- 9-SUBSTITUTED AMINO TRIAZOLO QUINAZOLINE DERIVATIVES AS ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE
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In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): (I), and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.
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Page/Page column 54; 72
(2020/06/19)
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- Synthetic method for (R)-N-tert-butoxycarbonyl-3-hydroxymethylpiperidine
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The invention discloses a synthetic method for (R)-N-tert-butoxycarbonyl-3-hydroxymethylpiperidine. The method comprises the following four steps: synthesizing ethyl 3-piperidinecarboxylate (compoundII), synthesizing ethyl (R)-nipecotate-L-tartarate (compound III), synthesizing ethyl (R)-N-Boc-3-piperidinecarboxylate (compound IV) and synthesizing the (R)-N-tert-butoxycarbonyl-3-hydroxymethylpiperidine (compound V); and the method comprises the following special steps: synthesizing the compound II by using 3-piperidinecarboxylic acid (compound I) as a raw material through chloroacylation andethanol esterification; performing a salt formation reaction to form the compound III; adding a Boc anhydride and performing a reaction to obtain the compound IV; and finally performing sodium borohydride reduction to obtain the compound V. The method provided by the invention has the advantages of mild reaction conditions, environmental friendliness, simple operation steps, better reproducibilityand high practicability, and is suitable for industrial mass production of the (R)-N-tert-butoxycarbonyl-3-hydroxymethylpiperidine.
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Paragraph 0022; 0026; 0029; 0033; 0036; 0040; 0043; 0044
(2019/08/12)
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- Process for preparation of (2S, 5R)-7-oxo-6-sulphooxy-2[((3R)-piperidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo [3.2.1]-octane
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A process for preparation of (2S,5R)-7-oxo-6-sulphooxy-2-[((3R)-piperidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza-bicyclo[3.2.1]octane of Formula (I) is disclosed which is comprising reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV). Crystalline compounds of Formula (I) are claimed.
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Page/Page column 8; 9
(2017/07/14)
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- A PROCESS FOR PREPARATION OF (2S, 5R)-7-OXO-6-SULPHOOXY-2-[((3R)-PIPERIDINE-3-CARBONYL)-HYDRAZINO CARBONYL]-1,6-DIAZA-BICYCLO [3.2.1]- OCTANE
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A process for preparation of (2S, 5R)-7-oxo-6-sulphooxy-2- [((3R)-piperidine-3-carbonyl)-hydrazino carbonyl]-1,6-diaza- bicyclo[3.2.1]octane of Formula (I) is disclosed which is comprising reacting a compound of Formula (II) with a compound of Formula (III) to obtain a compound of Formula (IV). Crystalline compounds of Formula (I) are claimed.
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Page/Page column 10
(2014/09/29)
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- Novel non-peptide nociceptin/orphanin FQ receptor agonist, 1-[1-(1-Methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl] -1H-benzimidazole: Design, synthesis, and structure-activity relationship of oral receptor occupancy in the brain for orally potent
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An endogenous heptadecapeptide, nociceptin/orphanin FQ (N/OFQ), and a G-protein-coupled receptor, N/OFQ peptide (NOP) receptor [or opioid-receptor-like-1 (ORL1) receptor], have been described in terms of its structure, distribution, and pharmacology. Thus
- Hayashi, Shigeo,Hirao, Akiko,Imai, Aki,Nakamura, Hiroshi,Murata, Yoshinori,Ohashi, Katsuyo,Nakata, Eriko
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experimental part
p. 610 - 625
(2009/12/29)
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- 4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: Design, synthesis and structure-activity relationships
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Single enantiomer [(aryloxy)(pyridinyl)methyl]piperidine and pyrrolidine derivatives 5-9 are inhibitors of monoamine reuptake. Structure-activity relationships established that monoamine reuptake inhibition are functions of amine, pyridine isomer, aryloxy ring substitution and stereochemistry. Consequently, selective NRIs, selective SRIs, dual SNRIs and triple SNDRIs were all identified. Dual SNRIs 5l-a and 9c were evaluated in additional pharmacology and pharmacokinetic studies as representative examples from this series.
- Fish, Paul V.,Andrews, Mark D.,Jonathan Fray,Stobie, Alan,Wakenhut, Florian,Whitlock, Gavin A.
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scheme or table
p. 2829 - 2834
(2010/03/03)
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- Asymmetric hydrogenation of pyridines: Enantioselective synthesis of nipecotic acid derivatives
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An asymmetric hydrogenation process of 3-substituted pyridine derivatives has been developed with the use of a Rh-TangPhos complex as the catalyst. The whole process consists of an efficient partial hydrogenation of nicotinate and a subsequent highly enan
- Lei, Aiwen,Chen, Mao,He, Minsheng,Zhang, Xumu
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p. 4343 - 4347
(2007/10/03)
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- Compounds with growth hormone releasing properties
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Disclosed are compounds of formula I formula I wherein R1, R2, R5, R6, R7, R8, G, J, L, M, a, b, c, d, e, and f are as defined in the specification, and compositions containing them. These
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- The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency
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In order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substitutents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC50 values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a Cmax of over 40 ng mL-1.
- Peschke, Bernd,Ankersen, Michael,Bauer, Michael,Hansen, Thomas Kruse,Hansen, Birgit Sehested,Nielsen, Karin Kramer,Raun, Kirsten,Richter, Lutz,Westergaard, Lisbet
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p. 487 - 501
(2007/10/03)
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- Synthesis of potent and highly selective inhibitors of human tryptase
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The serine protease tryptase has been implicated in allergic and inflammatory diseases and associated with asthma. The synthesis and SAR of a series of N1-activated-4-carboxy azetidinones are described, resulting in identification of BMS-363131 (2) as a potent inhibitor of human tryptase (IC503000-fold) for tryptase versus related serine proteases including trypsin.
- Slusarchyk, William A.,Bolton, Scott A.,Hartl, Karen S.,Huang, Ming-Hsing,Jacobs, Glenn,Meng, Wei,Ogletree, Martin L.,Pi, Zulan,Schumacher, William A.,Seiler, Steven M.,Sutton, James C.,Treuner, Uwe,Zahler, Robert,Zhao, Guohua,Bisacchi, Gregory S.
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p. 3235 - 3238
(2007/10/03)
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- Beta lactam compounds and their use as inhibitors of tryptase
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Compounds of the formulas: are disclosed. These compounds inhibit tryptase as well as other enzyme systems or are selective tryptase inhibitors and are useful as antiinflammatory agents particularly in the treatment of chronic asthma.
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Page column 253
(2010/11/29)
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- Synthesis of the sialidase inhibitor siastatin B.
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[structure] The resolved piperidinecarboxylate (R)-7 was converted to siastatin B (1) by an efficient and stereoselective sequence that includes a bromo-beta-lactonization and an N-acyliminium azidation. Two analogues (3 and 4) of siastatin were also prepared.
- Knapp,Zhao
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p. 4037 - 4040
(2007/10/03)
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