- GPR52 MODULATOR COMPOUNDS
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The disclosures herein relate to novel compounds of Formula (1): (1) and salts thereof, wherein R1, Q, X, Y and Z are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with GPR52 receptors.
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Page/Page column 54; 59-60
(2021/05/15)
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- HETEROCYCLIC COMPOUND
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The present invention provides a heterocyclic compound having an RIP1 kinase inhibitory action, which is useful for the prophylaxis or treatment of Gaucher's disease, Niemann-Pick disease, inflammatory bowel disease, multiple sclerosis, chronic kidney disease, acute kidney injury, acute hepatic failure, autoimmune hepatitis, hepatitis B, hepatitis C, alcohol steatohepatitis, non-alcohol steatohepatitis and the like. The present invention relates to a compound represented by the following formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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Paragraph 0539
(2018/09/14)
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- Synthesis of Substituted 3(2H)-Furanones Using Alkylative Intramolecular Cyclization of Sulfonium Salts
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The facile alkylative intramolecular cyclization of 3-alkoxycarbonyl-2-oxopropyldiphenylsulfonium salts is described. This simple method can be readily applied to the synthesis of a novel family of 4-alkylated 3(2H)-furanones in moderate to high yields under mild conditions via a one-pot process.
- Inagaki, Sho,Ukaku, Mika,Chiba, Akira,Takahashi, Fumi,Yoshimi, Yasuharu,Morita, Toshio,Kawano, Tomikazu
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p. 8363 - 8369
(2016/09/28)
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- Synthesis and Antifungal Activity of Novel Furan-2,4-dione Derivatives Containing Substituted Phenylhydrazine Moiety
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A series of novel 3-(2-(substituted phenyl)hydrazinylmethylidene)furan-2,4(3H,5H)-diones were designed and synthesized with ethyl 4-chloroacetoacetate as the starting material. Their structures were confirmed by FT-IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. Bioassay data demonstrated that these compounds exhibited remarkable antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici. Compound 3-(2-(4-bromophenyl)hydrazinylmethylidene)furan-2,4(3H,5H)-dione (5g) had excellent bioactivity against Botrytis cinerea with an EC50 value of 0.18 μg/mL - markedly lower than the 0.24 μg/mL of the commercial fungicide procymidone. The result revealed that introducing the halogenated phenylhydrazine at the 3-position of furan-2,4(3H, 5H)-dione was an effective way to design new tetronic acid derivatives as new fungicides. A series of novel furan-2,4-dione derivatives containing a substituted phenylhydrazine moiety were designed and synthesized. These compounds exhibited remarkable antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici. Compound 5g showed significantly better bioactivity than the control fungicides.
- Hu, Ying,Zhang, Li-Zhi,Ren, Zheng-Jiao,Zhao, Zheng,Xu, Wen-Qin,Yang, Chun-Long
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p. 495 - 500
(2015/06/23)
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- 3,4-DISUBSTITUTED 1 H-PYRAZOLE AND 4,5-DISUBSTITUTED THIAZOLE INHIBITORS OF SYK
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The present invention relates to the use of novel compounds of formula (I), wherein all variable substituents are defined as described herein, which are SYK inhibitors and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 91
(2014/05/24)
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- Synthesis, characterization, antifungal evaluation and 3D-QSAR study of phenylhydrazine substituted tetronic acid derivatives
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A series of 3-(1-(2-(substituted phenyl)hydrazinyl)alkylidene)furan-2,4(3H, 5H)-diones were designed and prepared using two synthetic routes. Their structures were confirmed by FT-IR, 1H NMR, 13C NMR, MS, elemental analysis and single-crystal X-ray diffraction. Their bioactivity was evaluated against Botrytis cinerea in vitro. Most target compounds exhibited remarkable antifungal activity. Two compounds 7f and 7h were highly effective and their EC50 values were 0.241 μg/mL and 0.167 μg/mL, respectively, close to that of the control drug procymidone. 3D-QSAR studies of CoMFA and CoMSIA were carried out. Models with good predictive ability were generated with the cross validated q2 values for CoMFA and CoMSIA being 0.565 and 0.823. Conventional r2 values were 0.983 and 0.945, respectively. The results provided a practical tool for guiding the design and synthesis of novel and more potent tetronic acid derivatives containing substituted phenylhydrazine moiety.
- Hu, Ying,Wang, Junjun,Lu, Aimin,Yang, Chunlong
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supporting information
p. 3772 - 3776
(2014/09/17)
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- 4-tert-butoxy-1-ethoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene. A new diene and its application to the synthesis of γ-alkylidenetetronic acids
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A new approach to γ-alkylidenetetronic acids is reported which is based on Me3SiOTf-catalyzed [3+2] cyclization of 4-tert-butoxy-1,3- bis(trimethylsilyloxy)-1,3-butadiene with oxalyl chloride, orthogonal protection of the α-hydroxy group by benzylation and subsequent deprotection of the β-hydroxy group.
- Van Nguyen, Thi Hong,Cam, Bui Duy,Ahmed, Zafar,Langer, Peter
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p. 836 - 840
(2013/08/23)
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- Biomimetic synthesis, antibacterial activity and structure-activity properties of the pyroglutamate core of oxazolomycin
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Biomimetic intramolecular aldol reactions on oxazolidine templates derived from serine may be used to generate densely functionalised pyroglutamates, which are simpler mimics of the right hand side of oxazolomycin. Some of the compounds from this sequence exhibit in vivo activity against S. aureus and E. coli, suggesting that pyroglutamate scaffolds may be useful templates for the development of novel antibacterials, and cheminformatic analysis has been used to provide some structure-activity data.
- Angelov, Plamen,Chau, Yui Kwan Sonia,Fryer, Paul J.,Moloney, Mark G.,Thompson, Amber L.,Trippier, Paul C.
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supporting information; experimental part
p. 3472 - 3485
(2012/06/01)
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- LIGAND-DIRECTED COVALENT MODIFICATION OF PROTEIN
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The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.
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Page/Page column
(2013/03/26)
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- Ru-catalyzed asymmetric hydrogenation of γ-heteroatom substituted β-keto esters
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A series of enantiomerically pure γ-heteroatom substituted β-hydroxy esters were synthesized with high enantioselectivities (up to 99.1% ee) by hydrogenation of γ-heteroatom substituted β-keto esters in the presence of Ru-(S)-SunPhos catalyst. These asymmetric hydrogenations provide key building blocks for a variety of naturally occurring and biologically active compounds.
- Fan, Weizheng,Li, Wanfang,Ma, Xin,Tao, Xiaoming,Li, Xiaoming,Yao, Ying,Xie, Xiaomin,Zhang, Zhaoguo
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experimental part
p. 9444 - 9451
(2012/01/13)
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- Process for the Preparation of Tetronic Acid
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Tetronic acid of following Formula (2): is industrially efficiently prepared through a reaction of 4-hydroxy- or 4-alkoxy-acetoacetic acid or an ester thereof of following Formula (1): wherein R1 and R2 each independently represent a hydrogen atom or an alkyl group, by carrying out the reaction in the presence of an organic solvent and an acid but substantially in the absence of water. Product tetronic acid is useful as an intermediate for fine chemicals such as pharmaceuticals, agricultural chemicals, and semiconductor resist polymers.
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Page/Page column 6
(2010/04/24)
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- 2 -AMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS
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2-Amino-pyrimidine derivatives of formula I, wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine receptor H4antagonists.
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Page/Page column 103
(2009/07/18)
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- Facile and convenient strategy towards synthesis of 4-substituted 2-aminothiazolo[4,5-d]pyridazinones
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Convenient synthesis of 4-substituted 2-aminothiazolo[4,5-d]pyridazinones has been achieved in 12 steps with overall yield of 19% by employing Grignard reaction as the key step. The route utilizes well established thiazole ring formation followed by Grign
- Thorave, Amol A.,Prajapati, Pinkal N.,Pethani, Jignesh P.,Kothari, Krunal C.,Jain, Mukul R.,Patel, Pankaj R.,Kharul, Rajendra K.
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supporting information; experimental part
p. 5660 - 5663
(2011/02/24)
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- SUBSTITUTED DIHYDROPYRIDINES AND METHODS OF USE
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Compounds are provided that are modulators of the C5a receptor. The compounds are substituted dihydropyridines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activtation of C5a receptors.
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Page/Page column 114
(2010/11/27)
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- PYRAZOLE-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER AND AUTOIMMUNE DISORDERS
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Compounds of formula (I) are inhibitors of PDK1 and CHK1 activity, and of use in the treatment of cancer and autoimmune disorders (I) : wherein R2 is a radical of formula R7-(CH2)n-, or a radical of formula -Alk
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Page/Page column 14; 15
(2008/06/13)
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- Discovery of a series of pyrrolidine-based endothelin receptor antagonists with enhanced ET(A) receptor selectivity
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Endothelins, ET-1, ET-2, and ET-3 are potent vasoconstricting and mitogenic 21-amino acid bicyclic peptides, which exert their effects upon binding to the ET(A) and ET(B) receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, and the ET(B) receptor mediates different effects in different tissues, including nitric oxide release from endothelial cells, and vasoconstriction in certain vascular cell types. Selective antagonists of endothelin receptor subtypes may prove useful in determining the role of endothelin in various tissue types and disease states, and hence as therapeutic agents for such diseases. The pyrrolidine carboxylic acid A-127722 has been disclosed as a potent and ET(A)-selective antagonist, and is currently undergoing clinical trials. In our efforts to find antagonists with altered selectivity (ET(A)-selective, ET(B)-selective, or nonselective), we investigated the SAR of the 2-substituent on the pyrrolidine. Compounds with alkyl groups at the 2-position possessed ET(A) selectivity improved over A-127722 (1400-fold selective), with the best of these compounds showing nearly 19,000-fold selectivity. Copyright (C) 1999 Elsevier Science Ltd.
- Boyd, Steven A.,Mantei, Robert A.,Tasker, Andrew S.,Liu, Gang,Sorensen, Bryan K.,Henry Jr., Kenneth J.,Von Geldern, Thomas W.,Winn, Martin,Wu-Wong, Jinshyun R.,Chiou, William J.,Dixon, Douglas B.,Hutchins, Charles W.,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.
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p. 991 - 1002
(2007/10/03)
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- Asymmetric total syntheses of (-)- and (+)-strychnine and the Wieland-Gumlich aldehyde
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The first asymmetric total syntheses of (-)-strychnine, ent-strychnine, and the Wieland-Gumlich aldehyde are described with full experimental details. The total synthesis of (-)-strychnine was realized in 24 steps and 3% overall yield from (1R,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate (28). This synthesis fully controls the six stereogenic centers and forms the C(20) double bond of (-)-strychnine with high diastereoselection (> 20:1). In the first stage of the synthesis, the (R)-cyclopentenylstannane 8 is prepared in nine steps and 30% overall yield (40% with one recycle of 38) as summarized in Scheme 4. Palladium-catalyzed carbonylative coupling of 8 with the 2-iodoaniline derivative 7 provides enone 6, which is converted to the 2-azabicyclo[3.2.1]octane 5 in seven additional steps. This latter sequence proceeds in 36% overall yield (Scheme 6). The central step of the total synthesis is aza-Cope-Mannich rearrangement of 5 which proceeds in 98% yield to form the pentacyclic intermediate 4 (Scheme 7). In five additional steps 4 is converted to the Wieland-Gumlich aldehyde 2, which is the ultimate precursor of (-)strychnine. A slight modification of this synthesis strategy allowed ent-strychnine to be prepared and provided the first samples of this unnatural enantiomer for pharmacological studies (Scheme 8). The efficiency and conciseness of this synthesis provide an important benchmark of the power of the aza-Cope rearrangement-Mannich reaction to solve formidable problems in alkaloid construction.
- Knight, Steven D.,Overman, Larry E.,Pairaudeau, Garry
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p. 5776 - 5788
(2007/10/02)
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- SYNTHESIS OF (S)-N-(BENZYLOXY)-4-ACETOXYMETHYL-2-AZETIDINONE, POTENTIAL INTERMEDIATE FOR CARBAPENEM ANTIBIOTICS, BY CHEMOMICROBIOLOGICAL APPROACH
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(R)-Ethyl 4-t-butoxy-3-hydroxybutanoate, which was prepared by baker's yeast reduction of ethyl 4-t-butoxy-3-oxobutanoate, was converted to (R)-3-hydroxybutyrolactone.After cleavage of the lactone ring with N-benzyloxyamine, β-lactam cyclization of the hy
- Yamada, Haruo,Sugiyama, Hajime,Kajiwara, Masahiro
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p. 2841 - 2844
(2007/10/02)
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- (R)-Ethyl 4-t-Butoxy-3-hydroxybutanoate, a Versatile Chiral Building Block for EPC (Enantiomerically Pure Compound) Syntheses, by Yeast Reduction of Ethyl 4-t-Butoxy-3-oxobutanoate
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Reduction of ethyl 4-t-butoxy-3-oxobutanoate with fermenting yeats yields (R)-ethyl 4-t-butoxy-3-hydroxybutanoate in 97percent e.e.Since the protective group is readily removed from the product of reduction, the present procedure provides a simple entry to the "world of chiral blocks" formally derived from (R)-malic acid.
- Seebach, Dieter,Eberle, Martin
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