Mutagenicity of isomeric alkanediazotates, precursors for ultimate alkylating species of carcinogenic N-nitroso compounds
摘要:
Alkanediazohydroxides are common key intermediates in carcinogenesis and mutagenesis of N-nitroso compounds, which are widely found in human environment. Mutagenicity of (E)- and (Z)-potassium alkanediazotates, as precursors of corresponding alkanediazohydroxides were evaluated to investigate the effect of geometric isomerism and also the effect of alkyl groups on their biological activity. Mutagenicity of N-nitroso-N-alkylureas which spontaneously produce alkanediazohydroxides after non-enzymatic hydrolysis were also tested in comparison to that of the corresponding diazotates and other activated chemical species of N-nitrosamines. When the mutagenicity was assayed in three microbial strains, Salmonella typhimurium TA1535, and Escherichia coli WP2 and WP2 wrA, the order of mutagenic potency of the compounds with the same alkyl group was as follows; (E)-diazotates > (Z)-diazotates > nitrosoureas. The effect of alkyl groups on the mutagenic potency was different in Salmonella strain and in E. coli strains, and this result could be explained by the efficiency of O-6-alkylguanine-DNA alkyltransferase. In each bacterial strain, this effect of alkyl groups was similar in mutagenicity induced by (E)- and (Z)-diazotates, N-nitroso-N-alkylureas and other activated N-nitrosodialkylamines such as alpha-hydroxy nitrosamines. The geometrical isomerism affected the mutagenicity of (E)- and (Z)-potassium alkanediazotates, and the result suggested that alkanediazohydroxides react through diazonium ions in a cage rather than through free alkyldiazonium ions which have no geometrical isomerism. Our results confirmed that (E)-potassium alkanediazotates, (Z)-potassium alkanediazotates and N-nitroso-N-alkylureas all decomposed through diazohydroxides, and that alkanediazohydroxides are the active alkylating species of N-nitroso compounds, and also that the geometrical isomerism is important for carcinogenic N-nitroso compounds to show their biological activity. (C) 1998 Elsevier Science B.V.
Synthesis of 4-Substituted Chlorophthalazines, Dihydrobenzoazepinediones, 2-Pyrazolylbenzoic Acid, and 2-Pyrazolylbenzohydrazide via 3-Substituted 3-Hydroxyisoindolin-1-ones
作者:Hanh Nho Nguyen、Victor J. Cee、Holly L. Deak、Bingfan Du、Kathleen Panter Faber、Hakan Gunaydin、Brian L. Hodous、Steven L. Hollis、Paul H. Krolikowski、Philip R. Olivieri、Vinod F. Patel、Karina Romero、Laurie B. Schenkel、Stephanie D. Geuns-Meyer
DOI:10.1021/jo3000628
日期:2012.4.20
hydrazine, followed by chlorination with POCl3. We have also discovered twonovel transformations of 3-vinyl- and 3-alkynyl-3-hydroxyisoindolinones. Addition of vinyl organometallic reagents to N,N-dimethylaminophthalimide (8a) provided dihydrobenzoazepinediones 15a–15c via the proposed ringexpansion of 3-vinyl-3-hydroxyisoindolinone intermediates. 3-Alkynyl-3-hydroxyisoindolinones react with hydrazine and
0]hept- 2-en-2-yl)oxy]-2H-1-benzopyrans and their analogues were synthesized and evaluated on potassium channel opening and hypotensive activities. Compound (-)-13B with a (4-methyl-5-oxo-3,4-diazabicyclo[4.1.0]hept-2-en-2-yl)oxy group for the 4-position of the benzopyran ring was 3 times as potent as EMD 57283 (II), the lead compound, in hypotensive activity. The results would demonstrate that 5-oxo-3,4-diazabicyclo[4
An efficient one-pot synthesis of carbazates and dithiocarbazates through the corresponding alcohols using Mitsunobu’s reagent
作者:A. K. Chaturvedi、D. Chaturvedi、N. Mishra、V. Mishra
DOI:10.1007/bf03249073
日期:2011.6
A novel Mitsunobu-based protocol has been developed for the synthesis of carbazates and dithiocarbazates through the variety of corresponding primary, secondary and tertiary alcohols and various kinds of substituted hydrazines using Mitsunobu’s reagent and CO2/CS2 system, in good to excellent yields.
[EN] IMMUNOCONJUGATES TARGETING PD-L1<br/>[FR] IMMUNOCONJUGUÉS CIBLANT LE PD-L1
申请人:BOLT BIOTHERAPEUTICS INC
公开号:WO2020190734A1
公开(公告)日:2020-09-24
The invention provides an immunoconjugate of formula (I) or (II). Antibody-adjuvant immunoconjugates of the invention, comprising an antibody construct that has an antigen binding domain that binds programmed death-ligand 1 (PD-L1) linked to one or more adjuvants, demonstrate superior pharmacological properties over conventional antibody conjugates. The invention further provides compositions comprising and methods of treating cancer with the immunoconjugate.
The polymerizable compound has a hydrazone moiety. The present invention also provides a polymerizable composition in which discoloration and reduction of aligning property do not easily occur. Furthermore, the present invention provides a polymer obtained by polymerizing a polymerizable composition containing a compound obtained by the production method and an optically anisotropic body using the polymer. The present invention provides a method for producing a polymerizable compound including a step of reacting a compound represented by General Formula (I-B-a) with a compound represented by General Formula (I-B-b) to obtain a compound represented by General Formula (I-C), and provides a composition which contains a compound obtained by this production method.