New amphetamine derivatives, antibodies against them and pharmaceutical compositions containing them

A compound having formula (II)

• 11
• wherein n is an integer between 1 and 6,
• R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
• R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and
• R5 is selected from the group consisting of hydrogen, a polymethylene chain:
• —(CH)m—R10 and an oxy-polymethylene chain:
• —O—(CH2)m—R10, wherein —R10 is selected from the group consisting of carboxyl, thiol, —CONHR13SH, and —CONHCHR11SH, wherein R13 is selected from the group consisting of —CH(COOH)CH2— and —(CH2)m— and wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain:
• —(CH2)m—COOH.

A compound having formula (IIIa):

• 14
• wherein;
• R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
• R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain:
• (CH2)n—COOH, wherein n is an integer between 1 and 6;
• R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and,
• R11 is selected from the group consisting of a polymethylene chain:
• —(CH2)m— and an oxy-polymethylene chain:
• —O(CH2)m—, wherein m is an integer between 1 and 4, with the proviso that when R1 is a methyl, then R11 is not a polymethylene chain:
• —(CH2)m—.

A compound having formula (IIIb)

• 16
• wherein,
• R1 and R3 are selected from the group consisting of hydrogen, and a C1-C3 alkyl;
• R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain:
• (CH2)n—COOH, wherein n is an integer between 1 and 6;
• R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and
• R12 is selected from the group consisting of a polymethylene chain:
• (CH2)mCONHR13 and an oxy-polymethylene chain:
• —O(CH2)mCONHCH—R13;
• wherein R13 is selected from the group consisting of —CH(COOH)CH2—and —(CH2)m—, wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain:
• —(CH2)m—COOH.

An amphetamine-related immunogen I1 comprising:

• a compound having formula (II) covalently conjugated to a carrier,
• 18
• wherein p is an integer between 1 and 6;
• wherein R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
• R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and
• R5 is selected from the group consisting of hydrogen, a polymethylene chain:
• —(CH)m—R10 and an oxy-polymethylene chain:
• —O—(CH2)m—R10, wherein —R10 is selected from the group consisting of carboxyl, thiol, —CONHR13SH, and —CONHCHR11SH, wherein R13 is selected from the group consisting of —CH(COOH)CH2—and —(CH2)m— and wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain:
• —(CH2)m—COOH.

An amphetamine-related immunogen 12 comprising:

• a compound having formula (IIIa) covalently conjugated to a carrier,
• 19
• wherein R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
• R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain:
• (CH2)n—COOH, wherein n is an integer between 1 and 6;
• R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and,
• R11 is selected from the group consisting of a polymethylene chain:
• —(CH2)m— and an oxy-polymethylene chain:
• —O(CH2)m—, wherein m is an integer between 1 and 4, with the proviso that when R1 is a methyl, then R 1 is not a polymethylene chain:
• —(CH2)m—.

An amphetamine-related immunogen I3 comprising:

• a compound having formula (IIIb) covalently conjugated to a carrier,
• 20
• wherein R1 and R3 are selected from the group consisting of hydrogen, and a C1-C3 alkyl;
• R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain:
• (CH2)n—COOH, wherein n is an integer between 1 and 6;
• R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —OR9 and —SR9, wherein R9 is hydrogen or a C1-C3 alkyl;
• and
• R12 is selected from the group consisting of a polymethylene chain:
• (CH2)mCONHR13 and an oxy-polymethylene chain:
• —O(CH2)mCONHCH—R13;
• wherein R13 is selected from the group consisting of —CH(COOH)CH2— and —(CH2)m—, wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain:
• —CH2)m.