Maytansinoids, pharmaceutical compositions thereof and method of use thereof

An antitumor composition which comprises as an active ingredient an effective amount of a compound of the formula:

• ##STR5## wherein X is H or Cl, and Y is Cl, OH, SH, CN, NO.sub.2, --OR or --S(O).sub.n R,
• wherein n is 0, 1 or 2, and
• R is C.sub.1-8 alkyl, phenyl, naphthyl, phenyl-C.sub.1-4 alkyl, 2- or 4-pyridyl, 2- or 4(6)-pyrimidyl, 3(6)-pyridazinyl, 2- or 3-pyrazinyl, 2-s-triazinyl, 2-(1,3,4-triazinyl), 2- or 4(5)-imidazolyl, 3(5)-pyrazolyl, 2-(1,3,4-triazolyl), 5-tetrazolyl, 2-piperzinyl, 2-pyrrolidinyl, 2-oxazolyl, 2-thiazolyl, 2- or 5-oxadiazolyl, 2- or 5-thiadiazolyl, 2-(2-thiazolinyl), 2-benzimidazolyl, 2-benzoxazolyl or 2-benzothiazolyl,
• said R group being unsubstituted or substituted by C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, di-C.sub.1-4 alkylamino, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfinyl, C.sub.1-4 alkylsulfonyl, sulfamoyl, mono- or di-C.sub.1-4 alkylsulfamoyl, oxo, thioxo, C.sub.1-4 alkanoylamino, C.sub.1-4 alkylsulfonylamino or --O(CH.sub.2 CH.sub.2 O).sub.m R.sup.1 wherein R.sup.1 is methyl or ethyl and m is an integer 1 to 4 inclusive,
• and a pharmaceutically acceptable carrier or diluent therefor.

A method for inhibiting the growth of tumor cells and prolonging the survival time of a tumor-bearing warm-blooded animal, which comprises administering to said animal an effective amount of a compound of the formula:

• ##STR6## wherein X is H or Cl, and Y is Cl, OH, SH, CN, NO.sub.2, --OR or --S(O).sub.n R,
• wherein n is 0, 1 or 2, and
• R is C.sub.1-8 alkyl, phenyl, naphthyl, phenyl-C.sub.1-4 alkyl, 2- or 4-pyridyl, 2- or 4(6)-pyrimidyl, 3(6)-pyridazinyl, 2- or 3-pyrazinyl, 2-s-triazinyl, 2-(1,3,4-triazinyl), 2- or 4(5)-imidazolyl, 3(5)-pyrazolyl, 2-(1,3,4-triazolyl), 5-tetrazolyl, 2-piperazinyl, 2-pyrrolidinyl, 2-oxazolyl, 2-thiazolyl, 2- or 5-oxadiazolyl, 2- or 5-thiadiazolyl, 2-(2-thiazolinyl, 2-benzimidazolyl, 2-benzoxazolyl or 2-benzothiazolyl,
• said R group being unsubstituted or substituted by C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, di-C.sub.1-4 alkylamino, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfinyl, C.sub.1-4 alkylsulfonyl, sulfamoyl, mono- or di-C.sub.1-4 alkylsulfamoyl, oxo, thioxo, C.sub.1-4 alkanoylamino, C.sub.1-4 alkylsulfonylamino or --O(CH.sub.2 CH.sub.2 O).sub.m R.sup.1 wherein R.sup.1 is methyl or ethyl and m is an integer 1 to 4 inclusive.