Alkaloid aminoester derivatives and medicinal composition thereof

1. A process for preparing a compound of formula (I):

wherein:

R1 is H or a group selected from the group consisting of (C 1 -C 10 )-alkyl, aryl, (C 3 -C 8 )-cycloalkyl, arylalkyl, and heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of halogen atoms, OH, oxo (═O), SH, NO 2 , CN, CON(R5) 2 , COOH, NHCOR5, COR5, CO 2 R5, CF 3 , (C 1 -C 10 )-alkoxycarbonyl, (C 1 -C 10 )-alkylsulfanyl, (C 1 -C 10 )-alkylsulfinyl, (C 1 -C 10 )-alkylsulfonyl, (C 1 -C 10 )-alkyl, and (C 1 -C 10 )-alkoxyl;

R2 is a group selected from the group consisting of (C 1 -C 10 )-alkyl, aryl, (C 3 -C 8 )-cycloalkyl, arylalkyl, and heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of halogen atoms, OH, oxo (═O), SH, NO 2 , CN, CON(R5) 2 , COOH, NHCOR5, COR5, CO 2 R5, CF 3 , (C 1 -C 10 )-alkoxycarbonyl, (C 1 -C 10 )-alkylsulfanyl, (C 1 -C 10 )-alkylsulfinyl, (C 1 -C 10 )-alkylsulfonyl, (C 1 -C 10 )-alkyl, and (C 1 -C 10 )-alkoxyl;

R3 is H or a group selected from the group consisting of (C 1 -C 10 )-alkyl, aryl, (C 3 -C 8 )-cycloalkyl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, OH, oxo (═O), SH, NO 2 , CN, CON(R5) 2 , COOH, CO 2 R5, CF 3 , (C 1 -C 10 )-alkoxycarbonyl, (C 1 -C 10 )-alkylsulfinyl, (C 1 -C l0 )-alkylsulfonyl, (C 1 -C 10 )-alkyl, and (C 1 -C 10 )-alkoxyl;

R6 represents a group of formula (i) or (ii) or (iii) or (iv):

wherein

* indicates the position at which R6 is bonded to formula (I);

m=1, 2, or 3;

n=1, 2, or 3;

A 31 is a physiologically acceptable anion;

R4 is a group of formula (Y)

—(CH 2 )p−P—(CH 2 )q−W  (Y)

wherein

p is 0 or an integer from 1 to 4;

q is 0 or an integer from 1 to 4;

P is absent or is selected from the group consisting of O, S, SO, SO 2 , CO, NR5, CH═CH, N(R5)SO 2 , N(R5)COO, N(R5)C(O), SO 2 N(R5), CO(O)N(R5), and C(O)N(R5);

W is H or a group selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, aryl, and heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of halogen atoms, OH, oxo (═O), SH, NO 2 , CN, CON(R5) 2 , COOH, NH 2 , NHCOR5, CO 2 R5, (C 1 -C 10 )-alkoxycarbonyl, (C 1 -C 10 )-alkylsulfanyl, (C 1 -C 10 )-alkylsulfinyl, (C 1 -C 10 )-alkylsulfonyl, (C 1 -C 10 )-alkyl, and (C 1 -C 10 )-alkoxyl;

R5 is H or a group selected from the group consisting of (C 1 -C 10 )alkyl, (C 1 -C 6 )alkylhalo, (C 2 -C 6 )alkynyl, (C 2 -C 6 )alkenyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkyl-(C 1 -C 6 )alkyl, heteroaryl, (C 1 -C 6 )alkyl-heteroaryl, and aryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, OH, oxo (═O), SH, NO 2 , CN, CONH 2 , COOH, (C 1 -C 10 )-alkoxycarbonyl, (C 1 -C 10 )-alkylsulfanyl, (C 1 -C 10 )-alkylsulfinyl, (C 1 -C 10 )-alkylsulfonyl, (C 1 -C 10 )-alkyl, and (C 1 -C 10 )-alkoxyl;

or a pharmaceutically acceptable salt thereof,

with the proviso that when R1 is H, R2 is phenyl, and R3 is H, then R6 is not a group of formula (iii),

said process comprising:

alkylating a compound of formula (VI):

with an alkylating agent of formula (XI):

A−R4  (XI)

wherein A is a suitable leaving group selected from the group consisting of halide and sulfonate, and R7 represents a group of formula (vi) or (vii) or (viii) or (ix):

wherein

* indicates the position at which R7 is bonded to formula (VI);

m=1, 2, or 3;

n=1, 2, or 3.

2. A process according to claim 1 , wherein said compound of formula (VI) is prepared by a process comprising:

alkylating an amine compound of formula (II):

with a compound of formula (III):

wherein LG is a suitable leaving group and K is either a hydroxyl group or a suitably protected hydroxyl group, to obtain a compound of formula (IV):

condensing said compound of formula (IV) with a compound of formula (V):

to obtain said compound of formula (VI).

3. A process according to claim 1 , wherein said compound of formula (VI) is prepared by a process comprising:

coupling an amine of formula (II):

with a ketone of formula (VII):

wherein K is either a hydroxyl group or a suitably protected hydroxyl group, to obtain a compound of formula (IV):

condensing said compound of formula (IV) with a compound of formula (V):

to obtain said compound (VI).

4. A process according to claim 1 , wherein said compound of formula (VI) is prepared by a process comprising:

reacting a compound of formula (IX):

wherein K is either a hydroxyl group or a suitably protected hydroxyl group, with an alkylating agent of formula (VIII):

wherein z is a carbonyl group or a suitable leaving group, to obtain a compound of formula (IV):

wherein R2 is hydrogen;

condensing said compound of formula (IV) with a compound of formula (V):

to obtain said compound of formula (VI).

5. A process according to claim 1 , wherein said compound of formula (VI) is prepared by a process comprising:

coupling a compound of formula (IIIa):

wherein W is a suitable leaving group or hydroxy and K is either a hydroxyl group or a suitably protected hydroxyl group,

with a compound of formula (V):

to obtain a compound of formula (X):

reacting said compound of formula (X) with an amine of formula (II):

to obtain said compound of formula (VI).