- A Bifunctional Copper Catalyst Enables Ester Reduction with H2: Expanding the Reactivity Space of Nucleophilic Copper Hydrides
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Employing a bifunctional catalyst based on a copper(I)/NHC complex and a guanidine organocatalyst, catalytic ester reductions to alcohols with H2 as terminal reducing agent are facilitated. The approach taken here enables the simultaneous activation of esters through hydrogen bonding and formation of nucleophilic copper(I) hydrides from H2, resulting in a catalytic hydride transfer to esters. The reduction step is further facilitated by a proton shuttle mediated by the guanidinium subunit. This bifunctional approach to ester reductions for the first time shifts the reactivity of generally considered "soft"copper(I) hydrides to previously unreactive "hard"ester electrophiles and paves the way for a replacement of stoichiometric reducing agents by a catalyst and H2.
- Kaicharla, Trinadh,Ngoc, Trung Tran,Teichert, Johannes F.,Tzaras, Dimitrios-Ioannis,Zimmermann, Birte M.
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supporting information
p. 16865 - 16873
(2021/10/20)
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- IMMUNOMODULATORY COMPOUNDS
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Disclosed are immunomodulatory compounds, pharmaceutical compositions containing them, and methods of making and using the compounds to treat diseases and disorders characterized by aberrant protein activity that can be targeted by cereblon.
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 246-247
(2020/10/21)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE
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This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are useful for the treatment of oncological, auto-immune, and inflammatory diseases caused by aberrant B-cell activation. Also disclosed are compositions containing compounds of Formula I and at least one carrier, diluent or excipient.
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- 3,4-Dihydro-1,3,5-triazin-2(1H)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer's Disease
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One of the main obstacles toward the discovery of effective anti-Alzheimer drugs is the multifactorial nature of its etiopathology. Therefore, the use of multitarget-directed ligands has emerged as particularly suitable. Such ligands, able to modulate different neurodegenerative pathways, for example, amyloid and tau cascades, as well as cognitive and neurogenic functions, are fostered to come. In this respect, we report herein on the first class of BACE-1/GSK-3β dual inhibitors based on a 3,4-dihydro-1,3,5-triazin-2(1H)-one skeleton, whose hit compound 1 showed interesting properties in a preliminary investigation. Notably, compound 2, endowed with well-balanced potencies against the two isolated enzymes (IC50 of 16 and 7 μM against BACE-1 and GSK-3β, respectively), displayed effective neuroprotective and neurogenic activities and no neurotoxicity in cell-based assays. It also showed good brain permeability in a pharmacokinetic assessment in mice. Overall, triazinone derivatives, thanks to the simultaneous modulation of multiple points of the diseased network, might emerge as suitable candidates to be tested in in vivo Alzheimer's disease models.
- Prati, Federica,De Simone, Angela,Armirotti, Andrea,Summa, Maria,Pizzirani, Daniela,Scarpelli, Rita,Bertozzi, Sine Mandrup,Perez, Daniel I.,Andrisano, Vincenza,Perez-Castillo, Ana,Monti, Barbara,Massenzio, Francesca,Polito, Letizia,Racchi, Marco,Sabatino, Piera,Bottegoni, Giovanni,Martinez, Ana,Cavalli, Andrea,Bolognesi, Maria L.
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p. 1665 - 1682
(2015/11/09)
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- TREATMENT OF DISEASES BY EPIGENETIC REGULATION
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The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of cancer, including NUT midline carcinoma, Burkitt's Lymphoma, Acute Myelogenous Leukemia, and Multiple Myeloma; autoimmune or inflammatory diseases or conditions, and sepsis.
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Paragraph 0581; 0583
(2013/11/05)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 47
(2008/12/07)
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- 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
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The present invention relates to novel compounds, in particular novel pyridinone de- rivat ives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds accord- ing to the invention are positive allosteric mod
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- AZOLE METHYLIDENE CYANIDE DERIVATIVES AND THEIR USE AS PROTEIN KINASE MODULATORS
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The present invention is related to azole derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such azole derivatives. Said azole derivatives are modulators of the protein kinase signalling pathways, particularly the one involving c-Jun N-terminal kinase and/or Glycogen Kinase Synthase 3. The present invention is furthermore related to novel azole derivatives as well as to methods of their preparation. X is O, S or NR0, with R0 being H or an unsubstituted or substituted C1 -C6 alkyl; A is 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl group.
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