Figure 1
Structures of carbamate-based drugs and prodrugs of different application (carbamate group is presented in blue; active substance of prodrugs is presented in red)
Figure 2
Possible resonance structures for the carbamate group (amino group is presented in red, and alkoxy group in blue) (adopted from ref. 14)
Figure 3
Cis and trans conformations of carbamates (adopted from ref. 14)
Figure 4
Alkaline hydrolysis of monosubstituted (A) and disubstituted (B) carbamates (adopted from ref. 22)
Table 1
Roles of the carbamate moiety in drugs and prodrugs
| Drug | The role of the carbamate moiety in the drug | Reference |
|---|---|---|
| Docetaxel | prolongs drug action, increases drug potency, improves water solubility | 39 |
| Mytomicin C | participates in the formation of an alkylating compound during reaction with target | 40 |
| Rivastigmine, neostigmine, physostigmine, pyridostigmine | key element for interaction with the target | 38 |
| Ritonavir, amprenavir, atazanavir, darunavir | improves drug bioavailability and potency, engaged in a backbone interaction with protease | 8 |
| Ombitasvir, elbasvir, daclatasavir | improves drug stability and lipophilicity | 41 |
| Febendazole, mebendazole, febantel, albendazole | improves aqueous solubility and bioavailability, increases cytotoxicity | 42 |
| Mehocarabamol, metaxalone | inhibits acetylcholinesterase at synapses in the autonomic nervous system, neuromuscular junction, and central nervous system | 43 |
| Felbamate | improves drug stability and bioavailability | 44, 45 |
| Retigabine | major pharmacophore responsible for interacting with residues in the KCNQ2–5 channels | 46 |
| Gabapentin enacarbil | improves bioavailability | 47 |
| Capecitabine | improves selectivity and bioavailability | 47 |
| Bambuterol | delays first-pass metabolism | 47 |
| Irinotecan | improves aqueous solubility | 47 |
Figure 5
Mechanism of action of mitomycin C (adopted from ref. 40)
Figure 6
Proposed targets and mechanism of action of felbamate and retigabine in postsynaptic neuron (adopted from refs. 62 and 63)
Figure 7
A proposed simplified mechanism for AChE inhibition by carbamates. Rapid formation of the covalent enzyme-carbamate intermediates, followed by slow regeneration of a free AChE prevents breaking down of acetylcholine in postsynaptic cleft by AChE (adopted from ref. 81)
Figure 8
Cymserine and its derivatives (carbamate group in blue) (adopted from ref. 82)
Figure 9
Chemical structure of secretase inhibitors tested with potential to be used in treatment of Alzheimer’s disease A – a 16-membered macrocycle compound; B – sulphonamide compound (adopted from ref. 8)
Figure 10
A simplified illustration of the prodrug concept
Figure 11
Irinotecan metabolism by carboxylesterases hCE-1 and hCE-2 (adopted from ref. 105)
Figure 12
Bambuterol metabolism into tertbutaline by cytochrome p450 and butyrylcholinesterase (BChE) (adopted from ref. 106)