BIOMAT Database Logo BIOMAT Database Logo

The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues. 1998

M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Department of Chemical & Physical Sciences, DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0500, USA.

Two series of cyclic ureas modified at the P1/P1' residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.

UI MeSH Term Description Entries
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D007700 Kinetics The rate dynamics in chemical or physical systems.
D006678 HIV Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2. AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D001381 Azepines Seven membered heterocyclic rings containing a NITROGEN atom. Hexamethyleneimines
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014508 Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Basodexan,Carbamide,Carmol
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D016333 HIV Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Proteinase,HTLV-III Protease,p16 pol gene product, HIV,p16 protease, HIV,HIV p16 protease,HTLV III Protease,Protease, HIV,Protease, HTLV-III
D017320 HIV Protease Inhibitors Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly. HIV Protease Inhibitor,Inhibitor, HIV Protease,Inhibitors, HIV Protease,Protease Inhibitor, HIV,Protease Inhibitors, HIV

Related Publications

M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
A pharmacokinetic evaluation of HIV protease inhibitors, cyclic ureas, in rats and dogs.
October 1994, Biopharmaceutics & drug disposition,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors.
January 1994, Science (New York, N.Y.),
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.
June 2000, Bioorganic & medicinal chemistry letters,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.
August 1996, Journal of medicinal chemistry,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Cyclic HIV protease inhibitors: design and synthesis of orally bioavailable, pyrazole P2/P2' cyclic ureas with improved potency.
June 1998, Journal of medicinal chemistry,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Increased antiviral activity of cyclic urea HIV protease inhibitors by modifying the P1/P1' substituents.
August 1999, Bioorganic & medicinal chemistry letters,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Environmentally benign synthesis of unsymmetrical ureas and their evaluation as potential HIV-1 protease inhibitors via a computational approach.
April 2024, Molecular diversity,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-disubstituted ureas.
August 2004, Bioorganic & medicinal chemistry letters,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Potent inhibitors of the HIV-1 protease incorporating cyclic urea P1-P2 scaffold.
November 2004, Bioorganic & medicinal chemistry letters,
M Patel, and L T Bacheler, and M M Rayner, and B C Cordova, and R M Klabe, and S Erickson-Viitanen, and S P Seitz
Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2' to P1/P1'.
February 2005, Bioorganic & medicinal chemistry,
Copied contents to your clipboard!