Taxoids, their preparation and pharmaceutical composition containing them
View Patent ↗New taxoids of general formula (I), their preparation and pharmaceutical compositions containing them. In general formula (I), Ar represents an aryl radical, R represents a hydrogen atom or an acetyl, alkoxyacetyl or alkyl radical, R 1 represents a benzoyl radical or a radical of formula R 2 —O—CO— in which R 2 represents an optionally substituted alkyl radical, an alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, phenyl or heterocyclyl radical. The new products of general formula (I) have a remarkable antitumor activity.
1. A taxoid of the formula
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
2. A taxoid of the formula:
in which G 1 represents hydrogen or acetyl.
3. 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
4. A method of treating breast cancer comprising administering to a human having breast cancer, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
5. A method of treating breast cancer comprising administering to a human having breast cancer, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
6. A method of treating ovarian cancer comprising administering to a human having ovarian cancer, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
7. A method of treating ovarian cancer comprising administering to a human having ovarian cancer, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
8. A method of treating melanoma comprising administering to a human having melanoma, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
9. A method of treating melanoma comprising administering to a human having melanoma, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
10. A method of treating colon cancer comprising administering to a human having colon cancer, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
11. A method of treating colon cancer comprising administering to a human having colon cancer, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
12. A method of treating pancreatic cancer comprising administering to a human having pancreatic cancer, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
13. A method of treating pancreatic cancer comprising administering to a human having pancreatic cancer, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.
14. A method of treating leukemia comprising administering to a human having leukemia, an effective amount of a taxoid of formula (I)
in which
R represents hydrogen or acetyl,
R 1 represents benzoyl or R 2 —O—CO— in which R 2 represents t-butyl, and
Ar represents phenyl or α- or β-naphthyl, said phenyl or naphthyl being unsubstituted or substituted by C 1-4 alkyl, C 1-4 alkoxy, halogen, or CF 3 , or Ar represents 2- or 3-thienyl or 2- or 3-furyl, said thienyl or furyl being unsubstituted or substituted by halogen.
15. A method of treating leukemia comprising administering to a human having lukemia, an effective amount of 4α-10β-diacetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-7β,8β-methylene-9-oxo-19-nor-11-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.