- Novel O-acylated amidoximes and substituted 1,2,4-oxadiazoles synthesised from (+)-ketopinic acid possessing potent virus-inhibiting activity against phylogenetically distinct influenza A viruses
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This article describes the synthesis and antiviral activity evaluation of new substituted 1,2,4-oxadiazoles containing a bicyclic substituent at position 5 of the heterocycle and O-acylated amidoximes as precursors for their synthesis. New compounds were
- Chernyshov, Vladimir V.,Yarovaya, Olga I.,Esaulkova, Iana L.,Sinegubova, Ekaterina,Borisevich, Sophia S.,Popadyuk, Irina I.,Zarubaev, Vladimir V.,Salakhutdinov, Nariman F.
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- Catalyst-free, one-pot strategy to access 3-substituted-5-amino-1,2,4-thiadiazoles in water
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A protocol has been devised for the synthesis of 3-substituted 5-amino-1,2,4-thiadiazoles utilizing isothiocyanates, amidoximes and water as an eco-friendly solvent. The strategy involves consecutive C?N and S?N bonds formation in a one-pot reaction under
- Nagaraju, Chaithra,Ashok, Swarup Hassan,Narayana, Yatheesh,Nagarakere, Sandhya C.,Kempegowda, Mantelingu,Kanchugarkoppal, Rangappa S.
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p. 3610 - 3619
(2021/10/14)
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- Discovery of BR102375, a new class of non-TZD PPARγ full agonist for the treatment of type 2 diabetes
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As a potential treatment of type 2 diabetes, a novel PPARγ non-TZD full agonist, compound 18 (BR102375) was identified from the original lead BR101549 by the SAR efforts of the labile metabolite control through bioisosteres approach. In vitro assessments
- Choung, Wonken,Yang, Deokmo,Kim,Choi, Hyukjoon,Lee, Bo Ram,Park, Min,Jang, Su Min,Lim, Jae Soo,Kim, Woo Sik,Kim, Kyung-Hee,Chin, Jungwook,Jung, Kyungjin,Lee, Geumwoo,Hong,Jang, Tae-ho,Joo, Jeongmin,Hwang, Hayoung,Myung, Jayhyuk,Kim, Seong Heon
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p. 2275 - 2282
(2019/06/27)
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- N-hydroxy-substituted 2-aryl acetamide analogs: A novel class of HIV-1 integrase inhibitors
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An in silico method has been used to discover N-hydroxy-substituted 2-aryl acetamide analogs as a new class of HIV-1 integrase inhibitors. Based on the molecular requirements of the binding pocket of catalytic active site, two molecules (compounds 2 and 4
- Debnath, Utsab,Kumar, Prachi,Agarwal, Aakanksha,Kesharwani, Ajay,Gupta, Satish K.,Katti, Seturam B.
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p. 527 - 534
(2017/09/14)
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- Nitrobenzofurazan derivatives of N′-hydroxyamidines as potent inhibitors of indoleamine-2,3-dioxygenase 1
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Tryptophan metabolism through the kynurenine pathway is considered as a crucial mechanism in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism in the immune system and it is also considered as an important therapeutic target for the treatment of cancer and other diseases that are linked with kynurenine pathway. In this study, a series of nitrobenzofurazan derivatives of N′-hydroxybenzimidamides (1) and N′-hydroxy-2-phenylacetimidamides (2) were synthesized and their inhibitory activities against human IDO1 enzyme were tested using in-vitro and cellular enzyme activity assay. The optimization leads to the identification of potent compounds, 1d, 2i and 2k (IC50 = 39-80 nM), which are either competitive or uncompetitive inhibitors of IDO1 enzyme. These compounds also showed IDO1 inhibition potencies in the nanomolar range (IC50 = 50-71 nM) in MDA-MB-231 cells with no/negligible amount of cytotoxicity. The stronger selectivity of the potent compounds for IDO1 enzyme over tryptophan 2,3-dioxygenase (TDO) enzyme (312-1593-fold) also makes them very attractive for further immunotherapeutic applications.
- Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Trivedi, Vishal,Manna, Debasis
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p. 364 - 375
(2016/06/13)
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- Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors
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A series of novel β-diketo derivatives which combined the virtues of dihydroxypyrimidine carboxamide derived from the evolution of DKA and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and
- Wang, Yujie,Rong, Jie,Zhang, Bin,Hu, Liming,Wang, Xiaoli,Zeng, Chengchu
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p. 735 - 741
(2015/02/19)
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- In Silico Exploration for New Antimalarials: Arylsulfonyloxy Acetimidamides as Prospective Agents
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A strategy is described to identify new antimalarial agents to overcome the drug resistance and/or failure issues through in silico screening of multiple biological targets. As a part of this, three enzymes namely CTPS, CK, and GST were selected, from among 56 drug targets of P. falciparum, and used them in virtual screening of ZINC database entries which led to the design and synthesis of arylsulfonyloxy acetimidamides as their consensus inhibitors. From these, two compounds showed good activity against sensitive (3D7; IC50, 1.10 and 1.45 μM) and resistant (K1; IC50, 2.10 and 2.13 μM) strains of the parasite, and they were further investigated through docking and molecular dynamics simulations. The findings of this study collectively paved the way for arylsulfonyloxy acetimidamides as a new class of antimalarial agents. (Chemical Presented).
- Verma, Saroj,Debnath, Utsab,Agarwal, Pooja,Srivastava, Kumkum,Prabhakar, Yenamandra S.
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p. 1708 - 1719
(2015/09/01)
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- OXADIAZOLE COMPOUNDS
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The present invention relates to a compound of formula (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein R1,R2,R3,L1,L2,L3,L4,L5 and n, have the same meaning as that defined in the claims and the description. The present invention also relates to compositions, in particular pharmaceuticals, comprising such compounds, and to uses of such compounds and compositions for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases, and/or protein misfolding disorders.
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Page/Page column 143; 144
(2015/11/11)
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- Design and discovery of 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide inhibitors of HIV-1 integrase
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Raltegravir (RAL) is a first clinically approved integrase (IN) inhibitor for the treatment of HIV but rapid mutation of the virus has led to chemo-resistant strains. Therefore, there is a medical need to develop new IN inhibitors to overcome drug resista
- Zhang, Daoguang,Debnath, Bikash,Yu, Shenghui,Sanchez, Tino Wilson,Christ, Frauke,Liu, Yang,Debyser, Zeger,Neamati, Nouri,Zhao, Guisen
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p. 5446 - 5453
(2014/12/11)
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- HIV INTEGRASE INHIBITORS
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The disclosure generally relates to the novel compounds of formula I, including their salts, which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.
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Page/Page column 34
(2011/05/05)
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- Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited
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A series of dihydroxypyrimidine (DHP) derivatives were designed as inhibitors of HIV integrase (IN) based on known homology models. Through chemical synthesis and biochemical assays it was found that the activity profile of these compounds largely deviate
- Tang, Jing,Maddali, Kasthuraiah,Pommier, Yves,Sham, Yuk Y.,Wang, Zhengqiang
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supporting information; experimental part
p. 3275 - 3279
(2010/08/19)
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- Acetic acid aldose reductase inhibitors bearing a five-membered heterocyclic core with potent topical activity in a visual impairment rat model
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A number of 1,2,4-oxadiazol-5-yl-acetic acids and oxazol-4-yl-acetic acids were synthesized and tested for their ability to inhibit aldose reductase (ALR2). The oxadiazole derivatives, 7c, 7f, 7i, and 8h, 8i, proved to be the most active compounds, exhibiting inhibitory levels in the submicromolar range. In this series, the phenyl group turned out to be the preferred substitution pattern, as its lengthening to a benzyl moiety determined a general reduction of the inhibitory potency. The lead compound, 2-[3-(4-methoxyphenyl)-1,2,4- oxadiazol-5-yl]acetic acid, 7c, showed an excellent in vivo activity, proving to prevent cataract development in severely galactosemic rats when administered as an eye-drop solution in the precorneal region of the animals. Computational studies on the ALR2 inhibitors were performed to rationalize the structure-activity relationships observed and to provide the basis for further structure-guided design of novel ALR2 inhibitors.
- La Motta, Concettina,Sartini, Stefania,Salerno, Silvia,Simorini, Francesca,Taliani, Sabrina,Marini, Anna Maria,Da Settimo, Federico,Marinelli, Luciana,Limongelli, Vittorio,Novellino, Ettore
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supporting information; experimental part
p. 3182 - 3193
(2009/04/06)
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- BICYCLIC PYRIMIDINONES AND USES THEREOF
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The present invention provides a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. Further provided is a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. A pharmaceutical composition or medicament comprising a compoundof Formula I is also provided.
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Page/Page column 143
(2008/12/06)
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- NOVEL HETEROCYCLIC COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to new compounds which are Heterocyclic derivatives of formula (I) wherein A, B, P, X, Y, Q, W, R1 and R2 are defined in the description. Invention compounds are useful for treating central or peripheral nervous system disorders and other disorders which are affected by the neuromodulatory effect of mGluR5 positive allosteric modulators such as cognitive decline and also to treat both positive and negative symptoms in schizophrenia.
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Page/Page column 44
(2010/11/25)
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- PHENYLTHIOACETIC ACID DERIVATIVES AND USE THEREOF
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The invention relates to novel phenylthioacetic acid derivatives of formula (I), to a method for the production thereof, to the use thereof for the treatment and/or prophylaxis of diseases, in addition to the use thereof in the production of medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prevention of cardiovascular diseases, in particular dyslipidaemia and arteriosclerosis. The compounds act as modulators for the PRAR-alpha receptor.
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Page/Page column 90
(2010/02/14)
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- NOVEL ALKYNYL DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to novel compounds of formula (I) wherein W, n, X and W’ are defined in the description; invention compounds are modulators of metabotropic glutamate receptors - subtype 5 (“mGluR5”) which are useful for the treatment of central nervous system disorders as well as other disorders modulated by mGluR5 receptors.
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Page/Page column 97
(2008/06/13)
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- Discovery of potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70
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A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200- 400-fold more potent than the native,
- Vu, Chi B.,Corpuz, Evelyn G.,Merry, Taylor J.,Pradeepan, Selvaluxmi G.,Bartlett, Catherine,Bohacek, Regine S.,Botfield, Martyn C.,Eyermann, Charles J.,Lynch, Berkley A.,MacNeil, Ian A.,Ram, Mary K.,Van Schravendijk, Marie Rose,Violette, Shelia,Sawyer, Tomi K.
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p. 4088 - 4098
(2007/10/03)
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