BRPI0609790A2 - moduladores de tetrahidrotiopirano pirazol canabinóide - Google Patents

Info

Publication number

BRPI0609790A2

BRPI0609790A2 BRPI0609790-1A BRPI0609790A BRPI0609790A2 BR PI0609790 A2 BRPI0609790 A2 BR PI0609790A2 BR PI0609790 A BRPI0609790 A BR PI0609790A BR PI0609790 A2 BRPI0609790 A2 BR PI0609790A2

Authority

BR

Brazil

Prior art keywords

phenyl

pyrazol

tetrahydro

thiopyran

dichloro

Prior art date

2005-03-31

Links

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• -1 tetrahydrothiopyran pyrazole Chemical compound 0.000 title claims description 93
• 229930003827 cannabinoid Natural products 0.000 title abstract description 76
• 239000003557 cannabinoid Substances 0.000 title abstract description 76
• 150000001875 compounds Chemical class 0.000 claims abstract description 245
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 238
• 208000035475 disorder Diseases 0.000 claims abstract description 130
• 208000011580 syndromic disease Diseases 0.000 claims abstract description 116
• 238000000034 method Methods 0.000 claims abstract description 112
• 201000010099 disease Diseases 0.000 claims abstract description 108
• 230000001404 mediated effect Effects 0.000 claims abstract description 66
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 claims description 181
• 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 151
• 239000002253 acid Substances 0.000 claims description 146
• 239000000203 mixture Substances 0.000 claims description 116
• 125000000217 alkyl group Chemical group 0.000 claims description 100
• 125000003118 aryl group Chemical group 0.000 claims description 78
• 229910052736 halogen Inorganic materials 0.000 claims description 76
• 150000002367 halogens Chemical class 0.000 claims description 75
• 125000003545 alkoxy group Chemical group 0.000 claims description 72
• 125000000623 heterocyclic group Chemical group 0.000 claims description 59
• 238000002560 therapeutic procedure Methods 0.000 claims description 49
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 41
• 125000002947 alkylene group Chemical group 0.000 claims description 38
• 239000013066 combination product Substances 0.000 claims description 36
• 229940127555 combination product Drugs 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
• 239000003433 contraceptive agent Substances 0.000 claims description 33
• 239000001961 anticonvulsive agent Substances 0.000 claims description 31
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 30
• 229940124558 contraceptive agent Drugs 0.000 claims description 25
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 24
• 208000008589 Obesity Diseases 0.000 claims description 23
• 239000003814 drug Substances 0.000 claims description 23
• 235000020824 obesity Nutrition 0.000 claims description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 22
• 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 claims description 20
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• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 18
• 150000001412 amines Chemical class 0.000 claims description 18
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• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 16
• 101710187010 Cannabinoid receptor 1 Proteins 0.000 claims description 16
• 102100033868 Cannabinoid receptor 1 Human genes 0.000 claims description 16
• 239000000556 agonist Substances 0.000 claims description 16
• 125000004104 aryloxy group Chemical group 0.000 claims description 16
• KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical group C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 15
• 229960003965 antiepileptics Drugs 0.000 claims description 15
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 15
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 15
• 206010012601 diabetes mellitus Diseases 0.000 claims description 14
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• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
• FJYWNYLUZBMVKI-UHFFFAOYSA-N 3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-amine Chemical compound C1CCC2CN(N)CC21 FJYWNYLUZBMVKI-UHFFFAOYSA-N 0.000 claims description 13
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 claims description 13
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• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 11
• 239000002469 receptor inverse agonist Substances 0.000 claims description 11
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• 125000001118 alkylidene group Chemical group 0.000 claims description 10
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• 229960004394 topiramate Drugs 0.000 claims description 10
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 claims description 9
• 206010010904 Convulsion Diseases 0.000 claims description 9
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 9
• 230000019771 cognition Effects 0.000 claims description 9
• 229940125425 inverse agonist Drugs 0.000 claims description 9
• CBYXIIFIKSBHEY-UHFFFAOYSA-N 2,2,4-trimethylbicyclo[2.2.1]heptan-3-amine Chemical compound C1CC2(C)C(N)C(C)(C)C1C2 CBYXIIFIKSBHEY-UHFFFAOYSA-N 0.000 claims description 8
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 8
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• 239000002207 metabolite Substances 0.000 claims description 8
• XBWOPGDJMAJJDG-ZETCQYMHSA-N (1s)-1-cyclohexylethanamine Chemical compound C[C@H](N)C1CCCCC1 XBWOPGDJMAJJDG-ZETCQYMHSA-N 0.000 claims description 7
• 229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 claims description 7
• 208000005392 Spasm Diseases 0.000 claims description 7
• 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 201000009032 substance abuse Diseases 0.000 claims description 7
• 208000011117 substance-related disease Diseases 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 208000007101 Muscle Cramp Diseases 0.000 claims description 6
• 239000005557 antagonist Substances 0.000 claims description 6
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 230000002757 inflammatory effect Effects 0.000 claims description 6
• 230000006742 locomotor activity Effects 0.000 claims description 6
• 210000000056 organ Anatomy 0.000 claims description 6
• 231100000736 substance abuse Toxicity 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• FDFOQQGDKMJZPW-UHFFFAOYSA-N 1-cyclohexa-2,4-dien-1-ylethanamine Chemical compound CC(N)C1CC=CC=C1 FDFOQQGDKMJZPW-UHFFFAOYSA-N 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
• 208000010412 Glaucoma Diseases 0.000 claims description 5
• 230000008602 contraction Effects 0.000 claims description 5
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
• RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
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• 239000000583 progesterone congener Substances 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 claims description 3
• 102000018208 Cannabinoid Receptor Human genes 0.000 claims description 3
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• OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 3
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• SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical compound NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 claims description 3
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• 230000000391 smoking effect Effects 0.000 claims description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 claims description 2
• 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 2
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 2
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• 229940011871 estrogen Drugs 0.000 claims description 2
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• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 29
• PDNHLCRMUIGNBV-ZCFIWIBFSA-N (1r)-1-pyridin-2-ylethanamine Chemical compound C[C@@H](N)C1=CC=CC=N1 PDNHLCRMUIGNBV-ZCFIWIBFSA-N 0.000 claims 27
• 150000002431 hydrogen Chemical group 0.000 claims 16
• UOCYIXGKOTWCPB-VIFPVBQESA-N n-[(1s)-1-phenylethyl]-1h-pyrazole-5-carboxamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)C=1C=CNN=1 UOCYIXGKOTWCPB-VIFPVBQESA-N 0.000 claims 5
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