Adduct formation with the DNA bases adenosine, cytidine and guanosine has been shown in vitro. The products were identified as 3-(2'-deoxyribofuranosyl)-7-formylimidazo(2,1-i)purine, chloropropenal derivatives of adenosine and cytidine, etheno derivatives of adenosine, cytidine and guanosine, ethanocarbaldehyde derivatives of adenosine and cytidine and adenosinylethenoadenosine derivatives of adenosine. The later products were postulated to be formed by oxidative properties of mucochloric acid (MCA). The formation of the chloroprenal derivatives, ethanocarbaldehyde derivatives and etheno derivatives from MCA is explained by an initial formation of mucoxychloric acid, which may be further broken down to chloroacetaldehyde, which could proceed via the chloromalonaldehyde that reacts with the nucleosides and forms subsequently the derivatives.
Human Health. There are no reliable experimental data on the toxicokinetic behavior of mucochloric acid (MCA) in vivo available. From the results of acute toxicity studies, it is very likely that MCA itself or its metabolites are systemically available after oral exposure. In vitro, MCA reacted with N-acetylcysteine, cysteine and glutathione (GSH). The acute toxicity (LD50) of MCA was between 300 and 400 mg/kg bw in rats after oral exposure and >200 mg/kg bw (highest tested dose) in rabbits after dermal exposure. The LC50 after 4-hour inhalation exposure of rats was >5.1 mg/L (highest tested concentration). Clinical signs included atonia and ataxia after oral exposure, preening, dyspnea and salivation during inhalation, and skin irritation after dermal exposure. MCA is corrosive to the rabbit skin and eye. A guinea pig sensitization test was negative, but limited experience from occupational exposure in humans indicates a skin sensitizing potential of MCA. There is limited data on repeated dose toxicity available, indicating that irritant/corrosive effects at the site of first contact are the main effects to be expected after repeated exposure. In pregnant rats, no systemic target organ has been identified after oral exposure from day 6 to 19 p.c. (LOAEL: 30 mg/kg bw/day, based on reduced food consumption and body weight gain together with minor clinical symptoms (ptyalism) and whitish foci in the stomach interpreted as local effects due to the corrosive properties of MCA; NOAEL: 5 mg/kg bw/day). No target organ was identified in mice after dietary exposure to 7 mg/kg bw/day for 18 months (only one dose tested). ... In vitro, MCA is a direct acting mutagen and clastogen in mammalian and bacterial cells, and forms exocyclic DNA adducts. In vivo, mucochloric acid caused a slight, but statistically significant increase in the incidence of total nuclear anomalies (including micronuclei, pyknotic nuclei and karyorrhectic nuclei) in the duodenum of mice after a single oral exposure to 60.8 and 79.4 mg/kg bw. MCA induced micronuclei in one animal out of ten per dose group in the duodenum of mice after single oral doses (38.9, 60.8, and 79.4 mg/kg bw). Based on the available in vitro and in vivo data, it can be concluded that MCA has a genotoxic potential. Because of its corrosive properties, and the very limited exposure potential, animal tests with MCA for its effects on fertility were not performed. In an oral developmental study performed in accordance with OECD TG 414 in rats, the NOAEL for maternal toxicity was 5 mg/kg bw/day. The NOAEL for developmental toxicity was 60 mg/kg bw/day, which was the highest dose level applied. There were no signs of developmental toxicity or teratogenicity. MCA did not induce aberrant crypt foci or intestinal tumors when given in drinking water at dose levels of 0.45 and 0.9 mg/mL over 6 weeks to rats or at dose levels of 0.18 and 0.35 mg/mL over 4 weeks with subsequent 12-weeks recovery to mice, respectively. The available data for MCA are not sufficient to judge its carcinogenicity. Given the available data for genotoxicity there are, however, concerns with regard to this endpoint.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
Dermatotoxin - 皮肤烧伤。
Dermatotoxin - Skin burns.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
毒性数据
LC50（大鼠）= 5,100 毫克/立方米/4小时
LC50 (rat) = 5,100 mg/m3/4h
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
人类毒性摘录
体征和症状：皮肤：可能会引起过敏性皮肤病。
/SIGNS AND SYMPTOMS/ Skin: May cause allergic skin reaction.
/SIGNS AND SYMPTOMS/ ... Symptoms of exposure may include burning sensation, coughing, wheezing, laryngitis, shortness of breath, headache, nausea, and vomiting. Inhalation may result in spasm, inflammation and edema of the larynx and bronchi, chemical pneumonitis, and pulmonary edema. Material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes, and skin.
A series of novel pyridazinone derivatives were designed and synthesized by replacing 4‐(tert‐butyl)phenyl moiety of pyridaben with 2‐phenylthiazole or oxazole fragments via activity substructure connecting approach. The structures of all target compounds were characterized through NMR, MS, and elemental analysis. Bioassay results exhibit that most compounds showed potent bioactivities against Aphis
4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), it exhibited good anticancer activity on MGC-803 cells. Besides, introducing fluorine, chlorine, or trifluoromethyl group onto the benzene ring, such as compound 5 m (2-(Tert-butyl)−4-chloro-5-((5-((4-(trifluoromethoxy)phenyl)amino)−1,3,4-thiadiazol-2-yl)thio)pyridazin-3(2H)-One), displayed good anticancer activity on MGC-803 and Bcap-37 cells. Graphical Abstract
摘要 合成了一系列含有1,3,4-噻二唑部分的新型哒嗪酮衍生物，并通过1H NMR、13C NMR、HRMS和IR光谱表征。其中，化合物5c的结构(2-(叔丁基)-4-氯-5-((5-((2-乙基苯基)氨基)-1,3,4-噻二唑-2-基)硫基)通过单晶 X 射线衍射分析明确证实了哒嗪-3(2H)-One)。通过MTT法测定所有目标化合物对MGC-803和Bcap-37的抑制活性，以阿霉素（抑制率分别为95.5±0.4%和95.7±1.0%）为对照。初步结果表明化合物5n(2-(叔丁基)-4-氯-5-((5-((3-氟苯基)氨基)-1,3,4-噻二唑-2-基) )thio)pyridazin-3(2H)-One) 优于其他。MGC-803和Bcap-37细胞在10 μmol/L浓度下的抑制率分别为86.3±2.2%和92.3±0.6%。初步的构效关系表明，当苯环的2-位被甲基取代时，如化合物
Preparation of aryl-substituted butenolides using mucohalic acids
申请人：Blazecka Garth Peter
公开号：US20050131239A1
公开（公告）日：2005-06-16
Methods and materials for preparing 3-aryl-2-buten-4-olides and 2,3-bisaryl-2-buten-4-olides are disclosed. The methods include reacting a mucohalic acid with a reducing agent to give a 2,3-dihalo-2-buten-4-olide, which undergoes at least one Pd catalyzed cross-coupling reaction with an arylboronic acid.
Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines
作者：Mikhail Krasavin、Anton Shetnev、Sergey Baykov、Stanislav Kalinin、Alessio Nocentini、Vladimir Sharoyko、Giulio Poli、Tiziano Tuccinardi、Mikhail Korsakov、Tatiana B. Tennikova、Claudiu T. Supuran
DOI：10.1016/j.ejmech.2019.02.044
日期：2019.4
concentration-dependent mode against normal (ARPE-19) and two cancercelllines (PANC-1 and SK-MEL-2) identified two lead compounds one of which displayed a notable cytotoxicity toward pancreatic cancercells while the other targeted the melanomacells. These findings significantly expand the knowledge base concerning the hCA IX inhibitors whose inhibitory potency against a recombinant enzyme translates
Aryl ether derivatives and processes for their preparation and herbicidal and desiccant compositions containing them
申请人：——
公开号：US20040267014A1
公开（公告）日：2004-12-30
Substituted aryl ether derived compounds represented by general structure (I) are described. X and Y are independent of each other and are represented by hydrogen, halogen, cyano, nitro, (C
1-4
)alkyl, (C
1-4
)haloalkyl, or (C
1-4
)haloalkoxy; Z is oxygen or sulfur, Q is selected form Q1 to Q6; A is oxygen, sulfur, or imino; R
1
is hydrogen, (C
1-4
)alkyl, (C
1-4
)haloalkyl, or amino and can be independent of each other in a single molecule; R
2
and R
3
are independent of each other and may be selected from the group consisting of hydrogen, halogen, cyano nitro, (C
1-4
)alkyl, (C
1-4
)haloalkyl, (C
2-4
)alkenyl, (C
2-6
)haloalkenyl and amino which may be optionally substituted with (C
1-4
)alkyl or (C
1-4
)haloalkyl; Ar is substituted or unsubstituted carbocyclic or heterocyclic aromatic ring being at least a five or six membered ring. This ring can be fused with another substituted or unsubstituted five or six membered carbocyclic or heterocyclic ring. When Q is Q5, unsubstituted or substituted phenyl is excluded. Also described are the processes for the manufacture of these compounds and argiculturally suitable compositions containing these as active ingredients which are useful as herbicides for general or selective pre-emergent or post-emergent control of undesired plant species and defoliants.
1
