1,4-dichloro-2-butene appears as a clear colorless liquid. Burns, though may be difficult to ignite. Corrosive to tissue. Denser than water and insoluble in water. Vapors heavier than air. Used to make other chemicals.
颜色/状态：
Colorless liquid
气味：
Sweet, pungent
溶解度：
Water solubility = 580 mg/l at 25 °C
蒸汽压力：
3 mm Hg @ 25 °C
分解：
When heated to decomposition it emits toxic fumes of /hydrogen chloride/.
腐蚀性：
Corrodes metal when wet. /Dichlorobutene/
折光率：
Index of refraction: 1.4863 @ 25 °C
计算性质
辛醇/水分配系数(LogP)：
1.7
重原子数：
6
可旋转键数：
2
环数：
0.0
sp3杂化的碳原子比例：
0.5
拓扑面积：
0
氢给体数：
0
氢受体数：
0
ADMET
代谢
某些卤代烯烃的双键氧化，这种氧化依赖于微粒体单加氧酶，可能是形成生物活性中间体的共同途径。
AN OXIDATION OF THE DOUBLE BOND IN CERTAIN HALO-OLEFINS, WHICH IS DEPENDENT ON MICROSOMAL MONO-OXYGENASES PROBABLY IS A COMMON PATHWAY IN THE FORMATION OF BIOLOGICALLY REACTIVE INTERMEDIATES.
Classification of carcinogenicity: evidence in animals: inadequate. No epidemiological data relevant to the carcinogenicity of trans-1,4-dichlorobutene were available. Overall summary evaluation of carcinogenic risk to humans is Group 3. The agent is not classifiable as to its carcinogenicity to humans.
Dermatotoxin - Skin burns.
Lacrimator (Lachrymator) - A substance that irritates the eyes and induces the flow of tears.
Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors.
ACGIH Carcinogen - Suspected Human.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
毒性数据
LC50 (大鼠) = 86 ppm/4小时
LC50 (rat) = 86 ppm/4hr
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Stabilization: Treatment is largely supportive. Watch for respiratory depression & arrhythmias. Obtain arterial blood gases. Administer oxygen if there is evidence of altered mental status or dyspnea. Treat hypotension with volume expansion & vasopression. Use lidocaine or beta-blockers for ventricular arrhythmias. Skin: Remove contaminated clothing. Wash affected area with soap & copious amounts or water. Eye: Irrigate the eye for 15-20 min. Obtain a consultation if symptoms persist. Oral: Most of the halogenated solvents ingested in quantities of 1-2 swallows may be partially removed by ipecac-induced emesis if admin within a few hr to a patient who has not lost the gag reflex, is not seizing, is not markedly lethargic, or is not in coma. Observe the patient in the upright position to lessen the possibility of aspiration. Activated charcoal is probably ineffective. Inhalation: Move from the contaminated area. Provide a source of oxygen & prepare for mechanical ventilation. If the patient is unconscious & the pulse is absent, initiate CPR measures. Enhancement of Elimination: Maintain good ventilation. Hemodialysis or hemoperfusion are not likely to be useful because of the high lipophilic properties of these solvents. Antidote: N-acetylcysteine may restore depleted glutathione stores, but no adequate clinical studies are available to validate this possible treatment. Supportive Care: Watch for cardiac dysrhythmias, aspiration pneumonitis, hepatotoxicity, & hypoxic encephalopathy. Monitor for arrhythmia for at least 24 hr & for hepatorenal failure for about 3 days. Obtain a chest x-ray, arterial blood gas, EKG, serum creatinine, & hepatic aminotransferase. Check electrolyte imbalance daily. Treat renal failure with dialysis & hepatic failure with fresh frozen plasma, vitamin K, a low-protein diet, neomycin, & lactulose. Watch fluid & electrolyte balance. /Halogenated hydrocarbons/
Chemically Diverse Helix-Constrained Peptides Using Selenocysteine Crosslinking
作者：Aline Dantas de Araujo、Samuel R. Perry、David P. Fairlie
DOI：10.1021/acs.orglett.8b00233
日期：2018.3.2
The use of selenocysteines and various cross-linkers to induce helicity in a bioactive peptide is described. The higher reactivity of selenocysteine, relative to cysteine, facilitates rapid cross-linking within unprotected linear peptides under mild aqueous conditions. Alkylating agents of variable topology and electrophilicity were used to link pairs of selenocysteines within a p53 peptide. Facile
The catalytic activity of β‐cyclodextrin immobilized on Dowexresin as an efficient solid‐liquid phase transfer catalyst was developed for the synthesis of alkyl thiocyanates and phenacyl derivatives in water. The nucleophilicsubstitutionreactions were performed under mild reaction condition and gave the products in excellent yields. Furthermore, the catalyst could be recycled by facile separation
Asymmetric Palladium(0) Catalyzed Tandem Alkylation and S<sub>N</sub>′ Cyclization of 1,4-Dichlorobut-2-ene by Chiral Imines of Aminoacetonitrile for the Total Synthesis of 1-Aminocyclopropanecarboxylic Acids
Chiral imines (-)- and (+)-8a, prepared from aminoacetonitrile and (-)- or (+)-1-hydroxypinanones, reacted with E- and Z-1,4-dichlorobut-2-enes 1 in the presence of (S)- or (R)-BINAP palladium(0) complexes to produce the diastereoselectively pure 1-amino-2-vinylcyclopropane carbonitrile E-13a, suitable precursor of ACCs. However subsequent Pd(0) induced reversible ring opening of the vinylcyclopropane moiety seems responsible for the low enantiomeric excesses obtained (≤32% ee).
Stereoselective Synthesis of Highly Functionalized Cyclopropanes. Application to the Asymmetric Synthesis of (1<i>S</i>,2<i>S</i>)-2,3-Methanoamino Acids
functionalized cyclopropanes (E)-4a-d, diastereoselectivity, (de 88-100%). Several attempts to achieve the asymmetric synthesis of the 1-amino-2-ethenylcyclopropanecarbonitrile (E)-9, by means of this new procedure, i.e., using chiral palladium ligands, chiral aminoacetonitriles (-)- and (+)-12 (from 1-hydroxypinanone) or chiral allyl chlorides (4S)-20b-d and (4R)-20e (from (2S) ethyl lactate) have pointed up
[EN] MACROCYCLIC FLUORINE SUBSTITUTED INDOLE DERIVATIVES AS MCL-1 INHIBITORS, FOR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS D'INDOLE MACROCYCLIQUES SUBSTITUÉS PAR DU FLUOR UTILISÉS EN TANT QU'INHIBITEURS DE MCL-1, DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU CANCER
申请人：BROAD INST INC
公开号：WO2019096909A1
公开（公告）日：2019-05-23
The present invention relates to macrocyclic indole derivatives of general formula (I) : in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.
