Abstract: The present invention relates to novel intermidiate compounds of formula(la) and is slats therof, wherein R is an amino protecting group,R1 is selected from the group consisting of hydrogen, an alkyl, arralkyl hydroxymethyl, carboxymethyl, acyloxymethyl, trialkysilyl or an N-substituted alkdy amine where nitrogen forms the linking atom.The invention also relates to the use of these novel intermediate compounds of formuls(Ia) for the prreparation of comtothecin analogues and its salts more particularly the anti-cancer drug irinotecan and its pharmaceutically accepted salts,
1. A compound of formula(Ia) and its sails thereof Wherein R is amino protecting group defined as -CO (CH2) n CH3 (n= 0 to4); - CO (CH2) n CH2 X (X= Halogen; n= 0 to 4); -COCX3 (X- Halogen) and R, is hydrogen, alkyl, araalkyl, hydroxyRg ethyl, carboxymethyl, acyloxy methyl silyl or N-substituted alkyl amine -CH2-N-R2 where N is a linking nitrogen atom, wherein R2 and R3 substituents on the N-atom may be defined as follows. i)R2 and Rj are each independently selected from hydrogen, alkyl, alkemyl, hydroxyalkyl, acyloxyalky! or acycloxy alkyl substituted group. ii)R2 and R3 together with the nitrogen linking atom can form heterocyclic unit
2. A compound of claim 1, wherein Rs is an ethyl group.
3. A compound of claim 1 that is an acid addition salt of compound of formula(Ia) with an acid selected from hydrochloric, hydrobromic,benzoic, tartaric, citric, fumaric. maleic ,alkyl monocarboxylic acid and alkyldicarboxylic acid having Q-C4 alkyl chain.
4. A process for the preparation of camptothecin analogues or its salts thereof, the said process comprising first step of contacting compound of formula (la) and a second step of preparing a sail of camptothecin analogues thus obtained.
5. A process of claim 4 , wherein irinotecan or its salt thereof is prepared by contacting compound of formula (la ,R1=C2H5) or its sail thereof with compound of formula (I).
6. A process for preparing compounds of formula(Ia) comprising step of contacting compound of of formula (Ha) with 4-piperidinopiperidine carbamyl chloride (IV),
7. A drug substance comprising therapeutically effective amount of irinotecan and/ or its salt thereof and compound of formula(Ia ) and /or its atleast one salt thereof in a detectable amount.
8. The drug substance of claim 7, wherein compound of formula(Ia ) and /or its atleast one salt thereof present in an amount not more than about 1%.
9. The drug substance of claim 7, wherein compound of formula(Ia ) and /or its atleast one salt thereof present in an amount not more than about 0.5%.
10. The drug substance of claim 7, wherein compound of formula(Ia ) and /or its atleast one salt thereof present in an amount not more than about 0.1%.
11. A drug substance comprising therapeutically effective amount of irinotecan and/ or its salt thereof and 7- ethyM O-hydroxy-camptothecin and /or its atleast one salt thereof in a detectable amount.
12. The drug substance of claim 11, wherein 7-ethyl-i O-hydroxy-camptothecin and /or its atleast one salt thereof present hi an amount, not more than about 1%.
13. The drug substance of claim 11, wherein 7-ethyl-10-hydroxy-camptothecin and /or its atleast one salt thereof present in an amount, not more than about 0.5%.
14. The drug substance of claim 11, wherein 7-ethyl-10-hydroxy-camptothecin and /or its atieast one salt thereof present in an amount, not more than about 0.1%.
15. A drug substance comprising therapeutically effective amount of irinotecan and/or its salt thereof and compound of formula(la) and /or its atieast one salt thereof and 7-ethyl-10-hydroxy-camptothecin and /or its atieast one salt thereof each present in a detectable amount.
16. The drug substance of claim 15, wherein compound of formula(la) and/or its atieast one salt thereof and 7-ethyi-10-hydroxy-camptothecin and /or its atieast one salt thereof each present in an amount not more thanl%. 17 , The drug substance of claim ]5, wherein compound of formulafia) and /or its atieast one salt thereof and 7-ethyl-10-hydroxy-camptothecin and /or its atieast one salt thereof each present in an amount not more than 0.5%.
18. The drug substance of claim 15 wherein compound of formulafla )and /or its atieast one salt thereof and 7-ethyl-10-hydroxy-camptothecin and /or its atieast one salt thereof each present in an amount not more than 0.1%.
| # | Name | Date |
|---|---|---|
| 1 | 1704-che-2006-form 5.pdf | 2011-09-03 |
| 2 | 1704-che-2006-form 3.pdf | 2011-09-03 |
| 3 | 1704-che-2006-form 1.pdf | 2011-09-03 |
| 4 | 1704-che-2006-description(provisional).pdf | 2011-09-03 |
| 5 | 1704-che-2006-correspondnece-others.pdf | 2011-09-03 |
| 6 | 1704-che-2006-abstract.pdf | 2011-09-03 |
| 7 | 1704-che-2006 form-26.pdf | 2011-09-03 |
| 8 | 1704-che-2006 description (complete).pdf | 2011-09-03 |
| 9 | 1704-che-2006 claims.pdf | 2011-09-03 |
| 10 | 1704-CHE-2006 CORRESPONDENCE PO.pdf | 2012-01-03 |