Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
A substituted benzoquinone ring has been employed as an “anchor” for aziridine rings in the experimental agents AZQ and BZQ. The aziridine moieties are deactivated by the withdrawal of electrons from their nitrogens into the quinone carbonyl groups via the six-membered ring. These molecules have been employed as experimental bioreductive prodrugs because reduction of the quinone ring to either the semiquinone or the hydroxyquinone species reverses the electron flow, thus increasing the basicity of the aziridine nitrogens which allows them to become activated via protonation. No benzoquinone agents of this type have yet been approved for clinical use.
Identification of proper herbs
C. P. Khare in Evidence-based Ayurveda, 2019
Taalisha still remains a drug of disputed source. Abies webbiana and Taxus wallichiana both are known as Taalisha patra. Two samples of needles and twigs from two different locations of central Nepal gave alpha-pinene 3.0, 10.3; fascile 3.5, 9.3; beta-pinene 5.1, 3.3; limonene 6.1, 2.3; bornyl acetate 4.2, 15.5; and carvone 5.8, 0.75%, respectively. Leaves obtained from Sikkim-Himalayan region gave a bioflavonoid, abiesin; two glycosides, methylbetuloside, and betuloside; n-triacontanol and beta-sitosterol. A new alkaloid, 1-(4’ methoxyphenyl)-aziridine was isolated.
Radiopharmaceuticals for SPECT
Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman in Molecular Imaging in Oncology, 2008
The antiestrogen tamoxifen has also been a substrate for radiolabeling. The first two radiolabeled analogs 8 and 9 (Fig. 12) were radioiodinated on the aromatic rings (193,194). Compound 9 exhibited low uptake in ER-rich tissue. The aliphatic portion of tamoxifen has been radioiodinated to give 123-ITX (195). Although aliphatic radiohalogens usually suffer from extensive deiodination in vivo, 123-ITX was tested in the clinic. In patients, this compound did not appear to be very promising; only 4 of 9 patients with ER+ tumors had their tumors visualized (196). Delpassand et al. attached diethylenetriamine-pentaacetic acid (DTPA) to the aliphatic portion of tamoxifen to give 10. The absolute uptake of the In-111-labeled compound in ER+ tumor xenografts was low; however, the tumors were clearly visualized (197). The ability of an ER-binding compound to contain such a large substituent may be surprising but this position likely corresponds to substituents on the 7α position of estradiol. Salituro et al. prepared a novel tamoxifen analog [125I]I-TAM-Az. This compound was a mixture of cis/trans isomers, had a vinyl radiohalogen, and the dimethylaminogroup was replaced with an aziridine moiety. This compound binds irreversibly to the ER via the aziridine group (198). In order to eliminate the possibility of cis/trans isomerization, the nonsteroidal vinyl-halo estrogens bis-hydroxy-triphenylethylenes [80m,77Br]Br-BHPE and [125,123I]I-BHPE (Fig. 12) were prepared (185,199,200). In rats, the specific uptake in ER target tissues by [77Br]Br-BHPE and [123I]I-BHPE were comparable to 11β-methoxy-(17α,20E)-[77Br]BrVE2 and -[125I]IVE2 (185,201). In rats, [125I]I-THPE, which has a third phenol moiety unexpectedly showed prolonged retention (up to three days) in ER target tissue and very high uterus to blood and ovary to blood ratios (202).
Exploitation of the Ugi–Joullié reaction in drug discovery and development
Published in Expert Opinion on Drug Discovery, 2019
Stefano Gazzotti, Giulia Rainoldi, Alessandra Silvani
Alongside the synthesis of peptidomimetics and depsipeptides, vast libraries of drug-like products are also reported in the literature and discussed in this review. Three-, five- and seven-membered cyclic imines were employed as starting materials, ending up in a great variety of nitrogen-containing heterocycles, such as highly functionalized aziridine, tiazolidine and hydroazepine derivatives. All reported multicomponent reactions were characterized by mild conditions, good yields and high diastereoselectivity. No doubt, the easy and cheap access to a vast array of Ugi-Joulliè starting components (carboxylic acids and isocyanides, besides cyclic imines) proves to be a key element for the fruitful exploitation of this reaction in the field of drug discovery.
Aromatic sulphonamides of aziridine-2-carboxylic acid derivatives as novel PDIA1 and PDIA3 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
D. Zelencova-Gopejenko, V. Andrianov, I. Domracheva, I. Kanepe-Lapsa, M. Milczarek, M. Stojak, K. Przyborowski, F. A. Fedak, M. Walczak, K. Kramkowski, J. Wietrzyk, S. Chlopicki, I. Kalvins
1-(p-tolylsulphonyl)aziridine-2-carbonitrile (C-3314) was prepared as described earlier15. 1-(p-tolylsulphonyl)aziridine-2-carbaldehyde (C-3262) was prepared according to the procedure of Lapinsky and Bergmeier16. 1–(4-Butylphenyl)sulphonylaziridine-2-carbaldehyde (C-3273) was synthesised by using the same method. 1-[1-(p-tolylsulphonyl)aziridin-2-yl]ethanone (C-3263) was prepared as described by Smith and Kim17. 1-[1–(4-Butylphenyl)sulphonylaziridin-2-yl]ethanone (C-3272) was prepared using the same method. Lithium 1-tosylaziridine-2-carboxylate (C-3612) was synthesised according to a method developed by Baldwin et al.18.
Significant role of cationic polymers in drug delivery systems
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Masoud Farshbaf, Soodabeh Davaran, Amir Zarebkohan, Nasim Annabi, Abolfazl Akbarzadeh, Roya Salehi
Poly(ethyleneeimine) (PEI), a none-degradable polymer comprising primary, secondary and tertiary amino groups which is one of the most commonly employed cationic polymers in various industries. PEI can be obtained in two various structures: (i) linear PEI (LPEI) is a solid form of PEI and (ii) branched PEI (BPEI) is a highly viscous liquid at the room temperature. LPEI contains primary and secondary amino groups, while BPEI, in addition to primary and secondary groups, also possesses tertiary amino groups (with ratio of 1:2:1) which makes BPEI more stable and suitable transfection vector [107]. It is worth noting that, at physiological conditions 25% of these amino groups are protonated which gives PEI high buffer capability that could be beneficial in endosomal escape mechanisms. Brissault et al. [108] synthesized LPEI by hydrolysis and/or reduction of poly(2-ethyl-2-oxazoline) (PEtOXZ) (Figure 12(A)). A mixture of PEtOXZ (1 g), hydrochloric acid (11 ml, 37%) and 8 ml water was heated at 110 °C for 3 h. After solvent evaporation, the obtained mixture was dissolved in water and pH was adjusted to 9–10 by adding a proper amount of NaOH. Then the aqueous phase was vaporized, the residue washed with methylene chloride and consequently, the organic layer (Na2SO4) dried and vaporized. Based on results, yield of the polymer was 320 mg (71%) [108]. In another study, Harpe et al. [109] used acid-catalyzed polymerization of aziridine for the synthesis of BPEI (Figure 12(B)). First, aziridine (5 ml) were dissolved in 50 ml distilled water and 0.5 ml of 32% (w/v) hydrochloric acid (HCl) were added to the solution, then the flask was sealed and submerged in oil bath in 65 °C and kept for 24 h. NaOH was added to the mixture in order to neutralization process and then water was vaporized and the obtained polymer was dried under vacuum for 24 h [109].
Related Knowledge Centers
- Acid Dissociation Constant
- Cyclopropane
- Ethylene Oxide
- Hydrocarbon
- Molecular Geometry
- Organic Compound
- Aziridines
- Open-Chain Compound
- Aliphatic Compound
- Conjugate