- Potent antiproliferative activity of bradykinin B2 receptor selective agonist FR-190997 and analogue structures thereof: A paradox resolved?
-
Βradykinin stimulation of B2 receptor is known to activate the oncogenic ERK pathway and overexpression of bradykinin receptors B1 and B2 has been reported to occur in glioma, colorectal and cervical cancers. B1R and B2R antagonists have been shown to reverse tumor proliferation and invasion. Paradoxically, B1R and B2R agonism has also been reported to elicit antiproliferative benefits. In order to complement the data accumulated to date with the natural substrate bradykinin and peptidic B2R antagonists, we decided to examine for the first time the response elicited by B2R stimulation in breast cancer lines with a non-peptidic small molecule B2R agonist. We synthesized and assessed the highly selective and potent B2R partial agonist FR-190997 in MCF-7 and MDA-MBA-231 breast cancer lines and found it possessed significant antiproliferative activity (IC50 2.14 and 0.08 μΜ, respectively). The modular nature of FR-190997 allowed us to conduct a focused SAR study and discover compound 10 which exhibits subnanomolar antiproliferative activity (IC 50 0.06 nΜ) in the TNBC MDA-MBA-231 cell line. This performance surpasses, in most cases by several orders of magnitude, those of established anticancer agents and FDA-approved breast cancer drugs. In line with the established literature we suggest that this remarkable activity precipitates from a dual mode of action involving agonist-induced receptor internalization/degradation combined with sequestration of functional intracellular B2 receptors and inhibition of the associated endosomal signaling. The latter mode may be realized by appropriate ligands regardless of B2R agonist/antagonist designation which only relates to membrane residing GCPRs. Under this prism the controversy over the antiproliferative effects of B2 agonists and antagonists is potentially neutralized.
- Rassias, Gerasimos,Leonardi, Sofia,Rigopoulou, Dionisia,Vachlioti, Eleanna,Afratis, Konstantinos,Piperigkou, Zoi,Koutsakis, Christos,Karamanos, Nikos K.,Gavras, Haralambos,Papaioannou, Dionissios
-
supporting information
(2020/11/12)
-
- Amino acid conjugates of aminothiazole and aminopyridine as potential anticancer agents: Synthesis, molecular docking and in vitro evaluation
-
Purpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3 (a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development. Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities. Results: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 μM and 11.52 μM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade. Conclusion: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.
- Ali, Tahir,Imran, Muhammad,Li, Jing Bo,Li, Shupeng,Nadeem, Humaira,Naz, Shagufta,Sarwar, Sadia,Shah, Fawad Ali,Tan, Zhen
-
p. 1459 - 1476
(2021/04/19)
-
- HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
-
The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
- -
-
Page/Page column 92; 93
(2021/06/22)
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- FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
-
The present invention relates to compound-linker constructs and antibody-drug-conjugates of compounds of formula (I) that are useful as modulators of STING (Stimulator of Interferon Genes).
- -
-
Page/Page column 128; 129
(2021/06/22)
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- Synthesis and Penicillin-binding Protein Inhibitory Assessment of Dipeptidic 4-Phenyl-β-lactams from α-Amino Acid-derived Imines
-
Monocyclic β-lactams revive the research field on antibiotics, which are threatened by the emergence of resistant bacteria. A six-step synthetic route was developed, providing easy access to new 3-amino-1-carboxymethyl-4-phenyl-β-lactams, of which the penicillin-binding protein (PBP) inhibitory potency was demonstrated biochemically.
- Decuyper, Lena,Juki?, Marko,Sosi?, Izidor,Amoroso, Ana Maria,Verlaine, Olivier,Joris, Bernard,Gobec, Stanislav,D'hooghe, Matthias
-
supporting information
p. 51 - 55
(2019/11/28)
-
- THERAPEUTIC COMPOUNDS
-
The present invention relates to compounds that are Nrf2 activators. The compounds have the structural formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of diseases or disorders associated with Nrf2 activation.
- -
-
Paragraph 00187
(2020/06/10)
-
- Synthesis of New Methanofullerenes with Phthalimide Fragment
-
Abstract: Bromo- and chloromethyl ketones based on N-phthalyl-substituted amino acids have been synthesized via the Arndt–Eistert reaction. The products [2+1] cycloaddition to the fullerene scaffold has afforded the monoadducts of fullerene C60.
- Mustafin, A. G.,Sakhautdinov, I. M.,Sakhautdinova, G. F.
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p. 244 - 248
(2020/04/17)
-
- A Convenient One-Pot Synthesis of 1,5-Disubstituted Tetrazoles Containing an Amino or a Carboxy Group
-
Abstract: A convenient method is proposed for constructing the tetrazole ring by a one-pot reaction of amides with phosphorus oxychloride and sodium azide. A series of 1,5-disubstituted tetrazoles containing an amino or a carboxy group, which present interest as buildings blocks for the synthesis of biologically active substances, were obtained.
- Obushak, M. D.,Pokhodylo, N. T.,Shyyka, O. Ya.
-
p. 802 - 812
(2020/07/03)
-
- A CONJUGATE OF AN AMANITA TOXIN WITH BRANCHED LINKERS
-
Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.
- -
-
Page/Page column 154
(2020/08/22)
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- AMINO ACID DERIVATIVES FOR THE TREATMENT OF INFLAMMATORY DISEASES
-
The present disclosure provides certain amino acid derivatives that inhibit NF-kB activation and are therefore useful for the treatment of inflammatory diseases. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
- -
-
Page/Page column 36
(2020/08/13)
-
- Synthesis, in silico study and antimicrobial activity of new piperine derivatives containing substituted δ-esters
-
A series of fifteen new piperine-derived diesters was synthesized through the substitution reaction between the salt of piperic acid, obtained through piperine basic hydrolysis, with the δ-chloro-esters, obtained through the cleavage of tetrahydrofuran (THF) with acyl chlorides in the presence of ZnCl2. The final compounds were obtained with yields ranging from 50 to 84% and were characterized by infrared (IR) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR). The new compounds were evaluated in silico in regard to their ADME (absorption, distribution, metabolism, and excretion) properties, and in vitro for their antimicrobial activity against bacteria strains (Staphylococcus aureus and Pseudomonas aeruginosas), yeast fungi (Candida albicans and C. tropicalis) and filamentous fungi (Aspergillus fumigatus, A. flavus and A. niger). The results from the in silico studies of Lipinski's rule of five showed that most compounds present good pharmacological possibilities, and the results from in vitro antimicrobial activity showed that 8 of the 15 synthesized compounds displayed antimicrobial activity, inhibiting the growth of 40-80% of tested strains, with a minimum inhibitory concentration (MIC) interval ranging from 1024 to 256 μg mL-1
- Barbosa-Filho, José M.,Brandao, Maria C. R.,De Athayde-Filho, Petr?nio F.,Dutra, Thalisson F.,Lima, Edeltrudes O.,Lira, Bruno F.,Neto, Hermes Diniz,Trindade, Emmely O.
-
p. 2590 - 2602
(2020/11/18)
-
- Quinazolinyl carboxylic ester derivative containing isoindolone group and application thereof
-
The invention discloses a quinazolinyl carboxylic ester derivative containing an isoindolone group, and the derivative has a structural general formula shown as the specification, wherein R is aryl substituted alkyl, aryl substituted cyclolky or biaryl. According to the invention, the novel isoindolone group-containing quinazolinyl carboxylic ester derivative is synthesized, can effectively inhibit the growth of antibiotic-sensitive or drug-resistant bacteria, and has a new action mechanism.
- -
-
Paragraph 0056-0058
(2021/01/04)
-
- A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
-
The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
- -
-
Paragraph 000720; 000721
(2021/03/02)
-
- A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS
-
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
- -
-
Page/Page column 264
(2021/01/23)
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- Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators
-
Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound 22d displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound 25b (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics.
- Surur, Abdrrahman S.,Bock, Christian,Beirow, Kristin,Wurm, Konrad,Schulig, Lukas,Kindermann, Markus K.,Siegmund, Werner,Bednarski, Patrick J.,Link, Andreas
-
supporting information
p. 4512 - 4522
(2019/05/17)
-
- Amide prodrug derivatives as protein kinase inhibitors
-
The invention relates to amide prodrug compounds of novel kinase inhibitors. The prodrugs are characterized in that amino of original drugs is subjected to amidation modification, so that bioavailability of the original drugs in vivo is significantly improved. The invention further relates to pharmaceutical composition containing the prodrugs and a method for treating cancer or other cell proliferative abnormal diseases by the prodrugs and the pharmaceutical composition.
- -
-
Paragraph 0126; 0129-0133
(2019/02/04)
-
- A chemically contiguous hapten approach for a heroin-fentanyl vaccine
-
Background: Increased death due to the opioid epidemic in the United States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin. Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine. Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin-fentanyl vaccine. Importantly, this is the first report of such a strategy in the opioid-drug-vaccine field.
- Natori, Yoshihiro,Hwang, Candy S.,Lin, Lucy,Smith, Lauren C.,Zhou, Bin,Janda, Kim D.
-
supporting information
p. 1020 - 1031
(2019/06/08)
-
- A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
-
The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
- -
-
Page/Page column 13; 235
(2019/07/17)
-
- Rh(III)-Catalyzed C-H Amidation of Arenes with N-Methoxyamide as an Amidating Reagent
-
The Rh(III)-catalyzed amidation of C(sp2)-H bonds has been reported by employing the N-methoxyamide as a novel amino source. An excellent level of functional group tolerance can be achieved when N-methoxyamide derivatives are used as the amidating reagents. Importantly, several known bioactive compounds such as Aminalon, Pregabalin, Gabapentin, and Probenecid can be transformed to effective amidating reagents, as a way to facilitate the development of new bioactive molecules.
- Ju, Guodong,Li, Guobao,Qian, Guanwen,Zhang, Jingyu,Zhao, Yingsheng
-
supporting information
p. 7333 - 7336
(2019/10/08)
-
- Decarboxylative Synthesis of Functionalized Oxindoles via An Iron-Initiated Radical Chain Process and Application in Constructing Diverse Fused-Indoline Heterocycles
-
Rapid construction of diverse fused-indoline?heterocycle (FIH) frameworks including high-value pyrroloindolines, furoindolines and thienoindolines in a two-step sequence has been described. The key to success hinges on the adoption of peresters as α-heteroatom alkyl radical precusors, which can smoothly react with N-arylacrylamides via a radical chain process initiated by inexpensive FeCl2?4H2O to afford the functionalized oxindoles, the key intermediates to FIH skeletons. The approach features operationally-simplicity, broad substrates scope and mild conditions. (Figure presented.).
- Cui, Zhihao,Du, Da-Ming
-
supporting information
p. 93 - 99
(2017/10/24)
-
- Synthesis and study of modified polyvinyl alcohol containing amino acid moieties as anticancer agent
-
A series of new phthalimides compounds[3-7]a-i were synthesized from reaction of Malic anhydride, phthalic anhydride, nitro phthalic anhydride, 2-phenyl-4H-benzo[d][1,3]oxazin-4-one, 2-(4-nitrophenyl)-4H-benzo[d][1,3]oxazin-4-one with different amino acids as glycine, alanine, valine, leucine, isoleucine, serine, threonine, tyrosine and Phenyl alanine [1]a-i under fusion conditions. Compounds [3-7]a-i react with SOCl2 in the presence of benzene to produce compounds [8-12]a-i. Chemical modification of Poly(vinyl alcohol)were obtained by reaction of PVA with compounds [8-12]a-i using the dimethyl formamide to give compounds [13-17]a-i. The structure of the synthesized compounds was characterized by their analytical and spectral data as, IR spectra, 1H, 13C-NMR, Elemental analysis (CHN), UV-Vis Spectroscopy, Scanning electron microscopy (SEM), Antibacterial activity were screened via two kinds of bacteria. Also, anticancer activity were examined for most of the modified polyvinyl alcohol.
- Samir, Ali H.,Saeed, Ruwaidah S.,Matty, Fadhel S.
-
p. 286 - 294
(2018/03/21)
-
- Novel bisphosphonates with antiresorptive effect in bone mineralization and osteoclastogenesis
-
Bisphosphonates such as zoledronic, alendronic and risedronic acids are a class of drugs clinically used to prevent bone density loss and osteoporosis. Novel P-C-P bisphosphonates were synthesized for targeting human farnesyl pyrophosphate synthase (hFPPS) and human geranylgeranyl pyrophosphate synthase (hGGPPS), key enzymes of the mevalonate pathway, and capable of anti-proliferative action on a number of cell lines (PC3, MG63, MC3T3, RAW 264.7, J774A.1, bone marrow cells and their co-colture with PC3) involved in bone homeostasis, bone formation and death. Among sixteen compounds, [1-hydroxy-2-(pyrimidin-2-ylamino)ethane-1,1-diyl]bis(phosphonic acid) (10) was effective in reducing PC3 and RAW 264.7 cell number in crystal-violet and cell-dehydrogenase activity assays at 100 μM concentration. 10 reduced differentiated osteoclasts number similarly with zoledronic acid in osteoclastogenesis assay. At nanomolar concentrations, 10 was more effective than zoledronic acid in inducing mineralization in MC3T3 and murine bone marrow cells. Further, 10 significantly inhibited the activity of hFPPS showing an IC50 of 0.31 μM and a remarkable hydroxyapatite binding of 90%. Docking calculations were performed identifying putative interactions between some representative novel bisphosphonates and both hFPPS and hGGPPS. Then, 10 was found to behave similarly or even better than zoledronic acid as a anti-resorptive agent.
- Savino, Salvatore,Toscano, Annamaria,Purgatorio, Rosa,Profilo, Emanuela,Laghezza, Antonio,Tortorella, Paolo,Angelelli, Mariacristina,Cellamarea, Saverio,Scala, Rosa,Tricarico, Domenico,Thomas Marobbio, Carlo Marya,Perna, Filippo,Vitale, Paola,Agamennone, Mariangela,Dimiccoli, Vincenzo,Tolomeo, Anna,Scilimati, Antonio
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p. 184 - 200
(2018/09/18)
-
- Amides of N-Deacetyllappaconitine and Amino Acids
-
Amides were prepared from N-deacetyllappaconitine and the amino acids glycine, taurine, and γ-aminobutyric acid.
- Gabbasov,Tsyrlina,Spirikhin,Yunusov
-
p. 951 - 955
(2018/09/27)
-
- 1,4-DI-(4-METHYLTHIOPHENYL)-3-PHTALOYLAZETIDINE-2-ONE AND THE DERIVATIVES THEREOF
-
The present invention relates to a compound with formula (I) or a salt and/or a pharmaceutically acceptable solvate thereof, the method for preparing same as well as the uses thereof, in particular the therapeutic use thereof, mainly in the treatment of diseases associated with a hyperactivity of the endocannabinoid system.
- -
-
Paragraph 0185-0186
(2018/11/02)
-
- Discovery of a Highly Selective Cell-Active Inhibitor of the Histone Lysine Demethylases KDM2/7
-
Histone lysine demethylases (KDMs) are of critical importance in the epigenetic regulation of gene expression, yet there are few selective, cell-permeable inhibitors or suitable tool compounds for these enzymes. We describe the discovery of a new class of inhibitor that is highly potent towards the histone lysine demethylases KDM2A/7A. A modular synthetic approach was used to explore the chemical space and accelerate the investigation of key structure–activity relationships, leading to the development of a small molecule with around 75-fold selectivity towards KDM2A/7A versus other KDMs, as well as cellular activity at low micromolar concentrations.
- Gerken, Philip A.,Wolstenhulme, Jamie R.,Tumber, Anthony,Hatch, Stephanie B.,Zhang, Yijia,Müller, Susanne,Chandler, Shane A.,Mair, Barbara,Li, Fengling,Nijman, Sebastian M. B.,Konietzny, Rebecca,Szommer, Tamas,Yapp, Clarence,Fedorov, Oleg,Benesch, Justin L. P.,Vedadi, Masoud,Kessler, Benedikt M.,Kawamura, Akane,Brennan, Paul E.,Smith, Martin D.
-
supporting information
p. 15555 - 15559
(2017/12/02)
-
- SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION
-
Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.
- -
-
Page/Page column 138
(2017/10/11)
-
- Immobilized boronic acid for Suzuki-Miyaura coupling: Application to the generation of pharmacologically relevant molecules
-
An synthetic strategy for the generation of a variety of biaryl and related derivatives, based on Suzuki-Miyaura coupling using immobilized boronic acid, is described. The importance of the methodology was demonstrated by its further application to biologically interesting compounds such as 4-biaryl-β-lactams, descripted as cholesterol absorption inhibitors and anti-MRSA active agents, neoflavonoids, imidazoles, isoxazolines, among others.
- Martinez-Amezaga,Delpiccolo,Mata
-
p. 34994 - 35003
(2017/07/24)
-
- Phthiobuzonum derivative and its preparation and use
-
The invention relates to a ftibamzone derivative and a preparation method and an application thereof, and belongs to the technical field of ftibamzone medicament synthesis. Pharmacological experiments prove that the ftibamzone derivative of the invention has obvious cytotoxic activity and antiviral activity, and can be used for treating viral diseases such as tumor, herpes, trachoma, and the like.
- -
-
Paragraph 0088; 0092
(2016/11/09)
-
- Silicon-containing poly(esters) with halogenated bulky side groups. Synthesis, characterization and thermal studies
-
Poly(esters) (PEs) derived from diacids containing bulky side groups, which have an halogenated (Cl, Br) imide ring, an aminoacidic residue (glycine, l-alanine, l-valine) and an amide group were obtained with a silicon-containing diphenol. Also PEs without the aminoacidic residue were obtained. PEs were characterized by IR and NMR spectroscopy, and the results were in agreement with the proposed structures. PEs were obtained with good yields and moderate or high ηinh values. PEs were soluble in aprotic polar solvents and were swollen in other solvents like m-cresol and THF. The Tg values were determined and it was possible to see a tendency in the sense that when the size of the atom (Cl, Br) bonded to the imidic ring is increased, the Tg values decreased, also for those PEs obtained without the aminoacidic residue. The thermal decomposition temperatures showed that only two PEs can be considered as thermostable, considering TDT values above 400°C at 10% of weight lost. The other PEs showed good thermal stability, showing in general a decrease of the TDT values when the volume of the side group, is increased. PEs showed UV-vis transparency at 400 nm lower than 20%, but between 500 and 600 nm, showed 80% transparency. PEs containing halogen atoms showed flame retardancy in a simple essay, with respect to PEs without halogen atoms in which the combustion was complete.
- Tagle,Terraza,Tundidor-Camba,Coll
-
p. 49132 - 49142
(2015/06/16)
-
- Synthesis of pyrazoles based on functionalized allenoates
-
Regiospecific synthesis of pyrazole-3-carboxylate derivatives by 1,3-dipolar cycloaddition of diazomethane with allenoates in presence of triethylamine is demonstrated. Reaction of allenoates with stearic acid moiety containing diazoketone is explored under ultrasonic conditions. Novel derivatives of pyrazole were achieved in excellent yields.
- Sakhautdinov, Ilshat M.,Gumerov, Aynur M.,Batyrshin, Ilnur R.,Fatykhov, Akhnaf A.,Suponitsky, Kyrill Yu.,Yunusov, Marat S.
-
p. 641 - 651
(2014/04/03)
-
- Synthesis, characterization, andcomputational studies on phthalic anhydride-based benzylidene-hydrazide derivatives as novel,potential anti-inflammatory agents
-
A series of phthalic anhydride-based substituted benzylidene-hydrazide derivatives (3a-i) was synthesized. The synthesized derivatives were authenticated by TLC, UV-visible, FTIR, NMR, and mass spectroscopic techniques and further screened for in vivo anti-inflammatory and analgesic activities by carrageenan-induced rat paw oedema and tail immersion methods, respectively, using diclofenac sodium as standard drug. The derivatives 3d, 3e, and 3h were found to be most active anti-inflammatory and analgesic agents among all the synthesized derivatives. The physico-chemical similarity of the derivatives with standard drugs was assessed by calculating various physicochemical properties using software programs. The percent similarity of synthesized derivatives was found to be good except 3i. The derivatives were subjected to QSAR by multilinear regression using Analyze it version 3.0 software and two statistically sound models were developed with R2 (0.933-0.960), Radj2 (0.595-0.762) and Q2 (0.999) with good F (2.76-4.84) values. Molecular docking studies were performed by MVD software (version 2012.5.0.0). The derivative 3h has emerged out as most potent anti-inflammatory agent with highest dock score, i.e., -93.64. Springer Science+Business Media 2013.
- Kajal, Anu,Bala, Suman,Kamboj, Sunil,Saini, Vipin
-
p. 2676 - 2689
(2014/05/06)
-
- A novel way to tricyclic heteroaromatics; Thiazolo[5,4- b ]thieno[3,2- e ]pyridine derivatives
-
Thiazolo[5,4-b]thieno[3,2-e]pyridine derivatives, novel tricyclic heteroaromatics, have been designed and synthesized by a one-pot reaction of diazepinethiones and aldehydes. This reaction is based on a novel rearrangement reaction of seven-membered 1,4-diazepine-2-thiones to six-membered 3-aminopyridine-2-thiols catalyzed by scandium(III) triflate. Georg Thieme Verlag Stuttgart. New York.
- Huang, Liye,Yu, Ruina,Leng, Ling,Gong, Feng,Zhu, Xinhai,Wan, Yiqian
-
p. 2317 - 2326
(2014/11/08)
-
- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
-
The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
-
supporting information; experimental part
p. 1598 - 1601
(2012/03/22)
-
- An efficient and convenient protocol for the synthesis of optically active 1,2,4-triazolo-[3,4-b]-[1,3,4]-thiadiazole, 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives having L-amino acid moieties
-
Aseries of novel bis triazolothiadiazole, 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives attached to L-amino acid moieties were synthesized in good yields using a simple and practical method. The structure of all synthesized compounds was confirmed by IR, 1H NMR, 13C NMR spectroscopy and elemental analysis.
- Foroughifara, Naser,Ebrahimib, Sattar,Mobinikhaldeic, Akbar,Mozafaric, Reza
-
experimental part
p. 1 - 4
(2012/05/05)
-
- Thermal oligomerization of methyl 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2- yl)buta-2,3-dienoate
-
Dimeric compounds formed as a result of thermal oligomerization of methyl 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)buta-2,3-dienoate were identified.
- Sakhautdinov, I. M.,Batyrshin, I. R.,Fatykhov, A. A.,Galin, F. Z.,Yunusov, M. S.
-
p. 793 - 798,6
(2020/08/31)
-
- Ionic liquid-catalyzed and microwave-assisted syntheses of pyrrolizine-and indolizinedione derivatives
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3H-Pyrrolo[2,1-a]isoindole-2,5-diones and isoindolo[2,1-a]quinoline-5,11- diones were synthesized by intramolecular cyclization of N-[2-oxo-3-(triphenyl- λ5-phosphanylidene)propyl]-and N-[2-(triphenyl- λ5-phosphanylidene)acetyl]phthalimides, respectively, in the presence of ionic liquid ([bmim][BF4], 10 mol %) as catalyst or under microwave irradiation.
- Sakhautdinov, I. M.,Batyrshin, I. R.,Sergeeva, N. A.,Galin, F. Z.,Yunusov, M. S.
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p. 788 - 792,5
(2020/08/31)
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- Synthesis and screening of cyclooxygenase inhibitory activity of some 1,3-dioxoisoindoline derivatives
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In this study, 15 compounds bearing N,Nphthaloylacetamide structure designed by the molecular simplification approach based on thalidomide structure were synthesized and evaluated for inhibitory potencies against cyclooxgenase (COX) isoenzymes, namely COX-1 and COX-2. The results suggested that the N,Nphthaloylacetamide structure, as a primary amide, has inhibitory activity against cyclooxygenase isoenzymes with a higher COX-1 selectivity. The conversion of the primary amide to secondary or tertiary derivatives lowered the potency but favored the COX-2 selectivity thus yielding the compounds with stronger COX-2 inhibiting activity. ECV · Editio Cantor Verlag.
- Cizmecioglu, Murat,Pabuccuoglu, Varol,Ballar, Petek,Pabuccuoglu, Aysun,Soyer, Zeynep
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experimental part
p. 186 - 190
(2011/10/10)
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- Amino acid-based reoxidants for aminohydroxylation: Application to the construction of amino acid-amino alcohol conjugates
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A viable nitrogen source for the aminohydroxylation reaction of terminal alkenes: By adding a N-O based reoxidant onto an amino acid acyl carbon atom, compounds were obtained that facilitated catalytic turnover and also promoted the conjugation of an amino acid with an alkene. High levels of regioselectivity were observed, as well as good stereoselectivity induced by catalytic amounts of a chiral ligand.
- Donohoe, Timothy J.,Callens, Cedric K. A.,Flores, Aida,Mesch, Stefanie,Poole, Darren L.,Roslan, Ishmael A.
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supporting information; experimental part
p. 10957 - 10960
(2012/01/05)
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- Selectivities in the reaction of vicinal diimines and acyl chlorides
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The reaction of vicinal diimines and acyl chlorides in the presence of triethylamine produces 3-imino-β-lactams and/or bis-β-lactams chemo-, regio-, and stereoselectively, which are important intermediates in pharmaceutical and organic synthesis. The selectivities in the reaction have been investigated. The results indicate that all diimines react with various ketenes generated from acyl chlorides in the presence of triethylamine to give rise to cis-4-imino-β-lactams (mono-cis-β-lactams) diastereoselectively due to the electron-withdrawing property of the imino group in the vicinal diimines. Bis-β-lactams were obtained from diimines via the mono-cis-β-lactams as intermediates. Only ketenes with strong electron-donating substituents can react with the mono-cis-β-lactams to yield bis-β-lactams, affording a pair of C2-symmetric cis-bis-β- lactams with symmetric diimines, two or four pairs of diastereomeric bis-β-lactams with ketoaldehyde-derived unsymmetric diimines depending on the steric hindrance of their N-substituents. The current investigation provides very important information for the selective preparation of mono- and bis-β-lactams from vicinal diimines.
- Wang, Zhixin,Chen, Ning,Xu, Jiaxi
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body text
p. 9690 - 9699
(2012/01/06)
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- Synthesis and antiviral activity of phthiobuzone analogues
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A series of phthiobuzone analogs, prepared from potassium phthalimide or phthalandione, have been evaluated for their antiviral activities. Among the candidates, compounds 5j and 5k, which contain the substituted 4-halogenated phenyl ring at N-4′,4″ position, show more potent antiviral activity than phthiobuzone against herpes simplex virus 1 (IC50=8.56 and 2.85 μ/ml, respectively) and herpes simplex virus 2 (IC50=1.75 and 4.11μg/ ml, respectively). Compounds 9c and 9d with a propylene linker between the phthalimide and bisthiosemicarbazone moieties display similar antiviral potency against herpes simplex virus 1 (IC50=2.85 and 4.11 μg/ml, respectively).
- Yang, Ya-Jun,Zhao, Jing-Hua,Pan, Xian-Dao,Zhang, Pei-Cheng
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experimental part
p. 208 - 211
(2010/08/06)
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- A simple and efficient procedure for synthesis of optically active 1, 3, 4-oxadiazole derivatives containing L-amino acid moieties
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Some new unsymmetrical and optically active 2, 5-disubstituted 1, 3, 4-oxadiazoles 5a-j were efficiently synthesized by cyclization reaction of diacylhydrazides 4a-j. The synthesis of the title compounds was achieved by the reaction of acyl hydrazides 3a-b and N-phetaloyl-L-amino acids 1a-e in the presence of the phosphoroxy chloride (POCl3) as an anhydrous reagent. tuebitak.
- Foroughifar, Naser,Mobinikhaledi, Akbar,Ebrahimi, Sattar
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scheme or table
p. 603 - 611
(2010/11/05)
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- Synthesis and antimicrobial activity of some new N-acyl substituted phenothiazines
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A series of 2-substituted N-acylphenothiazines were synthesized by using imides, N-carboxymethyl imides and the structures of these newly synthesized compounds were confirmed by spectral and elemental analyses. All new compounds were tested for their antibacterial and antifungal activities. Some compounds showed promising antibacterial and antifungal activities.
- Bansode, Tanaji N.,Shelke, Jayant V.,Dongre, Vaijanath G.
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experimental part
p. 5094 - 5098
(2010/01/06)
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- Synthesis, cleavage, and antifungal activity of a number of novel, water-soluble ester prodrugs of antifungal triazole CS-758
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In this study, the synthesis and evaluation of a number of esters of CS-758 as injectable prodrugs are described. Phosphoryl ester 1a was soluble in water (>30 mg/mL) and was converted to CS-758 in human liver microsome. It was also converted to CS-758 in rats after iv administration, wherein the bioavailability of CS-758 was 53%. Compound 1a (iv) reduced the viable cell counts in kidneys in a murine systemic Candida albicans infection model, wherein the effect was comparable to or slightly superior to that of CS-758 (po). The prodrug 1a proved to be a promising injectable antifungal agent whose further evaluation is warranted.
- Kagoshima, Yoshiko,Mori, Makoto,Suzuki, Eiko,Shibayama, Takahiro,Iida, Tamako,Kamai, Yasuki,Konosu, Toshiyuki
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scheme or table
p. 3559 - 3563
(2010/03/31)
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- METHOD FOR SYNTHESIZING ONE-DIMENSIONAL HELICAL NANOPOROUS STRUCTURES AND METHOD FOR SYNTHESIZING GLYCINE-DERIVED SURFACTANT FOR SYNTHESIZING HELICAL NANOPOROUS STRUCTURES
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Disclosed herein are a method for synthesizing one-dimensional helical mesoporous structure, in which a self-assembled structure of a glycine-derived surfactant is used as a template at room temperature to synthesize the one-dimensional helical mesoporous silica structures having a uniform pore size and a method for synthesizing a glycine-derived surfactant for synthesizing the helical nanoporous structures, in which relatively expensive surfactant can be easily recovered using an organic solvent and reused, which provides economical and environment friendly effects and the glycine-derived surfactant is synthesized by homogeneously heating a reaction product of glycine and phthalic anhydride by dielectric heating with irradiation of microwave, whereby it is possible to realize high yield of the glycine-derived surfactant, shortened synthesis time and increase in energy efficiency, leading to improvement in productivity and reduction in production cost.
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Page/Page column 15
(2009/12/05)
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- Oxazole cyclopeptides for chirality transfer in C3-symmetric octahedral metal complexes
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A straightforward synthesis of C3-symmetric oxazole-containing macrocyclic peptide scaffolds is presented. This type of macrocycles bears three functional groups on the oxazole rings, which allows fixing of various receptor arms on them in an easy manner. The chiral backbone of the macrocycle proved to be a powerful tool for chirality induction, thus predetermining the configuration of helically coordinated metal centres. The diastereoselective formation of CoII, NiII, CuII and Zn II complexes with tripodal bipyridyl ligand 4 was proved by UV- and CD-absorption spectrophotometric titration experiments. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Pinter, Aron,Haberhauer, Gebhard
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experimental part
p. 2375 - 2387
(2009/04/05)
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- Synthesis of phosphonodipeptide conjugates of ursolic acid and their homologs
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To prepare novel derivatives of naturally bioactive 3β-hydroxy-urs-12- en-28-oic acid (ursolic acid) with unusual properties and broad spectrum of activities, a number of chemical reactions were conducted. First, a variety of a-aminophosphonates were prepared by a series of reactions involving the three-component Mannich type reaction as a key step. Second, an array of phosphonodipeptides and their homologs was synthesized through multistep reactions including condensation of phthalic anhydride with glycine or β-alanine, chlorination of N-blocked amino acids, coupling of acid chloride with α-aminophosphonates and sequential hydrazinolysis. Finally, new classes of phosphonodipeptide conjugates of ursolic acid and their homologs were obtained by condensation of 3β-acetoxy-urs-12-en-28-oyl chloride with phosphonodipeptides and their homologs.
- Deng, Sheng-Lou,Baglin, Isabelle,Nour, Mohammed,Cave, Christian
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- Configurationally stable propeller-like triarylphosphine and triarylphosphine oxide
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Configurationally stable, propeller-like triarylphosphine and triarylphosphine oxide can be synthesized; a chiral scaffold based on Lissoclinum-cyclopeptides linked via three peptide bonds with a triphenylphosphine and triphenylphosphine oxide moiety, respectively, prevents effectively epimerization at the chiral phosphorus atom. The Royal Society of Chemistry.
- Pinter, Aron,Haberhauer, Gebhard,Hyla-Kryspin, Isabella,Grimme, Stefan
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p. 3711 - 3713
(2008/03/14)
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- Novel method for preparation of monoesters of symmetric diphenolic compounds like curcumin (1,7-bis(4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3,5- dione) via solid-phase synthesis
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Synthesis of a monoester of symmetrical diphenolic compound curcumin (1,7-bis(4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3,5-dione) with glycine has been carried out by anchoring one of its free phenolic groups to an insoluble polymeric solid-support resin controlled pore glass-long chain alkylamine (CPG-LCAA) via a 2-carbon linker by solid-phase synthesis. The other free phenolic was esterified selectively with N-protected glycinoyl chloride to give the monoester exclusively. Subsequent deprotection of the amino group and deblocking of the monoester from polymer support by treatment with hydriodic acid (HI) gave the desired product. We earlier reported synthesis of a large number of diesters of curcumin, but selective esterification of one phenolic has been accomplished by this novel method, which can be used for preparing monoesters of any symmetric diphenol in quantitative yields. Copyright Taylor & Francis Group, LLC.
- Dubey, Shiv Kumar,Dwivedi, Vishnu,Misra, Krishna
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p. 4265 - 4271
(2008/03/13)
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- Bisphosphonate complexation and calcium doping in silica xerogels as a combined strategy for local and controlled release of active platinum antitumor compounds
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The production of bone substitute biomimetic materials which could also act as antitumoral drug release agents is of enormous interest. We report in this paper the synthesis and characterization of a novel platinum dinuclear complex containing a geminal bisphosphonate and its embodiment into xerogels prepared by the sol-gel method. Our goal was to obtain a hybrid inorganic matrix that could release a platinum species active against bone tumors or metastases, upon local implant. Two silica xerogels were considered: one was composed of pure silica, while the other contained also some calcium as potential release-modulating agent thanks to its high affinity for bisphophonates. The platinum-complex loading capacity of the inorganic matrices, the release kinetics in buffer simulating physiological conditions, and the stability upon storage were investigated as a function of Pt-complex concentration and calcium addition. We found that the presence of calcium in the composites deeply influences not only the stability of the formulations but also the nature of the platinum complex liberated in solution. The Royal Society of Chemistry.
- Margiotta, Nicola,Ostuni, Rosa,Teoli, Deborah,Morpurgo, Margherita,Realdon, Nicola,Palazzo, Barbara,Natile, Giovanni
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p. 3131 - 3139
(2008/02/08)
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- SULPHONAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
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Disclosed are compounds having the general formula (I) as defined herein, the preparation thereof, and the use thereof for the prophylaxis or treatment of any disease involving a dysfunction associated with the orexin 2 receptor such as obesity, appetite or taste disorders including cachexia, anorexia and bulimia, diabetes, metabolic syndromes, vomiting and nausea, depression and anxiety, addictions, mood and behaviour disorders, schizophrenia, sleep disorders, restless legs syndrome, memory learning disorders, sexual and psychosexual dysfunctions, pain, visceral or neuropathic pain, hyperalgesia, allodynia, digestive disorders, irritable bowel syndrome, neuronal degenerescence, ischaemic or haemorrhagic attacks, Cushing's disease, Guillain-Barré syndrome, myotonic dystrophy, urinary incontinence, hyperthyroidism, pituitary function disorders, hypertension or hypotension.
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(2010/11/28)
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