- Design, synthesis and SAR of antitubercular benzylpiperazine ureas
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Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]
- Satish, Sohal,Chitral, Rohan,Kori, Amitkumar,Sharma, Basantkumar,Puttur, Jayashree,Khan, Afreen A.,Desle, Deepali,Raikuvar, Kavita,Korkegian, Aaron,Martis, Elvis A. F.,Iyer, Krishna R.,Coutinho, Evans C.,Parish, Tanya,Nandan, Santosh
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- Photocatalytic Water-Splitting Coupled with Alkanol Oxidation for Selective N-alkylation Reactions over Carbon Nitride
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Photocatalytic water splitting technology (PWST) enables the direct use of water as appealing “liquid hydrogen source” for transfer hydrogenation reactions. Currently, the development of PWST-based transfer hydrogenations is still in an embryonic stage. Previous reports generally centered on the rational utilization of the in situ generated H-source (electrons) for hydrogenations, in which photogenerated holes were quenched by sacrificial reagents. Herein, the fully-utilization of the liquid H-source and holes during water splitting is presented for photo-reductive N-alkylation of nitro-aromatic compounds. In this integrate system, H-species in situ generated from water splitting were designed for nitroarenes reduction to produce amines, while alkanols were oxidized by holes for cascade alkylating of anilines as well as the generated secondary amines. More than 50 examples achieved with a broad range scope validate the universal applicability of this mild and sustainable coupling approach. The synthetic utility of this protocol was further demonstrated by the synthesis of existing pharmaceuticals via selective N-alkylation of amines. This strategy based on the sustainable water splitting technology highlights a significant and promising route for selective synthesis of valuable N-alkylated fine chemicals and pharmaceuticals from nitroarenes and amines with water and alkanols.
- Xu, Yangsen,Zhang, Zhaofei,Qiu, Chuntian,Chen, Shaoqin,Ling, Xiang,Su, Chenliang
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p. 582 - 589
(2020/12/09)
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- Scalable preparation of stable and reusable silica supported palladium nanoparticles as catalysts for N-alkylation of amines with alcohols
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The development of nanoparticles-based heterogeneous catalysts continues to be of scientific and industrial interest for the advancement of sustainable chemical processes. Notably, up-scaling the production of catalysts to sustain unique structural features, activities and selectivities is highly important and remains challenging. Herein, we report the expedient synthesis of Pd-nanoparticles as amination catalysts by the reduction of simple palladium salt on commercial silica using molecular hydrogen. The resulting Pd-nanoparticles constitute stable and reusable catalysts for the synthesis of various N-alkyl amines using borrowing hydrogen technology without the use of any base or additive. By applying this Pd-based catalyst, functionalized and structurally diverse N-alkylated amines as well as some selected drug molecules were synthesized in good to excellent yields. Practical and synthetic utility of this Pd-based amination protocol has been demonstrated by upscaling catalyst preparation and amination reactions to several grams-scales as well as recycling of catalyst. Noteworthy, this Pd-catalyst preparation has been up-scaled to kilogram scale and catalysts prepared in both small (1 g) and large-scale (kg) exhibited similar structural features and activity.
- Alshammari, Ahmad S.,Natte, Kishore,Kalevaru, Narayana V.,Bagabas, Abdulaziz,Jagadeesh, Rajenahally V.
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p. 141 - 149
(2020/01/06)
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- Synthetic method of piribedil
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The invention relates to a synthetic method of piribedil. The synthetic method is a brand new process comprising the steps of synthesizing piperonyl piperazine in one step under the effects of pentamethyleneamine, piperazine pyrimidine and paraformaldehyde, and reacting by virtue of piperonyl piperazine and dichloropyrimidine so as to synthesize piribedil. Piperonyl piperazine has not been synthesized by virtue of the synthetic method before. Compared with a traditional synthetic method of piribedil, the synthetic method has the advantages that synthetic steps are simplified, the three wastes are reduced, the utilization ratio of pentamethyleneamine is remarkably increased, and the after-treatment is relatively environment-friendly.
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Paragraph 0014
(2017/04/03)
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- PLANT GROWTH-PROMOTION AGENT AND METHOD FOR PROMOTING PLANT GROWTH
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The present invention concerns: a plant growth-promoting agent comprising a compound represented by Formula (I) or a salt thereof: wherein Ar1 represents a substituted or unsubstituted phenyl group, NZ represents a nitrogen-containing heterocyclic ring group or an acyclic nitrogen-containing group having a partial structure of the nitrogen-containing heterocyclic ring group, n is 0, 1, or 2, R1 and R2 each represent a hydrogen atom, a substituted or unsubstituted C1-3-alkyl group, a cyano group, or a carboxyl group, R1 and R2 may together form an oxo group, and when n is 2, R1 or R2 may be the same or different; and a method for promoting plant growth using the plant growth-promoting agent.
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Paragraph 0139; 0141; 0142; 0143
(2017/11/11)
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- Reevaluation of the 2-nitrobenzyl protecting group for nitrogen containing compounds: An application of flow photochemistry
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Photochemistry under continuous flow conditions has many potential benefits for photochemical reactions that are problematic in batch. The 2-nitrobenzyl moiety is a photolabile protecting group for nitrogen. However, N-deprotection is generally impractical and, therefore, has not been extensively adopted. This Letter reports significant improvements in the N-deprotection of the 2-nitrobenzyl group through the application of continuous flow photolysis. This procedure was applied to a variety of substrates including indoles, indazoles, pyrazoles and secondary amines. Significant improvement in yield, reaction time and scalability was observed under continuous flow conditions.
- Wendell, Chloe I.,Boyd, Michael J.
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supporting information
p. 897 - 899
(2015/02/05)
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- Synthesis and antimalarial activity of hydroxyethylpiperazine derivatives
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The antimalarial activity of hydroxyethylpiperazine derivatives, synthesized from the reaction of (2S,3S)Boc-phenylalanine epoxide with benzylpiperazines in good yields (76-96%), has been evaluated in vitro against the Plasmodium falciparum W2 clone (chlo
- Cunico, Wilson,Gomes, Claudia R.B.,Moreth, Marcele,Manhanini, Diogo P.,Figueiredo, Isabela H.,Penido, Carmen,Henriques, Maria G.M.O.,Varotti, Fernando P.,Krettli, Antoniana U.
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body text
p. 1363 - 1368
(2009/09/27)
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- PIPERAZINYL AND PIPERIDINYL UREAS AS MODULATORS OF FATTY ACID AMIDE HYDROLASE
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Compounds of formula (I) : wherein, Z is -N-or>CH; R1 is -H or -C1-4alkyl; Ar1 is 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-primidinyl, 5-pyrimidinyl, or phenyl, each unsubstituted or substituted at a carbon ring member with one or two Ra moieties; Wher each Ra moiety is independently selected from the group consisting of -C1-4alkyl, -C2-4alkenyl, -OH, -OC1-4alkyl, halo, -CF3, -OCF3, -SCF3, -SH, -S(O)0-2C1-4alkyl, -OSO2C1-4alkyl, -CO2C1-4alkyl, -CO2H, -COC1-4alkyl, -N(Rb)Rc, -SO2NRbRc, -NRbSO2Rc, -C(=O)NRbRc, -NO2, and -CN, wherein Rb and Rc are each independently -H or -C1-4alkyl; and Ar2 is defined in the claims are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity. Thus, the compounds may be administered to treat, e.g., anxiety, pain, inflammation, sleep disorders, eating disorders, or movement disorders (such as multiple sclerosis).
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Page/Page column 91
(2008/06/13)
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- Oligomeric aminodiol-containing compounds, libraries thereof, and process of preparing the same
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Oligomeric compounds comprising a plurality of aminodiol monomer subunits joined by linking groups are provided, as well as libraries of such compounds and processes for preparing the oligomeric compounds and libraries.
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- Pharmaceutically active pyrrolidine derivatives as bax inhibitors
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The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CRR, NOR, NNRR; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NRR or represents a heterocyclic residue having the formula (II) wherein Q is NR, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
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- Pharmaceutically active pyrrolidine derivatives
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The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
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- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
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This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Non anticholinergic gastric acid secretion inhibitors. New piperazine and related derivatives
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Some of the new piperazine derived compounds exhibited interesting gastric antisecretory properties without anticholinergic action. 1 Piperonyl 4 (3,7,11 trimethyl 2,6,10 dodecatrienyl) piperazine was the most active as an antisecretory agent in rat. Some analogous compounds, with the piperazine ring replaced by other heterocyclic or acyclic amines, were also prepared. Structure activity relationships are discussed.
- Tricerri,Elitropi,Panto,et al.
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p. 555 - 562
(2007/10/08)
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