HRP20100691T1 - Heterociklicki-supstituirani piperidini kao orl-1 ligandi - Google Patents
Heterociklicki-supstituirani piperidini kao orl-1 ligandi Download PDFInfo
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- HRP20100691T1 HRP20100691T1 HR20100691T HRP20100691T HRP20100691T1 HR P20100691 T1 HRP20100691 T1 HR P20100691T1 HR 20100691 T HR20100691 T HR 20100691T HR P20100691 T HRP20100691 T HR P20100691T HR P20100691 T1 HRP20100691 T1 HR P20100691T1
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- 150000003053 piperidines Chemical class 0.000 title abstract 2
- 239000003446 ligand Substances 0.000 title 1
- 239000000203 mixture Chemical class 0.000 claims abstract 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract 6
- 238000000034 method Methods 0.000 claims abstract 5
- -1 Piperidine Compound Chemical class 0.000 claims abstract 4
- 241001465754 Metazoa Species 0.000 claims abstract 3
- 208000002193 Pain Diseases 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 18
- 150000003839 salts Chemical class 0.000 claims 9
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
- 125000001475 halogen functional group Chemical group 0.000 claims 7
- 125000001072 heteroaryl group Chemical group 0.000 claims 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 5
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 150000001602 bicycloalkyls Chemical group 0.000 claims 3
- 125000006371 dihalo methyl group Chemical group 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000006372 monohalo methyl group Chemical group 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 108010020615 nociceptin receptor Proteins 0.000 claims 3
- 125000006370 trihalo methyl group Chemical group 0.000 claims 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 208000019901 Anxiety disease Diseases 0.000 claims 2
- 206010006895 Cachexia Diseases 0.000 claims 2
- 206010010774 Constipation Diseases 0.000 claims 2
- 206010011224 Cough Diseases 0.000 claims 2
- 206010012735 Diarrhoea Diseases 0.000 claims 2
- 206010020772 Hypertension Diseases 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 206010046543 Urinary incontinence Diseases 0.000 claims 2
- 208000022531 anorexia Diseases 0.000 claims 2
- 230000036506 anxiety Effects 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 206010061428 decreased appetite Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- 238000000338 in vitro Methods 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000004193 piperazinyl group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000006413 ring segment Chemical group 0.000 claims 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 206010013654 Drug abuse Diseases 0.000 claims 1
- 208000026139 Memory disease Diseases 0.000 claims 1
- 101500026205 Rattus norvegicus Nociceptin Proteins 0.000 claims 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 claims 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000006870 function Effects 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 206010027175 memory impairment Diseases 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 208000011117 substance-related disease Diseases 0.000 claims 1
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
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Abstract
Spoj formule (I): ili njegov farmaceutski prihvatljiv derivat, naznacen time da: je svaki R2 neovisno odabran od: (a) -halo, -CN, -NO2, -OT3, -C(O)T3, -C(O)OT3, -C(O)N(T1)(T2), -S(O)3H, -S(O)T3, -S(O)2T3, -S(O)2N(T1)(T2), -N(T1)(T2), -N(T3)C(O)T3, -N(T3)C(O)N(T1)(T2), -N(T3)S(O)2T3, ili -N(T3)S(O)2N(T1)(T2); ili (b) -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -(C1-C6)alkoksija, -(C3-C7)cikloalkila, -(C6-C14)bicikloalkila, -(C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C5-C20)tricikloalkenila, -(5-ili 6-clanog)heterocikla, ili -(7- do 10-clanog)bicikloheterocikla, od kojih je svaki nesupstutuiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8; ili (c) -fenila, -naftalenila, -(C14)arila, ili -(5- ili 6-clanog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7;a je cijeli broj odabran od 0, 1 ili 2; R3 je odabran od: (a) -H; ili (b) -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -O(C1-C6)alkila, -O(C2-C6)alkenila, -O(C2-C6)alkinila, -(C3-C7)cikloalkila, -(C3-C7)cikloalkenila, -(C3-C7)cikloalkoksija, -(C6-C14)bicikloalkila, -(C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C8-C20)tricikloalkenila, -(3- do 7-clanog)heterocikla, ili -(7- do 10-clanog)bicikloheterocikla, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8; ili (c) -fenila, -naftalenila, -(C14)arila, ili -(5- ili 6-clanog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7; ili (d) -(C1-C6)alkil(=O)W1, -(C1-C6)alkil(=NH)W1, -C(O)OV1, -C(O)N(V1)2, -S(O)2N(V1)2, ili -S(O)2(C1-C6)alkila; ili (e) -(C1-C4)alkila supstituiranog s 1, 2 ili 3 supstituenta neovisno odabranim od -(C3-C7)cikloalkila, -(C3-C7)cikloalkenila, -(C3-C7)cikloalkoksija, -(C6-C14)bicikloalkila, - (C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C8-C20)tricikloalkenila, -(3- do 7-clanog)heterocikla, -(7- do 10- clanog)bicikloheterocikla, -fenila, -naftalenila, -(C14)arila, ili -(5- do 10-clanog)heteroarila; ili (f) -(C1-C3)alkila supstituiranog sa supstituentom odabranim od -N(R6)2, -S(O)2N(V1)2, -N(R9)C(O)W1, -N(R9)S(O)2W1, i -C(O)N(V1)2;svaki W1 je neovisno odabran od: (a) -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -O(C1-C6)alkila, -(C3-C7)cikloalkoksija, -CH2CH2OH, -N(R6)2; ili (b) -(5- ili 6-clanog)heteroarila opcionalno supstituiranog s 1, 2 ili 3 neovisno odabrana -(C1-C6)alkila; svaki V1 je neovisno odabran od -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -fenila, ili -benzila; svaki Y je neovisno odabran od O ili S; A i B su neovisno odabrani od: (a) -H, -CN, -C(O)OT3, -C(O)N(T)1(T2), -(C3-C12)cikloalkila, -(C3-C12)cikloalkoksija, -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila ili -(C1-C6)alkoksija, od kojih je svaki -(C3-C12)cikloalkil, -(C3-C12)cikloalkoksi, -(C1-C6)alkil, -(C2-C6)alkenil ili -(C2-C6)alkinil nesupstituiran ili supstituiran s 1 ili 2 supstituenta neo
Claims (28)
1. Spoj formule (I):
[image]
ili njegov farmaceutski prihvatljiv derivat, naznačen time da:
je svaki R2 neovisno odabran od:
(a) -halo, -CN, -NO2, -OT3, -C(O)T3, -C(O)OT3, -C(O)N(T1)(T2), -S(O)3H, -S(O)T3, -S(O)2T3, -S(O)2N(T1)(T2), -N(T1)(T2), -N(T3)C(O)T3, -N(T3)C(O)N(T1)(T2), -N(T3)S(O)2T3, ili -N(T3)S(O)2N(T1)(T2); ili
(b) -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -(C1-C6)alkoksija, -(C3-C7)cikloalkila, -(C6-C14)bicikloalkila, -(C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C5-C20)tricikloalkenila, -(5-ili 6-članog)heterocikla, ili -(7- do 10-članog)bicikloheterocikla, od kojih je svaki nesupstutuiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8; ili
(c) -fenila, -naftalenila, -(C14)arila, ili -(5- ili 6-članog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7;
a je cijeli broj odabran od 0, 1 ili 2;
R3 je odabran od:
(a) -H; ili
(b) -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -O(C1-C6)alkila, -O(C2-C6)alkenila, -O(C2-C6)alkinila, -(C3-C7)cikloalkila, -(C3-C7)cikloalkenila, -(C3-C7)cikloalkoksija, -(C6-C14)bicikloalkila, -(C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C8-C20)tricikloalkenila, -(3- do 7-članog)heterocikla, ili -(7- do 10-članog)bicikloheterocikla, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8; ili
(c) -fenila, -naftalenila, -(C14)arila, ili -(5- ili 6-članog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7; ili
(d) -(C1-C6)alkil(=O)W1, -(C1-C6)alkil(=NH)W1, -C(O)OV1, -C(O)N(V1)2, -S(O)2N(V1)2, ili -S(O)2(C1-C6)alkila; ili
(e) -(C1-C4)alkila supstituiranog s 1, 2 ili 3 supstituenta neovisno odabranim od -(C3-C7)cikloalkila, -(C3-C7)cikloalkenila, -(C3-C7)cikloalkoksija, -(C6-C14)bicikloalkila, - (C8-C20)tricikloalkila, -(C5-C10)cikloalkenila, -(C7-C14)bicikloalkenila, -(C8-C20)tricikloalkenila, -(3- do 7-članog)heterocikla, -(7- do 10- članog)bicikloheterocikla, -fenila, -naftalenila, -(C14)arila, ili -(5- do 10-članog)heteroarila; ili
(f) -(C1-C3)alkila supstituiranog sa supstituentom odabranim od -N(R6)2, -S(O)2N(V1)2, -N(R9)C(O)W1, -N(R9)S(O)2W1, i -C(O)N(V1)2;
svaki W1 je neovisno odabran od:
(a) -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -O(C1-C6)alkila, -(C3-C7)cikloalkoksija, -CH2CH2OH, -N(R6)2; ili
(b) -(5- ili 6-članog)heteroarila opcionalno supstituiranog s 1, 2 ili 3 neovisno odabrana -(C1-C6)alkila;
svaki V1 je neovisno odabran od -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -fenila, ili -benzila;
svaki Y je neovisno odabran od O ili S;
A i B su neovisno odabrani od:
(a) -H, -CN, -C(O)OT3, -C(O)N(T)1(T2), -(C3-C12)cikloalkila, -(C3-C12)cikloalkoksija, -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila ili -(C1-C6)alkoksija, od kojih je svaki -(C3-C12)cikloalkil, -(C3-C12)cikloalkoksi, -(C1-C6)alkil, -(C2-C6)alkenil ili -(C2-C6)alkinil nesupstituiran ili supstituiran s 1 ili 2 supstituenta neovisno odabrana od -OH, -S(O)2NH2, -N(R6)2, =NR6, -C(O)OT3, -C(O)N(R6)2, -N(R6)C(O)R9 i -(5- ili 6-članog)heterocikla ili 1, 2 ili 3 neovisno odabrana -halo; ili
(b) A-B koji zajedno formiraju (C2-C6)most, koji je nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8, i gdje most opcionalno sadrži -HC=CH- unutar (C2-C6)mosta; gdje piperazinski prsten koji je spojen na fenilnu skupinu može biti u endo- ili egzo- konformaciji u odnosu na A-B most; ili
(c) A-B zajedno formiraju -CH2-N(Ra)-CH2- most,
[image]
most, ili
[image]
most;
gdje piperazinski prsten koji je spojen na fenilnu skupinu može biti u endo- ili egzo- konformaciji u odnosu na A-B most;
Ra je odabran od -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -CH2-C(O)-Rc, -(CH2)-C(O)-ORc, -(CH2)-C(O)-N(Rc)2, -(CH2)2-O-Rc, -(CH2)2-S(O)2-N(Rc)2, Fc, ili -(CH2)2-N(Rc)S(O)2-Rc;
Rb je odabran od:
(a) -H, -(C1-C6)alkila, -(C3-C7)cikloalkila, -(3- do 7-članog)heterocikla, -N(Rc)2, -N(Rc)-(C3-C7)cikloalkila, ili -N(Rc)-(3- do 7-članog)heterocikla; ili
(b) -fenila, -naftalenila, ili-(5- ili 6-članog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7; ili
(c) -N(Rc)-fenila, -N(Rc)-naftalenila, -N(Rc)-(C14)arila, ili -N(Rc)-(5- do 10-članog)heteroarila, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7;
svaki Rc je neovisno odabran od -H ili -(C1-C4)alkila;
C je odabran od -H, -halo, -CN, -OT3, -C(O)OT3, -C(O)N(T)1(T2), -(C3-C12)cikloalkila, -(C3-C12)cikloalkoksija, -N(R6)2, -N(R6)C(O)R9, -NR6SO2N(R6)2, -NR6-C(=NR6)N(P-6)2, -(C1-C6)alkila, -(C2-C6)alkenila, ili -(C2-C6)alkinila, od kojih svaki -(C1-C6)alkil, -(C2-C6)alkenil ili -(C2-C6)alkinil je nesupstituiran ili supstituiran s 1 ili 2 supstituenta neovisno odabrana od -OH, -S(O)2NH2, -N(R6)2, =NR6, -C(O)OT3, -C(O)N(R6)2, -N(R6)C(O)R9 i -(5- ili 6-članog)heterocikla ili od 1 do 3 neovisno odabranih -halo;
isprekidana crta u piperidinu ili premoštenom centralnom prstenu piperidina označuje prisutnost ili odsutnost veze,
i gdje isprekidana crta označuje prisutnost veze tada je D odsutan, u protivnom D je:
(a) -H, -CN, -C(O)OT3, ili -C(O)N(T1)(T2); ili
(b) -(C1-C10)alkil koji je nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabranim skupinama R8 i, opcionalno, u kojem je svaki atom ugljika u skupini D osim atoma ugljika koji je vezan direktno na piperidin ili premošteni centralni prsten piperidina, neovisno zamijenjen s O ili S; ili
(c) -fenil, -naftalenil, ili -(5- ili 6-člani)heteroaril, od kojih je svaki nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R7;
Z je veza;
R1 je odabran od:
[image]
m je cijeli broj odabran od 0, 1, 2, 3, 4, 5, 6 ili 7;
e i f su svaki pojedinačno cijeli broj, gdje je e odabran od 1, 2, 3, 4 ili 5 i f je neovisno odabran od 0, 1, 2, 3, 4 ili 5 uz uvjet da 2 ≤ (e + f) ≤ 5;
j i k su svaki pojedinačno cijeli broj neovisno odabrani od 0, 1, 2, 3 ili 4 uz uvjet da 1 ≤ (j+k) ≤ 4;
svaki T1, T2, i T3 su neovisno -H ili -(C1-C10)alkil koji je nesupstituiran ili supstituiran s 1, 2 ili 3
neovisno odabrane skupine R8 i, opcionalno, u kojem je svaki ugljikov atom neovisno zamijenjen s O ili S, ili T1 i T2 zajedno mogu činiti 5- do 8-člani prsten gdje broj atoma u prstenu uključuje atom dušika na koji su vezani T1 i T2, navedeni 5- do 8-člani prsten je nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8 i, opcionalno, bilo koji ugljikov atom u navedenom 5- do 8-članom prstenu je neovisno zamijenjen s O ili S;
svaki R6 je neovisno odabran od -H, -(C1-C6)alkila, ili -(C3-C7)cikloalkila, ili dvije skupine R6 vezane za isti atom dušika mogu činiti 5- do 8-člani prsten, broj atoma u prstenu uključujući dušikov atom, u kojem je jedan od ugljikovih atoma prstena opcionalno zamijenjen s O ili S;
svaki R7 je neovisno odabran od -(C1-C4)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -OR9, -SR9, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, -halo, -N3, -NO2, -CH=NR9, -NR9OH, -C(O)OR9, -OC(O)R9, -OC(O)OR9, -S(O)R9, ili -S(O)2R9;
svaki R8 je neovisno odabran od -(C1-C4)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -OR9, -SR9, -C(halo)3, -CH(halo)2, -CH2(halo), -CN, okso, =S,-fenila, -halo, -N3, -NO2, -CH=NR9, -NR9OH, -C(O)OR9, -OC(O)R9, -OC(O)OR9, -S(O)R9, ili -S(O)2R9;
svaki R9 je neovisno odabran od -H, -(C1-C6)alkila, -(C2-C6)alkenila, -(C2-C6)alkinila, -(C3-C8)cikloalkila, -(C5-C8)cikloalkenila, -fenila, -benzila, -(3- do 7-članog)heterocikla, -C(halo)3, -CH(halo)2, ili -CH2(halo);
svaki p je cijeli broj neovisno odabran od 0 ili 1;
R11 je odabran od -H, -C(O)OR9, -C(O)N(R6)2, ili -(C1-C4)alkila koji je nesupstituiran ili supstituiran s -OH, -(C1-C4)alkoksi, -N(R6)2, -C(O)OR9, ili -C(O)N(R6)2; i
svaki halo je neovisno odabran od -F, -Cl, -Br, ili -I i gdje je farmaceutski prihvatljiv derivat odabran od skupine: farmaceutski prihvatljivih soli, slovata, radiomarkiranih derivata, stereoizomera, enantiomera, dijastereoizomera, drugih stereoizomerskih oblika, racemičnih smjesa, geometrijskih izomera i/ili tautomera.
2. Spoj prema zahtjevu 1, naznačen time da svaki Y je O.
3. Spoj prema bilo kojem zahtjevu od 1 do 2, naznačen time da je R3 odabran od:
(a) -C(O)OV1; ili
(b) -C(O)N(V1)2; ili
(c) -(C1-C2)alkila supstituiranog sa supstituentom odabranim od -NHS(O)2W1, -C(O)OV1, i -C(O)N(V1)2; ili
(d) –H.
4. Spoj prema bilo kojem zahtjevu od 1 do 3, naznačen time da R3 je -H.
5. Spoj prema bilo kojem zahtjevu od 1 do 4, naznačen time da Z je veza i -R1 je odabran od:
[image]
6. Spoj prema zahtjevu 5, naznačen time da je R1 odabran of formule (i), R11 je - H, i m je 5.
7. Spoj prema zahtjevu 6, naznačen time da p je 0 i R1 je ciklooktil ili ciklooktenil.
8. Spoj prema zahtjevu 5, naznačen time da je R1 odabran od formule (i), R11 je -H, i m je 3.
9. Spoj prema zahtjevu 8, naznačen time da p je 1 i R8 je -(C1-C4)alkil.
10. Spoj prema zahtjevu 8, naznačen time da R8 je izo-propil.
11. Spoj prema zahtjevu 5, naznačen time da je R1 odabran od formule (iii) i R11 je -H.
12. Spoj prema zahtjevu 11, naznačen time da p je 0 i j + k = 1.
13. Spoj prema bilo kojem zahtjevu od 1 do 12, naznačen time da A-B zajedno formiraju (C2-C6)most, koji se nesupstituiran ili supstituiran s 1, 2 ili 3 neovisno odabrane skupine R8, i čiji most opcionalno sadrži -HC=CH unutar (C2-C6)mosta.
14. Spoj prema zahtjevu 13, naznačen time da A-B zajedno formiraju (C2)most, -HC=CH- most, ili (C3)most.
15. Spoj prema bilo kojem zahtjevu od 1 do 14, naznačen time da a je 0.
16. Spoj prema bilo kojem zahtjevu od 1 do 14, naznačen time da a je 1 i R2 je - halo.
17. Spoj prema bilo kojem zahtjevu od 1 do 14, naznačen time da a je 1 i R2 je - F, -Cl ili -Br.
18. Spoj prema bilo kojem zahtjevu od 1 do 14, naznačen time da a je 1 i R2 je - F.
19. Spoj prema zahtjevu 1, naznačen time da je
[image]
[image]
20. Sastav koji sadrži učinkovitu količinu spoja ili farmaceutski prihvatljivog derivata spoja prema bilo kojem zahtjevu od 1 do 19 i farmaceutski prihvatljivog nosača ili ekscipijensa, naznačen time da je farmaceutski prihvatljiv derivat odabran iz skupine: farmaceutski prihvatljivih soli, slovata, radiomarkiranih derivata, stereoizomera, enantiomera, dijastereoizomera, drugih stereoizomerskih oblika, racemičnih smjesa, geometrijskih izomera i/ili tautomera.
21. In vitro metoda za moduliranje funkcije ORL-1 receptora u stanicama, koja sadrži dolaženje u kontakt sa stanicom koja može in vitro eksprimirati ORL-1 receptor pomoću učinkovite količine spoja ili farmaceutski prihvatljivog derivata spoja prema bilo kojem zahtjevu od 1 do 19, naznačena time da je farmaceutski prihvatljiv derivat odabran iz skupine: farmaceutski prihvatljivih soli, slovata, radiomarkiranih derivata, stereoizomera, enantiomera, dijastereoizomera, drugih stereoizomerskih oblika, racemičnih smjesa, geometrijskih izomera i/ili tautomera.
22. Metoda prema zahtjevu 21, naznačena time da spoj ili farmaceutski prihvatljiv derivat spoja djeluje kao agonist ORL-1 receptora.
23. Metoda prema zahtjevu 21, naznačena time da spoj ili farmaceutski prihvatljiv derivat spoja djeluje kao antagonist ORL-1 receptora.
24. Upotreba spoja prema bilo kojem zahtjevu od 1 do 19, naznačena time da je za proizvodnju lijeka korisnog za liječenje boli, poremećaja pamćenja, pretilosti, konstipacije, urinarne inkontinencije, anksioznosti, kašlja, dijareje, visokog krvnog tlaka, epilepsije, anoreksije/kaheksije, ili zloupotrebe droge kod životinja.
25. Oprema koja sadrži posudu koja sadrži učinkovitu količinu spoja ili farmaceutski prihvatljivog derivata spoja prema bilo kojem zahtjevu od 1 do 19, naznačena time da je farmaceutski prihvatljiv derivat odabran iz skupine: farmaceutski prihvatljivih soli, slovata, radiomarkiranih derivata, stereoizomera, enantiomera, dijastereoizomera, drugih stereoizomerskih oblika, racemičnih smjesa, geometrijskih izomera i/ili tautomera.
26. Metoda za pripremu sastava koja sadrži korak umješavanja spoja ili farmaceutski prihvatljivog derivata spoja prema bilo kojem zahtjevu od 1 do 19 i farmaceutski prihvatljivog nosača ili ekscipijensa, naznačena time da je farmaceutski prihvatljiv derivat odabran iz skupine: farmaceutski prihvatljivih soli, solvata, radiomarkiranih derivata, stereoizomera, enantiomera, dijastereoizomera, drugih stereoizomerskih oblika, racemičnih smjesa, geometrijskih izomera i/ili tautomera.
27. Spoj prema bilo kojem zahtjevu od 1 do 19, naznačen time da je za upotrebu kao lijek.
28. Spoj prema bilo kojem zahtjevu od 1 do 19, naznačen time da je za upotrebu u liječenju boli, poremećaja pamćenja, pretilosti, konstipacije, urinarne inkontinencije, anksioznosti, kašlja, dijareje, visokog krvnog tlaka, epilepsije, anoreksije/kaheksije, ili zloupotrebe droge kod životinja.
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- 2008-01-15 WO PCT/US2008/051096 patent/WO2008089201A2/en active Application Filing
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