Patent ID: 6943145

Claim:
A quaternary salt of the formula wherein: X − is the anion of a non-toxic, pharmaceutically acceptable acid; R 1 is C 1 -C 7 alkyl, C 1 -C 7 haloalkyl or C 7 -C 12 aralkyl; R 2 and R 3 , which are the same or different, are each selected from the group consisting of hydrogen, halo, cyano, C 1 -C 7 alkyl, C 1 -C 7 alkoxy, C 2 -C 8 alkoxycarbonyl, C 2 -C 8 alkanoyloxy, C 1 -C 7 haloalkyl, C 1 -C 7 alkylthio, C 1 -C 7 alkylsulfinyl, C 1 -C 7 alkylsulfonyl, —CH═NOR′″ wherein R′″ is hydrogen or C 1 -C 7 alkyl, and —CONR′R″ wherein R′ and R″, which are the same or different, are each hydrogen or C 1 -C 7 alkyl; or one of R 2 and R 3 together with the adjacent ring carbon atom forms a phenyl ring fused to the six-membered heterocyclic ring, which phenyl ring is unsubstituted or is substituted with one or two substituents, which are the same or different, selected from the group consisting of hydroxy, protected hydroxy, halo, cyano, C 1 -C 7 alkyl, C 1 -C 7 alkoxy, C 2 -C 8 alkoxycarbonyl, C 2 -C 8 alkanoyloxy, C 1 -C 7 haloalkyl, C 1 -C 7 alkylthio, C 1 -C 7 alkylsulfinyl, C 1 -C 7 alkylsulfonyl, —CH═NOR′″ wherein R′″ is hydrogen or C 1 -C 7 alkyl, and —CONR′R″ wherein R′ and R″, which are the same or different, are each hydrogen or C 1 -C 7 alkyl; the depicted ring system is a pyridinium, quinolinium or isoquinolinium ion; “spacer” is an L-amino acid unit or a di- or tripeptide consisting of 2 or 3 L-amino acid units, the N-terminal amino acid of said spacer being bonded to the depicted carbonyl carbon via an amide bond; and “peptide” is a peptide having 2 to 20 amino acid units having growth factor inhibitory activity which is octreotide or lanreotide, wherein the N-terminal phenylalanine or napthylalanine of said peptide is bonded to the C-terminal amino acid of said spacer via a peptide bond, and wherein the C-terminal threonine of said peptide: (a) has a C-terminal carboxyl group —COOH which has been replaced with a —COOR 4 group wherein R 4 is C 6 -C 30 polycycloalkyl-C p H 2p — wherein p is 0, 1, 2 or 3, or C 6 -C 30 polycycloalkenyl-C p H 2p — wherein p is defined as above; (b) has a C-terminal —CH 2 OH group which has been replaced with a —CH 2 OCOR 4 group wherein R 4 is defined as above; (c) has a C-terminal —CONH 2 group which has been replaced with a —CO-Gly-OR 4 group wherein R 4 is defined as above, said —CO-Gly-OR 4 group regenerating the C-terminal —CONH 2 group in vivo; (d) has a C-terminal —CONH 2 group; or (e) has a C-terminal —CH 2 OH group; with the provisos that: (1) when the C-terminal amino acid is as defined in (a), (b) or (c) above, the side chain —NH 2 group of lysine of the peptide is replaced with a —NHCOOR 5 group wherein R 5 is C 1 -C 7 alkyl or benzyl; and (2) when the C-terminal amino acid is as defined in (d) or (e) above, then the side chain —NH 2 group of lysine of the peptide is replaced with a —NHCOOR 4 group wherein R 4 is defined as above.