Muscarinic receptor agonists

• US 6,602,891 B2
• Filed: 12/20/2001
• Issued: 08/05/2003
• Est. Priority Date: 01/22/1999
• Status: Expired due to Fees

• Current Assignee: University of Toledo
• Original Assignee: University of Toledo
• Inventors: Cao, Yang, Messer, William S.
• Primary Examiner(s): FAN, JANE T
• Application Number:
  US10/034,229
• Publication Number:
  US 20030032658A1
• Time in Patent Office: 593 Days
• Field of Search: 546/268.1, 514/342
• US Class Current: 514/342
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

A compound of Formula (III):

wherein X is a linkage independently selected from (CH₂)₁₂ or (CH₂CH₂)₄O₃ and wherein R₃ is independently selected from H, CH₂CH₃, COCH₃ or

and acid addition salts, solvates and hydrates thereof. The compounds have unusually high affinity for muscarinic receptors, and exhibit agonist activity useful in the treatment of neurological and other disorders, in which stimulating cholinergic activity is desirable.

Claims

1. A method of treating a condition selected from pain and Alzheimer'"'"'s disease comprising administering to a patient in need of such treatment a muscarinic agonistic effective amount of a compound of formula (III):

wherein X is a linkage independently selected from (CH₂)₁₂ or (CH₂CH₂)₄O₃; and

wherein R₃ is independently selected from H, CH₂CH₃, COCH₃ or

2. The method of claim 1, wherein the compound is 12-[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yloxy]-1-dodecanol hydrochloride.

3. The method of claim 1, wherein the compound is 12-[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yloxy]-1-dodecyl acetate hydrochloride.

4. The method of claim 1, wherein the compound is tetra(ethylene glycol)mono[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether hydrochloride.

5. The method of claim 1, wherein the compound is tetra(ethylene glycol)ethyl[3-1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether hydrochloride.

6. The method of claim 1, wherein the compound is tetra(ethylene glycol)[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether acetate hydrochloride.

7. The method of claim 1, wherein the compound is tetra(ethylene glycol)(4-methoxy-1,2,5-thiadiazol-3-yl)[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl]ether hydrochloride.