Triterpene amine derivatives
AssigneesDfh Therapeutics, Inc., The United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsTheodore J. Nitz, Carl T. Wild, David E. Martin, Eric O. Freed
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Abstract
The present invention concerns novel pharmaceutically active triterpene amine derivatives, pharmaceutical compositions containing the same, their use as medicaments, and the use of the compounds for the manufacture of specific medicaments. The present invention also concerns a method of treatment involving administration of the triterpene amine compounds. Specifically, the compounds are derivatives of betulinic acid having substitutions at one or more of the C-3, C-28 and C-19 positions as further described herein. The novel compounds are useful as antiretroviral agents. In particular, the novel compounds are useful for the treatment of Human Immunodeficiency Virus-1 (HIV-1).
Claims14
A compound according to Formula I:
- or a pharmaceutically acceptable salt, tautomer thereof, wherein:
- R1 is selected from the group consisting of substituted or unsubstituted C3-C20 alkanoyl, carboxyalkanoyl, carboxycyloalkylalkanoyl, carboxyalkylcycloalkylalkanoyl, carboxycyloalkylcarbonyl, carboxyalkylcycloalkylcarbonyl, alkoxycarbonylcycloalkylcarbonyl, alkoxycarbonylalkylcycloalkylcarbonyl, trialkylsilylalkoxycarbonylcyloalkylcarbonyl, trialkylsilylalkoxycarbonylalkylcycloalkylcarbonyl, arylalkyloxycarbonylcycloalkylcarbonyl, arylalkyloxycarbonylalkylcycloalkylcarbonyl, alkoxycarbonylalkanoyl, alkoxycarbonylcyloalkylalkanoyl, alkoxycarbonylalkylcycloalkylalkanoyl, trialkylsilylalkoxycarbonylalkanoyl, trialkylsilylalkoxycarbonylcyloalkylalkanoyl, trialkylsilylalkoxycarbonylalkylcycloalkylalkanoyl, arylalkyloxycarbonylalkanoyl, arylalkyloxycarbonylcyloalkylalkanoyl, and arylalkyloxycarbonylalkylcycloalkylalkanoyl, wherein any alkyl or cycloalkyl group is independently substituted with one or more groups selected from the group consisting of hydrido, halo, or C1-C6 alkyl groups;
- n is an integer from one to six;
- R2 is hydrido, and R3 is selected from the group consisting of heteroaryl(CRaRb)m—, heterocyclyl(CRaRb)m—, and R4R5N(CRaRb)m—,
- wherein said heteroaryl or heterocyclyl is independently substituted with one or more groups selected from the group consisting of oxo, arylalkyl substituted with a halogen, haloalkyl, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, heterocyclylsulfonyl, (RcRdN)sulfonyl, and (RcRdN)sulfonylalkyl and wherein, when the heterocyclyl is pyrrolidinyl, the pyrrolidinyl is not substituted with oxo;
- R4 and R5 are independently selected from the group consisting of hydrido, alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, heterocyclylsulfonyl, (RcRdN)sulfonyl, and (RcRdIN)sulfonylalkyl,
- R6 is isopropyl, isopropenyl, or 1-methyl-1-cyclopropyl;
- Ra and Rb are independently selected from the group consisting of hydrido and C1-C6 alkyl, Ra and Rb are taken together with the carbon atom to form an oxo or substituted or unsubstituted cycloalkyl;
- Rc and Rd are independently selected from the group consisting of hydrido, C1-C6 alkyl, cycloalkyl, alkoxyalkyl, hydroxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, carboxyalkyl, hydroxyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl groups, or Rc and Rd can together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl group, wherein the heterocyclyl or heteroaryl can optionally include one or more heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen;
- and
- m is an integer from zero to six.
Dependencies are inferred from the claim text.