54394-00-2

Upstream product

• 113978-49-7 1-(butylsulfanyl)-3-nitrobenzene 
• 13511-86-9 S-(3-nitrophenyl) dimethylthiocarbamate 
• 3814-18-4 3-nitrothiophenol 

Downstream Products

• 54691-00-8 1-(3-carbomethoxy-2-thioureido)-2-nitro-4-n-butylthiobenzene 

Relevant academic research and scientific papers

Benzoazine mono-N-oxides and benzoazine 1,4 dioxides and compositions therefrom for the therapeutic use in cancer treatments

The present invention relates to a synergetistic composition comprising one or more benzoazine-mono-N-oxides, and one or more benzoazine 1,4 dioxides for use in cancer therapy. The invention also provides a range of novel 1,2,4 benzoazine-mono-N-oxides and related analogues. These can be used as potentiators of the cytotoxicity of existing anticancer drugs and therapies for cancer treatment.

Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine

Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive hypoxic cytotoxin currently in Phase II/III clinical trials in combination with radiotherapy and with cisplatin-based chemotherapy. As part of a program to develop TPZ analogues with improved solubility/potency and therapeutic indices, we synthesized 34 1,2,4-benzotriazin-3-amine 1,4-dioxides (BTO) to examine structure-activity relationships (SAR) for ring substitution. The electronic, hydrophobic, and steric parameters of substituents at the 5-, 6-, 7-, and 8-positions were systematically varied, and the aqueous solubility and one-electron reduction potentials [E(1)] of the analogues were determined. For each compound, we determined cell killing of mouse SCCVII tumor cells in vitro under aerobic and hypoxic conditions by clonogenic survival and determined their relative hypoxic toxicity (RHT; relative to TPZ) and hypoxic cytotoxicity ratio (HCR). A subset of compounds was independently evaluated using a 96-well SRB proliferation assay, the data from which correlated well with that derived by the clonogenic endpoint. Most substituents, except 5- and 8-dimethylamino and 8-diethylamino, gave analogues less soluble than TPZ. E(1) values ranged from -240 mV through -670 mV (with TPZ having a value of -456 mV) and correlated well with the electronic parameter σ for substituents at the 5-, 6-, 7-, and 8-positions. Aerobic cytotoxic potency showed a strong positive correlation with E(1) (i.e., electron-withdrawing substituents increased aerobic toxicity). Hypoxic cytotoxicity also generally increased with increasing E(1), with a maximum (RHT up to 3.9-fold) seen in halo- and trifluoromethyl-substituted BTO derivatives having E(1) between ca. -370 to -400 mV. Analogues with high HCRs (>50) all had E(1)s in the range -450 to -510 mV (weakly electron-donating substituents) with the exception of the 8-CF3 analogue, which had an HCR of 112 against SCCVII despite a high E(1) of -372 mV). The results suggest that ring-A substituents in BTO analogues can be used to predictably vary one-electron reduction potentials and also provide a much better definition than previously of the optimum range of these reduction potentials for a desirable biological activity profile (high HCR, RHT, and solubility).

5(6)-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity

Carbalkoxythioureidobenzene derivatives represented by the following formula: STR1 where R is a lower alkyl group having 1 to 4 carbon atoms; R1 is --SR2, --SOR2, --SO2 R2, --OR2, --SCN, --SC(O)NR3 R4, or --M'(CH2)n MR7 where n is 1-4; R2 is lower alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkynyl having 3 to 6 carbon atoms, aralkyl or aryl, provided that when R1 is --SO2 R2, R2 is not aralkyl or phenyl; R3 and R4 are independently hydrogen or lower alkyl having 1 to 6 carbon atoms; Y is amino, nitro, acylamino where the acyl portion has 1 to 6 carbon atoms, --NHC(O) (CH2)m COOH where m is 1-6, or --NHC(S)NHCOOR; M and M' are independently O, S or STR2 and R7 is lower alkyl having 1 to 4 carbon atoms or aryl. The R1 substitution is either at the 4- or 5-position. The compounds are useful as pesticides, particularly as anthelmintic and antifungal agents.