK homodimer.

Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, SDS of cas: 180698-19-5.

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

Huang, Yiyun published the artcileSynthesis of potent and selective serotonin 5-HT_1B receptor ligands, Synthetic Route of 180698-19-5, the publication is Bioorganic & Medicinal Chemistry Letters (2005), 15(21), 4786-4789, database is CAplus and MEDLINE.

A series of serotonin 5-HT_1B ligands were synthesized and evaluated for their potency and selectivity against other 5-HT receptor subtypes. Many of these new compounds displayed high affinity and selectivity for the 5-HT_1B receptor and one compound was found to have the in vitro binding profile necessary for development as a PET radioligand.

Bioorganic & Medicinal Chemistry Letters published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, Synthetic Route of 180698-19-5.

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

Deka, Nabajyoti published the artcileSynthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives for the treatment of metabolic syndrome, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is International Journal of Medicinal Chemistry (2013), 201580/1-201580/11, 11 pp., database is CAplus and MEDLINE.

Metabolic syndrome is a widely prevalent multifactorial disorder associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic disorder. Thiazolidinediones (TZDs) are potent PPARγ ligands and used as insulin sensitizers in the treatment of type 2 diabetes mellitus. They are potent insulin-sensitizing agents but due to adverse effects like hepatotoxicity, a safer alternative of TZDs is highly demanded. The synthesis of N-(6-(4-(piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide derivatives I (R = 2,4-Cl₂C₆H₃, 2,5-(OCH₃)₂C₆H₃, 2-thienyl, etc.) an alternate remedy for insulin resistance is reported.

International Journal of Medicinal Chemistry 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 C12H16N2O2, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

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