- Synthesis method of tetrahydrofuran-3-ketone
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The invention discloses a synthesis method of tetrahydrofuran-3-ketone. The method comprises the following steps of: under an alkaline condition, mixing glycolate (I) and acrylate (II) in a solvent, and carrying out condensation cyclization reaction to obtain 4-formic ester-tetrahydrofuran-3-ketone (III); then, under an acidic condition, performing reflux decarboxylation reaction on the 4-formic ester-tetrahydrofuran-3-ketone (III) so as to obtain thetetrahydrofuran-3-ketone (IV) . According to the synthesis method of the tetrahydrofuran-3-ketone, the yield is greater than 82%; and the method has the advantages of mild and easily-controlled conditions, mild reaction, simple and safe operation and environmental friendliness.
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Paragraph 0047-0054
(2021/07/31)
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- ISOXAZOLE CARBOXYLIC ACIDS AS LPA ANTAGONISTS
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The present invention provides compounds of Formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
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Page/Page column 96-97
(2021/01/22)
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- TRIAZOLE CARBOXYLIC ACIDS AS LPA ANTAGONISTS
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The present invention provides compounds of Formula (I), or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
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Page/Page column 92-93
(2021/01/22)
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- Discovery of BNC375, a Potent, Selective, and Orally Available Type i Positive Allosteric Modulator of α7 nAChRs
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Positive allosteric modulators (PAMs) of α7 nAChRs can have different properties with respect to their effects on channel kinetics. Type I PAMs amplify peak channel response to acetylcholine but do not appear to influence channel desensitization kinetics, whereas Type II PAMs both increase channel response and delay receptor desensitization. Both Type I and Type II PAMs are reported in literature, but there are limited reports describing their structure-kinetic profile relationships. Here, we report a novel class of compounds with either Type I or Type II behavior that can be tuned by the relative stereochemistry around the central cyclopropyl ring: for example, (R,R)-13 (BNC375) and its analogues with RR stereochemistry around the central cyclopropyl ring are Type I PAMs, whereas compounds in the same series with SS stereochemistry (e.g., (S,S)-13) are Type II PAMs as measured using patch-clamp electrophysiology. Further fine control over the kinetics has been achieved by changing the substitutions on the aniline ring: generally the substitution of aniline with strong electron withdrawing groups reduces the Type II character of these compounds. Our structure-activity optimization efforts have led to the discovery of BNC375, a small molecule with good CNS-drug like properties and clinical candidate potential.
- Harvey, Andrew J.,Avery, Thomas D.,Schaeffer, Laurent,Joseph, Christophe,Huff, Belinda C.,Singh, Rajinder,Morice, Christophe,Giethlen, Bruno,Grishin, Anton A.,Coles, Carolyn J.,Kolesik, Peter,Wagner, Stéphanie,Andriambeloson, Emile,Huyard, Bertrand,Poiraud, Etienne,Paul, Dharam,O'Connor, Susan M.
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supporting information
p. 754 - 760
(2019/04/17)
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- (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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- COMPOUNDS
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Provided are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for examp
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Page/Page column 104
(2018/09/08)
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- Discovery of Orally Bioavailable and Liver-Targeted Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PHD) Inhibitors for the Treatment of Anemia
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We report herein the design and synthesis of a series of orally active, liver-targeted hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors for the treatment of anemia. In order to mitigate the concerns for potential systemic side effects, we
- Liu, Ping,Wang, Liping,Dubois, Byron G.,Colandrea, Vincent J.,Liu, Rongqiang,Cai, Jiaqiang,Du, Xiaoxing,Quan, Weiguo,Morris, William,Bai, Jianwu,Bishwokarma, Bimjhana,Cheng, Mangeng,Piesvaux, Jennifer,Ray, Kallol,Alpert, Carla,Chiu, Chi-Sung,Zielstorff, Mark,Metzger, Joseph M.,Yang, Liming,Leung, Dennis,Alleyne, Candice,Vincent, Stella H.,Pucci, Vincenzo,Li, Xiaofang,Crespo, Alejandro,Stickens, Dominique,Hale, Jeffrey J.,Ujjainwalla, Feroze,Sinz, Christopher J.
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supporting information
p. 1193 - 1198
(2018/12/11)
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- INHIBITORS OF HIF PROLYL HYDROXYLASE
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The present invention concerns compounds of formula I or pharmaceutically acceptable salts thereof, which inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced endogenous production of erythropoietin such as anemia and like conditions, as well as pharmaceutical compositions comprising such a compound and a pharmaceutical carrier.
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Page/Page column 22; 23
(2016/04/20)
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- INHIBITORS OF HIF PROLYL HYDROXYLASE
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The present invention concerns compounds of formula I or a pharmaceutically acceptable salt thereof which inhibit HIF prolyl hydroxylase, their use for enhancing endogenous production of erythropoietin, and for treating conditions associated with reduced
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Page/Page column 20
(2016/04/20)
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- Syntheses of tetrahydrothiophenes and tetrahydrofurans and studies of their derivatives as melanocortin-4 receptor ligands
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Piperazinebenzylamine derivatives from trans-4-(4-chlorophenyl)tetrahydrothiophene-3-carboxylic acid 6 and its S-oxide 7 and sulfone 8, and the tetrahydrofuran 9 and its two regioisomers 11 and 13 were synthesized and studied for their binding affinities at the human melanocortin-4 receptor. These five-membered ring constrained compounds possessed similar or lower potency compared to the acyclic analogs.
- Tran, Joe A.,Chen, Caroline W.,Tucci, Fabio C.,Jiang, Wanlong,Fleck, Beth A.,Chen, Chen
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p. 1124 - 1130
(2008/09/18)
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- N-ARYL-5,7-DIHYDROFURO[3,4-D]PYRIMIDIN-4-AMINES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
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Disclosed are N-aryl-5,7-dihydrofuro[3,4-d]pyrimidin-4-amines and analogs thereof, represented by the Formula (I), wherein Ar, A, Q and R1 -R6 are defined herein. The present invention relates to the discovery that compounds having F
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Page/Page column 32
(2010/11/30)
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- Non-imidazole tertiary amines as histamine 3 receptor inhibitors for the treatment of cognitive and sleep disorders, obesity and other CNS disorders
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This invention relates to compounds having pharmacological activity, to compositions containing these compounds, and to a method of treatment employing the compounds and compositions. More particularly, this invention concerns certain non-imidazole tertiary amine derivatives and their salts and solvates. These compounds have H3 histamine receptor antagonist activity. This invention also relates to pharmaceutical compositions containing these compounds and to a method of treating disorders in which histamine H3 receptor blockade is beneficial.
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Page/Page column 19
(2008/06/13)
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- HCV INHIBITING BI-CYCLIC PYRIMIDINES
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The present invention relates to the use of bi-cyclic pyrimidines as inhibitors of HCV replication as well as their use in pharmaceutical compositions aimed to treat or combat HCV infections. In addition, the present invention relates to processes for pre
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Page/Page column 58
(2010/10/20)
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- LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO
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Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): (R4)s (R 2)n N~ X1-X2 (CR1aCRlb)q 1~ N R1-lm 1 O R3 (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4, X1 X2 and X3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.
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Page/Page column 78-79
(2010/02/11)
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- SUBSTITUTED BENZOPYRANS AS SELECTIVE ESTROGEN RECEPTOR-BETA AGONISTS
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This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have the formula: (I)
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- Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
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The present invention relates to novel compounds that can be used as antiinflammatory, immunomodulatory and antiproliferatory agents. In particular the invention refers to new compounds which inhibit dihydroorotate dehydrogenase (DHODH), a process for their manufacture, pharmaceutical compositions containing them and to their use for the treatment and prevention of diseases, in particular their use in diseases where there is an advantage in inhibiting dihydroorotate dehydrogenase (DHODH).
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- 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof
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Novel 6-heterocyclyl-pyrazolo[3,4-d]pyrimidin-4-ones, useful in treating cardiovascular disease, are prepared by reacting a 5-amino-1H-pyrazole-4-carboxamide with heterocyclylcarboxaldehyde or by reacting a 5-amino-1H-pyrazole-4-carbonitrile with a heterocyclylcarboxamidine, followed by diazotization and hydrolysis of the resulting 4-amino-6-heterocyclyl-pyrazolo[3,4-d]pyrimidine.
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- Free Radical Ring-Expansion Leading to Novel Six- and Seven-Membered Heterocycles
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Free radical promoted ring-expansion of nitrogen-, oxygen- and sulfur-containing heterocyclic β-keto esters is described.Treatment of the derived phenylselenomethyl derivatives with tri-n-butyltin hydride leads to smooth one-carbon ring expansion.
- Dowd, Paul,Choi, Soo-Chang
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p. 4847 - 4860
(2007/10/02)
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