- THIOBENZOIMIDAZOLE AS FUNGICIDES
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The present invention relates to 2-thiobenzimidazoles of formula (I) which are of use as fungicides.
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Page/Page column 65
(2018/08/03)
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- AZIRIDINE CONTAINING EPOTHILONE ANALOGS, METHODS OF SYNTHESIS, METHODS OF TREATMENT, AND DRUG CONJUGATES
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In one aspect, the present disclosure provides epothilone analogs of the formula: (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle 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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- EPOTHILONE ANALOGS, METHODS OF SYNTHESIS, METHODS OF TREATMENT, AND DRUG CONJUGATES THEREOF
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In one aspect, the present disclosure provides epothilone analogs of the formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.
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- 12,13-Aziridinyl Epothilones. Stereoselective Synthesis of Trisubstituted Olefinic Bonds from Methyl Ketones and Heteroaromatic Phosphonates and Design, Synthesis, and Biological Evaluation of Potent Antitumor Agents
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The synthesis and biological evaluation of a series of 12,13-aziridinyl epothilone B analogues is described. These compounds were accessed by a practical, general process that involved a 12,13-olefinic methyl ketone as a starting material obtained by ozonolytic cleavage of epothilone B followed by tungsten-induced deoxygenation of the epoxide moiety. The attachment of the aziridine structural motif was achieved by application of the Ess-Kürti-Falck aziridination, while the heterocyclic side chains were introduced via stereoselective phosphonate-based olefinations. In order to ensure high (E) selectivities for the latter reaction for electron-rich heterocycles, it became necessary to develop and apply an unprecedented modification of the venerable Horner-Wadsworth-Emmons reaction, employing 2-fluoroethoxyphosphonates that may prove to be of general value in organic synthesis. These studies resulted in the discovery of some of the most potent epothilones reported to date. Equipped with functional groups to accommodate modern drug delivery technologies, some of these compounds exhibited picomolar potencies that qualify them as payloads for antibody drug conjugates (ADCs), while a number of them revealed impressive activities against drug resistant human cancer cells, making them desirable for potential medical applications.
- Nicolaou,Rhoades, Derek,Wang, Yanping,Bai, Ruoli,Hamel, Ernest,Aujay, Monette,Sandoval, Joseph,Gavrilyuk, Julia
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p. 7318 - 7334
(2017/06/06)
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- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
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- QUINOLINES 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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- Novel 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Paragraph 0439; 0442
(2015/02/19)
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- MK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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- 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 126
(2014/03/26)
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- SUBSTITUTED BICYCLIC AZA-HETEROCYCLES AND ANALOGUES AS SIRTUIN MODULATORS
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Provided herein are novel substituted bicyclic aza-heterocycle 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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- 3 -AMINO- PYRAZOLE DERIVATIVES USEFUL AGAINST TUBERCULOSIS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof: Wherein: Het is a 5 to 10-membered heteroaromatic ring; Either X is N and Y is CR5; or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and C1-2alkyl; R2 is selected from H, C1-2alkyl, OH, —CH2OH and C1-2alkoxy; Each R3 is independently selected from OH, C1-3alkyl, F, Cl, Br, NH2, and C1-3alkoxy; R4 is selected from C1-3alkyl and haloC1-3alkyl; R5 is selected from H, C1-3alkyl and haloC1-3alkyl; R6 and R7 are either i) each independently selected from H, C1-3alkyl and C1-3alkoxy; or ii) R6 and R7 together with the ring to which they are attached form a 9-membered bicyclic ring; p is 0-3; and RA is selected from H and C1-3alkyl, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Paragraph 0232; 0233
(2013/08/15)
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- 3 -AMINO- PYRAZOLE DERIVATIVES USEFUL AGAINST TUBERCULOSIS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof: (I), Wherein: Het is a 5 to 10-membered heteroaromatic ring; Either X is N and Y is CR5; or X is C and Y is S; Z is selected from N and CH; R1 is selected from H and C1-2alkyl; R2 is selected from H, C1-2alkyl, OH, -CH2OH and C1-2alkoxy; Each R3 is independently selected from OH, C1-3alkyl, F, Cl, Br, NH2, and C1-3alkoxy; R4 is selected from C1-3alkyl and haloC1-3alkyl; R5 is selected from H, C1-3alkyl and haloC1-3alkyl; R6 and R7 are either i) each independently selected from H, C1-3alkyl and C1-3alkoxy; or ii) R6 and R7 together with the ring to which they are attached form a 9-membered bicylic ring; p is 0-3; and RA is selected from H and C1-3alkyl, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided.
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Page/Page column 26-27
(2012/05/04)
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- Design, synthesis of some new (2-aminothiazol-4-yl)methylester derivatives as possible antimicrobial and antitubercular agents
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A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by 1H NMR, 13C NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffractio
- Karuvalam, Ranjith P.,Haridas, Karickal R.,Nayak, Susanta K.,Guru Row, Tayur N.,Rajeesh,Rishikesan,Kumari, N. Suchetha
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experimental part
p. 172 - 182
(2012/03/27)
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- NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
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Compounds are provided which are activators of the enzyme glucokinase and thus are useful in treating diabetes and related diseases, which compounds have the structure wherein R1, R2, R3, R4, R5, R6, Y and X are as defined herein or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related disease employing the above compounds is also provided.
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- 3-SUBSTITUED IMIDAZO (4, 5-B) PYRIDINES AND 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 e
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- BENZIMIDAZOLES AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are sirtuin-modulating compounds of formula (II) 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 94
(2010/04/03)
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- 8-SUBSTITUTED QUINOLINES AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are 8-substituted quinolines and related analogues as sirtuin-modulating compounds of Structural Formula (I) 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 131
(2010/09/18)
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- BENZOXAZOLES, BENZTHIAZOLES 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 79-80
(2010/04/03)
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- AZABENZIMIDAZOLES 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 e
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Page/Page column 125-126
(2010/08/09)
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- IMIDAZOPYRIDINE 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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- NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
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Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R4 is —(CH2)n-Z-(CH2)m—PO(OR7)(OR8), —(CH2)nZ-(CH2)m—PO(OR7)Rg, —(CH2)n-Z-(CH2)m—OPO(OR7)Rg, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10);R5 and R6 are independently selected from H, alkyl and halogen;Y is R7(CH2)s or is absent; andX, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
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Page/Page column 89
(2008/06/13)
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- Naphthyridin derivatives
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The present invention relates to heterocyclic derivatives of formula I wherein R1, R2 and R3 are as defined in the description and claims, which compounds are metabotropic glutamate receptor 5 antagonists.
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Page/Page column 32
(2008/06/13)
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- Substituted heteroaryl amide modulators of glucocorticoid receptor, AP-1, and/or NF-kB activity and use thereof
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The present invention relates to new class of non-steroidal compounds which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory- and immune-associ
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Page/Page column 37-38
(2008/06/13)
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- Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes
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Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.
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Page column 139
(2010/02/07)
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- Heteroaromatic compounds containing a phosphonate group that are inhibitors of fructose-1,6-bisphosphatase
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FBPase inhibitors of the formula I and X are useful in the treatment of diabetes and other conditions associated with elevated blood glucose or excess glycogen storage.
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- Novel bisamidate phosphonate prodrugs
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Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA: and their use in the treatment of diabetes and other conditions associated with elevated blood glucose.
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