• Title/Summary/Keyword: sulfonylurea

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Chemical Stabilization Study for Sulfonylurea Herbicides (Sulfonylurea계(系) 제초제(除草劑)의 화학적(化學的) 안정성(安定性))

  • Chen, Chia-Chung
    • Korean Journal of Weed Science
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    • v.17 no.2
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    • pp.135-138
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    • 1997
  • Sulfonylureas are highly active herbicides which can be applied at very low rate(10-50g/ha) to control broadleaf weeds. The nature of this category of compound is, however, very unstable toward hydrolysis. Therefore, the preparation of these compounds as liquid formulation was not possible. Most of the current formulations of sulfonylurea are in dry forms such as water dispersible granule or wettable powder. Even in these dry forms, the active ingredients also encounter significant chemical decomposition. This study involves the preparation of the sulfonylurea salts by reacting the parent compound with base such as sodium hydroxide. The salt becomes stable toward hydrolysis and it turns soluble when diluted with water. This discovery makes the preparation for liquid formulation or soluble granule of sulfonylurea possible. The stoichiometry of base added to the neutral sulfonylurea is controlled quite precisely. The base has to be added enough to quench the acidic impurities in the technical material and to convert the active ingredient into salt. However, the base should not be overused to cause further saponification of the sulfonylurea salts. The chemical nature of these compounds is presented and the chemical reaction is described. New soluble liquid formulation and solid granule formulation of sulfonylurea are suggested.

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Successful switching from insulin to sulfonylurea in a 3-month-old infant with diabetes due to p.G53D mutation in KCNJ11

  • Yoon, Jong Seo;Park, Kyu Jung;Sohn, Young Bae;Lee, Hae Sang;Hwang, Jin Soon
    • Annals of Pediatric Endocrinology and Metabolism
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    • v.23 no.3
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    • pp.154-157
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    • 2018
  • Permanent neonatal diabetes mellitus is most commonly caused by mutations in the ATP-sensitive potassium channel ($K_{ATP}$) subunits. Prompt initiation of sulfonylurea treatment can improve glycemic control in children with KCNJ11 mutation. In this report, we present a case of permanent neonatal diabetes caused by a mutation in the KCNJ11 gene that was successfully treated via early switching of insulin to sulfonylurea treatment. A 53-day-old female infant presented with diabetic ketoacidosis. Insulin was administered for the ketoacidosis and blood glucose regulation. At 3 months of age, using genomic DNA extracted from peripheral lymphocytes, direct sequencing of KCNJ11 identified a heterozygous mutation of c.158G>A (p.G53D) and confirmed the diagnosis of permanent neonatal diabetes mellitus. Subsequently, treatment with sulfonylurea was initiated, and the insulin dose was gradually tapered. At 4 months of age, insulin therapy was discontinued, and sulfonylurea (glimepiride, 0.75 mg/kg) was administered alone. At 6 months after initiation of administration of sulfonylurea monotherapy, blood glucose control was stable, and no hypoglycemic events or developmental delays were reported. C-peptide levels increased during treatment with sulfonylurea. Early switching to sulfonylurea in infants with permanent diabetes mellitus owing to a KCNJ11 mutation could successfully help regulate glycemic control, which suggests the need for early genetic testing in patients presenting with diabetes before 6 months of age.

Hyperglycemic Effect of Conformationally Rigid Sulfonylurea Derivatives (Conformation이 고정된 Sulfonylurea 유도체의 혈당상승작용)

  • 박혜영;김연경;권진숙;김화정
    • Biomolecules & Therapeutics
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    • v.4 no.4
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    • pp.408-410
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    • 1996
  • 3, 4-Dihydro-3-oxo-2H-1, 2, 4-benzothiadiazine-1, 1-dioxides were synthesized as conformationally rigid analogues of sulfonylurea hypoglycemic agents. All the compounds prepared showed hyperglycemic activity. The hyperglycemic activity was enhanced for the diabetic rats in which the blood glucose level was increased by 30-70%.

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Synthesis of Sulfonylurea Derivatives by Oxalylchloride (Oxalylchloride를 이용한 Sulfonylurea계 유도체 합성에 관한 연구)

  • Kyung, Suk-Hun;Tak, Yoon-Heung
    • Korean Journal of Environmental Agriculture
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    • v.8 no.2
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    • pp.136-141
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    • 1989
  • An alternative method for the synthesis of sulfonylurea derivatives, some of which considered to be a new recommendable herbicides, with oxalylchloride was investigated. Sulfonamides read with oxalylchloride to sulfonyloxamoylchlorides, which convert easily under pyrolysis to sulfonylisocyanates. The isocyanates react further with amines to yield corresponding sulfonylurea derivative quantitatively.

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Successful sulfonylurea treatment in a patient with permanent neonatal diabetes mellitus with a novel KCNJ11 mutation

  • Ahn, Sung Yeon;Kim, Gu-Hwan;Yoo, Han-Wook
    • Clinical and Experimental Pediatrics
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    • v.58 no.8
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    • pp.309-312
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    • 2015
  • Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium ($K_{ATP}$) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the $K_{ATP}$ channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

Ameliorating Effects of Sulfonylurea Drugs on Insulin Resistance in Otsuka Long-Evans Tokushima Fatty Rats

  • Park, Jeong-Kwon;Kim, Sang-Pyo;Song, Dae-Kyu
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.1
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    • pp.7-12
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    • 2008
  • OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

Control of Sulfonylurea Herbicide-Resistant Lindernia dubia in Korean Rice Culture

  • Kuk, Yong-In
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.47 no.4
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    • pp.328-334
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    • 2002
  • A Lindernia dubia (L.) Pennell var. dubia accession from Jeonnam province, Korea was tested for resistance to sulfonylurea (SU) herbicides, imazosulfuron and pyrazosulfuron-ethyl in whole-plant response bioassay. The accession was confirmed resistant to both herbicides. The $GR_{50}$ (herbicide concentration that reduced shoot dry weight by 50%) values of resistant accession were 264 and 19 times higher to imazosulfuron and pyrazosulfuronethyl, respectively, than that of the standard susceptible accession. The surviving resistant L. dubia after pyrazosulfuron-ethyl + molinate application can be controlled by sequential applications of soil-applied herbicides, butachlor, dithiopyr, pyrazolate, and thiobencarb and foliar herbicides, bentazon. Sulfonylurea-based mixtures such as mixtures of azimsulfuron + anilofos, bensulfuron-methyl + oxadiazon, pyrazosulfuron-ethyl + fentrazamide, and pyrazosulfuron-ethyl + anilofos + carfentrazon can also be used to control the surviving resistant L. dubia. However, use of these mixtures should be restricted to a special need basis. Thus, we suggest that sequential applications of non-SU-based mixtures such as butachlor + pyrazolate and MCPB + molinate + simetryne be used to control the surviving resistant L. dubia after SU herbicide applications. Rice yield was reduced 24 % by resistant L. dubia that survived after the pyrazosulfuron-ethyl + molinate application compared with pyrazolate + butachlor in transplanted rice culture. In vitro ALS activity of the resistant biotype was 40 and 30 times more resistant to imazosulfuron and pyrazosulfuron-ethyl, respectively, than the susceptible biotype. Result of in vitro ALS assay that the resistance mechanism of L. dubia to SU herbicides may be due, in part, to an alteration in the target enzyme, ALS.

Cancer Risk in Patients with Type 2 Diabetes on Antidiabetic Monotherapy: A Population Based Cohort Study Using National Insurance Health Service Database (혈당강하제 단독요법 투여 당뇨병환자에서 암발생률 평가: 후향적 코호트 연구)

  • Jung, Han Yeong;Lee, Sukhyang
    • Korean Journal of Clinical Pharmacy
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    • v.29 no.3
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    • pp.186-192
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    • 2019
  • Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ${\geq}30$ years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31-0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.

Synthesis of sulfonylureas and their herbicidal effect (신규 Sulfonylurea 제초제의 합성과 제초 특성)

  • Ryu, Jae-Wook;Kim, Byung-Chul;Chung, Kun-Hoe;Chang, Hae-Sung;Ko, Young-Kwan;Woo, Jae-Chun;Koo, Dong-Wan;Kim, Dae-Whang
    • The Korean Journal of Pesticide Science
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    • v.6 no.4
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    • pp.320-323
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    • 2002
  • New and fast degradable sulfonylurea derivaties possessing N-methylureido group were synthesized and their herbicidal effects were tested under the upland in greenhouse. N-methylureido benzenesulfonylureas showed better herbicidal activity against grass weeds than broad leaf weeds under post emergence.

The Distribution and Occurrence of Sulfonylurea-Resistant Weeds in Paddy Fields of Gyeongbuk Province (경북 지역 Sulfonylurea계 저항성 논잡초 발생양상과 분포)

  • Kim, Sang Kuk;Kim, Hak Yoon
    • Weed & Turfgrass Science
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    • v.2 no.2
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    • pp.131-137
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    • 2013
  • The study was carried out to obtain the basic information on distribution and occurrence of weeds including resistant weeds to sulfonylurea herbicides in paddy fields of Gyeongbuk province. In weed distribution on life cycle, annual weed was occupied by 91.8% and perennials were 8.2%, respectively. In morphological distribution of weeds, broad leaf weeds were 85.7%, sedges was 9.1%, and grass weed was 3.8%, respectively. Sulfonylurea-resistant weeds in paddy fields of twelve regions were widely occurred except for Yecheon region. The six sulfonylurea resistant biotypes occurred in paddy fields of Gyeongbuk province were Lindernia dubia, Eleocharis kuroguwai, Monochoria vaginalis and Ludwigia prostrata. It revealed that occurrence rate and area of sulfonylurea-resistant weeds were about 15.9 % and 22,420 ha in Gyeongbuk province.