- Synthesis and biological evaluation of chalcone-linked pyrazolo[1,5-: A] pyrimidines as potential anticancer agents
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A series of pyrazolo[1,5-a]pyrimidines substituted at C5 with 1-phenylprop-2-en-1-one (6a-q) and 3-phenylprop-2-en-1-one (7a-k) was synthesized and evaluated for antiproliferative activity. Among them, 6h was found to be the most active compound against the MDA-MB-231 cell line with an IC50 of 2.6 μM. The antiproliferative activity of this series of compounds ranged from 2.6 to 34.9 μM against A549 (lung cancer), MDA-MB-231 (breast cancer) and DU-145 (prostate cancer) cell lines. FACS analysis revealed that these hybrids arrest the cell cycle at the subG1 phase. Western blot analysis and an immunofluorescence assay showed the inhibition of the EGFR and STAT3 axis, which plays an important role in cell survival and apoptosis. Western blot and RT-PCR analyses that displayed an increase in apoptotic proteins such as p53, p21 and Bax and a decrease in the anti-apoptotic proteins Bcl-2 and procaspase-9 confirmed the ability of these hybrids to trigger cell death by apoptosis. Molecular docking studies described the binding of these hybrids to the ATP binding site of EGFR.
- Bagul, Chandrakant,Rao, Garikapati Koteswara,Makani, Venkata Krishna Kanth,Tamboli, Jaki R.,Pal-Bhadra, Manika,Kamal, Ahmed
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Read Online
- Lewis acid-promoted synthesis of highly substituted pyrrole-fused benzoxazinones and quinoxalinones
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A synthesis of a series of novel fused tricyclic heterocyclic compounds has been achieved in one-pot reaction set up starting from (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one and 1,4-benzoxazinone/quinoxalinone derivatives promoted by tin(IV) chloride.
- Selvendran, Suresh,Rajendran, Saravanakumar
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supporting information
p. 437 - 445
(2020/10/22)
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- A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line
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Abstract: Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160?μM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure–activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable. Graphic abstract: [Figure not available: see fulltext.].
- Uygun, Meltem Tan,Amudi, Karina,Tura?l?, ?rem Do?an,Menges, Nurettin
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- Synthesis, in vitro anticancer activity and in silico studies of certain isoxazole-based carboxamides, ureates, and hydrazones as potential inhibitors of VEGFR2
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The ensuing research presents the results of in vitro anticancer activity of novel 28 compounds of isoxazole–based carboxamides 3(a-d); ureates 4(a-g), 5, 6, 7a,b, 8; and hydrazones 9(a-f), 10(a-d), 11a,b as potential inhibitors of VEGFR2. The carboxamide
- Abou-Seri, Sahar M.,Behery, Mohamed G. M.,Eissa, Amal A. M.,Omar, Farghaly A.
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- Design and synthesis of novel 5-arylisoxazole-1,3,4-thiadiazole hybrids as α-glucosidase inhibitors
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Background: α-Glucosidase inhibitors have occupied a significant position in the treatment of type 2 diabetes. In this respect, the development of novel and efficient non-sugar-based inhibitors is in high demand. Objective: Design and synthesis of new 5-arylisoxazole-1,3,4-thiadiazole hybrids possessing α-glucosidase inhibitory activity were developed. Methods: Different derivatives were synthesized by the reaction of various 5-arylisoxazole-3-carboxylic acids and ethyl 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)acetate. Finally, they were evalu-ated for their α-glucosidase inhibitory activity. Results: It was found that ethyl 2-((5-(5-(2-chlorophenyl)isoxazole-3-carboxamido)-1,3,4-thiadiazol-2-yl)thio)acetate (5j) was the most potent compound (IC50 = 180.1 μM) compared with acarbose as the reference drug (IC50 = 750.0 μM). Also, the kinetic study of 5j revealed a competitive inhibition and docking study results indicated desired interactions of that compound with amino acid residues located close to the active site of α-glucosidase. Conclusion: Good α-glucosidase inhibitory activity obtained by the title compounds introduced them as an efficient scaffold, which merits to be considered in anti-diabetic drug discovery developments.
- Akbarzadeh, Tahmineh,Eslami, Azadeh,Faramarzi, Mohammad Ali,Mahdavi, Mohammad,Mirfazli, Seyedeh Sara,Saeedi, Mina,Zardkanlou, Mahsa
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p. 436 - 444
(2021/10/04)
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- Design and Synthesis of Novel Arylisoxazole-Chromenone Carboxamides: Investigation of Biological Activities Associated with Alzheimer's Disease
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A novel series of hybrid arylisoxazole-chromenone carboxamides were designed, synthesized, and evaluated for their cholinesterase (ChE) inhibitory activity based on the modified Ellman's method. Among synthesized compounds, 5-(3-nitrophenyl)-N-{4-[(2-oxo-
- Akbarzadeh, Tahmineh,Edraki, Najmeh,Firuzi, Omidreza,Hariri, Roshanak,Mahdavi, Mohammad,Mirfazli, Seyedeh Sara,Rastegari, Arezoo,Saeedi, Mina
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- Green and efficient synthesis of new pyrido[2,3-d]pyrimidine derivatives using Pd/SBA-15 as a nanocatalyst
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N-Fused heterocycles have received significant attention over the years as valuable compounds due to their biological and pharmaceutical activities. Heterogeneous catalysts such as periodic mesoporous materials have played an important role in the synthes
- Bardajee, Ghasem Rezanejade,Delbari, Akram Sadat,Ghaedi, Aseyeh,Hekmat, Shohreh
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- Novel hybrid molecules of isoxazole chalcone derivatives: Synthesis and study of In Vitro cytotoxic activities
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Background: Now-a-days, the model of “hybrid drugs” has acquired recognition in medicine due to their significant role in the treatment of different health problems. Methods: We have synthesized new series of isoxazole-chalcone conjugates (14a-m) by the C
- Thiriveedhi, Arunkumar,Nadh, Ratnakaram Venkata,Srinivasu, Navuluri,Kaushal, Kishore
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p. 576 - 582
(2018/06/06)
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- Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators
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Antibiotic resistance among clinically significant bacterial pathogens is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. Utilizing computational docking method and structure-based optimization strategy, we rationally designed and synthesized two series of isoxazol-3-yl- and isoxazol-5-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compounds B14 and B16 that possessed the isoxazol-5-yl group showed strong antibacterial activity against various testing strains, including methicillin-resistant Staphylococcus aureus and penicillin-resistant S. aureus. Further molecular biological studies and docking analyses proved that the compound functioned as an effective inhibitor to alter the dynamics of FtsZ self-polymerization via a stimulatory mechanism, which finally terminated the cell division and caused cell death. Taken together, these results could suggest a promising chemotype for development of new FtsZ-targeting bactericidal agent.
- Bi, Fangchao,Song, Di,Zhang, Nan,Liu, Zhiyang,Gu, Xinjie,Hu, Chaoyu,Cai, Xiaokang,Venter, Henrietta,Ma, Shutao
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- Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents
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In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer ce
- ?al??kan, Burcu,?bi?, Kübra,Banoglu, Erden,Sinoplu, Esra,Akhan Güzelcan, Ece,?etin Atalay, Rengül
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p. 1352 - 1361
(2018/11/21)
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- Synthesis, Characterization and biological applications of pyrazole-benzothiazolamine conjugates
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Present paper describes the synthesis of some new pyrazole-benzothiazolamine conjugates by molecular conjunction by adopting appropriate synthetic routes. Purification of intermediates and final compounds has been done by recrystallization and chromatographic techniques. Characterization of all the newly synthesized pyrazole-benzothiazolamine derivatives was done by physical and spectral data. The experimental procedure for the preparation of seventeen pyrazole-benzthiazolamine conjugates has been incorporated. Data of synthesized compounds like IR, 1H NMR and Mass spectra were neatly presented. All these compounds were evaluated for their activity against Gram-positive and Gram-negative bacteria and various fungal strains. Anticancer activity has been carried out for the synthesized compounds using HeLa, DU145 and A549 cell lines using MTT assay and we found that the pyrazole-benzothiazolamine conjugates were possess antimicrobial, antifungal and anticancer activities.
- Sharma, Ramayanam S.K.,Kumar, Ramachandrula Krishna,Ravi Kumar,Havele, Shrikanth H.,Murali Mohan Rao
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p. 1029 - 1034
(2017/03/22)
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- Synthesis of new arylisoxazole–oxindole conjugates as potent antiproliferative agents
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A new series of arylisoxazole–oxindole derivatives (6a–r) were synthesized and evaluated for their antiproliferative activity against human cancer cell lines including non-small cell lung (A549), cervical (HeLa), breast (MCF-7), and prostate (DU-145) cancer cell lines. The synthesized compounds (6a–r) demonstrated excellent to moderate cytotoxicity with IC50 values ranging from 0.82 to 3.69?μm. Some new compounds (6m–r) exhibited profound cytotoxicity better or similar to positive control. More particularly, the compound 6q possesses donating substituent like methoxy group presented at 5-position on D ring exhibited remarkable antiproliferative activity against A-549 (lung cancer) with an IC50 value 0.82?μm. Further studies to determine the mechanistic aspects of these conjugates are under progress.
- Kumar, Gajjela Bharath,Bukhari, Syed Nasir Abbas,Qin, Hua-Li
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p. 634 - 638
(2017/04/06)
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- Design, synthesis and biological evaluation of novel pyrazolochalcones as potential modulators of PI3K/Akt/mTOR pathway and inducers of apoptosis in breast cancer cells
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Cancer has been established as the “Emperor of all maladies”. In recent years, medicinal chemistry has focused on identifying novel anti-cancer compounds; though discovery of these compounds appears to be a herculean task. In present study, we synthesized
- Shaik, Anver Basha,Rao, Garikapati Koteswara,Kumar, G. Bharath,Patel, Nibeditha,Reddy, Vangala Santhosh,Khan, Irfan,Routhu, Sunitha Rani,Kumar, C. Ganesh,Veena, Immadi,Chandra Shekar, Kunta,Barkume, Madan,Jadhav, Shailesh,Juvekar, Aarti,Kode, Jyoti,Pal-Bhadra, Manika,Kamal, Ahmed
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p. 305 - 324
(2017/08/14)
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- Novel heteroarylcarboxamide derivative or pharmacutically acceptable salt thereof, process for the preparation thereof and pharmaceutical composition for prevention or treatment of RAGE receptor related diseases containing the same as an active ingredient
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The present invention refers to novel heterocyclic biting Carbox probably the id derivative acceptable salt, and manufacturing method thereof including RAGE associated active acetylcholinesterase receptor or pharmaceutical composition for preventing or treating disease is directed to. Heterocycle by the present invention a derivative biting Carbox probably the id RAGE receptor antagonism in by, nerve cells with the beta loss oh with wheat id RAGE conjunction with receptor, inhibiting moving into brain, the resulting beta Amyloid plaque formed 21 is known to effectively inhibit generation.. Furthermore, memory a chemicals that are important in the acetylcholine for decomposing an aromatic thus inhibiting acetylcholine s reel sacrifice , RAGE disease associated active acetylcholinesterase receptor or Alzheimer's disease, cerebrovascular dementia, dementia due to damage bean curd, multi blockade dementia, Alzheimer's disease or the like dementia alcoholic or mixed dementia multi blockade and including dementia, pick (pick) bottle, a smartcrew [...] -Jakob (Creutzfeldt-jakob) bottle, that thyroid gland symptoms , bean curd a blade Parkinson (Parkinson) bottle, Huntington's disease (Huntington) which is useful in preventing or treating, can be used.
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Paragraph 0365-0368
(2021/11/02)
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- Diphenylpyrazoles as replication protein A inhibitors
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Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.
- Waterson, Alex G.,Kennedy, J. Phillip,Patrone, James D.,Pelz, Nicholas F.,Feldkamp, Michael D.,Frank, Andreas O.,Vangamudi, Bhavatarini,Souza-Fagundes, Elaine M.,Rossanese, Olivia W.,Chazin, Walter J.,Fesik, Stephen W.
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supporting information
p. 140 - 145
(2015/03/04)
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- Simple and efficient syntheses of novel benzo[4,5]imidazo[1,2-a]pyridine derivatives
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A novel series of benzo[4,5]imidazo[1,2-a]pyridine derivatives is synthesized through the reaction of 2-(1H-benzo[d]imidazol-2-yl)acetonitrile and different ethyl 2,4-dioxo-4-arylbutanoate derivatives in the presence of piperidine in refluxing EtOH. All the products are easily prepared within 25-45 min in good to excellent yields.
- Goli-Garmroodi, Fereshteh,Omidi, Marzieh,Saeedi, Mina,Sarrafzadeh, Farhad,Rafinejad, Ali,Mahdavi, Mohammad,Bardajee, Ghasem Rezanejade,Akbarzadeh, Tahmineh,Firoozpour, Loghman,Shafiee, Abbas,Foroumadi, Alireza
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p. 743 - 746
(2015/01/30)
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- Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors
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In an attempt to develop potent and selective anticancer agents, a series of twenty arylpyrazole linked benzimidazole conjugates (10a-t) were designed and synthesized as microtubule destabilizing agents. The joining of arylpyrazole to the benzimidazole mo
- Kamal, Ahmed,Shaik, Anver Basha,Polepalli, Sowjanya,Kumar, G. Bharath,Reddy, Vangala Santhosh,Mahesh, Rasala,Garimella, Srujana,Jain, Nishant
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p. 1082 - 1095
(2015/03/04)
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- Synthesis of (Z)-(arylamino)-pyrazolyl/isoxazolyl-2-propenones as tubulin targeting anticancer agents and apoptotic inducers
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A new class of pyrazole and isoxazole conjugates were synthesized and evaluated for their cytotoxic activity against various human cancer cell lines. These compounds have shown significant cytotoxicity with lower IC50 values. FACS results revealed that A549 cells treated with these compounds arrested cells at the G2/M phase of the cell cycle apart from activating cyclin B1 protein levels. Particularly, compounds 9a and 9b demonstrated a remarkable inhibitory effect on tubulin polymerization and showed a pronounced inhibitory effect on tubulin polymerization with IC50 values of 1.28 μM and 0.28 μM respectively, whereas nocodazole, a positive control, has shown lower antitubulin activity with an IC50 value of 2.64 μM. Furthermore, these compounds induced apoptosis by loss of mitochondrial membrane potential, propidium iodide (PI) staining and the activation of caspase-3. Results of a fluorescence based competitive colchicine binding assay suggest that these conjugates bind successfully at the colchicine binding site of tubulin. These investigations reveal that such conjugates containing pyrazole with a trimethoxy phenyl ring and indole moieties have potential for the development of newer chemotherapeutic agents. This journal is
- Kamal, Ahmed,Reddy, Vangala Santhosh,Shaik, Anver Basha,Kumar, G. Bharath,Vishnuvardhan,Polepalli, Sowjanya,Jain, Nishant
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p. 3416 - 3431
(2015/03/18)
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- Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents
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A series of twenty one compounds with pyrazole and oxindole conjugates were synthesized by Knoevenagel condensation and investigated for their antiproliferative activity on different human cancer cell lines. The conjugates are comprised of a four ring scaffold; the structural isomers 12b and 12c possess chloro-substitution in the D ring. Among the congeners 12b, 12c, and 12d manifested significant cytotoxicity and inhibited tubulin assembly. Treatments with 12b, 12c and 12d resulted in accumulation of cells in G2/M phase, disruption of microtubule network, and increase in cyclin B1 protein. Zebrafish screening revealed that 12b, and 12d caused developmental defects. Docking analysis demonstrated that the congeners occupy the colchicine binding pocket of tubulin.
- Kamal, Ahmed,Shaik, Anver Basha,Jain, Nishant,Kishor, Chandan,Nagabhushana, Ananthamurthy,Supriya, Bhukya,Bharath Kumar,Chourasiya, Sumit S.,Suresh, Yerramsetty,Mishra, Rakesh K.,Addlagatta, Anthony
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p. 501 - 513
(2015/01/30)
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- Design and synthesis of pyrazole/isoxazole linked arylcinnamides as tubulin polymerization inhibitors and potential antiproliferative agents
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As pyrazole and isoxazole based derivatives are well-known for displaying a considerable biological profile, an attempt has been made to unravel their cytotoxic potential. In this context, a number of pyrazole/isoxazole linked arylcinnamide conjugates (15
- Kamal, Ahmed,Shaik, Anver Basha,Rao, Bala Bhaskara,Khan, Irfan,Bharath Kumar,Jain, Nishant
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p. 10162 - 10178
(2015/10/28)
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- Facile, novel and efficient synthesis of new pyrazolo[3,4-b]pyridine products from condensation of pyrazole-5-amine derivatives and activated carbonyl groups
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An efficient synthesis of novel ethyl-1,3,4-triphenyl-1H-pyrazolo[3,4-b]pyridine-6-carboxylate products has been achieved via condensation of pyrazole-5-amine derivatives and activated carbonyl groups, in refluxing acetic acid. This process has been found to be useful in the preparation of new N-fused heterocycle products in good to excellent yields.
- Ghaedi,Bardajee,Mirshokrayi,Mahdavi,Shafiee,Akbarzadeh
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p. 89652 - 89658
(2015/11/10)
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- Synthesis of 3-(1,2-dioxoethyl)- and 2,3-dicarbonyl-containing pyrroles
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The transition metal-catalyzed reaction of 2H-azirines with 1,2,4-tricarbonyl compounds leads to 3-(1,2-dioxoethyl)- and 2,3-dicarbonyl-pyrrole derivatives, useful building blocks for the preparation of 3-heterocyclyl pyrroles and pyrroles fused with heterocycles. The influence of catalysts and the reaction conditions on the yields of pyrroles and the regioselectivity of the reaction were studied. Experimental and theoretical results suggest that the reaction proceeds via the formation of an intermediate azirine-metal complex and subsequent nucleophilic N-C3 bond cleavage.
- Galenko, Alexey V.,Khlebnikov, Alexander F.,Novikov, Mikhail S.,Avdontceva, Margarita S.
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p. 1940 - 1951
(2015/03/30)
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- Pyrazole-oxadiazole conjugates: Synthesis, antiproliferative activity and inhibition of tubulin polymerization
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A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates are comprised of pyrazole and oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. The Type I class has a trimethoxy substituent and the type II class has a 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates, 11a, 11d and 11f manifest potent cytotoxicity with IC50values ranging from 1.5 μM to 11.2 μM and inhibit tubulin polymerization with IC50values of 1.3 μM, 3.9 μM and 2.4 μM respectively. The cell cycle assay showed that treatment with these conjugates results in accumulation of cells in the G2/M phase and disrupts the microtubule network. Elucidation of zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
- Kamal, Ahmed,Shaik, Anver Basha,Polepalli, Sowjanya,Santosh Reddy, Vangala,Bharath Kumar,Gupta, Soma,Rama Krishna,Nagabhushana, Ananthamurthy,Mishra, Rakesh K.,Jain, Nishant
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p. 7993 - 8007
(2015/02/18)
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- Concise synthesis of α-(hydroxymethyl) alkyl and aryl vinyl ketones
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2,4-Diketoesters 2 have first been reported as starting materials for the synthesis of a new class of α-hydroxymethyl-α,β-unsaturated ketones 3. Thus, under heterogeneous liquid-liquid medium in the presence of concentrated aqueous potassium carbonate as a base, both aliphatic and aromatic 2,4-dioxoalkanoates 2 react with aqueous formaldehyde to afford the corresponding ketones 3 in fair to good yields. Copyright Taylor & Francis Group, LLC.
- Kraem, Jihene Ben,Amri, Hassen
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p. 110 - 117
(2012/10/30)
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- Synthesis and acrosin inhibitory activities of 5-phenyl-1H-pyrazole-3- carboxylic acid amide derivatives
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A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were mo
- Tian, Wei,Han, Guangqian,Zhu, Ju,Qi, Jingjing,Chen, Qianqian,Zhao, Juntao,Zheng, Canhui,Zhang, Ling,Zhou, Youjun,Lv, Jiaguo
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p. 4177 - 4184
(2013/07/25)
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- Pyrazole derivatives as inhibitors of arachidonic acid-induced platelet aggregation
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Antiplatelet drugs are promising therapeutics to intervene with platelet aggregation in arterial thrombosis, most prominently in myocardial infarction and ischemic stroke. Here, we describe the synthesis and structure-activity relationships of potent inhibitors of platelet aggregation based on the 1,5-diarylpyrazol-3-carboxamide scaffold. Analogs from this series demonstrated potent anti-aggregatory activities against arachidonic acid-induced platelet aggregation, as measured by turbidimetric method of Born. 1,5-Diarylpyrazole-3- carboxamides obtained with small-basic amines (7, 8, 50, 51, 61, 62) displayed the strongest activity with IC50 values in low nanomolar range (5.7-83 nM). On the basis of their high potency in cellular environment, these straightforward pyrazole derivatives may possess potential in the design of more potent compounds for intervention with cardiovascular diseases.
- Levent, Serkan,?ali?kan, Burcu,?ift?i, Murat,?zkan, Ye?im,Yenicesu, Idil,ünver, Hüseyin,Banoglu, Erden
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- AZAINDAZOLES
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Herein are disclosed azaindazoles of formula (I), (I), where the various groups are defined herein, and which are useful for treating cancer.
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Page/Page column 138; 166
(2013/03/28)
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- Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4- phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives
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A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5- carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents.
- Nagarapu, Lingaiah,Mateti, Jhansi,Gaikwad, Hanmant K.,Bantu, Rajashaker,Sheeba Rani,Prameela Subhashini
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scheme or table
p. 4138 - 4140
(2011/08/06)
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- Biarylmethoxy isonipecotanilides as potent and selective inhibitors of blood coagulation factor Xa
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New chloro-substituted biarylmethoxyphenyl piperidine-4-carboxamides were synthesized and assayed in vitro as inhibitors of the blood coagulation enzymes factor Xa (fXa) and thrombin. An investigation of effects of the amidine and isopropyl groups attache
- Lopopolo, Gianfranco,Fiorella, Filomena,De Candia, Modesto,Nicolotti, Orazio,Martel, Sophie,Carrupt, Pierre-Alain,Altomare, Cosimo
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experimental part
p. 180 - 191
(2012/01/05)
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- Design and synthesis of novel pyrazole-based Lp-PLA2 inhibitors
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A series of novel pyrazole-based lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors have been designed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully opt
- Wang, Yi,Xu, Weiren,Shao, Hua,Xie, Yafei,Wang, Jianwu
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experimental part
p. 2039 - 2048
(2012/03/26)
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- Synthesis and cytotoxicity evaluation of 1-[3-(9H-carbazol-4-yloxy)-2- hydroxypropyl]-3-aryl-1H-pyrazole-5-carboxylic acid derivatives
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Several novel molecules, 1-(3′-(9H-carbazol-4-yloxy)-2′- hydroxypropyl)-3-aryl-1H-pyrazole-5-carboxylic acid derivatives 3a-g were synthesized and screened to evaluate their cytotoxicity against cancer cells in vitro. The compounds 3a-g has been prepared by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 4-oxiranylmethoxy-9H-carbazole in moderate to excellent yields. The cytotoxicity of synthesized compounds was evaluated by a SRB (sulforhodamine B) assay against cancer cell such as SK-N-SH human neuroblastoma (NB), human A549 lung carcinoma, human breast cancer MCF-7 cell lines. The results showed that seven compounds can suppress SK-N-SH tumor cancer cell growth. Among them, compound 3d was the most effective small molecule in inhibiting SK-N-SH cell growth.
- Nagarapu, Lingaiah,Gaikwad, Hanmant K.,Sarikonda, Kartheeka,Mateti, Jhansi,Bantu, Rajashaker,Raghu,Manda, Krishna Madhuri,Kalvendi, Shasi Vardhan
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experimental part
p. 4720 - 4725
(2010/11/16)
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- Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles
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A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.
- Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Plaskon, Andrey S.,Dmytriv, Yuri V.,Grygorenko, Oleksandr O.,Mykhailiuk, Pavel K.,Krotko, Dmitriy G.,Pushechnikov, Alexei,Tolmachev, Andrey A.
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scheme or table
p. 510 - 517
(2010/09/05)
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- Regioselective synthesis of 4-acyl-1-hydroxy-2,3-benzodioates by chelation-controlled [3+3] annulation of 3-acyl-4-ethoxy-2-oxo-3-enoates with 1,3-bis(trimethylsilyloxy)-1,3-butadienes
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4-Acyl-1-hydroxy-2,3-benzodioates were regioselectively prepared by chelation-controlled [3+3] cyclization of 1,3-bis(trimethylsilyloxy)-1,3- butadienes with 3-acyl-4-ethoxy-2-oxo-3-enoates.
- Riahi, Abdolmajid,Shkoor, Mohanad,Fatunsin, Olumide,Khera, Rasheed Ahmad,Fischer, Christine,Langer, Peter
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supporting information; experimental part
p. 4248 - 4251
(2009/12/06)
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- NITROGENOUS FUSED HETEROAROMATIC RING DERIVATIVE
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The invention provides a compound or its pharmaceutically-acceptable salt of formula (I): wherein A1 is a hydrogen, etc.; j and k are 0 or 1; is a double bond, etc.; is a double bond, etc.; one of W1 and W2 is E-O-W, etc., and the other is a hydrogen atom, etc.; E is a divalent group derived from a benzene ring, etc., by removing two hydrogen atoms therefrom; W is a group of formula (II-1): which has a histamine-H3 receptor antagonistic effect or a histamine-H3 receptor inverse-agonistic effect and is useful for prevention or remedy of metabolic system diseases, circulatory system diseases or nervous system diseases.
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Page/Page column 40
(2010/11/24)
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- Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxyla te
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We synthesized a series of novel small molecules, ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxyla te derivatives 3a-3o, by the reaction of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 2-aryloxymethylepoxide in the presence of potassium c
- Wei, Fang,Zhao, Bao-Xiang,Huang, Bin,Zhang, Lu,Sun, Chun-Hui,Dong, Wen-Liang,Shin, Dong-Soo,Miao, Jun-Ying
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p. 6342 - 6347
(2007/10/03)
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- SUBSTITUTED PYRAZOLES AS PPAR AGONISTS
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A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof (I) wherein: p is O or 1; q is O or 1; R1 and R2 are independently H or C1-3 alkyl; R3 and R4 are independently H, C1-6 alkyl, -OC1-6 alkyl, halogen, OH, C2-6 alkenyl or CF3; R5 is H, C1-6 alkyl (optionally substituted by one or more halogens, -COphenyl, OC1-6 alkyl, phenyl morpholino or C2-6 alkenyl. R6 is C1-6 alkyl, halogen, -OCH2 phenyl, phenyl (optionally substituted by C1-3 alkiyl), morpholino, pyrrolidino, piperidino, thiophenyl, furanyl pyridinyl or -OC2-6 alkenyl. These compounds activate the alpha and gamma subtypes fo the hppar receptor and are useful e.g. in the treatment of diabetes, dyslipidemia or syndrome X.
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Page/Page column 137-138
(2010/02/12)
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- Slow-binding inhibition of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase
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2-Keto-3-deoxy-6-phosphogluconate (KDPG) aldolase is a key enzyme in the Entner-Doudoroff pathway of bacteria. It catalyzes the reversible production of KDPG from pyruvate and D-glyceraldehyde 3-phosphate through a class I Schiff base mechanism. On the basis of aldolase mechanistic pathway, various pyruvate analogues bearing β-diketo structures were designed and synthesized as potential inhibitors. Their capacity to inhibit aldolase catalyzed reaction by forming stabilized iminium ion or conjugated enamine were investigated by enzymatic kinetics and UV-vis difference spectroscopy. Depending of the substituent R (methyl or aromatic ring), a competitive or a slow-binding inhibition takes place. These results were examined on the basis of the three-dimensional structure of the enzyme.
- Braga, Remi,Hecquet, Laurence,Blonski, Casimir
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p. 2965 - 2972
(2007/10/03)
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- Synthesis and structural characterisation of the isotypic complexes MIIL2(py)2·2H2O (M = Cu, Zn); the interplay of lattice imposed ligand disposition and Jahn-Teller distortions [HL = 5-(4-methoxyphenyl)pyrazole-3-carboxylic acid]
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The mononuclear complexes of general formula ML2(H2O)2 (M = Zn, Cu, Ni, Co) and ML2(py)2?2H2O (M = Zn, Cu, Co) have been prepared [HL = 5-(4-methoxyphenyl)pyrazole-3-carboxylic acid, py = pyridine]. The crystal structures of ZnL2(py)2·2H2O and CuL2(py)2·2H2O have been determined and are isotypic. Two independent molecules are present in the structures, both of which are pseudo-octahedral with mutually trans stereochemistries. In the zinc case the two metal coordination environments differ only slightly and these differences are probably due to packing forces, but for copper the differences are greater and indicate that the direction of the Jahn-Teller distortion observed is dependent upon the subtle constraints imposed by the lattice. The occurrence of such molecular forms is unique for such donor sets and allows a special opportunity to observe the interplay of Jahn-Teller effects and packing forces.
- Crane, Jonathan D.,Fox, O. Danny,Sinn, Ekkehard
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p. 1461 - 1465
(2007/10/03)
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- Studies on anti-inflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives
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A series of novel 1,5-diarylpyrazole derivatives was synthesized and tested for anti-inflammatory and analgesic activities to develop anti- inflammatory agents with fewer side effects than existing nonsteroidal anti- inflammatory drugs. The structure-activity relationships in this series were extensively studied. Electron-withdrawing substituents such as CN and CF3 were optimal at the 3-position of the pyrazole ring. Replacement of these substituents with bulky ones gave less active compounds. The 4- (methylsulfonyl)phenyl group seemed to be the optimal group at the 5-position of the pyrazole ring. The most potent compound was 1-(4-fluorophenyl)-5-[4- (methylsulfonyl)phenyl]-pyrazole-3-carbonitrile (19a), with oral ED50 values of 0.030 and 0.47 mg/kg on adjuvant-induced arthritis and collagen- induced arthritis, respectively, and an ED30 value of 7.4 mg/kg in the yeast-induced hyperalgesia (Randall-Selitto) assay. Compound 19a also showed potent inducible cyclooxygenase (COX-2)-inhibitory activity (IC50=0.24μm) with no COX-1 inhibition even at 100μM.
- Tsuji, Kiyoshi,Nakamura, Katsuya,Konishi, Nobukiyo,Tojo, Takashi,Ochi, Takehiro,Senoh, Hachiro,Matsuo, Masaaki
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p. 987 - 995
(2007/10/03)
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- Pyridopyridazine compounds and their use
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An assay method which comprises utilizing chemiluminescence of a pyridopyridazine compound of the formula STR1 wherein R1 is a hydrocarbon group or a heterocyclic group each of which may be substituted and R2 is hydroxy group, thiol
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