Abstract: This invention relates to the use of cyclooxygenase-2 inhibitors or derivatives thereof in preventing and treating neoplasia. In particular, the invention describes the method of preventing and treating epithelial cell neoplasia in a subject, said method comprising treating the subject with a therapeutically-effective amount of a compound of Formula I.
Type:
Application
Filed:
August 23, 2002
Publication date:
November 27, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Karen Seibert, Jaime Masferrer, Gary B. Gordon
Abstract: Renal-selective prodrugs are described which are preferentially converted in the kidney to compounds capable of inhibiting synthesis of catecholamine-type neurotransmitters involved in renal sympathetic nerve activity. The prodrugs described herein are derived from inhibitor compounds capable of inhibiting one or more of the enzymes involved in catecholamine synthesis, such compounds being classifiable as tyrosine hydroxylase inhibitors, or as dopa-decarboxylase inhibitors, or as dopamine-&bgr;-hydroxylase inhibitors. These inhibitor compounds are linked to a chemical moiety, such as a glutamic acid derivative, by a cleavable bond which is recognized selectively by enzymes located predominantly in the kidney. The liberated inhibitor compound is then available in the kidney to inhibit one or more of the enzymes involved in catecholamine synthesis. Inhibition of renal catecholamine synthesis can suppress heightened renal nerve activity associated with sodium-retention related disorders such as hypertension.
Type:
Application
Filed:
May 20, 2002
Publication date:
November 27, 2003
Applicant:
G.D. Searle & Co.
Inventors:
David B. Reitz, John P. Koepke, Edward H. Blaine, Joseph R. Schuh, Robert E. Manning, Glenn J. Smits
Abstract: Succinoylamino hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Type:
Application
Filed:
September 9, 2002
Publication date:
November 27, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Michael L. Vazquez, Richard A. Mueller, John J. Talley, Daniel Getman, Gary A. DeCrescenzo, John N. Freskos
Abstract: N-Substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds of Formula I are effective in treatment of hepatitis infections, including hepatitis B and hepatitis C. In treating hepatitis infections, the compounds of Formula I may be used alone, or in combination with another antiviral agent selected from among nucleosides, nucleotides, immunomodulators, immunostimulants or various combinations of such other agents.
Type:
Application
Filed:
January 14, 2003
Publication date:
November 27, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Richard A. Mueller, Martin L. Bryant, Richard A. Partis
Abstract: A combination therapy comprising a therapeutically-effective amount of an epoxy-steroidal aldosterone receptor antagonist and a therapeutically-effective amount of a calcium channel blocker is described for treatment of circulatory disorders, including cardiovascular disorders such as hypertension, angina and congestive heart failure. Preferred calcium channel blockers are those compounds having high potency and bioavailability. Preferred epoxy-steroidal aldosterone receptor antagonists are 20-spiroxane steroidal compounds characterized by the presence of a 9&agr;,11&agr;-substituted epoxy moiety. A preferred combination therapy includes the calcium channel blocker amlodipine and the aldosterone receptor antagonist eplerenone.
Abstract: A combination comprising therapeutically-effective amount of an epoxy-steroidal aldosterone receptor antagonist and a therapeutically-effective amount of an angiotensin II receptor antagonist is described for treatment of circulatory disorders.
Type:
Grant
Filed:
January 9, 1997
Date of Patent:
November 25, 2003
Assignee:
G.D. Searle & Co.
Inventors:
John C. Alexander, Joseph R. Schuh, Richard J. Gorczynski
Abstract: Methods for producing mouse and human endostatin are disclosed. Methods for refolding and purifying endostatin from inclusion bodies expressed in bacteria and nucleic acids encoding full-length and truncated forms of endostatin are also disclosed.
Type:
Grant
Filed:
January 14, 1999
Date of Patent:
November 25, 2003
Assignee:
G. D. Searle & Co.
Inventors:
Bernard N. Violand, Elizabeth I. Harding
Abstract: Selected amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.
Type:
Application
Filed:
July 23, 2002
Publication date:
November 20, 2003
Applicant:
G. D. Searle & Co.
Inventors:
Daniel P. Getman, Gary A. DeCrescenzo, John N. Freskos, Michael L. Vazquez, James A. Sikorski, Balekudru Devadas, Srinivasan Nagarajan, David L. Brown, Joseph J. McDonald
Abstract: &agr;- and &bgr;-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Type:
Grant
Filed:
May 30, 2002
Date of Patent:
November 11, 2003
Assignee:
G. D. Searle & Co.
Inventors:
Michael L. Vazquez, Richard A. Mueller, John J. Talley, Daniel P. Getman, Gary A. DeCrescenzo, John N. Freskos, Deborah E. Bertenshaw, Robert M. Heintz
Abstract: Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and HMG Co—A reductase inhibitors for the treatment of hyperlipidemic conditions.
Type:
Grant
Filed:
February 15, 2002
Date of Patent:
November 4, 2003
Assignee:
G.D. Searle & Co.
Inventors:
Bradley T. Keller, Kevin C. Glenn, Robert E. Manning
Abstract: Selected bis-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.
Type:
Application
Filed:
March 15, 2002
Publication date:
October 30, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Daniel P. Getman, Gary A. DeCrescenzo, John N. Freskos, Michael L. Vazquez, James A. Sikorski, Balekudru Devadas, Srinivasan Raj Nagarajan, David L. Brown, Joseph J. McDonald
Abstract: A method of separating enantiomeric lactam esters. The lactam esters are contacted with a biocatalyst, such as an enzyme or a microorganism, in a solution wherein only one enantiomer is selectively hydrolyzed to give the optically active isomer of the corresponding acid. The hydrolysis product is then separated from the unreacted lactam esters. The enzyme is then recycled for reuse in the next enzymatic resolution. The undesired isomer is also racemized and reused in the next enzymatic resolution.
Type:
Grant
Filed:
June 6, 2001
Date of Patent:
October 28, 2003
Assignee:
G.D. Searle & Co.
Inventors:
Donald W. Hansen, Jr., Mahima Trivedi, Rolando E. Gapud, John S. Ng, Alok K. Awasthi, Ping T. Wang
Abstract: Stable cell lines are produced to express high levels of a gene product of interest using VP16, a herpes simplex virus transactivator, and a promoter from herpes simplex virus which is a target for VP16. The transactivator and promoter are introduced to a cell line separately using antibiotic resistance genes as selectable markers on separate vectors.
Type:
Grant
Filed:
April 30, 1996
Date of Patent:
October 21, 2003
Assignee:
G. D. Searle & Co.
Inventors:
Paul Jerome Hippenmeyer, Maureen Katherine Highkin
Abstract: Seryl-lysyl-based peptide and peptidomimetic compounds are described as inhibitors of the enzyme N-myristoyl transferase to provide selective control of the fungal organism Candida albicans. Peptidomimetic compounds of particular interest are those of the formula:
wherein R1 is selected form aminoalkyl, p-aminoalkylphenylalkyl, imidazolylalkylphenylalkyl, 2-alkylimidazolylalkylphenylalkyl, benzimidazolylalkylphenylalkyl and 2-alkylbenzimidazolylalkylphenylalkyl; wherein R2 is selected from hydrido, alkyl, cycloalkyl, akenyl, alkynyl, haloalkyl, benzyl, alkylphenylalkyl, alkoxyphenylalkyl, halophenylalkyl, phenethyl, cycloalkylalkyl, halocycloalkylalkyl, alkylcycloalkylalkyl, alkoxycycloalkylalkyl and naphthylalkyl; wherein Y is selected from carboxylic acid, hydroxamic acid, phosphonic acid and tetrazolyl; or a pharmaceutically-acceptable salt, amide or ester thereof. Compounds of the formula are species-specific inhibitors of C.
Type:
Grant
Filed:
March 26, 1999
Date of Patent:
October 14, 2003
Assignee:
G. D Searle & Co
Inventors:
James A. Sikorski, Devadas Balekudru, Daniel P. Getman, David L. Brown, Srinivasan Nagarajan, Mark E. Zupec, Jeffrey I. Gordon
Abstract: Selected sulfonylalkanoylamino hydroxyethylamine sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.
Type:
Application
Filed:
February 26, 2002
Publication date:
October 9, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Daniel P. Getman, Gary A. DeCrescenzo, John N. Freskos, Michael L. Vazquez, James A. Sikorski, Balekudru Devadas, Srinivasan Raj Nagarajan, Joseph J. McDonald
Abstract: A sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound that inter alia inhibits matrix metalloprotease activity is disclosed as are a treatment process that comprises administering a contemplated sulfonyl aromatic or heteroaromatic ring hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.
Type:
Application
Filed:
December 1, 2000
Publication date:
October 9, 2003
Applicant:
G. D. Searle & Co.,
Inventors:
Louis J. Bedell, Joseph J. McDonald, Thomas E. Barta, Daniel P. Becker, Shashidhar N. Rao, John N. Freskos, Brent V. Mischke, Daniel P. Getman, Gary A. DeCrescenzo, Clara I. Villamil
Abstract: &agr;- and &bgr;-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Type:
Application
Filed:
May 30, 2002
Publication date:
October 9, 2003
Applicant:
G.D. Searle & Co.
Inventors:
Michael L. Vazquez, Richard A. Mueller, John J. Talley, Daniel P. Getman, Gary A. DeCrescenzo, John N. Freskos, Deborah E. Bertenshaw, Robert M. Heintz
Abstract: The invention relates to substituted N-Aliphatic-N-Aromatic tertiary-Heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis, dyslipidemia, and other coronary artery disease.
Type:
Application
Filed:
December 16, 2002
Publication date:
October 9, 2003
Applicant:
G.D. Searle & Co.
Inventors:
James A. Sikorski, Richard C. Durley, Margaret L. Grapperhaus, Deborah A. Mischke, Emily J. Reinhard, Barry L. Parnas, Melvin L. Rueppel
Abstract: A class of 1-phenyl imidazol-2-one biphenylmethyl compounds is described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula
wherein each of R1, R2 and R3 is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, carboxyl, alkoxycarbonyl, formyl and acetyl; alkylcarbonyl and haloalkylcarbonyl; with the proviso that at least one of R1, R2 and R3 must be a substituent other than hydrido, and with the further proviso that when each of R1 and R3 is hydrido, then R2 cannot be chloro; wherein R4 is hydrido; wherein R5 is alkyl; and wherein R6 is tetrazolyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.