Patents Represented by Attorney, Agent or Law Firm Mark R. Daniel
  • Inhibitors of farnesyl-protein transferase
    Patent number: 5504212
    Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
    Type: Grant
    Filed: October 29, 1992
    Date of Patent: April 2, 1996
    Assignee: Merck & Co., Inc.
    Inventors: S. Jane de Solms, Samuel L. Graham, John S. Wai
  • Inhibitors of farnesyl protein transferase
    Patent number: 5504115
    Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
    Type: Grant
    Filed: June 28, 1994
    Date of Patent: April 2, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Albert A. Deana, deceased, S. Jane deSolms, Samuel L. Graham, Robert L. Smith
  • Method and system for determining the homogeneity of tablets
    Patent number: 5504332
    Abstract: A method and system for determining the homogeneity of one or more components of a mixture of ingredients, especially, is presented. Most importantly, it can be used to determine homogeneity of a tabletted mixture of the produced pharmaceuticals, including active and inactive ingredients. The method and system monitor the pharmaceutical material during tablet manufacture as a powder mix, granular mix and compressed tablets. This system uses near infrared technology for analyzing the uniformity and mass balance of the pharmaceutical mixture to control the tablet manufacturing process. As part of the system and method, a NIR spectral library, consisting of a pharmaceutical materials spanning the normal process range for is developed. Assessment of uniformity is accomplished by comparison of future production with the library of acceptable material.
    Type: Grant
    Filed: August 26, 1994
    Date of Patent: April 2, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Eric W. Richmond, Bruce R. Buchanan, Mark A. Baxter, Andy Duff, Oksana M. Tully, Samuel A. Thornton
  • 3-thioheteroaryl cephalosporin compounds, compositions and methods of use
    Patent number: 5498777
    Abstract: Cephalosporin compounds of the formula I ##STR1## are disclosed. The compounds are useful against MRSA/MRCNS. Compositions and methods of use are also included.
    Type: Grant
    Filed: July 20, 1994
    Date of Patent: March 12, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Lovji D. Cama, Mary F. Sasor, Milton L. Hammond
  • Carbapenem antibacterial compounds, compositions containing such compounds and methods of treatment
    Patent number: 5496816
    Abstract: Carbapenems of the formula: ##STR1## are disclosed as useful antibacterial agents. Pharmaceutical compositions and methods of use are also disclosed.
    Type: Grant
    Filed: December 20, 1994
    Date of Patent: March 5, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Timothy A. Blizzard, Ronald W. Ratcliffe, Sherman T. Waddell, Sandra P. Szumiloski, Robert R. Wilkening, Kenneth J. Wildonger
  • Scorpion peptide margatoxin with immunosuppressant activity
    Patent number: 5494895
    Abstract: A thirty-nine amino acid peptide, Margatoxin (MgTX), is purified to homogeneity from venom of the scorpion Centruroides margaritatus. The gene encoding MgTX is constructed and this gene is expressed in E. coli, to produce recombinant MgTX. MgTX is a potent and selective inhibitor of a voltage-dependent K.sup.+ channel present in human lymphocytes. MgTX exhibits immunosuppressant activity with human T-lymphocytes, and is useful as an immunosuppressant, in modeling nonpeptidyl K.sup.+ channel blockers, and in establishing biochemical assays based on ligand binding or other protocols with which to screen for other novel modulators of voltage dependent K.sup.+ channels in lymphocytes and other tissues including the brain. As an immunosuppressant, MgTX is useful in the treatment of autoimmune diseases, the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.
    Type: Grant
    Filed: July 22, 1993
    Date of Patent: February 27, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Maria L. Garcia, Gloria C. Koo, Reid J. Leonard, Chiu-Chuan S. Lin, Robert S. Slaughter, Scott P. Stevens, Joanne M. Williamson
  • Endothelin antagonists incorporating a cyclobutane
    Patent number: 5492917
    Abstract: Novel compounds of the general structural formula I: ##STR1## have endothelin antagonist activity and are therefore useful in treating cardiovascular disorders, such as hypertension, pulmonary hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, endotoxic shock, inflammatory diseases including Raynaud's disease and asthma.
    Type: Grant
    Filed: September 29, 1993
    Date of Patent: February 20, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Ralph A. Rivero, Peter D. Williams, Daniel F. Veber
  • Process for synthesizing carbapenem intermediates using a rhodium catalyst and lewis acid
    Patent number: 5493018
    Abstract: This invention relates to the synthesis of a bicyclic ketoester compound of the formula 1 obtained by cyclizing a diazo compound of formula 2: in the presence of a rhodium catalyst. ##STR1## By adding an effective amount of a Lewis acid to the cyclization reaction, the reaction selectively produces the 1-beta methyl isomer, and epimerization of the 1-beta methyl compound to the 1-alpha isomer is minimized.
    Type: Grant
    Filed: January 25, 1994
    Date of Patent: February 20, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Thomas Meng-Han Liu, Joseph E. Lynch, Ralph P. Volante
  • Inhibitors of farnesyl-protein transferase
    Patent number: 5491164
    Abstract: The present invention comprises dipeptide analogs that inhibit the farnesylation of Ras. These farnesyl-protein transferase inhibitors are characterized by the inclusion of a cyclic amine in the backbone of the dipeptide. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
    Type: Grant
    Filed: September 29, 1994
    Date of Patent: February 13, 1996
    Assignee: Merck & Co., Inc.
    Inventors: S. Jane deSolms, Samuel J. Graham
  • Child resistant medication container
    Patent number: 5489024
    Abstract: There is disclosed a medication container which is adapted to be side loaded with unit doses of medication during packaging operations. After being filled with the unit doses of medication, the container side is sealed. The medication doses can be removed by a user from the sealed container by means of a child resistant removable closure at one end of the container.
    Type: Grant
    Filed: August 8, 1994
    Date of Patent: February 6, 1996
    Assignee: Merck & Co., Inc.
    Inventor: Leonid Bunin
  • Process of making spirocycles and analogs thereof
    Patent number: 5484923
    Abstract: The present invention is directed to a process of making spirocycles of general structural formula: ##STR1## where R.sub.1 is selected from the group consisting of CO--C.sub.1-3 alkyl, cyano, carboxy, carboxy C.sub.1-6 alkyl ester, carboxamide, C.sub.1-6 alkyl sulfinyl, C.sub.1-6 alkyl sulfonyl, C.sub.1-6 methanesulfonamide and halogen; R.sub.2 is selected from the group consisting of keto or alcohol, R.sub.3 is cyano, resulting in compounds which are Class III antiarrhythmic.
    Type: Grant
    Filed: May 31, 1994
    Date of Patent: January 16, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Dongwei Cai, Richard Desmond, Yao-Jun Shi, David M. Tschaen, Thomas R. Verhoeven
  • Inhibitors of farnesyl protein transferase
    Patent number: 5480893
    Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
    Type: Grant
    Filed: May 13, 1994
    Date of Patent: January 2, 1996
    Assignee: Merck & Co., Inc.
    Inventors: Samuel L. Graham, S. Jane deSolms
  • Bioconversion products of 27-hydroxy avermectin
    Patent number: 5478929
    Abstract: There are disclosed novel compounds which are derived from 22,23-dihydro avermectin B1 aglycone. The compounds are both isomers of the 27-hydroxy adduct of the substrate avermectin compound that have been glycosylated at the 4" position to yield 4"-O-glucosyl 27-OH avermectin compounds. The compounds and the intermediates used to make them are highly potent antiparasitic, insecticidal and anthelmintic avermectin agents.
    Type: Grant
    Filed: May 20, 1994
    Date of Patent: December 26, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Byron H. Arison, Patrick J. Doherty, Marvin D. Schulman
  • Bioconversion process for the synthesis of transhydroxy sulfone by Rhodotorula rubra or Rhodotorula piliminae
    Patent number: 5474919
    Abstract: There is disclosed a novel microbial bioconversion process for the synthesis of a trans-hydroxy sulfone intermediate, which is the precursor to topical carbonic anhydrase inhibitors (TCAI's). TCAI's are effective in the treatment of glaucoma and ocular hypertension. The bioconversion process is carried out in the presence of the microorganism Rhodotorula rubra, or Rhodotorula piliminae and results in a trans-hydroxy sulfone which exhibits a diastereomeric excess of greater than 95%.
    Type: Grant
    Filed: September 13, 1994
    Date of Patent: December 12, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Michel M. Chartrain, Lorraine G. Katz, Steven A. King
  • Expression and purification of phosphoinositide-specific phospholipase C-.gamma.
    Patent number: 5474921
    Abstract: The present invention is directed to an assay which is used to determine the inhibitory activity of a test compound against a particular phosphoinositide-specific phospholipase C enzyme, that enzyme being phospholipase C.gamma.. The present invention is also directed to the preparation of phospholipase C.gamma. by recombinant expression in a bacterial cell and isolation of the expressed enzyme.
    Type: Grant
    Filed: October 15, 1993
    Date of Patent: December 12, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Kenneth S. Koblan, David L. Pompliano
  • E2F-2, a novel mammalian transcription factor
    Patent number: 5473056
    Abstract: The present invention is directed to a novel protein with E2F-like properties and the cDNA that encodes for that protein. The purified protein exhibits biological activity which is deemed important to medical science in the study of cell cycle regulation in general and the specific study of the Rb rumor suppressor protein and certain viral oncogenes. The protein may be employed in a complex with pRb or other cellular proteins to study inhibitors of biochemical transformations of those proteins, such as for example the phosphorylation of the pRb portion of the complex, therefore aiding in the study of potential pharmaceutical agents useful against certain oncoproteins encoded by DNA tumor viruses.
    Type: Grant
    Filed: October 13, 1993
    Date of Patent: December 5, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Mona Ivey-Hoyle, Allen I. Oliff, David C. Heimbrook
  • Inhibitors of geranylgeranyl-protein transferase
    Patent number: 5470832
    Abstract: The compounds disclosed am analogs of the CAAX motif of proteins that can be modified by geranylgeranylation in vivo that selectively inhibit the geranylgeranylation of several proteins. The relatively poor activity of the compounds against the farnesyl protein transferase, which modifies several proteins important in cellular replication, allows the use of the compounds of the instant invention to treat diseases which which am regulated by the function of a geranylgeranylated protein, such as certain cancers and inflammatory diseases. Further contained in this invention are chemotherapeutic compositions containing these geranylgeranyl protein transfcrase type I inhibitors and methods for their production.
    Type: Grant
    Filed: January 31, 1994
    Date of Patent: November 28, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Jackson B. Gibbs, Samuel L. Graham
  • Inhibitors of farnesyl-protein transferase
    Patent number: 5468733
    Abstract: The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.
    Type: Grant
    Filed: September 30, 1993
    Date of Patent: November 21, 1995
    Assignee: Merck & Co., Inc.
    Inventors: S. Jane deSolms, Elizabeth A. Giuliani, Samuel L. Graham
  • Dioxolenylmethyl carbamates pro moieties for amine drugs
    Patent number: 5466811
    Abstract: This invention relates to a the use of new oxodioxolenylmethyl carbamates to produce bioreversible neutral prodrugs from primary and secondary amines.
    Type: Grant
    Filed: July 18, 1994
    Date of Patent: November 14, 1995
    Assignee: Merck & Co., Inc.
    Inventor: Jose Alexander
  • Asymmetric bioreduction of 6-bromo-2-tetralone to (s)-6-bromo-2 tetraol by trichosporon capitatum
    Patent number: 5464762
    Abstract: Stereospecific (S)-6-bromo-2-tetraol is a key intermediate in the chemical synthesis of the chiral drug candidate, MK499, a ventricular arrythmias suppressant. The yeast strain Trichosporon capitatum (MY 1890) was employed for the bioconversion of 6-bromo-2-tetralone to the corresponding alcohol.
    Type: Grant
    Filed: June 24, 1994
    Date of Patent: November 7, 1995
    Assignee: Merck & Co., Inc.
    Inventors: Michel M. Chartrain, Jayanthi Reddy, David M. Tschaen