Maytansinoids

• US 4,309,428 A
• Filed: 07/23/1980
• Issued: 01/05/1982
• Est. Priority Date: 07/30/1979
• Status: Expired due to Term

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Akimoto, Hiroshi, Miyashita, Osamu
• Primary Examiner(s): Bond, Robert T.
• Application Number:
  US06/171,459
• Time in Patent Office: 531 Days
• Field of Search: 260/239.3 P, 424/248.54
• US Class Current: 514/229.5
• CPC Class Codes: C07D 498/18 Bridged systems

Abstract

Novel maytansinoids of the formula: ##STR1## wherein X is hydrogen or chlorine,

R¹ is C_2-4 alkyl,

R² is C_2-8 alkyl which may be substituted or methyl which is substituted,

have antimicrobial, antimitotic and antitumor activities.

Claims

1. A compound of the formula:

##STR6## wherein X is hydrogen or chlorine,

R¹ is C_2-4 alkyl

R² is C_1-5 alkyl substituted with oxo, C_2-5 alkoxycarbonyl, or/and phenyl.

2. A compound according to claim 1, wherein X is chlorine.

3. A compound according to claim 1, wherein R¹ is isopropyl.

4. A compound according to claim 1, wherein R² is methyl attached to a phenyl group which is substituted with C_1-4 alkyl, hydroxyl, C_1-4 -alkoxy, C_1-4 -alkanoyloxy, C_2-5 -alkoxycarbonyl, halogen, nitro, cyano, trifluoromethyl, amino, mono-C_1-4 -alkylamino, di-C_1-4 -alkylamino, or/and sulfinylamino.

5. A compound according to claim 1, wherein R² is C_2-5 alkyl substituted with oxo, C_2-5 alkoxycarbonyl or/and unsubstituted phenyl.

6. A compound according to claim 4, wherein the substituted phenyl is anilino or bis(2-chloroethyl)aminophenyl.

7. A compound according to claim 1, said compound being C₂₀ -phenacyl ether of 20-demethoxy-20-hydroxymaytansinol 3-isobutylate.

8. A compound according to claim 1, said compound being C₂₀ -γ

-ethoxycarbonylacetonyl ether of 20-demethoxy-20-hydroxymaytansinol 3-isobutylate.

9. A compound according to claim 1, said compound being C₂₀ -p-aminobenzyl ether of 20-demethoxy-20-hydroxymaytansinol 3-isobutylate.

10. C₂₀ -β

,β

-diethoxyethyl ether of 20-demethoxy-20-hydroxymaytansinol 3-isobutylate.

11. A pharmaceutical composition suitable for inhibiting the growth of tumor cells and prolonging the survival time of a tumor-bearing warm-blooded animal, which contains an amount effective for inhibiting the growth of tumor cells and prolonging the survival time of a tumor-bearing warm-blooded animal of a compound of the formula:

##STR7## wherein X is hydrogen or chlorine,

R¹ is C_2-4 alkyl

R² is C_1-5 alkyl substituted with oxo, C_2-5 alkoxycarbonyl, or/and phenyl.

12. 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 amount effective for inhibiting the growth of tumor cells and prolonging the survival time of a tumor-bearing animal of a compound of the formula:

##STR8## wherein X is hydrogen or chlorine,

R¹ is C_2-4 alkyl

R² is C_1-5 alkyl substituted with oxo, C_2-5 alkoxycarbonyl, or/and phenyl.