Twum, Elvis A.’s team published research in Bioorganic & Medicinal Chemistry in 23 | CAS: 57044-25-4

Bioorganic & Medicinal Chemistry published new progress about 57044-25-4. 57044-25-4 belongs to alcohols-buliding-blocks, auxiliary class Epoxides,Chiral,Aliphatic hydrocarbon chain,Alcohol, name is (R)-Oxiran-2-ylmethanol, and the molecular formula is C6H20Cl2N4, COA of Formula: C3H6O2.

Twum, Elvis A. published the artcileInitial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug systems, COA of Formula: C3H6O2, the publication is Bioorganic & Medicinal Chemistry (2015), 23(13), 3481-3489, database is CAplus and MEDLINE.

Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and alkylate in the minor groove of DNA. They are not selective for cancer cells, so prodrugs are required. CBIs can be formed at physiol. pH by Winstein cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydrobenzo[e]indoles (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein cyclisation similarly. A key triply orthogonally protected intermediate on the route to 5-NH2-seco-CBIs has been synthesized, via selective monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection, electrophilic iodination, selective allylation at the trifluoroacetamide and 5-exo radical ring-closure with TEMPO. This intermediate has potential for introduction of peptide prodrug masking units (deactivating the Winstein cyclisation and cytotoxicity), addition of diverse indole-amide side-chains (enhancing non-covalent binding prior to alkylation) and use of different leaving groups (replacing the usual chlorine, allowing tuning of the rate of Winstein cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco-CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive entity and the bioactivity of this system were confirmed through DNA-melting studies (ΔTm = 13 °C) and cytotoxicity against LNCaP human prostate cancer cells (IC50 = 18 nM).

Bioorganic & Medicinal Chemistry published new progress about 57044-25-4. 57044-25-4 belongs to alcohols-buliding-blocks, auxiliary class Epoxides,Chiral,Aliphatic hydrocarbon chain,Alcohol, name is (R)-Oxiran-2-ylmethanol, and the molecular formula is C6H20Cl2N4, COA of Formula: C3H6O2.

Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts