October 2022 | Page 38 of 62 | Heterocyclic Building Blocks-piperazine

Guianvarc’h, Dominique’s team published research in Journal of Medicinal Chemistry in 2004 | CAS: 1688-95-5

4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5) is a member of sulfamide. Sulfamide was used in the synthesis of: Schiff bases of the type ArCH=NSO2NH2; 1H,3H-2,1,3-benzothiadiazin-4-one-2,2-dioxide (BTDD); sulfamide analogs of oleoylethanolamide analogs in a study of PPARα activation.Formula: C5H11ClN2O2S

《Synthesis and Biological Activity of Sulfonamide Derivatives of Epipodophyllotoxin》 was written by Guianvarc’h, Dominique; Duca, Maria; Boukarim, Chawki; Kraus-Berthier, Laurence; Leonce, Stephane; Pierre, Alain; Pfeiffer, Bruno; Renard, Pierre; Arimondo, Paola B.; Monneret, Claude; Dauzonne, Daniel. Formula: C5H11ClN2O2S And the article was included in Journal of Medicinal Chemistry on April 22 ,2004. The article conveys some information:

A series of novel 4β-substituted sulfonamide derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin, I [R1 = SO2R, R = Me, n-Pr, (CH2)3NH2, 2-thienyl, piperidino, etc.] (II), has been synthesized. II were synthesized by silylating the alc. I (R1 = H), followed by reaction with RSO2Cl, and desilylation. Their effects on human DNA topoisomerase II and, in some cases, on tubulin polymerization were evaluated. Several of the compounds, e.g. II (R = Me), and the synthetic precursor, the 4β-azido compound, are potent topoisomerase II poisons that induce double-stranded breaks in DNA, with either improved or similar activity compared to etoposide. Only the amino precursor, compound I (R1 = H), was slightly active in tubulin polymerization inhibition assays. We observed that the derivatives bearing an aromatic ring on the 4β-sulfonamide substituent were either less cytotoxic or equivalent to the parent drug, while the sulfonamides containing an aliphatic side chain and the amino-sulfonamide derivatives, except II [R = (CH2)15Me, (CH2)3NH2], exhibited increased cytotoxicity compared to etoposide. In vivo, against the P388 leukemia and the A-549 orthotopic model of lung carcinoma, the most promising compounds were the morpholino- and the piperazino-containing sulfonamides derivatives II (R = morpholino, 4-methylpiperazino). In the part of experimental materials, we found many familiar compounds, such as 4-Methyl-1-piperazinesulfonyl Chloride(cas: 1688-95-5Formula: C5H11ClN2O2S)

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Paul, Anirudra’s team published research in Journal of the American Chemical Society in 2019 | CAS: 109-01-3

1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Electric Literature of C5H12N2

In 2019,Journal of the American Chemical Society included an article by Paul, Anirudra; Seidel, Daniel. Electric Literature of C5H12N2. The article was titled 《α-Functionalization of Cyclic Secondary Amines: Lewis Acid Promoted Addition of Organometallics to Transient Imines》. The information in the text is summarized as follows:

Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides is crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivities. In the experimental materials used by the author, we found 1-Methylpiperazine(cas: 109-01-3Electric Literature of C5H12N2)

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Paul, Anirudra’s team published research in Angewandte Chemie, International Edition in 2021 | CAS: 109-01-3

Paul, Anirudra; Kim, Jae Hyun; Daniel, Scott D.; Seidel, Daniel published their research in Angewandte Chemie, International Edition in 2021. The article was titled 《Diversification of Unprotected Alicyclic Amines by C-H Bond Functionalization: Decarboxylative Alkylation of Transient Imines》.Recommanded Product: 109-01-3 The article contains the following contents:

Despite extensive efforts by many practitioners in the field, methods for the direct α-C-H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a β-ketoacid under mild conditions to provide valuable β-amino ketones with unprecedented ease. Regioselective α’-alkylation is achieved for substrates with existing α-substituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a SNAr step. In the experiment, the researchers used many compounds, for example, 1-Methylpiperazine(cas: 109-01-3Recommanded Product: 109-01-3)

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Nguyen, William’s team published research in European Journal of Medicinal Chemistry in 2021 | CAS: 109-01-3

Nguyen, William; Dans, Madeline G.; Ngo, Anna; Gancheva, Maria R.; Romeo, Ornella; Duffy, Sandra; de Koning-Ward, Tania F.; Lowes, Kym N.; Sabroux, Helene Jousset; Avery, Vicky M.; Wilson, Danny W.; Gilson, Paul R.; Sleebs, Brad E. published an article in 2021. The article was titled 《Structure activity refinement of phenylsulfonyl piperazines as antimalarials that block erythrocytic invasion》, and you may find the article in European Journal of Medicinal Chemistry.Synthetic Route of C5H12N2 The information in the text is summarized as follows:

The optimization and further characterization of the phenylsulfonyl piperazine class I [R = 4-Me, 3-t-Bu, 4-Br, etc.; R1 = pyrrolidin-1-yl, piperidin-1-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl, etc.; X = -(N(CH2)2N(CH2)2)-CH(CH3), -(NCH(CH3)N(CH2)2)-CH(CH3), -(NC(CH3)2N(CH2)2)-CH(CH3), etc.] was described. During the optimization process the functionality required for P. falciparum asexual stage activity was defined and determined the alpha-carbonyl S-Me isomer was important for antimalarial potency. The optimized compounds I also possessed comparable activity against multidrug resistant strains of P. falciparum and displayed weak activity against sexual stage gametocytes. The optimized compounds I blocked erythrocyte invasion consistent with the asexual activity observed and therefore the phenylsulfonyl piperazine analogs described could serve as useful tools for studying Plasmodium erythrocyte invasion. After reading the article, we found that the author used 1-Methylpiperazine(cas: 109-01-3Synthetic Route of C5H12N2)

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Allan, Pia N M’s team published research in Synlett in 2019-12-31 | 197638-83-8

Synlett published new progress about Aromatic heterocyclic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Safety of 1-Boc-4-(4-Formylphenyl)piperazine.

Allan, Pia N. M.; Ostrowska, Martyna I.; Patel, Bhaven published the artcile< Acetic Acid Catalyzed One-Pot Synthesis of Pyrrolo[1,2- a ]quinoxaline Derivatives>, Safety of 1-Boc-4-(4-Formylphenyl)piperazine, the main research area is pyrroloquinoxaline preparation; benzaldehyde pyrrolylaniline Pictet Spengler reaction acetic acid catalyst.

An efficient acetic acid catalyzed reaction has been developed for the synthesis of 4-aryl substituted pyrrolo[1,2-a]quinoxalines I (R = H, 8-Me, 7-CF3, etc.; Ar = Ph, 2-MeOC6H4, 4-MeC6H4, etc.) from readily available starting materials. A range of structures have been synthesized in very good to excellent yields. The one-pot reaction proceeds through imine formation, cyclization followed by air oxidation

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Chopin, Nicolas’s team published research in European Journal of Organic Chemistry in 2015 | 197638-83-8

European Journal of Organic Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Product Details of C16H22N2O3.

Chopin, Nicolas; Yanai, Hikaru; Iikawa, Shinya; Pilet, Guillaume; Bouillon, Jean-Philippe; Medebielle, Maurice published the artcile< A Rapid Entry to Diverse γ-Ylidenetetronate Derivatives through Regioselective -Bromination of Tetronic Acid Derived γ-Lactones and Metal-Catalyzed Postfunctionalization>, Product Details of C16H22N2O3, the main research area is furanone tetronate preparation crystal mol structure.

The synthesis of a series of diverse Me and benzyl γ-ylidenetetronate derivatives was accomplished through the condensation of Me and benzyl tetronates with (hetero)aryl aldehydes in a new two-step or three-step aldolization/dehydration sequence. The bromination of Me and benzyl γ-ylidenetetronates occurred under mild conditions to provide the corresponding C-3-brominated γ-unsaturated lactones. Di- and tribrominated γ-lactones were prepared under slightly different conditions. Some brominated materials were employed in representative Stille, Suzuki-Miyaura , and Sonogashira cross-coupling reactions to yield functionalized Me and benzyl γ-ylidenetetronate derivatives Compounds that resulted from the Sonogashira cross-coupling reactions were desilylated and converted into 1,2,3-triazole derivatives through a copper(I)-catalyzed 1,3-dipolar cycloaddition reaction with benzyl azide. The synthesis of the target compounds was achieved by a reaction of 4-methoxy-2(5H)-furanone (Me tetronate), 4-(phenylmethoxy)-2(5H)-furanone (benzyl tetronate) with aldehydes. The title compounds thus formed included (5Z)-4-methoxy-5-(phenylmethylene)-2(5H)-furanone and related substances.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Wang, Lan’s team published research in Bioorganic & Medicinal Chemistry Letters in 2014-09-15 | 229009-40-9

Bioorganic & Medicinal Chemistry Letters published new progress about Crystal structure. 229009-40-9 belongs to class piperazines, and the molecular formula is C11H17BN2O2, Quality Control of 229009-40-9.

Wang, Lan; Stanley, Mark; Boggs, Jason W.; Crawford, Terry D.; Bravo, Brandon J.; Giannetti, Anthony M.; Harris, Seth F.; Magnuson, Steven R.; Nonomiya, Jim; Schmidt, Stephen; Wu, Ping; Ye, Weilan; Gould, Stephen E.; Murray, Lesley J.; Ndubaku, Chudi O.; Chen, Huifen published the artcile< Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors>, Quality Control of 229009-40-9, the main research area is fragment identification pyrrolo triazine MAP4K4 inhibitor; Fragment-based lead discovery; Kinase inhibitors; MAP4K4; P-loop conformation; Pyrrolotriazine.

MAP4K4 has been shown to regulate key cellular processes that are tied to disease pathogenesis. In an effort to generate small mol. MAP4K4 inhibitors, a fragment-based screen was carried out and a pyrrolotriazine fragment with excellent ligand efficiency was identified. Further modification of this fragment guided by X-ray crystal structures and mol. modeling led to the discovery of a series of promising compounds with good structural diversity and physicochem. properties. These compounds exhibited single digit nanomolar potency and compounds 35 and 44 achieved good in vivo exposure.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Watanabe, Toshihiro’s team published research in Chemical & Pharmaceutical Bulletin in 1997-09-30 | 197638-83-8

Chemical & Pharmaceutical Bulletin published new progress about Cardiotonics. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Computed Properties of 197638-83-8.

Watanabe, Toshihiro; Kakefuda, Akio; Kinoyama, Isao; Takizawa, Kenji; Hirano, Seiko; Shibata, Hiroshi; Yanagisawa, Isao published the artcile< Synthesis of novel succinamide derivatives having a 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one skeleton as potent and selective M2 muscarinic receptor antagonists. II>, Computed Properties of 197638-83-8, the main research area is pyridobenzodiazepinone preparation muscarinic receptor antagonist; succinamide pyridobenzodiazepinone preparation muscarinic receptor antagonist; structure activity pyridobenzodiazepinone muscarinic receptor antagonist; antibradycardiac pyridobenzodiazepinone piperazinylbenzylmethylamino preparation; cardiotonic pyridobenzodiazepinone piperazinylbenzylmethylamino preparation.

Title compounds I (R = H, OMe, Cl, Me, Et, i-Pr, MeS, HO, n-PrO, Me2N, pyrrolidino, morpholino, 4-alkyl-1-piperazinyl; R1 = Me, Et)(26 compounds) were prepared and evaluated for binding affinity to muscarinic receptors in vitro and for antagonism of bradycardia and salivation in vivo in comparison with AF-DX 116 (II). Structure-activity relationships studies in vitro indicated that the 4-(4-alkyl-1-piperazinyl)benzylamino moiety plays a crucial role in enhancing the affinity for M2 muscarinic receptors. I containing a 4-(4-isopropyl-1-piperazinyl)benzylmethylamino moiety, exhibited the highest affinity for M2 muscarinic receptors, being 200 times as potent as II, and I (R = C-4 4-ethyl-1-piperazinyl, R1 = Et)(III) containing a 4-(4-ethyl-1-piperazinyl)benzylethylamino moiety, showed the highest selectivity for M2 over M3 muscarinic receptors. III and I (R = C-4 4-isopropyl-1-piperazinyl, R1 = Me) also antagonized the oxotremorine-induced bradycardia in rats after i.v. or oral administration. Oral evaluation in conscious dogs showed that the efficacy for increasing the heart rate was at least 3-fold greater than that of II.

Chemical & Pharmaceutical Bulletin published new progress about Cardiotonics. 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Computed Properties of 197638-83-8.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Treuer, Adriana V’s team published research in Journal of Chemistry in 2017 | 197638-83-8

Journal of Chemistry published new progress about Aryl aldehydes, heteroaryl Role: RCT (Reactant), RACT (Reactant or Reagent). 197638-83-8 belongs to class piperazines, and the molecular formula is C16H22N2O3, Electric Literature of 197638-83-8.

Treuer, Adriana V.; De-La-Torre, Pedro; Gutierrez, Margarita I. published the artcile< Synthesis of new (E)-2-(1H-indole-3-ylcarbonyl)-3-heteroaryl-acrylonitriles via microwave-assisted Knoevenagel condensation>, Electric Literature of 197638-83-8, the main research area is indolylcarbonyl heteroaryl acrylonitrile preparation stereoselective green chem; heteroaryl aldehyde stereoselective Knoevenagel condensation cyanoacetyl indole microwave irradiation.

A series of new (E)-2-(1H-indole-3-ylcarbonyl)-3-heteroaryl-acrylonitriles I [R = 2-imidazolyl, 5-phenyl-3-isoxazolyl, 5-(4-chlorophenyl)-2-furyl, etc.] was obtained in 30-94% yields from 3-(cyanoacetyl)indole and the corresponding heteroaryl aldehydes RCHO by microwave-assisted (300 W) Knoevenagel reaction at 100 °C.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Oldenhius,NathanJ.’s team published research in Angewandte Chemie, International Edition in 2013 | 374930-88-8

Angewandte Chemie, International Edition published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, COA of Formula: C13H19BrN4O2.

Yang, Yang; Oldenhius, Nathan J.; Buchwald, Stephen L. published the artcile< Mild and general conditions for Negishi cross-coupling enabled by the use of palladacycle precatalysts>, COA of Formula: C13H19BrN4O2, the main research area is biaryl preparation; biheteroaryl preparation; heteroarylzinc preparation aryl halide Negishi cross coupling palladacycle catalyst.

A palladacycle-catalyzed Negishi cross coupling between in situ generated heteroaryl zinc reagents and aryl or heteroaryl halides is described. A series of biaryls and biheteroaryls were obtained in good to excellent yields.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics