Month: November 2022

Brown, Dennis A. published the artcileInvestigation of various N-heterocyclic substituted piperazine versions of 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol: Effect on affinity and selectivity for dopamine D3 receptor, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is Bioorganic & Medicinal Chemistry (2009), 17(11), 3923-3933, database is CAplus and MEDLINE.

The design and synthesis of several heterocyclic analogs belonging to the 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol series of mols., are reported. Compounds were subjected to [³H]spiperone binding assays, carried out with HEK-293 cells expressing either D2 or D3 dopamine receptors, in order to evaluate their inhibition constant (K_i) at these receptors. Results indicate that N-substitution on the piperazine ring can accommodate various substituted indole rings. The results also show that in order to maintain high affinity and selectivity for the D3 receptor the heterocyclic ring does not need to be connected directly to the piperazine ring as the majority of compounds included here are linked either via an amide or a methylene linker to the heterocyclic moiety. The enantiomers of the most potent racemic compound I exhibited differential activity with (-)-I (K _i; D2 = 47.5 nM, D3 = 0.57 nM) displaying higher affinity at both D2 and D3 receptors compared to its enantiomer (+)-I (K _i; D2 = 113 nM, D3 = 3.73 nM). Addnl., compound (-)-I was more potent and selective for the D3 receptor compared to either 7-OH-DPAT or 5-OH-DPAT. Among the bioisosteric derivatives, the indazole derivative and benzo[b]thiophene derivative exhibited the highest affinity for D2 and D3 receptors. In the functional GTP¦ÃS binding study, one of the lead mols., (-)-II, exhibited potent agonist activity at both D2 and D3 receptors with preferential affinity at D3.

Bioorganic & Medicinal Chemistry published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Application of tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

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

Kumar, Dhananjay published the artcileSynthesis of 2-N/S/C-Substituted Benzothiazoles via Intramolecular Cyclative Cleavage of Benzotriazole Ring, Quality Control of 87179-40-6, the publication is Journal of Organic Chemistry (2014), 79(1), 251-266, database is CAplus and MEDLINE.

The synthesis of numerous 2-N/S/C-substituted benzothiazoles was achieved from substituted thiocarbonylbenzotriazoles via free-radical intramol. cyclative cleavage of the benzotriazole ring in the presence of (TMS)₃SiH and AIBN under mild conditions. The developed methodol. demonstrates significant compatibility under microwave conditions and is important as it avoids the use of toxic metals for radical cyclization.

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, Quality Control of 87179-40-6.

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

Upton, Kristen published the artcileDesign and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase, PARP14, Recommanded Product: 1-Biphenyl-4-yl-piperazine, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(13), 2907-2911, database is CAplus and MEDLINE.

A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were synthesized and tested for their ability to inhibit the mono-(ADP-ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were established for this series and several compounds were identified as sub-micromolar inhibitors of PARP14, the most potent of which was compound 4t (I), IC₅₀ = 160 nM. Furthermore, profiling other members of this series identified compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity over PARP10, a closely related mono-(ADP-ribosyl)transferase.

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 C6H12O2, Recommanded Product: 1-Biphenyl-4-yl-piperazine.

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

Li, Gang published the artcileThe optimization of xanthine derivatives leading to HBK001 hydrochloride as a potent dual ligand targeting DPP-IV and GPR119, SDS of cas: 113534-02-4, the publication is European Journal of Medicinal Chemistry (2020), 112017, database is CAplus and MEDLINE.

A series of xanthine compounds derived from the previous hit I with modification on the terminal side chain was discovered through ring formation strategy. Systematic optimization of the compounds with rigid heterocycles in the hydrophobic side chain led to the new lead compound HBK001 (II) with the improved DPP-IV inhibition and moderate GPR119 agonism activity in vitro. As a continuing work to further study the PK and PD profiles, II and its hydrochloride (22) were synthesized on grams scale and evaluated on the ADME/T and oral glucose tolerance test (OGTT) in ICR mice. Compound 22 showed the improved bioavailability and blood glucose-lowering effect in vivo compared to its free base 21h probably attributed to its improved solubility and permeability. The preliminary toxicity studies on compound 22 exhibited that the result of mini-Ames was neg. and the preliminary acute toxicity LD₅₀ in mice was above 1.5 g/kg, while it showed moderate inhibition on hERG channel with IC₅₀ 4.9¦ÌM maybe due to its high lipophilicity. These findings will be useful for the future drug design for more potent and safer dual ligand targeting DPP-IV and GPR119 for the treatment of diabetes.

European 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, SDS of cas: 113534-02-4.

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

Liu, Hangyu published the artcileSynthesis of formamides containing unsaturated groups by N-formylation of amines using CO₂ with H₂, Quality Control of 87179-40-6, the publication is Green Chemistry (2017), 19(1), 196-201, database is CAplus.

The selective and efficient N-formylation of amines containing unsaturated groups using CO₂ and H₂ with a Cu(OAc)₂-4-dimethylaminopyridine (DMAP) catalytic system was described. The substrates were converted to the desired formamides, while the unsaturated groups, such as the carbonyl group, the C=C bond, CN bond and the ester group remained. The main reason for the excellent selectivity of the Cu(OAc)₂-DMAP catalytic system was that it was very active for the N-formylation reaction, but was not active for the hydrogenation of the unsaturated groups.

Green 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, Quality Control of 87179-40-6.

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

Hansen-Petrik, Melissa B. published the artcileSelective inhibition of ¦¤-6 desaturase impedes intestinal tumorigenesis, Computed Properties of 218136-59-5, the publication is Cancer Letters (Shannon, Ireland) (2002), 175(2), 157-163, database is CAplus and MEDLINE.

Arachidonic acid is an important polyunsaturated fatty acid involved in cell signaling. It is derived primarily from dietary linoleic acid, and the rate-limiting step in its biosynthesis is the initial desaturation of linoleic acid via ¦¤-6 desaturase. Evidence suggests that downstream metabolic products of arachidonic acid, e.g. prostaglandins, are involved in colorectal cancer, but involvement of the biosynthetic pathway of arachidonic acid has not been previously investigated. In the present study, the authors report the effects of a novel selective ¦¤-6 desaturase inhibitor, SC-26196, on tumorigenesis in two in vivo models of intestinal cancer. SC-26196 treatment resulted in 36-37% fewer tumors in Apc^Min/+ mice and 35% decrease in primary tumor size in nude mice bearing HT-29 human colon cancer cell xenografts. As expected, SC-26196 treatment resulted in significantly higher linoleic acid levels in tissue phospholipids and lower levels of arachidonic acid. The effects on both tissue fatty acid composition and tumorigenesis in Apc^Min/+ mice were abrogated by concomitant treatment with dietary arachidonic acid, indicating that the observed effects were due to interference with the biosynthetic pathway of arachidonic acid.

Cancer Letters (Shannon, Ireland) published new progress about 218136-59-5. 218136-59-5 belongs to piperazines, auxiliary class Metabolic Enzyme,D6D, name is 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, and the molecular formula is C27H29N5, Computed Properties of 218136-59-5.

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

Zhang, Yun published the artcileDicationic Electrophiles from Olefinic Amines in Superacid, Synthetic Route of 87179-40-6, the publication is Journal of Organic Chemistry (2003), 68(13), 5119-5122, database is CAplus and MEDLINE.

Olefins containing amine moieties undergo Friedel-Crafts alkylations with benzene and substituted benzenes in the presence of triflic acid to yield arenes in 49-99% yields. Suspension of the amine-containing olefins in triflic acid and an arene yields the product arenes. This method is used in brief syntheses of the anti-spasmodic agents fenpiprane and prozapine from 1-(trans-cinnamyl)piperidine and 1-(trans-cinnamyl)hexahydroazepine, resp. Alkenes can be immobilized on polystyrene beads with triflic acid to yield resin-bound amines and piperazines; beads crosslinked with 2% divinylbenzene are stable to the reaction conditions while macroporous beads are damaged under the reaction conditions. The alkylation reactions are proposed to occur via dicationic carbocation intermediates containing protonated amine salts; the ¹³C NMR spectra of a dication generated in situ from (4,4-diphenyl-3-butenyl)piperidine under superacidic conditions is obtained as evidence for the proposed intermediates.

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 C19H14O2, Synthetic Route of 87179-40-6.

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

Komami, Narumi published the artcilePalladium-Catalyzed Germylation of Aryl Bromides and Aryl Triflates Using Hexamethyldigermane, Computed Properties of 67914-60-7, the publication is Synthesis (2018), 50(10), 2067-2075, database is CAplus.

Pd-catalyzed germylation of aryl bromides and aryl triflates using com. available hexamethyldigermane is described. Optimized reaction conditions afforded various functionalized aryltrimethylgermanes, including drug-like mols., in moderate to good yields, demonstrating the versatility of the presented protocols.

Synthesis 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, Computed Properties of 67914-60-7.

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

Kapanda, Coco N. published the artcileSynthesis and Pharmacological Evaluation of 2,4-Dinitroaryldithiocarbamate Derivatives as Novel Monoacylglycerol Lipase Inhibitors, Application of (E)-1-Cinnamylpiperazine, the publication is Journal of Medicinal Chemistry (2012), 55(12), 5774-5783, database is CAplus and MEDLINE.

Monoacylglycerol lipase (MAGL) is responsible for signal termination of 2-arachidonoylglycerol (2-AG), an endocannabinoid neurotransmitter endowed with several physiol. effects. Previously, we showed that the arylthioamide scaffold represents a privileged template for designing MAGL inhibitors. A series of 37 compounds resulting from pharmacomodulations around the arylthioamide template were synthesized and tested to evaluate their inhibitory potential on MAGL activity as well as their selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. We have identified 2,4-dinitroaryldithiocarbamate derivatives as a novel class of MAGL inhibitors. Among the synthesized compounds, we identified [2,4-dinitrophenyl-4-(4-tert-butylbenzyl)piperazine-1-carbodithioate] (CK37, I), as the most potent MAGL inhibitor within this series (IC₅₀ = 154 nM). We have also identified [2,4-dinitrophenyl-4-benzhydrylpiperazine-1-carbodithioate] (CK16 ,II) as a selective MAGL inhibitor. These compounds are irreversible MAGL inhibitors that probably act by interacting with Cys208 or Cys242 and Ser122 residues of the enzyme. Moreover, CK37 is able to raise 2-arachidonoylglycerol (2-AG) levels in intact cells.

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, Application of (E)-1-Cinnamylpiperazine.

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

Yang, Shyh-Ming published the artcileDiscovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity, COA of Formula: C8H16N2O, the publication is Journal of Medicinal Chemistry (2018), 61(11), 4883-4903, database is CAplus and MEDLINE.

Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiol. and toxicol. functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDH1A1) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small mol. ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chem. optimization and biol. characterization led to the identification of analogs with significantly improved enzymic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isoenzymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.

Journal of Medicinal Chemistry 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 C5H10O2S, COA of Formula: C8H16N2O.

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