Patent
DELTA..sup.6,7 -taxols antineoplastic use and pharmaceutical compositions containing them
| العنوان: | DELTA..sup.6,7 -taxols antineoplastic use and pharmaceutical compositions containing them |
|---|---|
| Patent Number: | 5,965,739 |
| تاريخ النشر: | October 12, 1999 |
| Appl. No: | 08/557,034 |
| Application Filed: | December 07, 1995 |
| مستخلص: | This invention provides oxazolidine protected taxol analogs of the Formula: ##STR1## which are useful intermediates to make various taxol analogues. |
| Inventors: | Kelly, Robert C. (Augusta, MI); Skulnick, Harvey I. (Kalamazoo, MI) |
| Assignees: | Pharmacia & Upjohn Company (Kalamazoo, MI) |
| Claim: | What is claimed is |
| Claim: | 1. A process of preparing wherein R.sub.1 is selected from the ground consisting of |
| Claim: | --CH.sub.3 |
| Claim: | --C.sub.6 H.sub.5 or phenyl substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, halo, C.sub.1 -C.sub.3 alkylthio, trifluoromethyl, C.sub.2 -C.sub.6 dialkylamino, hydroxy or nitro |
| Claim: | -2-furyl, 2-thienyl, 1-naphthyl, 2-naphthyl or 3,4-methylenedioxyphenyl; |
| Claim: | R.sub.10 is --H or --C(O)CH.sub.3 ; |
| Claim: | R.sub.11 is phenyl substituted with --(OC.sub.1 -C.sub.2 alkyl).sub.n where n is 1 to 3; |
| Claim: | R.sub.12 is selected from the group consisting of |
| Claim: | --C(O)H |
| Claim: | --C(O)phenyl substituted with one, 2 or 3 C.sub.1 -C.sub.3 alkylthio, C.sub.2 -C.sub.6 dialkylamino, hydroxy or nitro |
| Claim: | --SO.sub.2 -4-methylphenyl |
| Claim: | --C(O)(CH.sub.2).sub.3 COOH |
| Claim: | --C(O)-4-(SO.sub.3 H)phenyl |
| Claim: | --C(O)-1-adamantyl |
| Claim: | --C(O)O-3-tetrahydrofuranyl |
| Claim: | --C(O)O-4-tetrahydropyranyl |
| Claim: | --C(O)NHC.sub.1 -C.sub.10 alkyl |
| Claim: | --C(O)NHPh substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, halo, C.sub.1 -C.sub.3 alkylthio |
| Claim: | trifluoromethyl, C.sub.2 -C.sub.6 dialkylamino, or nitro |
| Claim: | --C(O)C(CH.sub.3).sub.2 CH.sub.2 Cl |
| Claim: | --C(O)- 1-phenyl- 1-cyclopentyl |
| Claim: | --C(O)- 1-methyl- 1-cyclohexyl |
| Claim: | --C(S)NHC(CH.sub.3).sub.3 |
| Claim: | --C(O)NHC(CH.sub.3).sub.3 or |
| Claim: | --C(O)NHPh; |
| Claim: | R.sub.14 is selected from the group consisting of --C(O)C.sub.1 -C.sub.6 alkyl, --C(O)OC.sub.1 -C.sub.6 alkyl, --C(O)OCH.sub.2 CX.sub.3 where X is Halo, --C(O)OCH.sub.2 CH.sub.2 Si(R.sub.20).sub.3 (where R.sub.20 is C.sub.1 -C.sub.6 alkyl), or --Si(R.sub.20).sub.3 ; |
| Claim: | which comprises reacting an oxazolidine free acid of Formula 7 ##STR13## wherein R.sub.1, R.sub.11 and R.sub.12 are as defined above; with a baccatin compound of Formula 8 ##STR14## wherein R.sub.10 and R.sub.14 are as defined above; in the presence of a dehydrating agent. |
| Claim: | 2. A compound of the formula ##STR15## wherein R.sub.1 is selected from the group consisting of --CH.sub.3 |
| Claim: | R.sub.11 is phenyl substituted with --(OC.sub.1 -C.sub.2 alkyl).sub.n where n is 1 to 3; and |
| Claim: | --C(O)phenyl substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl |
| Claim: | C.sub.1 -C.sub.3 alkylthio, C.sub.2 -C.sub.6 dialkylamino, hydroxy or nitro |
| Claim: | --C(O)NHPh substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, halo, C.sub.1 .sub.C.sub.3 alkylthio |
| Claim: | trifluoromethyl, C.sub.2 -C.sub.6 dialkylamino, or nitro, or |
| Claim: | --C(O)-1-phenyl-1-cyclopentyl |
| Claim: | --C(O)-1-methyl-1-cyclohexyl |
| Claim: | wherein R.sub.10 and R.sub.14, being the same or different, are selected from the group consisting of --C(O)C.sub.1 -C.sub.6 alkyl, --C(O)OC.sub.1 -C.sub.6 alkyl, --C(O)OCH.sub.2 CX.sub.3 where X is Halo, --C(O)CH.sub.2 CH.sub.2 Si(R.sub.20).sub.3 R.sub.20 is C.sub.1 -C.sub.6 alkyl), or --Si(R.sub.20).sub.3. |
| Claim: | 3. A compound according to claim 1 wherein R.sub.12 is --C(O)NHC(CH.sub.3).sub.3. |
| Claim: | 4. A compound according to claim 3 wherein is R.sub.11 is phenyl substituted with --OCH.sub.3 in the ortho and para positions. |
| Claim: | 5. A compound according to claim 1 wherein R.sub.12 is selected from the group consisting of --C(O)NHC.sub.1 -C.sub.10 alkyl, --C(O)NHPh substituted with one, 2 or 3 C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, halo, C.sub.1 -C.sub.3 alkylthio, trifluoromethyl, C.sub.2 -C.sub.6 dialkylamino, or nitro, or --C(O)NHC(CH.sub.3).sub.3 and --C(O)NHPh. |
| Claim: | 6. A compound according to claim 5 wherein R.sub.11 is phenyl substituted with --OCH.sub.3 in the ortho and para positions. |
| Claim: | 7. The process according to claim 1 wherein the dehydrating agent is a carbodiimide and a basic catalyst. |
| Claim: | 8. 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: | 9. The process according to claim 7 wherein the basic catalyst is 4-dimethylaminopyridine. |
| Claim: | 10. 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. |
| Current U.S. Class: | 548/215; 549/510; 549/511 |
| Current International Class: | C07D26304; C07D30514; C07D26306 |
| Patent References Cited: | 4814470 March 1989 Colin et al. 4857653 August 1989 Colin et al. 4876399 October 1989 Holton et al. 4924011 May 1990 Denis et al. 4924012 May 1990 Colin et al. 4942184 July 1990 Hangwitz et al. 4960790 October 1990 Stella et al. 5015744 May 1991 Holton 5059699 October 1991 Kingston et al. 5136060 August 1992 Holton 5157049 October 1992 Haugwitz et al. 5227400 July 1993 Holton et al. 5248796 September 1993 Chen et al. 5254580 October 1993 Chen et al. 5294637 March 1994 Chen et al. 5476954 December 1995 Bourzat et al. 5532388 July 1996 Bouchard et al. 5550261 August 1996 Bouchard et al. 5571917 November 1996 Bouchard et al. 5576450 November 1996 Bouchard et al. 5580997 December 1996 Bouchard et al. 5580998 December 1996 Bouchard et al. 5587493 December 1996 Bouchard et al. 5599942 February 1997 Bouchard et al. 5616739 April 1997 Mas et al. 5621121 April 1997 Comercon et al. 5637723 June 1997 Commercon et al. |
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| Primary Examiner: | Trinh, Ba K. |
| Attorney, Agent or Firm: | Jameson, William G. |
| رقم الانضمام: | edspgr.05965739 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |