Novel derivatives and analogues of galanthamin

New compounds of general formula I

• 388
• in which the substituents have the meanings that are explained below:
• R1 and R2 are the same or different and mean:
• a) hydrogen, F, Cl, Br, I, CN, NC, OH, SH, NO2, SO3H, PO3H, NH2, CF3 OSO2 (CH2)nCF3, in which n is equal to 0, 1 or 2, —OSO2—aryl, —OSO-vinyl or —OSO2-ethinyl;
• b) a low (C2-C6), optionally branched, optionally substituted (Ar)alkyl, (Ar)alkoxy, cycloalkyl or cycloalkoxy group;
• c) an amino group, which optionally is substituted by one or two identical or different low (C1-C6), optionally branched, optionally substituted (Ar)alkyl or (Ar)alkylcarbonyl or (Ar)alkoxycarbonyl groups or by a group that is selected from an optionally substituted pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine, or homopiperazine radical;
• d) a —COOH, —COO(Ar)alkyl, —CO-amino group, which optionally is substituted as indicated under c), or a COH(Ar)alkyl group;
• e) a —(CH2)nX (in which X=Br, Cl, F or I), —(CH2)nOH, —(CH2)nCHO, —(CH2)nCOOH, —(CH2)nCN, —(CH2)nNC, —(CH )nCOalkyl, or —(CH2)nCOaryl group, in which n is 1-4;
• f) a —(CH2)nvinyl, —(CH2)nethinyl, or —(CH2)ncycloalkyl group in which n is 0, 1 or 2, whereby cycloalkyl is an aliphatic ring with 3 to 7 C atoms;
• g) a C3-C6-substituted alkenyl group (optionally substituted with H, F, Br, Cl, CN, CO2alkyl, COalkyl, COaryl);
• h) a C3-C6-substituted alkinyl group (optionally substituted with H, F, Br, Cl, CN, CO2alkyl, COalkyl, COaryl);
• or
• i) R1 and R2 together mean —CH═CH—CH═CH—, —O(CH2)n° (n=1 to 3), —CH═CHA1—(A1 is NH, O or S), or —CH2CH2—A1 (A1 is NH, O or S);
• R3 has the same meaning as R1, especially OH and OCH3, or
• R2 and R3 together mean —A2(CH2)nA2—, in which n is 1 to 3 and substituents A2 are the same or different and mean NH, O or S;
• R4 and R5 are either
• a) both hydrogen, or
• b) one of R4 and R5 is hydrogen, an (Ar)alkyl, (Ar)alkenyl or (Ar)alkinyl group, and the other of R4 and R5 is
• i) OR6, in which R6 means hydrogen, a low (C1-C10, optionally branched or substituted) alkyl group or cycloalkyl group, a C3-C10 substituted silyl group (for example, triethylsilyl, trimethylsilyl, t-butyldimethylsilyl or dimethylphenylsilyl), a C2-C10 alpha-alkoxyalkyl group, for example tetrahydropyranyl, tetrahydrofuranyl, methoxymethyl, ethoxymethyl, 2-methoxypropyl, ethoxyethyl, phenoxymethyl or 1-phenoxyethyl;
• ii) O—CS—NHR6 (thiourethane), in which R6 has the meanings indicated above under i);
• iii) O—CO—NHR7 with the meaning below:
• 389
• iv) O—CO—HR6, in which R6 has the meanings indicated above under i), especially ester with the substitution pattern of amino acids (both enantiomers), such as
• 390
• v) NR7R7, in which two substituents R7 are the same or different and mean hydrogen, a low (C1-C4), optionally branched, alkyl group or cycloalkyl group, or substituents R7 together are —(CH;)n—, in which n is 3 to 5;
• vi) NH—COR6 (amide), in which R6 has the meanings indicated above under i);
• vii) S—R6, in which R6 has the meaning indicated above under i);
• viii) SOnR8, in which n is 0, 1 or 2, and in which R8 is a (C1-C10), optionally branched or cyclic, optionally substituted (Ar)alkyl group;
• G1:
• —(CH2)x—, in which x is 1 or 2;
• G2:
• —(CH2)y, in which y is 0 to 2;
• G3:
• —(CH2)z—, in which z is 0 to 3, provided that the sum of x+y+z is at least 2 and at most 4, or in which G3 is carbonyl or thiocarbonyl, —CH(OH)— or —C(OH)═;
• W is:
• a) CR13R14R in which R13 means hydrogen and R14 means —(CH2)nNR7R7, —CO—NR7R7 or —COOR7, in which n is 0 to 2 and R7 has the above-mentioned meanings, or R7 and R7 form a ring via —(CH2)n in which n is 3 to 5, whereby substituents R13 and R14 can be exchanged;
• b) N-Phenyl (optionally substituted with fluorine, bromine, chlorine, (C1-C4) alkyl, CO2 alkyl, CN, CONH2, or alkoxy) means N-thien-2 or 3-yl, or N-fur-2 or 3-yl or an N-1,3,5-triazinyl, whereby the triazine radical can then be substituted with Cl, OR6 or NR7R7, and R6 or R7 has the meaning indicated above;
• c) One of the substituents that is presented below
• 391
• in which 1 means no bond or —(CH2)n—, whereby n=0 to 3, carbonyl, thiocarbonyl, O, S, —SO— or SO2, R6 has the meanings that are indicated above, and in which, Q is —(CH2)n—M*—(CH2)m, whereby n=0 to 4 and m=0 to 4 and M* means alkinyl, alkenyl, disubstituted phenyl, disubstituted thiophene, disubstituted furan, disubstituted pyrazine, disubstituted pyridazine, a spacer of one of the formulas presented below, a peptide spacer L or a heterocyclic spacer HS of the formulas below,
• 392
• in which R15means the side chain of D-, L-, D,L-aminoacids or unnatural amino acids, and for the case of n>1, R15 in the individual radicals in each case means the same or a different side chain of D-, L-, D,L-amino acids or unnatural amino acids, provided that atom N in addition to Q is connected in each case to groups G2 and G3 of formula I;
• d) a tricyclic substituent (Tr) that is optionally substituted at least in one place with at least one heterocyclic ring as a ring component and a binding site to a carbon atom of an anellated benzene ring thereof, which is connected via a spacer Q and the nitrogen atom that is adjacent to Q in each case with G2 and G3 of the compound of formula I, whereby Q has the meaning that is indicated above under c);
• or
• e) —NH—, —O—, —S—, —SO— or —SO2—.