- Comprehensive studies on dual excitation behavior of double proton versus charge transfer in 4-(N-substituted amino)-1H-pyrrolo[2,3-b]pyridines
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Comprehensive spectroscopic and dynamical studies on the dual excitation behavior of proton vs charge transfer for 4-(dimethylamino)-1H-pyrrolo[2,3-b]pyridine (DPP) and its related derivatives are reported. In cyclohexane, DPP dimer and/or dual hydrogen-bonded complex are formed with association constants Ka as high as ~4.2 × 103 and 5.2 × 104 M-1 (e.g., the DPP/acetic acid complex) at 298 K, respectively, which upon electronic excitation undergo ultrafast rate (?6.7 × 1010 s-1) of double-proton transfer, resulting in a unique tautomer emission. Dual fluorescence was observed in polar, aprotic solvents, in which the large Stokes shifted emission band originates from the charge-transfer species incorporating a dimethylamine and pyridine ring as electron donor and acceptor, respectively. Detailed solvent-polarity and temperature-dependent studies in combination with theoretical approaches have been performed to determine the excited-state charge-transfer properties such as dipole moment, orbital configuration, etc. Supplementary support for the dual charge/proton-transfer behavior was provided by the comparative spectroscopy and dynamics of various DPP-related derivatives. Further time-resolved measurements conclude that dual emissions share a common Franck-Condon excited state but undergo two independent relaxation channels. In protic solvents, such as ethanol, following fast solvent relaxation dynamics, the excited charge-transfer state further undergoes a solvent (i.e. alcohol) assisted proton-transfer reaction. The charge versus proton-transfer emission can be distinguished via the temporal spectral evolution. The results demonstrate DPP to be a unique model among 7-azaindole analogues in which the interplay between charge and proton-transfer reactions is operative in the excited state.
- Cheng, Chung-Chih,Chang, Chen-Pin,Yu, Wei-Shan,Hung, Fa-Tsai,Liu, Yun-I,Wu, Guo-Ray,Chou, Pi-Tai
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- Synthesis, biological evaluation, and docking studies of novel pyrrolo[2,3-b]pyridine derivatives as both ectonucleotide pyrophosphatase/phosphodiesterase inhibitors and antiproliferative agents
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Ecto-nucleotide pyrophosphatases/phosphodiesterases (NPPs) together with nucleoside triphosphate diphosphohydrolases (NTPDases) and alkaline phosphatases (APs) are nucleotidases located at the surface of the cells. NPP1 and NPP3 are important members of NPP family that are known as druggable targets for a number of disorders such as impaired calcification, type 2 diabetes, and cancer. Sulfonylurea derivatives have been reported as antidiabetic and anticancer agents, therefore, we synthesized and investigated series of sulfonylurea derivatives 1a-m possessing pyrrolo[2,3-b]pyridine core as inhibitors of NPP1 and NPP3 isozymes that are over-expressed in cancer and diabetes. The enzymatic evaluation highlighted compound 1a as selective NPP1 inhibitor, however, 1c was observed as the most potent inhibitor of NPP1 with an IC50 value of 0.80 ± 0.04 μM. Compound 1l was found to be the most potent and moderately selective inhibitor of NPP3 (IC50 = 0.55 ± 0.01 μM). Furthermore, in vitro cytotoxicity assays of compounds 1a-m against MCF-7 and HT-29 cancer cell lines exhibited compound 1c (IC50 = 4.70 ± 0.67 μM), and 1h (IC50 = 1.58 ± 0.20 μM) as the most cytotoxic compounds against MCF-7 and HT-29 cancer cell lines, respectively. Both of the investigated compounds showed high degree of selectivity towards cancer cells than normal cells (WI-38). Molecular docking studies of selective and potent enzyme inhibitors revealed promising mode of interactions with important binding sites residues of both isozymes i.e., Thr256, His380, Lys255, Asn277 residues of NPP1 and His329, Thr205, and Leu239 residues of NPP3. In addition, the most potent antiproliferative agent, compound 1h, doesn't produce hypoglycemia as a side effect when injected to mice. This is an additional merit of the promising compound 1h.
- Ullah, Saif,El-Gamal, Mohammed I.,El-Gamal, Randa,Pelletier, Julie,Sévigny, Jean,Shehata, Mahmoud K.,Anbar, Hanan S.,Iqbal, Jamshed
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- The Synthesis of 5-Azaindoles by Substitution-Rearrangement of 7-Azaindoles upon Treatment with Certain Primary Amines
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Certain 4-substituted 1H-pyrrolopyridines (7-azaindoles) undergo a nucleophilic substitution-rearrangement upon treatment with various primary amines at elevated temperatures to yield N-1-substituted 4-amino-1H-pyrrolopyridines (5-azaindoles).Treatment of the same 7-azaindoles with secondary amines under the same reaction conditions led to simple nucleophilic substitution products.
- Girgis, Nabih S.,Larson, Steven B.,Robins, Roland K.,Cottam, Howard B.
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p. 317 - 325
(2007/10/02)
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