US2007060563A1PendingUtilityA1
Quinuclidine derivatives binding to mucarinic m3 receptors
Est. expiryMay 2, 2023(expired)· nominal 20-yr term from priority
A61P 37/08A61P 43/00A61P 29/00A61P 11/00A61P 17/06A61P 11/02A61P 11/08A61P 11/06C07D 453/02
45
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Compounds of formula I in salt or zwitterionic form wherein, wherein R 1 , R 2 , R 3 , and R 4 have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.
Claims
exact text as granted — not AI-modified1 . A compound of formula I
in salt or zwitterionic form wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or —CR 1 R 2 R 3 together form a group of formula
where R is a bond, —O—, —S—, —CH 2 —, —CH═CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—;
R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy;
R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —OR 11 , —O—CO—NHR 12 , —O—CO—R 13 or —CO—O—R 14 ,
or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 5 is hydrogen or C 1 -C 8 -alkyl;
R 6 is C 1 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 7 is a C 3 -C 15 -carbocyclic group;
R 8 is a C 3 -C 15 -carbocyclic group;
R 9 is hydrogen or C 1 -C 8 -alkyl;
R 10 is hydrogen, C 1 -C 8 -alkyl optionally substituted by cyano, amino, nitro, carboxy, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group, or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 11 is hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkyl-C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl-O—R 15 ;
R 12 is a C 3 -C 15 -carbocyclic group;
R 13 is C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group;
R 14 is hydrogen, a C 3 -C 15 -carbocyclic group, C 1 -C 8 -alkenyl, or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group; and
R 15 is a C 3 -C 15 -carbocyclic group.
2 . A compound according to claim 1 , wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 2 , —O—CO—R 13 or —CO—O—R 4 , or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen or C 1 -C 8 -alkyl; R 6 is C 1 -C 8 -alkyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 15 -carbocyclic group; R 8 is a C 3 -C 15 -carbocyclic group; R 9 is hydrogen or C 1 -C 8 -alkyl; R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 15 -carbocyclic group; R 13 is C 1 -C 8 -alkyl; and R 14 is hydrogen, a C 3 -C 15 -carbocyclic group, C 1 -C 8 -alkenyl, or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group.
3 . A compound according to claim 2 , wherein
R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 2 , —O—CO—R 13 or —CO—O—R 4 , or R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen or C 1 -C 4 -alkyl; R 6 is C 1 -C 4 -alkyl, C 2 -C 8 -alkynyl or C 1 -C 4 -alkoxy in each case optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 6 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 10 -carbocyclic group; R 8 is a C 3 -C 10 -carbocyclic group; R 9 is hydrogen or C 1 -C 4 -alkyl; R 10 is C 1 -C 4 -alkyl optionally substituted by cyano, C 1 -C 4 -alkoxy, a C 3 -C 10 -carbocyclic group or by a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 10 -carbocyclic group; R 13 is C 1 -C 4 -alkyl; and R 14 is hydrogen, a C 3 -C 10 -carbocyclic group, C 1 -C 4 -alkenyl, or C 1 -C 4 -alkyl optionally substituted by a C 3 -C 10 -carbocyclic group.
4 . A compound of formula I
in salt or zwitterionic form wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or —CR 1 R 2 R 3 together form a group of formula
where R is a bond, —O—, —S—, —CH 2 —, —CH═CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—;
R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy;
R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —OR 11 , —O—CO—NHR 12 , —O—CO—R 13 or —CO—O—R 4 ,
or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 5 is hydrogen or C 1 -C 8 -alkyl;
R 6 is C 1 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 7 is a C 3 -C 15 -carbocyclic group;
R 8 is a C 3 -C 15 -carbocyclic group;
R 9 is hydrogen or C 1 -C 8 -alkyl;
R 10 is hydrogen, C 1 -C 8 -alkyl optionally substituted by cyano, amino, nitro, carboxy, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group, or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 11 is hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkyl-C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl-O—R 15 ;
R 12 is a C 3 -C 15 -carbocyclic group;
R 13 is C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group;
R 14 is hydrogen, a C 3 -C 15 -carbocyclic group, or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group; and
R 15 is a C 3 -C 15 -carbocyclic group.
5 . A compound according to claim 4 , wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 2 , —O—CO—R 13 or —CO—O—R 4 , or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen or C 1 -C 8 -alkyl; R 6 is C 1 -C 8 -alkyl, C 2 -C 10 -alkynyl or C 1 -C 8 -alkoxy in each case optionally substituted by a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 6 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 15 -carbocyclic group; R 8 is a C 3 -C 15 -carbocyclic group; R 9 is hydrogen or C 1 -C 8 -alkyl; R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 15 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 15 -carbocyclic group; R 13 is C 1 -C 8 -alkyl; and R 14 is hydrogen, a C 3 -C 15 -carbocyclic group or C 1 -C 8 -alkyl optionally substituted by a C 3 -C 15 -carbocyclic group.
6 . A compound according to claim 5 , wherein
R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—N H—R 12 , —O—CO—R 13 or —CO—O—R 14 , or R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen or C 1 -C 4 -alkyl; R 6 is C 1 -C 4 -alkyl, C 2 -C 8 -alkynyl or C 1 -C 4 -alkoxy in each case optionally substituted by a C 3 -C 10 -carbocyclic group or a 4- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 6 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 10 -carbocyclic group; R 8 is a C 3 -C 10 -carbocyclic group; R 9 is hydrogen or C 1 -C 4 -alkyl; R 10 is C 1 -C 4 -alkyl optionally substituted by cyano, C 1 -C 4 -alkoxy, a C 3 -C 10 -carbocyclic group or by a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 10 -carbocyclic group or a 4- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 10 -carbocyclic group; R 13 is C 1 -C 4 -alkyl; and R 14 is hydrogen, a C 3 -C 10 -carbocyclic group or C 1 -C 4 -alkyl optionally substituted by a C 3 -C 10 -carbocyclic group.
7 . A compound of formula I
in salt or zwitterionic form wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or —CR 1 R 2 R 3 together form a group of formula
where R is a bond, —O—, —S—, —CH 2 —, —CH═CH—, —CH 2 —CH 2 —, amino or —N(CH 3 )—;
R 2 is hydrogen, halo, hydroxy, C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl optionally substituted by hydroxy;
R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —OR 11 , —O—CO—NHR 2 , —O—CO—R 13 or —CO—O—R 14 ,
or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 5 is hydrogen or C 1 -C 8 -alkyl;
R 6 is C 1 -C 8 -alkyl or C 1 -C 8 -alkoxy in either case optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 6 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 7 is a C 3 -C 15 -carbocyclic group;
R 8 is a C 3 -C 15 -carbocyclic group;
R 9 is hydrogen or C 1 -C 8 -alkyl;
R 10 is hydrogen, C 1 -C 8 -alkyl optionally substituted by cyano, amino, nitro, carboxy, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group, or by a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur,
or R 10 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur;
R 11 is hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkyl-C 1 -C 8 -alkoxy or C 1 -C 8 -alkyl-O—R 15 ;
R 12 is a C 3 -C 15 -carbocyclic group;
R 13 is C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group;
R 14 is hydrogen, C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group; and
R 15 is a C 3 -C 15 -carbocyclic group.
8 . A compound according to claim 7 , wherein
R 1 and R 3 are each independently a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 2 , —O—CO—R 13 or —CO—O—R 14 , or R 4 is C 3 -C 10 -alkynyl optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen; R 6 is C 1 -C 8 -alkyl or C 1 -C 8 -alkoxy in either case optionally substituted by a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 6 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 15 -carbocyclic group; R 8 is a C 3 -C 15 -carbocyclic group; R 9 is hydrogen or C 1 -C 8 -alkyl; R 10 is C 1 -C 8 -alkyl optionally substituted by cyano, C 1 -C 8 -alkoxy, a C 3 -C 15 -carbocyclic group or by a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 15 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 15 -carbocyclic group; R 13 is C 1 -C 8 -alkyl; and R 14 is hydrogen, C 1 -C 8 -alkyl or a C 3 -C 15 -carbocyclic group.
9 . A compound according to claim 8 , wherein
R 1 and R 3 are each independently a C 6 -C 10 -carbocyclic aromatic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 2 is halo or hydroxy; R 4 is C 1 -C 8 -alkyl substituted by —NHR 5 , —NR 5 —CO—R 6 , —NR 5 —CO—NH—R 7 , —NR 5 —SO 2 —R 8 , —CO—NR 9 R 10 , —O—CO—NH—R 2 , —O—CO—R 13 or —CO—O—R 4 , or R 4 is C 3 -C 8 -alkynyl optionally substituted by a C 3 -C 10 -carbocyclic group or a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 5 is hydrogen; R 6 is C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy in either case optionally substituted by a C 3 -C 10 -carbocyclic group or a 5- to 12-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 5 is a C 3 -C 10 -carbocyclic group or a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 7 is a C 3 -C 10 -carbocyclic group; R 8 is a C 3 -C 10 -carbocyclic group; R 9 is hydrogen or C 1 -C 4 -alkyl; R 10 is C 1 -C 4 -alkyl optionally substituted by cyano, C 1 -C 4 -alkoxy, a C 3 -C 10 -carbocyclic group or by a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R 10 is a C 3 -C 10 -carbocyclic group or a 5- to 10-membered heterocyclic group having at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R 12 is a C 3 -C 10 -carbocyclic group; R 13 is C 1 -C 4 -alkyl; and R 14 is hydrogen, C 1 -C 4 -alkyl or a C 3 -C 10 -carbocyclic group.
10 . A compound according to claim 1 , which is also a compound of formula XIV
where R 1 , R 2 , R 3 , and R 4 are as shown in the following table:
R 1 and R 3
R 4
R 2
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
F
F
F
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
11 . A compound according to claim 1 , which is also a compound of formula XIV
where R 1 , R 2 , R 3 , and R 4 are as shown in the following table:
R 1 and R 3
R 4
R 2
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
12 . A compound according to claim 1 , which is also a compound of formula XIV
where R 1 , R 2 , R 3 , and R 4 are as shown in the following table:
R 1 and R 3
R 4
R 2
OH
OH
13 . A compound according to claim 1 in combination with another drug substance which is an anti-inflammatory, a bronchodilator, an antihistamine, a decongestant or an anti-tussive drug substance.
14 . (canceled)
15 . A pharmaceutical composition comprising as active ingredient a compound according to claim 1 in combination with another drug substance which is an anti-inflammatory, a bronchodilator, an antihistamine, a decongestant or an anti-tussive drug substance, optionally together with a pharmaceutically acceptable diluent or carrier.
16 - 17 . (canceled)
18 . A process for the preparation of a compound of formula I as claimed in claim 1 which comprises
(i) (A) reacting a compound of compound of formula II or a protected form thereof where R 1 , R 2 and R 3 are as defined in claim 1 , with a compound of formula III R 4 —X III where R 4 is as hereinbefore defined and X is chloro, bromo or iodo; (B) for the preparation of compounds of formula I where R 4 is C 1 -C 8 -alkyl substituted by —NR 5 —CO—R 6 where R 5 and R 6 are as defined in claim 1 , reacting a compound of formula IV or a protected form thereof where R 1 , R 2 , R 3 and R 5 are as defined in claim 1 , optionally in the presence of a coupling agent, and T denotes C 1 -C 8 -alkylene, with a compound of formula V where R 6 is as defined in claim 1 or an amide-forming derivative thereof such as an acid halide; (C) for the preparation of compounds of formula I where R 4 is C 1 -C 8 -alkyl substituted by —NR 5 —CO—NH—R 7 where R 5 and R 7 are as defined in claim 1 , reacting a compound of formula IV or a protected form thereof where R 1 , R 2 , R 3 and R 5 are as defined in claim 1 and T denotes C 1 -C 8 -alkylene, with a compound of formula VI O═C═N—R 7 VI where R 7 is as defined in claim 1; (D) for the preparation of compounds of formula I where R 4 is C 1 -C 8 -alkyl substituted by —NR 5 —SO 2 —R 8 where R 5 and R 8 are as defined in claim 1 , reacting a compound of formula IV or a protected form thereof where R 1 , R 2 , and R 3 are as defined in claim 1 and T denotes C 1 -C 8 -alkylene, with a compound of formula VII where R 8 is as defined in claim 1 and X is halo; or (E) for the preparation of compounds of formula I where R 4 is C 1 -C 8 -alkyl substituted by —CO—NR 9 R 10 where R 9 and R 10 are as defined in claim 1 , reacting a compound of formula VIII or a protected form thereof where R 1 , R 2 , and R 3 are as defined in claim 1 and T denotes C 1 -C 8 -alkylene, optionally in the presence of a coupling agent, or an amide-forming derivative thereof such as an acid halide, with a compound of formula IX where R 9 and R 10 are as defined in claim 1; and (ii) recovering the product in salt or zwitterionic form.
19 . A pharmaceutical composition comprising as active ingredient a compound according to claim 1 .
20 . A method of treating a condition mediated by the muscarinic M3 receptor in a subject in need of such treatment, which comprises administering to said subject an effective amount of a compound of formula I as defined in claim 1 in free form or in the form of a pharmaceutically acceptable salt.
21 . A method of treating an inflammatory or obstructive airways disease in a subject in need of such treatment, which comprises administering to said subject an effective amount of a compound of formula I as defined in claim 1 in free form or in the form of a pharmaceutically acceptable salt.Join the waitlist — get patent alerts
Track US2007060563A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.