- Fast Cyclization of a Proline-Derived Self-Immolative Spacer Improves the Efficacy of Carbamate Prodrugs
-
Self-immolative (SI) spacers are sophisticated chemical constructs designed for molecular delivery or material degradation. We describe herein a (S)-2-(aminomethyl)pyrrolidine SI spacer that is able to release different types of anticancer drugs (possessing either a phenolic or secondary and tertiary hydroxyl groups) through a fast cyclization mechanism involving carbamate cleavage. The high efficiency of drug release obtained with this spacer was found to be beneficial for the in vitro cytotoxic activity of protease-sensitive prodrugs, compared with a commonly used spacer of the same class. These findings expand the repertoire of degradation machineries and are instrumental for the future development of highly efficient delivery platforms.
- Belvisi, Laura,Borlandelli, Valentina,Corno, Cristina,Dal Corso, Alberto,Gennari, Cesare,Perego, Paola,Pignataro, Luca
-
p. 4176 - 4181
(2020/02/05)
-
- Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions
-
The recent discovery of hydropersulfides (RSSH) in mammalian systems suggests their potential roles in cell signaling. However, the exploration of RSSH biological significance is challenging due to their instability under physiological conditions. Herein, we report the preparation, RSSH-releasing properties, and cytoprotective nature of alkylamine-substituted perthiocarbamates. Triggered by a base-sensitive, self-immolative moiety, these precursors show efficient RSSH release and also demonstrate the ability to generate carbonyl sulfide (COS) in the presence of thiols. Using this dually reactive alkylamine-substituted perthiocarbamate platform, the generation of both RSSH and COS is tunable with respect to half-life, pH, and availability of thiols. Importantly, these precursors exhibit cytoprotective effects against hydrogen peroxide-mediated toxicity in H9c2 cells and cardioprotective effects against myocardial ischemic/reperfusion injury, indicating their potential application as new RSSH- and/or COS-releasing therapeutics.
- Khodade, Vinayak S.,Pharoah, Blaze M.,Paolocci, Nazareno,Toscano, John P.
-
supporting information
p. 4309 - 4316
(2020/03/05)
-
- Efficient solvent-free synthesis of urea derivatives using selenium-catalyzed carbonylation of amines with carbon monoxide and oxygen
-
In the presence of a catalytic amount of selenium under ambient pressure of carbon monoxide with oxygen, solvent-free facile synthesis of urea derivatives was developed; the aim is for green and sustainable chemistry. For example, N,N-dimethylethylenediamine (20 mmol) successfully afforded 1,3- dimethylimidazolidin-2-one (DMI) in 74% yield (1487% based on Se) using selenium catalyst (5 mol%) under mixed gas (CO/O2, 2:1) at 0.1 MPa, 20 C without any additive or solvent
- Mizuno, Takumi,Nakai, Takeo,Mihara, Masatoshi
-
experimental part
p. 4251 - 4255
(2011/03/17)
-
- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
-
The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
- -
-
-
- Novel synthesis of N, n′-dialkyl cyclic ureas using sulfur-assisted carbonylation and oxidation
-
The first example of cyclic urea synthesis from secondary amines by the use of sulfur-assisted carbonylation and oxidation was established. By combined sulfur-assisted carbonylation of secondary a, ay diamines under an ambient pressure of carbon monoxide
- Mizuno, Takumi,Nakai, Takeo,Mihara, Masatoshi
-
experimental part
p. 64 - 68
(2009/05/31)
-
- Method for producing cyclic carbamate ester
-
A method for producing a cyclic carbamate ester produces the cyclic carbamate ester by reacting an organic compound having at least two halogen atoms per molecule, an amine having at least two hydrogen atoms on a nitrogen atom, and carbon dioxide.
- -
-
Page/Page column 4
(2008/06/13)
-
- Synthesis of 4-[5-substituted or unsubstituted phenyl)-3-substituted-1H-pyrazol-1-yl]benzenesulfonamides
-
This invention encompasses a novel process for synthesizing the compound represented by formula I: These compounds are useful as non-steroidal anti-inflammatory agents.
- -
-
-
- Catalytic oxidative carbonylation of primary and secondary α,ω-diamines to cyclic ureas
-
(matrix presented) Primary and secondary diamines can be catalytically carbonylated to cyclic ureas using W(CO)6 as the catalyst, I2 as the oxidant, and CO as the carbonyl source. Preparation of five-, six-, and seven-membered cyclic ureas from the diamines RNHCH2(CH2)nCH2NHR (n = 0-2; R = H, Me) and RNHCH2CH2NHR (R = Et, i-Pr, Bz) was achieved in moderate to good yields.
- McCusker, Jennifer E.,Grasso, Cara A.,Main, Andrea D.,McEiwee-White, Lisa
-
p. 961 - 964
(2008/02/09)
-
- Process for producing cyclic ureas
-
A process for producing a cyclic urea is provided. The process comprises reacting a diamine expressed by the formula (II) wherein R represents hydrogen atom or a lower alkyl group and R' represent dimethylene group, a lower alkyl group-substituted dimethylene group, trimethylene group, a lower alkyl group-substituted trimethylene group, tetramethylene group, a lower alkyl group-substituted tetramethylene group, but a case where R represents hydrogen atom and R' represent dimethylene group, a case where R represents hydrogen atom and R' represents a lower alkyl group-substituted dimethylene group and a case where R represent methyl group and R' represents dimethylene group are excluded, with phosgene in the presence of a dehydrochlorinating agent. In the process, the diamine is first converted to its hydrochloride, followed by reacting the hydrochloride with phosgene in water solvent while maintaining a pH of the reaction liquid in the range of 5.0 to 8.0 by said dehydrochlorinating agent to obtain a cyclic urea expressed by the formula (I) STR1 wherein R and R' are each as defined above.
- -
-
-
- PHASE TRANSFER CATALYTIC PREPARATION OF THE DIPOLAR APROTIC SOLVENTS DMI AND DMPU
-
The title compounds are prepared by methylation of the respective cyclic ureas Me2SO4/catalyst/powdered NaOH (for DMI) or K2CO3 (for DMPU).Improved procedures are communicated for the preparation of 2-imidazolidine and trimethylene urea.
- Dehmlow, Eckehard V.,Rao, Y. Ramachandra
-
p. 487 - 494
(2007/10/02)
-
- PUSH-PULL OLEFINS FROM BIS(FORMAMIDINIUM) ETHERS
-
Bis(N,N,N',N'-tetraalkyl)formamidinium ethers, readily prepared from a N,N,N',N'-tetraalkyl urea and triflic anhydride, yield push-pull olefins with activated methylene compounds H2CXY, where X, Y are CN, COOR, C6H4-4-NO2.
- Maas, Gerhard,Feith, Bernhard
-
p. 1073 - 1080
(2007/10/02)
-
- MACROHETEROCYCLES. XV. SYNTHESIS AND ION-SELECTIVE CHARACTERISTICS OF CYCLIC N,N'-DIALKYLUREAS
-
A convenient method is proposed for the production of cyclic N,N'-dialkylureas by the reaction of cyclic thioureas with alkyl halides in the presence of aqueous alkali and phase-transfer catalysts.It was established that the reaction takes place through the formation of isothioureas with subsequent alkylation of the nitrogen atoms and hydrolytic cleavage of the obtained N,N'-dialkylthiouronium salt.This method was used for the synthesis of macrocyclic N,N'-dimethylpolyoxyethyleneureas.The ion-selective characteristics of the obtained crown compounds were studied.
- Bogat-skii, A. V.,Luk'yanenko, N. G.,Kirichenko, T. I.,Limich, V. V.,Karpenko, L. P.
-
-
- Cyclic Urea and Thiourea Derivatives as Inducers of Murine Erythroleukemia Differentiation
-
A series of derivatives of tetramethylurea, a known inducer of the differentiation of Friend erythroleukemia cells, has been synthesized and tested for its capacity to induce erythroid maturation, as measured by the synthesis of hemoglobin.Cyclic urea and thiourea derivatives consisting of five-, six-, and seven-membered ring systems containing N-alkyl substituents were prepared.Most of these agents were relatively effective inducers of differentiation, with N-alkyl substitution appearing to be essential for maximum response.The most potent agents developed wereN,N'-dimethyl cyclic ureas.Exposure to concentrations of 2 to 4 mM of these derivatives resulted in more than 90percent of the cell population achieving a differentiated state.Under these conditions, the parent compound, tetramethylurea, was slightly less efficacious, causing differentiation of only 68percent of the population at its maximum effective level of 4 mM.
- Li, Chau-der,Mella, Sharon L.,Sartorelli, Alan C.
-
p. 1089 - 1092
(2007/10/02)
-
