- Vicarious nucleophilic substitution: A dramatically shortened synthesis of 2-amino-6-nitrobenzoic acid labelled with carbon-14
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Literature preparations of 2-amino-6-nitrobenzoic acid are usually based on phthalic anhydride. In order to make [benzene-14C(U)]-2-amino-6- nitrobenzoic acid, [benzene-14C(U)]-phthalic anhydride has to be prepared in multiple steps from [14C(U)]-benzene, resulting in an unacceptably lengthy 14-step synthesis. We have been able to develop a completely different method of synthesis, producing [benzene- 14C(U)]-2-amino-6-nitrobenzoic acid from [14C(U)]-benzene in just four steps with an overall radiochemical yield of 32%.
- Kelly, Terence P.,Filer, Crist N.,Wright, Christopher
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- SOLID FORMS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES
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Solid forms comprising 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)- piperidine-2,6-dione, compositions comprising the solid forms, methods of making the solid forms and methods of their uses are disclosed.
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Paragraph 00427
(2018/09/28)
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- METHODS FOR TREATING CHRONIC LYMPHOCYTIC LEUKEMIA AND THE USE OF BIOMARKERS AS A PREDICTOR OF CLINICAL SENSITIVITY TO IMMUNOMODULATORY THERAPIES
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A method of identifying a subject having chronic lymphocytic leukemia (CLL) who is likely to be responsive to a treatment compound, comprising obtaining a first sample and a second sample from the subject having CLL; administering 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A) to the first sample and administering lenalidomide to the second sample; determining the level of a biomarker in the first sample and determining the level of the biomarker in the second sample; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the first sample is different from the level of the biomarker in the second sample.
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Paragraph 00342
(2017/02/28)
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- METHODS FOR TREATING DIFFUSE LARGE B-CELL LYMPHOMA AND THE USE OF BIOMARKERS AS A PREDICTOR OF RESPONSIVENESS TO DRUGS
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In one aspect, provided herein are methods for predicting the responsiveness of DLBCL patients to treatment with lenolidomide or Compound A; or a stereoisomer thereof; or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate thereof; or a polymorph thereof utilizing biomarkers or classfiers that correlate with responsiveness to one of these drugs. In another aspect, provided herein are methods for treating a DLBCL patient determined to be responsive to treatment with lenolidomide or Compound A; or a stereoisomer thereof; or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate thereof; or a polymorph thereof utilizing biomarkers or classifiers (or output thereof) that correlate with responsiveness to one of these drugs.
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Paragraph 00171
(2017/04/11)
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- CYCLING THERAPY USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE
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Provided herein are methods of treating, preventing and/or managing cancer, including lymphoma, which comprise administering to a patient 3-(5-amino-2-methyl-4- oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof in a cyclic therapy regimen.
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Paragraph 00203
(2017/08/04)
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- COMPOSITIONS AND METHODS FOR INDUCING CONFORMATIONAL CHANGES IN CEREBLON AND OTHER E3 UBIQUITIN LIGASES
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Provided herein are compositions, therapeutic methods, screening methods, computational methods and biomarkers based upon the elucidation of the interaction among cereblon, its substrates and certain compounds or agents, including small molecules, peptides, and proteins.
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Paragraph 00458
(2017/07/14)
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- METHODS FOR TREATING SOLID TUMORS AND THE USE OF BIOMARKERS AS A PREDICTOR OF CLINICAL SENSITIVITY TO IMMUNOMODULATORY THERAPIES
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A method of identifying a subject having a solid tumor who is likely to be responsive to a treatment compound, comprising: administering the treatment compound to a subject having the solid tumor; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject, and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker.
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Paragraph 00463
(2016/05/24)
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- Methods for the treatment of cancer and inflammatory diseases using cereblon as a predictor
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Uses of the protein cereblon as a predictor of clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.
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- Zn-Catalyzed Enantio- and Diastereoselective Formal [4 + 2] Cycloaddition Involving Two Electron-Deficient Partners: Asymmetric Synthesis of Piperidines from 1-Azadienes and Nitro-Alkenes
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We report a catalytic asymmetric synthesis of piperidines through [4 + 2] cycloaddition of 1-azadienes and nitro-alkenes. The reaction uses earth abundant Zn as catalyst and is highly diastereo- and regioselective. A novel BOPA ligand (F-BOPA) confers high reactivity and enantioselectivity in the process. The presence of ortho substitution on the arenes adjacent to the bis(oxazolines) was found to be particularly impactful, due to limiting the undesired coordination of 1-azadiene to the Lewis acid and thus allowing the reaction to be carried out at lower temperature. A series of secondary kinetic isotope effect studies using a range of ligands implicates a stepwise mechanism for the transformation, involving an initial Michael-type addition of the imine to the nitro-alkene followed by a cyclization event. The stepwise mechanism obviates the electronic requirement inherent to a concerted mechanism, explaining the successful cycloaddition between two electron-deficient partners. (Chemical Equation Presented).
- Chu, John C. K.,Dalton, Derek M.,Rovis, Tomislav
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supporting information
p. 4445 - 4452
(2015/04/14)
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- COMPOSITIONS AND METHODS FOR INDUCING CONFORMATIONAL CHANGES IN CEREBLON OTHER E3 UBIQUITIN LIGASES
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Provided herein are compositions, therapeutic methods, screening methods, computational methods and biomarkers based upon the elucidation of the interaction among cerebloR, its substrates and certain compounds or agents, including small molecules, peptides, and proteins.
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- METHODS FOR THE TREATMENT OF LOCALLY ADVANCED BREAST CANCER
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Provided herein are methods of treating, preventing and/or managing locally advanced breast cancer, including inflammatory breast cancer, which comprise administering to a patient one or more immunomodulatory compounds or enantiomers or mixtures of enantiomers thereof, or pharmaceutically acceptable salts, solvates, hydrates, co-crystals, clathrates, or polymorphs thereof.
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Page/Page column 59
(2014/03/26)
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- Substituent-guided switch between C-H activation and decarboxylative cross-coupling during palladium/copper-catalyzed cascade reactions of 2-aminobenzoates with 2-haloarylaldehydes
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Cascade switch: Phenanthridines, pyrazole[4,3-c]quinolines and isocryptolepine were prepared in one step from the Pd/Cu-catalyzed reaction between potassium 2-aminobenzoates and 2-haloarylaldehydes (see scheme). Although the reactions of 2-aminobenzoates proceeded via a cascade imination/C-H functionalization, the reactions of 6-nitro-2-aminobenzoates ensued via a tandem imination/decarboxylative cross-coupling. Copyright
- Bhowmik, Subhendu,Pandey, Garima,Batra, Sanjay
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supporting information
p. 10487 - 10491
(2013/08/23)
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- QUINAZOLINONE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 25-26
(2012/07/13)
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- METHODS OF TREATING CANCER USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE
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Provided herein are methods of treating, preventing and/or managing cancers, which comprise administering to a patient 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.
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- SOLID FORMS OF 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE, AND THEIR PHARMACEUTICAL COMPOSITIONS AND USES
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Solid forms comprising 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, compositions comprising the solid forms, methods of making the solid forms and methods of their uses are disclosed
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- PYRAZINYL CARBOXAMIDES AS FUNGICIDES
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This present disclosure is related to the field of pyrazine carboxamides and their derivatives and the use of these compounds as fungicides.
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Page/Page column 7
(2011/12/14)
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- PROCESS FOR THE PREPARATION OF AN ANTHRANILIC ACID DERIVATIVE
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The present invention relates to a novel a process for the preparation of a compound of formula (I) which process comprises adding 1 to 2 mol of sodium hypochlorite with a concentration of 8% to 15% by weight to a suspension of the compound of formula (II) in aqueous sodium hydroxide at a temperature of 5 to 60°C, wherein the concentration of sodium hydroxide in the suspension is from 5 to 25 % by weight; and acidifying the reaction mass with concentrated hydrochloric acid to a pH of 1.5 to 2.0 and wherein said process is carried out as a one-pot synthesis without isolation of intermediates.
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Page/Page column 4-5
(2011/09/15)
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- AUTOMATED RADIOSYNTHESIS
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The present invention provides a method to obtain radiofluorinated compounds useful for in vivo imaging GABAA receptors. The method of the invention is high-yielding and may conveniently be carried out on an automated synthesizer such as FastlabTM. A further aspect of the invention is a cassette suitable for carrying out the automated method of synthesis of the invention. Novel precursor compounds useful in the method of the invention are also provided, as are a number of novel compounds obtained by the method of the invention.
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Page/Page column 27
(2011/04/26)
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- METHODS FOR PRODUCING AMINONITROBENZOIC ACIDS
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Methods of producing aminonitrobenzoic acids are disclosed. A dinitrobenzoic acid may be reduced to an aminonitrobenzoic acid. In some specific embodiments, 2,6- dinitrobenzoic acid may be converted to 2-amino-6-nitrobenzoic acid. An end product may be used as an intermediate in the manufacture of various compounds including agricultural chemicals and pharmaceuticals.
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Page/Page column 9-10
(2010/04/30)
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- Pyrrolidine(thi)ones Substituted by Heterocyclic Substituents in The 3-Position
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Pyrrolidine(thi)one compounds substituted by heterocyclic substituents in the 3-position, their preparation and use in pharmaceutical compositions, in particular as immunomodulators for treatment and/or inhibition of inflammatory and autoimmune diseases and haematological-oncological diseases.
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Page/Page column 18
(2009/01/20)
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- 5-SUBSTITUTED QUINAZOLINONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
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Provided are 5-substituted quinazolinone compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
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Page/Page column 51
(2010/11/30)
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- PROCESS FOR THE PRODUCTION OF AMIDES
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The present invention relates to a process for the preparation of compounds of formula (I) wherein R1 and R2 are each independently of the other hydrogen or C1-C5alkyl and R3 is CF3or CF2H, by a) reaction of a compound of formula (Il) wherein R1 and R2 are as defined for formula (I), with at least one reducing agent to form a compound of formula (III) wherein R1 and R2 are as defined for formula (I), and b) reaction of that compound with at least one reducing agent to form a compound of formula (IV) wherein R1 and R2 are as defined for formula (I), and (c) reaction of that compound with a compound of formula (V) wherein Q is chlorine, fluorine, bromine, iodine, hydroxy or C1-C6alkoxy and R3 is as defined for formula (I), to form the compound of formula (I); and to novel intermediates for use in that process.
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Page/Page column 38
(2008/06/13)
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- 2-ureido-benzamide derivatives
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This invention is concerned with 2-ureido-benzamide compounds of the formula (1) STR1 in which R1 is H, halogen atom, (C1 -C4)alkyl, (C1 -C4)alkoxy or (C1 -C4)dialkylamino and R2 is H, halogen atom, hydroxy, nitro, (C1 -C4)alkyl, (C1 -C4)alkoxy, (C3 -C6) cycloalkylmethoxy, (C1 -C4) alkylthio, (C1 -C4) alkylsulfinyl, (C1 -C4)alkylsulfonyl or STR2 wherein j is an integer of from 0 to 2 and R3 and R4 are each independently H, (C1 -C4)alkyl, (C1 -C4)alkanoyl, (C1 -C4)alkylsulfonyl or (C1 -C4)alkylcarbamoyl, NR3 R4 can to form a pyrrolidine, piperidine, morpholine, imidazole or pyrazole ring; X is a (C3 -C15)alkyl, (C3 -C6) cycloalkyl, (C3 -C6) cycloalkylmethyl, ω-(C1 -C4) alkoxy-(C1 -C4) alkyl group or STR3 wherein k is an integer of from 1 to 4 and R5 and R6 are each independently H, Y is H or (C1 -C4)alkyl and Z is STR4 wherein m is an integer of from 0 to 4.
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- Thermal Stability Studies on a Homologous Series of Nitroarenes
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The thermal stabilities of a number of nitroarenes were examined in solution and in condensed phase.In general, increasing the number of nitro groups decreased thermal stability.Changing the substituent on 1-X-2,4,6-trinitrobenzene from X = H to NH2 to CH3 to OH accelerated decomposition; this effect was attributed to increased ease of intramolecular proton transfer to an ortho nitro group, thus weakening the carbon-nitrogen bond.In solution, the effect of increasing substitution from n = 1 to n = 3 on Xn(NO2)3C6H3-n was uniformly that of decreasing the thermal stability of the species.However, in condensed phase, results suggested that crystal habit may be more important than molecular structure; for X = Br, CH3, and NH2, the more substituted species was the more stable.
- Oxley, Jimmie C.,Smith, James L.,Ye, Hong,McKenney, Robert L.,Bolduc, Paul R.
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p. 9593 - 9602
(2007/10/02)
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- DESIGN OF ANTINEOPLASTIC AGENTS ON THE BASIS OF THE "2-PHENYLNAPHTHALENE-TYPE" STRUCTURAL PATTERN.I. SYHTHESIS OF SUBSTITUTED 3-PHENYLQUINAZOLONES, BENZOXAZOLOQUINAZOLONES AND BENZOTHIAZOLOQUINAZOLONES
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A number of substituted 3-phenylquinazolin-4-ones, 12H-benzoxazoloquinazolin-12-ones and 12H-benzothiazoloquinazolin-12-ones were designed and synthesized on the basis of a "2-phenylnaphthalene-type" structural pattern hypothesis.The posulated pattern, which was uncovered among a substantial number of compounds of both natural and synthetic origins, was noted to be associated with compounds possessing a variety of biological properties which include the antineoplastic activity.Several compounds designed for the present study were found to exhibit potentcytotoxicity against the growth of human promyelocytic leukemia (HL-60)cells.
- Cheng, Chia-Chung,Liu, Den-Fu,Chou, Ting-Chao
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p. 775 - 789
(2007/10/02)
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- Role of Intermolecular Reactions in Thermolysis of Aromatic Nitro Compounds in Supercritical Aromatic Solvents
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Several nitroarenes were decomposed isothermally in dilute supercritical solution in benzene or toluene and in the vapor phase in the temperature range of 290-380 deg C in sealed glass tubes with pressure up to 100 MPa.The mechanisms of thermolysis are inferred from kinetic studies and product analysis.The initial rate-controlling step for nitrobenzene and p-nitrotoluene decomposition is probably intermolecular hydrogen abstraction to form an ArNO2H radical intermediate.The nature of the transition state is deduced from the activation volume (ΔV*), H/D kinetic-isotope effect, and a linear free-energy relationship between the ionization potential of the hydrogen donor and the logarithm of the decomposition rate.A concurrent pathway for o-nitrotoluene is an intramolecular reaction in which anthranil is an intermediate.The behavior of 1,3-dinitrobenzene and 1,4-dinitrobenzene resembles that of nitrobenzene, whereas 2,4-dinitrotoluene and 2,6-dinitrotoluene decompose in the same manner as o-nitrotoluene.Activation parameters are given and detailed mechanisms proposed.
- Minier, Leanna M.,Brower, Kay R.,Oxley, Jimmie C.
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p. 3306 - 3314
(2007/10/02)
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