- Nickel-Catalyzed Favorskii-Type Rearrangement of Cyclobutanone Oxime Esters to Cyclopropanecarbonitriles
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A nickel-catalyzed base-promoted rearrangement of cyclobutanone oxime esters to cyclopropanecarbonitriles was developed. The ring opening of cyclobutanone oxime esters occurs at the sterically less hindered side. A base-promoted nickelacyclobutane intermediate, formed in situ, is assumed to be involved in the formation of the product.
- Shuai, Bin,Fang, Ping,Mei, Tian-Sheng
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p. 1637 - 1641
(2021/10/02)
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- Preparation method of arylcyclopropane compound
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The present invention discloses a method for preparing an arylcyclopropane compound, 1.0eq phenylacetonitrile and 1.1eq 1-bromo-2-chloroethane as the starting material, N, N- dimethylacetamide as a solvent, solvent dosage of 10V, plus 2.5eq sodium hydride
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Paragraph 0023-0028; 0034-0038
(2022/01/10)
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- MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
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Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. Formula I
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Page/Page column 32; 33
(2019/01/16)
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- Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Enantioselective C(sp3)-H Borylation of Cyclopropanes
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We herein report an Ir-catalyzed enantioselective C(sp3)-H borylation of cyclopropanecarboxamides using a chiral bidentate boryl ligand for the first time. A variety of substrates with α-quaternary carbon centers could be compatible in this reaction to provide β-borylated products with good to excellent enantioselectivities. We have also demonstrated that the borylated products can be used as versatile precursors engaging in stereospecific transformations of C-B bonds, including the synthesis of a bioactive compound Levomilnacipran.
- Shi, Yongjia,Gao, Qian,Xu, Senmiao
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supporting information
p. 10599 - 10604
(2019/08/28)
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- Efficient cyclopropanation of aryl/heteroaryl acetates and acetonitriles with vinyl diphenyl sulfonium triflate
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A convenient method was developed for the cyclopropanation of aryl acetates and aryl acetonitrile using vinyl diphenyl sulfonium triflate salt. The newly developed conditions are simple, mild, and compatible with a wide range of functional groups, without the need to apply an inert atmosphere, or alkali bases.
- Zhou, Mingwei,Hu, Yimin,En, Ke,Tan, Xuefei,Shen, Hong C.,Qian, Xuhong
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supporting information
p. 1443 - 1445
(2018/03/12)
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- INHIBITOR OF INDOLEAMINE-2,3-DIOXYGENASE (IDO)
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The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
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Paragraph 00182-00183
(2017/09/05)
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- Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl Amide
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A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.
- Wong, Ying-Chieh,Ke, Zhihai,Yeung, Ying-Yeung
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supporting information
p. 4944 - 4947
(2015/11/03)
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- Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8- (trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury
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Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.
- Huang, Adrian,Moretto, Alessandro,Janz, Kristin,Lowe, Michael,Bedard, Patricia W.,Tam, Steve,Di, Li,Clerin, Valerie,Sushkova, Natalia,Tchernychev, Boris,Tsao, Desiree H. H.,Keith Jr., James C.,Shaw, Gray D.,Schaub, Robert G.,Wang, Qin,Kaila, Neelu
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supporting information; experimental part
p. 6003 - 6017
(2010/11/19)
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- Novel pyrimidines as acid pump antagonists (APAs)
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A series of pyrimidine derivatives as acid pump antagonists (APAs) was synthesized and the inhibitory activities against H+/K+ ATPase isolated from hog gastric mucosa were determined. After elaborating on substituents at C2 and C4 po
- Yoon, Young Ae,Park, Chan Sun,Cha, Myung Hun,Choi, Hyunho,Sim, Jae Young,Kim, Jae Gyu
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scheme or table
p. 5735 - 5738
(2010/11/24)
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- Distinctive molecular inhibition mechanisms for selective inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
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11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the NADPH dependent interconversion of inactive cortisone to active cortisol. Excess 11β-HSD1 or cortisol leads to insulin resistance and metabolic syndrome in animal models and in humans. Inhibiting 11β-HSD1 activity signifies a promising therapeutic strategy in the treatment of Type 2 diabetes and related diseases. Herein, we report two highly potent and selective small molecule inhibitors of human 11β-HSD1. While compound 1, a sulfonamide, functions as a simple substrate competitive inhibitor, compound 2, a triazole, shows the kinetic profile of a mixed inhibitor. Co-crystal structures reveal that both compounds occupy the 11β-HSD1 catalytic site, but present distinct molecular interactions with the protein. Strikingly, compound 2 interacts much closer to the cofactor NADP+ and likely modifies its binding. Together, the structural and kinetic analyses demonstrate two distinctive molecular inhibition mechanisms, providing valuable information for future inhibitor design.
- Tu, Hua,Powers, Jay P.,Liu, Jinsong,Ursu, Stefania,Sudom, Athena,Yan, Xuelei,Xu, Haoda,Meininger, David,DeGraffenreid, Michael,He, Xiao,Jaen, Juan C.,Sun, Daqing,Labelle, Marc,Yamamoto, Hiroshi,Shan, Bei,Walker, Nigel P.C.,Wang, Zhulun
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experimental part
p. 8922 - 8931
(2009/04/06)
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- OXADIAZOLE COMPOUNDS AS CALCIUM CHANNEL ANTAGONISTS
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This invention relates to novel compounds of formula (I) wherein R1, R2, R3, R4, R5, G1, G2, Y, n, and Ar1 are as defined in the specification, pharmaceutical composit
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Page/Page column 37
(2008/12/05)
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- Methods and Compositions for Selectin Inhibition
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The present teachings relate to novel compounds of formula I: wherein the constituent variables are as defined herein. Compounds of the present teachings can act as antagonists of the mammalian adhesion proteins known as selecting. Methods for treating or preventing selectin-mediated disorders are provided, which include administration of these compounds in a therapeutically effective amount.
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Page/Page column 21
(2008/12/04)
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- OXADIAZOLE DERIVATIVES WITH CRTH2 RECEPTOR ACTIVITY
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Compounds of formula (I) are CRTH2 ligands, useful for treatment of inflammatory, autoimmune, respiratory or allergy disease: wherein R1 is hydrogen or methyl and R2 is optionally substituted cycloalkyl, or optionally substituted non
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Page/Page column 17; 22
(2008/06/13)
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- Efficient cyclopropanation of active methylene compounds. A serendipitous discovery
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Cyclopropanation of active methylene compounds has been achieved in good yields with ethylene carbonate as the cyclopropanating agent in the presence of a simple base.
- Arava, Veera Reddy,Siripalli, Udaya Bhaskara Rao,Dubey, Pramod Kumar
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p. 7247 - 7248
(2007/10/03)
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- 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1 INHIBITORS USEFUL FOR THE TREATMENT OF DIABETES, OBESITY AND DYSLIPIDEMIA
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Compounds having Formula (I), including pharmaceutically acceptable salts, hydrates and solvates thereof, are selective inhibitors of the 11β-HSD1 enzyme. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dylsipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM.
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