- GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
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A compound, enantiomer, prodrug, diastereomer, or salt is provided which is an activator of the enzyme glucokinase and thus is believed to be useful in treating diabetes and related diseases, which compound has the structure (I). A method for treating diabetes and related disease employing the compound, enantiomer, prodrug, diastereomer, or salt is also provided.
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Page/Page column 43; 44
(2018/02/28)
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- A extractant composition and its preparation method and application
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The invention discloses an extractant composition as well as a preparation method and an application thereof. The composition comprises the following components in percentages by weight: a component A: 80-99.99wt% of dialkyl phosphinic acid with a structure shown in a formula I; a component B: 0-5wt% of dialkyl phosphinic acid with a structure shown in a formula II; a component C: 0-5wt% of dialkyl phosphinic acid alkyl ester with a structure shown in a formula III; a component D: 0-10wt% of alkyl phosphorous acid mono alkyl ester with a structure shown in a formula IV; wherein, the component B, C and D are not zero at the same time, and the sum of the component A, B, C and D is always 100wt%. The extractant composition containing synergistic extractant components is prepared, the composition is used as an extractant and can be widely applied to rare earth metals, especially separation and purification of cobalt nickel bimetals, and compared with monocomponent extraction agents, the composition has more excellent extraction performance; compared with bis (2,4,4-trimethylpentyl)-phosphinic acid, other synergistic extractant components are easy to synthesize, and production cost of the product is reduced.
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Paragraph 0092; 0093
(2018/11/22)
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- Novel triclabendazole prodrug: A highly water soluble alternative for the treatment of fasciolosis
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In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 showed excellent aqueous stability (>95% after 26?h) at pH 7, making it ideal for developing pharmaceutical compositions in the form of solutions that can easily be hydrolyzed by the enzyme alkaline phosphatase (t?=?13.6?s) to liberate the precursor compound. An aqueous solution of MFR-5 administered intramuscularly to sheep at concentrations of 4, 6 and 8?mg/kg presented a fasciolicidal efficiency of 96.5%, 98.4% and 99.2%, respectively. In the in vivo experiments, MFR-5 reduced 100% the excretion of eggs in all of the above concentrations.
- Flores-Ramos, Miguel,Ibarra-Velarde, Froylán,Jung-Cook, Helgi,Hernández-Campos, Alicia,Vera-Montenegro, Yolanda,Castillo, Rafael
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supporting information
p. 616 - 619
(2017/01/17)
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- NOVEL HYDROSOLUBLE COMPOUNDS DERIVED FROM BENZIMIDAZOLE USED IN TREATING FASCIOLOSIS
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The present invention relates to hydrosoluble compounds derived from benzimidazole represented by general formula I: wherein: Y1 e Y2 are independently O or S, and at least one of Y1 and Y2 is O; R1 and R2 are independently hydrogen or a cation, both are hydrogen or both are cations; R3 is a C1-4 alkyl; R4 and R5 are independently halogen or a —OR6 alkoxide; R6 is C6-C10 aryl linked in 5- or 6-position of benzimidazole nucleus.
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Paragraph 0059-0062
(2017/12/15)
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- METHODS OF BLADDER CANCER TREATMENT WITH CICLOPIROX, CICLOPIROX OLAMINE, OR A CICLOPIROX PRODRUG
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A method of treating bladder cancer is provided. The method of treating bladder cancer can include: providing a pharmaceutical composition having ciclopirox or ciclopirox olamine or a ciclopirox-POM prodrug having a structure of one of the formulae provided herein or derivative thereof or stereoisomer thereof or pharmaceutically acceptable salt thereof; and administering the pharmaceutical composition to a subject having the bladder cancer. The ciclopirox or ciclopirox olamine or a ciclopirox-POM prodrug can be administered in a therapeutically effective amount.
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Paragraph 095
(2016/06/06)
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- 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator
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Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.
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Page/Page column 37
(2016/08/29)
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- METHOD OF TREATMENT WITH PRODRUGS OF 6-CYCLOHEXYL-1-HYDROXY-4-METHYLPYRIDIN IN-2-1H-ONE AND DERIVATIVES THEREOF
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A prodrug can have a structure of Formula 10 or derivative thereof or stereoisomer thereof or pharmaceutically acceptable salt thereof. The prodrug can be included in a pharmaceutical composition for use in treatment of fungus, cancer, dermatitis, superficial mycoses; inflammation, tinea pedis, tinea cruris, and tinea corporis, Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis, candidiasis (moniliasis), Candida albicans, tinea (pityriasis) vesicolor, Malassezia furfur, acute myeloid leukemia, acute lymphoid leukemia, chronic myelogenous leukemia, lymphoma or multiple myeloma.
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Paragraph 0063
(2015/04/28)
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- A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis
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This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
- Flores-Ramos, Miguel,Ibarra-Velarde, Froyln,Hernndez-Campos, Alicia,Vera-Montenegro, Yolanda,Jung-Cook, Helgi,Cant-Alarcn, Germinal J.,Del Rivero, Lauro Misael,Castillo, Rafael
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supporting information
p. 5814 - 5817
(2015/02/18)
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- Development of efficient processes for the preparation of Di-tert-butyl potassium phosphate and Di-tert-butyl (Chloromethyl) phosphate
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A new and efficient process to prepare di-tert-butyl (chloromethyl) phosphate, a key compound in the formation of many phosphon-oxymethyl pro-drugs, from chloromethyl chlorosulfate (CMCS) and di-tert-butyl potassium phosphate (DTBPP) is described. To develop a process to this important compound with overall efficiency, an improved synthesis of DTBPP was required. The two-step process to DTBPP starts from PCl3 and leverages a H2O 2/catalytic KI mediated oxidation of di-tert-butyl phosphite to provide DTBPP in 81% yield and high purity. In the development of the new process to di-tert-butyl (chloromethyl) phosphate, a comparison to the corresponding tosylate derivative was made. A rational selection of base, phase-transfer catalyst (PTC), and stabilizing additive minimized CMCS decomposition and led to an optimized yield (90% solution yield), improved product purity, and identification of a technique to enable the long-term storage of di-tert-butyl (chloromethyl) phosphate.
- Zheng, Bin,Fox, Richard J.,Sugiyama, Masano,Fritz, Alan,Eastgate, Martin D.
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p. 636 - 642
(2014/06/09)
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- Substituted 4-phenyl pyridines having anti-emetic effect
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Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor. The compounds have the general formula (I):
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Page/Page column 33
(2013/05/08)
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- Antibacterial Compounds
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The present invention provides a compound of the following formula, salts, racemates, diastereomers, enantiomers, esters, carbamates, phosphates, sulfates, deuterated forms and prodrugs thereof. Also provided is the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture.
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Paragraph 0652
(2013/10/07)
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- PHOSPHATE PRODRUGS
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Phosphate and phosphonate prodrug derivatives, for example of Formula IV; where p, A, LA, and R1, R3-R6 are as defined herein, are useful for treating various disorders, including diarrhea.
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Paragraph 0227; 0228
(2013/03/26)
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- PHENYLQUINAZOLINE DERIVATIVES
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Novel quinazolinamide derivatives of the formula (I), in which R1-R43 and X have the meanings indicated in claim 1, are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.
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Paragraph 0932; 0933
(2013/07/19)
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- PURINE COMPOUNDS AS PRODRUGS OF A2B ADENOSINE RECEPTOR ANTAGONISTS, THEIR PROCESS AND MEDICINAL APPLICATIONS
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The present disclosure relates to purine compounds of formula (I) or formula (II) or its tautomers, polymorphs, stereoisomers, solvates or a pharmaceutically acceptable salts, or pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by thereof as A2B adenosine receptor antagonists. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders that may be susceptible to improvement by the mediation of adenosine A2B receptor. Such conditions include, but are not limited to, asthma, chronic obstructive pulmonary disorder, angiogenesis, pulmonary fibrosis, emphysema, allergic diseases, inflammation, reperfusion injury, myocardial ischemia, atherosclerosis, hypertension, congestive heart failure, retinopathy, diabetes mellitus, obesity, inflammatory gastrointestinal tract disorders including inflammatory bowel disease, sickle cell disease, and/or autoimmune diseases, and to their use in treating mammals for various disease states, such as gastrointestinal disorders, immunological disorders, hypersensitivity disorders, neurological disorders, and cardiovascular diseases due to both cellular hyperproliferation and apoptosis, and the like. The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
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Paragraph 0295
(2013/07/19)
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- CHEMICAL COMPOUNDS
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The present invention relates to compounds of Formula (I): and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds inhibit Bcl-2 and/or Bcl-XL activities and may be used for the treatment of cancer.
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Page/Page column 52
(2012/02/15)
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- PURINE COMPOUNDS AS PRODRUGS OF A2B ADENOSINE RECEPTOR ANTAGONISTS, THEIR PROCESS AND MEDICINAL APPLICATIONS
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The present disclosure relates to purine compounds of formula (I) or formula (II) or its tautomers, polymorphs, stereoisomers, solvates or a pharmaceutically acceptable salts, or pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by thereof as A2B adenosine receptor antagonists. {Formulas should be inserted here} The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders that may be susceptible to improvement by the mediation of adenosine A2B receptor. Such conditions include, but are not limited to, asthma, chronic obstructive pulmonary disorder, angiogenesis, pulmonary fibrosis, emphysema, allergic diseases, inflammation, reperfusion injury, myocardial ischemia, atherosclerosis, hypertension, congestive heart failure, retinopathy, diabetes mellitus, obesity, inflammatory gastrointestinal tract disorders including inflammatory bowel disease, sickle cell disease, and/or autoimmune diseases. and to their use in treating mammals for various disease states, such as gastrointestinal disorders, immunological disorders, hypersensitivity disorders, neurological disorders, and cardiovascular diseases due to both cellular hyperproliferation and apoptosis, and the like. The present disclosure also relates to methods for the preparation of such compounds, and to pharmaceutical compositions containing them.
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Page/Page column 39
(2012/04/04)
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- Use of A2B Adenosine Receptor Antagonists for Treating Pulmonary Hypertension
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This disclosure relates generally to treating patients having pulmonary hypertension, or symptoms associated therewith, by administering a therapeutically effective amount of an A2B receptor antagonist to the patient.
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- RAF INHIBITORS AND THEIR USES
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The present invention provides imidazooxazole and imidazothiazole compounds and their syntheses. The compounds of the present invention are capable of inhibiting the activity of RAF kinase, such as B-RAF V600E. The compounds are useful for the treatment of cell proliferative disorders such as cancer.
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Page/Page column 38-39
(2010/06/20)
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- HETEROCYCLIC UREA DERIVATIVES AND METHODS OF USE THEREOF
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Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
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Page/Page column 66
(2010/12/29)
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- BHQ-CAGED NUCLEOTIDE PROBES PHOTOLYSABLE BY TWO-PHOTON EXCITATION
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The disclosure encompasses caged compounds such as caged nucleoside phosphoesters (caged nucleotides). In an embodiment, the caged nucleotides include compounds corresponding to those described by formula (I) that may be activated by two-photon excitation, and methods of synthesis of such compounds. 8-Bromo-7-hydroxyquinoline-caged ATP was synthesized and examined for its photochemistry as a biologically useful, temporally and spatially controlled ATP-releasing reagent. The combination of two-photon excitation hydrolysis and activation of caged ATP enables methods for finely focusing ATP activation at the sub-cellular level or to a greater depth of activation, thereby providing improved resolution of ATP-dependent processes at the cellular level.
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- CARBONATE PRODRUGS AND METHODS OF USING THE SAME
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The present invention provides carbonate prodrugs which comprise a carbonic phosphoric anhydride prodrug moiety attached to the hydroxyl or carboxyl group of a parent drug moiety. The prodrugs may provide improved physicochemical properties over the parent drug. Also provided are methods of treating a disease or condition that is responsive to the parent drug using the carbonate prodrugs, as well as kits and unit dosages.
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Page/Page column 38
(2009/12/27)
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- PRODRUGS AND METHODS OF MAKING AND USING THE SAME
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Prodrugs of parent drugs and methods of making and using the same are described. The prodrugs comprise an amine-containing parent drug moiety and a prodrug moiety, such as methoxyphosphonic acid or ethoxyphosphonic acid. The prodrugs may be employed in therapy for the treatment of various indications, such as pain, and in methods of decreasing the abuse potential of abuse-prone drugs and/or delaying the onset of parent drug activity and/or prolonging parent drug activity as compared to administration of a parent drug.
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Page/Page column 63
(2008/12/06)
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- QUINOLINE DERIVATIVES
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The invention relates to new quinoline derivatives which are active CLK-1 inhibitors. More specifically, the CLK-1 inhibitors of the invention are compounds of formula (A). The invention also relates to pharmaceutical compositions comprising such compounds and to methods for the prophylaxis and/or treatment of disorders or their associated symptoms for which the inhibition of CLK-1 is beneficial.
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Page/Page column 59
(2008/06/13)
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- Prodrugs of A2B adenosine receptor antagonists
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Disclosed are prodrugs of A2B adenosine receptor antagonists, and their use in treating mammals for various disease states.
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Page/Page column 12-13
(2008/06/13)
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- WATER SOLUBLE PRODRUGS OF TERTIARY AMINE CONTAINING DRUGS AND METHODS OF MAKING THEREOF
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The present invention is drawn to water soluble derivatives aliphatic acid aromatic secondary and tertiary amine containing drugs. The present invention is further drawn to methods of making water soluble derivatives of aliphatic and aromatic secondary and tertiary amine containing drugs.
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Page/Page column 15
(2008/06/13)
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- Novel prodrug approach for tertiary amines: Synthesis and preliminary evaluation of N-phosphonooxymethyl prodrugs
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The synthesis and preliminary evaluation of a novel prodrug approach for improving the water solubility of drugs containing a tertiary amine group are reported. The prodrug synthesis involves a nucleophilic substitution reaction between the parent tertiary amine and a novel derivatizing reagent, di-tert- butyl chloromethyl phosphate, resulting in formation of the quaternary salt. The tertiary butyl groups are easily removed under acidic conditions with trifluoroacetic acid giving the N-phosphonooxymethyl prodrug in the free phosphoric acid form, which can subsequently be converted to the desired salt form. The synthesis was successfully applied to a model compound (quinuclidine) and to three tertiary amine-containing drugs (cinnarizine, loxapine, and amiodarone). The prodrugs were designed to undergo a two-step bioreversion process. The first step was an enzyme-catalyzed rate-determining dephosphorylation followed by spontaneous chemical breakdown of the N- hydroxymethyl intermediate to give the parent drug. Selected prodrugs were shown to be substrates for alkaline phosphatase in vitro. A preliminary in vivo study confirmed the ability of the cinnarizine prodrug to be rapidly and completely converted to cinnarizine in a beagle dog following iv administration.
- Krise, Jeffrey P.,Zygmunt, Jan,Georg, Gunda I.,Stella, Valentino J.
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p. 3094 - 3100
(2007/10/03)
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- Synthesis of Trialkyl Phosphates from White Phosphorus
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A new method was proposed for preparing trialkyl phosphates directly from white phosphorus by its electrolysis in a mixture of acetonitrile, alcohol, and water with tetraethylammonium iodide as supporting electrolyte. To increase the amount of the product synthesized in the unit volume of the electrolyte solution and the productivity of the process, phosphorus and water are added to the electrolyte in portions, which allows synthesis of up to 1 mol of trialkyl phosphate in 1 1 of the electrolyte solution.
- Romakhin,Nikitin
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p. 1023 - 1026
(2007/10/03)
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- OXYGEN- AND SULFUR-CAPPED ORGANOTIN CLUSTERS
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The synthesis and structural features of the oxygen-capped cluster, t)2)3O>t)2> (1), are compared to that of the analogous formulations containing framework sulfur atoms in place of oxygens, t)2)3S>t)2>*2H2S*H2O (2) and (3).Solution NMR, 119Sn and 31P, indicate that the solid state structures determined by X-ray analysis are retained in solution.
- Schmid, Charles G.,Day, Roberta O.,Holmes, Robert R.
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