- PYRIMIDO[5,4-d]PYRIMIDINE DERIVATIVES AS ENT INHIBITORS FOR THE TREATMENT OF CANCERS, AND COMBINATION THEREOF WITH ADENOSINE RECEPTOR ANTAGONISTS
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The present invention relates to pyrimido[5,4-d]pyrimidine derivatives of formula (I), including pharmaceutically acceptable salts and solvates thereof. Compounds of the invention are inhibitors of ENT family transporter, especially of ENT1, and are useful as therapeutic compounds for the treatment of cancers. The invention also relates to the combined use of the pyrimido[5,4-d]pyrimidine derivatives with an adenosine receptor antagonist, for the treatment of cancers.
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Page/Page column 134; 173
(2021/09/04)
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- Synthesis, biological evaluation and structure-activity correlation study of a series of imidazol-based compounds as Candida albicans inhibitors
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A new series of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives was synthesized. The antifungal activity was evaluated in vitro against different fungal species. The biological results show that the most active compounds possess an antifungal activity comparable or higher than Fluconazole against Candida albicans, non-albicans Candida species, Cryptococcus neoformans and dermathophytes. Because of their racemic nature, the most active compounds 5f and 6c were tested as pure enantiomers. For 6c the (R)-enantiomer resulted more active than the (S)-one, otherwise for 5f the (S)-enantiomer resulted the most active. To rationalize the experimental data, a ligand-based computational study was carried out; the results of the modelling study show that (S)-5f and (R)-6c perfectly align to the ligand-based model, showing the same relative configuration. Preliminary studies on the human lung adenocarcinoma epithelial cells (A549) have shown that 6c, 5e and 5f possess a low cytotoxicity.
- Moraca, Francesca,De Vita, Daniela,Pandolfi, Fabiana,Di Santo, Roberto,Costi, Roberta,Cirilli, Roberto,D'Auria, Felicia Diodata,Panella, Simona,Palamara, Anna Teresa,Simonetti, Giovanna,Botta, Maurizio,Scipione, Luigi
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p. 665 - 673
(2014/07/22)
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- Strategy for 14C-labeling of a series of bis(heteroaryl) piperazines
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Four bis(heteroaryl)piperazines labeled with carbon-14 in the 2-position of imidazole moiety were prepared as part of a 4-step (or 5-step) sequence from 5-hydroxymethyl-2-mercapto-1-benzylimida-zole-[2-14C] as a key synthetic intermediate which
- Arjomandi, Omid Khalili,Saemian, Nader,Shirvani, Gholamhossein,Javaheri, Mohsen,Esmailli, Kameh
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scheme or table
p. 363 - 366
(2012/06/04)
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- PIPERAZINE AND PIPERIDINE MGLUR5 POTENTIATORS
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Compounds of Formula I or pharmaceutically acceptable salts or solvates thereof, wherein A, B, D, Ar1, Ar2, R2, R3, R4, a, m and n are defined in the specification, methods for the use thereof, processes for making and pharmaceutical compositions containing the same.
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Page/Page column 38
(2008/12/07)
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- Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
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High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11β-HSD1 IC50 = 3 nM).
- Sun, Daqing,Wang, Zhulun,Di, Yongmei,Jaen, Juan C.,Labelle, Marc,Ma, Ji,Miao, Shichang,Sudom, Athena,Tang, Liang,Tomooka, Craig S.,Tu, Hua,Ursu, Stefania,Walker, Nigel,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
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scheme or table
p. 3513 - 3516
(2009/04/11)
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- Substituted piperazines as metabotropic glutamate receptor antagonists
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The invention relates to compounds of formula I or pharmaceutically acceptable salts or solvates thereof: where Ar1, Ar2, Hy, L, R1, m and n are as defined in the description. The invention also includes pharmaceutical compositions and uses thereof, processes for making the compounds, as well as methods for the medical treatment of mGluR5-mediated disorders.
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Page/Page column 15
(2008/06/13)
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- THERAPEUTIC AGENTS USEFUL FOR TREATING PAIN
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Compounds of formulae (I) and (II) where X is S or O and Ar2, R1, R2, R3, R8, n, m, and t are disclosed herein, or a pharmaceutically acceptable salt thereof (a "3-substituted Pyridyl Compound"), comp
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Page/Page column 93; 94
(2008/06/13)
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- Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2- yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist
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High throughput screening using the recombinant human TRPV1 receptor was used to identify a series of pyridinylpiperazine ureas (3) as TRPV1 vanilloid receptor ligands. Exploration of the structure-activity relationships by parallel synthesis identified t
- Swanson, Devin M.,Dubin, Adrienne E.,Shah, Chandra,Nasser, Nadia,Chang, Leon,Dax, Scott L.,Jetter, Michele,Breitenbucher, J. Guy,Liu, Changlu,Mazur, Curt,Lord, Brian,Gonzales, Lisa,Hoey, Kenway,Rizzolio, Michele,Bogenstaetter, Michael,Codd, Ellen E.,Lee, Doo H.,Zhang, Sui-Po,Chaplan, Sandra R.,Carruthers, Nicholas I.
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p. 1857 - 1872
(2007/10/03)
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- Acetamides and benzamides that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- 4-(2-Pyridyl)piperazine-1-carboxamides: Potent vanilloid receptor 1 antagonists
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A series of 4-(2-pyridyl)piperazine-1-carboxamide analogues based on the lead compound 1 was synthesized and evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH (5.5)-induced (pH) FLIPR assays in a rat VR1-expressing HEK293 cell line. Potent VR1 antagonists were identified through SAR studies. From these studies, 18 was found to be very potent in the in vitro assay [IC50=4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F%=15.1).
- Sun, Qun,Tafesse, Laykea,Islam, Khondaker,Zhou, Xiaoming,Victory, Sam F.,Zhang, Chongwu,Hachicha, Mohamed,Schmid, Lori A.,Patel, Aniket,Rotshteyn, Yakov,Valenzano, Kenneth J.,Kyle, Donald J.
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p. 3611 - 3616
(2007/10/03)
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- Acetamides and benzamides that are useful in treating sexual dysfunction
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The present invention relates to the use of compounds of formula (I) for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
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- Synthesis and anti-HIV-1 activity of new delavirdine analogues carrying arylpyrrole moieties
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In our search for novel anti-human immunodeficiency virus (HIV)-1 agents, 14 delavirdine analogues were synthesized and evaluated as potential anti-HIV-1 agents in cell-based assays. Compound 1Aa exhibited potent and selective anti-HIV-1 activity in acutely infected MT4 cells, with effective concentration (EC50) values in the submicromolar range.
- Pinna,Loriga,Murineddu,Grella,Mura,Vargiu,Murgioni,La Colla
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p. 1406 - 1411
(2007/10/03)
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- Terephthalamide derivatives
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The present invention relates to novel terephthalamide derivatives and in particular to novel terephthalamide derivatives of the following formula 1, its pharmaceutically acceptable salts as antiviral agents having remarkable inhibitory actions against th
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- Novel 21-Aminosteroids That Inhibit Iron-Dependent Lipid Peroxidation and Protect against Central Nervous System Trauma
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A novel class of 21-aminosteroids has been developed.Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 μM.Furthermore, selected members enhance early neurolo
- Jacobsen, E. Jon,McCall, John M.,Ayer, Donald E.,VanDoornik, Fred J.,Palmer, John R.,et al.
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p. 1145 - 1151
(2007/10/02)
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- ANTIPSYCHOTIC CYCLIC IMIDE DERIVATIVES OF 2-(4-BUTYLPIPERAZIN-1-YL) PYRIDINES, COMPOSITIONS AND USE
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Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is a substituted pyridin-2-yl ring and the second substituent is a butylene chain attached to cyclic imide heterocycles such as azaspiro 4.5!decanedione, dialkylglutarimide, thiazolidinedione, spirocyclopentylthiazolidinedione, or morpholine-2,6-dione. The compounds have psychotropic properties and 2-4-4-(2,4-dioxo-1-thia-3-azaspiro 4. 5!nonane-3-yl)butyl!-1-piperazinyl!-pyridine-3-carboxaldehyde is a typical embodiment having selective antipsychotic activity.
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- ANTIPSYCHOTIC CYCLIC IMIDE DERIVATIVES OF 2-(4-BUTYLPIPERAZIN-1-YL)PYRIDINES, COMPOSITIONS AND USE
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Disubstituted N,N-piperazinyl derivatives are disclosed wherein one substituent is a substituted pyridin-2-yl ring and the second substituent is a butylene chain attached to cyclic imide heterocycles such as azaspiro 4.5!decanedione, dialkylglutarimide, thiazolidinedione, spirocyclopentylthiazolidinedione, or morpholine-2,6-dione. The compounds have psychotropic properties and 2-4-4-(2,4-dioxo-1-thia-3-azaspiro 4. 5!nonane-3-yl)butyl!-1-piperazinyl!pyridine-3-carboxaldehyde is a typical embodiment having selective antipsychotic activity.
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- TREATNG SEDATION WITH 1-(3-SUBSTITUTED-2-PYRIDINYL)PIPERAZINES
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1-(3-Substituted-2-pyridinyl)piperazines and their acid addition salts are selective α 2-adrenergic receptor antagonists and thereby useful as antidepressant agents and for treating sedation caused by antihypertensive therapy.
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- Pyridinylpiperazines, a new class of selective α2-adrenoceptor antagonists
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A series of 1-(2-pyridinyl)piperazine derivatives was synthesized and evaluated for adrenergic activity. In vitro activity was assessed through the antagonism of clonidine's effect in the rat, isolated, field-stimulated vas deferens and by the displacemen
- Saari, Walfred S.,Halczenko, Wasyl,King, Stella W.,Huff, Joel R.,Guare, James P.,et al.
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p. 1696 - 1701
(2007/10/02)
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