- A ternary tetracoordinated PdII complex with metformin and dipicolinate: Synthesis, characterization and crystal structure
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A proton transfer compound L, (MetH)2(dipic), (dipicH 2 = 2,6-pyridinedicarboxylic acid and Met = Metformin (N,N-dimethylebiguanidine), was synthesized and characterized by IR, 1H and 13C NMR spectroscopy. The reaction of L with PdCl2 in water results in the formation of novel tetracoordinated PdII complex [Pd(dipic)(Met)]·2H2O indicating the participation of both dipic2- and Met as chelating ligands. This complex was characterized by single crystal X-ray analysis. The crystal system is monoclinic with space group P21/c. The unit cell dimensions for PdII complex 1 is a = 8.8619(14) , b = 9.5072(9) , c = 19.153(3) .
- Moghimi,Khavassi,Dashtestani,Kordestani,Ekram Jafari,Maddah,Moosavi
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- Novel halogenated sulfonamide biguanides with anti-coagulation properties
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Apart from its hypoglycaemic properties, metformin also offers beneficial effects for the cardiovascular system resulting in significant reduction of diabetes-related death, and all-cause mortality. The aim of this study was to synthesize nine new benzenesulfonamide derivatives of metformin with a halogen substituent, and estimate their influence on selected parameters of plasma and vascular hemostasis. The study describes the synthesis of nine benzenesulfonamide biguanides with o-, m-, and p- chloro-, bromo-, and fluoro substituents. All orto- derivatives (chloro- (1), bromo- (4), and fluoro- (7)) significantly prolong prothrombin time (PT) and partially activated thromboplastin time (APTT). In addition compounds 4 and 7 slow the process of fibrin polymerization, and contribute to increased TT. Multiparametric CL-test revealed that compounds 1, 4, 7 and p-fluorobenzenesulfonamide (9) significantly prolong the onset of clot formation, decrease initial clot formation velocity, and maximum clotting. Analysis of human endothelial cell (HUVECs) and human aortal smooth muscle cell (AoSMCs) viability over the entire tested concentration range (0.001–3.0 μmol/mL) indicated that the examined compounds can undergo further tests up to 1.5 μmol/mL concentration without decreasing cellular viability. Furthermore, none of the synthesized compounds exert an unfavourable effect on erythrocyte integrity, and thus do not interact strongly with the lipid-protein bilayer. In summary, chemical modification of the metformin backbone into benzenesulfonamides containing halogen substituents at the o- position leads to the formation of potential agents with stronger anti-coagulant properties than the parent drug, metformin. Therefore, o-halogenated benzenesulfonamides can be regarded as an initial promising step in the development of novel biguanide-based compounds with anti-coagulant properties.
- Huttunen, Kristiina M.,Markowicz-Piasecka, Magdalena,Sikora, Joanna,Zajda, Agnieszka
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- Convenient microwave-assisted synthesis of lipophilic sulfenamide prodrugs of metformin
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A convenient microwave-assisted synthesis of lipophilic sulfenamide prodrugs of antidiabetic agent, metformin, is reported in this study. These acyclic prodrugs were synthesized directly from selected disulfides with basic metformin and silver nitrate by a one-pot reaction under microwave irradiation. The prepared prodrugs had significantly increased lipophilicity, which resulted in excellent permeability of the octylthio prodrug of metformin across a Caco-2 cell monolayer. According to our preliminary in vivo studies, the octylthio prodrug was also absorbed mostly intact after oral administration in rats. In conclusion, this study shows that these types of more lipophilic sulfenamide prodrugs can be promising candidates to improve permeability and passive absorption of highly water-soluble metformin.
- Huttunen, Kristiina M.,Lepp?nen, Jukka,Laine, Krista,Veps?l?inen, Jouko,Rautio, Jarkko
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- Solid state and solubility study of a potential anticancer drug-drug molecular salt of diclofenac and metformin
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To improve the physicochemical properties of diclofenac (DFA) and exert its potential anti-tumor effect in combined pharmacotherapy of metformin (MET), a new drug-drug molecular salt of DFA and MET (DFA-MET) is formed and characterized. The single-crystal X-ray diffraction analysis shows that DFA-MET is a three-dimensional (3D) supramolecular structure constructed by different hydrogen-bonding interactions between DFA and MET with 1:1 stoichiometry by proton transfer reaction. In addition, Hirshfeld Surface analysis shows that both the hydrogen-bonding interactions and the Vander Waals maintain the 3D supramolecular structure of DFA-MET together. Compared with pure DFA and pure diclofenac sodium (NaDFA), the dissolving behavior and permeability of DFA-MET by forming drug-drug molecular salt in physiological pH environments are enhanced remarkably.
- Feng, Wen-Quan,Wang, Ling-Yang,Gao, Jie,Zhao, Ming-Yu,Li, Yan-Tuan,Wu, Zhi-Yong,Yan, Cui-Wei
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Read Online
- Two N,N-dimethylbiguanidium salts displaying double hydrogen bonds to the counter-ions
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An investigation into the crystal structures of N,N-dimethylbiguanidium salts was made. Compound (I) in N,N-dimethylbiguanidium contained one N,N dimethylbiguanidium dictation, one oxalate anion and one water molecule. Compound (II) consisted of one N,N-d
- Lu, Li-Ping,Zhang, Hong-Mei,Feng, Si-Si,Zhu, Miao-Li
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Read Online
- Novel sulfonamide-based analogs of metformin exert promising anti-coagulant effects without compromising glucose-lowering activity
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Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 μmol/L for comp. 6 at 0.3 μmol/mL versus 11.4 ± 0.7 μmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not a ect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.
- Markowicz-Piasecka, Magdalena,Sadkowska, Adrianna,Sikora, Joanna,Broncel, Marlena,Huttunen, Kristiina M.
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Read Online
- Sulfonamide metformin derivatives induce mitochondrial-associated apoptosis and cell cycle arrest in breast cancer cells
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Metformin, an oral anti-diabetic drug, has attracted scientific attention due to its anti-cancer effects. This biguanide exerts preventive effects against cancer, and interferes with cancer-promoting signaling pathways at the cellular level. However, the direct cytotoxic or anti-proliferative effect of the drug is observed at very high concentrations, often exceeding 5–10 mM. This paper presents the synthesis of eight novel sulfonamide-based biguanides with improved cellular uptake in two breast cancer cell lines (MCF-7 and MDA-MB-231), and evaluates their effects on cancer cell growth. The synthesized sulfonamide-based analogues of metformin (1–5) were efficiently taken up in MCF-7 and MDA-MB-231 cells, and were characterized by stronger cytotoxic properties than those of metformin. Generally, compounds were more effective in MCF-7 than in MDA-MB-231. Compound 2, with an n-octyl chain, was the most active molecule with IC50 = 114.0 μmol/L in MCF-7 cells. The cytotoxicity of compound 2 partially results from its ability to induce early and late apoptosis. Increased intracellular reactive oxygen species (ROS) production and reduced mitochondrial membrane potential suggest that compound 2 promotes mitochondrial dysfunction and activates the mitochondrial-associated apoptosis-signaling pathway. In addition, compound 2 was also found to arrest cell cycle in the G0/G1 and G2/M phase and significantly inhibit cancer cell migration. In conclusion, this study supports the hypothesis that improved transporter-mediated cellular uptake of potential drug molecule is accompanied by its increased cytotoxicity. Therefore, compound 2 is a very good example of how chemical modification of a biguanide scaffold can affect its biological properties and improve anti-neoplastic potential.
- Huttunen, Johanna,Huttunen, Kristiina M.,Markowicz-Piasecka, Magdalena,Sikora, Joanna,Zajda, Agnieszka
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- 5-substituted 2,4-thiazolidinediones (thiohydantoins), pseudothiohydantoins, and propseudothiohydantoins for use as antiviral agents
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The present invention concerns the synthesis and use of formulations of 5-substituted 2, 4-thiazolidinediones, pseudothiohydantoins, and propseudothiohydantoins and 2, 4-thiazolidinediones metforminate salts for topical and systemic treatments of infections caused by herpes simplex viruses and varicella zoster viruses.
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Page/Page column 13-14
(2020/06/03)
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- MODIFICATIONS OF THERAPEUTIC AGENTS FOR ENHANCED DELIVERY TO TARGET SITES
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Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.
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Paragraph 0475; 0476
(2018/02/28)
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- RAPAMYCIN ANALOGS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00163; 00168
(2017/03/28)
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- Hydrogen sulfide donor in organic salt form and preparation method thereof
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The invention provides a hydrogen sulfide donor in an organic salt form and a preparation method thereof. The hydrogen sulfide donor is a salt structure formed by organic compounds with an alkaline structure and hydrogen sulfide. The structure of the hydrogen sulfide donor is simple. The preparation method is simple and easy to perform. Moreover, hydrogen sulfide donors in different forms can be obtained according to the needs of development and research. After the hydrogen sulfide donor enters an organism, the process of degradation in the organism and hydrogen sulfide supply is simple, rapid, and effective, there is not any requirement on enzyme or other complicated condition, and thus the hydrogen sulfide donor has a wide application prospect and a great application value.
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Paragraph 0022; 0023; 0024; 0025
(2017/12/09)
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- Easy kinetic resolution of some β-amino alcohols by Candida antarctica lipase B catalyzed hydrolysis in organic media
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Herein, we present an easy and eco-friendly pathway to obtain some enantiomerically enriched β-amino alcohols using essentially as β-blockers. The enzymatic hydrolysis is conducted in hydrophobic organic media, assisted by sodium carbonate and CAL-B. We describe a new and effective procedure in terms of the chemo- and enantioselectivity, which allows for the formation of both enantiomers: the 2-acetamido-1-arylacetates and 2-acetamido-1-arylethanols were obtained with high ee values (up to >99%), while the selectivities reached E >200. The obtained results show a high CAL-B affinity toward the deacylation of the 2-acetamido-1-arylacetates compared to the acylation one. The structure of the 2-acetamido-1-arylacetates had a significant influence on both reactivity and selectivity of the CAL-B catalyzed deacylation. A multigram scale O-deacylation of racemic 2-acetamido-1-phenylacetate has been carried out, giving access both enantiomers with high enantiomeric purity and good isolated chemical yields.
- Alalla, Affef,Merabet-Khelassi, Mounia,Riant, Olivier,Aribi-Zouioueche, Louisa
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supporting information
p. 1253 - 1259
(2016/11/23)
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- Compound for treating bone marrow injury caused by radiotherapy and chemotherapy
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The present invention provides a compound represented by a formula I, a preparation method of the compound, a pharmaceutical composition containing the compound, and uses of the drug in treatment of bone marrow injury caused by radiotherapy and chemotherapy, and assisted treatment of aplastic anemia. The formula I is defined in the specification.
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Paragraph 0067; 0068; 0069
(2016/10/08)
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- TGR5 AGONIST COMPLEXES FOR TREATING DIABETES AND CANCER
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Provided herein are complexes of metformin or metformin analogues and a TGR5 ligand that are useful in treating diseases including diabetes, cardiovascular disease, and cancer.
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Paragraph 0245
(2015/12/17)
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- MONOLITHIC TABLETS BASED ON CARBOXYL POLYMERIC COMPLEXES FOR CONTROLLED DRUG RELEASE
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The present document describes a dosage form for delivery of an active ingredient comprising: a first carboxylated polymer having carboxyl groups, having a degree of substitution of at least 0.2, a molecular weight of at least 200 kDa, and at least 30% of said carboxyl groups being complexed with a divalent cation; alone or in a co-complex with at least one of a) a control release polymer chosen from an insoluble polymer or a polymer having a reduced water solubility at 30°C, and a soluble polymer; and b) a second carboxylated polymer having carboxyl groups complexed with a divalent cation. The document also describes processes of making a carboxylated polymer having carboxyl groups, having a degree of substitution of at least 0.2, a molecular weight of at least 200 kDa, and at least 30% of said carboxyl groups being complexed with a divalent cation, and an inclusion complex, a co-complex, or both comprising the same.
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Page/Page column 45
(2015/11/23)
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- METFORMIN DERIVATIVES FOR TREATING DIABETES AND DIABETES COMPLICATIONS
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The invention provides mutual ternary salts of metformin, lipoic acid and acidic amino acids such as aspartic acid and glutamic acid. The invention further provides treatment of prediabetes, diabetes, diabetic complications and/or other conditions in mammals in a method that comprises administering an effective amount of one or more of the foregoing compositions to a mammal in need of such treatment.
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Page/Page column 4-5
(2014/08/19)
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- Synthesis of biguanide-functionalized single-walled carbon nanotubes (SWCNTs) hybrid materials to immobilized palladium as new recyclable heterogeneous nanocatalyst for Suzuki-Miyaura coupling reaction
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Pd supported on biguanide(metformine)-functionalized single-walled carbon nanotubes (SWCNT-Met/Pd2+) hybrid materials was fabricated for the first time. The prepared heterogeneous nanocatalyst was characterized by XRD, FT-IR, SEM, TGA and TEM. The catalytic activity of the prepared catalyst was investigated by employing Suzuki-Miyaura coupling reaction as a model reaction. A series of biphenyl compounds were synthesized through the Suzuki-Miyaura reaction using SWCNT-Met/Pd2+ as catalyst. The yields of the products were in the range from 80% to 95%. The catalyst can be readily recovered and reused at least 5 consecutive cycles without significant loss its catalytic activity.
- Veisi, Hojat,Khazaei, Ardeshir,Safaei, Maryam,Kordestani, Davood
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p. 106 - 113
(2014/01/06)
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- URSOLIC ACID SALTS FOR TREATING DIABETES AND OBESITY
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The present invention relates to compounds having a specified ursolic acid structure, wherein R is H or OH and x+ is protonated metformin, protonated arginine, protonated lysine and protonated meglumine. The invention also relates to intermediates used in the preparation of such compounds, processes for the preparation of such compounds and intermediates, pharmaceutical compositions comprising such compounds and the methods of treatment using such compounds as antidiabetic, antiobesity, and antisarcopenia agents.
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Page/Page column 15; 16
(2014/02/15)
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- Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation
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The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.
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- A novel metformin derivative, HL010183, inhibits proliferation and invasion of triple-negative breast cancer cells
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Mounting evidence suggests that metformin (N,N-dimethylbiguanide), a widely prescribed drug for the treatment of type II diabetes, exerts an anti-tumor effect on several cancers including breast cancer. Breast cancer has been estimated as one of the most commonly diagnosed types of cancer among women. In particular, triple-negative breast cancers are associated with poor prognosis and metastatic growth. In the present study, we synthesized a novel metformin derivative 5 (HL010183) and metformin salts, 9a, 9b, and 9c (metformin gamma-aminobutyric acid (GABA) salt, metformin pregabalin salt and metformin gabapentin salt), which exerted more potent inhibitory effects on the proliferation and invasiveness of Hs578T triple-negative breast carcinoma cells than metformin. Importantly, 5 showed approximately 100-fold more potent effects compared to metformin. In a triple-negative breast cancer xenograft model, 5 showed a comparable degree of inhibitory effect on in vivo tumor growth at the 100 mg/kg dose to that of metformin at 500 mg/kg. Our results clearly demonstrate that 5 exerts a potent anti-tumor effect both in vitro and in vivo, paving the way for a strategy for treatment of triple-negative breast cancer.
- Koh, Minsoo,Lee, Jong-Cheol,Min, Changhee,Moon, Aree
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p. 2305 - 2313
(2013/05/09)
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- Regioselective synthesis of pyrimido[1,2-a][1,3,5]triazin-6-ones via reaction of 1-(6-oxo-1,6-dihydropyrimidin-2-yl)guanidines with triethylorthoacetate: Observation of an unexpected rearrangement
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A novel thermal rearrangement, involving pyrimidine ring opening and subsequent ring closure leading to recyclization of the system, was identified in the reaction of (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 (where NR 1R2 = NH2, NH alkyl, NH aralkyl, NHCH 2Ph(R)) with triethyl orthoacetate, affording 4-substituted-2-methyl- 6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 6 and their ring opened products. However, no such rearrangement was observed with (6-oxo-1,6-dihydropyrimidin-2- yl)guanidines 3 bearing a tertiary amino or anilino substituent (i.e. where NR1R2 = N(CH3)2, indoline, morpholino, NHAr). As expected, 2-substituted-4-methyl-6H-pyrimido[1,2-a][1,3,5] triazin-6-ones 4 were obtained as the final products. Experimental structural determination and theoretical studies were carried out to get an understanding of the observed thermal rearrangement. In addition, an attempt to obtain similar pyrimido[1,2-a][1,3,5]triazin-6-ones using N,N-dimethylacetamide dimethyl acetal (DMA-DMA) as one carbon inserting synthon had furnished triazine ring annulated product 14 bearing N,N-dimethyl enamino substituent at position 4 as a result of further reaction with a second molecule of DMA-DMA.
- Sachdeva, Nikhil,Dolzhenko, Anton V.,Keung Chui, Wai
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scheme or table
p. 4586 - 4596
(2012/07/28)
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- BUTYRIC ACID SALT OF N,N-DIMETHYL IMIDOCARBON IMIDIC DIAMIDE, METHOD OF PREPARING SAME, AND PHARMACEUTICAL COMPOSITIONS AND COMBINATIONS CONTAINING SAME
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The present invention provides metformin butyric acid salt, a method of preparing the same, and pharmaceutical compositions and combinations containing the same. The metformin butyric acid salt according to the present invention has an excellent pharmacological effect as compared with metformin hydrochloride and is capable of achieving a therapeutic purpose by administering an amount less than metformin hydrochloride. Furthermore, the metformin butyric acid salt has excellent physicochemical properties, such as solubility, stability, hygroscopicity and adsorption preventing property, in processibility of formulations and thereby is capable of being usefully utilized as a pharmaceutically acceptable salt of the metformin.
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Page/Page column 5
(2012/06/16)
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- Metformin Salts of Salicylic Acid and Its Congeners
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The present invention relates to compounds, intermediates used in the preparation of such compounds, processes for the preparation of such compounds of the formula VI and formula VII and such intermediates, pharmaceutical compositions comprising such compounds of the formula VI and such compounds of the formula VII, and the uses of such compounds of the formula VI and such compounds of the formula VII as antidiabetic, pre-antidiabetic, antiobesity and cardioprotective agents.
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Page/Page column 5-6
(2012/12/13)
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- LIPID-LOWERING ANTIDIABETIC AGENT
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A composition which includes a salt of metformin and the use of the composition for treatment of or use in prediabetes, diabetes, lowering triglycerides and/or other conditions in mammals.
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Page/Page column 5
(2012/07/27)
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- The first report on chemoselective biguanide-catalyzed henry reaction under neat conditions
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An efficient synthetic method for direct Henry reaction catalyzed by a biguanide; namely metformin, as an organosuper-base, between a variety of aromatic and aliphatic aldehydes and nitromethane under neat conditions has been developed. Convenient procedure for removal of the catalyst, chemoselective acquiring of β-nitroalcohols as predominant products, as far as possible short reaction time with excellent conversions are advantages of the developed protocol.
- Alizadeh, Abdolhamid,Khodaei, Mohammad M.,Abdi, Gisya,KORdestani, Davood
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p. 3640 - 3644
(2013/01/16)
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- Oral B12 Therapy
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Methods of normalizing vitamin B12 levels in patients with low vitamin B12 and methods of normalizing intersubject variability in the treatment of such patients are described. Methods of reducing MMA and/or homocysteine levels, and pharmaceutical compositions useful to effect such changes are also described.
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- NOVEL PRODRUGS OF METFORMIN
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The present invention relates to novel prodrugs of metformin, their pharmaceutically acceptable salts, pharmaceutical compositions containing the prodrugs, and methods of using the prodrugs. In particular, the present invention relates to prodrugs wherein sulfur-containing promoieties are attached to metformin to form novel bioreversible sulfenyl guanidine (N-S) prodrugs of metformin with improved oral absorption, and consequently promoted bioavailability.
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Page/Page column 9-10
(2010/09/18)
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- CURABLE COMPOSITION
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The present invention has its object to provide a curable composition which comprises a guanidine compound as a non-organotin type catalyst, is less discolored, has good surface curability, depth curability, strength rise and adhesiveness, and can retain the curability even after storage; the above object can be achieved by a curable composition which comprises: (A) an organic polymer containing a silyl group capable of crosslinking under siloxane bond formation, the silyl group being a group represented by the general formula (1): -SiX 3 (1) (wherein X represents a hydroxyl group or a hydrolyzable group and the three X groups may be mutually the same or different), (B) a guanidine compound (B-1) as a silanol condensation catalyst, and (C) a plasticizer, wherein the content of the component (B-1) is not lower than 0.1 part by weight but lower than 8 parts by weight per 100 parts by weight of the component (A), and a non-phthalate ester plasticizer accounts for 80 to 100% by weight of the (C) component plasticizer.
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- PHARMACEUTICAL CO-CRYSTALS OF QUERCETIN
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Disclosed herein is synergistic pharmaceutical co-crystals composition comprising Quercetin and an antidiabetic agent(s) as combination drug that have unique physical properties and biological activity which differ from the active agent in pure form. The invention further discloses process for preparation of the same and pharmaceutical compositions comprising these synergistic co-crystals.
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Page/Page column 14
(2010/12/18)
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- N,N-DIMETHYL IMIDODICARBONIMIDIC DIAMIDE DICARBOXYLATE, METHOD FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Disclosed herein are a novel dicarboxylic acid salt of N,N-dimethylimidodicarbonimidic diamide, a preparation method thereof and a pharmaceutical composition comprising the same. More specifically, disclosed herein are a novel dicarboxylic acid salt of N,N-dimethylimidodicarbonimidic diamide, a crystalline acid addition salt prepared by allowing N,N-dimethylimidodicarbonimidic diamide to react with a specific dicarboxylic acid, which has improved physical and chemical properties including solubility, stability, non-hygroscopicity and anti-adhesive properties, and low toxicity, and thus is very effective in the prevention and treatment of not only diabetes and its complications in patients with so-called metabolic syndromes, in which diabetes, obesity, hyperlipidemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndromes, etc. appear in combination, but also p53 gene-deficient cancers, muscular pain, muscle cytotoxicity and rhabdomyolysis, as well as a preparation method thereof and a pharmaceutical composition comprising the same.
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Page/Page column 5
(2010/10/19)
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- METFORMIN FOLATE AND PREPARATION OF THE SAME
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The present invention discloses a novel biguanidine compound, i.e. folacin-metformin, and its manufacture with inorganic salt of metformin as raw material. Compared with metformin, the compound has the same clinic curative effect, such as lowering blood sugar, curing poly-cystic ovary syndrome (PCOS), losing weight and so on, without resulting in the increase of homocysteine concentration, even with a little decrease of homocysteine concentration in some cases.
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Page/Page column 4
(2010/05/13)
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- Microparticles With Modified Release of At Least One Active Principle and Oral Pharmaceutical Form Comprising Same
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The invention concerns microparticulate systems with modified release of oral active principle(s). The invention aims at providing a novel pharmaceutical with time-dependent and pH-dependent release mechanism, enabling: a) the latent period preceding the release of the active principle in the stomach; b) the pH triggering the release of the active principle in the intestine; c) the release speed of the active principle. This is achieved through the use of coated microparticles made from particles of active principle each coated with two coating films A and B. A comprises: film-forming (co)polymer (A1) insoluble in fluids of the gastrointestinal tract; ethylcellulose (co)polymer (A2) soluble in fluids of the gastrointestinal tract; plasticizing polyvinylpyrrolidone (A3); castor oil/optionally a surfactant and/or magnesium stearate lubricant (A4). B comprises a hydrophilic polymer (B1) bearing ionized groups with neutral pH (EUDRAGIT? L100-55) and a hydrophobic compound (B2) (LUBRITAB?). The invention also concerns medicines based on said microparticles.
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- The first bioreversible prodrug of metformin with improved lipophilicity and enhanced intestinal absorption
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Metformin is a potent antidiabetic agent and currently used as a first-line treatment for patients with type 2 diabetes. Unfortunately, the moderate absorption and uncomfortable gastrointestinal adverse effects associated with metformin therapy impair its
- Huttunen, Kristiina M.,Mannila, Anne,Laine, Krista,Kemppainen, Eeva,Leppanen, Jukka,Vepsalainen, Jouko,Jarvinen, Tomi,Rautio, Jarkko
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experimental part
p. 4142 - 4148
(2010/02/17)
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- N,N-DIMETHYL IMIDODICARBONIMIDIC DIAMIDE DICARBOXYLATE, METHOD FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Disclosed herein are a novel dicarboxylic acid salt of N,N- dimethylimidodicarbonimidic diamide, a preparation method thereof and a pharmaceutical composition comprising the same. More specifically, disclosed herein are a novel dicarboxylic acid salt of N,N- dimethylimidodicarbonimidic diamide, a crystalline acid addition salt prepared by allowing N,N-dimethylimidodicarbonimidic diamide to react with a specific dicarboxylic acid, which has improved physical and chemical properties including solubility, stability, non-hygroscopicity and anti-adhesive properties, and low toxicity, and thus is very effective in the prevention and treatment of not only diabetes and its complications in patients with so-called metabolic syndromes, in which diabetes, obesity, hyperlipidemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndromes, etc. appear in combination, but also p53 gene-deficient cancers, muscular pain, muscle cytotoxicity and rhabdomyolysis, as well as a preparation method thereof and a pharmaceutical composition comprising the same.
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Page/Page column 18; 23
(2009/04/25)
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- N, N- DIMETHYL IMIDODICARBONIMIDIC DIAMIDE ACETATE, METHOD FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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The present invention relates to N,N -dimethyl imidodicarbonimidic diamide acetate, a method of preparing the same and a pharmaceutical composition comprising the same, and more particularly, to N,N-dimethyl imidodicarbonimidic diamide acetate which is a crystalline acid addition salt prepared by reacting N,N-dimethyl imidodicarbonimidic diamide with acetic acid, and which is very effective as a therapeutic agent for treating metabolic syndromes that glycosuria and diabetes mellitus, obesity, hyperlipidemia, fatty liver, coronary heart disease, osteoporosis, polycystic ovarian syndrome, a cancer depleted of gene P53, etc. are complexly occurred; treating diabetes mellitus and preventing its complication; and treating a cancer and preventing myalgia, muscle cell cytotoxicity and rhabdomyolysis, etc. since the acid addition salt is excellent in physicochemical properties such as solubility, stability, non-hygroscopicity, anti-adhering property, etc., and low toxicity, a method of preparing the same and a pharmaceutical composition comprising the same.
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Page/Page column 26
(2008/12/07)
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- Antidiabetic agent for control of diabetic hyperglycemia and diabetic complications
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Described herein is a compound of Formula I, which is the metformin salt of the naturally occurring endogenous biological compound, (R)-(+) α lipoic acid, pharmaceutical compositions containing the compound of Formula I, and methods of treatment of diabetes or diabetic complications with the compound of Formula I.
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Page/Page column 5
(2008/06/13)
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- USE OF SUBSTITUTED 2 PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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The present invention relates to the use of a substituted 2-phenylbenzimidazole of formula I wherein R1, R2, R3, R 4, R5 and m have the meanings given in the claims, for the preparation of a medicament for the treatment or prevention of diseases involving glucagon receptors, as well as new compounds of formula I wherein R1 is a group of formula
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- COMPOSITIONS AND DOSAGE FORMS FOR ENHANCED ABSORPTION OF METFORMIN
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A complex comprised of metformin and a transport moiety, such as a fatty acid, is described. The complex has an enhanced absorption in the gastrointestinal tract, particularly the lower gastrointestinal tract. The complex, and compositions and dosage forms prepared using the complex, provide for absorption by the body of the drug through a period of ten to twenty-four hours, thus enabling a once-daily dosage form for metformin.
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Page/Page column 34
(2008/06/13)
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- 3-deoxyglucosone and skin
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The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.
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- Combinations comprising dipeptidylpeptidase-iv inhibitor
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The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, α-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and α2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.
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- Composition containing ascorbic acid
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L-ascorbic acid, L-ascorbic acid derivatives and salts thereof can reduce lactic acid levels in blood, and are useful for treating lactic acidosis and the like caused by administration of amoxapine, theophylline, metformin, phenformin, buformin, nalidixic acid, hopantenic acid, azidothymidine, dideoxycytidine, high caloric transfusion, propylene glycol, ethylene glycol, xylitol, lactose, sorbitol or the like.
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- Novel breakers of advanced glycation endproducts
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Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of a variety of debilitating diseases such as diabetes, atherosclerosis, Alzheimer's and rheumatoid arthritis, as well as in the normal aging process. Seven compounds are here reported to be active in breaking AGE-protein cross-links. These compounds are 1,4-benzene-bis[4-methyleneaminophenoxyisobutyric acid] (LR102); 4-[(3,5-dichlorophenylureidophenoxyisobutyryl]-4-aminobenzoic acid (LR99); L-bis-[4-(4-chlorobenzamidophenoxyisobutyryl)cystine] (LR20); 4-(3,5-dichlorophenylureido)phenoxyisobutyryl-1-amidocyclohexane-1-carboxylic acid (LR23); methylene bis [4,4′-(2-chlorophenylureidophenoxyisobutyric acid)] (LR90); 5-aminosalicylic acid (5-ASA); and metformin. These compounds may be used to reverse the debilitating effects of those diseases in which AGEs are formed.
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- Biguanides and derivatives thereof as inhibitors of advanced glycosylation of a target protein
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The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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