Month: February 2023

YAP-dependent proliferation by a small molecule targeting annexin A2 was written by Shalhout, Sophia Z.;Yang, Peng-Yu;Grzelak, Edyta M.;Nutsch, Kayla;Shao, Sida;Zambaldo, Claudio;Iaconelli, Jonathan;Ibrahim, Lara;Stanton, Caroline;Chadwick, Stormi R.;Chen, Emily;DeRan, Michael;Li, Sijia;Hull, Mitchell;Wu, Xu;Chatterjee, Arnab K.;Shen, Weijun;Camargo, Fernando D.;Schultz, Peter G.;Bollong, Michael J.. And the article was included in Nature Chemical Biology in 2021.Computed Properties of C12H25N3O2 This article mentions the following:

Abstract: The transcriptional coactivator Yes-associated protein 1 (YAP) orchestrates a pro-proliferative transcriptional program that controls the fate of somatic stem cells and the regenerative responses of certain tissues. As such, agents that activate YAP may hold therapeutic potential in disease states exacerbated by insufficient proliferative repair. Here we report the discovery of a small mol., termed PY-60, which robustly activates YAP transcriptional activity in vitro and promotes YAP-dependent expansion of epidermal keratinocytes in mouse following topical drug administration. Chem. proteomics revealed the relevant target of PY-60 to be annexin A2 (ANXA2), a protein that directly associates with YAP at the cell membrane in response to increased cell d. PY-60 treatment liberates ANXA2 from the membrane, ultimately promoting a phosphatase-bound, nonphosphorylated and transcriptionally active form of YAP. This work reveals ANXA2 as a previously undescribed, druggable component of the Hippo pathway and suggests a mechanistic rationale to promote regenerative repair in disease. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1Computed Properties of C12H25N3O2).

tert-Butyl 4-(3-aminopropyl)piperazine-1-carboxylate (cas: 373608-48-1) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Computed Properties of C12H25N3O2

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

Improved synthesis of 4-[4-(5-oxo-1,5-dihydro-[1,2,4 triazoyl-4-yl) phenyl]piperazine-1-carboxylic t-butyl ester was written by Sheng, Chunquan;Zhang, Wannian;Xu, Hui;Che, Xiaoying;Zhang, Min;Yao, Jianzhong;Miao, Zhenyuan. And the article was included in Zhongguo Yaowu Huaxue Zazhi in 2006.Computed Properties of C15H21N3O4 This article mentions the following:

To improve the synthetic process of 4-[4-(5-oxo-1,5-dihydro-[1,2,4] triazoyl-4-yl) phenyl] piperazine-1-carboxylic t-Bu ester, which was used as the key intermediate of triazole antifungal agents, the product was synthesized from 1-(4-nitrophenyl) piperazine by Boc protection, reduction of nitro group, acylation, hydrazinolysis and cyclization. The new synthetic process had several advantages such as facile reaction condition, convenient operation and purification without chromatog. The overall yield was improved from 39.10% to 71.94%. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6Computed Properties of C15H21N3O4).

1-Boc-4-(4-Nitrophenyl)piperazine (cas: 182618-86-6) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Computed Properties of C15H21N3O4

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

Amino-substituted heterocycles as isosteres of trans-cinnamides: design and synthesis of heterocyclic biaryl sulfides as potent antagonists of LFA-1/ICAM-1 binding was written by Wang, Gary T.;Wang, Sheldon;Gentles, Robert;Sowin, Thomas;Leitza, Sandra;Reilly, Edward B.;von Geldern, Thomas W.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2005.Synthetic Route of C7H16N2 This article mentions the following:

2-Amino-4-Ph pyridine and to a lesser extent, 4-amino-6-Ph pyrimidine were established as isosteres of trans-cinnamide moiety. Applying this isosterism to previously reported p-arylthio cinnamides resulted in the identification of 4-amino-6-(p-arylthio)phenylpyrimidines and 2-amino-4-(p-arylthio)phenylpyridines I (X = N, CH, R¹ = 2-Me₂CH; X = CH, R¹ = 2-MeO, 3,4-OCH₂CH₂O; R²R³N = pyrrolidinyl, 4-hydroxypiperidinyl, 4-formyl-1-piperazinyl, etc.) as potent antagonists of LFA-1/ICAM-1 binding. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Synthetic Route of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.Synthetic Route of C7H16N2

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

Chemotherapeutically active nitro compounds. 4. 5-Nitroimidazoles. Part II was written by Winkelmann, E.;Raether, W.;Sinharay, A.. And the article was included in Arzneimittel-Forschung in 1978.Application In Synthesis of 1-Propylpiperazine This article mentions the following:

About 190 nitroimidazoles I [R = morpholino, 4-methylpiperazino, N₃, p-ClC₆H₄COCH₂S, PhS, MeOCS₂, H₂NC(:NH)S, MeNH, etc.; R¹ = Me, Et] were prepared Thus, I (R = Cl, R¹ = Me) was treated with 2-mercaptopyridine to give 80% I (R = 2-pyridylthio, R¹ = Me). 1-Methyl-2-(S-isothiouroniummethyl)-5-nitroimidazole-HCl and 2-bromo-5-nitrofuran gave 65% I (R = 5-nitro-2-furylthio, R¹ = Me). The chemotherapeutic effect against several protozoa species was tabulated. Some I were also bactericidal, nematocidal, and fungicidal. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Application In Synthesis of 1-Propylpiperazine).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Application In Synthesis of 1-Propylpiperazine

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

Novel water-soluble sedative-hypnotic agents: isoindolin-1-one derivatives was written by Kanamitsu, Norimasa;Osaki, Takashi;Itsuji, Yutaka;Yoshimura, Masakazu;Tsujimoto, Hisashi;Soga, Manabu. And the article was included in Chemical & Pharmaceutical Bulletin in 2007.Synthetic Route of C7H16N2 This article mentions the following:

The authors developed new i.v. sedative-hypnotic compounds with the isoindolin-1-one skeleton focusing on the water-soluble property and in vivo safety. The authors synthesized approx. 170 derivatives and evaluated their hypnotic effects by i.v. administration of the compounds to mice. A series of the 2-phenyl-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]isoindolin-1-one analogs (I–IV) showed potent sedative-hypnotic activity with good water solubility and a wide safety margin. The hypnotic doses (HD₅₀s) of these 4 compounds when administered to mice were 2.35, 1.90, 2.17, and 3.12 mg/kg, resp., and the LDs (LD₅₀s) were 88.67, 64.69, >120, and >120 mg/kg, resp. The therapeutic indexes (LD₅₀/HD₅₀) were 37.73, 34.05, >55.30, and >38.46, resp. Among these IV is being considered as the most potential candidate for clin. trials in humans. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Synthetic Route of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 鎺矯 and boils at 125閳?30 鎺矯. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Synthetic Route of C7H16N2

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

Discovery of Substituted 1H-Pyrazolo[3,4-b]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors was written by Zhao, Bin;Li, Yixuan;Xu, Pan;Dai, Yang;Luo, Cheng;Sun, Yiming;Ai, Jing;Geng, Meiyu;Duan, Wenhu. And the article was included in ACS Medicinal Chemistry Letters in 2016.Computed Properties of C16H22N2O4 This article mentions the following:

Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biol. evaluation of a novel series of 1H-pyrazolo[3,4-b]pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent in vitro potency and favorable pharmacokinetic properties, compound I was selected for in vivo evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that I would be a promising candidate for further drug development. In the experiment, the researchers used many compounds, for example, 4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4Computed Properties of C16H22N2O4).

4-(4-(tert-Butoxycarbonyl)piperazin-1-yl)benzoic acid (cas: 162046-66-4) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Computed Properties of C16H22N2O4

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

Molecular Simplification of 1,4-Diazabicyclo[4.3.0]nonan-9-ones Gives Piperazine Derivatives That Maintain High Nootropic Activity was written by Manetti, Dina;Ghelardini, Carla;Bartolini, Alessandro;Dei, Silvia;Galeotti, Nicoletta;Gualtieri, Fulvio;Romanelli, Maria Novella;Teodori, Elisabetta. And the article was included in Journal of Medicinal Chemistry in 2000.SDS of cas: 21867-64-1 This article mentions the following:

Several 4-substituted 1-acylpiperazines, obtained by mol. simplification of 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones, have been synthesized and tested in vivo on the mouse passive avoidance test, to evaluate their nootropic activity. The results show that, apparently, an N-acylpiperazine group can mimic the 2-pyrrolidinone ring of 1,4-diazabicyclo[4.3.0]nonan-9-one, as the compounds of the new series maintain high nootropic activity. Moreover mol. simplification produces more clear-cut structure-activity relationships with respect to the parent series. The mechanism of action also appears to be similar in the two series. In fact, although the mol. mechanism remains to be elucidated, the most potent compound of each class is able to increase acetylcholine release in rat brain. Piperazine derivatives represent a new class of nootropic drugs with an in vivo pharmacol. profile very similar to that of piracetam, showing much higher potency with respect to the reference compound Among the compounds studied, 1-benzoyl-4-propionylpiperazine (DM235) shows outstanding potency, being active at a dose of 0.001 mg kg^-1 s.c. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1SDS of cas: 21867-64-1).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.SDS of cas: 21867-64-1

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

Iridium-Catalyzed C-H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism was written by Larsen, Matthew A.;Hartwig, John F.. And the article was included in Journal of the American Chemical Society in 2014.SDS of cas: 780705-64-8 This article mentions the following:

A study on the iridium-catalyzed C-H borylation of heteroarenes is reported. Several heteroarenes containing multiple heteroatoms were amenable to C-H borylation catalyzed by the combination of an iridium(I) precursor and tetramethylphenanthroline. The investigations of the scope of the reaction led to the development of powerful rules for predicting the regioselectivity of borylation, foremost of which is that borylation occurs distal to nitrogen atoms. One-pot functionalizations are reported of the heteroaryl boronate esters formed in situ, demonstrating the usefulness of the reported methodol. for the synthesis of complex heteroaryl structures. Application of this methodol. to the synthesis and late-stage functionalization of biol. active compounds is also demonstrated. Mechanistic studies show that basic heteroarenes can bind to the catalyst and alter the resting state from the olefin-bound complex observed during arene borylation to a species containing a bound heteroarene, leading to catalyst deactivation. Studies on the origins of the observed regioselectivity show that borylation occurs distal to N-H bonds due to rapid N-H borylation, creating an unfavorable steric environment for borylation adjacent to these bonds. Computational studies and mechanistic studies show that the lack of observable borylation of C-H bonds adjacent to basic nitrogen is not the result of coordination to a bulky Lewis acid prior to C-H activation, but the combination of a higher-energy pathway for the borylation of these bonds relative to other C-H bonds and the instability of the products formed from borylation adjacent to basic nitrogen. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8SDS of cas: 780705-64-8).

tert-Butyl 4-(pyrimidin-2-yl)piperazine-1-carboxylate (cas: 780705-64-8) belongs to piperazine derivatives. A form in which piperazine is commonly available industrially is as the hexahydrate, C4H10N2. 6H2O, which melts at 44 掳C and boils at 125鈥?30 掳C. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.SDS of cas: 780705-64-8

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

III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold was written by Kim, Seong Heon;Anilkumar, Gopinadhan N.;Zawacki, Lisa Guise;Zeng, Qingbei;Yang, De-Yi;Shao, Yuefei;Dong, Guizhen;Xu, Xiaolian;Yu, Wensheng;Jiang, Yueheng;Jenh, Chung-Her;Hall, James W. III;Carroll, Carolyn DiIanni;Hobbs, Doug W.;Baldwin, John J.;McGuinness, Brian F.;Rosenblum, Stuart B.;Kozlowski, Joseph A.;Shankar, Bandarpalle B.;Shih, Neng-Yang. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Recommanded Product: (S)-2-Ethylpiperazine This article mentions the following:

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. One compound with single-digit CXCR3 affinity and good rat PK and hERG profiles has been identified as a lead for further study. In the experiment, the researchers used many compounds, for example, (S)-2-Ethylpiperazine (cas: 207284-20-6Recommanded Product: (S)-2-Ethylpiperazine).

(S)-2-Ethylpiperazine (cas: 207284-20-6) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazine and its salts did not induce point mutations in a bacterial test. A series of mutagenicity studies in cells, both in vitro and in vivo, has been completed and showed no evidence of mutagenic effect.Recommanded Product: (S)-2-Ethylpiperazine

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

Novel 4-substituted 2-piperazinylquinazolines as potent anticonvulsive and antihypoxic agents was written by Hori, Manabu;Iemura, Ryuichi;Hara, Hideaki;Ozaki, Akio;Sukamoto, Takayuki;Ohtaka, Hiroshi. And the article was included in Chemical & Pharmaceutical Bulletin in 1990.Synthetic Route of C7H16N2 This article mentions the following:

Piperazinylquinazolines, e.g. I [R = Me, Ph, CH₂Ph, CH₂CH:CH₂, (CH₂)_nMe, R¹ = Me, CH₂Ph, (CH₂)_nMe, n = 2-4] were prepared and examined for anticonvulsive and antihypoxic activities. The anal. of quant. structure-activity relationships indicated that the anticonvulsive activity was related to the lipophilicity of the compounds Most of the alkoxyquinazolines I showed potent anticonvulsive and antihypoxic activities. There is a good correlation between the potencies of these activities. In the experiment, the researchers used many compounds, for example, 1-Propylpiperazine (cas: 21867-64-1Synthetic Route of C7H16N2).

1-Propylpiperazine (cas: 21867-64-1) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Synthetic Route of C7H16N2

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