- Novel isoxazole derivatives as potential antiparkinson agents: synthesis, evaluation of monoamine oxidase inhibitory activity and docking studies
-
Selective monoamine oxidase B inhibitors are potential drug candidates for the treatment of Parkinson’s disease. A series of phenyl substituted isoxazole carbohydrazides was designed by structural modification of isocarboxazid, a nonselective MAO inhibito
- Agrawal, Neetu,Mishra, Pradeep
-
-
Read Online
- Design, synthesis, biological evaluation and in silico studies of pyrazole‐based nh2‐acyl oseltamivir analogues as potent neuraminidase inhibitors
-
Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti‐influenza therapy. The 150‐cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150‐cavity
- Ye, Jiqing,Lin, Lin,Xu, Jinyi,Chan, Paul Kay-Sheung,Yang, Xiao,Ma, Cong
-
-
- Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies
-
The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents.
- Ye, Jiqing,Yang, Xiao,Xu, Min,Chan, Paul Kay-sheung,Ma, Cong
-
-
- CYCLIC SULFAMIDE COMPOUNDS AND METHODS OF USING SAME
-
The present disclosure provides, in part, cyclic sulfamide compounds, and pharmaceutical compositions thereof, useful as modulators of Hepatitis B (HBV) core protein, and methods of treating Hepatitis B (HBV) infection.
- -
-
Page/Page column 61; 69; 131
(2018/09/21)
-
- Synthetic method of OLED material intermediate benzoyl pyrimidine compound
-
The invention discloses a synthetic method of an OLED material intermediate benzoyl pyrimidine compound. The synthetic method comprises the following steps: mixing alkali, a solvent I as well as substituent acetophenone and oxalic acid diester which are u
- -
-
Paragraph 0090; 0091
(2018/07/15)
-
- Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies
-
A series of 2-oxo-2-phenylethylidene linked 2-oxo-benzo[1,4]oxazine analogues 17a–x and 18a–o, incorporated with a variety of electron-withdrawing as well as electron-donating groups at ring A and ring C, were synthesized under greener conditions in excel
- Jaiswal, Pradeep K.,Sharma, Vashundhra,Kumar, Surendra,Mathur, Manas,Swami, Ajit K.,Yadav, Dharmendra K.,Chaudhary, Sandeep
-
-
- Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo
-
Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment.
- Vickers, Clare F.,Silva, Ana P. G.,Chakraborty, Ajanta,Fernandez, Paulina,Kurepina, Natalia,Saville, Charis,Naranjo, Yandi,Pons, Miquel,Schnettger, Laura S.,Gutierrez, Maximiliano G.,Park, Steven,Kreiswith, Barry N.,Perlin, David S.,Thomas, Eric J.,Cavet, Jennifer S.,Tabernero, Lydia
-
p. 8337 - 8352
(2018/09/18)
-
- Bcl-2/MDM2 Dual Inhibitors Based on Universal Pyramid-Like α-Helical Mimetics
-
No α-helical mimetic that exhibits Bcl-2/MDM2 dual inhibition has been rationally designed due to the different helicities of the α-helixes at their binding interfaces. Herein, we extracted a one-turn α-helix-mimicking ortho-triarene unit from o-phenylene foldamers. Linking benzamide substrates with a rotatable C-N bond, we constructed a novel semirigid pyramid-like scaffold that could support its two-turn α-helix mimicry without aromatic stacking interactions and could adopt the different dihedral angles of the key residues of p53 and BH3-only peptides. On the basis of this universal scaffold, a series of substituent groups were installed to capture the key residues of both p53TAD and BimBH3 and balance the differences of the bulks between them. Identified by FP, ITC, and NMR spectroscopy, a compound 6e (zq-1) that directly binds to Mcl-1, Bcl-2, and MDM2 with balanced submicromolar affinities was obtained. Cell-based experiments demonstrated its antitumor ability through Bcl-2/MDM2 dual inhibition simultaneously.
- Wang, Ziqian,Song, Ting,Feng, Yingang,Guo, Zongwei,Fan, Yudan,Xu, Wenjie,Liu, Lu,Wang, Anhui,Zhang, Zhichao
-
supporting information
p. 3152 - 3162
(2016/05/19)
-
- Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents
-
A series of different heteroaromatic linked 4β-amidopodophyllotoxin conjugates (16a-i, 17a-i and 18a-d) were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound 17g showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric analysis showed that 17g arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis.
- Kamal, Ahmed,Tamboli, Jaki R.,Vishnuvardhan,Adil,Nayak, V. Lakshma,Ramakrishna
-
p. 273 - 280
(2013/02/25)
-
- Synthesis of some isoxazole derivatives as antimicrobial agents
-
A new series of 5-phenyl-3-isoxazole carboxamides (4a-j) have been synthesized by reacting 5-phenyl-3-isoxazole carboxylate with various amines. These compounds have been characterized by the spectral data and evaluated for antimicrobial activity against
- Sulakshana,Reddy, V.V. Narayan,Jyostna, T. Saritha,Reddy, K. Ramsubba
-
-
- Synthesis of novel 5-substituted isoxazole-3-carboxamide derivatives and cytotoxicity studies on lung cancer cell line
-
A series of novel 5-substituted isoxazole-3-carboxamide derivatives 6 have been prepared by coupling of 5-substituted isoxazole-3-carboxylic acids 3 with substituted-3-benzyloxyaniline 5 using DCC/HOBT as coupling agent. The products 6 have been evaluated for cytotoxicity on A549 lung cancer cell line and compounds 6a, 6b, 6e, 6j are found to show moderate proliferative activity and low cytotoxicity.
- Veeraswamy,Kurumurthy,Santhosh Kumar,Sambasiva Rao,Thelakkat, Kavya,Kotamraju, Srigiridhar,Narsaiah
-
p. 1369 - 1375
(2012/11/13)
-
- Anthranilamide-Pyrazolo[1,5-a]pyrimidine Conjugates as p53 Activators in Cervical Cancer Cells
-
A library of new anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates were designed, synthesized, and evaluated for their anticancer activity in cervical cancer cells such as HeLa and SiHa that possess low levels of p53. All 24 conjugates showed antiproliferative activity, while some of them exhibit significant cytotoxicity. In assays related to cell-cycle distribution, these conjugates induced G2/M arrest in HeLa cells and G1 cell-cycle arrest in SiHa cells. Immunocytochemistry assays revealed that these compounds cause nuclear translocation of p53, thereby indicating the activation of p53. In cervical cancer cells, the p53 protein is degraded by E6 oncoprotein. Immunoblot and RT-PCR analyses proved the presence of mitochondria-mediated apoptosis with involvement p53 target genes such as BAX, Bcl2, and p21 (CDKI). Moreover, these compounds increased the phosphorylated forms of p53 and provide signals for apoptosis induction. Interestingly, one of the conjugates, (2-phenyl-7-(3,4,5-trimethoxyphenyl)pyrazolo[1,5-a]pyrimidin-5-yl)(4-(2-(thiophen-2-ylmethylamino)benzoyl)piperazin-1-yl)methanone, is the most promising candidate in this series and has the potential to be taken up for further detailed studies.
- Kamal, Ahmed,Tamboli, Jaki R.,Ramaiah, M. Janaki,Adil,KoteswaraRao,Viswanath,Mallareddy, Adla,Pushpavalli,Pal-Bhadra, Manika
-
scheme or table
p. 1453 - 1464
(2012/11/07)
-
- AMIDE COMPOUNDS AND MEDICINAL USE THEREOF
-
The present invention relates to a compound of the formula wherein R1 is substituted aryl, heteroaryl and the like, R2 and R3 are hydrogen, alkyl, halogen, hydroxyl group and the like, Q is N, CH and the like, W is hydrogen, alkyl, hydroxycarbonylalkyl and the like, X is halogen, cyano, nitro, amino and the like, X' is hydrogen, halogen, cyano, nitro, and Y is alkyl, hydroxyl group, alkoxy, mercapto and the like and a salt thereof, and a medicine containing the said compound. The compound of the present invention shows a superior inhibitory effect on activated lymphocytes proliferation and is useful as an agent for the prophylaxis or treatment of various autoimmune diseases.
- -
-
-
- Inhibitors of acyl-coA:cholesterol O-acyltransferase. 2. Identification and structure-activity relationships of a novel series of N-alkyl-N- (heteroaryl-substituted benzyl)-N'-arylureas
-
A series of N-alkyl-N-(heteroaryl-substituted benzyl)-N'-arylurea and related derivatives represented by 2 and 3 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl group of this trisubstituted urea (i.e. 3, Ar1 = pyrazol-3- yl) was identified as a heteroaromatic ring providing a good profile of biological activity. As a result of optimization of the combination with the N-alkyl group (R) and N-aryl group (At3), compound 3aq (FR186054) was identified as a new, orally efficacious ACAT inhibitor, which exhibited potent in vitro ACAT inhibitory activity (rabbit intestinal microsomes IC50 = 99 nM) and excellent hypocholesterolemic effects in cholesterol-fed rats, irrespective of administration mode (ED50 = 0.046 mg/kg dosed via the diet, ED50 = 0.44 mg/kg administered by gavage in PEG400 vehicle). Moreover, a toxicological study revealed compound 3aq to be nontoxic to the adrenal glands of dogs when tested at a single dose of 10 mg/kg po.
- Tanaka, Akira,Terasawa, Takeshi,Hagihara, Hiroyuki,Sakuma, Yuri,Ishibe, Noriko,Sawada, Masae,Takasugi, Hisashi,Tanaka, Hirokazu
-
p. 2390 - 2410
(2007/10/03)
-
- Substituted pyrazolyl benzenesulfonamides for use in veterinary therapies
-
A method of using pyrazolyl benzenesulfonamide compounds in treating inflammation and inflammation-related disorders in companion animals is disclosed.
- -
-
-
- Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation
-
A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: STR1 or a pharmaceutically-acceptable salt thereof.
- -
-
-
- Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)
-
A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC- 236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-y1]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.
- Penning, Thomas D.,Talley, John J.,Bertenshaw, Stephen R.,Carter, Jeffery S.,Collins, Paul W.,Docter, Stephen,Graneto, Matthew J.,Lee, Len F.,Malecha, James W.,Miyashiro, Julie M.,Rogers, Roland S.,Rogier,Yu, Stella S.,Anderson, Gary D.,Burton, Earl G.,Cogburn, J. Nita,Gregory, Susan A.,Koboldt, Carol M.,Perkins, William E.,Seibert, Karen,Veenhuizen, Amy W.,Zhang, Yan Y.,Isakson, Peter C.
-
p. 1347 - 1365
(2007/10/03)
-
- Photosensitized Oxidation of Furans. Part 15. Limitations to the Formation of Carbonyl Oxides from 2-Alkoxyfurans, and Direct Evidence for the First 3H-1,2-Dioxole
-
Formation of the carbonyl oxides 3, via the furan endo-peroxides 1, can be accomplished only by dye-sensitized photo-oxygenation of 2-alkoxyfurans 2 unsubstituted at C-4, electron-withdrawing substituents at C-3 making the formation selective.Hydrogen or
- Graziano, M. Liliana,Iesce, M. Rosaria,Cermola, Flavio,Cimminiello, Guido,Scarpati, Rachele
-
p. 1479 - 1484
(2007/10/02)
-
