60 results about "Morpholino Oligos" patented technology

The present invention provides a kit and a method for targeting of a diagnostic or therapeutic agent to a target site in a mammal having a pathological condition. The kit comprises, in separate containers, (a) a first conjugate comprising a targeting moiety and a Morpholino oligomer, wherein the targeting moiety selectively binds to a primary, target-specific binding site of the target site or to a substance produced by or associated with the target site; (b) optionally, a clearing agent; and (c) a second conjugate comprising a complementary Morpholino oligomer and a diagnostic agent or therapeutic agent. The method comprises administering (a), optionally (b), and (c) to a mammal.

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picomoviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 1240 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.

This invention provides quinazoline derivatives represented by the structural formula: (I); wherein: R2 is hydrogen, NR′R″, C1-7 alkyl, arylC1-7 alkyl or C3-10 cycloalkyl; R4 is amino, C1-7 alkyl, C2-7 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, aryl, heterocyclic, arylalkyl, heterocyclic-substituted C1-7 alkyl or C3-10 cycloalkyl-C1-7 alkyl; R5 is hydrogen or C1-7 alkyl, or R5 and R4 together with the nitrogen atom to which they are attached form a heterocyclic ring; Y is a single bond, C1-7alkylene, C2-7 alkenylene or C2-7 alkynylene; R6 is halogen, heteroaryl or aryl; R′ and R″ are each independently hydrogen, C1-7 alkyl-carbonyl or C1-7 alkyl; provided that R4 is not phenyl substituted with morpholino when R2 is H and R5 is H, and provided that when NR4R5 is piperazinyl, said NR4R5 is either non-substituted or substituted with methyl or acetyl; a pharmaceutically acceptable addition salt, a stereoisomer, a mono- or a di-N-oxide, a solvate or a pro-drug thereof, for the treatment of viral infections.

The present invention relates to antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. Exemplary antisense antiviral compounds are substantially uncharged, or partially positively charged, morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 30 bases of the 5′ or 3′ terminus of the positive sense vcRNA; c) the 45 bases surrounding the AUG start codon of an influenza viral mRNA and; d) 50 bases surrounding the splice donor or acceptor sites of influenza mRNAs subject to alternative splicing.

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornoviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.

Morpholino-based oligomers suitable as antisense agent comprising modifications of phosphorodiamidate backbone or modification with 5-substituted pyrimidines of morpholino compound that is soluble in culture medium and sufficient for cell penetration thereby eliminating the need for injecting into the cells. Monomers comprising the said oligomers and its method of manufacture, method of manufacture of the said oligomers and its dye, flurophore, drug, biomolecule conjugate wherein the said oligomers find different end use but not limited to regulation of gene expression, tissue culture with improved transfection efficiency and related studies on cellular transfection.

The present invention provides bicyclic morpholino compounds and oligomeric compounds prepared therefrom. More particularly, incorporation of one or more of the bicyclic morpholino compounds into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

The present invention relates to heterocyclic compounds represented by the formula Iwherein X represents nitrogen atom or CH; R1 represents halogen atom or hydroxyl; R2 represents hydrogen atom, hydroxyl or amino; R3 represents morpholino (which may be substituted with one or two C1–C6 alkyl), pyrrolidinyl (which may be substituted with hydroxy C1–C6 alkyl) or NR6R7 [R6 represents C1–C6 alkyl and R7 represents piperidinyl (which may be substituted with C1–C6 alkyl)]; R4 and R5 each represents hydrogen atom or C1–C6 alkyl, with the proviso that R2 is hydrogen atom and R3 is pyrrolidinyl (which may be substituted with hydroxy C1–C6 alkyl) when R1 is hydroxyl

The invention provides sense antiviral compounds and methods of their use in inhibition of growth of viruses of the Flaviviridae, Picornoviridae, Caliciviridae, Togaviridae, Coronaviridae families and hepatitis E virus in the treatment of a viral infection. The sense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of (12-40) subunits, including at least (12) subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 3′-terminal end (40) bases of the negative-sense RNA strand of the virus.

The invention relates to a fluorescent probe used for conducting linkage detection on superoxide anions (O2.-) and hydrogen polysulfide, in particular to a fluorophore derivative for detecting superoxide anions and hydrogen polysulfide and application thereof. The fluorophore derivative is shown in the general formula I. In the general formula I, R1 represents a C1-22 alkyl group or a halogenated benzyl group or C1-C12 organic acid ester chains; R2 represents hydrogen, a sulfonic group or an amino group or a carboxyl group or a nitro group or halogen; X (a positioning functional group) represents -OH, a butyl triphenyl phosphonium group, an N-propyl morpholino group, a biotin group, a folic acid group, a glycosyl chain group, benzyl chloride or a C1-22 alkyl group; Y1 represents N, O or S; Y2 represents N, O or S. In the presence of the superoxide anions (O2.-) and the hydrogen polysulfide, corresponding fluorescence emission wavelength and intensity change, and the fluorescent probe can be used for detecting the superoxide anions (O2.-) and the hydrogen polysulfide in organisms, interference of external detection conditions can be greatly reduced, the detection signal to noise ratio is high, and sensitivity and selectivity are good. The fluorophore derivative has important significance in biomedicine.

The present invention relates to heterocyclic compounds represented by the formula I wherein X represents nitrogen atom or CH; R1 represents halogen atom or hydroxyl; R2 represents hydrogen atom, hydroxyl or amino; R3 represents morpholino (which may be substituted with one or two C1-C6 alkyl), pyrrolidinyl (which may be substituted with hydroxy C1-C6 alkyl) or NR6R7 [R6 represents C1-C6 alkyl and R7 represents piperidinyl (which may be substituted with C1-C6 alkyl)]; R4 and R5 each represents hydrogen atom or C1-C6 alkyl, with the proviso that R2 is hydrogen atom and R3 is pyrrolidinyl (which may be substituted with hydroxy C1-C6 alkyl) when R1 is hydroxyl

A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein X represents CH or N; represents a C1-C12 alkyl; R2 represents a hydrogen atom, or the like; R′ represents a C1-C6 alkyl or the like; q represents 0 or an integer of 1 to 7; Y represents a C1-C6 alkyl or the like; p represents 0 or an integer of 1 to 5; R represents a 2,3-dihydroindolyl or the like, which is used for preventive and / or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).

The invention provides a perfusion stock composition, for preserving a donor organ for transplantation, comprising: a source of 60 to 100 mM Na+; a source of 10 to 20 mM K+; a source of 5 to 10 mM Mg2−; a source of 0.25 to 0.75 mM Ca2+; 10 to 40 mM Tris(hydroxymethyl)aminomethane hydrochloride (Tris or THAM), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 3-(N-morpholino)propanesulfonic acid (MOPS), 2-(N-morpholino)ethanesulfonic acid (MES), N, / N-bis-(2-hydroxyethyl)-2-aminoethansulfonic acid (BES), or N / -tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES); a source of 10 to 30 mM HCO3−; 1 to 30 mM glucose; 1 to 20 U / L insulin; 1 to 10 mM fructose diphosphate or a salt thereof; 1 to 40 mM aspartate or glutamate; 1 to 10 mM adenosine, cAMP or cGMP; 1 to 10 mM reduced glutathione; and 30 to 100 mM lactobionate or mannitol; and optionally a diluent. The invention also provides a perfusion composition, a kit, a method, and a perfusion apparatus, each related to the perfusion stock composition.

The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

This invention provides pH buffered plant nutrient compositions, methods for fertilizing a plant growing or a seed germinating in a hydroponics system, methods for growing a plant in a hydroponics system, and methods for making a pH buffered plant nutrient composition. The compositions and methods of this invention are useful with distilled water, deionized water, filtered water, and United States municipal tap water. The compositions and methods of this invention are useful with most of the municipal water supplies in the United States. pH buffering agents useful in the practice of this invention include phosphate buffers, aquarium buffers, 2-[N-morpholino]ethanesulfonic acid, and mixtures thereof.

The present invention relates to a ractopamine immunomagnetic bead separation enrichment kit comprising ractopamine monoclonal antibody coupled magnetic beads, a reconstitution fluid and a magnet, the ractopamine monoclonal antibody coupled magnetic beads are prepared by mixing ractopamine monoclonal antibody and magnetic beads in the mass ratio of 1: 500 to 800 and dissolving in 2-(N-morpholino) ethanesulfonic acid monohydrate for coupling, and the ractopamine monoclonal antibody is prepared by using a conjugate obtained from ractopamine hapten and bovine serum albumin as an immunogen to immunize Balb / c mice. The present invention also relates to a sample pre-processing method of the ractopamine immunomagnetic bead separation enrichment kit for separating ractopamine, the method has high ractopamine specificity, recovery rate and accuracy, simplifies sample preprocessing steps, and avoids use of a variety and a large number of organic solvents in the sample preprocessing process.

The present invention provides a compound of the formula (I) wherein R1 is —H, —OH, —O(C1-C4 alkyl), —OCOC6H5, —OCO(C1-C6 alkyl), or —OSO2(C2-C6 alkyl); R0, R2 and R3 are each independently —H, —OH, —O(C1-C4 alkyl), —OCOC6H5, —OCO(C1-C6 alkyl), —OSO2(C2-C6 alkyl) or halo; R4 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; X is —S— or —HC═CH—; G is —O—, —S—, —SO—, SO2, or —N(R5), wherein R5 is —H or C1-C4 alkyl; and Y is —O—, —S—, —NH—, —NMe-, or —CH2—; or a pharmaceutically acceptable salt thereof; pharmaceutical compositions thereof, optionally in combination with estrogen and progestin; methods of inhibiting a disease associated with estrogen deprivation; and methods for inhibiting a disease associated with an aberrant physiological response to endogenous estrogen.

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof,wherein one of R1 and R2 is H, and the other is selected from C1-8-alkyl, C3-6-cycloalkyl and C1-8-alkyl-C5-10-aryl; R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl and 1-methylcyclopentyl; R9 is selected from the following:wherein:R4 is selected from C1-8-alkyl and C3-8-cycloalkyl; G is selected from: CH, CMe and N; E is selected from: O, S, SO2, NH, NMe and N-oxide (N→O); J and R are independently selected from: CH, N and N-oxide (N→O); andR41 is selected from amino, methylamino, dimethylamino, isopropylamino, isopropyl(methyl)amino, cyclopropylamino, cyclopropyl(methyl)amino, cyclopentylamino, morpholino, piperidin-1-yl, piperidin-1-ylmethyl, morpholinomethyl, 4-methylpiperazin-1-yl, 4-(2-methoxyethyl)piperazin-1-yl, 1-morpholino ethyl, 1-(dimethylamino)ethyl, 1-(methylamino)ethyl, 4-fluoro-1-methylpyrrolidin-2-yl, 4,4-difluoropiperidin-1-yl, piperidin-4-yl, 1-methylpiperidin-4-yl, pyridin-3-ylamino, pyridin-2-ylamino, 1-methylpyrrolidin-3-yl, methyl, isopropyl.The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of various diseases.

The invention relates to the use of Polycefin-LLL nanoconjugate as a means of cytoplasmic delivery of drugs. In one embodiment, the present invention provides a drug delivery molecule, comprising a polymerized carboxylic acid molecular scaffold covalently linked to L-leucylleucylleucine. In another embodiment, the Polycefin-LLL includes drug antisense morpholino oligos, targeting antibodies, and a pH-sensitive endosome escape unit. In addition, the drug could be siRNA, microRNA, and aptamer.

The invention relates to a promega for testing glycolated hemoglobin by using an enzymatic method, which contains the ingredients of hemolysis buffer: 10-1000 mmol / L of N-chclohexyl-2 ethyl amine sulfoacid, 10-1000mmol / L of morpholino propane sulfoacid, and 1-100g / L of polyethylene glycol oxide dodecyl ether; reagent R1a: 10-1000kU / L of pepsin of pig, 0.1-10mmol / L of 2-(iodophenyl)-3-(2, 4-dinitro benzene)-5-(2, 4-sulfophenyl)-2H tetrazole sodium salt, and 0.0001-0.1mol / L of HCl; reagent R1b: 0.1-10mmol / L of morpholino ethane sulfonic acid, and 0.5-50mmol / L of CaCl2; neutralization buffer: 0.0001-0.1mol / L of NaOH reagent, 2:1-1000kU / L of fructose valine oxidase, 30-600kU / L of peroxydase, 0.01-0.5mmol / L of N-(carboxymethyl aminocarbonyl)-4,4 quadri (dimethyl amine)-diphenylamine sodium salt, and 10-1000mmol / L of Tris-HCl. The promega has the zymohydrolysis effect which is better than alkalescence prolease, little dosage, low cost and accurate measuring result.

A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof: wherein X represents CH or N; C07D 413 / 04 C07D 413 / 14 A61K 31 / 5377 A61P 25 / 28 0 119 17 2005 / 9 / 9 101035781 2007 / 9 / 12 000000000 Mitsubishi Pharma Corp. Japan Watanabe Kazutoshi Uehara Fumiaki Hiki Shinsuke Kohara Toshiyuki Fukunaga Kenji Yokoshima Satoshi dingye beng zhangtian shu 11112 The MEdical and Hygienical Patent Agency of Beijing City No.59 Beiwei Road, Xuanwu District of Beijing 100050 Japan 2004 / 9 / 9 296926 / 2004 2007 / 3 / 9 PCT / JP2005 / 017080 2005 / 9 / 9 WO2006 / 028290 2006 / 3 / 16 English

The invention discloses a synthetic medium for Staphylococcus carnosus, and a preparation method and application of Staphylococcus carnosus fermentation broth. The synthetic medium for Staphylococcus carnosus comprises the following raw materials by weight: on the basis of a volume of 1 L, 10 to 50 g of anhydrous glucose, 0.1 to 1.5 g of lysine, 1.0 to 5.0 g of valine, 0.1 to 1.5 g of glycine, 1.0 to 5.0 g of arginine, 1.0 to 5.0 g of proline, 5 to 10.0 g of glutamic acid, 0.1 to 0.5 g of tryptophan, 0.1 to 1.5 g if cystine, 1.0 to 3.0 mg of thiamine hydrochloride, 1.0 to 3.0 mg of calcium pantothenate, 1.0 to 3.0 mg of nicotinic acid, 1.0 to 3.0 mg of manganese sulfate, 0.1 to 1.0 g of potassium dihydrogen phosphate, 0.1 to 0.8 g of magnesium sulfate heptahydrate, 0.005 to 0.010 g of ferrous sulfate heptahydrate, 1.0 to 5.0 g of dipotassium hydrogen phosphate trihydrate and 6 to 10 g of 3-(N-morpholino)propanesulfonic acid, with the balance being water. The invention also discloses a preparation method for the Staphylococcus aureus fermentation broth. The synthetic medium for Staphylococcus carnosus is reasonable in composition, rich in nutrients and capable of meeting the growth demands of Staphylococcus carnosus. The growth amount of Staphylococcus carnosus obtained through the synthetic medium provided by the invention is increased by 5% compared with the growth amount of Staphylococcus carnosus obtained through frequently used LB (Luria-Bertani) mediums.

A compound of Formula (I):or a salt or solvate thereof, wherein:One of R1 and R2 is H and the other represents —NHCONHR4,wherein R4 representsa phenyl or naphthyl group which may be optionally substituted by one or more substituents independently selected from —C1-6 alkyl, —C1-6 haloalkyl, halogen, C1-6 alkoxy, C1-6 haloalkoxy, OH, NO2,C3-7 cycloalkyl, indanyl, orR4 together with the NH to which it is bonded forms a morpholino group; andR3 is H or NHR5 wherein R5 isH, -quinolinyl or -isoquinolinyl,—(CONH)p phenyl wherein p is 0 or 1 and the phenyl is optionally substituted by one or more substituents independently selected from halogen, —C1-6 alkyl, —C1-6 haloalkyl, -morpholino, —SO2NH2, and methyl substituted benzothiazole.

The invention provides a method for preparing pinaverium bromide and an intermediate thereof, which relate to the pharmaceutical process. The cis isomer content of the intermediate 2-[2-(2-morpholino-2-ethoxy-ethyl)]-6, 6-dimethyl nopyl alkyl is high and the cis-isomer content of the obtained pinaverium bromide is more than or equal to 99 percent. The intermediate 2-[2-(2-morpholino-2-ethoxy-ethyl)]-6, 6-dimethyl nopyl alkyl is prepared by collecting cut fraction of 133-134 DEG C under 270 Pa.