20-O-Acylmaytansinoids

A compound of the formula:

• ##STR23## wherein X is chlorine or hydrogen, R.sub.1 is hydrogen or acyl;
• R.sub.2 is acyl;
• said acyl being represented by the formula:
• --CO--R.sub.3 (a)
• wherein R.sub.3 is hydrogen, C.sub.1-18 alkyl, C.sub.2-18 alkenyl, C.sub.3-10 cycloalkyl, C.sub.3-10 cycloalkenyl, heterocyclic group selected from the group consisting of azetidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1,2,3,4-tetrahydropyridyl, piperidyl, quinolyl, 1,2-dihydroquinolyl, 3-isoquinolyl, 4-isoquinolyl, 1,2-dihydroisoquinolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, indolyl, furyl, pyranyl, dihydropyranyl, benzofuryl, benzopyranyl, thienyl, benzothienyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, 2-imidazolyl, imidazolidinyl, benzoimidazolyl, indazolyl, quinoxalyl, quinazolinyl, cinnolinyl, 1,4-dioxanyl 1,4-benzodioxanyl, 1,2-dithiolanyl, 1,3-dithiolanyl, 1,3-dithianyl, isooxazolyl, oxazolyl, morpholinyl, benzoisoxazolyl benzoxazolyl, isothiazolyl, thiazolyl, benzoisothiazolyl, benzothiazolyl, benzothiazinyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, 1,3,5-triadinyl, benzotriazolyl and 1,2,3,4-tetrazolyl, said cycloalkyl, cycloalkenyl, phenyl or heterocyclic group being attached directly to the carbonyl carbon or through a C.sub.1-4 alkylene chain, said alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclic group being unsubstituted or substituted by C.sub.1-4 alkoxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, nitro, cyano, trifluoromethyl, di-C.sub.1-4 -alkylamino, C.sub.1-4 alkylthio methylsulfinyl, methylsulfonyl, oxo, thioxo, C.sub.1-4 alkanoylamido or carboxy group of the formula -COOR.sub.12 wherein R.sub.12 is hydrogen, C.sub.1-6 alkyl, phenyl or benzyl, and said cycloalkyl, cycloalkenyl, phenyl or heterocyclic group being unsubstituted or substituted by C.sub.1-4 alkyl;
• ##STR24## wherein R.sub.4 is hydrogen, C.sub.1-18 alkyl, C.sub.3-10 cycloalkyl, phenyl, indolyl or imidazolyl group, said cycloalkyl, phenyl, indolyl or imidazolyl groups being attached directly to the alpha-carbon atom or, through a C.sub.1-4 alkylene chain, said alkyl, cycloalkyl, phenyl, indolyl or imidazolyl being unsubstituted or substituted by C.sub.1-4 alkoxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, nitro, cyano, trifluoromethyl, di-C.sub.1-4 -alkylamino, C.sub.1-4 alkylthio, methylsulfinyl, methylsulfonyl, oxo, thioxo or C.sub.1-4 alkanoylamido, and said cycloalkyl, phenyl, indolyl or imidazolyl being unsubstituted or substituted by C.sub.1-4 alkyl;
• R.sub.5 is hydrogen, C.sub.1-18 alkyl, C.sub.3-10 cycloalkyl, C.sub.4-14 cycloalkylalkyl, phenyl or benzyl group, said alkyl, cycloalkyl, cycloalkylalkyl, phenyl or benzyl group being unsubstituted or substituted by C.sub.1-4 alkoxy, C.sub.2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, nitro, cyano, trifluoromethyl, di-C.sub.1-4 -alkylamino, C.sub.1-4 alkylthio, methylsulfinyl, methylsulfonyl, oxo, thioxo or C.sub.1-4 alkanoylamido, and said cycloalkyl cycloalkylalkyl, phenyl or benzyl group being unsubstituted or substituted by C.sub.1-4 alkyl;
• R.sub.6 is hydrogen, C.sub.1-7 alkoxy, bornyloxy, isobornyloxy, benzyloxy, C.sub.1-18 alkyl, C.sub.2-18 alkenyl, C.sub.3-10 cycloalkyl, C.sub.3-10 cycloalkenyl, phenyl or heterocyclic group selected from the group consisting of azetidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1,2,3,4-tetrahydropyridyl, piperidyl, quinolyl, 1,2-dihydroquinolyl, 3-isoquinolyl, 4-isoquinolyl, 1,2-dihydroisoquinolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, indolyl, furyl, pyranyl, dihydropyranyl, benzofuryl, benzopyranyl, thienyl, benzothienyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, 2-imidazolyl, imidazolidinyl, benzoimidazolyl, indazolyl, quinoxalyl, quinazolinyl, cinnolinyl, 1,4-dioxanyl, 1,4-benzodioxanyl, 1,2-dithiolanyl, 1,3-dithiolanyl, 1,3-dithianyl, isooxazolyl, oxazolyl, morpholinyl, benzoisoxazolyl, benzoxazolyl, isothiazolyl, thiazolyl, benzoisothiazolyl, benzothiazolyl, benzothiazinyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, 1,3,5-triadinyl, benzotriazolyl and 1,2,3,4-tetrazolyl, said cycloalkyl, cycloalkenyl, phenyl or heterocyclic groups being attached directly to the carbonyl carbon atom adjacent the nitrogen atom or through a C.sub.1-4 alkylene chain, said alkyl, alkenyl, cycloalkyl, cycloalkenyl, phenyl or heterocyclic group being unsubstituted or substituted by C.sub.1-4 alkoxy, C.sub. 2-4 alkanoyl, C.sub.2-4 alkanoyloxy, C.sub.2-4 alkoxycarbonyl, halogen, nitro, cyano, trifluoromethyl, di-C.sub.1-4 -alkylamino, C.sub.1-4 alkylthio, methylsulfinyl, methylsulfonyl, oxo, thioxo or C.sub.1-4 alkanoylamido, and said cycloalkyl, cycloalkenyl, phenyl or heterocyclic group being unsubstituted or substituted by C.sub.1-4 alkyl;
• ##STR25## wherein R.sub.7 and R.sub.8 may be the same or different and each is hydrogen, C.sub.1-18 alkyl, C.sub.2-18 alkenyl, C.sub.3-10 cycloalkyl, C.sub.3-10 cycloalkenyl, C.sub.4-14 cycloalkylalkyl, C.sub.4-10 cycloalkenylalky phenyl, phenyl-C.sub.1-4 -alkyl, phenyl-C.sub.3-10 -cycloalkyl, C.sub.3-10 cycloalkylphenyl, biphenyl or heterocyclic group selected from the group consisting of azetidinyl, pyrrolyl, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, pyrazinyl, triazinyl, quinolyl, quinazolyl, quinoxalyl, indolyl, benzofuranyl and benzothienyl, and wherein R.sub.7 and R.sub.8 together may form a heterocyclic group of azetidinyl, pyrrolidinyl, piperadinyl or morpholinyl taken together with the adjacent nitrogen atom, these groups being unsubstituted or substituted by C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, phenoxy, phenylthio, cyclohexyloxy, halogen, cyano, C.sub.2-5 alkoxycarbonyl, benzyloxycarbonyl, nitro, aminosulfonyl or di-C.sub.1-4 -alkylamino, and said cyclic moiety or heterocyclic group being unsubstituted or substituted by C.sub.1-4 alkyl;
• or
• --CO--O--R.sub.9 (d)
• wherein R.sub.9 is C.sub.1-18 alkyl, C.sub.3-10 cycloalkyl, phenyl or phenyl-C.sub.1-4 -alkyl, said groups being unsubstituted or substituted by C.sub.1-4 alkoxy, phenoxy, benzyloxy, halogen or cyano, and said cyclic moiety being unsubstituted or substituted by C.sub.1-4 alkyl.