Radiohalogenated small molecules for protein labeling

Details Radiohalogenated small molecules for protein labeling Radiohalogenated small molecules for protein labeling

1987-11-23

1991-09-03

Maples, John S.

Drug, bio-affecting and body treating compositions

Radionuclide or intended radionuclide containing; adjuvant...

548542, 558390, 564183, A61K 4902, A61K 4900

Patent

active

050453033

ABSTRACT:
Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent of preferably prior to the radiohalogenation.
Also compounds of the formula: R.sub.1 -Ar-R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.
The radiohalogenated small molecules are conjugated to proteins such as monoclonal antibodies for use in diagnosis and therapy.

REFERENCES:
patent: 3979506 (1976-09-01), Smith
patent: 4115374 (1978-09-01), Ryan et al.
patent: 4279887 (1981-07-01), Baldwin et al.
patent: 4284619 (1981-08-01), Lin
patent: 4450149 (1984-05-01), Kabalka
patent: 4473544 (1984-09-01), Machulla et al.
Z. V. Svitra et al., "Synthesis and Reactions of p-Trimethylsilylphenylpropionic Acid", Seventh Rocky Mountain Regional ACS Meeting, Albuquerque, N.M., Jun. 6-8, 1984.
D. S. Wilbur et al., "Radiolabeled Phenylalkanoic Acids for Protein Labeling. Investigation of Arylsilanes as Intermediates for Radiolabeled Phenylpropionic Acids and Acid Derivatives", International Chemical Congress of Pacific Basin Societies, Honolulu, Hi., Dec. 16-21, 1984.
Blau et al., "p-Iodobenzoyl Groups as a Paired Label for In Vitro Protein Distribution Studies: Specific Localization of Anti-Tissue Antibodies", International Journal of Applied Radiation and Isotopies 3:217-225, 1958.
Wilbur and Svitra, "Electrophilic Radiobrominations of Hippuric Acid: An Example of the Utility of Aryltrimethylsilane Intermediates", Journal of Labelled Compounds and Radiopharmaceuticals vol. XXI, No. 5, pp. 415-428, 1984.
Riley and Perham, "The Reaction of Protein Amino Groups with Methyl 5-Iodopyridine-2-Carboximidate", Biochem. J. 131:625-635, 1973.
Coleman et al., "Aromatic Radiobromination Without Added Carrier", J. Chem. Soc., Chem. Commun. 1982, pp. 1276-1277.
Visser et al., "The Preparation of Aromatic Astatine Compounds Through Aromatic Mercury-Compounds", Journal of labelled Compounds and Radiopharmaceuticals, vol. XVII, No. 5, pp. 657-665, 1980.
Gilliland et al., "Iodine Labelled Radiopharmaceuticals from Arylthallium Bis(trifluoroacetate) Intermediates", Journal of Radioanalytical Chemistry 65:107-113, 1981.
M. Kosugi et al., "Palladium Catalyzed Reaction of Hexabutylditin with Aryl Bromides: Preparation of Negatively Substituted Aryltributyltin", Chemistry Letters, pp. 829-830, The Chemical Society of Japan, 1981.
Parham and Jones, "Elaboration of Bromoarylinitriles", J. Org. Chem. 41:1187-1191, 1976.
Wursthorn and Kuivila, "Synthesis of Substituted Aryltrimethylstannanes by the Reaction of Trimethylstannylsodium with Aryl Bromides", Journal of Organometallic Chemistry 140:29-39, 1977.

Affiliated with

Also associated with

Rating

Radiohalogenated small molecules for protein labeling does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Radiohalogenated small molecules for protein labeling, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Radiohalogenated small molecules for protein labeling will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1007783