CA2756534A1 - Isothiazolo-pyrimidinedione derivatives as trpa1 modulators - Google Patents
Isothiazolo-pyrimidinedione derivatives as trpa1 modulators Download PDFInfo
- Publication number
- CA2756534A1 CA2756534A1 CA2756534A CA2756534A CA2756534A1 CA 2756534 A1 CA2756534 A1 CA 2756534A1 CA 2756534 A CA2756534 A CA 2756534A CA 2756534 A CA2756534 A CA 2756534A CA 2756534 A1 CA2756534 A1 CA 2756534A1
- Authority
- CA
- Canada
- Prior art keywords
- dimethyl
- dioxo
- acetamide
- pyrimidin
- thiazol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- CBFZADDDBQLSPS-UHFFFAOYSA-N [1,2]thiazolo[4,3-d]pyrimidine 2,2-dioxide Chemical class N1=CN=CC2=NS(=O)(=O)C=C21 CBFZADDDBQLSPS-UHFFFAOYSA-N 0.000 title description 2
- 101100482465 Caenorhabditis elegans trpa-1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 183
- 238000000034 method Methods 0.000 claims abstract description 133
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- -1 cyano, hydroxyl Chemical group 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 208000002193 Pain Diseases 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 238000010992 reflux Methods 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000001188 haloalkyl group Chemical group 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 7
- 208000004296 neuralgia Diseases 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 7
- 208000000094 Chronic Pain Diseases 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 150000005347 biaryls Chemical group 0.000 claims description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 208000021722 neuropathic pain Diseases 0.000 claims description 5
- 201000001119 neuropathy Diseases 0.000 claims description 5
- 230000007823 neuropathy Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- ZLSBGGFBYHZNRJ-UHFFFAOYSA-N n-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C(Cl)=C1 ZLSBGGFBYHZNRJ-UHFFFAOYSA-N 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 3
- 230000002917 arthritic effect Effects 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000003349 osteoarthritic effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 208000009935 visceral pain Diseases 0.000 claims description 3
- WMIAZCXMKZFMFT-UHFFFAOYSA-N 2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)-n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1 WMIAZCXMKZFMFT-UHFFFAOYSA-N 0.000 claims description 2
- ODCGQSLLUGLMSU-UHFFFAOYSA-N 2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-n-[4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC(F)=CC(C(F)(F)F)=C1 ODCGQSLLUGLMSU-UHFFFAOYSA-N 0.000 claims description 2
- OBMMAOIHXZHHJE-UHFFFAOYSA-N 2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)-n-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(C(F)(F)F)=C1 OBMMAOIHXZHHJE-UHFFFAOYSA-N 0.000 claims description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 208000008035 Back Pain Diseases 0.000 claims description 2
- 206010058019 Cancer Pain Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 2
- 206010011224 Cough Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000028389 Nerve injury Diseases 0.000 claims description 2
- 206010030216 Oesophagitis Diseases 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000008765 Sciatica Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 206010047700 Vomiting Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 201000003146 cystitis Diseases 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 208000000718 duodenal ulcer Diseases 0.000 claims description 2
- 230000009610 hypersensitivity Effects 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- YPLDZKGKWINHEO-UHFFFAOYSA-N n-[1-(4-bromophenyl)pyrazol-3-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(=N1)C=CN1C1=CC=C(Br)C=C1 YPLDZKGKWINHEO-UHFFFAOYSA-N 0.000 claims description 2
- OPLCKZVWSAXDFY-UHFFFAOYSA-N n-[1-(4-bromophenyl)pyrazol-3-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(=N1)C=CN1C1=CC=C(Br)C=C1 OPLCKZVWSAXDFY-UHFFFAOYSA-N 0.000 claims description 2
- FHXWGIBLDBVWKR-UHFFFAOYSA-N n-[3-(4-chlorophenyl)-1,2-oxazol-5-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(ON=1)=CC=1C1=CC=C(Cl)C=C1 FHXWGIBLDBVWKR-UHFFFAOYSA-N 0.000 claims description 2
- YFDODXYISNKXKN-UHFFFAOYSA-N n-[4-(2,4-dichloro-5-fluorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(Cl)C=C1Cl YFDODXYISNKXKN-UHFFFAOYSA-N 0.000 claims description 2
- HQTJKBGYEDGTEB-UHFFFAOYSA-N n-[4-(2,4-difluorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C=C1F HQTJKBGYEDGTEB-UHFFFAOYSA-N 0.000 claims description 2
- XRZOMCQELMQCEZ-UHFFFAOYSA-N n-[4-(3,4-difluorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(F)=C1 XRZOMCQELMQCEZ-UHFFFAOYSA-N 0.000 claims description 2
- KCZKVXKHCJRGLN-UHFFFAOYSA-N n-[4-(3,5-dichlorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC(Cl)=CC(Cl)=C1 KCZKVXKHCJRGLN-UHFFFAOYSA-N 0.000 claims description 2
- POXWZXDNVWIHJW-UHFFFAOYSA-N n-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC=C(Br)C=C1 POXWZXDNVWIHJW-UHFFFAOYSA-N 0.000 claims description 2
- FAEOCLUITYXFBQ-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C=C1 FAEOCLUITYXFBQ-UHFFFAOYSA-N 0.000 claims description 2
- XQMBHQKEVKETDZ-UHFFFAOYSA-N n-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C=C1 XQMBHQKEVKETDZ-UHFFFAOYSA-N 0.000 claims description 2
- LRBGOATYMAGCLX-UHFFFAOYSA-N n-[4-(4-cyclohexylphenyl)-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C(C=C1)=CC=C1C1CCCCC1 LRBGOATYMAGCLX-UHFFFAOYSA-N 0.000 claims description 2
- PYQZVIOQEOMABN-UHFFFAOYSA-N n-[4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1F PYQZVIOQEOMABN-UHFFFAOYSA-N 0.000 claims description 2
- KZQDZUKAGPBBST-UHFFFAOYSA-N n-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(C(F)(F)F)=C1F KZQDZUKAGPBBST-UHFFFAOYSA-N 0.000 claims description 2
- XCZDOORZBGHHNA-UHFFFAOYSA-N n-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(C(F)(F)F)=C1F XCZDOORZBGHHNA-UHFFFAOYSA-N 0.000 claims description 2
- YAVNENHABAPTST-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(C(F)(F)F)C(F)=C1 YAVNENHABAPTST-UHFFFAOYSA-N 0.000 claims description 2
- SVWZINJLIOWROA-UHFFFAOYSA-N n-[4-[3-chloro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(Cl)=C1 SVWZINJLIOWROA-UHFFFAOYSA-N 0.000 claims description 2
- VGIRVLGDGSLELS-UHFFFAOYSA-N n-[4-[3-chloro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC(Cl)=CC(C(F)(F)F)=C1 VGIRVLGDGSLELS-UHFFFAOYSA-N 0.000 claims description 2
- HZSPFWHTBFVEQD-UHFFFAOYSA-N n-[4-[4-(difluoromethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OC(F)F)C(F)=C1 HZSPFWHTBFVEQD-UHFFFAOYSA-N 0.000 claims description 2
- WVLJFLWKLNBOLE-UHFFFAOYSA-N n-[4-[4-(difluoromethoxy)-3-fluorophenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(SC=1)=NC=1C1=CC=C(OC(F)F)C(F)=C1 WVLJFLWKLNBOLE-UHFFFAOYSA-N 0.000 claims description 2
- RGXHZTKDEOKUAJ-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[3,4-d]pyrimidin-3-yl)acetamide Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=NSC=1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C(C(F)(F)F)=C1 RGXHZTKDEOKUAJ-UHFFFAOYSA-N 0.000 claims description 2
- VTBLEPLWRAMIAO-UHFFFAOYSA-N n-[5-(4-bromophenyl)-1,3,4-thiadiazol-2-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(S1)=NN=C1C1=CC=C(Br)C=C1 VTBLEPLWRAMIAO-UHFFFAOYSA-N 0.000 claims description 2
- CDMIAQZGBMCOOU-UHFFFAOYSA-N n-[5-(4-chlorophenyl)-1h-pyrazol-3-yl]-2-(5,7-dimethyl-4,6-dioxo-[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2SN=C1CC(=O)NC(NN=1)=CC=1C1=CC=C(Cl)C=C1 CDMIAQZGBMCOOU-UHFFFAOYSA-N 0.000 claims description 2
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
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- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003233 pyrroles Chemical class 0.000 claims description 2
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 12
- 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
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Classifications
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
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- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
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- Rheumatology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
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- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN665/MUM/2009 | 2009-03-23 | ||
| IN665MU2009 | 2009-03-23 | ||
| US17135509P | 2009-04-21 | 2009-04-21 | |
| US61/171,355 | 2009-04-21 | ||
| PCT/IB2010/000834 WO2010109328A1 (en) | 2009-03-23 | 2010-03-22 | Isothiazolo-pyrimidinedione derivatives as trpa1 modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2756534A1 true CA2756534A1 (en) | 2010-09-30 |
Family
ID=42236291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2756534A Abandoned CA2756534A1 (en) | 2009-03-23 | 2010-03-22 | Isothiazolo-pyrimidinedione derivatives as trpa1 modulators |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US8575178B2 (enExample) |
| EP (1) | EP2411397B1 (enExample) |
| JP (1) | JP2012521405A (enExample) |
| KR (1) | KR20120001746A (enExample) |
| CN (1) | CN102395592A (enExample) |
| AP (1) | AP2011005888A0 (enExample) |
| AU (1) | AU2010227224A1 (enExample) |
| BR (1) | BRPI1009372A2 (enExample) |
| CA (1) | CA2756534A1 (enExample) |
| DK (1) | DK2411397T3 (enExample) |
| EA (1) | EA201190191A1 (enExample) |
| ES (1) | ES2424340T3 (enExample) |
| IL (1) | IL215179A0 (enExample) |
| MX (1) | MX2011009821A (enExample) |
| PE (1) | PE20120764A1 (enExample) |
| PL (1) | PL2411397T3 (enExample) |
| PT (1) | PT2411397E (enExample) |
| SG (2) | SG174403A1 (enExample) |
| SI (1) | SI2411397T1 (enExample) |
| UA (1) | UA107342C2 (enExample) |
| WO (1) | WO2010109328A1 (enExample) |
| ZA (1) | ZA201107646B (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2010227225A1 (en) | 2009-03-23 | 2011-09-15 | Glenmark Pharmaceuticals, S.A. | Furopyrimidinedione derivatives as TRPA1 modulators |
| SG174402A1 (en) | 2009-03-23 | 2011-10-28 | Glenmark Pharmaceuticals Sa | Fused pyrimidine-dione derivatives as trpa1 modulators |
| US8592398B2 (en) | 2010-12-20 | 2013-11-26 | Glenmark Pharmaceuticals, S.A. | 2-amino-4-arylthiazole compounds as TRPA1 antagonists |
| EP2520566A1 (en) | 2011-05-06 | 2012-11-07 | Orion Corporation | New Pharmaceutical Compounds |
| RU2014100744A (ru) | 2011-06-13 | 2015-07-20 | Гленмарк Фармасьютикалс С.А. | Лечение респираторных нарушений с помощью trpa1 антагонистов |
| WO2012176105A1 (en) | 2011-06-22 | 2012-12-27 | Glenmark Pharmaceuticals Sa | Pharmaceutical composition comprising a trpa1 antagonist and a leukotriene receptor antagonist |
| JP2014517062A (ja) | 2011-06-22 | 2014-07-17 | グレンマーク ファーマシューティカルズ， エセ．アー． | ＴＲＰＡ１アンタゴニスト及びβ２アゴニストを含む医薬組成物 |
| WO2013014597A1 (en) | 2011-07-25 | 2013-01-31 | Glenmark Pharmaceuticals Sa | Pharmaceutical composition comprising a trpa1 antagonist and a steroid |
| TWI640519B (zh) * | 2011-11-29 | 2018-11-11 | 泰緯生命科技股份有限公司 | Ｈｅｃ１活性調控因子及其調節方法 |
| JP2015500278A (ja) | 2011-12-05 | 2015-01-05 | グレンマーク ファーマシューティカルズ， エセ．アー． | Ｔｒｐａ１アンタゴニストと抗コリン剤とを含む医薬組成物 |
| MX354014B (es) | 2012-06-08 | 2018-02-08 | Glenmark Pharmaceuticals Sa | Amidas de compuestos de 2-amino-4-ariltiazol y sus sales. |
| SI2903965T1 (sl) | 2012-10-01 | 2017-07-31 | Orion Corporation | Derivati n-prop-2-inil karboksamida in njihova uporaba kot antagonisti trpa1 |
| CA2884767A1 (en) | 2012-11-14 | 2014-05-22 | Stephan Bachmann | Imidazopyridine derivatives |
| HK1221161A1 (zh) | 2013-06-20 | 2017-05-26 | Glenmark Pharmaceuticals S.A. | 包含trpa1拮抗剂的纳米颗粒制剂 |
| CA2926389A1 (en) | 2013-10-15 | 2015-04-23 | Glenmark Pharmaceuticals S.A. | Pharmaceutical composition comprising a trpa1 antagonist and an analgesic agent |
| WO2015155306A1 (en) * | 2014-04-11 | 2015-10-15 | Almirall, S.A. | New trpa1 antagonists |
| US20190175599A1 (en) | 2014-09-16 | 2019-06-13 | Glemark Pharmaceuticals S.A. | Trpa1 antagonist for the treatment of pain associated to diabetic neuropathic pain |
| WO2017060488A1 (en) | 2015-10-09 | 2017-04-13 | Almirall, S.A. | New trpa1 antagonists |
| WO2017064068A1 (en) | 2015-10-14 | 2017-04-20 | Almirall, S.A. | New trpa1 antagonists |
| WO2018233648A1 (zh) * | 2017-06-21 | 2018-12-27 | 南京明德新药研发股份有限公司 | 作为TLR8激动剂的异噻唑并[4,3-d]嘧啶-5,7-二胺衍生物 |
| CN112794860B (zh) * | 2021-03-24 | 2021-06-29 | 上海肇钰医药科技有限公司 | 噁唑嘧啶酮酰胺类化合物或其可药用盐，制备方法及用途 |
| CN114656480B (zh) * | 2022-04-27 | 2024-01-26 | 成都施贝康生物医药科技有限公司 | 噻吩并嘧啶类化合物、异构体或盐及其制备方法和用途 |
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| DE2248231A1 (de) * | 1972-10-02 | 1974-04-11 | Basf Ag | 3-aminoisothiazolo eckige klammer auf 3,4-d eckige klammer zu pyrimidine |
| SE9701398D0 (sv) | 1997-04-15 | 1997-04-15 | Astra Pharma Prod | Novel compounds |
| ES2193839B1 (es) | 2001-06-22 | 2005-02-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de 6-fenildihidropirrolpirimidindiona. |
| AU2003253165A1 (en) | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidine fused bicyclic metalloproteinase inhibitors |
| AU2003290066A1 (en) | 2002-12-18 | 2004-07-09 | Novartis Ag | Anktm1, a cold-activated trp-like channel expressed in nociceptive neurons |
| SE0300119D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| WO2005077959A1 (en) * | 2004-02-11 | 2005-08-25 | Smithkline Beecham Corporation | Pth agonists |
| US20070196866A1 (en) | 2004-03-13 | 2007-08-23 | Irm Llc | Modulators of ion channel trpa1 |
| US20090062258A1 (en) | 2005-02-03 | 2009-03-05 | Takeda Pharmaceutical Company Limited | Fused pyrimidine derivative and use thereof |
| JP5858557B2 (ja) * | 2005-12-22 | 2016-02-10 | ハイドラ バイオサイエンシズ インコーポレイテッドＨｙｄｒａ Ｂｉｏｓｃｉｅｎｃｅｓ，Ｉｎｃ． | 疼痛を処置するためのｔｒｐａ１阻害剤 |
| TW200800997A (en) | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
| AR065081A1 (es) | 2007-01-29 | 2009-05-13 | Xenon Pharmaceuticals Inc | Compuestos de quinazolinona y pirimidona fusionados y composicion farmaceutica |
| WO2009002933A1 (en) * | 2007-06-22 | 2008-12-31 | Hydra Biosciences, Inc. | Methods and compositions for treating disorders |
| WO2009158719A2 (en) | 2008-06-27 | 2009-12-30 | Hydra Biosciences, Inc. | Methods and compositions for treating disorders |
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2010
- 2010-03-22 MX MX2011009821A patent/MX2011009821A/es unknown
- 2010-03-22 WO PCT/IB2010/000834 patent/WO2010109328A1/en not_active Ceased
- 2010-03-22 PE PE2011001703A patent/PE20120764A1/es not_active Application Discontinuation
- 2010-03-22 KR KR1020117023383A patent/KR20120001746A/ko not_active Withdrawn
- 2010-03-22 EP EP10716049.1A patent/EP2411397B1/en not_active Not-in-force
- 2010-03-22 ES ES10716049T patent/ES2424340T3/es active Active
- 2010-03-22 AP AP2011005888A patent/AP2011005888A0/xx unknown
- 2010-03-22 US US13/257,241 patent/US8575178B2/en not_active Expired - Fee Related
- 2010-03-22 SG SG2011066495A patent/SG174403A1/en unknown
- 2010-03-22 EA EA201190191A patent/EA201190191A1/ru unknown
- 2010-03-22 SI SI201030232T patent/SI2411397T1/sl unknown
- 2010-03-22 CA CA2756534A patent/CA2756534A1/en not_active Abandoned
- 2010-03-22 PT PT107160491T patent/PT2411397E/pt unknown
- 2010-03-22 SG SG2012069464A patent/SG184766A1/en unknown
- 2010-03-22 CN CN2010800168801A patent/CN102395592A/zh active Pending
- 2010-03-22 BR BRPI1009372A patent/BRPI1009372A2/pt not_active IP Right Cessation
- 2010-03-22 DK DK10716049.1T patent/DK2411397T3/da active
- 2010-03-22 PL PL10716049T patent/PL2411397T3/pl unknown
- 2010-03-22 JP JP2012501411A patent/JP2012521405A/ja not_active Withdrawn
- 2010-03-22 AU AU2010227224A patent/AU2010227224A1/en not_active Abandoned
- 2010-03-23 UA UAA201111149A patent/UA107342C2/ru unknown
-
2011
- 2011-09-15 IL IL215179A patent/IL215179A0/en unknown
- 2011-10-19 ZA ZA2011/07646A patent/ZA201107646B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SG174403A1 (en) | 2011-10-28 |
| PL2411397T3 (pl) | 2013-10-31 |
| EA201190191A1 (ru) | 2012-11-30 |
| JP2012521405A (ja) | 2012-09-13 |
| KR20120001746A (ko) | 2012-01-04 |
| EP2411397B1 (en) | 2013-05-29 |
| PT2411397E (pt) | 2013-06-06 |
| US20120010223A1 (en) | 2012-01-12 |
| HK1166081A1 (en) | 2012-10-19 |
| EP2411397A1 (en) | 2012-02-01 |
| ZA201107646B (en) | 2012-06-25 |
| SI2411397T1 (sl) | 2013-07-31 |
| PE20120764A1 (es) | 2012-06-27 |
| AU2010227224A1 (en) | 2011-09-29 |
| AU2010227224A2 (en) | 2011-10-27 |
| US8575178B2 (en) | 2013-11-05 |
| CN102395592A (zh) | 2012-03-28 |
| ES2424340T3 (es) | 2013-10-01 |
| SG184766A1 (en) | 2012-10-30 |
| MX2011009821A (es) | 2012-01-25 |
| AP2011005888A0 (en) | 2011-10-31 |
| IL215179A0 (en) | 2011-12-29 |
| UA107342C2 (en) | 2014-12-25 |
| BRPI1009372A2 (pt) | 2016-05-31 |
| WO2010109328A1 (en) | 2010-09-30 |
| DK2411397T3 (da) | 2013-08-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20150324 |