- Intramolecular radical rearrangement reactions of 2-methyleneaziridines: Application to the synthesis of substituted piperidines, decahydroquinolines, and octahydroindolizines
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(matrix presented) Intramolecular 5-exo cyclization of 3-(2-methyleneaziridin-1-yl)propyl radicals leads to the generation of a highly strained, bicyclic aziridinylcarbinyl radical that undergoes C-N bond fission to the ring-expanded aminyl radical. This
- Prevost, Natacha,Shipman, Michael
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- Stereoselective Diboration of Spirocyclobutenes: A Platform for the Synthesis of Spirocycles with Orthogonal Exit Vectors
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The diastereo- and enantioselective diboration of spirocyclobutenes provides a platform for the rapid preparation of a wide variety of chiral spirocyclic building blocks. The chemoselective functionalization of the carbon-boron bond in the products, including a stereospecific sp3-sp2 Suzuki–Miyaura cross-coupling reaction, provides a powerful tool to control the directionality and the nature of the exit vectors in the spirocyclic framework.
- Nóvoa, Luis,Trulli, Laura,Parra, Alejandro,Tortosa, Mariola
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supporting information
p. 11763 - 11768
(2021/04/26)
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- AMIDE DERIVATIVES COMPRISING HETEROCYCLOALKYL RING
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PROBLEM TO BE SOLVED: To provide compounds or pharmacologically acceptable salts thereof that have excellent EP300 and/or CREBBP histone acetyltransferase inhibitory activity. SOLUTION: The invention provides compounds represented by the formula (1) in the figure or pharmacologically acceptable salts thereof. (In the formula (1), ring Q1, ring Q2, ring Q3, X and L are as defined in the specification.) SELECTED DRAWING: None COPYRIGHT: (C)2020,JPO&INPIT
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Paragraph 0239-0241
(2020/05/20)
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- Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders
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Dermatologic disorders such as atopic dermatitis arise from genetic and environmental causes and are complex and multifactorial in nature. Among possible risk factors, aberrant immunological reactions are one of the leading etiologies. Immunosuppressive agents including topical steroids are common treatments for these disorders. Despite their reliability in clinical settings, topical steroids display side effects, typified by skin thinning. Accordingly, there is a need for alternate effective and well-tolerated therapies. As part of our efforts to investigate new immunomodulators, we have developed a series of JAK inhibitors, which incorporate novel three-dimensional spiro motifs and unexpectedly possess both excellent physicochemical properties and antidermatitis efficacy in the animal models. One of these compounds, JTE-052 (ent-60), also known as delgocitinib, has been shown to be effective and well-tolerated in human clinical trials and has recently been approved in Japan for the treatment of atopic dermatitis as the first drug among Janus kinase inhibitors.
- Noji, Satoru,Hara, Yoshinori,Miura, Tomoya,Yamanaka, Hiroshi,Maeda, Katsuya,Hori, Akimi,Yamamoto, Hiroshi,Obika, Shingo,Inoue, Masafumi,Hase, Yasunori,Orita, Takuya,Doi, Satoki,Adachi, Tsuyoshi,Tanimoto, Atsuo,Oki, Chika,Kimoto, Yukari,Ogawa, Yoshihiro,Negoro, Tamotsu,Hashimoto, Hiromasa,Shiozaki, Makoto
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p. 7163 - 7185
(2020/09/11)
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- SPIROCYCLIC MOLECULES AS PROTEIN KINASE INHIBITORS
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The present invention relates to spirocyclic compounds of formula I, namely spirocyclic (1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fiuorophenyl) ethoxy)pyridin-2-amines having protein kinase inhibitory activity, and methods of synthesizing and using such compounds. Preferred compounds are c-Met and/or ALK inhibitors useful for the treatment of abnormal cell growth, such as cancers
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Paragraph 00253-00255
(2013/03/26)
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- New spirocyclic Δ2-isoxazoline derivatives related to selective agonists of α7 neuronal nicotinic acetylcholine receptors
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A set of structural analogues of spirocyclic quinuclidinyl- Δ2-isoxazolines, characterized as potent and selective α7 nicotinic agonists, was prepared and assayed for binding affinity at α7 and α4β2 neuronal nicotinic acetylcholine receptors (nAChRs). The investigated derivatives (3a-3c, 4a-4c, 5a-5c, 6a-6c, and 7a-7c), synthesized via the 1,3-dipolar cycloaddition of nitrile oxides to suitable dipolarophiles, showed an overall reduced affinity at the α7 subtype when compared with their model compounds. Solely Δ2-isoxazolines 3a, 3b, and 6c maintained a binding affinity in the nanomolar range at the α7 nAChRs (Ki = 230, 420 and 700 nM, respectively). The quaternary ammonium salt 6c retained also a noteworthy α7 vs. α4β2 subtype selectivity, whereas 3a and 3b showed a sharp reduction in selectivity compared with 1a and 1b, their quinuclidinyl higher homologues.
- Dallanoce, Clelia,Frigerio, Fabio,Grazioso, Giovanni,Matera, Carlo,Visconti, Giacomo Luca,De Amici, Marco,Pucci, Luca,Pistillo, Francesco,Fucile, Sergio,Gotti, Cecilia,Clementi, Francesco,De Micheli, Carlo
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scheme or table
p. 5790 - 5799
(2012/01/05)
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- THIENOPYRIDAZINE COMPOUNDS, THEIR PREPARATIONS, PHARMACEUTICAL COMPOSITIONS AND USES
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The present invention relates to thienopyridazine compounds of formula (I), their pharmaceutically acceptable salts or hydrates, wherein R1 and R2 are independently H or C1-4 alkyl, R3 is a saturated or unsaturated 5- or 6- membered ring containing N, S or O, or its optical isomers, R4 is a halophenyl monosubstituted or disubstituted at any position. The present invention provides the preparation methods of these compounds, pharmaceutical compositions containing these compounds and the uses of these compounds, particularly in treating cancer.
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Page/Page column 28-29
(2010/11/03)
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- Novel Compounds and Therapeutic Use Thereof for Protein Kinase Inhibition
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Novel compound having the following formula: Also disclosed are a pharmaceutical compositions comprising the same, methods for treating cancer using the same, and methods for the synthesis of the same. The novel compounds of the present invention are found to inhibit protein kinases, especially Checkpoint kinase Chk1/Chk2.
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Page/Page column 13; 17
(2009/12/02)
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- INHIBITORS OF PHOSPHODIESTERASE TYPE-IV
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The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.
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Page/Page column 44
(2008/06/13)
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- NOVEL BENZOFURAN DERIVATIVES, WHICH CAN BE USED IN PROPHYLAXIS OR TREATMENT OF 5-HT6 RECEPTOR-RELATED DISORDER
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The present invention relates to compounds of formula (I): wherein P, R3, W1, and W2 are as described herein, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament against 5-HT6 receptor-related disorders.
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Page/Page column 165-166
(2010/02/12)
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- Synthesis of substituted piperidines, decahydroquinolines and octahydroindolizines by radical rearrangement reactions of 2-alkylideneaziridines
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Rearrangement of a variety of 3-(2-methyleneaziridin-1-yl)propyl radicals, generated using Bu3SnH/AIBN by homolytic cleavage of phenylselenide substituted 2-methyleneaziridines, produces 3-methylenepiperidines in yields ranging from 58 to 68%.
- Prévost, Natacha,Shipman, Michael
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p. 7165 - 7175
(2007/10/03)
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