INORGANIC CYANIDE ION IS CONJUGATED WITH SULFUR TO FORM THIOCYANATE. ... THE CONJUGATION IS CATALYZED BY ... RHODANESE WHICH IS WIDELY DISTRIBUTED IN MOST ANIMAL TISSUES EXCEPT BLOOD, LIVER BEING PARTICULARLY ACTIVE. ... RHODANESE MECHANISM IS CAPABLE OF DETOXICATING ONLY LIMITED AMT OF CYANIDE, SUCH AS ARE FORMED DURING NORMAL METAB. /ANOTHER SULFUR DONOR IS 3-MERCAPTOPYRUVATE. THE ENZYME, MERCAPTOSULFUR TRANSFERASE IS LOCALIZED IN CYTOSOL./ /CYANIDE/
/ONE OF/ THE MAJOR MECHANISMS FOR REMOVING CYANIDE FROM THE BODY IS ITS ENZYMATIC CONVERSION, BY THE MITOCHONDRIAL ENZYME RHODANASE (TRANSSULFURASE), TO THIOCYANATE, WHICH IS RELATIVELY ... /LESS TOXIC/. /CYANIDE/
来源:Hazardous Substances Data Bank (HSDB)
代谢
假单胞菌putida利用氰化物作为唯一的碳源和氮源。筛选了琼脂、藻酸盐和角叉菜胶作为封装P. putida的基质。藻酸盐固定的P. putida细胞比非固定细胞或琼脂或角叉菜胶固定的细胞更有效地降解了氰化钠（NaCN）。氰化物生物降解的终产物被鉴定为氨（NH3）和二氧化碳（CO2）。这些产品改变了培养基的pH值。在生物反应器中，氰化物降解速率随着通气速率的增加而增加。在200 ml min-1的通气速率下观察到氰化物的最大利用。P. putida的固定化细胞将氰化物、氰酸盐和硫氰酸盐降解为NH3和CO2。使用Na(14C)-CN表明，Na(14C)-CN的70%的碳转化为14CO2，只有10%与细胞生物量相关。底物依赖性动力学表明，P. putida对底物NaCN的米氏常数（Km）和最大反应速率（Vmax）分别为14 mM和29 nmol氧气消耗mg蛋白质-1 min-1。
Pseudomonas putida utilizes cyanide as the sole source of carbon and nitrogen. Agar, alginate, and carrageenan were screened as the encapsulating matrices for P. putida. Alginate-immobilized cells of P. putida degraded sodium cyanide (NaCN) more efficiently than non-immobilized cells or cells immobilized in agar or carrageenan. The end products of biodegradation of cyanide were identified as ammonia (NH3) and carbon dioxide (CO2). These products changed the medium pH. In bioreactors, the rate of cyanide degradation increased with an increase in the rate of aeration. Maximum utilization of cyanide was observed at 200 ml min-1 of aeration. Immobilized cells of P. putida degraded cyanides, cyanates and thiocyanates to NH3 and CO2. Use of Na(14C)-CN showed that 70% of carbon of Na(14C)-CN was converted into 14CO2 and only 10% was associated with the cell biomass. The substrate-dependent kinetics indicated that the Km and Vmax values of P. putida for the substrate, NaCN were 14 mM and 29 nmol of oxygen consumed mg protein-1 min-1 respectively.
Copper is mainly absorbed through the gastrointestinal tract, but it can also be inhalated and absorbed dermally. It passes through the basolateral membrane, possibly via regulatory copper transporters, and is transported to the liver and kidney bound to serum albumin. The liver is the critical organ for copper homoeostasis. In the liver and other tissues, copper is stored bound to metallothionein, amino acids, and in association with copper-dependent enzymes, then partitioned for excretion through the bile or incorporation into intra- and extracellular proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes. Copper may induce the production of metallothionein and ceruloplasmin. The membrane-bound copper transporting adenosine triphosphatase (Cu-ATPase) transports copper ions into and out of cells. Physiologically normal levels of copper in the body are held constant by alterations in the rate and amount of copper absorption, compartmental distribution, and excretion. Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96, L277, L279)
Basic Treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Copper and related compounds/
Advanced Treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious. Start an IV with lactated Ringer's /SRP: "To keep open", minimal flow rate/. Watch for signs of fluid overload. For hypotension with signs of hypovolemia, admin fluid cautiously. Consider vasopressors if hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Copper and related compounds/
Basic Treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 l/min. Administer amyl nitrite ampules as per protocol and physician order ... . Monitor for shock and treat if necessary ... . Monitor for pulmonary edema and treat if ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Cyanide and related compounds/
Advanced Treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Administer cyanide antidote kit as per protocol and physician order ... . Monitor and treat cardiac arrhythmias if necessary ... . Consider vasopressors to treat hypotension without signs of hypovolemia ... . Consider drug therapy for pulmonary edema ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Cyanide and related compounds/
Initial medical exam /should include/: a complete history & physical exam ... to detect existing conditions that might place the exposed employee at incr risk & to establish a baseline for future health monitoring. ... Exam of cardiovascular, nervous, & upper resp systems, & thyroid should be stressed. The skin should be exam for evidence of chronic disorders. ... The aforementioned medical exam should be repeated on an annual basis. /Cyanides/
IN 30 DAYS, 72% OF (14)C FROM IP DOSE OF (14)C-CYANIDE TO MICE WAS EXCRETED IN URINE & FECES, 25% IN EXPIRED AIR, & 3% WAS RETAINED ... PEAK EXCRETION OCCURRED WITHIN 10 MIN IN EXPIRED AIR & WITHIN 6-24 HR IN URINE & FECES. /CYANIDE/
CYANIDE ION IS READILY ABSORBED AFTER ORAL OR PARENTERAL ADMIN. PROLONGED LOCAL CONTACT WITH CYANIDE SOLN OR WITH HYDROGEN CYANIDE MAY RESULT IN ABSORPTION OF TOXIC AMT THROUGH SKIN. PART OF ABSORBED CYANIDE IS EXCRETED UNCHANGED BY THE LUNG. ... LARGER PORTION ... CONVERTED BY ... SULFURTRANSFERASE TO RELATIVELY NONTOXIC THIOCYANATE ION. /CYANIDE ION/
CYANIDES ARE RAPIDLY ABSORBED FROM SKIN & ALL MUCOSAL SURFACES & ARE MOST DANGEROUS WHEN INHALED, BECAUSE TOXIC AMT ARE RAPIDLY ABSORBED THROUGH BRONCHIAL MUCOSA & ALVEOLI. /CYANIDES/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
氰化物通过血液分布到所有器官和组织，其中红细胞中的氰化物浓度比血浆中的高两到三倍。
Cyanide is distributed to all organs and tissues via the blood, where its concn in red cells is greater than that in plasma by a factor of two or three. /Cyanide/
2-Amino-6-arylsulfonylbenzonitriles as Non-nucleoside Reverse Transcriptase Inhibitors of HIV-1
作者：Joseph H. Chan、Jean S. Hong、Robert N. Hunter、G. Faye Orr、Jill R. Cowan、Douglas B. Sherman、Steven M. Sparks、Barbara E. Reitter、C. Webster Andrews、Richard J. Hazen、Marty St Clair、Lawrence R. Boone、Rob G. Ferris、Katrina L. Creech、Grace B. Roberts、Steven A. Short、Kurt Weaver、Ronda J. Ott、Jingshan Ren、Andrew Hopkins、David I. Stuart、David K. Stammers
DOI：10.1021/jm0004906
日期：2001.6.1
A series of 2-amino-5-arylthiobenzonitriles (1) was found to be active against HIV-1. Structural modifications led to the sulfoxides (2) and sulfones (3). The sulfoxides generally showed antiviral activity against HIV-1 similar to that of 1. The sulfones, however, were the most potent series of analogues, a number having activity against HIV-1 in the nanomolar range. Structural-activity relationship
The highly oxygenated 6/8/6-membered ABC-ring 2 of taxol was assembled in a convergent fashion. A decarbonylative radical reaction between α-alkoxyacyl telluride 4 and cyanocyclohexenone 5 linked the A- and C-rings and stereoselectively installed the C2- and C3-tertiary carbon centers of 3. After the C8-quaternary stereocenter was constructed, the C9-methyl ketone and the C11-vinyl triflate of 30 participated
[EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
申请人：GALAPAGOS NV
公开号：WO2017012647A1
公开（公告）日：2017-01-26
The present invention discloses compounds according to Formula (I), wherein R1, R3, R4, R5, L1, and Cy are as defined herein. The present invention also provides compounds, methods for the production of said compounds of the invention, pharmaceutical compositions comprising the same and their use in allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 and/or interferons. The present invention also methods for the prevention and/or treatment of the aforementioned diseases by administering a compound of the invention.
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
An anticoagulant agent which comprises, as an active ingredient, an aromatic amidine derivative represented by the following general formula (1) or a salt thereof: ##STR1## wherein the group represented by ##STR2## is a group selected from indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, naphthyl, tetrahydronaphthyl and indanyl; X is a single bond, an oxygen atom, a sulfur atom or a carbonyl group; and Y is a saturated or unsaturated 5- or 6-membered heterocyclic moiety or cyclic hydrocarbon moiety optionally having a substituent group, an amino group optionally having a substituent group or an aminoalkyl group optionally having a substituent group. The inventive compound has a high anticoagulant capacity based on its excellent FXa inhibition activity.
