Category: piperazines

Brebion, Franck published the artcileDiscovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis, HPLC of Formula: 180698-19-5, the publication is Journal of Medicinal Chemistry (2021), 64(6), 2937-2952, database is CAplus and MEDLINE.

There are currently no approved disease-modifying osteoarthritis (OA) drugs (DMOADs). The aggrecanase ADAMTS-5 is key in the degradation of human aggrecan (AGC), a component of cartilage. Therefore, ADAMTS-5 is a promising target for the identification of DMOADs. We describe the discovery of GLPG1972/S201086, a potent and selective ADAMTS-5 inhibitor obtained by optimization of a promising hydantoin series following an HTS. Biochem. activity against rat and human ADAMTS-5 was assessed via a fluorescence-based assay. ADAMTS-5 inhibitory activity was confirmed with human aggrecan using an AGC ELISA. The most promising compounds were selected based on reduction of glycosaminoglycan release after interleukin-1 stimulation in mouse cartilage explants and led to the discovery of GLPG1972/S201086. The anticatabolic activity was confirmed in mouse cartilage explants (IC₅₀ < 1.5μM). The cocrystal structure of GLPG1972/S201086 with human recombinant ADAMTS-5 is discussed. GLPG1972/S201086 has been investigated in a phase 2 clin. study in patients with knee OA (NCT03595618).

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, HPLC of Formula: 180698-19-5.

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

Ehrlich, Katharina published the artcileDopamine D₂, D₃, and D₄ Selective Phenylpiperazines as Molecular Probes To Explore the Origins of Subtype Specific Receptor Binding, Recommanded Product: 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine, the publication is Journal of Medicinal Chemistry (2009), 52(15), 4923-4935, database is CAplus and MEDLINE.

Assembling phenylpiperazines with 7a-azaindole via different spacer elements, we developed subtype selective dopamine receptor ligands, e.g. I, preferentially interacting with D₄, D₂, and D₃, resp. To complete this set, the methylthio analogs exceeding the affinity of methoxy derivatives by one order of magnitude and a structural intermediate II were synthesized. These chem. similar but biol. divergent target compounds served as mol. probes for radioligand displacement experiments, mutagenesis, and docking studies on homol. models based on the recent crystal structure of the β₂-adrenergic receptor. Specific interactions with the highly conserved amino acids Asp^3.32 and His^6.55 and less conserved residues at positions 2.61, 2.64, 3.28, and 3.29 were identified. Inclusion of a carefully modeled extracellular loop 2 displayed two nonconserved residues in EL2 that differently contribute to ligand binding. Obviously, subtype selectivity is caused by nonconserved but frequently mediated by conserved amino acids.

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, Recommanded Product: 2-((4-(4-Chlorophenyl)piperazin-1-yl)methyl)pyrazolo[1,5-a]pyridine.

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

Singh, Gagandip published the artcileModeling of LIM-kinase 2 inhibitory activity of pyrrolopyrimidine analogues: useful in treatment of ocular hypertension and glaucoma, Category: piperazines, the publication is Medicinal Chemistry (2013), 9(3), 402-409, database is CAplus and MEDLINE.

The LIM-Kinase 2 (LIMK2) inhibitory activity of a series of pyrrolopyrimidine analogs has been analyzed through combinatorial protocol in multiple linear regressions (CP-MLR) and partial least square (PLS) using different descriptors obtained from DRAGON software. The empirical, topol. and charge descriptors have led to statistically significant QSAR models and showed good external predictivity as reflected in test set R² values (0.782 to 0.888). The obtained structure-activity correlations underlined the significance of bulkiness and mol. polarizability in improving the activity. The topol. descriptors suggested that open chain or branched substituents are favorable while cyclic /ring substituents are unfavorable for the activity. The descriptors identified in the study showed that pyrrolopyrimidine scaffold holds scope for modulating LIMK2 inhibitory activity. The study gives a direction for further exploration of chem. space of pyrrolopyrimidine analogs as LIMK2 inhibitors.

Medicinal Chemistry published new progress about 1116571-01-7. 1116571-01-7 belongs to piperazines, auxiliary class Other Aromatic Heterocyclic,Piperazine,Chiral,Nitrile,Bromide,Carbamidine,Amine,Benzene, name is (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide, and the molecular formula is C8H7NaO4S, Category: piperazines.

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

Boursalian, Gregory B. published the artcileCharge-transfer-directed radical substitution enables para-selective C-H functionalization, Product Details of C16H18N2, the publication is Nature Chemistry (2016), 8(8), 810-815, database is CAplus and MEDLINE.

Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theor. tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.

Nature 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, Product Details of C16H18N2.

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

Guarino, Carla published the artcileProlonged pharmacological inhibition of cathepsin C results in elimination of neutrophil serine proteases, Application of 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, the publication is Biochemical Pharmacology (Amsterdam, Netherlands) (2017), 52-67, database is CAplus and MEDLINE.

Cathepsin C (CatC) is a tetrameric cysteine dipeptidyl aminopeptidase that plays a key role in activation of pro-inflammatory serine protease zymogens by removal of an N-terminal pro-dipeptide sequence. Loss of function mutations in the CatC gene is associated with lack of immune cell serine proteases activities and cause Papillon-Lefevre syndrome (PLS). Also, only very low levels of elastase-like protease zymogens are detected by proteome anal. of neutrophils from PLS patients. Thus, CatC inhibitors represent new alternatives for the treatment of neutrophil protease-driven inflammatory or autoimmune diseases. The authors aimed to exptl. inactivate and lower neutrophil elastase-like proteases by pharmacol. blocking of CatC-dependent maturation in cell-based assays and in vivo. Isolated, immature bone marrow cells from healthy donors pulse-chased in the presence of a new cell permeable cyclopropyl nitrile CatC inhibitor almost totally lack elastase. The authors confirmed the elimination of neutrophil elastase-like proteases by prolonged inhibition of CatC in a non-human primate. The authors also showed that neutrophils lacking elastase-like protease activities were still recruited to inflammatory sites. These preclin. results demonstrate that the disappearance of neutrophil elastase-like proteases as observed in PLS patients can be achieved by pharmacol. inhibition of bone marrow CatC. Such a transitory inhibition of CatC might thus help to rebalance the protease load during chronic inflammatory diseases, which opens new perspectives for therapeutic applications in humans.

Biochemical Pharmacology (Amsterdam, Netherlands) published new progress about 914610-39-2. 914610-39-2 belongs to piperazines, auxiliary class Piperazine,Boronic acid and ester,Sulfamide,Benzene,Piperazine,Boronate Esters,Boronic acid and ester,, name is 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine, and the molecular formula is C17H27BN2O4S, Application of 1-Methyl-4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)sulfonyl)piperazine.

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

Civiello, Rita L. published the artcileSynthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines, Synthetic Route of 180698-19-5, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(4), 1229-1232, database is CAplus and MEDLINE.

Calcitonin gene-related peptide (CGRP) is a potent neuropeptide implicated in the pathophysiol. of migraine. In seeking CGRP antagonists with improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower mol. weight, structurally simpler piperidine and piperazine analogs of BMS-<694153≥ were prepared Several have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed.

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

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

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

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

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