RU2006134025A - Производные пиперидиналкилкарбаматов, их получение и их применение в качестве ингибиторов фермента faah - Google Patents
Производные пиперидиналкилкарбаматов, их получение и их применение в качестве ингибиторов фермента faah Download PDFInfo
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- RU2006134025A RU2006134025A RU2006134025/04A RU2006134025A RU2006134025A RU 2006134025 A RU2006134025 A RU 2006134025A RU 2006134025/04 A RU2006134025/04 A RU 2006134025/04A RU 2006134025 A RU2006134025 A RU 2006134025A RU 2006134025 A RU2006134025 A RU 2006134025A
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- -1 of piperidine alkyl carbamates Chemical class 0.000 title claims abstract 20
- 238000004519 manufacturing process Methods 0.000 title claims 3
- 101000918494 Homo sapiens Fatty-acid amide hydrolase 1 Proteins 0.000 title claims 2
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract 4
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims abstract 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract 3
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000002541 furyl group Chemical group 0.000 claims abstract 2
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract 2
- 125000001041 indolyl group Chemical group 0.000 claims abstract 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims abstract 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims abstract 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims abstract 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims abstract 2
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 2
- 239000001301 oxygen Substances 0.000 claims abstract 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract 2
- 125000004076 pyridyl group Chemical group 0.000 claims abstract 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims abstract 2
- 229910052717 sulfur Inorganic materials 0.000 claims abstract 2
- 125000004434 sulfur atom Chemical group 0.000 claims abstract 2
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims abstract 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract 2
- 125000001544 thienyl group Chemical group 0.000 claims abstract 2
- 125000001425 triazolyl group Chemical group 0.000 claims abstract 2
- 150000003839 salts Chemical class 0.000 claims 10
- 239000012453 solvate Substances 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 7
- 239000002253 acid Substances 0.000 claims 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000002947 alkylene group Chemical group 0.000 claims 3
- 125000004429 atom Chemical group 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 208000002193 Pain Diseases 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 230000001154 acute effect Effects 0.000 claims 2
- 125000004419 alkynylene group Chemical group 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 230000007170 pathology Effects 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- LORWOIVBXBTIRF-UHFFFAOYSA-N 3-(1-benzylpiperidin-4-yl)-1,3-oxazolidine-2,4-dione Chemical compound O=C1COC(=O)N1C1CCN(CC=2C=CC=CC=2)CC1 LORWOIVBXBTIRF-UHFFFAOYSA-N 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 208000030814 Eating disease Diseases 0.000 claims 1
- 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 208000019693 Lung disease Diseases 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 206010028813 Nausea Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 206010063897 Renal ischaemia Diseases 0.000 claims 1
- 206010046543 Urinary incontinence Diseases 0.000 claims 1
- 206010047700 Vomiting Diseases 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 125000004450 alkenylene group Chemical group 0.000 claims 1
- 230000000172 allergic effect Effects 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 238000005915 ammonolysis reaction Methods 0.000 claims 1
- 208000010668 atopic eczema Diseases 0.000 claims 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 235000014632 disordered eating Nutrition 0.000 claims 1
- 208000002173 dizziness Diseases 0.000 claims 1
- 206010015037 epilepsy Diseases 0.000 claims 1
- 208000030533 eye disease Diseases 0.000 claims 1
- 208000026278 immune system disease Diseases 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000002458 infectious effect Effects 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 230000008693 nausea Effects 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 claims 1
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 230000003071 parasitic effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 125000004001 thioalkyl group Chemical group 0.000 claims 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 1
- 125000005490 tosylate group Chemical group 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 230000008673 vomiting Effects 0.000 claims 1
- YBMFFLZLOZRFDD-UHFFFAOYSA-N 2,3-dihydrothieno[3,2-b]pyridine Chemical compound C1=CC=C2SCCC2=N1 YBMFFLZLOZRFDD-UHFFFAOYSA-N 0.000 abstract 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 abstract 1
- YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical compound C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 abstract 1
- 125000004306 triazinyl group Chemical group 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
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Abstract
1. Соединение, отвечающее формуле (I)в которойm означает целое число от 1 до 4;n означает целое число, равное 1, 2 или 3;o целое число, равное 1 или 2;A выбран из одной или нескольких групп X, Y и/или Z;X означает метиленовую группу, необязательно замещенную одной или двумя группами, представляющими C-алкил, C-циклоалкил или C-циклоалкил-C-алкилен;Y означает C-алкениленовую группу, необязательно замещенную одной или двумя группами, представляющими C-алкил, C-циклоалкил или C-циклоалкил-C-алкилен; или C-алкиниленовую группу;Z означает группу формулы:p означает целое число от 1 до 5;q и r означают целые числа и определены так, что r+q является числом от 1 до 5;B означает ковалентную связь или C-алкиленовую группу;G означает ковалентную связь, атом кислорода или серы или группу -CH(OH)-, CO, SO или SO;Rозначает группу R, необязательно замещенную одной или несколькими группами Rи/или R;Rозначает группу, выбранную из фуранила, пирролила, тиенила, оксазолила, изоксазолила, тиазолила, изотиазолила, имидазолила, пиразолила, тиадиазолила, изотиадиазолила, оксадиазолила, тиадиазолила, триазолила, тетразолила, фенила, пиридинила, пиридазинила, пиримидинила, пиразинила, триазинила, нафтила, хинолинила, тетрагидрохинолинила, изохинолинила, тетрагидроизохинолинила, фталазинила, хиназолинила, хиноксалинила, циннолинила, нафтиридинила, имидазопиримидинила, тиенопиримидинила, бензофуранила, дигидробензофуранила, бензотиенила, дигидробензотиенила, бензимидазолила, бензоксазолила, бензизоксазолила, бензотиазолила, бензизотиазолила, индолила, изоиндолила, индазолила, пирролопиридинила, фуропиридинила, дигидрофуропиридинила, тиенопиридинила, дигидротиенопириди
Claims (14)
1. Соединение, отвечающее формуле (I)
в которой
m означает целое число от 1 до 4;
n означает целое число, равное 1, 2 или 3;
o целое число, равное 1 или 2;
A выбран из одной или нескольких групп X, Y и/или Z;
X означает метиленовую группу, необязательно замещенную одной или двумя группами, представляющими C1-6-алкил, C3-7-циклоалкил или C3-7-циклоалкил-C1-3-алкилен;
Y означает C2-алкениленовую группу, необязательно замещенную одной или двумя группами, представляющими C1-6-алкил, C3-7-циклоалкил или C3-7-циклоалкил-C1-3-алкилен; или C2-алкиниленовую группу;
Z означает группу формулы:
p означает целое число от 1 до 5;
q и r означают целые числа и определены так, что r+q является числом от 1 до 5;
B означает ковалентную связь или C1-6-алкиленовую группу;
G означает ковалентную связь, атом кислорода или серы или группу -CH(OH)-, CO, SO или SO2;
R1 означает группу R4, необязательно замещенную одной или несколькими группами R5 и/или R6;
R4 означает группу, выбранную из фуранила, пирролила, тиенила, оксазолила, изоксазолила, тиазолила, изотиазолила, имидазолила, пиразолила, тиадиазолила, изотиадиазолила, оксадиазолила, тиадиазолила, триазолила, тетразолила, фенила, пиридинила, пиридазинила, пиримидинила, пиразинила, триазинила, нафтила, хинолинила, тетрагидрохинолинила, изохинолинила, тетрагидроизохинолинила, фталазинила, хиназолинила, хиноксалинила, циннолинила, нафтиридинила, имидазопиримидинила, тиенопиримидинила, бензофуранила, дигидробензофуранила, бензотиенила, дигидробензотиенила, бензимидазолила, бензоксазолила, бензизоксазолила, бензотиазолила, бензизотиазолила, индолила, изоиндолила, индазолила, пирролопиридинила, фуропиридинила, дигидрофуропиридинила, тиенопиридинила, дигидротиенопиридинила, имидазопиридинила, пиразолопиридинила, оксазолопиридинила, изоксазолопиридинила, тиазолопиридинила;
R5 означает атом галогена, группу циано, нитро, гидроксильную, C1-6-алкил, C1-6-алкокси, C1-6-тиоалкил, C1-6-фторалкил, C1-6-фторалкокси, C1-6-фтортиоалкил, C3-7-циклоалкил, C3-7-циклоалкил-C1-3-алкилен, NR7R8, NR7COR8, NR7CO2R8, NR7SO2R8, COR7, CO2R7, CONR7R8, SO2R7, SO2NR7R8 или -O-(C1-3-алкилен)-O-;
R6 означает фенильную группу, фенилокси, бензилокси, пиридинил, пиразинил, пиридазинил, пиримидинил или пиримидинилокси; причем группа или группы R6 могут быть замещены одной или несколькими группами R5, одинаковыми или отличающимися друг от друга;
R7 и R8 независимо друг от друга означают атом водорода или C1-6-алкильную группу, или вместе с атомом или атомами, с которыми они связаны, образуют цикл, выбранный из азетидинового, пирролидинового, пиперидинового, морфолинового, тиоморфолинового, азепинового или пиперазинового цикла, причем этот цикл необязательно замещен С1-6-алкильной или бензильной группой;
R2 означает атом водорода или C1-6-алкильную группу;
R3 означает атом водорода или группу C1-6-алкил, C3-7-циклоалкил, C3-7-циклоалкил-C1-3-алкилен;
в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата.
2. Соединение формулы (I) по п.1, отличающееся тем, что
m означает целое число от 1 до 4;
n означает целое число, равное 1 или 2;
o целое число, равное 1 или 2;
A выбран из одной или нескольких групп X и/или Y;
X означает метиленовую группу, необязательно замещенную одной или двумя C1-6-алкильными группами;
Y означает C2-алкиниленовую группу;
B означает ковалентную связь или C1-6-алкиленовую группу;
G означает ковалентную связь или атом кислорода;
R1 означает группу R4, необязательно замещенную одной или несколькими группами R5 и/или R6;
R4 означает группу, выбранную из оксазолила, изоксазолила, тиазолила, фенила, пиридинила, нафтила, хинолинила, изохинолинила;
R5 означает атом галогена, группу циано, NR7R8, группу C1-6-алкил, C1-6-алкокси, C1-6-фторалкил или C1-6-фторалкокси;
R6 означает фенильную группу, фенилокси или пиримидинилокси; причем группа или группы R6 могут быть замещены одной или несколькими группами R5, одинаковыми или отличающимися друг от друга;
R7 и R8 независимо друг от друга означают C1-6-алкильную группу;
R2 означает атом водорода или C1-6-алкильную группу;
R3 означает атом водорода или группу C1-6-алкил, C3-7-циклоалкил, C3-7-циклоалкил-C1-3-алкилен;
в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата
3. Соединение формулы (I) по п.1 или 2, отличающееся тем, что m означает целое число, равное 1 или 2; в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата.
4. Соединение формулы (I) по п.1 или 2, отличающееся тем, что n равно 2; o равно 2; в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата.
5. Соединение формулы (I) по п.1 или 2, отличающееся тем, что R1 означает группу R4, необязательно замещенную одной или несколькими группами R5 и/или R6;
R4 означает группу, выбранную из оксазолила, изоксазолила, фенила или нафтила;
R5 означает атом галогена, группу циано, NR7R8, группу C1-6-алкил, C1-6-алкокси, C1-6-фторалкил или C1-6-фторалкокси;
R6 означает фенильную группу, фенилокси или пиримидинилокси; причем группа или группы R6 могут быть замещены одной или несколькими группами R5, одинаковыми или отличающимися друг от друга;
R7 и R8 независимо друг от друга означают C1-6-алкильную группу;
в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата.
6. Соединение формулы (I) по п.1 или 2, отличающееся тем, что
R2 означает атом водорода;
R3 означает атом водорода или C1-6-алкильную группу;
в состоянии основания, кислотно-аддитивной соли, гидрата или сольвата.
7. Способ получения соединения формулы (I) по любому из пп.1-6, включающий стадию, состоящую в превращении оксазолидиндиона общей формулы (IIa)
в которой A, B, G, R1, R2, m, n и o определены в формуле (I) по п.1,
протекающем при аммонолизе амином общей формулы R3NH2, в которой R3 определен в формуле (I) по п.1.
8. Способ получения соединения формулы (I) по любому из п.п. с 1 по 6, включающий стадию, состоящую в превращении производного карбамата-амида общей формулы (Ia)
в которой B, R2, R3, n и o определены в формуле (I) по п.1,
протекающем в ходе реакции с производным общей формулы (III)
в которой W означает мезилатную, тозилатную группу или атом хлора, брома или йода, и m, G, A и R1 определены в формуле(I) по п.1.
11. Фармацевтическая композиция, содержащая по меньшей мере одно соединение формулы (I) по любому из пп.1-6 в состоянии фармацевтически приемлемого основания, соли, гидрата или сольвата и необязательно один или несколько фармацевтически приемлемых эксципиентов.
12. Соединение формулы (I) по любому из пп.1-6 в виде фармацевтически приемлемого основания, соли, гидрата или сольвата для его применения в качестве лекарственного средства.
13. Применение соединения формулы (I) по любому из пп.1-6 в виде фармацевтически приемлемого основания, соли, гидрата или сольвата, для получения лекарственного средства, предназначенного для предупреждения или лечения патологии, в которую вовлечены эндогенные каннабиоиды и/или любые другие субстраты, метаболизированные ферментом FAAH.
14. Применение соединения формулы (I) по любому из пп.1-6 в состоянии фармацевтически приемлемого основания, соли, гидрата или сольвата для получения лекарственного средства, предназначенного для предупреждения или лечения острых или хронических болей, головокружений, рвоты, тошноты, нарушений пищевого поведения, неврологических и психиатрических патологий, острых или хронических нейродегенеративных заболеваний, эпилепсии, нарушений сна, сердечно-сосудистых заболеваний, почечной ишемии, рака, расстройств иммунной системы, аллергических заболеваний, инфекционных паразитарных, вирусных или бактериальных заболеваний, воспалительных заболеваний, остеопороза, глазных болезней, болезней легких, желудочно-кишечных заболеваний или недержания мочи.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0401952A FR2866885B1 (fr) | 2004-02-26 | 2004-02-26 | Derives de piperidinylalkylcarbamates, leur prepation et leur application en therapeutique |
| FR0401952 | 2004-02-26 |
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| RU2006134025A true RU2006134025A (ru) | 2008-04-10 |
| RU2384569C2 RU2384569C2 (ru) | 2010-03-20 |
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| EP (1) | EP1720550B1 (ru) |
| JP (1) | JP4796046B2 (ru) |
| KR (1) | KR20060134081A (ru) |
| CN (1) | CN1921858A (ru) |
| AR (1) | AR047818A1 (ru) |
| AT (1) | ATE428417T1 (ru) |
| AU (1) | AU2005224140B2 (ru) |
| BR (1) | BRPI0508072A (ru) |
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| CY (1) | CY1109231T1 (ru) |
| DE (1) | DE602005013923D1 (ru) |
| DK (1) | DK1720550T3 (ru) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2866884B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-piperidinecarboxylates, leur preparation et leur application en therapeutique |
| FR2866886B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-akylcarbamates, leur preparation et leur application en therapeutique |
| FR2866888B1 (fr) * | 2004-02-26 | 2006-05-05 | Sanofi Synthelabo | Derives de alkylpiperazine- et alkylhomopiperazine- carboxylates, leur preparation et leur application en therapeutique |
| US7541359B2 (en) | 2005-06-30 | 2009-06-02 | Janssen Pharmaceutica N.V. | N-heteroarylpiperazinyl ureas as modulators of fatty acid amide hydrolase |
| US20090111778A1 (en) * | 2005-11-18 | 2009-04-30 | Richard Apodaca | 2-Keto-Oxazoles as Modulators of Fatty Acid Amide Hydrolase |
| WO2007070760A2 (en) | 2005-12-15 | 2007-06-21 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| US7935715B2 (en) | 2006-07-28 | 2011-05-03 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| MX2009002888A (es) | 2006-09-25 | 2009-03-31 | Boehringer Ingelheim Int | Compuestos que modulan el receptor cb2. |
| CA2704684A1 (en) | 2007-11-07 | 2009-05-14 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| CA2730037A1 (en) | 2008-07-10 | 2010-01-14 | Boehringer Ingelheim International Gmbh | Sulfone compounds which modulate the cb2 receptor |
| PE20110397A1 (es) | 2008-09-25 | 2011-07-01 | Boehringer Ingelheim Int | Compuestos que modulan selectivamente el receptor cb2 |
| FR2941696B1 (fr) * | 2009-02-05 | 2011-04-15 | Sanofi Aventis | Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| FR2945531A1 (fr) * | 2009-05-12 | 2010-11-19 | Sanofi Aventis | Derives de 7-aza-spiro°3,5!nonane-7-carboxylates, leur preparation et leur application en therapeutique |
| US8299103B2 (en) | 2009-06-15 | 2012-10-30 | Boehringer Ingelheim International Gmbh | Compounds which selectively modulate the CB2 receptor |
| JP5756800B2 (ja) | 2009-06-16 | 2015-07-29 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Cb2受容体を調節するアゼチジン2−カルボキサミド誘導体 |
| EP2480544A1 (en) | 2009-09-22 | 2012-08-01 | Boehringer Ingelheim International GmbH | Compounds which selectively modulate the cb2 receptor |
| EP2523936A1 (en) | 2010-01-15 | 2012-11-21 | Boehringer Ingelheim International GmbH | Compounds which modulate the cb2 receptor |
| US8329735B2 (en) | 2010-03-05 | 2012-12-11 | Boehringer Ingelheim International Gmbh | Tetrazole compounds which selectively modulate the CB2 receptor |
| WO2012012307A1 (en) | 2010-07-22 | 2012-01-26 | Boehringer Ingelheim International Gmbh | Sulfonyl compounds which modulate the cb2 rece |
| EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
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| DE3235565A1 (de) * | 1982-09-25 | 1984-03-29 | Boehringer Ingelheim KG, 6507 Ingelheim | Piperidinderivate, ihre herstellung und verwendung |
| RU2216540C2 (ru) * | 1997-11-18 | 2003-11-20 | Тейджин Лимитед | Производные циклических аминов, способ ингибирования |
| CA2308850C (en) * | 1997-11-24 | 2007-07-10 | The Scripps Research Institute | Inhibitors of gap junction communication |
| JP2004532229A (ja) * | 2001-04-27 | 2004-10-21 | ブリストル−マイヤーズ スクイブ カンパニー | 脂肪酸アミド加水分解酵素阻害剤 |
| PL373970A1 (en) * | 2002-02-08 | 2005-09-19 | Bristol-Myers Squibb Company | (oxime)carbamoyl fatty acid amide hydrolase inhibitors |
| FR2843964B1 (fr) * | 2002-08-29 | 2004-10-01 | Sanofi Synthelabo | Derives de dioxane-2-alkylcarbamates, leur preparation et leur application en therapeutique |
| FR2850377B1 (fr) * | 2003-01-23 | 2009-02-20 | Sanofi Synthelabo | Derives d'arylalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2854633B1 (fr) * | 2003-05-07 | 2005-06-24 | Sanofi Synthelabo | Derives de piperidinyl-et piperazinyl-alkylcarbamates, leur preparation et leur application en therapeutique |
| FR2860514A1 (fr) * | 2003-10-03 | 2005-04-08 | Sanofi Synthelabo | Derives d'arylalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2866886B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-akylcarbamates, leur preparation et leur application en therapeutique |
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Also Published As
| Publication number | Publication date |
|---|---|
| SI1720550T1 (sl) | 2009-10-31 |
| DE602005013923D1 (de) | 2009-05-28 |
| ES2325376T3 (es) | 2009-09-02 |
| MA28366A1 (fr) | 2006-12-01 |
| US7781590B2 (en) | 2010-08-24 |
| AU2005224140B2 (en) | 2010-12-02 |
| WO2005089759A1 (fr) | 2005-09-29 |
| CY1109231T1 (el) | 2014-07-02 |
| BRPI0508072A (pt) | 2007-07-17 |
| PT1720550E (pt) | 2009-06-04 |
| HRP20090294T1 (en) | 2009-06-30 |
| US20100279998A1 (en) | 2010-11-04 |
| CA2554608A1 (fr) | 2005-09-29 |
| AU2005224140A1 (en) | 2005-09-29 |
| DK1720550T3 (da) | 2009-08-10 |
| IL177534A (en) | 2011-01-31 |
| PL1720550T3 (pl) | 2009-09-30 |
| RU2384569C2 (ru) | 2010-03-20 |
| IL177534A0 (en) | 2006-12-10 |
| JP2007524706A (ja) | 2007-08-30 |
| US20070021403A1 (en) | 2007-01-25 |
| NZ550007A (en) | 2010-06-25 |
| ATE428417T1 (de) | 2009-05-15 |
| EP1720550A1 (fr) | 2006-11-15 |
| CN1921858A (zh) | 2007-02-28 |
| FR2866885B1 (fr) | 2007-08-31 |
| AR047818A1 (es) | 2006-02-22 |
| EP1720550B1 (fr) | 2009-04-15 |
| KR20060134081A (ko) | 2006-12-27 |
| JP4796046B2 (ja) | 2011-10-19 |
| FR2866885A1 (fr) | 2005-09-02 |
| ZA200606964B (en) | 2008-01-30 |
| TW200529816A (en) | 2005-09-16 |
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