HRP20110694T1 - Novi spojevi kao modulatori opioidnog receptora - Google Patents
Novi spojevi kao modulatori opioidnog receptora Download PDFInfo
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- HRP20110694T1 HRP20110694T1 HR20110694T HRP20110694T HRP20110694T1 HR P20110694 T1 HRP20110694 T1 HR P20110694T1 HR 20110694 T HR20110694 T HR 20110694T HR P20110694 T HRP20110694 T HR P20110694T HR P20110694 T1 HRP20110694 T1 HR P20110694T1
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- Prior art keywords
- alkyl
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- phenyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract 49
- 102000003840 Opioid Receptors Human genes 0.000 title 1
- 108090000137 Opioid Receptors Proteins 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract 55
- 125000003118 aryl group Chemical group 0.000 claims abstract 53
- 125000001424 substituent group Chemical group 0.000 claims abstract 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 47
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 37
- -1 hydroxy, cyano, amino Chemical group 0.000 claims abstract 37
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 33
- 239000001257 hydrogen Substances 0.000 claims abstract 33
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 17
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 49
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 34
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 17
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 16
- 125000003545 alkoxy group Chemical group 0.000 claims 16
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 15
- 229910052736 halogen Inorganic materials 0.000 claims 15
- 150000002367 halogens Chemical class 0.000 claims 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 14
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 14
- 229910052799 carbon Inorganic materials 0.000 claims 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 13
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims 12
- 125000002541 furyl group Chemical group 0.000 claims 11
- 125000004076 pyridyl group Chemical group 0.000 claims 11
- 208000002193 Pain Diseases 0.000 claims 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 10
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 229910052757 nitrogen Inorganic materials 0.000 claims 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 9
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 8
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims 6
- 125000001153 fluoro group Chemical group F* 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 125000004104 aryloxy group Chemical group 0.000 claims 5
- 125000001246 bromo group Chemical group Br* 0.000 claims 5
- 125000005241 heteroarylamino group Chemical group 0.000 claims 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims 5
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 4
- 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 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 4
- 125000000304 alkynyl group Chemical group 0.000 claims 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 4
- 125000001769 aryl amino group Chemical group 0.000 claims 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims 3
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims 3
- 230000001404 mediated effect Effects 0.000 claims 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 3
- 125000002950 monocyclic group Chemical group 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 2
- 125000006602 (C1-C3) alkylsulfonylamino group Chemical group 0.000 claims 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- 206010012735 Diarrhoea Diseases 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 208000004296 neuralgia Diseases 0.000 claims 2
- 208000021722 neuropathic pain Diseases 0.000 claims 2
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
- QFNHIDANIVGXPE-UHFFFAOYSA-N 5-[[[2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)propanoyl]-[1-(5-phenyl-1h-imidazol-2-yl)ethyl]amino]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN(C(=O)C(N)CC=1C(=CC(=CC=1C)C(N)=O)C)C(C)C1=NC(C=2C=CC=CC=2)=CN1 QFNHIDANIVGXPE-UHFFFAOYSA-N 0.000 claims 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 208000006561 Cluster Headache Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 206010010774 Constipation Diseases 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- 206010027603 Migraine headaches Diseases 0.000 claims 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims 1
- 206010054048 Postoperative ileus Diseases 0.000 claims 1
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 claims 1
- 208000026137 Soft tissue injury Diseases 0.000 claims 1
- 208000037386 Typhoid Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 108700023159 delta Opioid Receptors Proteins 0.000 claims 1
- 102000048124 delta Opioid Receptors Human genes 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
- 230000004899 motility Effects 0.000 claims 1
- 102000051367 mu Opioid Receptors Human genes 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 210000001428 peripheral nervous system Anatomy 0.000 claims 1
- 208000037821 progressive disease Diseases 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 206010044652 trigeminal neuralgia Diseases 0.000 claims 1
- 201000008297 typhoid fever Diseases 0.000 claims 1
- 108020001612 μ-opioid receptors Proteins 0.000 claims 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/417—Imidazole-alkylamines, e.g. histamine, phentolamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
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- A61K9/20—Pills, tablets, discs, rods
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
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- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
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Abstract
Spoj formule (I) naznačen time da: R1 je izabran iz skupine koju čine vodik, C1-6alkil, cikloalkil, heterociklil, aril(C1-6)alkil, i heteroaril(C1-6)alkil; pri čemu kada R1 je fenil(C1-6)alkil, fenil je proizvoljno fuzioniran na heterociklil ili cikloalkil; pri čemu kada R1 je C1-2alkil, navedeni C1-2alkil je proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkoksi, aril, cikloalkil, heterociklil, hidroksi, cijano, amino,
Claims (45)
1. Spoj formule (I)
[image]
naznačen time da:
R1 je izabran iz skupine koju čine vodik, C1-6alkil, cikloalkil, heterociklil, aril(C1-6)alkil, i heteroaril(C1-6)alkil;
pri čemu kada R1 je fenil(C1-6)alkil, fenil je proizvoljno fuzioniran na heterociklil ili cikloalkil;
pri čemu kada R1 je C1-2alkil, navedeni C1-2alkil je proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkoksi, aril, cikloalkil, heterociklil, hidroksi, cijano, amino, C1-6alkilamino, (C1-6alkil)2amino, trifluorometil, te karboksi;
te nadalje, pri čemu kada R1 je C3-6alkil, navedeni C3-6alkil je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine C1-6alkoksi, aril, cikloalkil, heterociklil, hidroksi, cijano, amino, C1-6alkilamino, (C1-6alkil)2amino, trifluorometil, te karboksi;
pri čemu cikloalkil i heterociklil od C1-2alkila i C3-6alkila su proizvoljno supstituirani sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, hidroksi(C1-6)alkil, C1-6alkoksi, hidroksi, cijano, amino, C1-6alkilamino, (C1-6alkil)2amino, trifluorometil, karboksi, aril(C1-6)alkoksikarbonil, C1-6alkoksikarbonil, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, i aminosulfonil;
te nadalje, pri čemu cikloalkil i heterociklil od R1 su proizvoljno supstituirani sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, hidroksi(C1-6)alkil, C1-6alkoksi, hidroksi, cijano, amino, C1-6alkilamino, (C1-6alkil)2amino, trifluorometil, karboksi, aril(C1-6)alkoksikarbonil, C1-6alkoksikarbonil, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, i aminosulfonil;
osim toga, pri čemu arilni i heteroarilni dio od R1 supstituenata aril(C1-6)alkila i heteroaril(C1-6)alkila, su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil; hidroksi(C1-6)alkil; C1-6alkoksi; C6-10aril(C1-6)alkil; C6-10aril(C1-6)alkoksi; C6-10aril; heteroaril proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-4alkil, C1-4alkoksi, te karboksi; cikloalkil; heterociklil; C6-10ariloksi; heteroariloksi; cikloalkiloksi; heterocikliloksi; amino; C1-6alkilamino; (C1-6alkil)2amino; C3-6cikloalkilaminokarbonil; hidroksi(C1-6)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonilom; heterociklilkarbonil; karboksi; C1-6alkoksikarbonil; C1-6alkoksikarboniloksi; C1-6alkilkarbonil; C1-6alkilkarbonilamino; aminokarbonil; C1-6alkilaminokarbonil; (C1-6alkil)2aminokarbonil; cijano; halogen; trifluorometil; trifluorometoksi; i hidroksi;
uz uvjet da je ne više od jedan R11 supstituent izabran iz skupine koju čine C6-10aril(C1-6)alkil; C6-10aril(C1-6)alkoksi; C6-10aril; heteroaril proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-4alkil, C1-4alkoksi, te karboksi; cikloalkil; heterociklil; C6-10ariloksi; heteroariloksi; cikloalkiloksi; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonilom; heterociklilkarbonil, te heterocikliloksi;
R2 je vodik, C1-8alkil, hidroksi(C1-8)alkil, C6-10aril(C1-6)alkoksi(C1-6)alkil, ili C6-10aril(C1-8)alkil;
pri čemu C6-10aril skupina u supstituentima R2 koji sadrže C6-10aril je proizvoljno supstituirana sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, C1-6alkoksi, hidroksi, amino, C1-6alkilamino, (C1-6alkil)2amino, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, cijano, fluoro, kloro, bromo, trifluorometil, i trifluorometoksi; te pri čemu C1-6alkil i C1-6alkoksi supstituenti arila su proizvoljno supstituirani sa hidroksi, amino, C1-6alkilamino, (C1-6alkil)2amino, ili arilom;
A je a-1,
proizvoljno supstituiran s R3 i R5;
[image]
pri čemu A-B je N-C;
R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, aril, aril(C1-6)alkil, aril(C2-6)alkenil, aril(C2-6)alkinil, heteroaril, heteroaril(C1-6)alkil, heteroaril(C2-6)alkenil, heteroaril(C2-6)alkinil, amino, C1-6alkilamino, (C1-6alkil)2amino, arilamino, heteroarilamino, ariloksi, heteroariloksi, trifluorometil, i halogen; pri čemu aril, heteroaril, i aril i heteroaril od aril(C1-6)alkil, aril(C2-6)alkenil, aril(C2-6)alkinil, heteroaril(C1-6)alkil, heteroaril(C2-6)alkenil, heteroaril(C2-6)alkinil, arilamino, heteroarilamino, ariloksi, i heteroariloksi, su proizvoljno supstituirani sa jednim do pet fluoro supstituenta ili jednim do tri supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, hidroksi(C1-6)alkil, C1-6alkoksi, C6-10aril(C1-6)alkil, C6-10aril(C1-6)alkoksi, C6-10aril, C6-10ariloksi, heteroaril(C1-6)alkil, heteroaril(C1-6)alkoksi, heteroaril, heteroariloksi, C6-10arilamino, heteroarilamino, amino, C1-6alkilamino, (C1-6alkil)2amino, karboksi(C1-6)alkilamino, karboksi, C1-6alkilkarbonil, C1-6alkoksikarbonil, C1-6alkilkarbonilamino, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, karboksi(C1-6)alkilaminokarbonil, cijano, halogen, trifluorometil, trifluorometoksi, hidroksi, C1-6alkilsulfonil, i C1-6alkilsulfonilamino; uz uvjet da ne više od jednog takvog supstituenta na arilnom ili heteroarilnom dijelu od R3 je izabran iz skupine koju čine C6-10aril(C1-6)alkil, C6-10aril(C1-6)alkoksi, C6-10aril, C6-10ariloksi, heteroaril(C1-6)alkil, heteroaril(C1-6)alkoksi, heteroaril, heteroariloksi, C6-10arilamino, heteroarilamino;
te pri čemu C1-6alkil i C1-6alkil od aril(C1-6)alkila i heteroaril(C1-6)alkila su proizvoljno supstituirani sa supstituentom izabranim iz skupine koju čine hidroksi, karboksi, C1-4alkoksikarbonil, amino, C1-6alkilamino, (C1-6alkil)2amino, aminokarbonil, (C1-4)alkilaminokarbonil, di(C1-4)alkilaminokarbonil, aril, heteroaril, arilamino, heteroarilamino, ariloksi, heteroariloksi, aril(C1-4)alkoksi, i heteroaril(C1-4)alkoksi;
R4 je C6-10aril ili heteroaril izabran iz skupine koju čine furil, tienil, pirolil, oksazolil, tiazolil, imidazolil, pirazolil, piridinil, pirimidinil, pirazinil, indolil, izoindolil, indolinil, benzofuril, benzotienil, benzimidazolil, benztiazolil, benzoksazolil, kinolizinil, kinolinil, izokinolinil i kinazolinil;
pri čemu R4 je proizvoljno supstituiran sa jednim do tri R41 supstituenta nezavisno izabrana iz skupine koju čine (C1-6)alkil proizvoljno supstituiran sa amino, C1-6alkilamino, ili (C1-6alkil)2amino; (C1-6)alkoksi; fenil(C1-6)alkoksi; fenil(C1-6)alkilkarboniloksi pri čemu C1-6alkil je proizvoljno supstituiran sa amino; ne fuzionirani 5-člani-heteroaril(C1-6)alkilkarboniloksi; ne fuzionirani 5-člani-heteroaril; hidroksi; halogen; aminosulfonil; formilamino; aminokarbonil; C1-6alkilaminokarbonil
pri čemu (C1-6)alkil je proizvoljno supstituiran sa amino, C1-6alkilamino ili (C1-6alkil)2amino; (C1-6alkil)2aminokarbonil pri čemu svaki (C1-6)alkil je proizvoljno supstituiran sa amino, C1-6alkilamino ili (C1-6alkil)2amino; heterociklilkarbonil pri čemu heterociklil je 5-7 člani prsten koji sadrži dušik i navedeni heterociklil je spojen na karbonil ugljik preko atoma dušika; karboksi; ili cijano; i pri čemu fenilni dio od fenil(C1-6)alkilkarboniloksi je proizvoljno supstituiran sa (C1-6)alkil (C1-6)alkoksi, halogen, cijano, amino, ili hidroksi;
uz uvjet da ne više od jedan R41 je C1-6alkil supstituiran sa C1-6alkilamino ili (C1-6alkil)2amino; aminosulfonil; formilamino; aminokarbonil; C1-6alkilaminokarbonil; (C1-6alkil)2aminokarbonil; heterociklilkarbonil; hidroksi; karboksi; ili fenil- ili supstituent koji sadrži heteroaril-;
R5 je supstituent na atomu dušika prstena A izabran iz skupine koju čine vodik i C1-4alkil;
R6 je vodik ili C1-6alkil;
R7 je vodik ili C1-6alkil;
Ra i Rb su nezavisno izabrani iz skupine koju čine vodik, C1-6alkil, i C1-6alkoksikarbonil; alternativno, kada Ra i Rb svaki nisu vodik, Ra i Rb su proizvoljno uzeti zajedno sa dušikom na koji su oba spojeni da oblikuju pet do osam člani monociklički prsten;
L je O;
i njihovi farmaceutski prihvatljivi enantiomeri, diastereomeri, racemati i soli.
2. Spoj prema zahtjevu 1 naznačen time da R1 je izabran iz skupine koju čine vodik, C1-6alkil, aril(C1-4)alkil, i heteroaril(C1-4)alkil;
pri čemu arilni i heteroarilni dio od aril(C1-4)alkil i heteroaril(C1-4)alkil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-6alkoksi; heteroaril proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-4alkil, C1-4alkoksi, te karboksi; karboksi; C1-4alkoksikarbonil; C1-4alkoksikarboniloksi; aminokarbonil; C1-4alkilaminokarbonil; C3-6cikloalkilaminokarbonil; hidroksi(C1-6)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-6alkoksikarbonilom; heterociklilkarbonil; cijano; halogen; trifluorometoksi; i hidroksi; uz uvjet da ne više od jedan R11 je heteroaril (proizvoljno supstituiran sa jednim do dva C1-4alkil supstituenta); C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonil; ili heterociklilkarbonil.
3. Spoj prema zahtjevu 1 naznačen time da R1 je izabran iz skupine koju čine C6-10aril(C1-4)alkil, piridinil(C1-4)alkil, i furanil(C1-4)alkil; pri čemu C6-10aril, piridinil, i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-3alkoksi; tetrazolil; karboksi; C1-4alkoksikarbonil; aminokarbonil; C1-4alkilaminokarbonil; C1-3alkilaminokarbonil; C3-6cikloalkilaminokarbonil; hidroksi(C1-4)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonil; morfolin-4-ilkarbonil; cijano; halogen; i trifluorometoksil; uz uvjet da ne više od jedan R11 je C6-10arilaminokarbonil.
4. Spoj prema zahtjevu 1 naznačen time da R1 je izabran iz skupine koju čine fenil(C1-3)alkil, piridinil(C1-3)alkil, i furanil(C1-3)alkil; pri čemu fenil, piridinil, i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-3alkoksi; tetrazolil, C3-6cikloalkilaminokarbonil; hidroksi(C1-4)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonilom; morfolin-4-ilkarbonil; kloro; fluoro; trifluorometoksi; C1-4alkoksikarbonil; i karboksi; uz uvjet da ne više od jedan R11 je C6-10arilaminokarbonil.
5. Spoj prema zahtjevu 1 naznačen time da R1 je fenilmetil, piridinilmetil, ili furanilmetil; pri čemu fenil, piridinil, i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine metoksi; tetrazolil; ciklopropilaminokarbonil; (2-hidroksiet-1-il)aminokarbonil; metoksikarbonil; fenilaminokarbonil pri čemu fenil je proizvoljno supstituiran sa karboksi; morfolin-4-ilkarbonil; i karboksi.
6. Spoj prema zahtjevu 1 naznačen time da R2 je supstituent izabran iz skupine koju čine vodik, C1-4alkil, hidroksi(C1-4)alkil, i fenil(C1-6)alkoksi(C1-4)alkil; pri čemu navedeni fenil je proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-3alkil, C1-3alkoksi, hidroksi, cijano, fluoro, kloro, bromo, trifluorometil, i trifluorometoksi.
7. Spoj prema zahtjevu 1 naznačen time da R2 je supstituent izabran iz skupine koju čine vodik i C1-4alkil.
8. Spoj prema zahtjevu 1 naznačen time da R2 je vodik ili metil.
9. Spoj prema zahtjevu 1 naznačen time da R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, halogen, i aril; pri čemu aril je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine halogen, karboksi, aminokarbonil, C1-3alkilsulfonilamino, cijano, hidroksi, amino, C1-3alkilamino, i (C1-3alkil)2amino.
10. Spoj prema zahtjevu 1 naznačen time da R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine C1-3alkil, bromo i fenil; pri čemu fenil je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine kloro, fluoro, jodo, karboksi, aminokarbonil i cijano.
11. Spoj prema zahtjevu 1 naznačen time da R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine metil i fenil; pri čemu fenil je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine kloro i karboksi.
12. Spoj prema zahtjevu 1 naznačen time da najmanje jedan R3 supstituent je fenil.
13. Spoj prema zahtjevu 1 naznačen time da R3 je supstituent izabran iz skupine koju čine metil i fenil; pri čemu fenil je proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine kloro i karboksi.
14. Spoj prema zahtjevu 1 naznačen time da R4 je C6-10aril proizvoljno supstituiran sa jedan do tri R41 supstituenta nezavisno izabrana iz skupine koju čine (C1-3)alkil, (C1-6)alkoksi, fenil(C1-6)alkoksi; hidroksi; halogen; formilamino; aminokarbonil; C1-6alkilaminokarbonil; (C1-6alkil)2aminokarbonil; heterociklilkarbonil pri čemu heterociklil je 5-7 člani prsten koji sadrži dušik i navedeni heterociklil je spojen na karbonil ugljik preko atoma dušika; karboksi; i cijano; uz uvjet da ne više od jedan R41 supstituent je formilamino, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, heterociklilkarbonil, hidroksi, karboksi, ili supstituent koji sadrži fenil.
15. Spoj prema zahtjevu 1 naznačen time da R4 je fenil supstituiran sa jednim do tri R41 supstituenta nezavisno izabrana iz skupine koju čine (C1-3)alkil, (C1-3)alkoksi, fenil(C1-3)alkoksi, hidroksi, C1-6alkilaminokarbonil i aminokarbonil; uz uvjet da ne više od jedan R41 supstituent je aminokarbonil, C1-6alkilaminokarbonil, hidroksi ili supstituent koji sadrži fenil.
16. Spoj prema zahtjevu 1 naznačen time da R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonil ili aminokarbonil, te proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine metil, metoksi i benziloksi.
17. Spoj prema zahtjevu 1 naznačen time da R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonilom ili aminokarbonilom, te je proizvoljno supstituiran sa jednim do dva metil supstituenta.
18. Spoj prema zahtjevu 1 naznačen time da R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonilom ili aminokarbonilom i supstituiran na 2- poziciji i 6-poziciji sa metil supstituentima.
19. Spoj prema zahtjevu 1 naznačen time da R5 je vodik ili metil.
20. Spoj prema zahtjevu 1 naznačen time da R5 je vodik.
21. Spoj prema zahtjevu 1 naznačen time da R6 je vodik ili metil.
22. Spoj prema zahtjevu 1 naznačen time da R6 je vodik.
23. Spoj prema zahtjevu 1 naznačen time da R7 je vodik ili metil.
24. Spoj prema zahtjevu 1 naznačen time da R7 je vodik.
25. Spoj prema zahtjevu 1 naznačen time da Ra i Rb su nezavisno izabrani iz skupine koju čine vodik i C1-3alkil; ili kada Ra i Rb svaki nisu vodik, Ra i Rb su proizvoljno uzeti zajedno sa dušikom na koji su oba spojeni da oblikuju pet do sedam člani monociklički prsten.
26. Spoj prema zahtjevu 1 naznačen time da Ra i Rb su nezavisno vodik ili metil.
27. Spoj prema zahtjevu 1 naznačen time da Ra i Rb su svaki vodik.
28. Spoj prema zahtjevu 1 naznačen time da koji je prisutan u njihovim RR, SS, RS i SR konfiguracijama.
29. Spoj prema zahtjevu 1 naznačen time da je u njegovoj S,S konfiguraciji.
30. Spoj formule (Ia):
[image]
naznačen time da:
R1 je izabran iz skupine koju čine vodik, C1-6alkil, aril(C1-4)alkil i heteroaril(C1-4)alkil; pri čemu arilni i heteroarilni dio od aril(C1-4)alkil i heteroaril(C1-4)alkil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-6alkoksi; heteroaril proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-4alkil, C1-4alkoksi i karboksi; karboksi; C1-4alkoksikarbonil; C1-4alkoksikarboniloksi; aminokarbonil; C1-4alkilaminokarbonil; C3-6cikloalkilaminokarbonil; hidroksi(C1-6)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonil; heterociklilkarbonil; cijano; halogen; trifluorometoksi; i hidroksi; uz uvjet da ne više od jedan R11 je heteroaril (proizvoljno supstituiran sa jednim do dva C1-4alkil supstituenta); C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonilom; ili heterociklilkarbonil;
R2 je izabran iz skupine koju čine vodik, C1-4alkil, hidroksi(C1-4)alkil i fenil(C1-6)alkoksi(C1-4)alkil;
pri čemu navedeni fenil je proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine C1-3alkil, C1-3alkoksi, hidroksi, cijano, fluoro, kloro, bromo, trifluorometil i trifluorometoksi;
R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine C1-6alkil, halogen i aril; pri čemu aril je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine halogen, karboksi, aminokarbonil, C1-3alkilsulfonilamino, cijano, hidroksi, amino, C1-3alkilamino i (C1-3alkil)2amino;
R4je C6-10aril proizvoljno supstituiran sa jedan do tri R41 supstituenta nezavisno izabrana iz skupine koju čine (C1-3)alkil, (C1-6)alkoksi, fenil(C1-6)alkoksi; hidroksi; halogen; formilamino; aminokarbonil; C1-6alkilaminokarbonil; (C1-6alkil)2aminokarbonil; heterociklilkarbonil pri čemu heterociklil je 5-7 člani prsten koji sadrži dušik i navedeni heterociklil je spojen na karbonil ugljik preko atoma dušika; karboksi; i cijano; uz uvjet da ne više od jedan R41 supstituent je formilamino, aminokarbonil, C1-6alkilaminokarbonil, (C1-6alkil)2aminokarbonil, heterociklilkarbonil, hidroksi, karboksi ili supstituent koji sadrži fenil;
R5 je vodik ili metil;
Ra i Rb su nezavisno vodik ili C1-3alkil; ili, kada Ra i Rb svaki nisu vodik, Ra i Rb su proizvoljno uzeti zajedno sa dušikom na koji su oba spojeni da oblikuju pet do sedam člani monociklički prsten; i njihovi farmaceutski prihvatljivi enantiomeri, diastereomeri, racemati i soli.
31. Spoj formule (Ia) naznačen time da:
R1 je izabran iz skupine koju čine C6-10aril(C1-4)alkil, piridinil(C1-4)alkil i furanil(C1-4)alkil; pri čemu C6-10aril, piridinil i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine C1-3alkoksi; tetrazolil; aminokarbonil; C1-4alkilaminokarbonil; C1-3alkilaminokarbonil; C3-6cikloalkilaminokarbonil; hidroksi(C1-4)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonil; morfolin-4-ilkarbonil; cijano; halogen; trifluorometoksi; C1-4alkoksikarbonil; ili karboksi; uz uvjet da ne više od jedan R11 je C6-10arilaminokarbonil;
R2 je vodik ili C1-4alkil;
R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine C1-3alkil, bromo i fenil; pri čemu fenil je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine kloro, fluoro, karboksi, aminokarbonil i cijano;
R4 je fenil supstituiran sa jednim do tri supstituenta nezavisno izabrana iz skupine koju čine (C1-3)alkil, (C1-3)alkoksi, fenil(C1-3)alkoksi, hidroksi, C1-6alkilaminokarbonil i aminokarbonil; uz uvjet da ne više od jedan R41 supstituent je aminokarbonil, C1-6alkilaminokarbonil, hidroksi ili supstituent koji sadrži fenil;
R5 je vodik;
Ra i Rbsu nezavisno vodik ili metil; i njihovi farmaceutski prihvatljivi enantiomeri, diastereomeri, racemati i soli.
32. Spoj formule (Ia) naznačen time da:
R1 je izabran iz skupine koju čine fenil(C1-3)alkil, piridinil(C1-3)alkil i furanil(C1-3)alkil; pri čemu fenil, piridinil i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine je C1-6alkoksi; tetrazolil, C3-6cikloalkilaminokarbonil; hidroksi(C1-4)alkilaminokarbonil; C6-10arilaminokarbonil pri čemu C6-10aril je proizvoljno supstituiran sa karboksi ili C1-4alkoksikarbonil; morfolin-4-ilkarbonil; kloro; fluoro; trifluorometoksi; metoksikarbonil; i karboksi; uz uvjet da ne više od jedan R11 je C6-10arilaminokarbonil;
R2 je vodik ili metil;
R3 je jedan do dva supstituenta nezavisno izabrana iz skupine koju čine metil i fenil; pri čemu fenil je proizvoljno supstituiran s jednim do tri supstituenta nezavisno izabrana iz skupine koju čine kloro i karboksi;
R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonil ili aminokarbonil, te proizvoljno supstituiran sa jednim do dva supstituenta nezavisno izabrana iz skupine koju čine metil, metoksi i benziloksi;
R5 je vodik;
Ra i Rb su svaki vodik;
i njihovi farmaceutski prihvatljivi enantiomeri, diastereomeri, racemati i soli.
33. Spoj prema zahtjevu 32 naznačen time da R1 je fenilmetil, piridinilmetil ili furanilmetil; pri čemu fenil, piridinil i furanil su proizvoljno supstituirani sa jednim do tri R11 supstituenta nezavisno izabrana iz skupine koju čine metoksi, tetrazolil, ciklopropilaminokarbonil, (2-hidroksiet-1-il)aminokarbonil, fenilaminokarbonil pri čemu fenil je proizvoljno supstituiran sa karboksi, morfolin-4-ilkarbonil, metoksikarbonil i karboksi; uz uvjet da ne više od jedan R11 je fenilaminokarbonil.
34. Spoj prema zahtjevu 32 naznačen time da R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonil ili aminokarbonil, te proizvoljno supstituiran sa jednim do dva metil supstituenta.
35. Spoj prema zahtjevu 32 naznačen time da R4 je fenil supstituiran na 4-poziciji sa hidroksi, C1-3alkilaminokarbonil ili aminokarbonil i supstituiran na 2-poziciji i 6-poziciji sa metil supstituentima.
36. Spoj formule (Ib)
[image]
naznačen time da L je O i R1, R2, R3-1, R3-2, R5, Ra, Rb i R41 su zavisno izabrani iz skupine koju čine:
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
37. Spoj formule (Ic)
[image]
naznačen time da L je O i R1, R2, R3-1, R3-2, R5, Ra, Rb i R41 su zavisno izabrani iz skupine koju čine:
[image]
38. Spoj formule (Id)
[image]
pri čemu L je O i R1, R2, R3-1, R3-2, R5, Ra, Rb i R41 su zavisno izabrani iz skupine koju čine:
[image]
39. Spoj formule (Ie)
[image]
naznačen time da L je O i R1, R2, R3-1, R3-2, R5, Ra, Rb i R41 su zavisno izabrani iz skupine koju čine:
[image]
40. Spoj naznačen time da je izabran iz skupine koju čine
[image]
[image]
[image]
[image]
[image]
[image]
[image]
[image]
41. Spoj prema zahtjevu 1, naznačen time da spoj je 5-({[2-Amino-3-(4-karbamoil-2,6-dimetil-fenil)-propionil]-[1-(4-fenil-1H-imidazol-2-il)-etil]-amino}-metil)-2-metoksi-benzojeva kiselina ili njezina farmaceutski prihvatljiva sol.
42. Spoj prema zahtjevu 41, naznačen time da spoj je dihidrokloridna sol.
43. Pripravak naznačen time da koji sadrži spoj prema bilo kojem od zahtjeva 1 do 42 i farmaceutski prihvatljiv nosač.
44. Postupak za dobivanje pripravka naznačen time da se sastoji od miješanja spoja prema bilo kojem od zahtjeva 1 do 42 i farmaceutski prihvatljivog nosača.
45. Spoj prema bilo kojem od zahtjeva 1 do 42 ili pripravak prema zahtjevu 43 ili pripravak dobiven postupkom prema zahtjevu 44 naznačen time da je za uporabu kod liječenja ili ublažavanja poremećaja koji je posredovan sa δ- ili μ-opioidnim receptorom, kao što su: bol, naročito bol nastala posredovanjem središnjeg živčanog sustava, bol nastala posredovanjem perifernog živčanog sustava, bol povezana sa strukturalnom ozljedom ili ozljedom mekog tkiva, bol vezana uz upalu, bol povezana s progresivnom bolesti, neuropatska bol, akutna bol ili kronična bol, na primjer bol uzrokovana neuropatskim bolnim stanjima, dijabetičkom perifernom neuropatijom, post-herpetičkom neuralgijom, trigeminalnom neuralgijom, bolni sindromi nastali nakon udara ili cluster ili migrenske glavobolje ili gastrointestinalni poremećaj, naročito sindrom dijareje, poremećaj motiliteta kao što je prevladavajuća dijareja, prevladavajuća konstipacija, izmjenični sindrom crijevne nadraženosti, post-operativni ileus ili konstipacija ili sindromom iritabilnog crijeva, na primjer ulcerozni kolitis i Crohnova bolest.
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| HRP20150305TT HRP20150305T1 (hr) | 2004-03-15 | 2015-03-18 | Postupak za pripravu intermedijera spojeva korisnih kao modulatori opioid receptora |
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