- Phase Separation Macrocyclization in a Complex Pharmaceutical Setting: Application toward the Synthesis of Vaniprevir
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A phase separation/continuous flow strategy employing an oxidative Glaser-Hay coupling of alkynes has been applied toward the synthesis of the macrocyclic core of complex pharmaceutical vaniprevir. The phase separation/continuous flow strategy afforded similar yields at 100-500 times the concentration and at shorter reaction times than common slow addition/high dilution techniques. In addition, dendritic PEG cosolvents were employed in the phase separation strategy for the first time and shown to allow productive macrocyclization at concentrations up to 200 mM.
- Godin, éric,Bédard, Anne-Catherine,Raymond, Micha?l,Collins, Shawn K.
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Read Online
- SELECTIVE NEURONAL NITRIC OXIDE SYNTHASE INHIBITORS
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Disclosed are 7-phenyl-2-aminoquinoline compounds that are shown to inhibit the biological activity of neuronal nitric oxide synthases (nNOSs). Also disclosed are pharmaceutical compositions comprising the compounds, and methods of using the compounds and
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Paragraph 0286; 0303
(2021/04/30)
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- INHIBITORS OF MLH1 AND/OR PMS2 FOR CANCER TREATMENT
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The present invention relates to compounds of Formula (I) that target the MLH1 and/or PMS2 proteins that are components of the DNA Mismatch Repair (MMR) process: Formula (I) wherein R1, R2, R3, R4, R6
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Paragraph 00423-00424
(2021/12/28)
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- PI3 KINASE INHIBITORS AND USES THEREOF
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A compound of the formula (II); a pharmaceutical composition comprising same; and methods for treating a fibrotic disease in a subject.
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Paragraph 00137
(2021/10/15)
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- FUSED PYRAZOLE AND IMIDAZOLE BASED COMPOUNDS AND USE THEREOF AS GLI1 INHIBITORS
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The present invention is directed to a composition and a method for use thereof, such as for the treatment and prevention of a neurological disorder or cancer in a subject.
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Paragraph 00197; 00200
(2021/11/20)
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- First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate
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Inhibition of neuronal nitric oxide synthase (nNOS), an enzyme implicated in neurodegenerative disorders, is an attractive strategy for treating or preventing these diseases. We previously developed several classes of 2-aminoquinoline-based nNOS inhibitor
- Cinelli, Maris A.,Reidl, Cory T.,Li, Huiying,Chreifi, Georges,Poulos, Thomas L.,Silverman, Richard B.
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supporting information
p. 4528 - 4554
(2020/05/05)
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- ISOINDOLINE DERIVATIVES FOR THE TREATMENT OF CNS DISEASES
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A compound of the formula (I) wherein R1 represents hydrogen atom and R2 represents moiety of the formula G1, or R1 and R2 are connected with each other to form with nitrogen atom to which they are attached a moiety of the formula G2; A is selected from the group consisting of phenyl substituted with one or two substituents selected from the group consisting of halogen atom, straight or branched C1- C4 alkyl, C1-C2 alkoxyl, CF3, CN, and -OCF3, naphthyl, quinolinyl, thienyl, thienyl substituted with halogen atom, and pyridyl; X is selected from the group consisting of -NR4, -0-, and -CHN(R5)2; R3is selected from the group consisting of hydrogen atom, methyl, ethyl, and cyclopropyl; R4is selected from the group consisting of hydrogen atom, straight or branched C1-C4 alkyl, straight or branched C1-C4 alkyl substituted with one or two halogen atoms, cyclopropyl and methylcyclopropyl; R5represents C1-C2 alkyl; k is an integer equal 1 or 2; I is an integer equal 1 or 2; m is an integer equal 0, 1 or 2; n is an integer 0 or 1 when X represents -NR4"or -CHN(R5) 2, wherein n is 1 only when m is 1; and n is 0 when X represents -0-; and acid addition salts thereof, can be useful as selective inhibitors of 5HT6 in the treatment of CNS diseases.
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Page/Page column 11; 12
(2019/06/09)
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- ISOINDOLINES AS HDAC INHIBITORS
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The present disclosure relates to inhibitors of zinc-dependent histone deacetylases (HDACs), having the formula: (I) wherein Z, X1, X2, Y1, Y2, Y3, L, Z, and R are described herein.
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Paragraph 00130
(2019/11/12)
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- 2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER
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The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.
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Page/Page column 55; 214
(2017/10/11)
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- CARBAZOLE DERIVATIVES
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Disclosed are compounds of Formula (I): (I) or a salt thereof, wherein Q, R1a, R1b, R2a, R2b, R3, R4, R5a, R5b, R6a, R6c, R7a, R7b, R7c, and R7d are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
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Page/Page column 118
(2016/05/24)
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- Certain pyrazoline derivatives with kinase inhibitory activity
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The present invention provides certain pyrazoline compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions and methods of using the compositions in the treatment of various diseases.
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Page/Page column 104
(2008/12/06)
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