- Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?
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Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.
- Adkison, Kim K.,Barrett, David G.,Deaton, David N.,Gampe, Robert T.,Hassell, Anne M.,Long, Stacey T.,McFadyen, Robert B.,Miller, Aaron B.,Miller, Larry R.,Payne, J. Alan,Shewchuk, Lisa M.,Wells-Knecht, Kevin J.,Willard Jr., Derril H.,Wright, Lois L.
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p. 978 - 983
(2007/10/03)
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- 6,6-BICYCLIC RING SUBSTITUTED HETEROBICYCLIC PROTEIN KINASE INHIBITORS
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Compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein XI, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.
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Page/Page column 392-395
(2008/06/13)
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- Potent and selective, sulfamide-based human β3-adrenergic receptor agonists
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A series of sulfamide-based analogs related to L-796568 were prepared and evaluated for their biological activity at the human β3- adrenergic receptor (AR). This modification allows for a significant reduction in molecular weight, while maintai
- Dow, Robert L.,Paight, Ernest S.,Schneider, Steven R.,Hadcock, John R.,Hargrove, Diane M.,Martin, Kelly A.,Maurer, Tristan S.,Nardone, Nancy A.,Tess, David A.,DaSilva-Jardine, Paul
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p. 3235 - 3240
(2007/10/03)
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- Synthesis and structure of 2-N,N-dimethyl- and 2-N,N-diethylsulfamoyl-1-(3-indolyl)-1,2-dihydroisoquinolines
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New sulfamoyl derivatives of (3-indolyl)-1,2-dihydroisoquinoline were prepared by reaction of isoquinoline and indole with sulfamoyl chlorides. The compounds were shown to exist in two isomeric forms by semiempirical quantum-chemical calculation in AMl ap
- Skrypnik,Vasil'eva,Lyashchuk,Bezrodnyi,Enya
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p. 577 - 580
(2007/10/03)
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- Sulfamates as antiglaucoma agents
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Sulfamate esters of the formula where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O)2 NR1 R2 groups attached to carbons of the alkyl moiety and is always at least one; R1 and R2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.
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- Compounds having one or more aminosulfaonyloxy radicals useful as pharmaceuticals
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Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:(HO)p--A--[--OS(O) 2 NR 1 R 2 ] zwherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O) 2 NR 1 R 2 groups and is always at least one; R 1 and R 2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.
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- Preparation of 2-chloro-5-methyl-pyridine
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A process for the preparation of 2-chloro-5-methylpyridine of the formula STR1 which comprises reacting 3-methyl-pyridine-1-oxide of the formula STR2 with a chlorinating agent of the formula STR3 in which R1 represents alkyl, halogenoalkyl, cycloalkyl, optionally substituted aryl, NR2 R3 or OR4 in which R2 and R3 individually represent alkyl, cycloalkyl or aryl or together represent alkanediyl or oxaalkanediyl and R4 represents alkyl, cycloalkyl or optionally substituted aryl, in the presence of a basic organic nitrogen compound and in the presence of a diluent at a temperature between about -20° C. and +150° C.
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- Aryl and aryloxyalkyl sulfamate esters useful as anticonvulsants
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Herein disclosed is a method of treating convulsions with a pharmaceutical composition containing a compound of the formula: where A is an aryl, arylalkyl, or aryloxyalkyl group and is substituted on 1 or more carbon atoms with a sulfamate group (--OSO2 NR1 R2) wherein R1 and R2, same or different, are hydrogen or loweralkyl wherein p is 0 or 1 and is the number of untreated hydroxyl groups and z is 1 or 2 and is the number of --OS(O2)NR1 R2 groups. Aryl is selected from phenyl, substituted phenyl, pyridinyl, naphthyl, quinolinyl, and the like. Phenyl substituents are selected from hydrogen, halo, hydroxy, phenyl, phenoxy, benzoyl, loweralkyl, loweralkoxy, carboxy, amino, loweralkylamino, diloweralkylamino, acetamido, cyano, nitro, loweralkoxycarboyl, aminosulfonyl, imidazolyl, triazolyl, and the like. Novel compounds not previously disclosed are also described.
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- Electrophilic Addition of Chloramine and Dimethylchloramine to Sulphur Dioxide and Oxidative Coupling of Sulphamide by Chloramine
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The addition of dimethylchloramine to sulphur dioxide is smooth and gives high yields of dimethylsulphamoyl chloride.A complex reaction of chloramine with sulphur dioxide occurs from which identification of sulphamoyl chloride is made by derivatization to
- Prakash, Hari,Sisler, Harry H.
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p. 935 - 937
(2007/10/02)
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