US 7,022,492 B2 · Ecstasy haptens and immunogens

Abstract

Methods, compositions and kits are disclosed. Enzyme conjugates of Formula I are employed in assays for the determination of an methylenedioxyamphetamine, a methylene-dioxyethamphetamine, and/or a methylenedioxymethamphetamine. Immunogenic conjugates of Formula I are employed to prepare antibodies for an methylenedioxyamphetamine, a methylenedioxyethamphetamine, and/or for a methylene-dioxymethamphetamine for use in assays for the determination of an methylenedioxyamphetamine, a methylenedioxyethamphetamine, and/or a methylene-dioxymethamphetamine. The enzyme conjugates may also be employed to screen antibodies for use in such methods.

Claims68

Dependent claims

A compound of the formula:

wherein:
R19 is lower alkyl or is taken together with R20 to form a ring, which may be a five- or six-member ring, usually a five-member ring;
R20 is lower alkyl, or is taken together with R19 to form a ring as discussed above,
R1 is H or lower alkyl,
R2 is
(a) —(CH2)aC(O)(CH2)bSR3, wherein a is 0 to 5, b is 1 to 5 and R3 is lower alkyl or (CH2)cC(O)NR4R5 wherein c is 1 to 5, R4 is H or lower alkyl and R5 is H, an immunogenic carrier or a label, or
(b) (A)d(Q)n wherein Q is H or —(CH2)eCH(R8)(CH2)fOC(O)(CH2)gR9 being H only when d is 1 wherein A is —C(O)(CH2)hC(O)NR10((CH2)jO(CH2)kO)m(CH)2NR11—, d is 0 or 1, n is 0 or 1 wherein one of d or n is 1, h is 1 to 5, R10 is H or lower alkyl, j is 1 to 5, k is 1 to 5, m is 1 to 3, R11 is H or lower alkyl, e is 1 to 5, R8 is OH or H, f is 1 to 5, g is 0 to 5, and R9 is H, an immunogenic carrier or a label;
W is H or JR14 being H when R2 is other than H or lower alkyl, wherein
J is O or S,
R14 is H, lower alkyl, a protecting group, or —(CH2)rC(O)NR15(CH2)s(D)tR16, wherein r is 1 to 5, R15 is H or lower alkyl, s is 1 to 5, D is S, O, or NH, t is 0 or 1 being 0 when R16 is maleimidyl or succinimidyl, R16 is H, maleimidyl, succinimidyl, or —(CH2)qC(O)NR17R18,
q is 1 to 5,
R17 is H or lower alkyl,
R18 is H, lower alkyl, an immunogenic carrier or label,
and including the acid salts thereof.

11 more elements

A method for determining methylenedioxyamphetamine and/or methylenedioxymethamphetamine and/or methylenedioxyethamphetamine in a sample suspected of containing methylenedioxyamphetamine and/or methylenedioxymethamphetamine and/or methylenedioxyethamphetamine, said method comprising:

(a) providing in combination in a medium:
(i) said sample,
(ii) conjugate of an enzyme and a methylenedioxyamphetamine analog and/or a conjugate of an enzyme and a methylenedioxymethamphetamine analog and/or a conjugate of an enzyme and a methylenedioxyethamphetamine analog,
(i) an antibody for methylenedioxyamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is H,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(iv) an antibody for methylenedioxymethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is methyl,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(v) an antibody for methylenedioxyethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is ethyl,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and
(b) examining said medium for the presence of a complex comprising said methylenedioxyamphetamine and said antibody for methylenedioxyamphetamine and/or a complex of said methylenedioxymethamphetamine and said antibody for methylenedioxymethamphetamine and/or a complex of said methylenedioxyethamphetamine and said antibody for methylenedioxyethamphetamine, the presence thereof indicating the presence of said methylenedioxyamphetamine and/or methylenedioxymethamphetamine and/or methylenedioxyethamphetamine in said sample.

31 more elements

A method for determining methylenedioxyamphetamine and/or methylenedioxymethamphetamine in a sample suspected of containing methylenedioxyamphetamine and/or methylenedioxymethamphetamine, said method comprising:

(a) providing in combination in a medium:
(i) said sample,
(ii) a conjugate of an enzyme and an methylenedioxyamphetamine analog and/or a conjugate of an enzyme and a methylenedioxymethamphetamine analog and/or a conjugate of an enzyme and a methylenedioxyethamphetamine analog,
(i) an antibody for methylenedioxyamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(iv) an antibody for methylenedioxymethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is methyl,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(v) an antibody for methylenedioxyethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is ethyl,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and
(b) examining said medium for the presence of a complex comprising said methylenedioxyamphetamine and said antibody for methylenedioxyamphetamine and/or a complex of said methylenedioxymethamphetamine and said antibody for methylenedioxymethamphetamine and/or a complex of said methylenedioxyethamphetamine and said antibody for methylenedioxyethamphetamine, the presence thereof indicating the presence of said amphetamine and/or methamphetamine and/or methylenedioxyethamphetamine in said sample.

28 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/736,018Filed 15 Dec 2003

Published

US 2005/0130225 A116 Jun 2005

Granted

4 Apr 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 405/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 317/60
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring: radicals…
C07D 317/64
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
C07D 403/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Abstract

Claims68

Dependent claims

A compound of the formula:

wherein:
R19 is lower alkyl or is taken together with R20 to form a ring, which may be a five- or six-member ring, usually a five-member ring;
R20 is lower alkyl, or is taken together with R19 to form a ring as discussed above,
R1 is H or lower alkyl,
R2 is
(a) —(CH2)aC(O)(CH2)bSR3, wherein a is 0 to 5, b is 1 to 5 and R3 is lower alkyl or (CH2)cC(O)NR4R5 wherein c is 1 to 5, R4 is H or lower alkyl and R5 is H, an immunogenic carrier or a label, or
(b) (A)d(Q)n wherein Q is H or —(CH2)eCH(R8)(CH2)fOC(O)(CH2)gR9 being H only when d is 1 wherein A is —C(O)(CH2)hC(O)NR10((CH2)jO(CH2)kO)m(CH)2NR11—, d is 0 or 1, n is 0 or 1 wherein one of d or n is 1, h is 1 to 5, R10 is H or lower alkyl, j is 1 to 5, k is 1 to 5, m is 1 to 3, R11 is H or lower alkyl, e is 1 to 5, R8 is OH or H, f is 1 to 5, g is 0 to 5, and R9 is H, an immunogenic carrier or a label;
W is H or JR14 being H when R2 is other than H or lower alkyl, wherein
J is O or S,
R14 is H, lower alkyl, a protecting group, or —(CH2)rC(O)NR15(CH2)s(D)tR16, wherein r is 1 to 5, R15 is H or lower alkyl, s is 1 to 5, D is S, O, or NH, t is 0 or 1 being 0 when R16 is maleimidyl or succinimidyl, R16 is H, maleimidyl, succinimidyl, or —(CH2)qC(O)NR17R18,
q is 1 to 5,
R17 is H or lower alkyl,
R18 is H, lower alkyl, an immunogenic carrier or label,
and including the acid salts thereof.

11 more elements

(a) providing in combination in a medium:
(i) said sample,
(ii) conjugate of an enzyme and a methylenedioxyamphetamine analog and/or a conjugate of an enzyme and a methylenedioxymethamphetamine analog and/or a conjugate of an enzyme and a methylenedioxyethamphetamine analog,
(i) an antibody for methylenedioxyamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is H,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(iv) an antibody for methylenedioxymethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is methyl,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(v) an antibody for methylenedioxyethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
R2′ is ethyl,
r′ is 1 to 5,
s′ is 1 to 5,
q′ is 1 to 5,
Z′ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and
(b) examining said medium for the presence of a complex comprising said methylenedioxyamphetamine and said antibody for methylenedioxyamphetamine and/or a complex of said methylenedioxymethamphetamine and said antibody for methylenedioxymethamphetamine and/or a complex of said methylenedioxyethamphetamine and said antibody for methylenedioxyethamphetamine, the presence thereof indicating the presence of said methylenedioxyamphetamine and/or methylenedioxymethamphetamine and/or methylenedioxyethamphetamine in said sample.

31 more elements

(a) providing in combination in a medium:
(i) said sample,
(ii) a conjugate of an enzyme and an methylenedioxyamphetamine analog and/or a conjugate of an enzyme and a methylenedioxymethamphetamine analog and/or a conjugate of an enzyme and a methylenedioxyethamphetamine analog,
(i) an antibody for methylenedioxyamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is H,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(iv) an antibody for methylenedioxymethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is methyl,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and/or
(v) an antibody for methylenedioxyethamphetamine, said antibody being raised against a compound of the formula:
wherein:
R1′ is ethyl,
a′ is 1 to 5,
y′ is 1,
Z″ is an immunogenic protein or a non-poly(amino acid) immunogenic carrier,
c′ is 1 to 5,
n″ is an integer between 1 and the molecular weight of said immunogenic protein or said immunogenic carrier divided by about 500;
and
(b) examining said medium for the presence of a complex comprising said methylenedioxyamphetamine and said antibody for methylenedioxyamphetamine and/or a complex of said methylenedioxymethamphetamine and said antibody for methylenedioxymethamphetamine and/or a complex of said methylenedioxyethamphetamine and said antibody for methylenedioxyethamphetamine, the presence thereof indicating the presence of said amphetamine and/or methamphetamine and/or methylenedioxyethamphetamine in said sample.

28 more elements

Dependencies are inferred from the claim text.

Ecstasy haptens and immunogens

Life of this patent

Abstract

Claims68

Ecstasy haptens and immunogens

Life of this patent

Abstract

Claims68