- Practical synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl prodrug derivatives of acetaminophen, theophylline, and 6-mercaptopurine
-
We report a novel synthesis of N-alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6-mercaptopurine by alkylation of the corresponding drug molecule with N-alkyl-N- alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N-alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N-alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p-nitrophenylcarbonate esters, followed by their reaction with alkyl amines. Copyright Taylor & Francis Group, LLC.
- Majumdar, Susruta,Sloan, Kenneth B.
-
-
Read Online
- Biological evaluation and docking studies of new carbamate, thiocarbamate, and hydrazide analogues of ACYL homoserine lactones as vibrio fischeri-quorum sensing modulators
-
A series of carbamate, thiocarbamate, and hydrazide analogues of acylhomoserine lactones (AHLs) were synthesized and their ability to modulate Vibrio fischeri-quorum sensing was evaluated. The compounds in the series exhibit variable side chain length and the possible presence of a diversely substituted phenyl substituent. Biological evaluation on the Vibrio fischeri quorum sensing system revealed that the ethyl substituted carbamate (1) display a weak agonistic activity whereas compounds with longer chain length or benzyl substituents display significant antagonistic activity. The most active compounds in the series were the 4-nitrobenzyl carbamate and thiocarbamate 7 and 11 which exhibited an IC50 value of about 20 μM. These activities are in the range of other reported of AHL-structurally related quorum sensing (QS) inhibitors. Docking experiments conducted on the LuxR model showed that, compared to the natural ligand OHHL, the additional heteroatom of the carbamate group induces a new hydrogen bond with Tyr70 leading to a different global hydrogen-bond network. Tyr70 is an important residue in the binding site and is strictly conserved in the LuxR family. For the 4-nitrobenzyl carbamate and thiocarbamate analogues, the docking results highlight an additional hydrogen bond between the nitro group and Lys178. For hydrazide analogues, which are deprived of any activity, docking shows that the orientation of the carbonyl group is opposite as compared with the natural ligand, leading to the absence of a H-bond between the C=O with Tyr62. This suggests that, either this later interaction, or the influence of the C=O orientation on the overall ligand conformation, are essential for the biological activity.
- Zhang, Qiang,Queneau, Yves,Soulère, Laurent
-
-
- COMPOUNDS USEFUL IN HIV THERAPY
-
The invention relates to compounds of Formula (I), salts thereof, pharmaceutical compositions thereof, as well as methods of treating or preventing HIV in subjects.
- -
-
Page/Page column 88
(2020/09/20)
-
- PRODRUGS OF KALLIKREIN INHIBITORS
-
Disclosed are compounds of formula I, II, and III, and pharmaceutically acceptable salts thereof, which are inhibitors of kallikrein. Also provided are pharmaceutical compositions comprising such a compound, and methods involving use of the compounds and compositions in the treatment and prevention of acquired or hereditary angioedema, or other diseases and conditions characterized by aberrant kallikrein activity. (I) (II) (III)
- -
-
Page/Page column 115
(2018/05/24)
-
- A darbey adds the group ester preparation method
-
The invention relates to a preparation method of Dabigatran etexilate. In a preparation process, acyl chloride or anhydride is used for replacing N, N minute-Carbonyldiimidazole (CDI ) or palladium on activated carbon, which must be used and is expensive in the prior art, the cost is greatly lowered, and used materials are cheap and are easily available, the process is simple and feasible, aftertreatment steps are simplified, column chromatography purification is not needed in whole operation steps, so that the process of the whole preparation method is simplified, and industrialization is convenient to realize; when a compound with a formula 2 is compounded, a sodium amide and ammonium salt system is adopted, and generation of a mass of acid pickle is avoided, so the production is safe, the environment is not polluted, and the preparation process is convenient and easy; when a compound with a formula 1 is compounded, a stable-property compound with a formula 7 is adopted, great convenience is brought for production, and the yield of the Dabigatran etexilate is effectively improved; the total yield of the Dabigatran etexilate prepared by the method reaches 60 to 70 percent.
- -
-
Paragraph 0049; 0052; 0057; 0065
(2017/09/01)
-
- A PROCESS FOR PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND INTERMEDIATES THEREOF
-
The present invention relates to an improved process for the preparation of Dabigatran etexilate and its acid addition salts thereof, wherein the said process substantially eliminates the potential impurities. The present invention also relates to an intermediate of Dabigatran etexilate and process for preparation thereof.
- -
-
Page/Page column 48
(2015/09/28)
-