Sulfathiazole is a white crystalline powder. Is dimorphous: form I is consists of prismatic rods and form II of six-sided plates and prisms. Insoluble in water and soluble in dil aqueous acid and aqueous base.
颜色/状态：
Brown plates, rods or powder from 45% alcohol
蒸汽压力：
4.22X10-8 mm Hg at 25 °C (est)
稳定性/保质期：
The stability of sulfamethazine (sulfadimidine) sulfathiazole, sulfameter (sulfamethoxydiazine), and sulfacetamide during acid hydrolysis in one mol/L of hydrochloric acid under increased temperature was examined using high pressure liquid chromatography. Kinetic characteristics of the process of decomposition were calculated from the found values of the concentration of undecomposed sulfonamide in relation to time. The calculated values of activation energy for the individual sulfonamides are given. The paper stresses the illustrativeness of HPLC in the examination of decomposition products.
分解：
When heated to decomposition it emits very toxic fumes of /nitrogen and sulfur oxides/.
解离常数：
pKa1 = 2.2; pKa2= 7.24
碰撞截面：
150.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
Metabolism of sulfonamide drugs in animals includes conjugation at the N4-position (acetyl, sulfate, glucuronic acid, and glucose), conjugation at the N1-position (sulfate and glucuronic acid), removal of the p-amino group (formation of the desamino metabolite), ring hydroxylation, and conjugation of the ring hydroxylation products. Dietary nitrite enhances the production of the desamino metabolite of sulfathiazole. The intermediate leading to the desamino metabolite of sulfamethazine is weakly mutagenic in the Ames test (Nelson et al., 1987; Paulson et al., 1987).
Although the liver is the major site of metabolism, sulfonamides may also be metabolized in other body tissues. Most sulfonamides are metabolized mainly by N4-acetylation. The degree of acetylation, which is a function of time, varies from less than 5% for sulfamethizole to up to 40% for sulfadiazine. The N4-acetyl metabolites, which do not possess antibacterial activity, have greater affinity for plasma albumin than does the nonacetylated drug and are usually less soluble than the parent sulfonamide, particularly in acidic urine. Like acetyl derivatives, glucuronide derivatives do not possess antibacterial activity; however, glucuronide derivatives are water soluble, appear to resemble the nonacetylated sulfonamide in plasma binding capacity, and have not been associated with adverse effects. /Sulfonamides/
Metabolism of sulfonamide drugs in animals includes conjugation at the N4-position (acetyl, sulfate, glucuronic acid, and glucose), conjugation at the N1-position (sulfate and glucuronic acid), removal of the p-amino group (formation of the desamino metabolite), ring hydroxylation, and conjugation of the ring hydroxylation products. Dietary nitrite enhances the production of the desamino metabolite of sulfathiazole.
Sulfathiazole...is one of the short-acting sulfonamides & in man is excreted in urine as unchanged sulfathiazole (63% of dose), N4-acetylsulfathiazole (29%), sulfathiazole-N4-glucuronide (0.8%), sulfathiazole-N4-sulfate (0.5%) & sulfathiazole-N1-glucuronide (3.8%).
Deposition kinetics, metabolism and urinary excretion of sulfathiazole were investigated in German black head sheep following single oral administration (100 mg/kg). Kinetic evaluation of plasma levels was performed using a two-compartment best fit model. Sulfathiazole is significantly metabolized to N4-acetyl metabolite in the rumen fluid. The drug is very poorly absorbed since the minimum effective concentration in plasma was not attained at any time following oral administration. The prolonged elimination half-life in sheep may be due to a low rate of drug absorption from the rumen and gastro-intestinal tract. Sulfathiazole was mainly excreted in the urine as free drug and N4-acetyl metabolite.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Individual sulfonamides differ markedly in their absorption, distribution, and elimination. With the exception of sulfapyrimidine and sulfasalazine, which are only slightly absorbed, sulfonamides are generally well absorbed from the GI tract. Approximately 70-90% of an oral dose of the absorbable sulfonamides is reportedly absorbed from the small intestine; small amounts may also be absorbed from the stomach. Sulfamethizole and sulfisoxazole (no longer commercially available in the US) are absorbed rapidly; peak blood concentrations are usually obtained within 2-4 hours. Sulfadiazine and sulfapyridine are absorbed at a slower rate with peak blood concentrations occurring within 3-7 hours. Administration of oral sulfonamides with food appears to delay, but not reduce, absorption of the drugs. /Sulfonamides/
Absorption of sulfonamides from the vagina, respiratory tract, or abraded skin is variable and unreliable; however, enough drug may be absorbed to induce sensitization or toxicity. /Sulfonamides/
Although only free (unmetabolized and unbound) sulfonamides are microbiologically active, blood concentrations are often determined on the basis of total sulfonamide concentration. Generally, sulfonamide plasma concentrations are approximately twice the blood concentrations. Wide variations in blood concentrations have been reported in different individuals receiving identical doses of the same sulfonamide. Blood total sulfonamide concentrations of 12-15 mg/dL have been reported to be optimal; blood concentrations greater than 20 mg/dL have been associated with an increased incidence of adverse reactions. /Sulfonamides/
Absorbable sulfonamides are widely distributed in the body. Although most sulfonamides appear to cross cell membranes, sulfisoxazole appears to be distributed only in extracellular fluid. Sulfonamides may appear in pleural, peritoneal, synovial, amniotic, prostatic, and seminal vesicular fluid, and aqueous humor. Concentrations of some sulfonamides in the CSF may reach 35-80% of blood concentrations. Small amounts of sulfonamides are also distributed into sweat, tears, saliva, and bile. /Sulfonamides/
The present application provides compounds of formula: Methods of using these compounds for killing bacterial growth and treating bacterial infections are also provided.
本申请提供了以下化合物的公式：还提供了使用这些化合物杀灭细菌生长和治疗细菌感染的方法。
New quinoxaline compounds as DPP-4 inhibitors and hypoglycemics: design, synthesis, computational and bio-distribution studies
作者：Yasmin M. Syam、Manal M. Anwar、Somaia S. Abd El-Karim、Samia A. Elseginy、Basma M. Essa、Tamer M. Sakr
DOI：10.1039/d1ra06799k
日期：——
The current work represents the design and synthetic approaches of a new set of compounds 6-10 bearing the 1,4-dimethyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide scaffold. The biological evaluation revealed that most of the newcompounds were promising selective dipeptidyl peptidase-IV (DPP-4) inhibitors and in vivo hypoglycemic agents utilizing linagliptin as a standard drug. The acute
Design, synthesis and SAR of new-di-substituted pyridopyrimidines as ATP-competitive dual PI3Kα/mTOR inhibitors
作者：Aisha A.K. Al-Ashmawy、Fatma A. Ragab、Khaled M. Elokely、Manal M. Anwar、Oscar Perez-Leal、Mario C. Rico、John Gordon、Eugeney Bichenkov、George Mateo、Emad M.M. Kassem、Gehan H. Hegazy、Magid Abou-Gharbia、Wayne Childers
DOI：10.1016/j.bmcl.2017.05.044
日期：2017.7
PI3Kα/mTOR ATP-competitiveinhibitors are considered as one of the promising molecularly targeted cancer therapeutics. Based on lead compound A from the literature, two similar series of 2-substituted-4-morpholino-pyrido[3,2-d]pyrimidine and pyrido[2,3-d]pyrimidine analogs were designed and synthesized as PI3Kα/mTOR dual inhibitors. Interestingly, most of the series gave excellent inhibition for both
PI3Kα/ mTOR ATP竞争性抑制剂被认为是有前途的分子靶向癌症治疗剂之一。基于文献中的铅化合物A，设计并合成了两个相似的2-取代-4-吗啉代-吡啶并[3,2- d ]嘧啶和吡啶并[2,3- d ]嘧啶类似物系列，并将其合成为PI3Kα/ mTOR dual抑制剂。有趣的是，大多数系列均对两种酶均具有优异的抑制作用，IC 50值范围从一位到两位数nM。与许多PI3Kα/ mTOR双重抑制剂不同，我们的化合物显示出对PI3Kα的选择性。基于其强大的酶抑制活性，对PI3Kα的选择性以及在2D细胞培养活力测定中良好的治疗指数，化合物4h选择在3D培养中评估其针对MCF7乳腺癌细胞的IC 50以及与这两种酶的对接研究。
[EN] 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LA 3-PHOSPHOGLYCÉRATE DÉSHYDROGÉNASE ET LEURS UTILISATIONS
申请人：RAZE THERAPEUTICS INC
公开号：WO2017156181A1
公开（公告）日：2017-09-14
The present invention provides compounds, compositions thereof, and methods of using the same.
本发明提供了化合物、其组合物以及使用这些化合物的方法。
Kappa agonist compounds and pharmaceutical formulations thereof
申请人：——
公开号：US20030144272A1
公开（公告）日：2003-07-31
Compounds having kappa opioid agonist activity, compositions containing them and method of using them as analgesics are provided.
The compounds of formulae I, II, IIA, III, IIIA, IIIB, IIIB-i, IV and IVA have the structure:
1
2
wherein
R
1
, R
2
, R
3
, R
4
; and
X, X
4
, X
5
, X
7
, X
9
;
Y, Z and n are as described in the specification.
