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US 5,175,343 AGranted
Metal radionuclide labeled proteins for diagnosis and therapy
AssigneeNeoRx Corporation
InventorsAlan R. Fritzberg, Sudhakar Kasina, Ananthachari Srinivasan, Daniel S. Wilbur
Life of this patent
Estimating the term…
Abstract
Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.
Claims12
A compound of the formula:
- ##STR32## wherein:
- one of Z.sup.1, Z.sup.2, Z.sup.3, or Z.sup.4 is ##STR33## and the others are H.sub.2 or .dbd.O;
- wherein (CH.sub.2).sub.m and (CH.sub.2).sub.m ' are aliphatic groups and m=(1-6) and m'=(1-3) and m+m'=(1-6).
- W is H.sub.2 or .dbd.NH or .dbd.O, with the proviso that the W bonded to the carbon atom bonded to Y is H.sub.2 when Y is --NH.sub.2 ;
- n is 0 or 1;
- T is a removable sulfur protective group, hydrogen, or an alkali metal ion;
- Y is a leaving group of an active ester that reacts with a polypeptide in an aqueous medium to form an amide or amidine bond, wherein said active ester is a carboxylic ester or an imide ester, --NH.sub.2, --NHNH.sub.2, or a polypeptide of at least two amino acids;
- X is a bond, methylene, or CHZ.sup.4 ;
- and
- the A's are the same or different and are hydrogen or lower alkyl of from 1 to 3 carbon atoms.
7 more elements
A compound of the formula:
- ##STR35## wherein:
- each T, when taken together with the sulfur atom to be protected, defines a hemithioacetal sulfur protective group of the formula:
- ##STR36## wherein R.sup.3 represents a lower alkyl group of from about two to about five carbon atoms, R.sup.4 represents a lower alkyl group of from one to about three carbon atoms, and R.sup.5 represents hydrogen or a lower alkyl group of from one to about three carbon atoms, and Y represents the leaving group of an active ester, wherein said active ester is a carboxylic ester or an imide ester.
A compound of the formula:
- ##STR37## wherein:
- one of Z.sup.1, Z.sup.2, Z.sup.3, or Z.sup.4 is (CH.sub.2).sub.n -CWY, wherein n=1-6, and the others are H.sub.2 or .dbd.O;
- W is H.sub.2 or .dbd.NH or .dbd.O, with the proviso that W is H.sub.2 when Y is --NH.sub.2 ;
- Y is a leaving group of an active ester that reacts with a polypeptide in an aqueous medium to form an amide or amidine bond, wherein said active ester is a carboxylic ester or an imide ester, --NH.sub.2, --NHNH.sub.2, or a polypeptide of at least two amino acids;
- X is a bond, methylene, or CHZ.sup.4 ;
- the A's are the same or different and are hydrogen or lower alkyl 3 carbon atoms;
- and
- each T, when taken together with the sulfur atom to be protected, defines a hemithioacetal sulfur protective group of the formula:
- ##STR38## wherein R.sup.3 represents a lower alkyl group of from about two to about five carbon atoms, and R.sup.4 represents a lower alkyl group of from one to about three carbon atoms, and R5 represents hydrogen or a lower alkyl group of from one to about three carbon atoms.
6 more elements
A compound of the formula:
- ##STR39##
A compound of the formula:
- ##STR40## wherein:
- Y represents a leaving group selected from ##STR41## and each T, when taken together with the sulfur atom to be protected, defines a hemithioacetal sulfur protective group of the formula:
- ##STR42## wherein R.sup.3 represents a lower alkyl group of from about two to about five carbon atoms, R.sup.4 represents a lower alkyl group of from one to about three carbon atoms, and R.sup.5 represents hydrogen or a lower alkyl group of from one to about three carbon atoms.
A compound of the formula:
- ##STR43## wherein:
- one of Z.sup.1, Z.sup.2, Z.sup.3, or Z.sup.4 is --(CH.sub.2).sub.n --CWY, wherein n is 1-3, and the others are H.sub.2 or .dbd.O;
- W is .dbd.NH or .dbd.O;
- Y is the leaving group of an active ester that reacts with a polypeptide in an aqueous medium to form an amide or amidine bond, wherein said active ester is a carboxylic ester or an imide ester;
- X is a bond, methylene, or CHZ.sup.4 ;
- the A's are the same or different and are hydrogen or noncyclic lower alkyl of from 1 to 3 carbon atoms;
- and
- each T, when taken together with the sulfur atom to be protected, defines a hemithioacetal sulfur protective group of the formula:
- ##STR44## wherein R.sup.3 represents a lower alkyl group of from about two to about five carbon atoms, R.sup.4 represents a lower alkyl group of from one to about three carbon atoms, and R.sup.5 represents hydrogen or a lower alkyl group of from one to about three carbon atoms.
6 more elements
Dependencies are inferred from the claim text.