- Synthesis and molecular docking based exploration of salicylic acid derivatives
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In present study, four salicylic acid derivatives viz., 2-acetoxybenzoic acid (2a), 2-(1H-indol-2-yl)benzoic acid (3a), 5-chloro-2-acetoxybenzoic acid (2b) and 5-chloro-2-(1H-indol-2-yl)benzoic acid (3b) were synthesized and studied for molecular docking on 3JUS and 3UPI protein selected from pdb. The studies show that all of the four synthesized compounds were found to be docked. Compound 3a and 3b showed the best ligand pose energy -10.8163 kcal/mol and -11.1354 kcal/mol with docking run: elapsed time 9 s and 12 s, respectively in respect of 3JUS Further, compounds 3a and 3b showed the best ligand pose energy -9.17851 and -9.54722 kcal/mol with docking run: elapsed time 10 and 14 s, respectively in case of 3UPI. Hence, studies showed that 5-chloro-2-(1H-indol-2-yl)benzoic acid (3b) emerged as potent compound which might show diverse nature of biological and therapeutic activity.
- Singh, Navneet,Garg, Geetika
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- Synthesis and antioxidant activities of berberine 9-: O -benzoic acid derivatives
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Although berberine (BBR) shows antioxidant activity, its activity is limited. We synthesized 9-O-benzoic acid berberine derivatives, and their antioxidant activities were screened via ABTS, DPPH, HOSC and FRAP assays. The para-position was modified with halogen elements on the benzoic acid ring, which led to an enhanced antioxidant activity and the substituent on the ortho-position was found to be better than the meta-position. Compounds 8p, 8c, 8d, 8i, 8j, 8l, and especially 8p showed significantly higher antioxidant activities, which could be attributed to the electronic donating groups. All the berberine derivatives possessed proper lipophilicities. In conclusion, compound 8p is a promising antioxidant candidate with remarkable elevated antioxidant activity and moderate lipophilicity.
- Liu, Yanfei,Long, Shuo,Zhang, Shanshan,Tan, Yifu,Wang, Ting,Wu, Yuwei,Jiang, Ting,Liu, Xiaoqin,Peng, Dongming,Liu, Zhenbao
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p. 17611 - 17621
(2021/05/29)
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- Synthesis and biological evaluation of novel N-substituted benzamides as anti-migration agents for treatment of osteosarcoma
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A novel series of novel N-substituted (indole or indazole) benzamides were synthesized, and their anti-tumor properties were evaluated. The majority of tested compounds possessed moderate cytotoxicity, but inspiringly, we verified that active compound 5d presents an astonishing advantage by inhibiting the adhesion, migration, and invasion of osteosarcoma (OS) cells in vitro. Mechanistically, we confirmed 5d inhibited the migration ability of OS cells via the expression of genes related to adhesion, migration, and invasion. This effects of 5d suggest that it can be used as a potential chemotherapeutic drug to some aggressive and/or metastatic cancers, as well as in combination with other clinical anti-cancer drugs. In turn, this could enhance the therapeutic effect or reduce the risk of cell migration.
- Chen, Xiaojing,Wang, Guangbao,Mohammed Alsayed, Ali Mohammed,Du, Zongxuan,Lu liu,Ma, Yue,Liu, Peng,Zhang, Qianwen,Chen, Xianxin,Chen, Wenbin,Ye, Faqing,Zheng, Xiaohui,Liu, Zhiguo
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- Chlorinated cobalt alkyne complexes derived from acetylsalicylic acid as new specific antitumor agents
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[(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), an organometallic derivative of the irreversible cyclooxygenase-1/2 (COX-1/2) inhibitor acetylsalicylic acid (ASS), demonstrated high growth-inhibitory potential against various tumor cell lines and inhibition of both COX isoenzymes. With the objective of increasing the selectivity for COX-2, we introduced a chlorine substituent in position 3, 4, 5, or 6 of the ASS moiety, respectively. Increased COX-2 selectivity is desirable as this isoenzyme is predominantly related to the development of cancer and abnormal tissue growth. The new compounds were investigated in comprehensive cellular biological assays to identify the impact of the chlorine substitution at the complex on COX-1/2 inhibition, antiproliferative activity, apoptosis, metabolic activity, cell-based COX inhibition, and cellular uptake. Chlorination distinctly reduced the effects at isolated COX-1 (about 25% inhibition at 10 μM; Co-ASS: 82.7%), while those at COX-2 remained almost unchanged (about 65% inhibition at 10 μM; Co-ASS: 78.5%). In cellular systems, with exception of the 6-Cl derivative, all compounds showed notable antitumor activity in COX-1/2 expressing tumor cells (HT-29 (IC50 = 1.5-2.7 μM), MDA-MB-231 (IC50 = 5.2-8.0 μM)), but were distinctly less active in the COX-1/2-negative MCF-7 breast cancer cell line (IC50 = 15.2-22.9 μM). All complexes possess high selectivity for tumor cells, because they did not influence the growth of the non-tumorigenic, human bone marrow stromal cell line HS-5. These findings clearly demonstrate that the interference with the COX-1/2 cascade contributes to the mode of anticancer action of the cobalt alkyne complexes.
- Obermoser, Victoria,Baecker, Daniel,Schuster, Carina,Braun, Valentin,Kircher, Brigitte,Gust, Ronald
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supporting information
p. 4341 - 4351
(2018/03/26)
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- Development of 5-nitrothiazole derivatives: Identification of leads against both replicative and latent Mycobacterium tuberculosis
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Twenty eight 5-nitrothiazole derivatives were synthesized and evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against HEK 293T. Among the compounds, 5-nitro-N-(5-nitrothiazol-2-yl)furan-2- carboxamide (20) was found to be the most active compound in vitro with MICs of 5.48 μM against log-phase culture of MTB and also non-toxic up to 100 μM.
- Jeankumar, Variam Ullas,Chandran, Manoj,Samala, Ganesh,Alvala, Mallika,Koushik, Pulla Venkat,Yogeeswari, Perumal,Salina, Elena G.,Sriram, Dharmarajan
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p. 7414 - 7417
(2013/02/22)
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- Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors
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HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl]benzoic acid (25) was selectively active against integrase strand transfer, with an IC 50 of 3.7 μM. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4- bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3′-processing and strand transfer with IC50 values of 11 ± 4 and 5 ± 2 μM, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl]benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 μM, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r2 of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q2 and r2 values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC50 values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors.
- Sharma, Horrick,Patil, Shivaputra,Sanchez, Tino W.,Neamati, Nouri,Schinazi, Raymond F.,Buolamwini, John K.
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experimental part
p. 2030 - 2045
(2011/05/05)
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- Influence of impurities on the crystallisation of 5-X-aspirin and 5-X-aspirin anhydride polymorphs (X = Cl, Br, Me)
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Crystallisation of 5-X-aspirin (X = Cl, Br) by ambient evaporation from organic solvents commonly yields a mixture of polymorphs I and II for X = Cl, but only polymorph I for X = Br. Addition of 5-X-aspirin anhydride (5-20 mol %) leads to sole production
- Solanko, Katarzyna A.,Bond., Andrew D.
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experimental part
p. 6991 - 6996
(2012/05/31)
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- COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
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Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.
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- NF-KB ACTIVATION INHIBITORS
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A medicament having inhibitory activity against NF-κB activation which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is 1○ a fused polycyclic heteroaryl group wherein the ring which binds directly to ―CONH― group in the formula (I) is a benzene ring, 2○ unsubstituted thiazol-2-yl group, or 3○ unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula -CONH-E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula ― CONH―E wherein E has the same meaning as that defined above.
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- THERAPEUTIC AGENT FOR CANCER
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A medicament for the prevention and/or treatment of cancers and the like which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is 1? a fused polycyclic heteroaryl group wherein the ring which binds directly to ―CONH― group in the formula (I) is a benzene ring, 2? unsubstituted thiazol-2-yl group, or 3? unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula ―CONH―E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula ―O―A wherein A has the same meaning as that defined above and the group represented by formula ― CONH―E wherein E has the same meaning as that defined above.
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(2010/02/11)
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- REMEDIES FOR NEURODEGENERATIVE DISEASES
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A medicament for preventive and/or therapeutic treatment of neurodegenerative diseases such as Alzheimer's disease or the like which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein A represents hydrogen atom or acetyl group, E represents a 2,5-di-substituted or a 3,5-di-substituted phenyl group, or a monocyclic or a fused polycyclic heteroaryl group which may be substituted, provided that the compound wherein said heteroaryl group is 1○ a fused polycyclic heteroaryl group wherein the ring which binds directly to -CONH- group in the formula (I) is a benzene ring, 2○ unsubstituted thiazol-2-yl group, or 3○ unsubstituted benzothiazol-2-yl group is excluded, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -CONH-E wherein E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -CONH-E wherein E has the same meaning as that defined above.
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(2010/02/12)
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- IMMUNITY-RELATED PROTEIN KINASE INHIBITORS
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[From equivalent EP1510210A1] A medicament having an inhibitory activity against IKK-Aβ and/or MEKK-1 or other protein kinases structurally similar thereto, which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above.
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(2010/02/10)
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- INHIBITORS AGAINST THE ACTIVATION OF AP-1 AND NFAT
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A medicament inhibiting the activation of AP-1 which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above.
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Page/Page column 118
(2008/06/13)
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- ANTIALLERGIC
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A medicament for the preventive and/or therapeutic treatment of allergic diseases and/or endometriosis and/or hysteromyoma which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula -O-A wherein A has the same meaning as that defined above and the group represented by formula -X-E wherein each ofX and E has the same meaning as that defined above.
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Page/Page column 124
(2010/02/11)
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- Novel short-step synthesis of functionalized γ-phenyl-β- hydroxybutenoates and their cyclization to 4-hydroxycoumarins via the N-hydroxybenzotriazole methodology
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A novel method for the synthesis of functionalized 3-substituted 4-hydroxycoumarins is reported. C-Acylation compounds were derived from the reaction of the N-hydroxybenzotriazole ester of the functionalized acetyl salicylic acids and a variety of active methylene compounds and cyclized to the title compounds. The synthesis is simple and the compounds are produced in yields varying from 39 to 80%. The structure of the newly prepared C-acylation compounds was thoroughly studied through NMR spectroscopy for the first time in the literature.
- Athanasellis, Giorgos,Melagraki, Georgia,Chatzidakis, Haralambos,Afantitis, Antreas,Detsi, Anastasia,Igglessi-Markopoulou, Olga,Markopoulos, John
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p. 1775 - 1782
(2007/10/03)
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- Synthesis and First Evaluation of New 18F-Labelled Sulfonylureas for the Determination of the Beta-Cell Status In Vivo
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The syntheses and first in vitro evaluations for two fluoride bearing sulfonylurea derivatives are reported. Firstly, the tolbutamide derivative 1-[4-(2-[18F]fluoroethoxy)benzenesulfonyl]-3-butyl urea (2-[18F]fluoroethyltolbutamide) could be labeled efficiently with [18F]fluoride. Subsequently, the glibenclamid derivative N-(2-(4-(N-((cyclohexylamino)carbonyl)sulfonylamino)phenyl)ethyl) 2-(5-chloro-2-[18F]fluoroethoxy)phenyl formamide (2-[18F]fluoroethyl-glibenclamide) was labeled with [18F]fluoride in high yields. Its ability to induce insuline secretion from rat beta-cells in relation to the original glibenclamide was determined.
- Schirrmacher, R.,Shiue, G.,Shiue, S. J.,Alavi, A.,Feilen, P. J.,Schneider, S.,Beyer, J.,Roesch, F.
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p. S418 - S420
(2007/10/03)
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- A highly practical route to 2-methylchromones from 2-acetoxybenzoic acids
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2-Methylchromones were accessed via a keto ester condensation on 2-acetoxybenzoyl chloride, followed by cyclization and decarboxylation. No column chromatography was required in the process.
- Jung,Min,Park
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p. 1837 - 1845
(2007/10/03)
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- A Novel Synthesis of 4H-Chromen-4-ones via Intramolecular Wittig Reaction
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formula presented The acylphosphoranes formed in a sequential manner from the reaction of the silyl ester of O-acyl(aroyl)salicylic acids and (trimethylsilyl)-methylenetriphenylphosphorane undergo intramolecular Wittig cyclization on the ester carbonyl to afford the 4H-chromen-4-ones in good to excellent yields.
- Kumar, Pradeep,Bodas, Mandar S.
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p. 3821 - 3823
(2007/10/03)
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- Medicaments for the selective treatment of tumor tissues
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Medicinal products for the selective control of tumor tissue and a method for control of such tumor tissue by administration of such product to a host. The products comprise: (a) two different compounds having a pH below 7 when the compounds are present i
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- Synthesis and structure-activity relationships of carboxylated chalcones: A novel series of CysLT1 (LTD4) receptor antagonists
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The synthesis and CysLT1 antagonistic activities of a new series of 2- , 3-, and 4-(2-quinolinylmethoxy)- and 3- and 4-[2-(2-quinolinyl)ethenyl]- substituted, 2'-, 3'-, 4'-, or 5'-carboxylated chalcones are described. Structure-activity relationship studies indicate a preference for the presence of a negatively charged (acidic) moiety, although in some cases nitrile or ester analogues also exhibit moderate activity. The quinoline moiety may be substituted at either the 3- or the 4-position. Replacement of this heterocycle by other aromatic groups results in compounds with comparable affinities [2-(7-chloroquinoline), 1-(1-methyl-2-benzimidazole), or 1-(2-benzothiazole)] or substantially lower activities [1-(1- ethoxyethyl)-2-benzimidazole, 2-naphthyl, or phenyl]. The quinoline and chalcone moieties may be connected by either an ethenyl or a methoxy spacer. The acidic moiety at the chalcone B ring may be attached to the 2'-, 3'-, 4'- , or 5'-position, for both the 3- and 4-substituted chalcones. There are no general patterns to specify which substitution positions gave the most potent compounds. The series contains several potent CysLT1 receptor antagonists, with K(D) values approaching the nanomolar range, as measured by the displacement of [3H]LTD4 from guinea pig lung membranes. Antagonism of LTD4-induced contraction of guinea pig ileum, the inhibition of antigen- induced contraction of guinea pig trachea in vitro, and the inhibition of LTD4-induced increase of vascular permeability in vivo are determined for chalcones with high CysLT1 receptor affinities (K(D) values below 0.1μM). 2'-Hydroxy-4-(2-quinolinylmethoxy)-5'-(5-tetrazolyl)chalcone (14, VUF 4819) showed good activity in both in vitro and in vivo assays and has been selected for further evaluation.
- Zwaagstra, Mari?l E.,Timmerman, Hendrik,Tamura, Masahiro,Tohma, Tsutomu,Wada, Yasushi,Onogi, Kazuhiro,Zhang, Ming-Qiang
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p. 1075 - 1089
(2007/10/03)
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- Synthesis and biological activity of novel 1,3-benzoxazine derivatives as K+ channel openers
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A new series of 1,3-benzoxazine derivatives with a 2-pyridine 1-oxide group at C4 was designed to explore novel K+ channel openers. Synthesis was carried out by using a palladium(0)-catalyzed carbon-carbon bond formation reaction of imino-triflates with organozinc reagents and via a new one-pot 1,3-benzoxazine skeleton formation reaction of benzoylpyridines. The compounds were tested for vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2-induced and high KCl-induced contraction of rat aorta to identify potential K+ channel openers, and also for oral hypotensive effects in spontaneously hypertensive rats. An electron- withdrawing group with the proper shape at C6 and a methyl or halogens group at C7 of the 1,3-benzoxazine nucleus were required for the development of optimal vasorelaxant and hypotensive activity. In particular, 2-(6-bromo-7- chloro-2,2-dimethyl-2H-1,3-benzoxazin-4-yl)pyridine 1-oxide (71) showed more potent vasorelaxant activity (EC50=0.14 μM) against TEA and BaCL2- induced contraction and longer-lasting hypotensive effects than cromakalim (1).
- Yamamoto, Satoshi,Hashiguchi, Shohei,Miki, Shokyo,Igata, Yumiko,Watanabe, Toshifumi,Shiraishi, Mitsuru
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p. 734 - 745
(2007/10/03)
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- Analogs of 3-(1-Phenyl-3-oxobutyl)-4-hydroxycoumarin (Warfarin) Prepared from Substituted Salicylic Acids
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Some derivatives of salicylic acid containing substituents meta to the carboxyl group were used to prepare analogs of the anticoagulant drug warfarin, 3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin, containing substituents in either the 6- or 8-position of the coumarin ring.When the substituent was the hydroxyl group, the resulting products are previously identified metabolites of warfarin.The substituted salicylic acid is first acetylated with acetic anhydride, then either converted to the acid chloride and condensed with diethyl malonate in the presence of sodium hydroxide or converted to the mixed anhydride with formic acid and condensed with ethoxymagnesium diethyl malonate to yield, in either case, the corresponding 3-carbethoxy-4-hydroxycoumarin substituted in the 6- or 8-position of the coumarin ring.These compounds readily condense with benzalacetone to form the corresponding substituted warfarin in the presence of 5 mole percent tertiary amine catalyst.This method offers an improved route for the synthesis or 8-hydroxywarfarin.
- Obaseki, Andrew O.,Steffen, James E.,Porter, William R.
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p. 529 - 533
(2007/10/02)
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- Substituted 2-amino chromones and process for the preparation thereof
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This invention relates to substituted 2-amino chromones of the general structure I: SPC1 wherein R1, R2, R3, and R4 may be hydrogen, hydroxy, lower alkyl or lower alkoxy of 1-6 carbon atoms, halogen such as chloro or bromo, or aryl such as phenyl, and X may be cyano or carboxamido. Two novel procedures for preparing substituted 2-amino chromones having the Formula I, starting with salicylic acid or substituted salicylic acid, are described. The compounds of this invention are active in the prevention of allergic and asthmatic reactions in mammals.
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