- COMPOUNDS FOR TREATING AND PREVENTING GROWTH HORMONE RECEPTOR-DEPENDENT CONDITIONS
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The invention relates to compounds, in particular pyrimidine-2,4-diamines, analogues and salts thereof and pharmaceutical compositions comprising pyrimidine-2,4-diamines analogues and salts thereof for use in the treatment and prevention of a disease, in particular a growth hormone receptor-dependent condition. The invention also relates to methods of using these compounds and compositions to treat physiological dsorders related to the amount or activity of growth hormone. In a particular embodiment, the invention relates to a compound according to formula 1 for use in the treatment or prevention of a disease in a subject
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Paragraph 0064-0066
(2021/04/29)
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- T-TYPE CALCIUM CHANNEL BLOCKER
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To provide a novel T-type calcium channel blocker. A compound represented by the following General Formula (I), a tautomer or a stereoisomer of the compound, a pharmaceutically acceptable salt of the compound, or a solvate of the compound, the tautomer, the stereoisomer, or the salt is used as a T-type calcium channel blocker. wherein A represents a phenyl which may have a substituent, a 4-membered to 6-membered heteroaryl ring composed of one to three identical or different heteroatoms selected from an oxygen atom, a sulfur atom, and a nitrogen atom and carbon atoms as ring-constituting atoms, or a heterocondensed ring composed of the heteroaryl ring and either a benzene ring or a 6-membered heteroaryl ring composed of one to two nitrogen atoms and carbon atoms, wherein the heteroaryl ring or the heterocondensed ring may have a substituent and is bonded to a nitrogen atom of the adjacent cyclic amino by means of a carbon atom constituting these rings; B represents a phenyl which may have a substituent, a 5-membered or 6-membered heteroaryl ring composed of one to three identical or different heteroatoms selected from an oxygen atom, a sulfur atom, and a nitrogen atom and carbon atoms as ring-constituting atoms, or a heterocondensed ring composed of the heteroaryl ring and either a benzene ring or a 6-membered heteroaryl ring composed of one to two nitrogen atoms and carbon atoms, wherein the heteroaryl ring or the heterocondensed ring may have a substituent and is bonded to the adjacent cyclopropyl ring by means of a carbon atom constituting these rings; R1 and R2, which may be identical or different, each represent a hydrogen atom, a halogen atom, or the like; R3 represents a hydrogen atom, a halogen atom, or the like; n and m, which may be identical or different, each represent 0 or 1; and p represents 1 or 2.
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Paragraph 0437-0438
(2021/05/29)
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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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- Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Free Carboxylic Acids
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A monoprotected aminoethyl amine chiral ligand based on an ethylenediamine backbone was developed to achieve Pd-catalyzed enantioselective C(sp3)-H arylation of cyclopropanecarboxylic and 2-aminoisobutyric acids without using exogenous directing groups. This new chiral catalyst affords new disconnection for preparing diverse chiral carboxylic acids from simple starting materials that are complementary to the various ring forming approaches.
- Shen, Peng-Xiang,Hu, Liang,Shao, Qian,Hong, Kai,Yu, Jin-Quan
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supporting information
p. 6545 - 6549
(2018/05/23)
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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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- Development of a palladium-catalyzed α-arylation of cyclopropyl nitriles
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1,1-Disubstituted aryl cyclopropyl nitriles are useful moieties in biologically active compounds and provide access to a range of cyclopropyl derivatives. Herein, we describe the development of a palladium-catalyzed α-arylation of cyclopropyl, cyclobutyl, and cyclopentyl nitriles that affords these functional groups in one step from a variety of aryl bromides in good to excellent yields. Furthermore, we demonstrate the transformation of aryl cyclopropyl nitriles into aryl trifluoromethyl cyclopropanes.
- McCabe Dunn, Jamie M.,Kuethe, Jeffrey T.,Orr, Robert K.,Tudge, Matthew,Campeau, Louis-Charles
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supporting information
p. 6314 - 6317
(2015/02/19)
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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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- 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 17-18
(2008/12/04)
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- SUBSTITUTED ARYLPYRAZOLOPYRIDINES AND SALTS THEREOF, PHARMACEUTICAL COMPOSITIONS COMPRISING SAME, METHODS OF PREPARING SAME AND USES OF SAME
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The invention relates to substituted arylpyrazolopyridines according to the general formula (I) : in which A, B, D, E, Ra, R1, R2, R3, R4, R5 and q are as defined in the claims, and salts t
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Page/Page column 69
(2008/06/13)
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