US 2006/0223825 A1Published application

Piperazinyl substituted cyclohexane-1,4-diamines

AssigneeJanssen Pharmaceutica NV

InventorsGeorge Chiu, Shengjian Li, Peter Connolly, Virginia Pulito, Jingchun Liu, Steven Middleton

Life of this patent

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Abstract

The present invention relates to piperazine substituted cyclohexane- 1,4-diamine compounds of Formula (I) and pharmaceutically acceptable forms thereof, as α1a/α1d adrenoreceptor modulators for the treatment of benign prostatic hypertrophy and lower urinary tract symptoms. The present invention also relates to pharmaceutical compositions comprising said new compounds, new processes to prepare these new compounds and new uses as a medicine as well as methods of treatment.

Claims33

Dependent claims

A compound of Formula (I)

or a pharmaceutically acceptable form thereof, wherein
R1 is selected from the group consisting of
(1) aryl,
(2) aryl-C1-8alkyl,
(3) C3-8cycloalkyl,
(4) C3-8cycloalkyl-C1-8alkyl,
(5) heteroaryl,
(6) heteroaryl-C1-8alkyl,
(7) heterocyclyl, and
(8) heterocyclyl-C1-8alkyl,
wherein each aryl, C3-8cycloalkyl, heteroaryl and heterocyclyl is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C1-8alkyl,
(ii) C1-8alkoxy,
(iii) C1-8alkoxy-C1-8alkyl,
(iv) halo-C1-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-C1-8alkyl,
(vii) C1-8alkoxy-carbonyl,
(viii) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(ix) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy,
(xiii) nitro,
(xiv) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl,
(xv) aryl-C1-8alkyl,
(xvi) aryl-C1-8alkoxy,
(xvii) heteroaryl-C1-8alkyl,
(xviii) heterocyclyl-C1-8alkyl;
(xix) C(O) substituted with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xx) S(O) substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxi) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxii) SO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiii) NHSO2 substituted on sulfur with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiv) NHC(O) substituted on carbonyl with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxv) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxvi) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxvii) C3-8cycloalkyl,
(xxviii) aryl,
(xxix) heteroaryl, and
(xxx) heterocyclyl;
R2 is selected from the group consisting of hydrogen and C1-8alkyl;
R3 is zero, one, two, three or four substituents independently selected from the group consisting of
(1) C1-8alkyl,
(2) C1-8alkoxy,
(3) C1-8alkoxy-C1-8alkyl,
(4) halo-C1-8alkyl,
(5) halo-C1-8alkoxy,
(6) hydroxy-C1-8alkyl,
(7) C1-8alkoxy-carbonyl,
(8) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(9) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(10) cyano,
(11) halogen,
(12) hydroxy,
(13) nitro,
(14) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl,
(15) aryl,
(16) aryl-C1-8alkyl,
(17) aryl-C1-8alkoxy,
(18) C3-8cycloalkyl,
(19) C3-8cycloalkyl-C1-8alkyl,
(20) C3-8cycloalkyl-C1-8alkoxy,
(21) heteroaryl,
(22) heteroaryl-C1-8alkyl,
(23) heterocyclyl,
(24) heterocyclyl-C1-8alkyl,
(25) C(O) substituted with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(26) S(O) substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(27) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(28) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(29) SO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(30) NHSO2 substituted on sulfur with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(31) NHC(O) substituted on carbonyl with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(32) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(33) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl, and
(34) C3-8cycloalkoxy;
wherein each aryl, C3-8cycloalkyl, heteroaryl and heterocyclyl is unsubstituted or substituted with one or two substituents independently selected from the group consisting of
(i) C1-8alkyl,
(ii) C1-8alkoxy,
(iii) C1-8alkoxy-C1-8alkyl,
(iv) halo-C1-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-C1-8alkyl,
(vii) C1-8alkoxy-carbonyl,
(viii) C1-8alkyl-sulfonyl,
(ix) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy,
(xiii) nitro, and
(xiv) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl;
and
R4 and R5 is each selected from hydrogen or is each one or two substituents independently selected from the group consisting of C1-8alkyl, C1-8alkoxy, amino, C1-8alkyl-amino, cyano, halogen, oxo and nitro.

91 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/376,432Filed 15 Mar 2006
Priority: 29 Mar 2005
Published: 5 Oct 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
A61P 13/08
Drugs for disorders of the urinary system: of the prostate
A61P 13/10
Drugs for disorders of the urinary system: of the bladder
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Application60/665,952Us provisional application · filed 29 Mar 2005
US 7,482,348 B2Related patent
US 2006/0223825 A1This patent

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

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Abstract

A compound of Formula (I)

or a pharmaceutically acceptable form thereof, wherein
R1 is selected from the group consisting of
(1) aryl,
(2) aryl-C1-8alkyl,
(3) C3-8cycloalkyl,
(4) C3-8cycloalkyl-C1-8alkyl,
(5) heteroaryl,
(6) heteroaryl-C1-8alkyl,
(7) heterocyclyl, and
(8) heterocyclyl-C1-8alkyl,
wherein each aryl, C3-8cycloalkyl, heteroaryl and heterocyclyl is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C1-8alkyl,
(ii) C1-8alkoxy,
(iii) C1-8alkoxy-C1-8alkyl,
(iv) halo-C1-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-C1-8alkyl,
(vii) C1-8alkoxy-carbonyl,
(viii) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(ix) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy,
(xiii) nitro,
(xiv) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl,
(xv) aryl-C1-8alkyl,
(xvi) aryl-C1-8alkoxy,
(xvii) heteroaryl-C1-8alkyl,
(xviii) heterocyclyl-C1-8alkyl;
(xix) C(O) substituted with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xx) S(O) substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxi) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxii) SO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiii) NHSO2 substituted on sulfur with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiv) NHC(O) substituted on carbonyl with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxv) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxvi) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxvii) C3-8cycloalkyl,
(xxviii) aryl,
(xxix) heteroaryl, and
(xxx) heterocyclyl;
R2 is selected from the group consisting of hydrogen and C1-8alkyl;
R3 is zero, one, two, three or four substituents independently selected from the group consisting of
(1) C1-8alkyl,
(2) C1-8alkoxy,
(3) C1-8alkoxy-C1-8alkyl,
(4) halo-C1-8alkyl,
(5) halo-C1-8alkoxy,
(6) hydroxy-C1-8alkyl,
(7) C1-8alkoxy-carbonyl,
(8) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(9) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(10) cyano,
(11) halogen,
(12) hydroxy,
(13) nitro,
(14) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl,
(15) aryl,
(16) aryl-C1-8alkyl,
(17) aryl-C1-8alkoxy,
(18) C3-8cycloalkyl,
(19) C3-8cycloalkyl-C1-8alkyl,
(20) C3-8cycloalkyl-C1-8alkoxy,
(21) heteroaryl,
(22) heteroaryl-C1-8alkyl,
(23) heterocyclyl,
(24) heterocyclyl-C1-8alkyl,
(25) C(O) substituted with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(26) S(O) substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(27) SO2 substituted with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(28) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(29) SO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(30) NHSO2 substituted on sulfur with a substituent selected from the group consisting of C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(31) NHC(O) substituted on carbonyl with a substituent selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(32) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(33) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl, and
(34) C3-8cycloalkoxy;
wherein each aryl, C3-8cycloalkyl, heteroaryl and heterocyclyl is unsubstituted or substituted with one or two substituents independently selected from the group consisting of
(i) C1-8alkyl,
(ii) C1-8alkoxy,
(iii) C1-8alkoxy-C1-8alkyl,
(iv) halo-C1-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-C1-8alkyl,
(vii) C1-8alkoxy-carbonyl,
(viii) C1-8alkyl-sulfonyl,
(ix) amino unsubstituted or mono- or di-substituted with C1-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy,
(xiii) nitro, and
(xiv) amino-C1-8alkyl unsubstituted or mono- or di-substituted on amino with C1-8alkyl;
and
R4 and R5 is each selected from hydrogen or is each one or two substituents independently selected from the group consisting of C1-8alkyl, C1-8alkoxy, amino, C1-8alkyl-amino, cyano, halogen, oxo and nitro.

91 more elements

Facts

Application

11/376,432Filed 15 Mar 2006

Priority

29 Mar 2005

Published

5 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 213/74
Nitrogen atoms: amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
A61P 13/08
Drugs for disorders of the urinary system: of the prostate
A61P 13/10
Drugs for disorders of the urinary system: of the bladder
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00