Patents Represented by Attorney Kenneth R. Walton
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Patent number: 6531617Abstract: Enantiomerically enriched hydroxychromanones are obtained by the AlCl3-catalyzed intramolecular Friedel-Crafts acylation of the corresponding 3-phenoxy-2-alkylcarbonyloxy-propionic acid followed by cleavage of the carboxylate in the presence of an alkali metal peroxide or hydroperoxide. Enantiomerically enriched cis-aminochromanols can then be prepared by treating the hydroxychromanones with a hydroxylamine and hydrogenating the resulting oxime. The cis-aminochromanols can be employed as intermediates in the production of HIV protease inhibitors which are useful for treating HIV infection and AIDS.Type: GrantFiled: October 24, 2001Date of Patent: March 11, 2003Assignee: Merck & Co., Inc.Inventors: Karl Hansen, Paul Devine, Philippe M. Rabbat
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Patent number: 6531484Abstract: Pyrrolidine compounds of Formula I: (wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, j, k, 1, m, and n are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.Type: GrantFiled: October 10, 2001Date of Patent: March 11, 2003Assignee: Merck & co., Inc.Inventors: Christopher A. Willoughby, Keith Rosauer, Kevin T. Chapman, Sander G. Mills, Dong-Ming Shen, Min Shu
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Patent number: 6511994Abstract: Compounds of Formula I: (wherein R1, R2, R3, R4, Q, and X are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.Type: GrantFiled: October 10, 2001Date of Patent: January 28, 2003Assignee: Merck & Co., Inc.Inventors: Ronald M. Kim, Jiang Chang, Kevin T. Chapman, Sander G. Mills
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Patent number: 6506777Abstract: The present invention is directed to compounds of the formula I: (wherein R1, R2, R3, R4, R5, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: June 8, 2000Date of Patent: January 14, 2003Assignee: Merck & Co., Inc.Inventors: Paul E. Finke, Jennifer L. Loebach, Malcolm Maccoss, Sander G. Mills
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Patent number: 6506908Abstract: Processes are disclosed for preparing 3-hydroxymethylcyclopentanone compounds, which are useful as intermediates in the preparation of HIV chemokine CCR-5 receptor antagonists. A process is described in which the compounds are prepared by opening the cyclopropyl ring of a (1-alkoxycarbonyl-2-oxo)-trans-bicyclo[3.1.0]hexane compound by addition of a nucleophile to the cyclopropyl ring, and then decarboxylating the resulting 2-alkoxycarbonyl-3-(Nu-methyl)-cyclopentanone (Nu=the added nucleophilic group) via base solvolysis. Also described is a process for preparing the bicyclo[3.1.0]hexane precursors by the catalyzed cyclopropanation of a suitable alpha-diazo-beta-ketoester. The preparation of the alpha-diazo-beta-ketoesters and precursors thereto are also disclosed.Type: GrantFiled: April 20, 2001Date of Patent: January 14, 2003Assignee: Merck & Co., Inc.Inventors: Nobuyoshi Yasuda, Michael Palucki, Joann M. Um, David Alan Conlon, Barry M. Trost
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Patent number: 6500844Abstract: The present invention is directed to compounds of the formula I: (wherein R1, R2, R3, R7, R8, X, Y, Z, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: June 8, 2000Date of Patent: December 31, 2002Assignee: Merck & Co., Inc.Inventors: Paul E. Finke, Kevin T. Chapman, Malcolm Maccoss, Sander G. Mills, Bryan Oates
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Patent number: 6498161Abstract: The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: April 4, 2000Date of Patent: December 24, 2002Assignee: Merck & Co., Inc.Inventors: Charles G. Caldwell, Kevin T. Chapman, Jeffrey Hale, Dooseop Kim, Christopher Lynch, Malcolm MacCoss, Sander G. Mills, Christopher Willoughby, Scott Berk, Ronald M. Kim
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Patent number: 6492423Abstract: Diketoacids of Formula (A) are useful as inhibitors of viral polymerases. In particular hepatitis C virus RNA dependent RNA polymerase (HCV RdRp), hepatitis B virus polymerase (HBV pol) and reverse transcriptase of human immunodeficiency virus (HIV RN.) The group R may be broadly chosen and is an organic moiety which contains 2 to 24 carbon atoms and includes an optionally cyclic or heterocyclic group in which the atom directly bonded to the adjacent carbonyl in the diketoacid is part of the ring structure.Type: GrantFiled: January 26, 2001Date of Patent: December 10, 2002Assignee: Istituto di Ricerche di Biologia Molecolare Pangeletti SpAInventors: Altamura Sergio, Licia Tomei, Uwe Koch, Philippe Jean Sigfried Neuner, Vincenzo Summa
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Patent number: 6482952Abstract: Acetonides are obtained in a one-step reaction of a carboxylic acid halide, a 1,2-aminoalcohol, and 2-alkoxypropene or 2,2-dialkoxypropane in an ether solvent and in the presence of an inorganic base. Acetonides are also obtained in a two-step reaction scheme in which an acid halide and 1,2-aminoalcohol are reacted in an ether solvent in the presence of LiOH to form a hydroxyamide, which is then reacted with 2-alkoxypropene or 2,2-dialkoxypropane in the presence of acid to form the acetonide. The acetonides resulting from the one-step and two-step protocols can be further reacted with an allylating agent such as an allyl halide in the presence of a strong base to provide the corresponding allyl acetonide. The acetonides and allyl acetonides can serve as intermediates in the production of certain HIV protease inhibitors which are useful for treating HIV infection and AIDS.Type: GrantFiled: June 18, 2001Date of Patent: November 19, 2002Assignee: Merck & Co., Inc.Inventors: Steven J. Cianciosi, Gregory L. Tewalt, Eric T. Pisk, Ilia A. Zavialov, Glenn A. Hulvey
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Patent number: 6476054Abstract: The present invention is directed to cyclic amines of the formula I: (wherein R1, R2, R3, m and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.Type: GrantFiled: October 17, 2000Date of Patent: November 5, 2002Assignee: Merck & Co., Inc.Inventors: Charles G. Caldwell, Paul E. Finke, Malcolm Maccoss, Sander G. Mills, Bryan Oates, Dooseop Kim, Shankaran Kothandaraman, Liping Wang
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Patent number: 6472410Abstract: The present invention is directed to compounds of the formula I: (wherein R1, R3, R4, R5, R6, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: June 8, 2000Date of Patent: October 29, 2002Assignee: Merck & Co., Inc.Inventors: Paul E. Finke, Kevin T. Chapman, Malcolm Maccoss, Sander G. Mills, Jennifer L. Loebach, Bryan Oates
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Patent number: 6436962Abstract: Arylhydantoin derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.Type: GrantFiled: September 27, 2000Date of Patent: August 20, 2002Assignee: Merck & Co., Inc.Inventors: Jacob M. Hoffman, Mark G. Bock, Robert M. DiPardo, Linda S. Payne, Michael A. Patane
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Patent number: 6432981Abstract: The present invention is directed to compounds of the formula I: (wherein R1, R2, R3, R4, R5, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: June 8, 2000Date of Patent: August 13, 2002Assignee: Merck & Co., Inc.Inventors: Paul E. Finke, Kerry A. Hilfiker, Jennifer L. Loebach, Malcolm Maccoss, Sander G. Mills, Dong-Ming Shen, Bryan Oates
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Patent number: 6410554Abstract: This invention relates to combination therapy for the treatment of benign prostatic hyperplasia comprising an alpha-1a antagonist and an endothelin antagonist. More specifically, the use of a selective alpha-1a adrenergic receptor antagonist in combination with a subtype non-selective endothelin antagonist provides relief of lower urinary tract symptoms in patients with symptomatic prostatism or benign prostatic hyperplasia. This combination therapy improves lower urinary tract symptoms including increasing urine flow rate, decreasing residual urine volume and improving overall obstructive and irritative symptoms in patients with benign prostatic hyperplasia or symptomatic prostatism.Type: GrantFiled: March 23, 1999Date of Patent: June 25, 2002Assignee: Merck & Co., Inc.Inventors: Theodore P. Broten, Peter K. S. Siegl, Steven A. Nichtberger
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Patent number: 6403347Abstract: Natural products such as certain chaetochromins are described. These compounds are useful in the inhibition of HIV integrase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.Type: GrantFiled: October 25, 1999Date of Patent: June 11, 2002Assignee: Merck & Co., Inc.Inventors: Gerald F. Bills, Russell B. Lingham, Ali Shafiee, Keith C. Silverman, Sheo Bux Singh, Deborah L. Zink, Fernando Pelaez, Ana M. Teran
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Patent number: 6399619Abstract: The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.Type: GrantFiled: April 4, 2000Date of Patent: June 4, 2002Assignee: Merck & Co., Inc.Inventors: Scott Berk, Charles G. Caldwell, Kevin T. Chapman, Jeffrey Hale, Christopher Lynch, Malcolm MacCoss, Sander G. Mills, Christopher Willoughby
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Patent number: 6395743Abstract: Compounds useful in the inhibition of HIV integrase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines are described. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. The culture Actinoplanes sp. MA7220 (ATCC 202188) is also disclosed, as well as processes for making compounds of the present invention employing the culture.Type: GrantFiled: October 12, 2000Date of Patent: May 28, 2002Assignee: Merck & Co., Inc.Inventors: Brian Heimbuch, Sheo Singh, Deborah L. Zink, Magda Gagliardi, Olga Genilloud, Ana Teran
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Patent number: 6387893Abstract: Spirotricyclic azacycloalkyl compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds is also described. One application of these compounds, which are alpha 1a adrenergic receptor antagonists, is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.Type: GrantFiled: September 27, 2000Date of Patent: May 14, 2002Assignee: Merck & Co., Inc.Inventors: Ben E. Evans, Jacob M. Hoffman, Kevin F. Gilbert, Kenneth E. Rittle
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Patent number: 6384244Abstract: cis-aminochromanols are obtained in high yield and with high selectivity over their trans counterparts by hydrogenating the corresponding oximes in the presence of a catalyst and an acid selected from HBr, HCl, and organic sulfonic acid. The cis-aminochromanols can be employed as intermediates in the production of HIV protease inhibitors which are useful for treating HIV infection and AIDS.Type: GrantFiled: May 11, 2001Date of Patent: May 7, 2002Assignee: Merck & Co., Inc.Inventors: Ian Davies, Karl Hansen, Paul N. Devine, Louis Matty, Jr., Yuan Cheng, Philippe M. Rabbat
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Patent number: 6380249Abstract: Certain six-membered aromatic and heteroaromatic-dioxobutyric acid derivatives are described as inhibitors of HIV integrase and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.Type: GrantFiled: June 1, 1999Date of Patent: April 30, 2002Assignees: Merck & Co., Inc., Tularik Inc.Inventors: Steven D. Young, Melissa Egbertson, Linda S. Payne, John S. Wai, Thorsten E. Fisher, James P. Guare, Jr., Mark W. Embrey, Lekhanh Tran, Linghang Zhuang, Joseph P. Vacca, H. Marie Langford, Jeffrey Melamed, Juan C. Jaen, David L. Clark, Julio C. Medina