- Total synthesis and biological studies of TMC-205 and analogues as anticancer agents and activators of SV40 promoter
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TMC-205 is a natural fungal metabolite with antiproliferative activity against cancer cell lines. The light- and air-sensitivity prevented in-depth exploitation of this novel indole derivative. Herein, we report the first synthesis of TMC-205. On the basi
- Gao, Yang,Osman, Sami,Koide, Kazunori
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- A simple and efficient total synthesis of anticancer indole alkaloids TMC-205 and its analogues
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A concise synthesis of TMC-205 was accomplished in two steps via a protecting-group-free (PGF) and redox-economical strategy. In this approach, a high yield Pinnick oxidation and a practical Heck-dehydration reaction with high atom economy as well as a high regio- and stereo-selectivity (E-isomer) were used and further applied to the total synthesis of its active analogues. This newly established route would be beneficial for future structure–activity relationship (SAR) and biological studies. The synthetic strategy and methodologies demonstrated in this paper could be extended to related biologically active natural products.
- Jiang, Shizhi,Lei, Ting,Li, Tao,Song, Jinjie,Wang, Fusheng,Wang, Lihua
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- REV-ERB AGONISTS FOR THE TREATMENT OF TH17-MEDIATED INFLAMMATORY DISORDERS
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The present disclosure provides compounds of Formula IA and Formula IB and their pharmaceutical compositions as selective agonists of REV-ERB-α: where R1, R2, R3, R4, R5, RX1, RX2, nA, nB, X, Y, and Z are described herein. The compounds are useful in various methods and uses, such as in the treatment of diseases including hyperglycemia, dyslipidemia, atherosclerosis, and autoimmune and inflammatory disorders or diseases, and as cancer therapeutics, such as for the treatment of glioblastoma, hepatocellular carcinoma, and colorectal cancer, and for immune-oncology purposes.
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Paragraph 00710-00712
(2022/01/05)
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- PHOSPHONATE COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula (I), or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is a phosphonate substituent (R32) are provided. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.
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Paragraph 0461; 0523
(2017/03/14)
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- AROMATIC HETEROCYCLIC COMPOUNDS AND THEIR APPLICATION IN PHARMACEUTICALS
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Provided herein are novel aromatic heterocyclic compounds or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and methods for using such compounds or pharmaceutical compositions thereof to treat Alzheimer's disease.
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Paragraph 00416; 00424
(2015/07/07)
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- LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
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Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.
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Paragraph 0978; 0979
(2014/07/23)
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- 8 - SUBSTITUTED 2 -AMINO - [1,2,4] TRIAZOLO [1, 5 -A] PYRAZINES AS SYK TRYROSINE KINASE INHIBITORS AND GCN2 SERIN KINASE INHIBITORS
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Compounds of the formula I in which R1, R2 and R4 have the meanings indicated in Claim 1, are inhibitors of Syk, and can be employed, inter alia, for the treatment of cancer, rheumatoid arthritis and / or systemic lupus
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Page/Page column 171; 172
(2013/09/12)
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- NOVEL BIS-INDOLIC DERIVATIVES, A PROCESS FOR PREPARING THE SAME AND THEIR USES AS A DRUG
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Paragraph 0147; 0148
(2013/03/26)
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- BIS-INDOLIC DERIVATIVES, A PROCESS FOR PREPARING THE SAME AND THEIR USES AS A DRUG
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The present invention relates to novel bis-indolic derivatives, processes for their preparation, and their potential use as new antibacterial drugs.
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Page/Page column 26; 28
(2013/03/26)
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- BICYCLIC HETEROARYLS AS KINASE INHIBITORS
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The invention is directed to heteroaryl compounds useful as inhibitors of various kinase enzymes. In various embodiments, the invention provides a heteroaryl compound having inhibitory bioactivity with respect to a Rho kinase, an AKT kinase, a p70S6K kinase, a LIM kinase, an IKK kinase, a Flt kinase, an Aurora kinase, or a Src kinase, or any combination thereof. Compounds of the invention include bicyclic heteroaryl compounds of formula (I), which can contain a bridging nitrogen atom at a ring junction. The invention further provides methods of synthesis of compounds of the invention, pharmaceutical compositions, pharmaceutical combinations, and methods of treatment of malconditions using compounds of the invention.
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Page/Page column 80-81
(2011/05/06)
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- Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)
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Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC 50 = 1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II.
- Chowdhury, Sarwat,Sessions, E. Hampton,Pocas, Jennifer R.,Grant, Wayne,Schr?ter, Thomas,Lin, Li,Ruiz, Claudia,Cameron, Michael D.,Schürer, Stephan,Lograsso, Philip,Bannister, Thomas D.,Feng, Yangbo
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scheme or table
p. 7107 - 7112
(2012/01/05)
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- Indole-3-carboxamides as glucokinase activators
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The present invention provides glucokinase activators of formula I: wherein R1, R2 and R3 are defined in the specification. Glucokinase activators are useful for increasing insulin secretion in the treatment of type II diabetes.
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- REACTION OF INDOLES WITH TRIFLUORACETIC ACID
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3-Trifluoracetyl indoles are formed by the action of trifluoracetic acid on indole-2-carboxylic acid and its benzo-substituted derivatives.When unsubstituted indole is refluxed with trifluoracetic acid, it gives 3-triflouracetylindole in 30percent yield.
- Kost, A. N.,Budylin, V. A.,Romanova, N. N.,Matveeva, E. D.
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p. 921 - 923
(2007/10/02)
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