Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2002-08-06
2004-09-14
Peselev, Elli (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S022100, C564S107000
Reexamination Certificate
active
06790836
ABSTRACT:
TECHNICAL FIELD
This invention is a useful invention in the field of medicine. More detailedly, this invention relates to an industrially suitable process for preparation of a useful compound in the field of medicine, and novel preparation intermediates necessary for the preparation process and processes for preparation of the intermediates.
BACKGROUND ART
An indolopyrrolocarbazole derivative prepared by the preparation process of the invention and represented by the formula [I]:
is a compound which has a carcinostatic activity and is now under clinical tests (Mitsuru Ohkubo et al., Bioorganic & Medicinal Chemistry Letters, volume 9, pages 3307-3312 (1999).
As to a process for preparation of the compound, there is a disclosure in WO95/30682.
The object of the invention lies in obviating undesirable points as an industrial preparation process from the process disclosed in WO95/30682. Namely, the object of the invention lies in deleting the steps shown below where highly physiologically active compounds are handled (Preparation steps of Compounds [b] and [c]), in the preparation process disclosed in WO95/30682.
In the above, R
a
represents a hydrogen atom, a lower alkyl group, a benzyloxymethyl group or an aralkyl group, and R
b
, R
c
, R
d
, R
e
and R
f
each represent a protective group of a hydroxyl group such as, for example, a benzyl group, a tolyl group, a p-methoxybenzyl group or a benzyloxymethyl group.
DISCLOSURE OF INVENTION
The present inventors have made sequential research into a process for preparation of the indolopyrrolocarbazole derivative [I], and as a result, they found the present preparation process of the indolopyrrolocarbazole derivative [I] which is excellent as an industrial process in the point that the step handling a highly physiologically active compound can be made to be only the final step, and completed the invention. Further, they also found that the respective preparation intermediates used in the preparation process of the indolopyrrolocarbazole derivative [I] of the invention are novel compounds.
Namely, the invention relates to the matters described in the following items (1) to (36).
(1) A process for preparation of an indolopyrrolocarbazole derivative represented by the formula [I]
which comprises removing the protective groups of a compound represented by the general formula [II]:
wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
may be the same or different and each represent a protective group of a hydroxyl group, and R
7
and R
8
may be the same or different and each represent a hydrogen atom or a protective group of a hydroxyl group.
(2) The process according to item (1) wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
and R
8
are benzyl groups.
(3) The process according to item (1) wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are benzyl groups and R
7
and R
8
are hydrogen atoms.
(4) The process according to item (1) wherein the compound represented by the general formula [II] is obtained by reacting a compound represented by the general formula [IV]:
wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
may be the same or different and each represent a protective group of a hydroxyl group, with a hydrazinediol derivative acid addition salt represented by the general formula [III]:
wherein X represents an acid molecule, and R
7
and R
8
may be the same or different and each represent a hydrogen atom or a protective group of a hydroxyl group, in the presence of an acid-capturing agent.
(5) The process according to item (4) wherein R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
and R
8
are benzyl groups.
(6) The process according to item (4) wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are benzyl groups and R
7
and R
8
are hydrogen atoms.
(7) The process according to item (4) wherein X is oxalic acid.
(8) The process according to item (4) wherein the compound represented by the general formula [IV] is obtained by treating a compound represented by the general formula [V]:
wherein Y
1
represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a phenyl group, a benzyloxymethyl group or an aralkyl group, and R
1
, R
2
, R
3
, R
4
, R
5
and R
6
may be the same or different and each represent a protective group of a hydroxyl group, with a base in an inert solvent.
(9) The process according to item (8) wherein Y
1
is a methyl group.
(10) The process according to item (8) wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are benzyl groups.
(11) A compound represented by the general formula [IV]:
wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
may be the same or different and each represent a protective group of a hydroxyl group.
(12) The compound according to item (11) wherein R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are benzyl groups.
(13) A hydrazinediol derivative acid addition salt represented by the general formula [III]:
wherein X represents an acid molecule, and R
7
and R
8
may be the same or different and each represent a hydrogen atom or a protective group of a hydroxyl group.
(14) The compound according to item (13) wherein R
7
and R
8
are benzyl groups.
(15) The compound according to item (13) wherein R
7
and R
8
are hydrogen atoms.
(16) The compound according to item (13) wherein X is oxalic acid.
(17) A hydrazinediol derivative represented by the general formula [III-a]:
wherein R
7a
and R
8a
may be the same or different and each represent a protective group of a hydroxyl group.
(18) The compound according to item (17) wherein R
7a
and R
8a
are benzyl groups.
(19) A process for preparation of a hydrazinediol derivative acid addition salt represented by the general formula [III]:
wherein R
7a
and R
8a
maybe the same or different and each represent a protective group of a hydroxyl group, and X represents an acid molecule,
which comprises reacting a hydrazinediol derivative represented by the general formula [III-a]:
wherein R
7a
and R
8a
are as defined above, with an acid.
(20) The process according to item (19) wherein R
7a
and R
8a
are benzyl groups.
(21) The process according to item (19) wherein the hydrazinediol derivative represented by the general formula [III-a] is obtained by eliminating the protective group of the amino group of a hydrazinediol derivative represented by the general formula [III-b]:
wherein R
7a
and R
8a
may be the same or different and each represent a protective group of a hydroxyl group.
(22) The process according to item (21) wherein R
7a
and R
8a
are benzyl groups and R
9
is a t-butoxycarbonyl group.
(23) The process according to item (21) wherein the hydrazinediol derivative represented by the general formula [III-b] is obtained by reducing a hydrazone derivative represented by the general formula [III-c]:
wherein R
7a
and R
8a
may be the same or different and each represent a protective group of a hydroxyl group, and R
9
represents a protective group of an amino group.
(24) The process according to item (23) wherein R
7a
and R
8a
are benzyl groups and R
9
is a t-butoxycarbonyl group.
(25) The process according to item (23) wherein the hydrazone derivative represented by the general formula [III-c] is obtained by reacting a dihydroxyacetone derivative represented by the general formula [III-e]:
wherein R
7a
and R
8a
may be the same or different and each represent a protective group of a hydroxyl group,
with a hydrazine derivative represented by the general formula [III-d]:
wherein R
9
represents a protective group of an amino group, in a mixed solvent.
(26) The process according to item (25) wherein R
7a
and R
8a
are benzyl groups and R
9
is a t-butoxycarbonyl group.
(27) The process according to item (25) wherein the dihydroxyacetone derivative represented by the general formula [III-e] is obtained by reacting a propanetriol derivative represented by the general formula [III-f]:
where
Akao Atsushi
Hagiwara Masayuki
Hiraga Shouichi
Kamatani Asayuki
Kawasaki Masashi
Banyu Pharmaceutical Co. Ltd.
Nixon & Vanderhye P.C.
Peselev Elli
LandOfFree
Process for preparing indolopyrrolocarbazole derivatives,... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing indolopyrrolocarbazole derivatives,..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing indolopyrrolocarbazole derivatives,... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3268083