- Synthetic method 5- of -4- (-1- I -3-)-(C)-(C)-ethyl-methyl-indol. (by machine translation)
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To the method, the 3 - indole chromogenic 5 - substrate is obtained, by hydrolyzing the indole phenol with acetic. anhydride, under an acidic condition with acetic, anhydride to form an indole, chromogenic substrate by hydrolyzing the, indole phenol, with acetic anhydride under an acidic, condition with acetic anhydride under an acidic condition 5 - 5 . (by machine translation)
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- INHIBITORS OF RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Compounds of Formula I and the pharmaceutically acceptable salts thereof are provided as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
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- Indoxylic acid esters as convenient intermediates towards indoxyl glycosides
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Indoxylic acid methyl and allyl esters with varied halide-substitution patterns were obtained in excellent yields using a scalable route. Phase-transfer glycosylation of these key intermediates was carried out with various glycosyl halides. Subsequent mild silver-mediated decarboxylation followed by Zemplen deacetylation led to indoxyl glycosides in good overall yields. Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme-activity monitoring. In the past, their synthesis has been difficult, so this new approach has led to a variety of useful structures. Indoxyl glycosides with varied halide-substitution patterns were synthesized using indoxylic acid esters as key intermediates. Glycosylation under phase-transfer conditions, ester cleavage, and mild decarboxylation led to the indoxyl glycosides in good yields. This approach enables access to a number of different indoxyl compounds. Copyright
- Boettcher, Stephan,Thiem, Joachim
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p. 564 - 574
(2014/02/14)
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- PYRAZOLINE DERIVATIVES AND THEIR USE AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The invention relates to a compound of formula (I) in free form or in pharmaceutically acceptable salt form (I), in which the substituents are as defined in the specification; to compounds of formula (I) for use as androgen receptor modulators. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
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- Novel efficient routes to indoxyl glycosides for monitoring glycosidase activities
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A new efficient synthesis for broad access to indoxyl glycosides was developed. Indoxylic acid allyl ester linked to a sugar structure served as the key intermediate in this route. Selective ester cleavage and mild decarboxylation led to the corresponding indoxyl glycosides in good yields. This synthesis was applied for preparation of indoxyl glycosides of fucose, sialic acid, and 6′-sialyl lactose.
- Boettcher, Stephan,Hederos, Markus,Champion, Elise,Dekany, Gyula,Thiem, Joachim
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supporting information
p. 3766 - 3769
(2013/08/23)
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- PYRAZOLINE DERIVATIVES AND THEIR USE AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The invention relates to a compound of formula (I) in free form or in pharmaceutically acceptable salt form (I), in which the substituents are as defined in the specification; to compounds of formula (I) for use as androgen receptor modulators. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition
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- ARYL FLUOROETHYL UREAS ACTING AS ALPHA 2 ADRENERGIC AGENTS
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The invention provides well-defined aryl fluoroethyl ureas that are useful as selective alpha2 adrenergic agonists. As such, the compounds described herein are useful in treating a wide variety of disorders associated with modulation of alpha2 adrenergic receptors.
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Page/Page column 24-25
(2008/12/07)
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- Discovery of potent and muscle selective androgen receptor modulators through scaffold modifications
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A novel series of imidazolin-2-ones were designed and synthesized as highly potent, orally active and muscle selective androgen receptor modulators (SARMs), with most of the compounds exhibiting low nM in vitro potency in androgen receptor (AR) binding and functional assays. Once daily oral treatment with the lead compound 11a (AR Ki = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in rats demonstrated that the lead compound 11a had oral bioavailability of 65% and a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the SARMs in this series are expected to provide beneficial anabolic effects on muscle with minimal androgenic effects on prostate tissue.
- Li, James J.,Sutton, James C.,Nirschl, Alexandra,Zou, Yan,Wang, Haixia,Sun, Chongqing,Pi, Zulan,Johnson, Rebecca,Krystek Jr., Stanley R.,Seethala, Ramakrishna,Golla, Rajasree,Sleph, Paul G.,Beehler, Blake C.,Grover, Gary J.,Fura, Aberra,Vyas, Viral P.,Li, Cindy Y.,Gougoutas, Jack Z.,Galella, Michael A.,Zahler, Robert,Ostrowski, Jacek,Hamann, Lawrence G.
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p. 3015 - 3025
(2008/02/06)
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- Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
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Pharmacokinetic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. Subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential.
- Hamann, Lawrence G.,Manfredi, Mark C.,Sun, Chongqing,Krystek Jr., Stanley R.,Huang, Yanting,Bi, Yingzhi,Augeri, David J.,Wang, Tammy,Zou, Yan,Betebenner, David. A.,Fura, Aberra,Seethala, Ramakrishna,Golla, Rajasree,Kuhns, Joyce E.,Lupisella, John A.,Darienzo, Celia J.,Custer, Laura L.,Price, Jennifer L.,Johnson, James M.,Biller, Scott A.,Zahler, Robert,Ostrowski, Jacek
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p. 1860 - 1864
(2008/02/04)
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- Novel bicyclic compounds as modulators of androgen receptor function and method
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The present invention relates to bicyclic compounds according to formula I, pharmaceutical compositions containing such compounds and methods of using such compounds in the treatment of androgen receptor-associated conditions, such as age-related diseases, for example sarcopenia, wherein R1, R2, R5, X and n are defined herein.
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Page/Page column 16-17
(2010/11/25)
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- SUBSTITUTED N-ARYLPYRROLIDINES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula I or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly frailty, osteoporosis, osteopenia, and male and female sexual dysfunction comprising administering to a patient in need thereof an effective amount of a compound of Formula I.
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Page/Page column 64
(2010/11/25)
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- MONOCYCLIC N-ARYL HYDANTOIN MODULATORS OF ANDROGEN RECEPTOR FUNCTION
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The present invention relates to novel compounds useful in the treatment of androgen receptor associated conditions, such as age-related diseases, pharmaceutical compositions containing at least one of the compounds of the present invention and methods of treating a patient in need of therapy for an androgen receptor associated condition by administering a therapeutically effective amount of at least compound of the present invention.
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Page/Page column 43
(2010/02/12)
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- Novel bicyclic compounds as modulators of androgen receptor function and method
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The present invention relates to bicyclic compounds according to formula I, pharmaceutical compositions containing such compounds and methods of using such compounds in the treatment of androgen receptor-associated conditions, such as age-related diseases, for example sarcopenia, wherein R1, R2, R2′ R5, G, n and W are defined herein.
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Page/Page column 17
(2010/02/13)
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- Bicyclic modulators of androgen receptor function
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The invention provides for a pharmaceutical composition capable of modulating the androgen receptor comprising a compound of formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia. Also provided are pharmaceutical compositions containing such compounds and processes for preparing some of the compounds of the invention.
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- BICYCLIC MODULATORS OF ANDROGEN RECEPTOR FUNCTION
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The invention provides compounds according to formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia. Also provided are pharmaceutical compositions containing such compounds and processes for preparing some of the compounds of the invention.
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