US 2005/0032789 A1Published application

Novel compounds useful in pain management

AssigneeAstraZeneca Canada Inc.

InventorsDaniel Delorme, Vlad Gregor, Edward Roberts, Eric Sun

Life of this patent

Estimating the term…

Abstract

Compounds of general formula I are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts, pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain.

Claims22

Dependent claims

A compound according to formula I

wherein
m and n is each and independently an integer of from 1-3, and one or more of the hydrogens in such an alkylene-chain may optionally be substituted by anyone of C1-C6 alkyl, C1-C6 alkoxy, or hydroxy;
or
one or more of the methylene groups may optionally be substituted by a heteroatom such as O, N or S;
R1 is selected from hydrogen, a branched or straight C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, C4-C8(alkyl-cycloalkyl) wherein the alkyl is C1-C2 alkyl and the cycloalkyl is C3-C6 cycloalkyl;
R2 is selected from any of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl];
(iv) —[(CH2)r-heteroaryl] where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
and wherein q and r is each and independently an integer of from 0 to 3;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(vii) heteroaryl having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
or
R1 and R2 may optionally form a heterocyclic ring;
R3 is selected from anyone of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) —[(C3-C6 cycloalkyl)-(CH2)q] wherein q is an integer of from 1 to 3;
R4 is selected from
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(vii) heteroaryl having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
R5 is selected from anyone of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
wherein
R7, R8, R9, R10 and R11 is each and independently selected from
(a) hydrogen;
(b) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(c) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(d) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(e) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(f) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
or
R4 and R5 may optionally form a heterocyclic ring;
Y is each and independently selected from any of hydrogen, CH3;
—(CH2)p1CF3;
halogen;
C1-C3 alkoxy;
hydroxy;
—NO2;
—OCF3;
—CONRaRb;
—COORa;
—CORa;
—CH2)p2NRaRb;
—(CH2)p3CH3, (CH2)p4SORaRb;
—(CH2)p5SO2Ra;
—(CH2)p6SO2NRa;
C4-C8(alkyl-cycloalkyl) wherein alkyl is C1-C2 alkyl and cycloalkyl is C3-C6 cycloalkyl;
1 or 2 heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O;
and oxides such as N-oxides or sulfoxides;
and wherein
Ra and Rb is each and independently selected from hydrogen, a branched or straight C1-C6 alkyl, C1-C6 alkenyl, C3-C8 cycloalkyl;
and wherein
p1, p2, p3, p4, p5 and p6 is each and independently 0, 1 or 2;
as well as pharmaceutically acceptable salts, isomers, hydrates, isoforms and prodrugs thereof.

76 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/877,967Filed 28 Jun 2004
Priority: SE 9802209-822 Jun 1998
Published: 10 Feb 2005
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

A61K 51/0406
Lipids, e.g. triglycerides; Polycationic carriers: amines, polyamines, e.g. spermine, spermidine, amino acids, guanidines
A61K 51/0446
Having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins: having five-membered rings with one nitrogen as the only ring hetero atom,…
C07C 273/1854
Of substituted ureas: by reactions not involving the formation of the N-C-N- moiety
C07C 275/28
Derivatives of urea, i.e. compounds containing any of the groups [IMAGE cpc-sch-C07C-0967.gif], the nitrogen atoms not being part of nitro or…:…

Family

Application09/555,575Continuation · filed 1 Jun 2000
Application10/877,967Continuation · filed 28 Jun 2004
US 6,777,561 B1Related patent
US 2005/0032789 A1This patent

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

Timeline

Citations

Open elsewhere

Building an agent or pulling many patents? Use the API or MCP server instead of scraping pages. Get an API key

patentgrep

Loading patent…

Abstract

A compound according to formula I

wherein
m and n is each and independently an integer of from 1-3, and one or more of the hydrogens in such an alkylene-chain may optionally be substituted by anyone of C1-C6 alkyl, C1-C6 alkoxy, or hydroxy;
or
one or more of the methylene groups may optionally be substituted by a heteroatom such as O, N or S;
R1 is selected from hydrogen, a branched or straight C1-C6 alkyl, C2-C6 alkenyl, C3-C8 cycloalkyl, C4-C8(alkyl-cycloalkyl) wherein the alkyl is C1-C2 alkyl and the cycloalkyl is C3-C6 cycloalkyl;
R2 is selected from any of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl];
(iv) —[(CH2)r-heteroaryl] where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
and wherein q and r is each and independently an integer of from 0 to 3;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(vii) heteroaryl having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
or
R1 and R2 may optionally form a heterocyclic ring;
R3 is selected from anyone of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) —[(C3-C6 cycloalkyl)-(CH2)q] wherein q is an integer of from 1 to 3;
R4 is selected from
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(vi) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(vii) heteroaryl having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
R5 is selected from anyone of
(i) hydrogen;
(ii) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(iii) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(iv) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(v) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
wherein
R7, R8, R9, R10 and R11 is each and independently selected from
(a) hydrogen;
(b) a straight or branched C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl;
(c) —[(CH2)q-aryl] wherein q is an integer of from 0 to 3, and wherein the aryl may optionally be substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
(d) heteoaryl-(C5-C10 alkyl), where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O, and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(e) C3-C10 cycloalkyl, optionally comprising one or more unsaturations and optionally susbtituted by one or more heteroaryl(s) where the heteroaryl has from 5 to 10 atoms and the heteroatom being selected from any of S, N and O;
and wherein the aryl and heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y where each Y is as defined below;
(f) C6-C10 aryl, optionally and independently substituted by one or more heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O and wherein the heteroaryl may optionally and independently be substituted by 1 or 2 substituents Y wherein each Y is as defined below;
or
R4 and R5 may optionally form a heterocyclic ring;
Y is each and independently selected from any of hydrogen, CH3;
—(CH2)p1CF3;
halogen;
C1-C3 alkoxy;
hydroxy;
—NO2;
—OCF3;
—CONRaRb;
—COORa;
—CORa;
—CH2)p2NRaRb;
—(CH2)p3CH3, (CH2)p4SORaRb;
—(CH2)p5SO2Ra;
—(CH2)p6SO2NRa;
C4-C8(alkyl-cycloalkyl) wherein alkyl is C1-C2 alkyl and cycloalkyl is C3-C6 cycloalkyl;
1 or 2 heteroaryl(s) having from 5 to 10 atoms and the heteroatom(s) being selected from any of S, N and O;
and oxides such as N-oxides or sulfoxides;
and wherein
Ra and Rb is each and independently selected from hydrogen, a branched or straight C1-C6 alkyl, C1-C6 alkenyl, C3-C8 cycloalkyl;
and wherein
p1, p2, p3, p4, p5 and p6 is each and independently 0, 1 or 2;
as well as pharmaceutically acceptable salts, isomers, hydrates, isoforms and prodrugs thereof.

76 more elements

Facts

Application

10/877,967Filed 28 Jun 2004

Priority

SE 9802209-822 Jun 1998

Published

10 Feb 2005

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

A61K 51/0406
Lipids, e.g. triglycerides; Polycationic carriers: amines, polyamines, e.g. spermine, spermidine, amino acids, guanidines
A61K 51/0446
Having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins: having five-membered rings with one nitrogen as the only ring hetero atom,…
C07C 273/1854
Of substituted ureas: by reactions not involving the formation of the N-C-N- moiety
C07C 275/28
Derivatives of urea, i.e. compounds containing any of the groups [IMAGE cpc-sch-C07C-0967.gif], the nitrogen atoms not being part of nitro or…:…