- Parallel synthesis in an EOF-based micro reactor
-
We present herein a micro reactor set-up that enables parallel syntheses to be performed under electroosmotic flow conditions. The Royal Society of Chemistry.
- Wiles, Charlotte,Watts, Paul
-
-
Read Online
- Chemoselective hydrogenation of nitrobenzyl ethers to aminobenzyl ethers catalyzed by palladium-nickel bimetallic nanoparticles
-
A highly efficient and chemoselective hydrogenation of nitrobenzyl ethers to aminobenzyl ethers was developed by using a novel palladium-nickel bimetallic nanocatalyst. Since the catalytic selectivity was resulted from the synergistic effects between two metals rather than the traditional catalyst poisons, the hydrogenation proceeded smoothly under additive-free conditions. Thus, the work-up procedure was as simple as to recover the catalyst by a magnetic separation and then to evaporate the solvent.
- Chen, Wenwen,Bao, Hailin,Wang, Dingsheng,Wang, Xinyan,Li, Yadong,Hu, Yuefei
-
p. 9240 - 9244
(2015/11/27)
-
- Quaternary ammonium salts and their use
-
This invention is to provide a compound for antagonizing CCR5, said compound being represented by the formula: wherein R1 is an optionally substituted phenyl or an optionally substituted thienyl; Y is -CH2-, -S- or -O-; and R2, R3 and R4 are independently an optionally substituted aliphatic hydrocarbon group or an optionally substituted alicyclic heterocyclic ring group, and being effective for the prevention and treatment of infectious disease of HIV.
- -
-
-
- Anilide derivative, production and use thereof
-
This invention is to provide a compound of the formula: wherein R1 is an optionally substituted 5- to 6-membered ring: C is a divalent group of the formula: wherein the ring A is an optionally substituted 5- to 6-membered aromatic ring, X is an optionally substituted C, N or O atom, and the ring B is an optionally substituted 5- to 7-membered ring; Z is a chemical bond or a divalent group; R2 is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, etc., or a salt thereof, which is useful for antagonizing MCP-1 receptor.
- -
-
-
- Bicyclic nitrogen heterocycles
-
Amino-substituted dihydropyrimido[4,5-d]pyrimidinones of the formula in which R1 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, R2 represents lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, and R3 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl, lower cycloalkenyl or lower cycloalkyl-lower alkyl, and pharmaceutically acceptable salts thereof are protein kinase inhibitors. They can be used in the treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular disorders, in the treatment of asthma, central nervous system disorders or diabetic complications or for the prevention of graft rejection following transplant surgery.
- -
-
-
- Self-immolative nitrogen mustard prodrugs for suicide gene therapy
-
Four new potential self-immolative prodrugs derived from phenol and aniline nitrogen mustards, four model compounds derived from their corresponding fluoroethyl analogues and two new self-immolative linkers were designed and synthesized for use in the suicide gene therapy termed GDEPT (gene-directed enzyme prodrug therapy). The self-immolative prodrugs were designed to be activated by the enzyme carboxypeptidase G2 (CPG2) releasing an active drug by a 1,6-elimination mechanism via an unstable intermediate. Thus, N-[(4-{[4-(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (23), N-[(4-{[4(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenoxy)carbonyl]-L-glutamic acid (30), N-[(4-{N-(4-(bis[2- chloroethyl]amino}}pheny)carbamoyloxy]methyl}phenoxy)carbonyl]-L-glutmic acid (37), and N-[(4-{[N-(4-{bis[2- chloroethyl]amino}phenyl)carbamoyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (40) were synthesized. They are bifunctional alkylating agents in which the activating effects of the phenolic hydroxyl or amino functions are masked through an oxycarbonyl or a carbamoyl bond to a benzylic spacer which is itself]inked to a glutamic acid by an oxycarbonyl or a carbamoyl bond. The corresponding fluoroethyl compounds 25, 32, 42, and 44 were also synthesized. The rationale was to obtain model compounds with greatly reduced alkylating abilities that would be much less reactive with nucleophiles compared to the corresponding chloroethyl derivatives. This enabled studies of these model compounds as substrates for CPG2, without incurring the rapid and complicated decomposition pathways of the chloroethyl derivatives. The prodrugs were desired to be activated to their corresponding phenol and aniline nitrogen mustard drugs by CPG2 for use in GDEPT. The synthesis of the analogous novel parent drugs (21b, 51) is also described. A colorectal cell line was engineered to express CPG2 tethered to the outer cell surface. The phenylenediamine compounds were found to behave as prodrugs, yielding IC50 prodrug/IC50 drug ratios between 20- and 33-fold (for 37 and 40) and differentials of 12-14-fold between CPG2-expressing and control LacZ- expressing clones. The drugs released are up to 70-fold more potent than 4- [(2-chloroethyl)(2-mesyloxyethyl)amino]benzoic acid that results from the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMBA) which has been used previously for GDEPT. These data demonstrate the viability of this strategy and indicate that self-immolative prodrugs can be synthesized to release potent mustard drugs selectively by cells expressing CPG2 tethered to the cell surface in GDEPT.
- Niculescu-Duvaz, Dan,Niculescu-Duvaz, Ion,Friedlos, Frank,Martin, Janet,Spooner, Robert,Davies, Lawrence,Marais, Richard,Springer, Caroline J.
-
p. 5297 - 5309
(2007/10/03)
-