- 2-Azaallyl anions: key models for the elaboration of alkyl-, amino- and hydroxy-1,7-naphthyridine derivatives
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A variety of 5-alkyl-, 5-amino- and 5-hydroxy-6,8-diaryl-1,7-naphthyridines have been efficiently prepared by the treatment of suitable 2-azaallyl anions with diversely functionalized 2-halogenopyridines.
- Couture, Axel,Grandclaudon, Pierre,Simion, Cristian,Woisel, Patrice
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Read Online
- Design, synthesis and molecular docking studies of new azomethine derivatives as promising anti-inflammatory agents
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Herein, we synthesized a series of Ibuprofen-based 4a-k, quinoxaline-based 9a-f and pyridine-based 13a-h azomethine derivatives and studied their anti-inflammatory potency. The in-silico docking studies of the synthesized compounds 4a-k revealed better af
- Desai, Sulaksha R.,Desai, Vidya G.,Pissurlenkar, Raghuvir R.
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supporting information
(2022/01/24)
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- 2-(1H-pyrazol-3-yl) pyridine derivative as well as preparation method and application thereof
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The invention belongs to the field of medicinal chemistry, particularly relates to a compound shown in a formula I, or a stereoisomer, salt, prodrug or solvate thereof, and also relates to a preparation method of the compound and application of the compound in preparation of drugs for treating related diseases mediated by histone demethylase JMJD6.
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Paragraph 0071-0074
(2021/06/22)
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- Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes
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CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chemical probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934, a total of 32 compounds, composed of single-ring, 5,6-, and 6,6-fused heteroaromatic cores, were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. Compared to GSK650394 and STO-609, 13 compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs.
- Asquith, Christopher R. M.,Awad, Dominik,Catta-Preta, Carolina M. C.,Cou?ago, Rafael M.,Drewry, David H.,Eduful, Benjamin J.,Frigo, Daniel E.,Hossain, Mohammad Anwar,Langendorf, Christopher G.,Liang, Yi,Lin, Chenchu,Nay, Kévin,O'Byrne, Sean N.,Oakhill, Jonathan S.,Picado, Alfredo,Pilotte, Joseph R.,Pulliam, Thomas L.,Santiago, André De S.,Scott, John W.,Temme, Louisa,Wells, Carrow I.,Willson, Timothy M.,Zonzini Ramos, Priscila,Zuercher, William J.
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p. 10849 - 10877
(2021/08/03)
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- Discovery of a new class of JMJD6 inhibitors and structure–activity relationship study
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JmjC domain-containing protein 6 (JMJD6) has been thought as a potential target for various diseases particularly cancer. However, few selective JMJD6 inhibitors have been reported. In this investigation, molecular docking and biological activity evaluation were performed to retrieve new JMJD6 inhibitors, which led to the identification of a hit compound, J2. Further structural optimization and structure–activity relationship (SAR) analysis towards J2 were carried out, which gave a new potent JMJD6 inhibitor, 7p. This compound showed an IC50 value of 0.681 μM against JMJD6, but displayed no activity against other tested JmjC domain-containing protein family members, indicating good selectivity (>100 fold). Collectively, this investigation offers a selective JMJD6 inhibitor, which could be taken as a lead compound for subsequent drug discovery targeting JMJD6.
- Wang, Tianqi,Zhang, Rong,Liu, Yang,Fang, Zhen,Zhang, Hailin,Fan, Yan,Yang, Shengyong,Xiang, Rong
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supporting information
(2021/05/27)
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- Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents
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A series of 2-anilinopyridyl linked benzothiazole-hydrazone conjugates (5a-aa) were designed, synthesized and evaluated for their in vitro cytotoxic potency against a panel of cancer cell lines like mouse skin melanoma (B16F10), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), triple negative breast cancer (MDA-MB-231) and normal lung epithelial (L132) cell lines. Preliminary screening results revealed that some of these conjugates like 5i and 5l exhibited a significant antiproliferative effect against human breast cancer (MCF-7) with IC50 values of 1.03 and 1.69 μM respectively. Further, detailed biological studies of this promising conjugate (5i) were carried out on MCF-7 cells. The flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase in a dose dependent manner. Furthermore, in order to determine the effect of the conjugate on cell viability, various cell based assays such as clonogenic assay, ethidium bromide staining, Hoechst staining, detection of ROS generation and annexin V-FITC/PI assays were performed. In these studies, apoptotic features were clearly observed indicating that this conjugate inhibited cell proliferation by apoptosis.
- Sultana, Faria,Saifi, Mohd Aslam,Syed, Riyaz,Mani, Geeta Sai,Shaik, Siddiq Pasha,Osas, Egharevba God'Shelp,Godugu, Chandraiah,Shahjahan, Syeda,Kamal, Ahmed
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p. 7150 - 7161
(2019/05/17)
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- A microwave synthesis 2 - halogenated nicotinate and intermediates thereof
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The invention discloses a method for synthesizing 2-halogenated nicotinic acid ester and intermediates thereof through microwave method. The method comprises the following steps: adding substitute amino acrolein, a catalyst and cyan-acetic ester into a reactor, carrying out reaction under microwave radiation, and tracking the reaction till substitute amino acrolein disappears to prepare and obtain reaction liquid of the intermediates of 2-halogenated nicotinic acid ester; adding hydrogen halide into the reaction liquid, continuously carrying out reaction, and tracking and monitoring the reaction till the reaction is complete; adding alkali liquor into the reaction liquid to adjust the pH value to 5-6; carrying out standing delamination to obtain an aqueous layer and an organic layer; extracting the aqueous layer with an organic solvent, combining the extracted aqueous layer with the organic layer, and carrying out refinement to prepare and obtain 2-halogenated nicotinic acid ester. The synthesis method of 2-halogenated nicotinic acid ester related to the invention has the advantages of beingenvironment-friendly, short in reaction time, simple to operate, high in product yield and good in quality.
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Paragraph 0047; 0048
(2018/05/16)
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- A ultrasonic process for synthesizing 2 - halogenated nicotinate and intermediates thereof
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The invention discloses a method for synthesizing 2-halogenated ester nicotinate and a 2-halogenated ester nicotinate intermediate according to an ultrasonic method. The method comprises the following steps: adding substituent amino acrolein, a catalyst and cyanacetic ester into a reactor for a reaction under ultrasonic radiation; tracing the reaction till substituent amino acrolein is disappeared, thereby obtaining a reaction solution I containing the 2-halogenated ester nicotinate intermediate; then, adding halogen hydride into the reaction solution I for another reaction to obtain a reaction solution II; tracing and monitoring the reaction till completion; adding a lye into the reaction solution II to adjust the pH value of the reaction solution II to be 5-6; carrying out standing stratification to obtain a water layer and an organic layer; conducting extraction on the water layer by utilizing an organic solvent, and then combining the extraction solution with the organic layer; carrying out refining to obtain 2-halogenated ester nicotinate. Through the adoption of the method, an organic synthesis reaction can be effectively facilitated, the reaction speed and yield can be improved, and the environmental protection can be promoted; the reaction time is short and the operation is simple, that is, the organic synthesis reaction can be finished within 2 hours in general; the product yield and quality are high; specifically, the product yield can reach 90% or higher, and exceed that achieved according to the conventional solvent heating reflux method.
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Paragraph 0042; 0043
(2018/04/21)
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- A method for producing 2 - chloro nicotinic acid
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The invention relates to a method for producing 2-chloro nicotinic acid. Propiolic alcohol and diisopropylamine are catalyzed and oxidized to obtain diisopropylamine acrolein. Then Konevenagel reaction is carried out to the diisopropylamine acrolein and ethyl cyanacetate to generate 2-cyan-5-diisopropylamine-2, 4-pentadiene ethyl gallate. Dried hydrogen chloride is let in, and the obtained ethyl 2-chloronicotinate is acidized to obtain 2-chloro nicotinic acid after basic hydrolysis. Compared with the prior art, the method for producing the 2-chloro nicotinic acid employs raw materials easy to purchase, has no rigor condition in the process, and is friendly to environment and suitable for industrialization production.
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Paragraph 0032-0033
(2017/07/13)
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- Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors
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N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.
- Bayliss, Tracy,Robinson, David A.,Smith, Victoria C.,Brand, Stephen,McElroy, Stuart P.,Torrie, Leah S.,Mpamhanga, Chido,Norval, Suzanne,Stojanovski, Laste,Brenk, Ruth,Frearson, Julie A.,Read, Kevin D.,Gilbert, Ian H.,Wyatt, Paul G.
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p. 9790 - 9806
(2017/12/26)
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- Method using hydrothermal method to synthesize 2-halogeneated nicotinate and 2-halogeneated nicotinic acid
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The invention discloses a method using a hydrothermal method to synthesize 2-halogeneated nicotinate and 2-halogeneated nicotinic acid and relates to the field of chemical synthesizing. The method uses substituted amino acrolein, catalyst, catalyst assistant, water and cyanoacetate as raw materials to synthesize the 2-halogeneated nicotinate and the 2-halogeneated nicotinic acid through the hydrothermal method. Compared with the prior art, the method is environmentally friendly, easy in separation, high in product yield, good in product quality, capable of achieving large-scale industrial production favorably, and the like.
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Paragraph 0041; 0042
(2017/11/01)
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- An ionic liquid method of synthesizing 2 - halogenated nicotinate and intermediates thereof
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The invention discloses a method for synthesizing 2-halogenated nicotinate and an intermediate thereof through an ionic liquid method. The method comprises the steps that cyan-acetic ester, ionic liquid and substituted amino acrolein are evenly mixed and heated to a preset temperature for conducting a reaction, the reaction is tracked till the substituted amino acrolein disappears, reaction liquid is cooled to the room temperature and extracted for multiple times through organic solvents, the residual phase of the ionic liquid is reused after being washed and dried, and the intermediate of the 2-halogenated nicotinate is obtained by evaporating the organic solvents from the organic phase; when the 2-halogenated nicotinate is synthesized, the organic solvents do not need to be separated from the intermediate of the 2-halogenated nicotinate, the reaction is continuously conducted by adding hydrogen halide into the organic phase, and the tracking monitoring is conducted till the reaction is completed; the 2-halogenated nicotinate product is prepared after separation. The synthesizing method of the 2-halogenated nicotinate has the advantages of being green and environmentally friendly, easy to operate, high in product yield and good in quality of the synthesized product.
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Paragraph 0044; 0045; 0046; 0047; 0048
(2017/10/13)
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- Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors
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A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 μM to 20 μM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.
- Kamal, Ahmed,Ashraf,Basha, Shaik Thokhir,Ali Hussaini,Singh, Shamshair,Vishnuvardhan,Kiran, Boppana,Sridhar, Balasubramanian
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p. 1382 - 1394
(2016/02/03)
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- Agents and methods for treating ischemic and other diseases
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This invention relates to compounds that modulate TRPM7 protein activity and use of the same for treatment or prophylaxis of ischemia, cancer, pain or glaucoma.
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Page/Page column 97
(2016/06/01)
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- Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability
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A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and
- Ashraf, Md.,Shaik, Thokhir B.,Malik, M. Shaheer,Syed, Riyaz,Mallipeddi, Prema L.,Vardhan, M.V.P.S. Vishnu,Kamal, Ahmed
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supporting information
p. 4527 - 4535
(2016/08/24)
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- Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents
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A series of 2-anilinopyridyl-triazole conjugates (6a-t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.1 μM. Structure-activity relationships were elucidated with various substitutions on these conjugates. Flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase and induce cell death by apoptosis. The tubulin polymerization assay and immunofluorescence analysis showed that these compounds (6q, 6r and 6s) effectively inhibited the microtubule assembly in human prostate cancer cells (DU-145). The docking studies showed that 6s interacts and binds efficiently with the tubulin protein at the colchicine binding site. This was further confirmed by the colchicine competitive binding assay. Moreover, compounds 6q, 6r and 6s possess anti-tubulin activity both in vitro and within cells as demonstrated by the ratio of soluble versus polymerized tubulin. Further the apoptotic effects of compounds were confirmed by Hoechst staining, caspase 3 activation, annexin-V FITC, mitochondrial membrane potential and DNA fragmentation analysis. Interestingly, these compounds did not affect the normal human embryonic kidney cells, HEK-293.
- Kamal, Ahmed,Subba Rao,Vishnuvardhan,Srinivas Reddy,Swapna, Konderu,Bagul, Chandrakant,Subba Reddy,Srinivasulu, Vunnam
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p. 4879 - 4895
(2015/05/05)
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- Synthesis of 2-anilinopyridine-arylpropenone conjugates as tubulin inhibitors and apoptotic inducers
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A series of new (Z)-3-(arylamino)-1-(2-(arylamino)pyridin-3-yl)prop-2-en-1-one conjugates 9a-p were synthesized and evaluated for their cytotoxic activity against some human cancer cell lines. Some of the treated compounds like 9a, 9g and 9j showed significant activity with IC50 values ranging from 0.51 to 1.29 μM. Flow cytometry results revealed that for A549 cells these compounds caused accumulation of cells in the G2/M phase. Interestingly, compound 9a demonstrated a considerable inhibitory effect on tubulin polymerization and showed significant inhibition of tubulin polymerization with an IC50 value of 1.34 μM, whereas nocodazole showed antitubulin activity with an IC50 value 2.64 μM. Further, Hoechst staining and activation of caspase-3 suggested that these conjugates induced cell death by apoptosis. Fluorescence based competitive colchicine binding assay and docking studies suggest that these conjugates 9a and 9g bind to the tubulin perfectly at the colchicine binding site.
- Kamal, Ahmed,Reddy, Vangala Santhosh,Vishnuvardhan,Kumar, G. Bharath,Shaik, Anver Basha,Chourasiya, Sumit S.,Reddy, M. Kashi,Sayeed, Ibrahim Bin,Adiyala, Praveen Reddy,Jain, Nishant
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p. 97367 - 97380
(2015/12/01)
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- Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers
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A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC 50 value of 4.01 μM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.
- Kamal, ?hmed,Ashraf, Md.,Vishnu Vardhan,Faazil, Shaikh,Nayak, V. Lakshma
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supporting information
p. 147 - 151
(2014/01/17)
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- Synthesis, biologicalevaluation, and molecular modeling of (E)-2-aryl-5-styryl-1,3,4-oxadiazolederivatives as acetylcholine esterase inhibitors
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A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a-o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a-q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC50 values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein-ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives. Springer Science+Business Media 2013.
- Kamal, Ahmed,Shaik, Anver Basha,Reddy, G. Narender,Kumar, C. Ganesh,Joseph, Joveeta,Kumar, G. Bharath,Purushotham, Uppula,Sastry, G. Narahari
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p. 2080 - 2092
(2014/05/06)
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- Synthesis of 2-anilinopyridine dimers as microtubule targeting and apoptosis inducing agents
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A series of 2-anilinopyridine dimers have been synthesized and evaluated for their anticancer potential. Most of the compounds have showed significant growth inhibition of the cell lines tested and compound 4d was most effective amongst the series display
- Kamal, Ahmed,Ali Hussaini,Lakshma Nayak,Shaheer Malik,Lakshmi Sucharitha,Shaik, Thokhir Basha,Ashraf, Md.,Bagul, Chandrakant
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p. 6755 - 6767
(2015/02/02)
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- 2-PHENYLNICOTINIC ACID DERIVATIVE
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The present invention is to provide the compounds useful as a treating or preventing agent for gout and hyperuricemia which are 2-phenylnicotinic acid derivatives having a uric acid lowering action due to an excellent xanthine oxidase inhibitory action. Since the 2-phenylnicotinic acid derivatives of the present invention exhibit a uric acid lowering action due to an excellent xanthine oxidase inhibitory action and also hypolipemic action, their utility is very high as a treating or preventive agent for gout and hyperuricemia which are often accompanied by hyperlipemia as a complication.
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Page/Page column 8
(2009/12/23)
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- Claisen condensation of N-methylpyrrolidinone and α-chloronicotinic esters
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Reaction between α-halo-nicotinic esters and a nucleophilic source such as the N-methylpyrrolidin-2-one (NMP) gave unexpected results. The presence of the halide on the pyridine gave a very interesting migration reaction. Extension to 6-methylnicotinic ester derivatives lead to an unexpected carbanion condensation.
- Kaminski, Thomas,Kirsch, Gilbert
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p. 229 - 234
(2008/09/19)
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- Efficient route to medium-ring benzo- and azabenzo-lactones
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The synthesis of precursors of medium-ring benzo- and azabenzo-lactones is performed efficiently from simple ortho-halo aryl and heteroaryl aldehydes. Copyright Taylor & Francis Group, LLC.
- Metay, Estelle,Leonel, Eric,Nedelec, Jean-Yves
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p. 889 - 904
(2008/09/17)
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- 2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials
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A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors.
- Olepu, Srinivas,Suryadevara, Praveen Kumar,Rivas, Kasey,Yokoyama, Kohei,Verlinde, Christophe L.M.J.,Chakrabarti, Debopam,Van Voorhis, Wesley C.,Gelb, Michael H.
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p. 494 - 497
(2008/09/20)
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- Cis-imidazolines
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There are provided compounds of the formula I wherein R, V1, V2 and Ring A are described herein. The compounds exhibit anticancer activity.
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Page/Page column 6
(2010/11/27)
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- Synthesis of a new class of 2-anilino substituted nicotinyl arylsulfonylhydrazides as potential anticancer and antibacterial agents
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A series of N′-1-[2-anilino-3-pyridyl]carbonyl-1-benzenesulfonohydrazide derivatives (7a-i) was synthesized and five of them were selected by the National Cancer Institute (NCI) and evaluated for their in vitro anticancer activity. Three of the investigat
- Kamal, Ahmed,Khan, M. Naseer A.,Srinivasa Reddy,Rohini
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p. 1004 - 1013
(2007/10/03)
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- Synthesis of new flat polyheterocyclic systems potential DNA intercalating agents diazines part 47
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Using a regioselective metallation in connection with Stille cross-coupling reaction, we report here an original synthetic route to obtain in few steps various flat tetra- or pentaheterocyclic compounds which could be potential intercalating DNA agents.
- Audoux, Jerome,Achelle, Sylvain,Turck, Alain,Marsais, Francis,Ple, Nelly
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p. 1497 - 1503
(2007/10/03)
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- SPIROFUROPYRIDINE ARYL DERIVATIVES
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Compounds of formula (I): and pharmaceutically-acceptable salts thereof, wherein: Ar is a moiety of formula (II) or (III): and A, B, and R1 are as defined in the specification, compositions containing such compounds and the use of such compounds and compositions for use in therapy.
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Page/Page column 18; 19
(2008/06/13)
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- Novel Extension of Meyers' Methodology: Stereoselective Construction of Axially Chiral 7,5-Fused Bicyclic Lactams
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A novel extension of Meyer's lactamization is reported for the preparation of seven-membered ring lactams 1a-d incorporating a biaryl unit. The required keto-esters 2a-c were readily accessible via the Suzuki coupling reaction. A borylation-Suzuki couplin
- Penhoat, Mael,Levacher, Vincent,Dupas, Georges
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p. 9517 - 9520
(2007/10/03)
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- Syntheses of substituted pyridines, quinolines and diazines via palladium-catalyzed cross-coupling of aryl Grignard reagents
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The palladium-catalyzed cross-coupling reactions between arylmagnesium halides (phenylmagnesium chloride, mesitylmagnesium bromide, 4-(methoxycarbonyl)phenylmagnesium chloride and 4-cyanophenylmagnesium chloride) and halopyridines allowed the synthesis of substituted pyridines. Owing to the remarkably mild conditions used (often below 0°C), the reaction could be extended to the use of functionalized halopyridines, haloquinolines and halodiazines.
- Bonnet, Véronique,Mongin, Florence,Trécourt, Fran?ois,Quéguiner, Guy,Knochel, Paul
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p. 4429 - 4438
(2007/10/03)
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- Amino acid derivative having anti-CCK activity
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A compound represented by the formula (1): STR1 wherein, m is an integer of 1 to 3; n is an integer 0 or 1; A represents CH or N atom, and forms together with the N atom bonded to the carbonyl group a piperidine ring or a piperazine ring; R1 independently represents a straight or branched chain alkyl group having 1 to 4 carbon atoms; a cycloalkyl group having 3 to 8 carbon atoms; a phenyl group, unsubstituted or substituted with a halogen atom or with an alkoxy group having 1 to 4 carbon atoms; or a pyridyl group; or two R1, together with the group >CH-- to which they bind, form a dibenzo cycloheptenyl group or a fluorenyl group; R2 represents a phenyl group substituted with a carboxyl or substituted carboxyl group; a pyridyl group substituted with a carboxyl or substituted carboxyl group, a pyrazyl group substituted with a carboxyl or substituted carboxyl group, an oxazolyl substituted with a carboxyl or substituted carboxyl group, a triazolyl substituted with one or two carboxyl or substituted carboxyl groups, or a phosphonopyridyl group; and R3 represents an indolyl group unsubstituted or substituted with a substituent selected from the group consisting of a halogen atom, a hydroxy group, an alkoxy group having 1 to 4 carbon atoms and methoxycarbonyl ethyl group and the pharmaceutically acceptable salts thereof.
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- Nicotinic acid esters
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Novel compounds of the formula: STR1 wherein R is selected from saturated or unsaturated alkyls, saturated or unsaturated cycloalkyls, heterocyclic compounds, or from (a) or (b) wherein G is carbon wherein G is carbon or nitrogen; m is 0-10, wherein R1, R2, and R3 are the same or different and selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbons or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl and the pharmacologically acceptable salts thereof; being useful for treating disorder in the central nervous system.
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- Tandem Wolff rearrangement-'tert-amino effect' sequence: Synthesis of 2-oxoindolinium enolate derivatives
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The thermolysis of 1-diazo-2-oxo-(2-N,N-disubstituted aminophenyl)ethylphosphonates 1 gave rise to 2-oxoindolinium enolate derivatives 4 through Wolff rearrangement and interaction of the tert-amino moiety with the ketene functionality. Variable amounts of either ammonium ylides 5 or of products resulting from their transformations were also formed during the course of the reaction. If the amino moiety was substituted by a benzyl or an allyl group, indolinones, resulting from [1,3] or [1,2] benzylic or allylic shifts, were isolated in place of compounds 4 and 5.
- Leost, Francoise,Chantegrel, Bernard,Deshayes, Christian
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p. 7557 - 7576
(2007/10/03)
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- Cyclic compounds and their use
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The present invention relates to a compounds represented by the following formula or salts thereof. STR1 The above compounds have strong angiotensin II antagonistic action, antihypertensive action and action on central nervous system, which are useful for
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- Processes for producing 2-Halo-nicotinic acid derivatives and precursors thereto
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Disclosed are preferred processes for the preparation of 2-halo-nicotinic acid derivatives of formula (IV): STR1 by cyclocondensation of a 4-halo-4-cyanocarbonyl compound of formula (III): STR2 wherein X is Cl or Br; Y is a carbonyl group and R1, R2 and R3 are each, independently, H, Cl, Br or an organic radical. Further preferred aspects include the preparation of the above-noted 4-halo-4-cyanocarbonyl compound via Michael addition of a 2-halonitrile with an α,β-unsaturated aldehyde or ketone, and the preparation of the 2-halonitrile by redistribution of halogen between a 2,2-dihalonitrile and a parent nitrile.
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- Regioselective synthesis of 2-chloro 3-pyridinecarboxylates
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2-Chlorocyanoacetate was found to undergo base-catalyzed Michael addition to α,β-unsaturated ketones or aldehydes to afford 5-oxopentenenitrile derivatives. In the presence of anhydrous HCl, these compounds cyclize to yield 2-chloro-3-pyridinecarboxylates. The process is highly regiospecific and useful in the synthesis of 2,3-disubstituted pyridines.
- Zhang,Stout,Keay,Scriven,Toomey,Goe
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p. 13177 - 13184
(2007/10/03)
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- 2-(Alkylamino)nicotinic Acid and Analogs. Potent Angiotensin II Antagonists
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A series of pyridines and other six-membered ring heterocycles connected to a biphenyltetrazole with a-CH2-NR'-link (1) were discovered to be potent angiotensin II antagonists.In the pyrimidine carboxylic acid series (W = CR, X = N, Y = CH, Z = COOH), compounds with an alkyl group (R') on the exocyclic nitrogen were much more potent than compounds with an alkyl group (R) on the heterocyclic ring.The corresponding pyridine, pyridazine, pyrazine, and 1,2,4-triazine carboxylic acids also showed potent in vitro angiotensin II antagonism.The pyridine (W, X, Y = CH, Z = COOH, R' = n-C3H7) demonstrated potent in vitro activity (pA2 = 10.10, rabbit aorta, and Ki = 0.61 nM, receptor binding in rat liver) as well as exceptional oral antihypertensive activity and bioavailability.Any nonacidic replacement for the carboxylic acid was detrimental for activity.
- Winn, Martin,De, Biswanath,Zydowsky, Thomas M.,Altenbach, Robert J.,Basha, Fatima Z.,et al.
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p. 2676 - 2688
(2007/10/02)
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- Angiotensin II receptor antagonists
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Compounds are disclosed having the formula: STR1 The compounds of the invention are angiotensin II receptor antagonists.
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- Preparation of 2-chloropyridine 3-carboxylic acid esters
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2-chloropyridine 3-carboxylic acid esters are prepared by cyclization of 1,3-butadiene derivatives in the presence of hydrogen chloride.
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- Site-Selectivity in the Reaction of 3-Substituted Pyridine 1-Oxides with Phosphoryl Chloride
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Site-selectivity in the reaction of 3-substituted pyridine 1-oxide with phosphoryl chloride was investigated.When a strongly electron-withdrawing group (e.g.CN, CONRR', COOR, or NO2) was substituted at the 3-position, the reaction of 3-substituted pyridine 1-oxides with phosphoryl chloride yielded 3-substituted 2-chloropyridines as the main products.Keywords- site-selectivity; 3-substituted pyridine 1-oxide; phosphoryl chloride; 3-substituted 2-chloropyridine; chlorination
- Yamanaka, Hiroshi,Araki, Tomio,Sakamoto, Takao
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p. 2244 - 2247
(2007/10/02)
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