4,5-Deoxymaytansinoids, their use and pharmaceutical compositions thereof
First Claim
Patent Images
1. A compound of the formula:
- ##STR7## wherein X is hydrogen, C1-8 alkyl which is unsubstituted or substituted with halogen, carboxyl, C2-5 alkoxycarbonyl, phenoxycarbonyl, C1-4 alkoxy, benzyloxy, C1-4 alkylthio, benzylthio, phenylthio, C1-4 alkylsulfinyl, benzylsulfinyl, phenylsulfinyl, C1-4 alkylsulfonyl, benzylsulfonyl, phenylsulfonyl, C1-5 alkanoyloxy, benzoyloxy, phenylacetyloxy, cyano, di(C1-4 alkyl)amino, oxo, (C1-4)-1-alkylidene, phenyl, α
- or β
-naphthyl, vinyl, ethynyl, C3-6 cycloalkyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, piperidinyl, piperazinyl, pyrrolyl, pyrrolidinyl, pyrrolinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, furyl, furanyl, tetrahydrofuryl, thienyl, morpholino, oxazolyl, oxazolinyl, thiazolyl, thiazolinyl, oxadiazolyl, thiadiazolyl, oxiranyl, dioxolanyl or/and dithiolanyl,or X is acyl derived from a C1-20 carboxylic acid of the formula;
space="preserve" listing-type="equation">--COR.sup.1wherein R1 is hydrogen, C1-18 alkyl, C2-10 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, phenyl, naphthyl, any of said groups being unsubstituted or substituted by C1-4 alkoxy, C2-4 alkanoyl, C2-4 alkanoyloxy, C2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkanesulfonyl, oxo, thioxo or C1-4 alkanoylamino, and said cycloalkyl, cycloalkenyl, phenyl and naphthyl being attached, directly or through C1-4 alkylene, to the carbonyl radical in the acyl group,or X is of the formula;
##STR8## wherein R2 is hydrogen, C1-18 alkyl, C3-10 cycloalkyl, phenyl or naphthyl,R3 is hydrogen, C1-18 alkyl, C3-10 cycloalkyl, phenyl or naphthyl, andR4 is hydrogen, C1-18 alkyl, C2-10 alkenyl, C3-10 cycloalkyl, phenyl or naphthyl, any of said groups in R2, R3 and R4 being unsubstituted or substituted by C1-4 alkoxy, C2-4 alkanoyl, C2-4 alkanoyloxy, C2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, amino, mono(C1-4 alkyl) amino, di(C1-4 alkyl) amino, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkanesulfonyl, oxo, thioxo or C1-4 alkanoylamino, and said cycloalkyl, cycloalkenyl, phenyl and naphthyl in R2, R3 and R4 being attached, directly or through C1-4 alkylene, to the α
-carbon atom, N-atom or the carbonyl group on the N-atom,or wherein X is acyl derived from an organic sulfonic acid of the formula;
space="preserve" listing-type="equation">--SO.sub.2 R.sup.5 whereinR5 is C1-4 alkyl or C7-9 aralkyl or acyl derived from carbamic acid of the formula;
space="preserve" listing-type="equation">--CONR.sup.6 R.sup.7 whereinR6 and R7 are the same or different and each is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, benzyl, phenethyl, phenyl or α
- or β
-naphthyl;
Y is hydrogen or chlorine; and
R is hydrogen or acyl derived from C1-20 carboxylic acid of the formula;
space="preserve" listing-type="equation">--COR.sup.1 wherein R1 is the same as defined above, or R is of the formula;
##STR9## wherein R2, R3 and R4 are the same as defined above.
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Abstract
This invention relates to 4,5-deoxymaytansinoid compounds represented by the formula ##STR1## wherein X is a hydrogen atom or an alkyl or acyl group, Y is a hydrogen or chlorine atom, and R is a hydrogen atom or a carboxylic acid-derived acyl group, and methods of producing the same. The compounds are useful as antitumor, antiprotozoal and antifungal agents.
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Citations
12 Claims
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1. A compound of the formula:
- ##STR7## wherein X is hydrogen, C1-8 alkyl which is unsubstituted or substituted with halogen, carboxyl, C2-5 alkoxycarbonyl, phenoxycarbonyl, C1-4 alkoxy, benzyloxy, C1-4 alkylthio, benzylthio, phenylthio, C1-4 alkylsulfinyl, benzylsulfinyl, phenylsulfinyl, C1-4 alkylsulfonyl, benzylsulfonyl, phenylsulfonyl, C1-5 alkanoyloxy, benzoyloxy, phenylacetyloxy, cyano, di(C1-4 alkyl)amino, oxo, (C1-4)-1-alkylidene, phenyl, α
- or β
-naphthyl, vinyl, ethynyl, C3-6 cycloalkyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazinyl, piperidinyl, piperazinyl, pyrrolyl, pyrrolidinyl, pyrrolinyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolinyl, pyrazolidinyl, imidazolidinyl, triazolidinyl, furyl, furanyl, tetrahydrofuryl, thienyl, morpholino, oxazolyl, oxazolinyl, thiazolyl, thiazolinyl, oxadiazolyl, thiadiazolyl, oxiranyl, dioxolanyl or/and dithiolanyl,or X is acyl derived from a C1-20 carboxylic acid of the formula;
space="preserve" listing-type="equation">--COR.sup.1wherein R1 is hydrogen, C1-18 alkyl, C2-10 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, phenyl, naphthyl, any of said groups being unsubstituted or substituted by C1-4 alkoxy, C2-4 alkanoyl, C2-4 alkanoyloxy, C2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkanesulfonyl, oxo, thioxo or C1-4 alkanoylamino, and said cycloalkyl, cycloalkenyl, phenyl and naphthyl being attached, directly or through C1-4 alkylene, to the carbonyl radical in the acyl group, or X is of the formula;
##STR8## wherein R2 is hydrogen, C1-18 alkyl, C3-10 cycloalkyl, phenyl or naphthyl,R3 is hydrogen, C1-18 alkyl, C3-10 cycloalkyl, phenyl or naphthyl, and R4 is hydrogen, C1-18 alkyl, C2-10 alkenyl, C3-10 cycloalkyl, phenyl or naphthyl, any of said groups in R2, R3 and R4 being unsubstituted or substituted by C1-4 alkoxy, C2-4 alkanoyl, C2-4 alkanoyloxy, C2-4 alkoxycarbonyl, halogen, hydroxyl, nitro, cyano, trifluoromethyl, amino, mono(C1-4 alkyl) amino, di(C1-4 alkyl) amino, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkanesulfonyl, oxo, thioxo or C1-4 alkanoylamino, and said cycloalkyl, cycloalkenyl, phenyl and naphthyl in R2, R3 and R4 being attached, directly or through C1-4 alkylene, to the α
-carbon atom, N-atom or the carbonyl group on the N-atom,or wherein X is acyl derived from an organic sulfonic acid of the formula;
space="preserve" listing-type="equation">--SO.sub.2 R.sup.5wherein R5 is C1-4 alkyl or C7-9 aralkyl or acyl derived from carbamic acid of the formula;
space="preserve" listing-type="equation">--CONR.sup.6 R.sup.7wherein R6 and R7 are the same or different and each is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, benzyl, phenethyl, phenyl or α
- or β
-naphthyl;Y is hydrogen or chlorine; and R is hydrogen or acyl derived from C1-20 carboxylic acid of the formula;
space="preserve" listing-type="equation">--COR.sup.1wherein R1 is the same as defined above, or R is of the formula;
##STR9## wherein R2, R3 and R4 are the same as defined above. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- ##STR7## wherein X is hydrogen, C1-8 alkyl which is unsubstituted or substituted with halogen, carboxyl, C2-5 alkoxycarbonyl, phenoxycarbonyl, C1-4 alkoxy, benzyloxy, C1-4 alkylthio, benzylthio, phenylthio, C1-4 alkylsulfinyl, benzylsulfinyl, phenylsulfinyl, C1-4 alkylsulfonyl, benzylsulfonyl, phenylsulfonyl, C1-5 alkanoyloxy, benzoyloxy, phenylacetyloxy, cyano, di(C1-4 alkyl)amino, oxo, (C1-4)-1-alkylidene, phenyl, α
Specification
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Current AssigneeJames River Paper Company, Inc. (KOCH Industries Incorporated)
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Original AssigneeTakeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
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InventorsAkimoto, Hiroshi, Kawai, Akiyoshi
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Primary Examiner(s)BOND, ROBERT
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Application NumberUS06/306,776Time in Patent Office490 DaysField of Search260/239.3 T, 260/239.3 P, 424/248.54, 424/248.51US Class Current514/183CPC Class CodesA61P 31/04 Antibacterial agentsA61P 33/02 Antiprotozoals, e.g. for le...A61P 35/00 Antineoplastic agentsC07D 498/08 Bridged systems
