- Discovery of highly selective brain-penetrant vasopressin 1a antagonists for the potential treatment of autism via a chemogenomic and scaffold hopping approach
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From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar human vasopressin 1a (hV1a) receptor antagonist 38. Initial optimization of the mouse V1a activities delivered suitable tool compounds which demonstrated a V1a mediated central in vivo effect. This novel series was further optimized through parallel synthesis with a focus on balancing lipophilicity to achieve robust aqueous solubility while avoiding P-gp mediated efflux. These efforts led to the discovery of the highly potent and selective brain-penetrant hV1a antagonist RO5028442 (8) suitable for human clinical studies in people with autism.
- Ratni, Hasane,Rogers-Evans, Mark,Bissantz, Caterina,Grundschober, Christophe,Moreau, Jean-Luc,Schuler, Franz,Fischer, Holger,Alvarez Sanchez, Ruben,Schnider, Patrick
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Read Online
- Novel indole derivative and medicine containing the same (by machine translation)
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[A] formation of Amyloid fibrils can be compounds, including therapeutic or prophylactic agent for neurodegenerative disease Amyloid fibrils formation inhibitor compound and of. (I) or its pharmaceutically acceptable compound represented by the formula [a] or a salt or solvate thereof includes the, Amyloid fibrils formation inhibitor. [R1 And R2 Each independently is H, an alkyl group, a cyano group or the like; R3 And R4 Each independently is H, or an alkyl group; R3 And R4 The, joint may form a ring; Ar1 And Ar2 The substituted or unsubstituted heteroaryl group are independently substituted/unsubstituted aryl groups /; X and Y are each independently a single bond, - (=O) - C etc., Z is O or CH2 ; N is an integer of 1 - 3][Drawing] no (by machine translation)
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Paragraph 0133; 0134
(2018/06/30)
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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; 00420
(2015/07/07)
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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 0153; 0154
(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; 29
(2013/03/26)
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- INDOLES
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The present invention is concerned with novel indol-3-yl-carbonyl-piperidine-benzopyrrolone, -benzoxazolone and -benzotriazole derivatives as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use for the tr
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Page/Page column 14
(2008/12/06)
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- AZASPIRO DERIVATIVES
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The present invention is concerned with novel indol-3-yl-carbonyl-azaspiropiperidine derivatives as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use for the treatment of anxiety and depressive disorder
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Page/Page column 17
(2008/12/06)
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- INDOLE COMPOUNDS
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Compounds of formula (I) or a pharmaceutically acceptable derivative thereof; (formula I) wherein X, R1,R2, and R3are as defined in the specification, a process for the preparation of such compounds, pharmaceutical composi
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Page/Page column 22
(2008/06/13)
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- Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping
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We describe the medicinal chemistry approach that generated a novel indole series of EP1 receptor antagonists. The SAR of this new template was evaluated and culminated in the identification of compound 12g which demonstrated in vivo efficacy i
- Hall, Adrian,Billinton, Andy,Brown, Susan H.,Chowdhury, Anita,Giblin, Gerard M.P.,Goldsmith, Paul,Hurst, David N.,Naylor, Alan,Patel, Sadhana,Scoccitti, Tiziana,Theobald, Pamela J.
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p. 2684 - 2690
(2008/12/21)
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- Indol-3-y-carbonyl-piperidin and piperazin-derivatives
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The present invention relates to indol-3-yl-carbonyl-piperidin and piperazin derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the residues R1 to R3 are as defined herein. The invention
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Page/Page column 21
(2010/11/25)
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- Indol-3-yl-carbonyl-azaspiro derivatives
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This invention relates to indol-3-yl-carbonyl-azaspiro derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the azaspiro-head group A and the residues R1, R2 and R3 are as defin
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Page/Page column 14
(2010/11/26)
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- Indol-3-yl-carbonyl-spiro-piperidine derivatives
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This invention relates to indol-3-yl-carbonyl-spiro-piperidine derivatives which act as Via receptor antagonists and which are represented by Formula I: wherein the spiropiperidine-head group A and the residues R1, R2 and R3 /s
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Page/Page column 16
(2010/11/27)
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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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