- Novel 3-fluoro-4-morpholinoaniline derivatives: Synthesis and assessment of anti-cancer activity in breast cancer cells
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Heterocyclic morpholine compounds are well-known for their anti-cancer activity. In this study, novel morpholine and its sulfonamide derivatives were designed and synthesized as potential anti-tumor agents. The new compounds were obtained from amine derivatives via nucleophilic addition reactions, providing the desired products in 70 to 90% yield. The docking analysis was performed for all thirty-one compounds. Out of them, we represent the docking poses for compounds NAM-5 and NAM-7 as representatives. After docking analysis, compounds NAM-5 and NAM- 7 were tested for in vitro antitumor activity against breast cancer cell lines (MCF-7 and MDA-MB-231) and healthy mouse embryonic fibroblast cell line (3T3L-1). Amongst these, sulfonamide group-containing compound NAM-5 showed significant anti-proliferative activity with IC50 of 1.811 μM and 2.143 μM for MCF-7 and MDA-MB-231 cells, respectively. On the other hand, NAM-7 showed good anti-proliferative activity against MCF-7 (IC50 1.883 μM) but slightly lower activity against MDA-MB-231 cells (IC50 4.688 μM). The activity of both the compound was also tested on 3T3L-1 Cell line which showed activity similar to clinically approved anti-cancer drug doxorubicin (DOX). The cell death analysis by flow-cytometry confirmed apoptosis mediated cell death in 3T3L-1, MCF-7 and MDA-MB-231 cells when treated with the NAM-5 and NAM-7, respectively. The results demonstrated that the synthesized sulfonamide derivatives have significant potential as anti-cancer agents and have a substantial importance in cancer therapeutics with favourable safety profile. Structural analysis of docked poses of sulfonamide derivatives attempts to shed light on the structural basis of sulfonamide derivatives based anti-cancer effect.
- Gajbhiye, Jayant M.,Gajbhiye, Virendra,Jadhao, Nitin L.,Meshram, Rohan J.,More, Namita A.,Sabane, Jagjivan K.,Salve, Rajesh A.,Sawant, Sanskruti N.,Tambe, Prajakta
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- Benzofuroxan Derivatives as Potent Agents against Multidrug-Resistant Mycobacterium tuberculosis
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Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo[c][1,2,5]oxadiazole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC90 values below 0.28 μM against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis.
- Fernandes, Guilherme F. S.,Campos, Débora L.,Da Silva, Isabel C.,Prates, Jo?o L. B.,Pavan, Aline R.,Pavan, Fernando R.,Dos Santos, Jean L.
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supporting information
p. 1268 - 1282
(2021/02/16)
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- Spectroscopic identification of intermediates and final products of the chiral pool synthesis of sutezolid
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Sutezolid is a new oxazolidinone derivative currently in clinical trials to determine its safety and efficacy towards highly drug-resistant tuberculosis. The aim of the study was the spectroscopic identification of selected key intermediate products of th
- Bocian, Wojciech,Cielecka-Piontek, Judyta,Lewandowska, Kornelia,Michalska, Katarzyna,Mizera, Miko?aj,Pa?ys, Barbara
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- RETRACTED ARTICLE: Design, synthesis of novel oxazolidino-amides/sulfonamides conjugates and their impact on antibacterial activity
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Abstract: In view of generating new compounds for future drug development, we have synthesized oxazolidinones library of aryl amides and aryl sulfonamide derivatives. These compounds were screened in vitro against panel of susceptible and resistant Gram-p
- Bharath, Yarlagadda,Alugubelli, Gopi Reddy,Sreenivasulu, Reddymasu,Rao, Mandava. V. Basaveswara
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p. 457 - 468
(2018/02/09)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The invention relates to the field of medicine, discloses new nitrogen heterocyclic derivatives, preparation method thereof and as medicament in particular as the treatment and prevention of treating tissue fibrosis of the medicament. The invention also discloses a pharmaceutically acceptable compound of the present invention comprise a pharmaceutical composition and methods for using the composition for the treatment of the human or animal tissue fibrosis of diseases, in particular for treating the human or animal renal interstitial fibrosis, glomerular sclerosis, hepatic fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, skin fibrosis, after the operation of adhering, benign prostate hypertrophy, bone-myocardial, scleroderma, multiple sclerosis, pancreas fibrosis, liver cirrhosis, myosarcoma, neurofibromatosis, interstitial pulmonary fibrosis, diabetic nephropathy, Alzheimer's disease or vascular fibrosis disease in use. (by machine translation)
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Paragraph 125; 126
(2018/06/01)
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- Structure-based hybridization, conventional and microwave irradiated synthesis, biological evaluation and molecular docking studies of new compounds derived from thiomorpholin
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Background: The amine 2 obtained via two steps starting from thiomorpholine was converted into the corresponding 1,3-thiazole (4), arylmethileneamino (5a-d) and hydrazide (7) derivatives using conventional and also microwave techniques. The synthesis of 1
- Demirci, Serpil,Aksakal, Fatma,Colak, Nesrin,Ulker, Serdar,Demirbas, Ahmet,Demirbas, Neslihan
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p. 444 - 463
(2017/03/17)
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- Nitrogenous Heterocyclic Derivatives And Their Application In Drugs
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 0531
(2015/03/31)
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- Novel lead generation of an anti-tuberculosis agent active against non-replicating mycobacteria: Exploring hybridization of pyrazinamide with multiple fragments
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The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited >10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log10 kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.
- Markad, Shankar D.,Kaur, Parvinder,Kishore Reddy,Chinnapattu, Murugan,Raichurkar, Anandkumar,Nandishaiah, Radha,Panda, Manoranjan,Iyer, Pravin S.
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p. 2986 - 2992
(2015/03/14)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 00279
(2014/02/15)
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- NOVEL 2,6-SUBSTITUTED-3-NITROPYRIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION INCLUDING SAME
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The present invention relates to a novel 2,6-substituted-3-nitropyridine derivative compound, a method for preparing the same, and a pharmaceutical composition including the same for prevention and treatment of osteoporosis. The 2,6-substituted-3-nitropyr
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Page/Page column 14
(2012/01/03)
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- NOVEL 2,6-SUBSTITUTED-3-NITROPYRIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION INCLUDING SAME
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The present invention relates to a novel 2,6-substituted-3-nitropyridine derivative compound, a method for preparing the same, and a pharmaceutical composition including the same for prevention and treatment of osteoporosis. The 2,6-substituted-3-nitropyr
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Page/Page column 22
(2012/01/03)
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- Syntheses and antibacterial activity studies of new oxazolidinones from nitroso Diels-Alder chemistry
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A series of novel oxazolidinone antibiotics having [2.2.1] and [2.2.2] bicyclic oxazine moieties at the C-5 side chain of the A-ring was synthesized by nitroso Diels-Alder reactions, from three linezolid analogs containing morpholine, piperazine and thiomorpholine, respectively, as the C-ring components. Subsequent N-O bond cleavage generated oxazolidinones with 4-amino cyclo-2-en-1-ol substituents. The in vitro antibacterial activities of these oxazolidinone analogs were evaluated.
- Yan, Shanshan,Miller, Marvin J.,Wencewicz, Timothy A.,Moellmann, Ute
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supporting information; experimental part
p. 1302 - 1305
(2010/06/15)
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- THIAZOLE AND OXAZOLE KINASE INHIBITORS
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The present invention provides thiazole and oxazole compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
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Page/Page column 109
(2009/04/25)
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- N-(3,4-disubstituted phenyl) salicylamide derivatives
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A compound represented by the following formula (I) or a salt thereof: wherein R1, R2, R3 and R4 represent hydrogen atom, a halogen atom, cyano group, nitro group, a C1-4 alkyl group, a halogenated C
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Page/Page column 33
(2008/12/07)
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- N-[4-(1,1'-biphenylyl)methyl]-4-(4-thiomorpholinylmethyl) benzenamines, a new class of synthetic antituberculosis agents active against Mycobacterium avium
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Various N-derivatives of 4-(4-thiomorpholinyl)aniline and 4-(4- thiomorpholinylmethyl)aniline were synthesized and tested for in vitro antibacterial activities against Mycobacterium avium CIP 103317 and other mycobacteria including M. tuberculosis CIP 103471. Appropriate substituents were introduced at the nitrogen of aniline portion in order to exploit their potential antimycobacterial activities. Only derivatives with the biphenylylmethyl group bound to the 4-(4-thiomorpholinylmethyl)aniline moiety were found to possess appreciable antibacterial activities against atypical mycobacteria and M. tuberculosis. Several compounds (7c-g and 7j) were two and sixteen times more potent than azithromycin and isoniazid, respectively, in the in vitro assays against M. avium.
- Mai, Antonello,Sbardella, Gianluca,Artico, Marino,Massa, Silvio,Lampis, Giorgio,Deidda, Delia,Pompeit, Raffaello
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p. 149 - 161
(2007/10/03)
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- Substituted oxazine and thiazine oxazolidinone antimicrobials
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A compound of structural Formula I: STR1 or pharmaceutically acceptable salts thereof wherein: X is O, S, SO, SO2, SNR10 or S(O)NR10 ; R is (a) hydrogen, (b) C1 -C8 alkyl optionally substituted with one or more of the following: F, Cl, hydroxy, C1 -C8 alkoxy, C1 -C8 acyloxy or --O--CH2 --Ph, (c) C3 -C6 cycloalkyl, (d) amino, (e) C1 -C8 alkylamino, (f) C1 -C8 dialkylamino or (g) C1 -C8 alkoxy; R1 is H, except when X is O then R1 can be H, CH3, CN, CO2 H, CO2 R or (CH2)m R11 (m is 1 or 2); R2 is independently H, F or Cl; R3 is H except when X is O and R1 is CH3 then R3 can be H or CH3 ; R10 is independently H, C1 -C4 alkyl (optionally substituted with chloro, fluoro, hydroxy, C1 -C8 alkoxy, amino, C1 -C8 alkylamino, or C1 -C8 dialkylamino) or p-toluenesulfonyl; R11 is hydrogen, OH, OR, OCOR, NH2, NHCOR or N(R10)2 ; and n is 0, 1 or 2. The oxazine and thiazine oxazolidinone derivatives are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms such as Bacteroides spp. and Clostridia spp. species, and acid-fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.
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- Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity.
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During the course of our investigations in the oxazolidinone antibacterial agent area, we have identified a subclass with especially potent in vitro activity against mycobacteria. The salient structural feature of these oxazolidinone analogues, 6 (U-10048
- Barbachyn, Michael R.,Hutchinson, Douglas K.,Brickner, Steven J.,Cynamon, Michael H.,Kilburn, James O.,et al.
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p. 680 - 685
(2007/10/03)
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