- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00803; 00129-00131
(2021/06/26)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety capable of binding to IRAK4 and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.
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Paragraph 00920; 002780-002782
(2021/01/23)
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- Towards New Tricyclic Motifs: Intramolecular C–H Arylation as the Key Step in a Formal [3+3] Cyclocondensation Strategy
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Tricyclic scaffolds structurally related to the well-known benzodiazepine class of drugs show diverse biological activities strikingly different from those of their benzodiazepine counterparts. Interested by this scaffold-hopping perspective, we previousl
- Vrijdag, Johannes L.,De Ruysscher, Dries,De Borggraeve, Wim M.
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p. 1465 - 1474
(2017/04/01)
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- SUBSTITUTED AZOANTHRACENE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
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The present invention is directed to substituted azoanthracene derivatives or pharmaceutically acceptable salts thereof that modulate the human GLP-1 receptor and that may be useful in the treatment of diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial, such as diabetes mellitus type 2. The invention is also directed to pharmaceutical compositions comprising these compounds and to the use of these compounds and compositions in the treatment of such diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial.
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Page/Page column 373-374
(2010/11/03)
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- Pyrazolo[3,4-b]pyridine compounds, and their use as a PDE4 inhibitors
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n-butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl-, —CN, or —CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n-propyl, —C(O)-Me, or —C(O)—C1fluoroalkyl; and R5 is: —C(O)—(CH2)n—Ar, —C(O)-Het, —C(O)—C1-6alkyl, —C(O)—C1 fluoroalkyl, —C(O)—(CH2)2—C(O)—NR15bNR15b, —C(O)—CH2—C(O)—NR15bNR15b, —C(O)—NR15b—(CH2)m1—Ar, —C(O)—NR15b—Het, —C(O)—NR15b—C1-6alkyl, —C(O)—NR5aR5b, —S(O)2—(CH2)m2—Ar, —S(O)2-Het, —S(O)2—C1-6alkyl, or —CH2—Ar; or R4 and R5 taken together are —(CH2)p1—, —(CH2)2—X5—(CH2)2—, —C(O)—(CH2)p2—, —C(O)—N(R15)—(CH2)p3—; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as COPD and the like.
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Page/Page column 141-143
(2009/05/28)
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- Large-scale preparation of 2-methyloxazole-4-carboxaldehyde
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The large-scale preparation of 2-methyloxazole-4-carboxaldehyde presents a significant challenge due to the physical characteristics of the molecule. A method for the preparation of 10-kg batches of 2-methyloxazole-4-carboxaldehyde is described. The key reaction is the reduction of the corresponding N-methoxy-N-methyl amide using lithium aluminium hydride, followed by workup and isolation by crystallization.
- Benoit, Georges-Emmanuel,Carey, John S.,Chapman, Alan M.,Chima, Ranjit,Hussain, Nigel,Popkin, Matthew E.,Roux, Guillaume,Tavassoli, Bahareh,Vaxelaire, Carine,Webb, Michael R.,Whatrup, David
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- Total synthesis of (-)-ulapualide A, a novel tris-oxazole macrolide from marine nudibranchs, based on some biosynthesis speculation
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A new, second generation, total synthesis of ulapualide A (1), whose stereochemistry was recently determined from X-ray analysis of its complex with the protein actin, is described. The synthesis is designed and based on some speculation of the biosynthet
- Pattenden, Gerald,Ashweek, Neil J.,Baker-Glenn, Charles A. G.,Kempson, James,Walker, Gary M.,Yee, James G. K.
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supporting information; experimental part
p. 1478 - 1497
(2008/10/09)
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- PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS, AND THEIR USE AS PDE4 INHIBITORS
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The invention provides a compound of formula (I) or a salt thereof: wherein R2 is H, C1-3alkyl, n butyl, C1-2fluoroalkyl, cyclopropyl, cyclobutyl, (cyclopropyl)methyl , CN, or CH2OH; R3 is inter alia optionally substituted C4-7cycloalkyl or an optionally substituted heterocyclic group (aa), (bb) or (cc); Ra is H, methyl or ethyl; Rb is H or methyl; R4 is H, methyl, ethyl, n propyl, C(O) Me, or C(O) C1fluoroalkyl; and R5 is: C(O) (CH2)n Ar, C(O) Het, C(O) C1 6alkyl, C(O) C1fluoroalkyl, C(O) (CH2)2 C(O) NR15bNR15b, C(O) CH2 C(O) NR15bNR15b, C(O) NR15b (CH2)m1 Ar, C(O) NR15b Het, C(O) NR15b C1-6 alkyl, C(O) NR5aR5b, S(O)2 (CH2)m2-Ar, S(O)2 Het, S(O)2-C1-6alkyl, or CH2 Ar; or R4 and R5 taken together are-(CH2)p1-, (CH2)2 X5 (CH2)2 , C(O) (CH2)p2 ,-C(O)-N(R15) (CH2)p3 ; or NR4R5 is of sub-formula (y), (y1), (y2) or (y3). The invention also provides the use of the compounds as inhibitors of phosphodiesterase type IV (PDE4) and/or for the treatment and/or prophylaxis of inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, allergic rhinitis, psoriasis or atopic dermatitis.
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Page/Page column 211-212; 214-215
(2010/11/26)
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- Towards a total synthesis of ulapualide A. Concise synthetic routes to the tris-oxazole ring system and tris-oxazole macrolide core in ulapualides, kabiramides, halichondramides, mycalolides and halishigamides
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A range of methods for the synthesis of mono-, bis- and tris-2,4-disubstituted oxazoles were evaluated, which led ultimately to a concise synthesis of the three contiguous oxazole ring system 26 in the ulapualide family of 25-membered macrolides, e.g. 1, found in marine organisms. The tris-oxazole macrolide core 30 in ulapualide A (1) was also synthesised based on a macrolactamisation strategy from the two functionalised mono-oxazole precursors 28 and 29, followed by oxazoline 45 and oxazole ring formation, exploiting the methodologies established in the synthesis of linear bis- and tris-oxazoles in the formation of 18 and 26. The tris-oxazole 26 was converted into the corresponding phosphonium salt 5 in readiness for elaboration to ulapualide A (1). The Royal Society of Chemistry 2000.
- Chattopadhyay, Shital K.,Kempson, James,McNeil, Alan,Pattenden, Gerald,Reader, Michael,Rippon, David E.,Waite, David
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p. 2415 - 2428
(2007/10/03)
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