Novel quinuclidine derivatives and medicinal compositions containing the same

Abstract

Carbamates of formula (I) or pharmaceutically acceptable salts thereof, including quaternary ammonium salts of formula (II) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as antagonists of M3 muscarinic receptors.

1 - 35 . (canceled) 
     
     
         36 . A method for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by antagonism of M3 muscarinic receptors, comprising administering to said subject an effective amount of at least one compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; and 
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two, or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″; —CO 2 R′; —C(O)—NR′R″; —N(R′″)C(O)—R′; and —N(R′″)—C(O)NR′R″, wherein R′, R″, and R′″, which may be identical or different, are each independently chosen from a hydrogen atom, and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent; 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azabicyclic ring; and 
 R1 is a phenyl group, which is optionally substituted with one or two, identical or different, substituents chosen from chlorine, fluorine, bromine, methyl, hydroxy and cyano; 
 
 then R2 cannot be one of: unsubstituted cyclopropylmethyl; unsubstituted cyclobutylmethyl; unsubstituted cyclopentylmethyl; cyclohexylmethyl optionally substituted with a methyl or an isopropenyl group; unsubstituted cyclohexenyl; unsubstituted norbornenyl; unsubstituted bicyclo[2,2,1]heptanyl; unsubstituted benzo[1,3]dioxolyl; unsubstituted 2,3-dihydrobenzo[1,4]dioxinyl; unsubstituted benzyl; a benzyl group which is substituted with one or two, identical or different, substituents chosen from fluorine, chlorine, bromine, methoxy, methyl, trifluoromethyl, ethyl, tertbutyl, hydroxy, hydroxymethyl, cyano, aminocarbonyl, trifluoromethoxy, benzyloxy, and isopropyloxy; or a benzyl group which is substituted with three fluorine atoms; 
 or a pharmaceutically acceptable salt thereof or a stereoisomer thereof, 
 with the proviso that the compound of formula (I) is not one of 
 
       Diphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Ethylphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Quinuclidin-3-yl benzo[d][1,3]dioxol-5-ylmethyl(phenyl)carbamate, or 
       Quinuclidin-3-yl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl(m-tolyl)carbamate. 
     
     
         37 . The method according to  claim 36 , wherein the pathological condition is chosen from a respiratory, urological, and gastrointestinal disease or disorder. 
     
     
         38 . A combination product comprising, 
       (i) at least one first compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; and 
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two, or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″; —CO 2 R′; —C(O)—NR′R″; —N(R′″)C(O)—R′; and —N(R′″)—C(O)NR′R″, wherein R′, R″, and R′″, which may be identical or different, are each independently chosen from a hydrogen atom, and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent; 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azabicyclic ring; and 
 R1 is a phenyl group, which is optionally substituted with one or two, identical or different, substituents chosen from chlorine, fluorine, bromine, methyl, hydroxy and cyano; 
 
 then R2 cannot be one of: unsubstituted cyclopropylmethyl; unsubstituted cyclobutylmethyl; unsubstituted cyclopentylmethyl; cyclohexylmethyl optionally substituted with a methyl or an isopropenyl group; unsubstituted cyclohexenyl; unsubstituted norbornenyl; unsubstituted bicyclo[2,2,1]heptanyl; unsubstituted benzo[1,3]dioxolyl; unsubstituted 2,3-dihydrobenzo[1,4]dioxinyl; unsubstituted benzyl; a benzyl group which is substituted with one or two, identical or different, substituents chosen from fluorine, chlorine, bromine, methoxy, methyl, trifluoromethyl, ethyl, tertbutyl, hydroxy, hydroxymethyl, cyano, aminocarbonyl, trifluoromethoxy, benzyloxy, and isopropyloxy; or a benzyl group which is substituted with three fluorine atoms; 
 or a pharmaceutically acceptable salt thereof or a stereoisomer thereof, 
 with the proviso that the compound of formula (I) is not one of 
 
       Diphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Ethylphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Quinuclidin-3-yl benzo[d][1,3]dioxol-5-ylmethyl(phenyl)carbamate, or 
       Quinuclidin-3-yl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl(m-tolyl)carbamate; and 
       (ii) at least one second compound effective in the treatment of at least one pathological condition chosen from respiratory, urological, and gastrointestinal disease or disorder, wherein the at least one first compound and the at least one second compound are administered simultaneously, separately, or sequentially. 
     
     
         39 . A combination product comprising, 
       (i) at least one first compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; and 
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two, or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″; —CO 2 R′; —C(O)—NR′R″; —N(R′″)C(O)—R′; and —N(R′″)—C(O)NR′R″, wherein R′, R″, and R′″, which may be identical or different, are each independently chosen from a hydrogen atom, and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent; 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azabicyclic ring; and 
 R1 is a phenyl group, which is optionally substituted with one or two, identical or different, substituents chosen from chlorine, fluorine, bromine, methyl, hydroxy and cyano; 
 
 then R2 cannot be one of: unsubstituted cyclopropylmethyl; unsubstituted cyclobutylmethyl; unsubstituted cyclopentylmethyl; cyclohexylmethyl optionally substituted with a methyl or an isopropenyl group; unsubstituted cyclohexenyl; unsubstituted norbornenyl; unsubstituted bicyclo[2,2,1]heptanyl; unsubstituted benzo[1,3]dioxolyl; unsubstituted 2,3-dihydrobenzo[1,4]dioxinyl; unsubstituted benzyl; a benzyl group which is substituted with one or two, identical or different, substituents chosen from fluorine, chlorine, bromine, methoxy, methyl, trifluoromethyl, ethyl, tertbutyl, hydroxy, hydroxymethyl, cyano, aminocarbonyl, trifluoromethoxy, benzyloxy, and isopropyloxy; or a benzyl group which is substituted with three fluorine atoms; 
 or a pharmaceutically acceptable salt thereof or a stereoisomer thereof, 
 with the proviso that the compound of formula (I) is not one of 
 
       Diphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Ethylphenylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester, 
       Quinuclidin-3-yl benzo[d][1,3]dioxol-5-ylmethyl(phenyl)carbamate, or 
       Quinuclidin-3-yl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl(m-tolyl)carbamate; and 
       (ii) at least one second compound chosen from a ∃ 2  agonist, steroid, antiallergic drug, phosphodiesterase IV inhibitor, and a leukotriene D4 (LTD4) antagonist, wherein the at least one first compound and the at least one second compound are administered simultaneously, separately, or sequentially in the treatment of a respiratory disease. 
     
     
         40 . A method for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by antagonism of M3 muscarinic receptors, comprising administering to said subject an effective amount of at least one compound of formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″, —CO 2 R′, —C(O)—NR′R″, —N(R′″)C(O)—R′, and —N(R′″)—C(O)NR′R″ groups, wherein R′, R″ and R′″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent;
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 m is an integer ranging from 0 to 8; 
 n is an integer ranging from 0 to 4; 
 A represents a group chosen from —CH 2 —; —CH═CR′—; —CR′═CH—; —CR′R″—; —C(O)—, —O—, —S—, —S(O)—, —S(O) 2 — and —NR′—, wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 B represents a hydrogen atom, or a group chosen from straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; cyano; nitro; —CH═CR′R″; —C(O)OR′; —OC(O)R′; —SC(O)R′; —C(O)NR′R″; —NR′C(O)OR″; —NR′C(O)NR″; cycloalkyl; phenyl; naphthanelyl; 5,6,7,8-tetrahydronaphthanelyl; benzo[1,3]dioxolyl; heteroaryl; and heterocyclyl; wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and 
 
 wherein the cyclic groups represented by B are optionally substituted by one, two, or three, identical or different, substituents chosen from halogen; hydroxy; straight or branched, optionally substituted lower alkyl; phenyl; —OR′; —SR′; —NR′R″; —NHCOR′; —CONR′R″; —CN; —NO 2 ; and —COOR′; wherein R′ and R″ are each independently chosen from a hydrogen atom, or a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and
 X −  represents a pharmaceutically acceptable anion of a mono or polyvalent acid; 
 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azoniabicyclic ring having (3R)-configuration; 
 R1 is a phenyl group which is optionally substituted with a fluorine atom or a methyl group; 
 R2 is an unsubstituted cyclohexylmethyl group or a benzyl group which is optionally substituted with one or three fluorine atoms; and 
 X −  is iodine; 
 
 then, the sequence B—(CH 2 ) n -A-(CH 2 ) m — cannot be a methyl group; 
 
       or a stereoisomer thereof; or a mixture of stereoisomers thereof, or a mixture of at least one stereoisomer of a compound of formula (II) and at least one stereoisomer of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
     
     
         41 . The method according to  claim 40 , wherein the pathological condition is chosen from respiratory, urological, and gastrointestinal disease or disorder. 
     
     
         42 . A combination product comprising, 
       (i) at least one first compound of formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″, —CO 2 R′, —C(O)—NR′R″, —N(R′″)C(O)—R′, and —N(R′″)—C(O)NR′R″ groups, wherein R′, R″ and R′″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent;
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 m is an integer ranging from 0 to 8; 
 n is an integer ranging from 0 to 4; 
 A represents a group chosen from —CH 2 —; —CH═CR′—; —CR′═CH—; —CR′R″—; .—C(O)—, —O—, —S—, —S(O)—, —S(O) 2 — and —NR′—, wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 B represents a hydrogen atom, or a group chosen from straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; cyano; nitro; —CH═CR′R″; —C(O)OR′; —OC(O)R′; —SC(O)R′; —C(O)NR′R″; —NR′C(O)OR″; —NR′C(O)NR″; cycloalkyl; phenyl; naphthanelyl; 5,6,7,8-tetrahydronaphthanelyl; benzo[1,3]dioxolyl; heteroaryl; and heterocyclyl; wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and 
 
 wherein the cyclic groups represented by B are optionally substituted by one, two, or three, identical or different, substituents chosen from halogen; hydroxy; straight or branched, optionally substituted lower alkyl; phenyl; —OR′; —SR′; —NR′R″; —NHCOR′; —CONR′R″; —CN; —NO 2 ; and —COOR′; wherein R′ and R″ are each independently chosen from a hydrogen atom, or a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and
 X −  represents a pharmaceutically acceptable anion of a mono or polyvalent acid; 
 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azoniabicyclic ring having (3R)-configuration; 
 R1 is a phenyl group which is optionally substituted with a fluorine atom or a methyl group; 
 R2 is an unsubstituted cyclohexylmethyl group or a benzyl group which is optionally substituted with one or three fluorine atoms; and 
 X −  is iodine; 
 
 
       then, the sequence B—(CH 2 ) n -A-(CH 2 ) m — cannot be a methyl group; and 
       (ii) at least one second compound effective in the treatment of at least one pathological condition chosen from respiratory, urological, and gastrointestinal disease or disorder, wherein the at least one first compound and the at least one second compound are administered simultaneously, separately, or sequentially. 
     
     
         43 . A combination product comprising, 
       (i) at least one first compound of formula (II): 
       
         
           
           
               
               
           
         
       
       wherein:
 R1 represents a group chosen from phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, and thiophen-3-ylmethyl; 
 R2 represents a group chosen from optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, saturated or unsaturated cycloalkyl, saturated or unsaturated cycloalkylmethyl, phenyl, benzyl, phenethyl, furan-2-ylmethyl, furan-3-ylmethyl, thiophen-2-ylmethyl, thiophen-3-ylmethyl, pyridyl, and pyridylmethyl; wherein the carbocyclic moieties in the cycloalkyl, cycloalkylmethyl, phenyl, benzyl or phenethyl groups are optionally bridged or fused to another saturated, unsaturated or aromatic carbocyclic moiety or to a cyclic moiety comprising carbon atoms and 1 or 2 oxygen atoms; 
 wherein the cyclic groups present in R1 and R2 are optionally substituted by one, two or three, which may be identical or different, substituents chosen from halogen; straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; —SH; straight or branched optionally substituted lower alkylthio; nitro; cyano; —NR′R″, —CO 2 R′, —C(O)—NR′R″, —N(R′″)C(O)—R′, and —N(R′″)—C(O)NR′R″ groups, wherein R′, R″ and R′″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 wherein when the cyclic group present in R1 is unsubstituted or has only one substituent, R2 has at least one substituent;
 p is 1 or 2 and the carbamate group is attached at positions 2, 3, or 4 of the azabicyclic ring; 
 m is an integer ranging from 0 to 8; 
 n is an integer ranging from 0 to 4; 
 A represents a group chosen from —CH 2 —; —CH═CR′—; —CR′═CH—; —CR′R″; —C(O)—, —O—, —S—, —S(O)—, —S(O) 2 — and —NR′—, wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; 
 B represents a hydrogen atom, or a group chosen from straight or branched, optionally substituted lower alkyl; hydroxy; straight or branched, optionally substituted lower alkoxy; cyano; nitro; —CH═CR′R″; —C(O)OR′; —OC(O)R′; —SC(O)R′; —C(O)NR′R″; —NR′C(O)OR″; —NR′C(O)NR″; cycloalkyl; phenyl; naphthanelyl; 5,6,7,8-tetrahydronaphthanelyl; benzo[1,3]dioxolyl; heteroaryl; and heterocyclyl; wherein R′ and R″, which may be identical or different, are each independently chosen from a hydrogen atom and a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and 
 
 wherein the cyclic groups represented by B are optionally substituted by one, two, or three, identical or different, substituents chosen from halogen; hydroxy; straight or branched, optionally substituted lower alkyl; phenyl; —OR′; —SR′; —NR′R″; —NHCOR′; —CONR′R″; —CN; —NO 2 ; and —COOR′; wherein R′ and R″ are each independently chosen from a hydrogen atom, or a straight or branched, optionally substituted lower alkyl group, or R′ and R″ together with the atom to which they are attached form a cyclic group; and
 X −  represents a pharmaceutically acceptable anion of a mono or polyvalent acid; 
 
 wherein when:
 p is 2; 
 the carbamate group is attached at position 3 of the azoniabicyclic ring having (3R)-configuration; 
 R1 is a phenyl group which is optionally substituted with a fluorine atom or a methyl group; 
 R2 is an unsubstituted cyclohexylmethyl group or a benzyl group which is optionally substituted with one or three fluorine atoms; and 
 X −  is iodine; 
 
 
       then, the sequence B—(CH 2 ) n -A-(CH 2 ) m — cannot be a methyl group; and 
       (ii) at least one second compound chosen from a ∃ 2  agonist, steroid, antiallergic drug, phosphodiesterase IV inhibitor, and a leukotriene D4 (LTD4) antagonist, wherein the at least one first compound and the at least one second compound are administered simultaneously, separately, or sequentially in the treatment of a respiratory disease.