- (S)-2-Amino-3-(5-methyl-3-hydroxyisoxazol-4-yl)propanoic Acid (AMPA) and Kainate Receptor Ligands: Further Exploration of Bioisosteric Replacements and Structural and Biological Investigation
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Starting from 1-4 and 7 structural templates, analogues based on bioisosteric replacements (5a-c vs 1, 2 and 6 vs 7) were synthesized for completing the SAR analysis. Interesting binding properties at GluA2, GluK1, and GluK3 receptors were discovered. The requirements for GluK3 interaction were elucidated by determining the X-ray structures of the GluK3-LBD with 2 and 5c and by computational studies. Antinociceptive potential was demonstrated for GluK1 partial agonist 3 and antagonist 7 (2 mg/kg ip).
- Brogi, Simone,Brindisi, Margherita,Butini, Stefania,Kshirsagar, Giridhar U.,Maramai, Samuele,Chemi, Giulia,Gemma, Sandra,Campiani, Giuseppe,Novellino, Ettore,Fiorenzani, Paolo,Pinassi, Jessica,Aloisi, Anna Maria,Gynther, Mikko,Venskutonyte, Raminta,Han, Liwei,Frydenvang, Karla,Kastrup, Jette Sandholm,Pickering, Darryl S.
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supporting information
p. 2124 - 2130
(2018/03/21)
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- BICYCLIC AMINES AS NOVEL JAK KINASE INHIBITORS
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The present invention relates to a compound according to formula (I) wherein R1 represents alkyl; n is 1 or 2; R2 is selected from the group consisting of hydrogen, cyano, -SO2Ra, -SO2NRbR
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Page/Page column 43
(2018/08/12)
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- Preparation method for omarigliptin midbody
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The invention provides an efficient and simple preparation method for omarigliptin midbody pyrrole and [3,4-c] pyrazol-5(2H,4H,6H)-carboxylic acid tert-butyl ester, wherein the total recovery ratio is close to 50%. The preparation method is easy to operate, the recovery ratio is higher, three produced wastes are less, and the method is suitable for industrialized production.
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Paragraph 0030-0032
(2017/07/19)
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- ANTI-ANGIOGENESIS COMPOUND, INTERMEDIATE AND USE THEREOF
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Disclosed are an anti-abnormal proliferation of angiogenesis compound represented by formula I, use and intermediate thereof. The compound has good effect against abnormal proliferation of angiogenesis, and the activity of the compound is produced by inhibiting VEGFR2. The compound can be used for treating diseases, such as wet macular degeneration, inflammation, malignant tumor and the like, caused by abnormity of angiogenesis and protein kinases such as VEGFR2, FGFR2 and the like.
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- ANTI-ANGIOGENESIS COMPOUND, INTERMEDIATE AND USE THEREOF
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Disclosed are an anti-abnormal proliferation of angiogenesis compound represented by formula I, use and intermediate thereof. The compound has good effect against abnormal proliferation of angiogenesis, and the activity of the compound is produced by inhibiting VEGFR2. The compound can be used for treating diseases, such as wet macular degeneration, inflammation, malignant tumor and the like, caused by abnormity of angiogenesis and protein kinases such as VEGFR2, FGFR2 and the like.
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- HCV PROTEASE INHIBITORS AND USES THEREOF
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This invention relates to: (a) compounds of formula I and salts thereof that, inter alia, are useful as hepatitis C virus (HCV) inhibitors; (b) intermediates useful for the preparation of such compounds and salts; (c) pharmaceutical compositions comprising such compounds and salts; and (d) methods of use of such compounds, salts, and compositions.
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Page/Page column 20
(2010/03/02)
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- Novel stereoselective synthesis of all four diastereomers of 3a-methyl-pyrrolo[3,4-c]piperidine from glycine ethyl ester
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Asymmetric synthesis of all four diastereomers of 3a-methyl-pyrrolo[3,4-c]piperidine is described herein. The key steps in this synthesis are the highly diastereoselective hydrogenation of an alkenyl nitrile through a hydroxyl-directed or sterically contr
- Kim, Sung-Gon,Lee, Sang Ho,Park, Tae-Ho
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p. 5023 - 5026
(2008/02/10)
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- Glycosylated foldamers to probe the carbohydrate-carbohydrate interaction
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The synthesis of a triglycosylated helical foldamer based on a combination of cyclopentyl- and pyrrolidinyl-based amino acids is described. This structure is stable in water, maintaining as it does a series of carbohydrate units in proximity to one another, and represents the basis of a new approach to the study of carbohydrate-carbohydrate interactions. Copyright
- Simpson, Graham L.,Gordon, Andrew H.,Lindsay, David M.,Promsawan, Netnepa,Crump, Matthew P.,Mulholland, Keith,Hayter, Barry R.,Gallagher, Timothy
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p. 10638 - 10639
(2007/10/03)
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- Synthesis and biological activity of novel 1β-Methylcarbapenems with oxyiminopyrrolidinylamide moiety
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The synthesis and antibacterial activity of novel 1β- methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem.
- Lee, Ji Hoon,Lee, Kyung Seok,Kang, Yong Koo,Yoo, Kyung Ho,Shin, Kye Jung,Kim, Dong Chan,Kong, Jae Yang,Lee, Yeonhee,Lee, Sook Ja,Kim, Dong Jin
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p. 4399 - 4403
(2007/10/03)
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- Peptides containing an arginine mimetic for the treatment of bone metabolic disorders, their production, and drugs containing these compounds
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Arginine mimetic peptides according to Formula I of this application have a stimulating effect on bone formation and are useful for the treatment of bone metabolic disorders.
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- Baker's Yeast Reductions of β-Oxopyrrolidinecarboxylates: Synthesis of (+)-cis-(2R,3S)-3-Hydroxyproline and (-)-(1S,5S)-Geissman-Waiss Lactone, a Useful Precursor to Pyrrolizidine Alkaloids
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Baker's yeast reduction of the β-oxo proline derivative 5 leads to the cis-hydroxy ester 6 and thence to (+)-cis-(2R,3S)-3-hydroxyproline 7, with >90percent enantiomeric enrichment.Subsequent one-carbon homologation leads to the (-)-Geissman-Waiss lactone
- Cooper, Jeremy,Gallagher, Peter T.,Knight, David W.
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p. 1313 - 1318
(2007/10/02)
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