- NON-PEPTIDE OPIOID RECEPTOR MODULATORS
-
Non-peptide MOR opioid receptor modulators are provided. The compounds exhibit predominantly central activity and are used to treat e.g. opioid addiction. The compounds described herein are generally delivered (administered) in a pharmaceutical compositio
- -
-
-
- INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN
-
Compounds and compositions for modulating fibroblast activation protein (FAP) are described. The compounds and compositions may find use as therapeutic agents for the treatment of diseases, including hyperproliferative diseases.
- -
-
Paragraph 0563; 0567-0569
(2019/07/03)
-
- Design, Synthesis, and Biological Evaluation of the Third Generation 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4′-pyridyl)carboxamido]morphinan (NAP) Derivatives as μ/κ Opioid Receptor Dual Selective Ligands
-
μ opioid receptor (MOR) agonists have been widely applied for treating moderate to severe pain. However, numerous adverse effects have been associated with their application, including opioid-induced constipation (OIC), respiratory depression, and addicti
- Zheng, Yi,Obeng, Samuel,Wang, Huiqun,Jali, Abdulmajeed M.,Peddibhotla, Bharath,Williams, Dwight A.,Zou, Chuanchun,Stevens, David L.,Dewey, William L.,Akbarali, Hamid I.,Selley, Dana E.,Zhang, Yan
-
p. 561 - 574
(2019/01/30)
-
- Nitrogen introduction of spirobifluorene to form α-, β-, γ-, and δ-aza-9,9′-spirobifluorenes: New bipolar system for efficient blue organic light-emitting diodes
-
Four aza-9,9′-spirobifluorenes (aza-SBFs) with nitrogen atom at different positions of one fluorene moiety were synthesized to study the structure-properties relationships. α-Aza-SBF and β-aza-SBF possessed almost completely separated the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), while γ-aza-SBF and δ-aza-SBF showed overlapped HOMO and LUMO orbitals. The aza-SBFs showed excellent bipolar features and good thermal stabilities than those of SBFs. The maximum current efficiencies (CE) of α-, β-, γ-, and δ-aza-SBF-based OLEDs were 28.8, 24.9, 25.5, and 27.2 cd/A, respectively. Compared to the SBF, all of four aza-SBFs showed better devices performances. The CE and power efficiency (PE) of OLED based on α-aza-SBF was 28.8 cd/A and 22.6 lm/W, while the SBF-based OLED was only 12.3 cd/A and 8.2 lm/W. The maximum external quantum efficiency of α-aza-SBF-based OLED was 15.4%, which was 2.5 times than that of the SBF-based one (6.6%) due to introduction of nitrogen improving electron transporting. Novel materials based on these components and their potential applications in organic electronics were expected due to their excellent bipolar features.
- Wu, Peng,Zhu, Jun,Zhang, Zhen,Dou, Dehai,Wang, Hedan,Wei, Bin,Wang, Zixing
-
p. 185 - 191
(2018/04/17)
-
- 9-Hydroxyazafluorenes and their use in thrombin inhibitors
-
Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-L-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (Ki = 0.49 nM for human thrombin, 2× APTT = 0.37 μM in human plasma) and pharmacokinetic properties (F = 39%, iv T1/2 = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-L-prolyl-2-aminomethyl-5- chlorobenzylamide (19b), with high potency (Ki = 0.40 nM, 2× APTT = 0.18 μM), excellent pharmacokinetic properties (F = 55%, T 1/2 = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl3-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 μg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.
- Stauffer, Kenneth J.,Williams, Peter D.,Selnick, Harold G.,Nantermet, Philippe G.,Newton, Christina L.,Homnick, Carl F.,Zrada, Matthew M.,Lewis, S. Dale,Lucas, Bobby J.,Krueger, Julie A.,Pietrak, Beth L.,Lyle, Elizabeth A.,Singh, Rominder,Miller-Stein, Cynthia,White, Rebecca B.,Wong, Bradley,Wallace, Audrey A.,Sitko, Gary R.,Cook, Jacquelyn J.,Holahan, Marie A.,Stranieri-Michener, Maria,Leonard, Yvonne M.,Lynch Jr., Joseph J.,McMasters, Daniel R.,Yan, Youwei
-
p. 2282 - 2293
(2007/10/03)
-
