5657-51-2Relevant articles and documents
Design and synthesis of novel PARP-1 inhibitors based on pyridopyridazinone scaffold
Elmasry, Ghada F.,Aly, Enayat E.,Awadallah, Fadi M.,El-Moghazy, Samir M.
, p. 655 - 666 (2019)
Various pyridopyridazinone derivatives were designed as Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. The pyridopyridazinone scaffold was used as an isostere of the phthalazine nucleus of the lead compound Olaparib in addition to some modifications in the tail part of the molecule. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to Olaparib in nanomolar level. The best PARP-1 inhibitory activity was observed for compound 8a with (IC50 = 36 nM) compared to Olaparib as a reference drug (IC50 = 34 nM). Molecular modeling simulation revealed that, the designed compounds docked well into PARP-1 active site and their complexes are stabilized by three key hydrogen bond interactions with both Gly863 and Ser904 as well as other favorable π-π and hydrogen-π stacking interactions with Tyr907 and Tyr896, respectively. Computational ADME study predicted that the target compounds 8a and 8e have proper pharmacokinetic and drug-likeness properties. These outcomes afford a new structural framework for the design of novel inhibitors for PARP-1.
ADENOSINE RECEPTOR BINDING COMPOUNDS
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Paragraph 00538-00539, (2020/02/06)
The present invention relates to pharmaceutical compounds and compositions of Formula (I) and methods of treatment using the compounds and compositions, especially for the treatment and/or prevention of a proliferation disorder, such as cancer. Compounds of Formula (I) as further described herein are shown modulators of the adenosine A2A receptor and exhibit antiproliferative activity. Accordingly, these compounds are useful to treat proliferative disorders such as cancer, and other adenosine receptor-related conditions including an inflammatory disease, renal disease, diabetes, vascular disease, lung disease, or an autoimmune disease.
Zinc and Cadmium Complexes of Pyridinemethanol Carboxylates: Metal Carboxylate Zwitterions and Metal–Organic Frameworks
Lin, Shi-Xin,Liu, Quan,Liu, Yan,Niu, Ru-Jie,Young, David J.,Zhang, Wen-Hua
, p. 832 - 837 (2020/06/03)
The heterofunctional lactone furo[3,4-b]pyridin-5(7H)-one (L1) undergoes a coordination-induced ring-opening reaction with Zn(NO3)2 ? 6H2O to yield the zwitterionic [Zn(L1′)2(H2O)2] (1, L1′=2-(hydroxymethyl)nicotinate) with an uncoordinated carboxylate. The same reaction with Cd(NO3)2 ? 4H2O provides a two-dimensional (2D) network of [Cd(L1′)2]n (3) with the carboxylates coordinated to cadmium(II) propagating the assembly. The corresponding reactions of Zn(NO3)2 ? 6H2O and Cd(NO3)2 ? 4H2O with 2-(hydroxymethyl)isonicotinic acid (HL2) generated zwitterionic [Zn(L2)2(H2O)2] (2) and a 2D network [Cd(L2)2]n?nDMF (4, DMF=N,N′-dimethylformamide), respectively. Complexes 1–4 are weakly emissive, giving ligand-centered emissions at 409 nm (1), 412/436 nm (2), 404 nm (3), and 412/436 nm (4) in CHCl3 solutions upon excitation at 330 nm. This work points to the potential of using ‘hidden’ functionalities widely found in small organic molecules and natural products for the construction of coordination complexes with new functionality and potential applications.
AZA-A-RING INDENOISOQUINOLINE TOPOISOMERASE I POISONS
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Paragraph 00104; 00120, (2017/10/13)
The invention described herein pertains to four series of aza-A-ring indenoisoquinolines, which are inhibitors of topoisomerase IB (Top1), and the processes for preparing said aza-A-ring indenoisoquinolines. Also described are methods for treating cancer
Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase i Poisons
Beck, Daniel E.,Reddy, P. V. Narasimha,Lv, Wei,Abdelmalak, Monica,Tender, Gabrielle S.,Lopez, Sophia,Agama, Keli,Marchand, Christophe,Pommier, Yves,Cushman, Mark
, p. 3840 - 3853 (2016/05/24)
Several indenoisoquinolines have shown promise as anticancer agents in clinical trials. Incorporation of a nitrogen atom into the indenoisoquinoline scaffold offers the possibility of favorably modulating ligand-binding site interactions, physicochemical properties, and biological activities. Four series of aza-A-ring indenoisoquinolines were synthesized in which the nitrogen atom was systematically rotated through positions 1, 2, 3, and 4. The resulting compounds were tested to establish the optimal nitrogen position for topoisomerase IB (Top1) enzyme poisoning activity and cytotoxicity to human cancer cells. The 4-aza compounds were the most likely to yield derivatives with high Top1 inhibitory activity. However, the relationship between structure and cytotoxicity was more complicated since the potency was influenced strongly by the side chains on the lactam nitrogen. The most cytotoxic azaindenoisoquinolines 45 and 46 had nitrogen in the 2- or 3-positions and a 3′-dimethylaminopropyl side chain, and they had MGM GI50 values that were slightly better than the corresponding indenoisoquinoline 64.
Dual fluorescent N-Aryl-2,3-naphthalimides: Applications in ratiometric DNA detection and white organic light-emitting devices
Nandhikonda, Premchendar,Heagy, Michael D.
supporting information; experimental part, p. 4796 - 4799 (2011/01/03)
A ten element matrix of 5- and 6-substituted-(2,3)-naphthalimides was prepared for the appropriate placement of substituents necessary to promote dual fluorescence (DF). As prescribed by our balanced seesaw photophysical model this matrix yielded nine new DF dyes out of a possible ten compounds. From this set of nine DF dyes, 4-fluoronaphthalic amide (37) was selected as a probe for ratiometric detection of DNA and demonstration of panchromatic emission.
Aza-analogue dibenzepinone scaffolds as p38 mitogen-activated protein kinase inhibitors:Design, synthesis, and biological data of inhibitors with improved physicochemical properties
Karcher, Solveigh C.,Laufer, Stefan A.
supporting information; experimental part, p. 1778 - 1782 (2010/03/01)
We recently described a promising novel class of p38 mitogen activated protein (MAP) kinase inhibitors with dibenzepinone-scaffolds. To optimize their physicochemical properties, characterized by calculated log P values and measured lipophilicity (chromatographic hydrophobicity index=CHI), we synthesized aza-analogue dibenzepinones. Here, we present the synthesis and biological data of compounds with the novel aza-dibenzepinone scaffolds. Although these aza-analogues revealed an improved aqueous solubility, introduction of nitrogen was not effective in the p38 MAPK enzyme assay.
HETEROARYL DIHYDROINDOLONES AS KINASE INHIBITORS
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Page/Page column 17-18, (2010/11/30)
The present invention provides a compound represented by the formula: wherein the variables R1, b, R6, Y, Z, X, R and a are defined in the specification. Said compound may be used in a method for treating diseases related to unregula
A facile synthesis of substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines
Inoue, Kunimi,Sugaya, Toru,Ogasa, Takehiro,Tomioka, Shinji
, p. 113 - 116 (2007/10/03)
5-Amino-5,11-dihydro[1]benzoxepino[3,4-b]pyridines (1) show anti-ulcer and antiarrhythmic activity. An efficient method for the preparation of a key intermediate, furo[3,4-b]pyridin-5(7H)-one (4), and the facile synthesis of 1 were described. The reduction of quinolinic anhydride (5) with sodium borohydride in the presence of acetic acid regioselectively gave the lactone 4. Lactone 4 was then reacted with substituted phenols under basic conditions and the resultant products, 2-(phenoxymethyl)-3-pyridinecarboxylic acids (3), underwent Friedel-Crafts cyclizations to produce the 5,11-dihydro[1]benzoxepino[3,4-b]pyridin-5-ones (2). Compounds 2 were then converted to imines with amines and successively reduced with zinc in acetic acid to the desired compounds 1.
Magnesium Ion Assisted Highly Regio- and Chemoselective Reduction of 5H-Pyrrolopyridine-5,7(6H)-diones with Sodium Borohydride. A Convenient Synthesis of 6,7-Dihydro-7-hydroxy-5H-pyrrolopyridin-5-ones
Goto, Takehiko,Konno, Michio,Saito, Minoru,Sato, Ryu
, p. 1205 - 1210 (2007/10/02)
6-Substituted and unsubstituted 6,7-dihydro-7-hydroxy-5H-pyrrolopyridin-5-ones were predominantly obtained in excellent yield by the reduction of the corresponding 5,7-diones with sodium borohydride in the presence of Mg ion at 0 deg C.The highly r
