US5965739A
Expired / Lapsed
US
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Δ6,7 -taxols antineoplastic use and pharmaceutical compositions containing them
Assignee: Pharmacia and Upjohn Co
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Filing: 1994-06-03
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Granted: 1999-10-12
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Expires: 2014-06-03
Abstract
Abstract PCT No. PCT/US94/06035 Sec. 371 Date Dec. 7, 1995 Sec. 102(e) Date Dec. 7, 1995 PCT Filed Jun. 3, 1994 PCT Pub. No. WO94/29288 PCT Pub. Date Dec. 22, 1994This invention provides oxazolidine protected taxol analogs of the Formula: which are useful intermediates to make various taxol analogues.
Inventors
- 👤 Robert C. Kelly
- 👤 Harvey I. Skulnick
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 13:24
CPC Classifications
C; C07; C07D; C07D263/00; C07D263/02; C07D263/04; A; A61; A61P; A61P35/00; A61P35/02; A61P35/04; C07D263/06; C07D305/00; C07D305/14; C07D405/00; C07D405/02; C07D405/12; C07D407/00; C07D407/02; C07D407/12; C07D409/00; C07D409/02; C07D409/12; C07D413/00; C07D413/02; C07D413/12; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
289 words
A process of preparing wherein R 1 is selected from the ground consisting of --CH 3 , --C 6 H 5 or phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, hydroxy or nitro, -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; R 10 is --H or --C(O)CH 3 ; R 11 is phenyl substituted with --(OC 1 -C 2 alkyl) n where n is 1 to 3; R 12 is selected from the group consisting of --C(O)H, --C(O)phenyl substituted with one, 2 or 3 C 1 -C 3 alkylthio, C 2 -C 6 dialkylamino, hydroxy or nitro, --SO 2 -4-methylphenyl, --C(O)(CH 2 ) 3 COOH, --C(O)-4-(SO 3 H)phenyl, --C(O)-1-adamantyl, --C(O)O-3-tetrahydrofuranyl, --C(O)O-4-tetrahydropyranyl, --C(O)NHC 1 -C 10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro, --C(O)C(CH 3 ) 2 CH 2 Cl, --C(O)- 1-phenyl- 1-cyclopentyl, --C(O)- 1-methyl- 1-cyclohexyl, --C(S)NHC(CH 3 ) 3 , --C(O)NHC(CH 3 ) 3 or --C(O)NHPh; R 14 is selected from the group consisting of --C(O)C 1 -C 6 alkyl, --C(O)OC 1 -C 6 alkyl, --C(O)OCH 2 CX 3 where X is Halo, --C(O)OCH 2 CH 2 Si(R 20 ) 3 (where R 20 is C 1 -C 6 alkyl), or --Si(R 20 ) 3 ; which comprises reacting an oxazolidine free acid of Formula 7 ##STR13## wherein R 1 , R 11 and R 12 are as defined above; with a baccatin compound of Formula 8 ##STR14## wherein R 10 and R 14 are as defined above; in the presence of a dehydrating agent.
Claim 2
Dependent Claim
289 words
A process of preparing wherein R 1 is selected from the ground consisting of --CH 3 , --C 6 H 5 or phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, hydroxy or nitro, -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; R 10 is --H or --C(O)CH 3 ; R 11 is phenyl substituted with --(OC 1 -C 2 alkyl) n where n is 1 to 3; R 12 is selected from the group consisting of --C(O)H, --C(O)phenyl substituted with one, 2 or 3 C 1 -C 3 alkylthio, C 2 -C 6 dialkylamino, hydroxy or nitro, --SO 2 -4-methylphenyl, --C(O)(CH 2 ) 3 COOH, --C(O)-4-(SO 3 H)phenyl, --C(O)-1-adamantyl, --C(O)O-3-tetrahydrofuranyl, --C(O)O-4-tetrahydropyranyl, --C(O)NHC 1 -C 10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro, --C(O)C(CH 3 ) 2 CH 2 Cl, --C(O)- 1-phenyl- 1-cyclopentyl, --C(O)- 1-methyl- 1-cyclohexyl, --C(S)NHC(CH 3 ) 3 , --C(O)NHC(CH 3 ) 3 or --C(O)NHPh; R 14 is selected from the group consisting of --C(O)C 1 -C 6 alkyl, --C(O)OC 1 -C 6 alkyl, --C(O)OCH 2 CX 3 where X is Halo, --C(O)OCH 2 CH 2 Si(R 20 ) 3 (where R 20 is C 1 -C 6 alkyl), or --Si(R 20 ) 3 ; which comprises reacting an oxazolidine free acid of Formula 7 ##STR13## wherein R 1 , R 11 and R 12 are as defined above; with a baccatin compound of Formula 8 ##STR14## wherein R 10 and R 14 are as defined above; in the presence of a dehydrating agent.
Claim 3
Dependent Claim
246 words
A compound of the formula ##STR15## wherein R 1 is selected from the group consisting of --CH 3 , --C 6 H 5 or phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, hydroxy or nitro, -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; R 11 is phenyl substituted with --(OC 1 -C 2 alkyl) n where n is 1 to 3; and R 12 is selected from the group consisting of --C(O)H, --C(O)phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkylthio, C 2 -C 6 dialkylamino, hydroxy or nitro, --SO 2 -4-methylphenyl, --C(O)(CH 2 ) 3 COOH, --C(O)-4-(SO 3 H)phenyl, --C(O)-1-adamantyl, --C(O)O-3-tetrahydrofuranyl, --C(O)O-4-tetrahydropyranyl, --C(O)NHC 1 -C 10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 C 3 alkylthio trifluoromethyl, C 2 -C 6 dialkylamino, or nitro, or --C(O)C(CH 3 ) 2 CH 2 Cl, --C(O)-1-phenyl-1-cyclopentyl, --C(O)-1-methyl-1-cyclohexyl, --C(S)NHC(CH 3 ) 3 , --C(O)NHC(CH 3 ) 3 or --C(O)NHPh; wherein R 10 and R 14 , being the same or different, are selected from the group consisting of --C(O)C 1 -C 6 alkyl, --C(O)OC 1 -C 6 alkyl, --C(O)OCH 2 CX 3 where X is Halo, --C(O)CH 2 CH 2 Si(R 20 ) 3 R 20 is C 1 -C 6 alkyl), or --Si(R 20 ) 3 .
Claim 4
Dependent Claim
246 words
A compound of the formula ##STR15## wherein R 1 is selected from the group consisting of --CH 3 , --C 6 H 5 or phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, hydroxy or nitro, -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; R 11 is phenyl substituted with --(OC 1 -C 2 alkyl) n where n is 1 to 3; and R 12 is selected from the group consisting of --C(O)H, --C(O)phenyl substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkylthio, C 2 -C 6 dialkylamino, hydroxy or nitro, --SO 2 -4-methylphenyl, --C(O)(CH 2 ) 3 COOH, --C(O)-4-(SO 3 H)phenyl, --C(O)-1-adamantyl, --C(O)O-3-tetrahydrofuranyl, --C(O)O-4-tetrahydropyranyl, --C(O)NHC 1 -C 10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 C 3 alkylthio trifluoromethyl, C 2 -C 6 dialkylamino, or nitro, or --C(O)C(CH 3 ) 2 CH 2 Cl, --C(O)-1-phenyl-1-cyclopentyl, --C(O)-1-methyl-1-cyclohexyl, --C(S)NHC(CH 3 ) 3 , --C(O)NHC(CH 3 ) 3 or --C(O)NHPh; wherein R 10 and R 14 , being the same or different, are selected from the group consisting of --C(O)C 1 -C 6 alkyl, --C(O)OC 1 -C 6 alkyl, --C(O)OCH 2 CX 3 where X is Halo, --C(O)CH 2 CH 2 Si(R 20 ) 3 R 20 is C 1 -C 6 alkyl), or --Si(R 20 ) 3 .
Claim 5
Dependent Claim
15 words
A compound according to claim 1 wherein R 12 is --C(O)NHC(CH 3 ) 3 .
Claim 6
Dependent Claim
22 words
A compound according to claim 3 wherein is R 11 is phenyl substituted with --OCH 3 in the ortho and para positions.
Claim 7
Dependent Claim
59 words
A compound according to claim 1 wherein R 12 is selected from the group consisting of --C(O)NHC 1 -C 10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C 1 -C 4 alkyl, C 1 -C 3 alkoxy, halo, C 1 -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro, or --C(O)NHC(CH 3 ) 3 and --C(O)NHPh.
Claim 8
Dependent Claim
21 words
A compound according to claim 5 wherein R 11 is phenyl substituted with --OCH 3 in the ortho and para positions.
Claim 9
Dependent Claim
17 words
The process according to claim 1 wherein the dehydrating agent is a carbodiimide and a basic catalyst.
Claim 10
Dependent Claim
28 words
The process according to claim 7 wherein the carbodiimide is selected from the group consisting of dicyclohexyl carbodiimide, diisopropyl carbodiimide, di-p-tolyl carbodiimide and ethyl dimethylarinopropyl carbodiimide hydrochloride salt.
Claim 11
Dependent Claim
12 words
The process according to claim 7 wherein the basic catalyst is 4-dimethylaminopyridine.
Claim 12
Dependent Claim
34 words
The process according to claim 7 wherein the basic catalyst is 4-dimethylaminopyridine and the carbodlimide is selected from the group consisting of dicyclohexyl carbodiimide, diisopropyl carbodiimide, di-p-tolyl carbodiimide and ethyl dimethylaminopropyl carbodlimide hydrochloride salt.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2002-10-11 | 2003-04-12 | 2003-10-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-10-11 | 2007-04-12 | 2007-10-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-10-11 | 2011-04-12 | 2011-10-12 | $7700.00 | Window Closed / Lapsed |