- Bronchospasmolytic activity and adenosine receptor binding of some newer 1,3-dipropyl-8-phenyl substituted xanthine derivatives
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The aldehyde derivatives of 1,3-dipropyl xanthines as described in this paper, constitutes a new series of selective adenosine ligands displaying bronchospasmolytic activity. The effect of substitution at third- and fourth-position of 8-phenyl xanthine ha
- Gumber, Divya,Yadav, Divya,Yadav, Rakesh,Kachler, Sonja,Klotz, Karl Norbert
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p. 600 - 609
(2020/03/23)
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- COMPOUNDS FOR MODULATING DDAH AND ADMA LEVELS, AS WELL AS METHODS OF USING THEREOF TO TREAT DISEASE
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Disclosed are compounds that can modulate DDAH and the amount of asymmetric dimethylarginine (ADMA) in a subject. Also provided are pharmaceutical compositions comprising these compounds, as well as methods of using these compositions to treat and/or prevent diseases associated with elevated or low levels of DDAH and ADMA.
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Page/Page column 136; 137
(2019/11/19)
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- Discovery and structure-activity relationship of novel 2,3- dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2 h)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 Inhibitors
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Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3′,4′-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4′-hydroxyl/4′-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.
- Patel, Maulik R.,Bhatt, Aaditya,Steffen, Jamin D.,Chergui, Adel,Murai, Junko,Pommier, Yves,Pascal, John M.,Trombetta, Louis D.,Fronczek, Frank R.,Talele, Tanaji T.
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p. 5579 - 5601
(2014/08/05)
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- IMIDAZO [4, 5 - B] PYRIDINE DERIVATIVES AS ALK AND JAK MODULATORS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
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This application relates to compounds of the Formula I as defined herein, and/or salts thereof. This application further relates to compositions and methods of using these compounds and/or salts thereof. The compounds of Formula I are useful as ALK and JAK modulators for the treatment of proliferative disorders.
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Page/Page column 220
(2013/08/15)
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- Synthesis and antimicrobial activity of novel analogs of trifenagrel
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Novel analogs of trifenagrel were synthesized by using inexpensive and reusable phosphotungstic acid, H3[PW12O40] (3 mol %) catalyst under classical heating. Two of the newly synthesized triaryl imidazoles exhibited moderate antibacterial activity.
- Nagarapu, Lingaiah,Aneesa,Satyender, Apuri,Chandana,Bantu, Rajaskaker
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experimental part
p. 195 - 200
(2009/07/19)
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- Synthesis of a series of 8-(substituted-phenyl)xanthines and a study on the effects of substitution pattern of phenyl substituents on affinity for adenosine A1 and A2A receptors
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A new series of 8-(substituted-phenyl)xanthines have been synthesized and compounds were evaluated for their affinity for A1 and A2 adenosine receptors (AR) using radioligand binding assays. The effects of varying the positions of 8-phenyl substituents on affinity and selectivity at A1 and A2A adenosine receptors have been studied. Isovanilloid 1,3-dimethyl-8-[4-methoxy-3-(2-morpholin-4-ylethoxy)phenylxanthine (9d) displayed the highest affinity and selectivity towards A2A AR subtypes with Ki = 100 nM over A1 receptors (Ki > 100 mM). It has been observed that substitution pattern on 8-phenyl group greatly affects the affinity and selectivity at adenosine receptors, with A2A tolerating bulkier substituents than did A1 receptors.
- Bansal, Ranju,Kumar, Gulshan,Gandhi, Deepika,Young, Louise C.,Harvey, Alan L.
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experimental part
p. 2122 - 2127
(2009/09/30)
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- Compounds for the treatment of ischemia
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A3 agonists, methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists. The A3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia
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- Butenolide endothelin antagonists with improved aqueous solubility
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Continued development around our ET(A)-selective endothelin (ET) antagonist 1 (CI-1020) has led to the synthesis of analogues with improved aqueous solubility profiles. Poor solubility characteristics displayed by 1 required a complex buffered formulation
- Patt, William C.,Cheng, Xue-Min,Repine, Joseph T.,Lee, Chet,Reisdorph, Bill R.,Massa, Mark A.,Doherty, Annette M.,Welch, Kathleen M.,Bryant, John W.,Flynn, Michael A.,Walker, Donnelle M.,Schroeder, Richard L.,Haleen, Stephen J.,Keiser, Joan A.
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p. 2162 - 2168
(2007/10/03)
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