10477-72-2Relevant articles and documents
Synthesis of androstene oxime-nitrogen mustard bioconjugates as potent antineoplastic agents
Acharya, Pratap Chandra,Bansal, Ranju
, p. 73 - 83 (2017)
In the present study, synthesis and antineoplastic activity of phenylacetic acid and benzoic acid nitrogen mustard conjugates of various steroidal oximes are reported for the first time. The conjugation was achieved through a more stable oxime-ester linkage and the resulting newly synthesized conjugates were evaluated in vitro on various human cancer cell lines for cytotoxicity. The extent of their alkylating activity was investigated by the in vitro colorimetric 4-(p-nitrobenzyl)pyridine (NBP) assay. The 17E-steroidal oxime-benzoic acid mustard ester 3β-acetoxy-17E-[p-(N,N-bis(2-chloroethyl)amino)]benzoyloxyimino-androst-5-ene (8) emerged as the most potent conjugate having significant cytotoxicity on most of the NCI 60-cell lines. Outstanding growth inhibition was observed on the IGROV1 ovarian cancer cell line with GI50?=?0.937?μM. In general, the D-ring derived androstene oxime-nitrogen mustard conjugates were found to possess better antineoplastic activity over a variety of cancer cells in comparison to those derived from other rings of the steroid skeleton.
Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA
Fang, Kun,Dong, Guoqiang,Wang, Hongyu,He, Shipeng,Wu, Shanchao,Wang, Wei,Sheng, Chunquan
, p. 30 - 36 (2017/12/26)
Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.
Nitrogen Mustard Derivatives
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Paragraph 0092, (2014/10/16)
The disclosure includes compounds of Formula (1): wherein X1, X2, Q, Z, R1, and R2 are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.
Coronarin D conjugated to methylene homologues of chlorambucil: Synthesis and evaluation of their cytotoxicity
Khunnawutmanotham, Nisachon,Chimnoi, Nitirat,Champathong, Wattanachai,Lerdsirisuk, Pradit,Khotmor, Theeraphon,Techasakul, Supanna
experimental part, p. 374 - 378 (2012/10/08)
Methylene homologues of chlorambucil were synthesised and conjugated to the labdane diterpene coronarin D. The products were evaluated for their in vitro cytotoxicity, and were found to exhibit selective activity against MOLT-3 cell line. Two homologues o
Benzimidazole derivatives
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, (2008/06/13)
Disclosed are compounds represented by the following chemical formula (I) and pharmacologically acceptable salts thereof which are novel compounds useful as anticancer agents, antiviral agents or antimicrobial agents. STR1
New mustard prodrugs for antibody-directed enzyme prodrug therapy: Alternatives to the amide link
Dowell, Robert I.,Springer, Caroline J.,Davies, David H.,Hadley, Elizabeth M.,Burke, Philip J.,Boyle, F. Thomas,Melton, Roger G.,Connors, Thomas A.,Blakey, David C.,Mauger, Anthony B.
, p. 1100 - 1105 (2007/10/03)
Antibody-directed enzyme prodrug therapy (ADEPT) is a two-step approach for the treatment of cancer which seeks to generate a potent cytotoxic agent selectively at a tumor site. In this work described the cytotoxic agent is generated by the action of an enzyme CPG2 on a relatively nontoxic prodrug. The prodrug 1 currently on clinical trial is a benzamide and is cleaved by CPG2 to a benzoic acid mustard drug 1a. We have synthesized a series of new prodrugs 3-8 where the benzamide link has been replaced by, for example, carbamate or ureido. Some of these alternative links have been shown to be good substrates for CPG2 and therefore new candidates for ADEPT. The active drugs 3a and 4a derived from the best of these prodrugs are potent cytotoxic agents (1-2 μM) some 100 times more than 1a. The prodrugs 3 and 4 are some 100-200-fold less cytotoxic, in a proliferating cell assay, than their corresponding active drugs 3a and 4a.
SYNTHESIS AND SPONTANEOUS DECOMPOSITION OF THE N-OXIDES OF DI(2-CHLOROALKYL)AMINOPHENYLALKANOIC ACIDS
Degutene, A.,Dzhyuvene, D.,Shukyalene, D.,Degutis, Yu.
, p. 1968 - 1972 (2007/10/02)
A convenient method was developed for the production of the N-oxides of di(2-chloroethyl)aminophenylalkanoic acids.In an acidic medium the main products from their spontaneous decomposition are the corresponding di(2-chloroalkyl)aminophenylalkanoic acids, while in an alkaline medium they are 2-chloroalkylaminophenylalkanoic acids and the simple aldehydes.The cleavage of the N-oxides of di(2-chloroethyl)aminophenylalkanoic acids leads to the formation of formaldehyde, whereas the dissociation of the di(2-chloropropyl)-N-oxide group gives a mixture of formaldehyde and acetaldehyde in a ratio of 1:1.The analogous N-oxides containing oxygen instead of the halogen atoms do not decompose under these conditions.
