- Photochemistry of Axially Chiral (Arylmethylene)cycloalkanes: A Search for Suitable Photoswitchable Liquid Crystalline Materials
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A series of chiral (arylmethylene)cycloalkanes was synthesized in racemic and optically active form to examine their suitability for incorporation in a liquid crystal-based optical switch.Irradiation of these compounds with UV light leads to their rapid p
- Lemieux, Robert P.,Schuster, Gary B.
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- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds of formula (I) useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Paragraph 0592-0593; 0744-0746
(2021/05/15)
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- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Paragraph 0602; 0603; 0604
(2020/05/21)
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- DIHYDROPYRIMIDINE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF HBV INFECTION OR OF HBV-INDUCED DISEASES
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The application describes dihydropyrimidine derivatives which are useful in the treatment or prevention of HBV infection or of HBV-induced diseases, more particularly of HBV chronic infection or of diseases induced by HBV chronic infection, as well as pharmaceutical or medical applications thereof.
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Page/Page column 39; 80
(2020/01/24)
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- HETEROARYLDIHYDROPYRIMIDINE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS
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Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.
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Page/Page column 121; 122
(2019/01/17)
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- Copper-Catalyzed Radical C-C Bond Cleavage and [4+1] Annulation Cascade of Cycloketone Oxime Esters with Enaminothiones
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Carbon-carbon bond formation is among the most important reactions in organic synthesis. Reconstruction of a carbon-carbon bond through ring-opening C-C bond cleavage of a strained carbocycle usually occurs via a thermodynamically preferable pathway. However, carbon-carbon bond formation through thermodynamically less favorable C-C bond cleavage has seldom been documented. Herein, we disclose an unusual C-C bond cleavage of cycloketone oxime esters for [4+1] annulation. Under anaerobic copper(I) catalysis, cycloketone oxime esters underwent regioselective, thermodynamically less favorable radical C-C bond cleavage followed by annulation with enaminothiones; that is, α-thioxo ketene N,S-acetals efficiently affording 2-cyanoalkyl-aminothiophene derivatives. Cyclobutanone, -pentanone, -hexanone, and -heptanone oxime esters could act as the effective C1 building blocks in the annulation reaction. An iminyl radical mechanism is proposed for the rare C-C bond cleavage/[4+1] annulation cascade.
- He, Yuan,Lou, Jiang,Wu, Kaikai,Wang, Hongmei,Yu, Zhengkun
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supporting information
(2019/02/14)
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- Structure-based design of tricyclic NF-κB inducing kinase (NIK) inhibitors that have high selectivity over phosphoinositide-3-kinase (PI3K)
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We report here structure-guided optimization of a novel series of NF-κB inducing kinase (NIK) inhibitors. Starting from a modestly potent, low molecular weight lead, activity was improved by designing a type 11/2 binding mode that accessed a back pocket past the methionine-471 gatekeeper. Divergent binding modes in NIK and PI3K were exploited to dampen PI3K inhibition while maintaining NIK inhibition within these series. Potent compounds were discovered that selectively inhibit the nuclear translocation of NF-κB2 (p52/REL-B) but not canonical NF-κB1 (REL-A/p50).
- Castanedo, Georgette M.,Blaquiere, Nicole,Beresini, Maureen,Bravo, Brandon,Brightbill, Hans,Chen, Jacob,Cui, Hai-Feng,Eigenbrot, Charles,Everett, Christine,Feng, Jianwen,Godemann, Robert,Gogol, Emily,Hymowitz, Sarah,Johnson, Adam,Kayagaki, Nobuhiko,Kohli, Pawan Bir,Knüppel, Kathleen,Kraemer, Joachim,Krüger, Susan,Loke, Pui,McEwan, Paul,Montalbetti, Christian,Roberts, David A.,Smith, Myron,Steinbacher, Stefan,Sujatha-Bhaskar, Swathi,Takahashi, Ryan,Wang, Xiaolu,Wu, Lawren C.,Zhang, Yamin,Staben, Steven T.
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supporting information
p. 627 - 640
(2017/02/05)
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- HETEROCYCLIC COMPOUND
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The present invention provides a compound having an MAGL inhibitory action, and useful as an agent for the prophylaxis or treatment of neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, glaucoma, multiple sclerosis etc.), anxiety disorder, pains (e.g., inflammatory pain, cancerous pain, neurogenic pain etc.), epilepsy, depression and the like. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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Paragraph 0685; 0686
(2017/10/17)
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- Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease
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Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). To further extend this concept, we designed and synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors, and we validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate our hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into molecules with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit), and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing (Cuadrado-Tejedor, M.; Garcia-Barroso, C.; Sánchez-Arias, J. A.; Rabal, O.; Mederos, S.; Ugarte, A.; Franco, R.; Segura, V.; Perea, G.; Oyarzabal, J.; Garcia-Osta, A. Neuropsychopharmacology 2016, in press, doi: 10.1038/npp.2016.163).
- Rabal, Obdulia,Sánchez-Arias, Juan A.,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,García-Barroso, Carolina,Ugarte, Ana,Estella-Hermoso De Mendoza, Ander,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
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supporting information
p. 8967 - 9004
(2016/10/22)
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- NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
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Page/Page column 77
(2014/09/16)
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- AMINO ACID COMPOUNDS
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[Problem] To provide novel compounds that are S1P1 receptor agonists and exhibit an immunosuppressive activities by inducing lymphocyte sequestration in secondary lymphoid tissues. In addition, to provide a pharmaceutical agent which comprises the compounds as an effective component, in particular to provide a therapeutic and/or prophylactic agent for an autoimmune disease and the like. [Solving Means] Amino acid compounds that are represented by the following Formula (1) are provided
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Page/Page column 44
(2009/12/23)
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- AMINO CYCLOBUTYLAMIDE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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The present invention is directed to compounds of the formulas I and II : wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R15, R16, R17, R18, R19, R25, R26, Y, Z, l, m, n and the broken lines are as defined herein which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.
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