- BIFUNCTIONAL MOLECULES CONTAINING AN E3 UBIQUITINE LIGASE BINDING MOIETY LINKED TO A BCL6 TARGETING MOIETY
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Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00358; 00359
(2021/04/23)
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- COMPOUNDS AND METHODS FOR TARGETED DEGRADATION OF KRAS
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Bifunctional compounds, which find utility as modulators of Kirsten ras sarcoma protein (KRas or KRAS), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the Von Hippel-Lindau E3 ubiquitin ligase and on the other end a moiety which binds KRas, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The heterobifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00238
(2021/10/15)
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- POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1464; 1465
(2020/03/29)
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- MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 00686-00687; 00887-00888
(2019/10/29)
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- HYDROXYL PURINE COMPOUNDS AND USE THEREOF
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Disclosed are a series of hydroxyl purine compounds and the use thereof as PDE2 or TNFα inhibitors, in particular, the compounds as shown in formula (I), or tautomers thereof or pharmaceutically acceptable salts thereof.
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Paragraph 0159; 0160; 0161
(2018/04/05)
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- TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 0661
(2018/05/24)
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- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BROMODOMAIN-CONTAINING PROTEINS
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The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.
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Paragraph 00226
(2017/03/21)
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- NOVEL COMPOUNDS
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Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 72; 73
(2015/12/17)
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- Catalytic asymmetric cyclopropanation of heteroaryldiazoacetates
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Rh2(S-DOSP)4-catalyzed decomposition of heteroaryldiazoacetates in the presence of styrene results in highly diastereoselective and enantioselective cyclopropanations. Heteroaryldiazoacetates containing both electron-rich and electron-deficient heterocycles, such as thiophene, furan, pyridine, indole, oxazole, isoxazole, and benzoxazole, are effective in this chemistry. These studies broaden the range of diazo compounds containing both electron-withdrawing and electron-donating groups, which undergo highly diastereoselective cyclopropanations.
- Davies,Townsend
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p. 6595 - 6603
(2007/10/03)
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- 7-[3-Substituted isoxazol-5-yl]-acetamido-cephalosporanic acids and their anti-bacterial use
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Novel heterocyclic amides of the formula STR1 wherein R is selected from the group consisting of lower alkyl and aryl optionally substituted with at least one member of the group consisting of chlorine, fluorine, nitro, amino and lower alkyl and a tertiary alkyl group, R1 is selected from the group consisting of hydrogen, lower alkyl, carboxyl, lower alkoxycarbonyl, an alkali metal, alkaline earth metal or amine salt of carboxyl, a carbamyl, cyano, an amino and chlorine, R2 is selected from the group consisting of hydrogen, halogen, cyano, an amino, lower aralkoxycarbonylamino, lower alkyl, carboxyl esterified with lower alkyl, aryl or aralkyl and carbamoyl optionally substituted on the nitrogen atom with lower alkyl or a phenyl and Q is selected from the group consisting of STR2 X is selected from the group consisting of hydrogen, hydroxy and lower alkanoyloxy and U is selected from the group consisting of amido forming groups or a group OY, wherein Y is selected from the group consising of hydrogen, salt forming groups, and ester forming groups, or COOY and CH2 X together form a lactone or lactam, having antibacterial properties, their preparation and novel intermediates thereof.
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