- The impact of 5-substituted uracil derivatives on immortalized embryo lung cells
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Background: Pyrimidine-based drugs stimulate tissue regeneration and immunity, two components that need to be improved in a number of respiratory diseases of different etiology (e.g. influenza and asthma). In the present study we investigated relationships between the character of substitutions in the uracil structure and the impact of the respective uracil derivatives on the immortalized lung cells. Methods: The level of cell proliferation, maximum tolerated dose and toxic effect of 5-substituted uracil derivatives (12 compounds) were studied on the immortalized lung epithelial cells and compared with the ones of 6-methyluracil. Results: 5-Carboxyuracil and 1,3-dimethyl-5-carboxyuracil had the lowest cytotoxicity among the studied compounds. Their maximal tolerated dosage values were 5 times higher whereas the proliferation index was increased by 25% and 75%, respectively, compared to 6-methyluracil, known for its positive effects on cell regeneration. Conclusion: 5-Carboxyuracil and 1,3-dimethyl-5-carboxyuracil have the best perspectives for further studies on their biological effects.
- Kabal’nova, Natalia N,Grabovskiy, Stanislav A.,Andriayshina, Nadezhda M.,Egorov, Vladislav I.,Valiullin, Lenar R.,Nabatov, Alexey A.,Raginov, Ivan S.,Murinov, Yurii I.
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p. 1409 - 1414
(2017/12/28)
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- 7-Substituted-pyrrolo[3,2-d]pyrimidine-2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: A promising approach for treating pain and inflammation
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The transient receptor potential ankyrin 1 (TRPA1) channel is activated by a series of by-products of oxidative/nitrative stress, produced under inflammatory conditions or in the case of tissue damage, thus generating inflammatory and neuropathic pain and
- Baraldi, Pier Giovanni,Romagnoli, Romeo,Saponaro, Giulia,Aghazadeh Tabrizi, Mojgan,Baraldi, Stefania,Pedretti, Pamela,Fusi, Camilla,Nassini, Romina,Materazzi, Serena,Geppetti, Pierangelo,Preti, Delia
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scheme or table
p. 1690 - 1698
(2012/04/23)
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- FUSED PYRIMIDINE-DIONE DERIVATIVES AS TRPA1 MODULATORS
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The invention described herein relates to novel fused pyrimidinediones derivatives of formula (I) which are TRPA (Transient Receptor Potential subfamily A) modulators. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders modulated by TRPAl (Transient Receptor Potential subfamily A, member 1). This invention also provides processes for preparing compounds described herein, intermediates used in their synthesis, pharmaceutical compositions thereof, and methods for treating or preventing diseases, conditions and/or disorders modulated by TRPAl. Formula (I)
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Page/Page column 27-28
(2010/11/03)
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- New pyrrolopyrimidin-6-yl benzenesulfonamides: Potent A2B adenosine receptor antagonists
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A new series of 4-(1,3-dialkyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6 -yl)benzenesulfonamides has been identified as potent A2B adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A2B, A1 and A3 adenosine receptors. 6-(4-{[4-(4-Bromobenzyl)piperazin-1-yl]sulfonyl}phenyl)-1,3-dimethyl-1H- pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione (16) showed a high affinity for the A2B adenosine receptor (IC50 = 1 nM) and selectivity (A1: 183x; A3: 12660x). Synthesis and SAR of this novel class of compounds showing improved absorption properties is presented herein.
- Esteve, Cristina,Nueda, Arsenio,Diaz, Jose Luis,Beleta, Jorge,Cardenas, Alvaro,Lozoya, Estrella,Cadavid, Maria Isabel,Loza, Maria Isabel,Ryder, Hamish,Vidal, Bernat
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p. 3642 - 3645
(2008/09/21)
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- A2B ADENOSINE RECEPTOR ANTAGONISTS
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Disclosed are novel compounds that are A2B adenosine receptor antagonists having the following structure (I) wherein R1 and R2 are independently chosen from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl, and R4 is an optionally substituted heteroaryl moiety. The compounds of the invention are useful for treating various disease states, including asthma, chronic obstructive pulmonary disorder, pulmonary inflammation, emphysema, diabetic disorders, inflammatory gastrointestinal tract disorders, immunological/inflammatory disorders, cardiovascular diseases, neurological disorders, and diseases related to angiogenesis.
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Page/Page column 39
(2008/06/13)
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- Antiparasitic activity of highly conjugated pyrimidine-2,4-dione derivatives
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4-[2-(1,3-Dimethyl-5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl) vinyl]benzaldehyde was synthesized in four steps from 6-methyl-1H,3H-pyrimidine- 2,4-dione. This aldehyde was functionalized by various substituted anilines or substituted benzylamines. Antiparasitic activities of the corresponding azomethines were assessed against Plasmodium falciparum, Trichomonas vaginalis and Leishmania infantum compared to their toxicity versus human cells.
- Azas, Nadine,Rathelot, Pascal,Djekou, Serge,Delmas, Florence,Gellis,Di Giorgio, Carole,Vanelle, Patrice,Timon-David, Pierre
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p. 1263 - 1270
(2007/10/03)
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- Pyrrolodiazine derivatives as stabilizers for chilorine-containing polymers
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The invention relates to compositions comprising a) a chlorine-containing polymer and b) at least one compound containing at least one radical of the formula I STR1 in which A is the additional groups or atoms necessary to form an unsubstituted or substituted six-membered heterocyclic ring containing two nitrogen ring atoms.
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- Synthesis and structure-activity relationships of deazaxanthines: Analogs of potent A1- and A2-adenosine receptor antagonists
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A set of 22 9-deazaxanthines (pyrrolo[3,2-d]pyrimidine-2,4-diones) and three 7-deazaxanthines (pyrrolo[2,3-d]pyrimidine-2,4-diones) with various substituents in the 1-, 3-, 7- or 9-, and 8-positions was synthesized and investigated in A1 and A2a adenosine receptor binding assays at rat brain cortical membranes and rat brain striatal membranes, respectively. 9- Deazaxanthines showed structure-activity relationships that were similar to those of xanthines. They were about equipotent to the corresponding xanthines at A2a adenosine receptors. 9-Deazaxanthines were generally at least 1-3- fold more potent than xanthines at A1 receptors and therefore exhibited higher A1 selectivities compared to the xanthines. 1,3-Dimethyl-8-(2- naphthyl)-9-deazaxanthine (19e) showed high affinity (K(i) = 26 nM) and selectivity for A1 adenosine receptors. A hydroxyl function at N7 of 9- deazaxanthines was unfavorable for A1 and A2a receptor binding. 7- Deazaxanthines were considerably less potent compared to xanthines and to 9- deazaxanthines at both receptor subtypes.
- Grahner,Winiwarter,Lanzner,Muller
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p. 1526 - 1534
(2007/10/02)
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- Novel Reaction of Uracil Derivatives Possessing Electron-withdrawing Groups at the 5-Position with Amines: Exchange Reaction between the N1-Portion of Uracils and Amines
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The reaction of 1,3-disubstituted uracils possessing an electron-withdrawing group such as nitro, carbamoyl, and cyano at 5-position with primary amines resulted in the exchange of the N1-portion of the uracil ring with the amine moiety.The exchange reactions were influenced by the nature of substituents at the 5- and N1-position.The reaction sequence is explained in terms of addition, ring-opening, and ring-closure.
- Hirota, Kosaku,Kitade, Yukio,Sajiki, Hironao,Maki, Yoshifumi,Yogo, Motoi
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p. 367 - 373
(2007/10/02)
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