- Sequence-Defined Dithiocarbamate Oligomers via a Scalable, Support-free, Iterative Strategy
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Precise control over the monomeric sequence on natural sequence-defined polymers (SDPs) leads to their structural diversity and functions. However, absolute control over the monomeric sequence on a synthetic polymer remains a challenging process. Herein, we describe a support-free, protection-deprotection-free, cost-effective, and fast iterative strategy for multigram production of a new class of SDP with a unique functional group, dithiocarbamate, a potential group for material and biomedical applications. The strategy is based on a unique monomer, named as amine-hydroxyl monomer, and a three-component reaction between the monomer, CS2, and terminal chloro group of the growing chain. The fast strategy allows us to synthesize a 5-mer sequence-defined oligomer in 6 h. For a proof of concept, a range of aliphatic and aromatic groups have been incorporated at different sequences in the sequence-defined oligomer. This SDP platform has further been advanced by two ways: (i) multiple approaches for postsynthetic modification of SDP and (ii) increasing the chain length in a single step.
- Nanjan, Pandurangan,Jose, Anna,Thurakkal, Liya,Porel, Mintu
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p. 11019 - 11026
(2020/12/22)
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- Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists
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5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.
- Wang, Wenli,Zheng, Lan,Li, Wei,Zhu, Chen,Peng, Weiqing,Han, Bing,Fu, Wei
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p. 235 - 248
(2020/02/18)
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- Design, synthesis, biological evaluation and molecular modeling study of new thieno[2,3-d]pyrimidines with anti-proliferative activity on pancreatic cancer cell lines
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Pancreatic cancer is one of the most challenging diseases with seven months only as median survival time due to its poor prognosis. Several enzymes are blamed for the progress of pancreatic cancer especially, platelet-derived growth factor receptors (PDGFRs), this in turn makes them promising targets for its treatment. In this study, twenty eight new compounds based on thieno[2,3-d]pyrimidine scaffold were synthesized as anti-pancreatic cancer agents mimicking the benzofuro[3,2-d]pyrimidine derivative, amuvatinib. Various linkers including amides, esters, ketones, urea and thiourea derivatives were utilized to study their effect on the anti-proliferative activity of these compounds. Most of the tested compounds revealed good cytotoxic activities against pancreatic carcinoma cell line PANC-1. Compound 9d showed the highest cytotoxicity with an IC50 value of 5.4 μM. Furthermore, 9d showed excellent platelet derived growth factor receptor (PDGFR-α) inhibitory activity, with IC50 value 0.155 μM. Docking study was carried out into PDGFR-α active site which showed comparable binding mode to that of FDA approved PDGFR-α inhibitor, imatinib. 3D-Quantitative structure activity relationship (QSAR) model was built up with five-featured pharmacophore which could be implemented for emerging effective lead structures. These compounds could serve as a new chemotype for discovering new agents for pancreatic cancer therapy.
- Salem, Mohamed S.H.,Abdel Aziz, Yasmine M.,Elgawish, Mohamed S.,Said, Mohamed M.,Abouzid, Khaled A.M.
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- Intramolecular carbene C-H insertion reactions of 2-diazo-2-sulfamoylacetamides
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The intramolecular C-H insertions of carbenes derived from 2-diazo-2-sulfamoylacetamides were studied. 2-Diazo-2-sulfamoylacetamides were first prepared from chloroacetyl chloride and secondary amines through acylation followed by sequential treatments with sodium sulfite, phosphorus oxychloride, secondary amines, and 4-nitrobenzenesulfonyl azide. The results indicate that: (1) 2-diazo-N,N-dimethyl-2-(N,N-diphenylsulfamoyl)acetamide can take the formal aromatic 1,5-C-H insertion in its N-phenylsulfonamide moiety to afford the corresponding 1,3-dihydrobenzo[c]isothiazole-3-carboxamide 2,2-dioxide derivative; (2) no aliphatic C-H insertions occur for 2-diazo-2-(N,N-dialkylsulfamoyl)acetamides; and (3) for 2-diazo-N-phenyl-2-(N-phenylsulfamoyl)acetamides, the formal aromatic 1,5-C-H insertion in the N-phenylacetamide moiety is favorable to afford the corresponding 3-sulfamoylindolin-2-one derivatives as sole or major products. The intramolecular competitive aromatic 1,5-C-H insertion reactions of 2-diazo-2-sulfamoylacetamides with aryl groups on both amide and sulfonamide groups reveal that the N-aryl substituents on acetamide are more active than those on sulfonamide. The chemoselectivity is controlled by electronic effect of the aryl group.
- Que, Chuqiang,Huang, Peipei,Yang, Zhanhui,Chen, Ning,Xu, Jiaxi
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- Preparation method for N-phenyl indolone
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The invention especially relates to a preparation method for N-phenyl indolone, belonging to the field of organic synthesis. The preparation method for N-phenyl indolone comprises the following steps:subjecting diphenylamine (a compound as shown in a formula II) and chloroacetyl chloride (a compound as shown in a formula III) to a condensation reaction to prepare 2-chloro-N,N-diphenylacetamide (acompound as shown in a formula IV); subjecting 2-chloro-N,N-diphenylacetamide and acetate to an esterification reaction so as to obtain 2-acetoxy-N,N-diphenylacetamide (a compound as shown in a formula V); and subjecting 2-acetoxy-N,N-diphenylacetamide to a ring closure reaction so as to obtain N-phenyl indolone. The preparation method provided by the invention is a clean high-efficiency synthesis method for N-phenyl indolone; in the whole preparation process, high-contamination raw materials are discarded, and reaction temperature is lowered; and the method is friendly to environment and safe and simple to operate, and has great industrial application value.
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Paragraph 0030; 0040; 0041; 0042
(2018/09/21)
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- Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase
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A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. Furthermore, we explored the structure-activity relationships of N-10 haloacetamides that influence the potency of such analogs toward inhibition of L. major promastigote growth in vitro. With respect to the mechanism of action, selected compounds were evaluated for time-dependent inactivation of Trypanosoma brucei trypanothione reductase. Our results are indicative of a covalent interaction which could account for potent antiprotozoal activities.
- Marcu, Ana,Schurigt, Uta,Müller, Klaus,Moll, Heidrun,Krauth-Siegel, R. Luise,Prinz, Helge
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supporting information
p. 436 - 443
(2015/12/24)
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- Efficiently functionalized oxacalix[4]arenes: Synthesis, characterization and exploration of their biological profile as novel HDAC inhibitors
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A series of novel substituted oxacalix[4]arene has been synthesized and explored for their biological profile by evaluating anticancer, antifungal and antibacterial properties. The derivatives have been characterized by various spectroscopic techniques su
- Mehta, Viren,Athar, Mohd,Jha,Panchal, Manthan,Modi, Krunal,Jain
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supporting information
p. 1005 - 1010
(2016/05/24)
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- Visible light photoredox-catalysed intermolecular radical addition of α-halo amides to olefins
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We present α-chloro amides as a new class of α-acetyl radical precursors, which undergo a tin-free, photoredox-catalysed intermolecular α-alkylation with various olefins exclusively in an anti-Markovnikov fashion. The reaction represents a reductive atom
- Nakajima, Masaki,Lefebvre, Quentin,Rueping, Magnus
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supporting information
p. 3619 - 3622
(2014/04/03)
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- One-pot synthesis of indolo[2,3-c]quinolin-6-ones by sequential photocyclizations of 3-(2-azidophenyl)-N-phenylacrylamides
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A one-pot synthesis of indolo[2,3-c]quinolin-6(7H)-ones was achieved by sequential photocyclizations of 3-(2-azidophenyl)-N-phenylacrylamides in moderate to high yields. The reactions proceeded via photochemical cyclization of aryl azides to form N-phenylindol-2-carbamides and subsequent 6π-electrocyclic reaction and oxidative aromatization to afford the corresponding indolo[2,3-c]quinolin-6(7H)-ones. Georg Thieme Verlag Stuttgart · New York.
- Li, Zhanshan,Wang, Weixia,Zhang, Xiaotian,Hu, Congcong,Zhang, Wei
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supporting information
p. 73 - 78
(2013/04/24)
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- Photoinduced and N-bromosuccinimide-mediated cyclization of 2-azido-N-phenylacetamides
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An efficient synthesis of quinoxalin-2(1H)-ones or spiro[cyclohexene-1, 2′-imidazol]-4′-ones has been achieved in moderate to high yields by the visible light-induced and N-bromosuccinimide-mediated cyclization reaction of 2-azido-N-phenylacetamides at ambient temperature. Both the regioselectivity and the speed of cyclization are affected by the substituents attached to the phenyl ring. For example, quinoxalin-2-ones are produced as the main products when the substrates bear electron-withdrawing groups at the para-position of the phenyl ring; in contrast, spiro[cyclohexene-1,2′-imidazol]-4′-ones are obtained as the main products when the substrates bear electron-donating groups at the para-position.
- Li, Zhan-Shan,Wang, Wei-Xia,Yang, Ji-Dong,Wu, Yue-Wei,Zhang, Wei
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supporting information
p. 3820 - 3823
(2013/09/02)
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- Design, synthesis, pharmacological evaluation and descriptor based similarities study of N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl] acetamides as potential antipsychotics
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A series of novel N,N-diphenyl-2-[4-(substituted phenyl)piperazin-1-yl] acetamides was designed, synthesized and evaluated for anti-dopaminergic activity, anti-serotonergic activity and catalepsy induction studies in mice as an approach to novel potential antipsychotic agent. Antipsychotic activity of these compounds in terms of blocking of dopaminergic transmission was evaluated by their ability to inhibit apomorphine induced climbing behavior in mice and antiserotonergic activity of synthesized compounds was assessed by studying inhibition of 5-HTP induced head twitches. All the synthesized compounds were found to exhibit anti-dopaminergic and anti-serotonergic activity in behavioral models. The compound 3f showed better antipsychotic potential among the different synthesized compounds. The descriptor based similarities study for blood brain permeation established a good similarity between the synthesized compounds with standard atypical antipsychotics.
- Dash, Radha Charan,Bhosale, Sharad H.,Shelke, Suhas M.,Suryawanshi, Mugdha R.,Mahadik, Kakasaheb R.
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p. 1069 - 1075,7
(2012/12/12)
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- Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants
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A series of novel N1-substituted-N2,N 2-diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines
- Nikalje, Anna Pratima G.,Ghodke, Mangesh,Girbane, Amol
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experimental part
p. 57 - 64
(2012/03/26)
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- Triazoloamides as potent γ-secretase modulators with reduced hERG liability
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Synthesis and SAR studies of novel aryl triazoles as gamma secretase modulators (GSMs) are presented in this communication. Starting from our aryl triazole leads, optimization studies were continued and the series progressed towards novel amides and lactams. Triazole 57 was identified as the most potent analog in this series, displaying single-digit nanomolar Aβ42 IC 50 in cell-based assays and reduced affinity for the hERG channel.
- Fischer, Christian,Zultanski, Susan L.,Zhou, Hua,Methot, Joey L.,Shah, Sanjiv,Nuthall, Hugh,Hughes, Bethany L.,Smotrov, Nadja,Hill, Armetta,Szewczak, Alexander A.,Moxham, Christopher M.,Bays, Nathan,Middleton, Richard E.,Munoz, Benito,Shearman, Mark S.
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scheme or table
p. 3140 - 3146
(2012/06/04)
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- Synthesis and antifungal activity of some substituted phenothiazines and related compounds
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Several phenothiazines and related compounds were synthesized and their antifungal activity was evaluated in vitro. The results observed for α-chloro-N-acetyl phenothiazine led us to choose this compound as a lead in the search of antifungal agents.
- Sarmiento, Gabriela P.,Vitale, Roxana G.,Afeltra, Javier,Moltrasio, Graciela Y.,Moglioni, Albertina G.
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experimental part
p. 101 - 105
(2011/02/25)
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- Synthesis, computational studies and preliminary pharmacological evaluation of 2-[4-(aryl substituted) piperazin-1-yl] N, N-diphenylacetamides as potential antipsychotics
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A series of 2-[4-(aryl substituted) piperazin-1-yl] N, N-diphenylacetamides have been synthesized and the target compounds (3a-j) were evaluated for atypical antipsychotic activity in apomorphine induced climbing, 5-HTP induced head twitches behavior and catalepsy studies in mice. The physicochemical similarity of the target compounds with respect to standard drugs clozapine, ketanserin and risperidone was calculated by using software programs. Among them, compound 3e showed maximum atypical antipsychotic like profile.
- Kumar, Sushil,Wahi,Singh, Ranjit
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experimental part
p. 4753 - 4759
(2011/11/04)
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- Reversal agent and linker variants of reversed chloroquines: Activities against Plasmodium falciparum
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We have shown that "reversed chloroquine molecules" constructed from chloroquine-like and resistance "reversal-agent"-like cores can be powerful drugs against malaria (J. Med. Chem. 2006, 49, 5623-5625). Several reversed chloroquines are now presented that probe parameters governing the activities against chloroquine-resistant and chloroquine-sensitive malaria strains. The design is tolerant to linker and reversal agent changes, but a piperazinyl group adjacent to the quinoline, at least for the group of compounds studied here, may be detrimental. 2009 American Chemical Society.
- Andrews, Simeon,Burgess, Steven J.,Skaalrud, Deborah,Kelly, Jane Xu,Peyton, David H.
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supporting information; experimental part
p. 916 - 919
(2010/07/05)
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- Highly enantioselective palladium-catalyzed alkylation of acyclic amides
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(Chemical Equation Presented) Even acyclic amides are suitable nucleophile subtrates for asymmetric allylic alkylations. The allylation products are formed in high yields in the presence of a palladium catalyst with a 1,1′-P,N ferrocene ligand (see scheme; R = (S)-1,1′-bi-2-naphthol). The nature of the substituents on the nitrogen atom of the amide has a critical effect on the efficiency and selectivity of the reaction.
- Zhang, Kai,Peng, Qian,Hou, Xue-Long,Wu, Yun-Dong
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supporting information; experimental part
p. 1741 - 1744
(2009/02/06)
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- ORGANIC COMPOUNDS
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The invention relates to novel diamines of the formula (I) in which all variables are as defined in the specification, in free base form or in acid addition salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
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Page/Page column 29-30
(2008/06/13)
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- Design, synthesis and?in?vivo anticonvulsant screening in?mice of?Novel phenylacetamides
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A set of seven novel N-substituted 2-anilinophenylacetamides were designed by pharmacophore generation and using flexible alignment module of MOE software. The novel molecules were synthesized and screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Test compounds were found to be potent in MES test. Compounds 12 and 14 were found to be more potent with ED50 values 24.0 and 8.0?mg kg-1, respectively, and their activity was comparable to standard drugs (Phenytoin, Carbamazepine). Test compounds did not show significant activity in ScPTZ test. Compounds 12 and 14 also exhibited higher protective indices (20.3 and 87.5, respectively) when assessed for neurotoxicity by rotarod test as compared to the standards.
- Shindikar,Khan,Viswanathan
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p. 786 - 792
(2007/10/03)
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- Substituted indoles as inhibitors of poly (ADP-ribose) polymerase (PARP)
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The present invention relates to a series of substituted indole derivatives of the formula I: wherein R, R1, R2, R3, R4, X and Y are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5′-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.
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Page/Page column 15
(2010/02/11)
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- Synthesis and antimicrobial activities of some imidazole substituted indoles
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The compounds 1-substituted 2-(imidazol-1-yl)-3-(4,5-diarylimidazol-2-yl) indoles 2, 1-substituted 2-(imidazol-1-yl)-3-(phenanthro[9,10-d]imidazol-2-yl) indoles 3 and 1-substituted 2-(imidazol-1-yl)-3-(benzimidazol-2-yl)indoles 4 have been synthesized from 1-substituted 2-(imidazol-1-yl)-3-formylindole 1. The structural elucidation of the synthesised compounds has been performed by IR, 1H NMR and mass spectroscopic data and elemental analyses. Antimicrobial activities of the compounds are examined and notable antifungal activity is obtained from some of the compounds as expected in comparison with the control agent ketoconazole.
- Benkli, Kadriye,Demirayak, Seref,Gundogdu-Karaburun, Nalan,Kiraz, Nuri,Iscan, Gokalp,Ucucu, Umit
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p. 174 - 179
(2007/10/03)
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- Novel cyclic amide derivatives
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Novel compounds represented by the following formula (I) that act as a ligand to sigma receptor/binding cite and a medicament comprising the same as an active ingredient: wherein X represents an alkyl group, an aryl group, a heterocyclic group or the like; Q represents a group represented by —CH2—, —CO—, —O—, —CH(OR7)— or the like wherein R7 represents a hydrogen atom, an alkyl group or the like; n represents an integer of from 0 to 5; R1 and R2 each represent a hydrogen atom, an alkyl group or the like; B represents either of the following groups: wherein R3, R4, R5, and R6 each represent a hydrogen atom, a halogen atom, an alkoxyl group or the like; m represents 1 or 2; and the ring of: represents an aromatic heterocyclic ring.
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- A convenient preparation of N-alkyl and N-arylamines by smiles rearrangement - Synthesis of analogues of diclofenac
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Smiles rearrangement of substituted aryloxyacetamides in which oxygen and nitrogen are separated by COCH2 group has been successful even when the aryloxy ring carries weak or no electron withdrawing group. Earlier reports of such reactions involved either strong electron withdrawing groups or a special catalyst. The diphenylamines thus obtained gave analogues of diclofenac in only one case.
- Wadia,Patil
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p. 2725 - 2736
(2007/10/03)
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- Synthesis of substituted oxindoles from α-chloroacetanilides via palladium-catalyzed C - H functionalization
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A novel method for the synthesis of oxindoles is described. In the presence of catalytic palladium acetate and 2-(di-tert-butylphosphino)biphenyl, α-chloroacetanilides are converted to oxindoles in good to excellent yields with high functional group compatibility using triethylamine as a stoichiometric base. The cyclization is highly regioselective, obviating the need for prefunctionalized arenes. Plausible mechanistic pathways for the reaction are discussed. Copyright
- Hennessy, Edward J.,Buchwald, Stephen L.
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p. 12084 - 12085
(2007/10/03)
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- Discovery of a new class of centrally active M1 selective muscarinic antagonists related to pirenzepine
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A series of lipophilic analogs of the antimuscarinic ligand pirenzepine (1) were prepared and assessed for their antimuscarinic activity in a radioligand binding assay on the five muscarinic subtypes expressed in CHO or A9L cells. It was found that biaryl
- Van Hijfte, Luc,Zerr, Veronique,Richards, Mary H.,Moser, Paul,Hibert, Marcel F.,Van Giersbergen, Paul L.M.
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p. 190 - 196
(2007/10/03)
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- Diaryl piperazineacetamides as antimuscarinic agents
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Diaryl piperzineacetamide compounds useful as antimuscarinic agents for treating a variety of indications such as Parkinson's disease, motion sickness and for the inhibition of gastric acid secretion.
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- Synthesis and quantitative structure-activity relationships of diclofenac analogues
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The synthesis of a series of 2-anilinophenylacetic acid, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.
- Moser,Sallmann,Wiesenberg
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p. 2358 - 2368
(2007/10/02)
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- A Novel Class of "GABAergic" Agents: 1-Aryl-3-(aminoalkylidene)oxindoles
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Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles.Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dimethylamino)ethylidene and N-methyl-2-pyrrolidinylidene side chains.The precise mechanism of action of these agents is unclear at this time; however, they are not GABA mimics and they do not affect GABA levels.Like other GABAergic agents, these compounds are potent enhancers of benzodiazepine binding and they antagonize cyclic GMP elevations induced by isoniazid.Compounds from this series may therefore have potential therapeutic utility as anticonvulsants or anxiolytics.
- Sarges, Reinhard,Howard, Harry R.,Koe, B. Kenneth,Weissman, Albert
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p. 437 - 444
(2007/10/02)
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- Cycloadditions, 9: Intramolecular Diels-Alder Reaction of Allenecarboxanilides; Incorporation of the Amide Nitrogen Atom in Benzo- and Dibenzo-condensated Five-, Six-, and Seven-membered Rings
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The allenecarboxanilides 6a-f, the amide nitrogen atom of which is part of a benzo-condensated five-, six-, or seven-membered ring, are synthesized via phosphorus ylides.Thermolysis of 6 in refluxing xylene induces the intramolecular Diels-Alder reaction only in those cases, where the heterocycle is six- or seven-membered.The allenecarboxamide 6b with the six-membered ring bearing only one benzene nucleus in addition furnishes the quinoline derivatives 9 and 10 as main products, while in the case of the allenecarboxamides 6a,c possessing a five-membered heterocycle no reaction takes place whatever.It is tried to explain this different thermolytic behaviour by taking into consideration the spatial arrangement of the two reacting ?-systems (allene and arene) determined by the structure.
- Diehl, Klaus,Himbert, Gerhard
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p. 2874 - 2888
(2007/10/02)
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