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US 7,629,380 B2Granted
Antitumor agents
AssigneeThe Regents of the University of California
InventorsTrevor C. McMorris, Michael J. Kelner
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of the general formula I: wherein R1, R2, R3, R4, R5, and R6 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising compounds of formula I, intermediates and processes useful for preparing compounds of formula I, and methods comprising inhibiting tumor growth or treating cancer by administering one or more compounds of formula I.
Claims25
A compound of formula I:
- wherein
- R1 is —(CH2)n—(X)—(Y);
- n is 1 to 4;
- X is oxy, thio, or —N(Ra)—, wherein Ra is hydrogen, (C1-6)alkyl, (C1-C6)alkanoyl, phenyl, or benzyl;
- Y is a peptide, or (C1-C6)alkyl substituted with a peptide;
- R2 is hydrogen or (C1-C6)alkyl;
- R3 is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, aryl, heteroaryl, aryloxy, or heteroaryloxy;
- R4 is hydrogen or (C1-C6)alkyl;
- and R5 is hydroxy, (C1-C6)alkoxy, or (C1-C6)alkanoyloxy;
- or R4 and R5 taken together are ethylenedioxy;
- R6 is hydrogen, carboxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, halo(C1-C6)alkyl, —C(═O)NRfRg, a saccharide, an amino acid, a peptide, or (C1-C6)alkyl optionally substituted by 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, carboxy, amino acids, peptides, saccharides, or —C(═O)NRfRg;
- Rf and Rg are each independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rf and Rg, together with the nitrogen to which they are attached, are pyrrolidino, piperidino, or morpholino;
- wherein any aryl, heteroaryl, aryloxy, or heteroaryloxy of Y, or R3 may optionally be substituted by 1, 2, or 3 (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy, halo, carboxy, mercapto, nitro, or —N(Rh)(Rj);
- wherein each Rh and Rj is independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rh and Rj together with the nitrogen to which they are attached are pyrrolidino, piperidino, or morpholino;
- or a pharmaceutically acceptable salt thereof.
14 more elements
A compound of formula I:
- wherein
- R1 is —(CH2)n—(X)—(Y);
- n is 1 to 4;
- X is oxy, thio, or —N(Ra)—, wherein Ra is hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl, or benzyl;
- Y is (C2-C6)alkenyl, optionally substituted with 1 or 2 oxo, hydroxy, carboxy, halo, mercapto, nitro, —N(Rb)(Rc), (C3-C6)cycloalkyl, aryl, heteroaryl, saccharides, amino acids, or peptides;
- R2 is hydrogen or (C1-C6)alkyl;
- R3 is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, aryl, heteroaryl, aryloxy, or heteroaryloxy;
- R4 is hydrogen or (C1-C6)alkyl;
- and R5 is hydroxy, (C1-C6)alkoxy, or (C1-C6)alkanoyloxy;
- or R4 and R5 taken together are ethylenedioxy;
- R6 is hydrogen, carboxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, halo(C1-C6)alkyl, —C(═O)NRfRg, a saccharide, an amino acid, a peptide, or (C1-C6)alkyl optionally substituted by 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, carboxy, amino acids, peptides, saccharides, or —C(═O)NRfRg;
- Rb, Rc, Rf and Rg are each independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rb and Rc, or Rf and Rg, together with the nitrogen to which they are attached, are pyrrolidino, piperidino, or morpholino;
- wherein any aryl, heteroaryl, aryloxy, or heteroaryloxy of Y, or R3 may optionally be substituted by 1, 2, or 3 (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy, halo, carboxy, mercapto, nitro, or —N(Rh)(Rj);
- wherein each Rh and Rj is independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rh and Rj together with the nitrogen to which they are attached are pyrrolidino, piperidino, or morpholino;
- or a pharmaceutically acceptable salt thereof.
14 more elements
A compound of formula I:
- wherein
- R1 is —CH2-[sulfur-linked-cysteine]-Rx wherein Rx is an amino acid or a peptide comprising 2 to 24 amino acids;
- R2 is hydrogen or (C1-C6)alkyl;
- R3 is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, aryl, heteroaryl, aryloxy, or heteroaryloxy;
- R4 is hydrogen or (C1-C6)alkyl;
- and R5 is hydroxy, (C1-C6)alkoxy, or (C1-C6)alkanoyloxy;
- or R4 and R5 taken together are ethylenedioxy;
- R6 is hydrogen, carboxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, halo(C1-C6)alkyl, —C(═O)NRfRg, a saccharide, an amino acid, a peptide, or (C1-C6)alkyl optionally substituted by 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, carboxy, amino acids, peptides, saccharides, or —C(═O)NRfRg;
- Rf and Rg are each independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rf and Rg, together with the nitrogen to which they are attached, are pyrrolidino, piperidino, or morpholino;
- wherein any aryl, heteroaryl, aryloxy, or heteroaryloxy of R3 may optionally be substituted by 1, 2, or 3 (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy, halo, carboxy, mercapto, nitro, or —N(Rh)(Rj);
- wherein each Rh and Rj is independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rh and Rj together with the nitrogen to which they are attached are pyrrolidino, piperidino, or morpholino;
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound of formula I:
- wherein
- R1 is —CH2-[sulfur-linked-N-acylcysteine]-Rx wherein Rx is an amino acid or a peptide comprising 2 to 24 amino acids;
- R2 is hydrogen or (C1-C6)alkyl;
- R3 is hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, aryl, heteroaryl, aryloxy, or heteroaryloxy;
- R4 is hydrogen or (C1-C6)alkyl;
- and R5 is hydroxy, (C1-C6)alkoxy, or (C1-C6)alkanoyloxy;
- or R4 and R5 taken together are ethylenedioxy;
- R6 is hydrogen, carboxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, halo(C1-C6)alkyl, —C(═O)NRfRg, a saccharide, an amino acid, a peptide, or (C1-C6)alkyl optionally substituted by 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, carboxy, amino acids, peptides, saccharides, or —C(═O)NRfRg;
- Rf and Rg are each independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rf and Rg, together with the nitrogen to which they are attached, are pyrrolidino, piperidino, or morpholino;
- wherein any aryl, heteroaryl, aryloxy, or heteroaryloxy of R3 may optionally be substituted by 1, 2, or 3 (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, (C1-C6)alkoxycarbonyl, hydroxy(C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy, halo, carboxy, mercapto, nitro, or —N(Rh)(Rj);
- wherein each Rh and Rj is independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rh and Rj together with the nitrogen to which they are attached are pyrrolidino, piperidino, or morpholino;
- or a pharmaceutically acceptable salt thereof.
11 more elements
A compound of formula I:
- wherein
- R1 is hydrogen;
- R2 is hydrogen;
- R3 is hydrogen;
- R4 is hydrogen or (C1-C6)alkyl;
- R5 is hydroxy, (C1-C6)alkoxy, or (C1-C6)alkanoyloxy;
- R6 is hydrogen, carboxy, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, halo(C1-C6)alkyl, —C(═O)NRfRg, a saccharide, an amino acid, a peptide, or (C1-C6)alkyl optionally substituted by 1 or 2 hydroxy, (C1-C6)alkoxy, (C1-C6)alkanoyloxy, carboxy, amino acids, peptides, saccharides, or —C(═O)NRfRg;
- and
- Rf and Rg are each independently hydrogen, (C1-C6)alkyl, (C1-C6)alkanoyl, phenyl or benzyl;
- or Rf and Rg, together with the nitrogen to which they are attached, are pyrrolidino, piperidino, or morpholino;
- or a pharmaceutically acceptable salt thereof.
8 more elements
Dependencies are inferred from the claim text.