US 7,141,671 B2Granted

Biphenyl derivatives

AssigneeTheravance, Inc.

InventorsMathai Mammen, Sarah Dunham, Adam Hughes, Tae Weon Lee, Craig Husfeld, Eric Stangeland, Yan Chen

Life of this patent

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Abstract

This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Claims42

Dependent claims

A compound of formula I:

wherein:
a is 0 or an integer of from 1 to 3;
each R1 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR1a, —C(O)OR1b, —SR1c, —S(O)R1d, —S(O)2R1e and —NR1fR1g;
each of R1a, R1b, R1c, R1d, R1e, R1f and R1g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
b is 0 or an integer of from 1 to 3;
each R2 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR2a, —C(O)OR2b, —SR2c, —S(O)R2d, —S(O)2R2e and —NR2fR2g;
each of R2a, R2b, R2c, R2d, R2e, R2f and R2g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
W is attached to the 3- or 4-position with respect to the nitrogen atom in the piperidine ring and represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
c is 0 or an integer of from 1 to 4;
each R3 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR3a, —C(O)OR3b, —SR3c, —S(O)R3d, —S(O)2R3e and —NR3fR3g;
or two R3 groups are joined to form (1–3C)alkylene, (2–3C)alkenylene or oxiran-2,3-diyl;
each of R3a, R3b, R3c, R3d, R3e, R3f and R3g is independently hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)c-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4C)alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 16 contiguous atoms;
R5 hydrogen or (1–4C)alkyl;
R6 is —NR6aCR6b(O) or —CR6cR6dOR6e and R7 is hydrogen;
or R6 and R7 together form —NR7aC(O)—CR7b═CR7c—, —CR7d═CR7e—C(O)—NR7f—, —NR7gC(O)—CR7hR7i—CR7jR7k— or —CR7lR7m—CR7nR7o—C(O)—NR7p—;
each of R6a, R6b, R6c, R6d and R6e is independently hydrogen or (1–4C)alkyl;
and
each of R7a, R7b, R7c, R7d, R7e, R7f, R7g, R7h, R7i, R7j, R7k, R7l, R7m, R7n, R7o and R7p is independently hydrogen or (1–4C)alkyl;
or a pharmaceutically acceptable salt or solvate or stercoisomer thereof.

27 more elements

A compound of formula II:

wherein
W represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)e-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy;
or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and:
each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 14 contiguous atoms;
or a pharmaceutically acceptable salt or solvate or stereoisomer thereof.

13 more elements

A compound of formula III:

wherein
W represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)e-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4C)alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy;
or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 14 contiguous atoms;
or a pharmaceutically acceptable salt or solvate or stereoisomer thereof.

12 more elements

A compound of formula IV:

wherein
W represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)e-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4C)alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy;
or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 14 contiguous atoms;
or a pharmaceutically acceptable salt or solvate or stereoisomer thereof.

12 more elements

A compound of formula I:

wherein:
a is 0 or an integer of from 1 to 3;
each R1 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR1a, —C(O)OR1b, SR1c, —S(O)R1d, —S(O)2R1e, and —NR1fR1g;
each of R1a, R1b, R1c, R1d, R1e, R1f and R1g is independently hydrogen or (1–4C)alkyl;
b is 0 or an integer of from 1 to 3;
each R2 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR2a, —C(O)OR2b, SR2c, —S(O)R2d, —S(O)2R2e, and —NR2fR2g;
each of R2a, R2b, R2c, R2d, R2e, R2f and R2g is independently hydrogen or (1–4C)alkyl;
W is attached to the 3- or 4-position with respect to the nitrogen atom in the piperidine ring, and represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
c is 0 or an integer of from 1 to 4;
each R3 is a substituent on carbon independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR3a, —C(O)OR3b, SR3c, —S(O)R3d, —S(O)2R3e, and NR3fR3g;
each of R3a, R3b, R3c, R3d, R3e, R3f and R3g is independently hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)c-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl(1–4C)-alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, (2–9C)heteroarylene and (3–6C)heterocyclene;
wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, and —N(Qj)C(O)O—;
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi and Qj are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4;
wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy;
or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl;
wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 8 to 14 contiguous atoms;
R5 represents hydrogen or (1–4C)alkyl;
R6 is —NR6aCR6b(O) and R7 is hydrogen, or R6 and R7 together form —NR7aC(O)—CR7b═CR7c—, —CR7d═CR7e—C(O)—NR7f—, —NR7gC(O)—CR7hR7i—CR7jR7k— or —CR7lR7m—CR7nR7o—C(O)—NR7p—;
each of R6a and R6b is independently hydrogen or (1–4C)alkyl;
and
each of R7a, R7b, R7c, R7d, R7e, R7f, R7g, R7h, R7i, R7j, R7k, R7l, R7m, R7n, R7o and R7p is independently hydrogen or (1–4C)alkyl;
or a pharmaceutically acceptable salt or solvate or stereoisomer thereof.

29 more elements

A compound selected from:

1-biphenyl-2-yl-3-(1-{9-[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}piperidin-4-yl)urea;
biphenyl-2-ylcarbamic acid 1-{9-[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-(3-formylamino-4-hydroxy-phenyl)-2-hydroxyethylamino]nonyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2,3,4-tetrahydroqunolin-5-yl)ethylamino]nonyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentylcarbamoyl}ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexanoyl}methylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentyl}-ureido)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(3-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentyl}-ureido)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]nonyl}piperidin-4-yl ester;
1-biphenyl-2-yl-3-(1-{9-[2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylamino]nonyl}piperidin-4-yl)urea;
biphenyl-2-ylcarbamic acid 1-{2-[(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}cyclohexylmethyl)carbamoyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({(1R,3S)-3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)ethylamino]cyclopentanecarbonyl}amino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentylsulfamoyl}-ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzenesulfonyl)methylamino]ethyl}-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzyl)ureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{3-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)phenyl]propyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-fluoro-3-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}piperidin-1-ylmethyl)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenoxy)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{[(R)-2-hydroxy-2-(8-hydxoxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}piperidin-1-yl)-propyl]piperidin-4-yl ester;
biphenyl2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{7-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]heptyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{8-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]octyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)ureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}piperidin-1-yl)-3-oxopropyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-cyclohexanecarbonyl)amino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({(1R,3S)-3-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]-cyclopentanecarbonyl}amino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{5-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]pentyl}ureido)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(3-{5-[2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]pentyl}ureido)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}piperidine-1-carbonyl)amino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}-phenylamino)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzylcarbamoyl)ethyl]piperidin-4-yl ester;
3-[4-(3-biphenyl-2-yl-ureido)piperidin-1-yl]-N-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenyl)propionamide;
biphenyl-2-ylcarbamic acid 1-{2-[(6-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}pyridin-2-ylmethyl)carbamoyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-cyclohexylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-cyclohexylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({(1R,3S)-3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]cyclopentanecarbonyl}amino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoyl)methylamino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-cyclohexanecarbonyl)methylamino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{(S)-1-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{(R)-1-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-((S)-1-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentanoyl}pyrrolidin-2-ylmethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[(S)-1-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoyl)pyrrolidin-2-ylmethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxy-phenyl)-2-hydroxy-ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{(R)-1-[(R)-2-(3-formylamino-4-hydroxy-phenyl)-2-hydroxy-ethylamino]ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-chloro-3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
N-{2-[4-(3-biphenyl-2-yl-ureido)-piperidin-1-yl]ethyl}-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzamide;
1-biphenyl-2-yl-3-{1-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}piperidin-1-yl)-3-oxo-propyl]piperidin-4-yl}urea;
3-[4-(3-biphenyl-2-yl-ureido)piperidin-1-yl]-N-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzyl)propionamide;
biphenyl-2-ylcarbamic acid 1-(2-fluoro-3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-4-methyl-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2,6-dichloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[1-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzoyl)-piperidin-4-ylmethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxy-phenyl)-2-hydroxyethylamino]methyl}-benzoylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[ethyl-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenyl)carbamoyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(3-{4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]piperidin-1-yl}-3-oxo-propyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-thiophene-2-carbonyl)amino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-3-nitro-benzoyl)methylamino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-cyclohexylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]cyclohexanecarbonyl}-methylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-fluoro-3-{4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]piperidin-1-ylmethyl}benzyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(6-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}pyridine-3-carbonyl)amino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(5-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}-thiophen-2-yl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxy-ethylamino]ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-fluoro-3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}piperidin-1-ylmethyl)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-trifluoromethoxy-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{3-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)phenyl]propyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{2-[(S)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-iodo-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-6-methylphenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{5-[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentylcarbamoyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-bromo-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{3-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5yl)ethylamino]ethyl}phenylamino)-phenyl]propyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-fluoro-3-(4-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}piperidin-1-ylmethyl)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methoxy-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[5-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)pentyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[1-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)-piperidin-4-yl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-1-methyl-ethyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)cyclohexyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-fluoro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)phenyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2,5-difluoro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}-benzoylamino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[6-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}piperidin-1-ylmethyl)pyridin-2-ylmethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}-naphthalen-1-ylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[1-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoyl)piperidin-4-yl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propionylamino}phenyl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-1H-benzoimidazol-2-yl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propionylamino}cyclohexyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentanoylamino}cyclohexyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexanoylamino}cyclohexyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(1-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propionyl}piperidin-4-yl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenyl)ureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(2-{4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]cyclohexyl}-ethyl)methylamino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2,3,5,6-tetrafluoro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)-ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2,6-diiodo-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(1-{4-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]-butyry}piperidin-4-yl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(1-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentanoyl}piperidin-4-yl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(1-{6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexanoyl}piperidin-4-yl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxy-phenyl)-2-hydroxyethylamino]methyl}-benzylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzyl)ureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}benzyl)-ureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-methyl-phenylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(3-{4-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}piperidin-1-yl)ethyl]phenoxy}propyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}-benzylcarbamoyl)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetyl]methylamino}ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetyl]methylamino}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}furan-2-carbonyl)methylamino]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-thiophene-2-carbonyl)methylamino]ethyl}-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethoxy}phenoxy)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoylamino)cyclohexyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(2-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]cyclohexyl}ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]cyclohexyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]cyclohexyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}furan-2-carbonyl)amino]cyclohexyl}-ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-thiophene-2-carbonyl)amino]cyclohexyl}-ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{1-[2-(2-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetyl]piperidin-4-yl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{1-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetyl]piperidin-4-yl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetyl]piperidin-4-yl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[1-(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}furan-2-carbonyl)piperidin-4-yl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[1-(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-thiophene-2-carbonyl)piperidin-4-yl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoylamino)phenyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoylamino)phenyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(2-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]phenyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]phenyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)acetylamino]phenyl}ethyl)-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}furan-2-carbonyl)amino]phenyl}ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{4-[(5-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-thiophene-2-carbonyl)amino]phenyl}-ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-benzoylamino)cyclohexyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(3-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)-propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-hydroxy-3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)butyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-({2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]acetylamino}methyl)phenylcarbamoyl]ethyl}-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[4-(2-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]acetylamino}methyl)phenylcarbamoyl]ethyl}-piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-cyclohexylmethyl)carbamoyl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexanoylamino}-ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(3-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethoxy}phenoxy)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-{2-[(S)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethoxy}phenoxy)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenoxy)benzyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexylcarbamoyl}ethyl)piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-({(1R,3S)-3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2dihydroquinolin-5-yl)ethylamino]cyclopentanecarbonyl}amino)ethyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)butyl]piperidin-4yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(5-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}furan-2-yl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[3-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenyl)-1-methylureido]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{2-[1-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylcarbamoyl)piperidin-4-yl]ethyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(3-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}phenyl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[3-(5-{3-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]propyl}tetrahydrofuran-2-yl)propyl]piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethylcarbamoyl}phenoxy)ethyl]piperidin-4-yl ester;
(5-bromobiphenyl-2-yl)carbamic acid 1-{9-[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}-piperidin-4-yl ester;
(2′-fluorobiphenyl-2-yl)carbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}-piperidin-4-yl ester;
(3′-chloro-3,5-difluorobiphenyl-2-yl)carbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]nonyl}piperidin-4-yl ester;
(3′,5′-dichloro-3,5-difluorobiphenyl-2-yl)carbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]nonyl}piperidin-4-yl ester;
(3,5-difluorobiphenyl-2-yl)carbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}piperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-phenylcarbamoyl)ethyl]-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}phenylcarbamoyl)-ethyl]-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]nonyl}-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{5-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]pentylcarbamoyl}-ethyl)-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{5-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]pentylcarbamoyl}ethyl)-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{6-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]hexanoylamino}ethyl)-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-(2-{6-[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]hexanoylamino}ethyl)-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}benzoylamino)ethyl]-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}benzoylamino)ethyl]-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-{3-[4-(4-{2-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]ethyl}phenylamino)phenyl]propyl}-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}phenylcarbamoyl)ethyl]-4-methylpiperidin-4-yl ester;
biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]-4-methylpiperidin-4-yl ester;
4-(biphenyl-2-ylcarbamoyloxy)-1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]nonyl}-1-azoniabicyclo[2.2.2]octane;
biphenyl-2-ylcarbamic acid 8-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}-8-azabicyclo[3.2.1]oct-3-yl ester;
7-(biphenyl-2-ylcarbamoyloxy)-9-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)-ethylamino]nonyl}-9-methyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane;
and
biphenyl-2-ylcarbamic acid 9-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}-3-oxa-9-aza-tricyclo[3.3.1.02,4]non-7-yl ester;
or a pharmaceutically acceptable salt or solvate thereof.

185 more elements

A process for preparing a compound of formula I:

wherein:
a is 0 or an integer of from 1 to 3;
each R1 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR1a, —C(O)OR1b, —SR1c, —S(O)R1d, —S(O)2R1e and NR1fR1g;
each of R1a, R1b, R1c, R1d, R1e, R1f and R1g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
b is 0 or an integer of from 1 to 3;
each R2 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR2a, —C(O)OR2b, —SR2c, —S(O)R2d, —S(O)2R2c and —NR2fR2g;
each of R2a, R2b, R2c, R2d, R2e, R2f and R2g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
W is attached to the 3- or 4-position with respect to the nitrogen atom in the piperidine ring and represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
c is 0 or an integer of from 1 to 4;
each R3 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR3a, —C(O)OR3b, —SR3c, —S(O)R3d, —S(O)2R3e and —NR3fR3g;
or two R3 groups are joined to form (1–3C)alkylene, (2–3C)alkenylene or oxiran-2,3-diyl;
each of R3a, R3b, R3c, R3d, R3e, R3f and R3g is independently hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)c-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from, halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4C)alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 14 contiguous atoms;
R5 hydrogen or (1–4C)alkyl;
R6 is —NR6aCR6b(O) or —CR6cR6dOR6e and R7 hydrogen;
or R6 and R7 together form —NR7aC(O)—CR7b═CR7c—, —CR7d═CR7e—C(O)—NR7f—, —NR(7gC(O)—CR7hR7i—CR7jR7k— or —CR7lR7m—CR7nR7o—C(O)—NR7p—;
each of R6a, R6b, R6c, R6d and R6e is independently hydrogen or (1–4C)alkyl;
and
each of R7a, R7b, R7c, R7d, R7e, R7f, R7g, R7h, R7i, R7j, R7k, R7l, R7m, R7n, R7o and R7p is independently hydrogen or (1–4C)alkyl;
or a stereoisomer thereof;
the process comprising:
(a) reacting a compound of formula 1:
or a salt thereof;
with a compound of formula 2:
wherein X1 represents a leaving group, and P1 and P2 each independently represent a hydrogen atom or a hydroxyl-protecting group;
(b) reacting a compound of formula 3:
or salt thereof;
with a compound of formula 4:
wherein X2 represents a leaving group, and P3 and P4 each independently represent a hydrogen atom or a hydroxyl-protecting group;
(c) coupling a compound of formula 5:
with a compound of formula 6:
wherein XQa and XQb each independently represent functional groups that couple to form a group Q, P5a represents a hydrogen atom or an amino-protecting group;
and P5b and P6 each independently represent a hydrogen atom or a hydroxyl-protecting group;
(d) for a compound of formula I wherein R5 represents a hydrogen atom, reacting a compound of formula 3 with a compound of formula 7:
or a hydrate thereof (e.g., a glyoxal), in the presence of a reducing agent, wherein P7 represents a hydrogen atom or a hydroxyl-protecting group;
(e) reacting a compound of formula 1 with a compound of formula 8:
or a hydrate thereof, in the presence of a reducing agent, wherein P8 and P9 each independently represent a hydrogen atom or a hydroxyl-protecting group, P10 represents a hydrogen atom or an amino-protecting group, and R4′ represents a residue that, together with the carbon to which it is attached, affords a group R4 upon completion of the reaction;
(f) reacting a compound of formula 9:
wherein X3 represents a leaving group, with a compound of formula 10:
wherein P11 and P12 each independently represent a hydrogen atom or a hydroxyl-protecting group, and P13 represents a hydrogen atom or an amino-protecting group;
or
(g) reacting a compound of formula 11:
or a hydrate thereof;
wherein R4′ represents a residue that, together with the carbon to which it is attached, affords a group R4 upon completion of the reaction;
with a compound of formula 10 in the presence of a reducing agent;
and then
removing any protecting group P1, P2, P3, P4, P5a, P5b, P6, P7, P8, P9, P10, P11, P12 or P13 to provide a compound of formula I.

54 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/779,157Filed 13 Feb 2004 · us provisional application
Priority: 14 Feb 2003
Published: US 2004/0167167 A126 Aug 2004
Granted: 28 Nov 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 211/46
Attached in position 4: having a hydrogen atom as the second substituent in position 4
A61K 31/445
Non condensed pyridines; Hydrogenated derivatives thereof: non condensed piperidines, e.g. piperocaine
A61K 31/452
Non condensed piperidines, e.g. piperocaine: piperidinium derivatives
A61P 5/40
Of the suprarenal hormones: mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids

Family

Application60/447,843Us provisional application · filed 14 Feb 2003
Application60/467,035Us provisional application · filed 1 May 2003
US 2004/0167167 A1Pre-grant publication · published 26 Aug 2004
US 7,141,671 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula I:

wherein:
a is 0 or an integer of from 1 to 3;
each R1 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR1a, —C(O)OR1b, —SR1c, —S(O)R1d, —S(O)2R1e and —NR1fR1g;
each of R1a, R1b, R1c, R1d, R1e, R1f and R1g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
b is 0 or an integer of from 1 to 3;
each R2 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR2a, —C(O)OR2b, —SR2c, —S(O)R2d, —S(O)2R2e and —NR2fR2g;
each of R2a, R2b, R2c, R2d, R2e, R2f and R2g is independently hydrogen, (1–4C)alkyl or phenyl-(1–4C)alkyl;
W is attached to the 3- or 4-position with respect to the nitrogen atom in the piperidine ring and represents O or NWa;
Wa is hydrogen or (1–4C)alkyl;
c is 0 or an integer of from 1 to 4;
each R3 is independently selected from (1–4C)alkyl, (2–4C)alkenyl, (2–4C)alkynyl, (3–6C)cycloalkyl, cyano, halo, —OR3a, —C(O)OR3b, —SR3c, —S(O)R3d, —S(O)2R3e and —NR3fR3g;
or two R3 groups are joined to form (1–3C)alkylene, (2–3C)alkenylene or oxiran-2,3-diyl;
each of R3a, R3b, R3c, R3d, R3e, R3f and R3g is independently hydrogen or (1–4C)alkyl;
R4 is a divalent group of the formula:
—(R4a)d-(A1)c-(R4b)f-Q-(R4c)g-(A2)h-(R4d)i—
wherein
d, e, f, g, h and i are each independently selected from 0 and 1;
R4a, R4b, R4c and R4d are each independently selected from (1–10C)alkylene, (2–10C)alkenylene and (2–10C)alkynylene, wherein each alkylene, alkenylene or alkynylene group is unsubstituted or substituted with from 1 to 5 substituents independently selected from (1–4C)alkyl, fluoro, hydroxy, phenyl and phenyl-(1–4C)alkyl;
A1 and A2 are each independently selected from (3–7C)cycloalkylene, (6–10C)arylene, —O-(6–10C)arylene, (6–10C)arylene-O—, (2–9C)heteroarylene, —O-(2–9C)heteroarylene, (2–9C)heteroarylene-O— and (3–6C)heterocyclene, wherein each cycloalkylene is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl, and each arylene, heteroarylene or heterocyclene group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl, (1–4C)alkoxy, —S-(1–4C)alkyl, —S(O)-(1–4C)alkyl, —S(O)2-(1–4C)alkyl, —C(O)O(1–4C)alkyl, carboxy, cyano, hydroxy, nitro, trifluoromethyl and trifluoromethoxy;
Q is selected from a bond, —O—, —C(O)O—, —OC(O)—, —S—, —S(O)—, —S(O)2—, —N(Qa)C(O)—, —C(O)N(Qb)-, —N(Qc)S(O)2—, —S(O)2N(Qd)-, —N(Qe)C(O)N(Qf)-, —N(Qg)S(O)2N(Qh)-, —OC(O)N(Qi)-, —N(Qj)C(O)O— and —N(Qk);
Qa, Qb, Qc, Qd, Qe, Qf, Qg, Qh, Qi, Qj and Qk are each independently selected from hydrogen, (1–6C)alkyl, A3 and (1–4C)alkylene-A4, wherein the alkyl group is unsubstituted or substituted with from 1 to 3 substituents independently selected from fluoro, hydroxy and (1–4C)alkoxy or together with the nitrogen atom and the group R4b or R4c to which they are attached, form a 4–6 membered azacycloalkylene group;
A3 and A4 are each independently selected from (3–6C)cycloalkyl, (6–10C)aryl, (2–9C)heteroaryl and (3–6C)heterocyclyl, wherein each cycloalkyl is unsubstituted or substituted with from 1 to 4 substitutents selected independently from (1–4C)alkyl and each aryl, heteroaryl or heterocyclyl group is unsubstituted or substituted with from 1 to 4 substituents independently selected from halo, (1–4C)alkyl and (1–4C)alkoxy;
provided that the linkage of contiguous atoms between the two nitrogen atoms to which R4 is attached has from 4 to 16 contiguous atoms;
R5 hydrogen or (1–4C)alkyl;
R6 is —NR6aCR6b(O) or —CR6cR6dOR6e and R7 is hydrogen;
or R6 and R7 together form —NR7aC(O)—CR7b═CR7c—, —CR7d═CR7e—C(O)—NR7f—, —NR7gC(O)—CR7hR7i—CR7jR7k— or —CR7lR7m—CR7nR7o—C(O)—NR7p—;
each of R6a, R6b, R6c, R6d and R6e is independently hydrogen or (1–4C)alkyl;
and
each of R7a, R7b, R7c, R7d, R7e, R7f, R7g, R7h, R7i, R7j, R7k, R7l, R7m, R7n, R7o and R7p is independently hydrogen or (1–4C)alkyl;
or a pharmaceutically acceptable salt or solvate or stercoisomer thereof.

27 more elements

Facts

Application

10/779,157Filed 13 Feb 2004 · us provisional application

Priority

14 Feb 2003

Published

US 2004/0167167 A126 Aug 2004

Granted

28 Nov 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 211/46
Attached in position 4: having a hydrogen atom as the second substituent in position 4
A61K 31/445
Non condensed pyridines; Hydrogenated derivatives thereof: non condensed piperidines, e.g. piperocaine
A61K 31/452
Non condensed piperidines, e.g. piperocaine: piperidinium derivatives
A61P 5/40
Of the suprarenal hormones: mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids