62012-15-1Relevant articles and documents
Effect of molecular structure on thermoresponsive behaviors of pyrrolidone-based water-soluble polymers
Sun, Jun,Peng, Yifeng,Chen, Ying,Liu, Yu,Deng, Junjie,Lu, Lican,Cai, Yuanli
, p. 4041 - 4049 (2010)
This paper describes the molecular structure dependent thermoresponsive behaviors of pyrrolidone-based water-soluble polymers. A series of well-defined poly[N-(2-methacryloyloxyethyl)pyrrolidone] (PNMEP), poly[N-(3- acryloyloxypropyl)pyrrolidone] (PNAPP), and poly[N-(3-methacryloyloxypropyl) pyrrolidone] (PNMPP) were synthesized via visible light activating RAFT polymerization at 25 °C. Kinetic studies indicate a rapid and well-controlled behavior of this polymerization. Gel permeation chromatography (GPC) and 1H NMR analysis confirm their intact molecular structure, well-defined molecular weight, and narrow distribution. Laser light scattering and temperature-variable 1H NMR analyses demonstrate that the cloud point of a PNMEP sample at a degree of polymerization (DP) of 96 is 1.5 °C lower than that of PNAPP at a DP = 104. Additional backbone methyl groups in PNMPP lead to a dramatic cloud point lowering, e.g., cloud point of PNMPP at a DP = 100 is 37 °C lower than that of PNAPP at a DP = 104. This is contrary to what was observed in poly(N-isopropylacrylamide) (PNIPA) and its polymethacrylamide analogues. These pyrrolidone-based polymers show a dramatic solvent isotopic effect that is different from that of PNIPA; e.g., the cloud point of PNMEP at a DP = 237 is 8.5 °C lower in D2O than in H2O. Increasing polymer chain length or hydrophobicity may suppress this solvent isotopic effect. This phase transition is correlated to Hofmeister series but more sensitive than PNIPA. Na2CO3 dramatically lowers cloud point, while NaI significantly improves cloud point, up to full dissolution in H2O at 95 °C. The solvent isotopic effect in NaCl or Na2CO3 solution is the same as what observed in solution absent of salt. Upon heating D2O solution of PNMEP, the polymer first forms the hydrated irregular colloidal aggregates near the cloud point, the phase transition occurs at the fully hydrated state at cloud point, and further heating leads to the dehydration and separation from D2O. However, in NaCl solution, the dehydration of PNMEP occurs subsequently from apolar backbones, spacers, and finally pyrrolidone groups.
Pilsicainide and its oxymethylene analog: Facile alternative syntheses and in vitro testing on human skeletal muscle sodium channels
Bruno, Claudio,Catalano, Alessia,Desaphy, Jean-Francois,Cavalluzzi, Maria M.,Carocci, Alessia,Dipalma, Antonella,Franchini, Carlo,Lentini, Giovanni,Camerino, Diana Conte,Tortorella, Vincenzo
, p. 2011 - 2026 (2008/09/18)
Facile, alternative synthetic routes gave access to both pilsicainide [N-(2,6-dimethylphenyl)-2-tetrahydro-lH-pyrrolizin-7a(5H)-ylacetamide, 1], a well-known Ic antiarrhythmic drug, and its oxymethylene analog 2. Both compounds were tested on human skeletal muscle voltage-gated sodium channels, hNavl.4, transfected in tsA201 cells. 7a-[2-(2,6-Dimethylphenoxy)ethyl]hexahydro-lH-pyrrolizine (2) behaved as a bioisostere of 1, exerting a 4-fold more potent use-dependent block.
Quinazoline derivatives and pharmaceutical compositions containing them
-
, (2008/06/13)
The invention relates to quinazoline derivatives of formula (1) wherein m is an integer from 1 to 2; R1represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6(wherein R5and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR7CO—, —CONR8—, —SO2NR9—, —NR10SO2— or —NR11— (wherein R7, R8, R9, R10and R11each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); R4represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
