Claims for Patent: 5,330,737

Summary for Patent: 5,330,737

Title:	Nitrogen-sulfur ligands as opiate receptor drug mimics
Abstract:	The present invention relates particularly to novel aminothiol ligands that are suitable for complexing with a radionuclide, such as Tc, Re, or Ga, and are useful as general imaging agents for diagnostic purposes. The ligands have the general formulae (I) and (II): ##STR1## wherein for formula I, R.sup.1 -R.sup.4, R.sup.6, R.sup.7 and R.sup.9 -R.sup.14 can each be one of H, alkyl, aryl, hydroxyalkyl, alkoxycarbonyl, etc.; R.sup.5 and R.sup.8 are suitable sulfur protecting groups; m and n are 1-3; B can be one of C(O)CHR.sup.6 CHR.sup.7 SR.sup.8, CHR.sup.9 CHR.sup.10 C(O)NHR.sup.11, or C(O)CHR.sup.12 CHR.sup.13 NHR.sup.14 ; and wherein for formula II, R.sup.15 -R.sup.18, R.sup.20 and R.sup.21 are defined in the same manner as R.sup.1 above; D and E are either C(O) or CHR.sup.17 ; F is either (CH.sub.2).sub.d NR.sup.18 (CH.sub.2).sub.e SR.sup.19 or CHNR.sup.20 R.sup.21 (CH.sub.2).sub.f SR.sup.22 ; R.sup.19 and R.sup.22 are defined in the same manner as R.sup.5 above; d, e and f are 1-3.
Inventor(s):	Rajagopalan; Raghavan (St. Louis County, MO)
Assignee:	Mallinckrodt Medical, Inc. (St. Louis, MO)
Application Number:	07/804,852
Patent Claims:	1. A ligand useful in forming radionuclide complexes, said ligand having the general formula: ##STR38## wherein R.sup.1 is selected from the group consisting of hydrogen, hydroxyl, and lower alkoxyl; A is ##STR39## wherein R.sup.2, and R.sup.3 are defined in the same manner as R.sup.1 above, and wherein X is ##STR40## wherein n and m are 1 to 3, R.sup.4 is selected from the group consisting of hydrogen, lower alkyl, benzyl, and cyclobutylmethyl, and R.sup.5 is a suitable protecting group selected from the group consisting of acetyl, benzoyl, alkoxycarbonyl, carbamoyl, methoxymethyl, and tetrahydropyranyl; and B is selected from the group consisting of ##STR41## wherein R.sup.6, R.sup.7 and R.sup.9 to R.sup.14 are defined in the same manner as R.sup.1 above, and R.sup.8 is a suitable protecting group defined in the same manner as R.sup.5 above. 2. A ligand according to claim 1, wherein R.sup.1 is hydrogen or hydroxyl; A is ##STR42## wherein R.sup.2 and R.sup.3 are each hydrogen, and X is ##STR43## wherein R.sup.4 is methyl, R.sup.5 is benzoyl, n=1, and m=2; and B is ##STR44## wherein R.sup.6 and R.sup.7 are each hydrogen, and R.sup.8 is benzoyl. 3. A radionuclide complex having the general formula: ##STR45## wherein M is a radionuclide; and wherein R.sup.1 is hydrogen, hydroxyl, or methoxyl; and R.sup.4 is hydrogen, methyl, benzyl, or cyclobutylmethyl. 4. A complex according to claim 3, wherein M is technetium, rhenium, or gallium. 5. A complex according to claim 3, wherein R.sup.1 is hydrogen or hydroxyl; and R.sup.4 is methyl, benzyl, or cyclobutylmethyl. 6. A complex according to claim 5, wherein R.sup.4 is methyl. 7. A radionuclide complex having the general formula: ##STR46## wherein M is a radionuclide; and wherein R.sup.1 is hydrogen, hydroxyl, or methoxyl, and R.sup.4 and R.sup.11 may be the same or different and are selected from the group consisting of hydrogen, methyl, benzyl, and cyclobutylmethyl. 8. A complex according to claim 7, wherein M is technetium, rhenium, or gallium. 9. A complex according to claim 7, wherein R.sup.4 and R.sup.11 are each methyl. 10. A radiographic imaging agent comprising a complex having the general formula: ##STR47## wherein M is a radionuclide; and wherein R.sup.1 is hydrogen, hydroxyl, or methoxyl; and R.sup.4 is hydrogen, methyl, benzyl, or cyclobutylmethyl; and a pharmaceutically acceptable radiological vehicle. 11. An imaging agent according to claim 10, wherein M is technetium, rhenium, or gallium. 12. An imaging agent according to claim 10, wherein said vehicle is suitable for injection or aspiration and is selected from the group consisting of human serum albumin, aqueous buffer solutions, sterile water, physiological saline, and balanced ionic solutions containing chloride salts, bicarbonate salts, or blood plasma cations. 13. An imaging agent according to claim 10, wherein the concentration of said complex in said vehicle is from about 1.0 to 50 millicuries. 14. A radiographic imaging agent comprising a complex having the general formula: ##STR48## wherein M is a radionuclide; and wherein R.sup.1 is hydrogen, hydroxyl, or methoxyl, and R.sup.4 and R.sup.11 may be the same or different and are selected from the group consisting of hydrogen, methyl, benzyl, and cyclobutylmethyl; and a pharmaceutically acceptable radiological vehicle. 15. An imaging agent according to claim 14, wherein M is technetium, rhenium, or gallium. 16. An imaging agent according to claim 14, wherein said vehicle is suitable for injection or aspiration and is selected from the group consisting of human serum albumin, aqueous buffer solutions, sterile water, physiological saline, and balanced ionic solutions containing chloride salts, bicarbonate salts, or blood plasma cations. 17. An imaging agent according to claim 14, wherein the concentration of said complex in said vehicle is from about 1.0 to 50 millicuries.

Details for Patent 5,330,737

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2039-09-23