- PD-1/PD-L1 small-molecule inhibitor and preparation method and application thereof
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The invention discloses a PD-1/PD-L1 small-molecule inhibitor and a preparation method and application thereof. Specifically, the invention discloses a compound with the structure shown in the formulaL, a stereoisomer or a tautomer thereof, or pharmaceutically acceptable salts or hydrates or solvates thereof, and please see the specification for specific definitions. The compound has excellent effects for restraining PD-1/PD-L1. Please see the specification for the formula.
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- Palladium-Catalyzed Regioselective C-2 Arylation of Benzofurans with N′-Acyl Arylhydrazines
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A novel ligand-free palladium-catalyzed C-2 arylation of benzofurans has been developed using N′-acyl arylhydrazines as the coupling partners and TEMPO as an oxidant. This protocol features a wide functional-group tolerance and highly regioselective products with good to excellent yields.
- Cao, Jun,Chen, Zi-Li,Li, Shu-Min,Zhu, Gao-Feng,Yang, Yuan-Yong,Wang, Cong,Chen, Wen-Zhang,Wang, Jian-Ta,Zhang, Ji-Quan,Tang, Lei
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supporting information
p. 2774 - 2779
(2018/06/21)
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- HEMOGLOBIN MODIFIER COMPOUNDS AND USES THEREOF
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Described herein are compounds, including pharmaceutically acceptable salts thereof, methods of making such compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, prevent or diagnose blood-based diseases, disorders or conditions.
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Paragraph 00395
(2018/02/28)
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- An improved and scale-up synthesis of 6-hydroxybenzofuran
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An optimized process for the preparation of 6-hydroxybenzofuran is described. This process consists of three steps: the reaction of 2-hydroxy-4-methoxybenzaldehyde with chloroacetic acid, the formation of the 6-methoxybenzofuran in acetic anhydride, and t
- Song, Shu-Yong,Lu, He-Lin,Wang, Gui-Fei,Yang, Yi-Qiu,Huang, Yun-Sheng
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p. 4433 - 4442
(2016/07/06)
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- Concise synthesis of 6-cyanobenzo[ b ]furan, a useful building block
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A new three-step synthesis of 6-cyanobenzo[b]furan (6) was developed, starting from commercially available 6-hydroxybenzo[b]furan-3-one (18). Key steps in this process were the first step, which was the reductive dehydration of 18 to produce 6-hydroxybenzo[b]furan (19), and the last step, which converted the aryl triflate 20 to the aryl cyanide 6 in a palladium-catalyzed cross-coupling protocol. Overall yield for this new synthesis was 49%.
- Nguyen, Son T.,Williams, John D.,Majgier-Baranowska, Helena,Li, Bing,Neelagiri, Venugopal R.,Kim, Hwa-Ok,Peet, Norton P.
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p. 1307 - 1313
(2014/04/17)
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- LFA-1 INHIBITOR AND POLYMORPH THEREOF
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Methods of preparation and purification of a compound, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA -1 mediated diseases are also disclosed.
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Paragraph 00131; 00132; 00133; 00134; 00135
(2014/02/16)
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- Synthetic models related to methoxalen and menthofuran-cytochrome P450 (CYP) 2A6 interactions. Benzofuran and coumarin derivatives as potent and selective inhibitors of CYP2A6
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Human microsomal cytochrome P450 (CYP) 2A6 contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. We prepared a series of benzofuran and coumarin derivatives that have inhibitory effects on the activity of human CYP2A6. The reported compounds methoxalen and menthofuran had potent inhibitory effects on the activity of CYP2A6 with IC50 values of 0.47 μM and 1.27 μM, respectively. Synthetic benzofuran (4-methoxybenzofuran: IC50=2.20 μM) and coumarin (5-methoxycoumarin: IC50=0.13 μM and 6-methoxycoumarin: IC50=0.64 μM) derivatives, which have more selective effects than those of methoxalen and menthofuran, exhibited comparable activities against CYP2A6. These compounds can be used as a lead compounds in the design of CYP2A6 inhibitor drugs to reduce smoking and tobacco-related cancers.
- Yamaguchi, Yuki,Akimoto, Ichie,Motegi, Kyoko,Yoshimura, Teruki,Wada, Keiji,Nishizono, Naozumi,Oda, Kazuaki
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p. 997 - 1001
(2013/11/19)
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- Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: Synthesis of benzo[b]thiophene 2,3-oxide
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Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.
- Boyd, Derek R.,Sharma, Narain D.,Brannigan, Ian N.,Evans, Timothy A.,Haughey, Simon A.,McMurray, Brian T.,Malone, John F.,McIntyre, Peter B. A.,Stevenson, Paul J.,Allen, Christopher C. R.
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scheme or table
p. 7292 - 7304
(2012/10/07)
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- Discovery and development of potent LFA-1/ICAM-1 antagonist SAR 1118 as an ophthalmic solution for treating dry eye
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LFA-1/ICAM-1 interaction is essential in support of inflammatory and specific T-cell regulated immune responses by mediating cell adhesion, leukocyte extravasation, migration, antigen presentation, formation of immunological synapse, and augmentation of T-cell receptor signaling. The increase of ICAM-1 expression levels in conjunctival epithelial cells and acinar cells was observed in animal models and patients diagnosed with dry eye. Therefore, it has been hypothesized that small molecule LFA-1/ICAM-1 antagonists could be an effective topical treatment for dry eye. In this letter, we describe the discovery of a potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonist (SAR 1118) and its development as an ophthalmic solution for treating dry eye.
- Zhong, Min,Gadek, Thomas R.,Bui, Minna,Shen, Wang,Burnier, John,Barr, Kenneth J.,Hanan, Emily J.,Oslob, Johan D.,Yu, Chul H.,Zhu, Jiang,Arkin, Michelle R.,Evanchik, Marc J.,Flanagan, W. Mike,Hoch, Ute,Hyde, Jennifer,Prabhu, Saileta,Silverman, Jeffrey A.,Wright, Jasmin
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supporting information; scheme or table
p. 203 - 206
(2012/05/04)
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- Structural modification of a specific antimicrobial lead against Helicobacter pylori discovered from traditional Chinese medicine and a structure-activity relationship study
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Psoralen (1a) was found to be a specific and potent antimicrobial lead against Helicobacter pylori (H. pylori) from a traditional Chinese medicine (TCM) in the bioassay directed isolation. A series of structurally diverse analogues of 1a were thus designed and synthesized to improve the antimicrobial potency, some of which showed more potent activities than the lead compound (1a) against H. pylori. Among them, compound 25a is 16-fold stronger (MIC = 0.39 μg/mL) than 1a (MIC = 6.25 μg/mL), and is even potent than the positive control metronidazole (MIC = 0.50 μg/mL). The in vitro antimicrobial activities against H. pylori of these structurally diverse analogues based on the scaffold of 1a have also led to an outline of structure-activity relationship.
- Zhang, Bang-Le,Fan, Cheng-Qi,Dong, Lei,Wang, Fang-Dao,Yue, Jian-Min
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scheme or table
p. 5258 - 5264
(2011/01/04)
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- MODULATORS OF CFTR
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Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"). The present invention also relates to methods of treating CFTR mediated diseases using compounds of the present invention.
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Page/Page column 77-78
(2009/01/20)
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- ANTIDIABETIC BICYCLIC COMPOUNDS
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Tricyclic compounds containing a cyclopropyl carboxylic acid or carboxylic acid derivative (e.g. amide) fused to a bicyclic ring, including pharmaceutically acceptable salts and prodrugs thereof, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 12
(2008/06/13)
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- 9-AZABICYCLO [3 . 3 . 1] NONANE DERIVATIVES AS MONOAMINE REUPTAKE INHIBITORS
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The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1-5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2-5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9-methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
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Page/Page column 40
(2010/11/26)
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- A new efficient method for the total synthesis of linear furocoumarins
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A new efficient method for the synthesis of linear furocoumarins by a Nef reaction and intramolecular cyclocondensation in one pot results in the construction of a benzofuran ring. This method provides a new strategy to furnish the benzofuran framework easily, and also allows the convenient synthesis of furocoumarin derivatives with different substituents on the coumarin ring by a subsequent Pechmann reaction. This strategy has also been applied to the preparation of four additional benzofuran derivatives. Georg Thieme Verlag Stuttgart.
- Zhang, Bang-Le,Wang, Fang-Dao,Yue, Jian-Min
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p. 567 - 570
(2007/10/03)
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- Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis.
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3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.
- Coleman, Paul J,Brashear, Karen M,Askew, Ben C,Hutchinson, John H,McVean, Carol A,Duong,Feuston, Bradley P,Fernandez-Metzler, Carmen,Gentile, Michael A,Hartman, George D,Kimmel, Donald B,Leu, Chih-Tai,Lipfert, Lorraine,Merkle, Kara,Pennypacker, Brenda,Prueksaritanont, Thomayant,Rodan, Gideon A,Wesolowski, Gregg A,Rodan, Sevgi B,Duggan, Mark E
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p. 4829 - 4837
(2007/10/03)
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- Anilide derivative, production and use thereof
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This invention is to provide a compound of the formula: wherein R1is an optionally substituted 5- to 6-membered ring; the ring A is an optionally substituted 6- to 7-membered ring; the ring B is an optionally substituted benzene ring; n is an integer of 1 or 2; Z is a chemical bond or a divalent group; R2is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula: ?wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium; and R5and R6are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, and R5and R6may bind to each other to form a cyclic group together with the adjacent phosphorus atom, or a salt thereof , which is useful for antagonizing CCR5 and also for the prevention and treatment of infectious disease of HIV.
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- Syntheses of 5- and 6-[2,3]-dihydrobenzofuran β-amino acids
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Efficient stereoselective syntheses of 5- and 6-[2,3]-dihydrobenzofuran β-amino acids are described. These 3-aryl β-amino acids are aspartic acid mimetics that are structurally related to known benzodioxole systems. In many cases, the benzodioxole can inhibit and induce cytochrome P-450; neither of these dihydrobenzofuran β-amino esters is a potent inhibitor of several human P-450 enzymes. (C) 2000 Elsevier Science Ltd.
- Coleman, Paul J.,Hutchinson, John H.,Hunt, Cecilia A.,Lu, Ping,Delaporte, Enock,Rushmore, Tom
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p. 5803 - 5806
(2007/10/03)
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- Depigmenting cosmetic or dermatologic composition containing a benzofuran derivative and its use in depigmentating skin
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A depigmenting cosmetic or dermatologic composition for use in bleaching the skin or treating pigmental spots contains in a vehicle suitable for topical application to the skin a benzofuran derivative having the formula STR1 wherein the OH function occupies position 5 or 6, R1 and R2, each independently, represent hydrogen or alkyl having 1-4 carbon atoms, n is 0 or 1, when n is 0, the C2 -C3 bond is a double bond, and when n is 1, the C2 -C3 bond is a single bond.
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- Structures and Stereochemical Assignments of Some Novel Chiral Synthons Derived from the Biotransformation of 2,3- Dihydrobenzofuran and Benzofuran by Pseudomonas putida
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Metabolism of 2,3-dihydrobenzofuran using intact cells of Pseudomonas putida UV4 gave mainly (3S)-3-hydroxy-2,3-dihydrobenzofuran which was in turn oxidized to an unstable intermediate, (3S,4R,5S)-3,4,5-trihydroxy-2,3,4,5-tetrahydrobenzofuran.Spontaneous dehydration of this cis,cis-triol occurred in the carbocyclic ring to give (3S)-3,5-dihydroxy 2,3-dihydrobenzofuran and in the heterocyclic ring to yield (4R,5S)-cis-4,5-dihydroxy-4,5-dihydrobenzofuran.Bacterial metabolism of benzofuran was found to occur in the carbocyclic ring to form (6S,7S)-cis-6,7-dihydroxy-6,7-dihydrobenzofuran and its dehydration product, 6-hydroxybenzofuran.Dioxygenase-catalysed cis-dihydrodiol formation in the heterocyclic ring of benzofuran (to give cis-2,3-dihydroxy-2,3-dihydrobenzofuran as a transient intermediate) is proposed to account for the appearance of (1R)-1,2-dihydroxy-1-(2'-hydroxyphenyl)ethane as a major metabolite of benzofuran. cis-4,5-Dihydroxy-4,5-dihydrobenzofuran and cis-6,7-dihydroxy-6,7-dihydrobenzofuran are potentially valuable chiral synthons which can be added to the small pool of bicyclic cis-dihydrodiol metabolites currently available for synthesis.
- Boyd, Derek R.,Sharma, Narain D.,Boyle, Rosemary,Malone, John F.,Chima, Jagdeep,Dalton, Howard
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p. 1307 - 1324
(2007/10/02)
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- Transition Metal Directed Synthesis of Moracin M, a Phytoalexin of Morus alba Linn.
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2-(5-Resorcinyl)benzofurans have been synthesised by the palladium catalysed cross coupling of 2-trimethylstannyl- or 2-bromozinc benzofurans with the appropriately functionalised 5-iodoresorcinols.These were synthesised by the tri-isopropylsilyloxy direc
- Mann, Inderjit S.,Widdowson, David A.,Clough, John M.
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p. 7981 - 7990
(2007/10/02)
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