JP5657638B2 - Ｔｒｐａ１調節因子としての縮合ピリミジンジオン誘導体 - Google Patents

Info

Publication number

JP5657638B2

JP5657638B2 JP2012501401A JP2012501401A JP5657638B2 JP 5657638 B2 JP5657638 B2 JP 5657638B2 JP 2012501401 A JP2012501401 A JP 2012501401A JP 2012501401 A JP2012501401 A JP 2012501401A JP 5657638 B2 JP5657638 B2 JP 5657638B2

Authority

JP

Japan

Prior art keywords

acetamide

thiazol

dioxo

pyrimidin

tetrahydro

Prior art date

2009-03-23

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.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 title claims description 6
• 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 title claims description 5
• 150000008512 pyrimidinediones Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 187
• -1 1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-5H-pyrrolo [3,2-d] pyrimidin-5-yl Chemical group 0.000 claims description 134
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 100
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 73
• 208000002193 Pain Diseases 0.000 claims description 31
• 239000000203 mixture Substances 0.000 claims description 29
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
• 230000036407 pain Effects 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 150000003839 salts Chemical class 0.000 claims description 21
• 208000024891 symptom Diseases 0.000 claims description 18
• 201000010099 disease Diseases 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 238000011282 treatment Methods 0.000 claims description 11
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
• 208000004296 neuralgia Diseases 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 7
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 6
• 208000000094 Chronic Pain Diseases 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 6
• 208000021722 neuropathic pain Diseases 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 201000001119 neuropathy Diseases 0.000 claims description 5
• 230000007823 neuropathy Effects 0.000 claims description 5
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
• 125000001331 3-methylbutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 4
• 230000004054 inflammatory process Effects 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 208000009935 visceral pain Diseases 0.000 claims description 4
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 206010011224 Cough Diseases 0.000 claims description 3
• 206010020751 Hypersensitivity Diseases 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 201000008482 osteoarthritis Diseases 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• WGSXKYXKAARAKD-UHFFFAOYSA-N 1-fluoro-3-isocyanato-5-(trifluoromethyl)benzene Chemical group FC1=CC(N=C=O)=CC(C(F)(F)F)=C1 WGSXKYXKAARAKD-UHFFFAOYSA-N 0.000 claims description 2
• PWFCNAOHVWWKNG-UHFFFAOYSA-N 2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)-n-[4-(2,3,4-trichlorophenyl)-1,3-thiazol-2-yl]acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C(Cl)=C1Cl PWFCNAOHVWWKNG-UHFFFAOYSA-N 0.000 claims description 2
• VJXIKTQSMMQMOO-UHFFFAOYSA-N 2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)-n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1 VJXIKTQSMMQMOO-UHFFFAOYSA-N 0.000 claims description 2
• HHGALMGKEXDRBM-UHFFFAOYSA-N 2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)-n-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(C)(C)C)C(F)=C1 HHGALMGKEXDRBM-UHFFFAOYSA-N 0.000 claims description 2
• DTXASEKLDRHEQO-UHFFFAOYSA-N 2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-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=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(C(F)(F)F)=C1 DTXASEKLDRHEQO-UHFFFAOYSA-N 0.000 claims description 2
• 208000008035 Back Pain Diseases 0.000 claims description 2
• 206010058019 Cancer Pain Diseases 0.000 claims description 2
• 201000004624 Dermatitis Diseases 0.000 claims description 2
• 208000001640 Fibromyalgia Diseases 0.000 claims description 2
• 206010017886 Gastroduodenal ulcer Diseases 0.000 claims description 2
• 208000004454 Hyperalgesia Diseases 0.000 claims description 2
• 208000035154 Hyperesthesia 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
• 208000008469 Peptic Ulcer Diseases 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
• 208000026935 allergic disease Diseases 0.000 claims description 2
• 208000010668 atopic eczema Diseases 0.000 claims description 2
• 201000003146 cystitis Diseases 0.000 claims description 2
• 208000006881 esophagitis Diseases 0.000 claims description 2
• 231100000029 gastro-duodenal ulcer Toxicity 0.000 claims description 2
• 230000009610 hypersensitivity Effects 0.000 claims description 2
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
• 208000028867 ischemia Diseases 0.000 claims description 2
• 206010027599 migraine Diseases 0.000 claims description 2
• 201000006417 multiple sclerosis Diseases 0.000 claims description 2
• XGDWUOTWCBUFBF-UHFFFAOYSA-N n-[4-(2,4-difluorophenyl)-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C=C1F XGDWUOTWCBUFBF-UHFFFAOYSA-N 0.000 claims description 2
• QKIWOLBTEJUIKO-UHFFFAOYSA-N n-[4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(=O)NC(SC=1)=NC=1C1=CC=C(F)C(C(F)(F)F)=C1F QKIWOLBTEJUIKO-UHFFFAOYSA-N 0.000 claims description 2
• MIQCXSCTXQXGMO-UHFFFAOYSA-N n-[4-[3,5-dichloro-4-(2,2-dimethylpropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(Cl)=C(OCC(C)(C)C)C(Cl)=C1 MIQCXSCTXQXGMO-UHFFFAOYSA-N 0.000 claims description 2
• MSAYCLQQORKAFC-UHFFFAOYSA-N n-[4-[3,5-dichloro-4-(3,3,3-trifluoropropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(Cl)=C(OCCC(F)(F)F)C(Cl)=C1 MSAYCLQQORKAFC-UHFFFAOYSA-N 0.000 claims description 2
• MJKVMFJIWCAVBS-UHFFFAOYSA-N n-[4-[3,5-dichloro-4-(3,3,4,4,4-pentafluorobutoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(Cl)=C(OCCC(F)(F)C(F)(F)F)C(Cl)=C1 MJKVMFJIWCAVBS-UHFFFAOYSA-N 0.000 claims description 2
• PNDMPMPPVJPCBO-UHFFFAOYSA-N n-[4-[3,5-dichloro-4-(cyclobutylmethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C(C=C1Cl)=CC(Cl)=C1OCC1CCC1 PNDMPMPPVJPCBO-UHFFFAOYSA-N 0.000 claims description 2
• QMTNZUVGQYBRTR-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(F)(F)F)C(F)=C1 QMTNZUVGQYBRTR-UHFFFAOYSA-N 0.000 claims description 2
• MMHXOTLTEZVHSY-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(F)(F)F)C(F)=C1 MMHXOTLTEZVHSY-UHFFFAOYSA-N 0.000 claims description 2
• NLQAMAXKCHXKCL-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(F)(F)F)C(F)=C1 NLQAMAXKCHXKCL-UHFFFAOYSA-N 0.000 claims description 2
• OKQXLYYFMPXFAX-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(3,3,3-trifluoropropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCCC(F)(F)F)C(F)=C1 OKQXLYYFMPXFAX-UHFFFAOYSA-N 0.000 claims description 2
• HMHDLTBMXATXHH-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(3-methylbutoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=C(F)C(OCCC(C)C)=C(F)C=C1C1=CSC(NC(=O)CN2C=3C(=O)N(C)C(=O)N(C)C=3C=C2)=N1 HMHDLTBMXATXHH-UHFFFAOYSA-N 0.000 claims description 2
• FAGOKVRNGXRBLZ-UHFFFAOYSA-N n-[4-[3-bromo-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(OCC(F)(F)F)C(Br)=C1 FAGOKVRNGXRBLZ-UHFFFAOYSA-N 0.000 claims description 2
• MPFSSCWDMILAOW-UHFFFAOYSA-N n-[4-[3-chloro-4-(2,2-dimethylpropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C1=CC=C(OCC(C)(C)C)C(Cl)=C1 MPFSSCWDMILAOW-UHFFFAOYSA-N 0.000 claims description 2
• SLOZYXXAOWEARH-UHFFFAOYSA-N n-[4-[3-chloro-5-fluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(F)(F)F)C(Cl)=C1 SLOZYXXAOWEARH-UHFFFAOYSA-N 0.000 claims description 2
• DVEXKZCKMAEQGO-UHFFFAOYSA-N n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1 DVEXKZCKMAEQGO-UHFFFAOYSA-N 0.000 claims description 2
• JPMLQKMNYAURPB-UHFFFAOYSA-N n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1 JPMLQKMNYAURPB-UHFFFAOYSA-N 0.000 claims description 2
• HYUWZKXSCQQPNU-UHFFFAOYSA-N n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(C)=CN2CC(=O)NC(SC=1)=NC=1C1=CC=C(C(F)(F)F)C(F)=C1 HYUWZKXSCQQPNU-UHFFFAOYSA-N 0.000 claims description 2
• AZAOVWSEIOTYCH-UHFFFAOYSA-N n-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(C)(C)C)C(F)=C1 AZAOVWSEIOTYCH-UHFFFAOYSA-N 0.000 claims description 2
• MOBOEILXZWMKQG-UHFFFAOYSA-N n-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(C)(C)C)C(F)=C1 MOBOEILXZWMKQG-UHFFFAOYSA-N 0.000 claims description 2
• MROYRQVEHRGXHI-UHFFFAOYSA-N n-[4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,7-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(C)=CN2CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OCC(C)(C)C)C(F)=C1 MROYRQVEHRGXHI-UHFFFAOYSA-N 0.000 claims description 2
• ZVGKXJDRPSRLQF-UHFFFAOYSA-N n-[4-[4-(2,2-dimethylpropoxy)-3-fluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C1=CC=C(OCC(C)(C)C)C(F)=C1 ZVGKXJDRPSRLQF-UHFFFAOYSA-N 0.000 claims description 2
• OYHGLGOLPALEOM-UHFFFAOYSA-N n-[4-[4-(cyclobutylmethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3,6-trimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound CC1=CC=2N(C)C(=O)N(C)C(=O)C=2N1CC(=O)NC(SC=1)=NC=1C(C=C1F)=CC(F)=C1OCC1CCC1 OYHGLGOLPALEOM-UHFFFAOYSA-N 0.000 claims description 2
• RHMISVBJYQSDSS-UHFFFAOYSA-N n-[4-[4-(cyclopropylmethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C(C=C1F)=CC(F)=C1OCC1CC1 RHMISVBJYQSDSS-UHFFFAOYSA-N 0.000 claims description 2
• IAZLFUFODLEFKX-UHFFFAOYSA-N n-[4-[4-(difluoromethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC(F)=C(OC(F)F)C(F)=C1 IAZLFUFODLEFKX-UHFFFAOYSA-N 0.000 claims description 2
• UZCBRKYSYQOZEM-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C1=CC=C(Cl)C(C(F)(F)F)=C1 UZCBRKYSYQOZEM-UHFFFAOYSA-N 0.000 claims description 2
• 230000008764 nerve damage Effects 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
• 208000023504 respiratory system disease Diseases 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 230000008673 vomiting Effects 0.000 claims description 2
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims 2
• 239000000969 carrier Substances 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• 208000012201 sexual and gender identity disease Diseases 0.000 claims 1
• 208000015891 sexual disease Diseases 0.000 claims 1
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 210
• 238000000034 method Methods 0.000 description 206
• 239000000543 intermediate Substances 0.000 description 129
• 239000007787 solid Substances 0.000 description 124
• 239000000047 product Substances 0.000 description 114
• 238000005481 NMR spectroscopy Methods 0.000 description 95
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
• 229910000104 sodium hydride Inorganic materials 0.000 description 68
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
• 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 66
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 54
• 239000011541 reaction mixture Substances 0.000 description 42
• 238000010168 coupling process Methods 0.000 description 40
• 125000000217 alkyl group Chemical group 0.000 description 36
• 230000008878 coupling Effects 0.000 description 35
• 238000005859 coupling reaction Methods 0.000 description 35
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
• 239000000243 solution Substances 0.000 description 34
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
• 125000000623 heterocyclic group Chemical group 0.000 description 27
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 27
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 26
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• 229910052739 hydrogen Inorganic materials 0.000 description 25
• 239000002904 solvent Substances 0.000 description 25
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 24
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 235000019439 ethyl acetate Nutrition 0.000 description 22
• 239000001257 hydrogen Substances 0.000 description 22
• 125000003118 aryl group Chemical group 0.000 description 20
• 229910052736 halogen Inorganic materials 0.000 description 20
• 150000002367 halogens Chemical class 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• 238000005160 1H NMR spectroscopy Methods 0.000 description 17
• 125000000753 cycloalkyl group Chemical group 0.000 description 16
• 125000001188 haloalkyl group Chemical group 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 125000003342 alkenyl group Chemical group 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• 125000003545 alkoxy group Chemical group 0.000 description 13
• 125000000304 alkynyl group Chemical group 0.000 description 13
• 238000013459 approach Methods 0.000 description 13
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 13
• 238000001914 filtration Methods 0.000 description 13
• 230000002829 reductive effect Effects 0.000 description 13
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 12
• 125000004438 haloalkoxy group Chemical group 0.000 description 12
• 125000001072 heteroaryl group Chemical group 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 125000003710 aryl alkyl group Chemical group 0.000 description 11
• 150000002431 hydrogen Chemical class 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• 238000010898 silica gel chromatography Methods 0.000 description 11
• 230000002194 synthesizing effect Effects 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
• 125000004122 cyclic group Chemical group 0.000 description 9
• 125000000392 cycloalkenyl group Chemical group 0.000 description 9
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 9
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 125000004093 cyano group Chemical group *C#N 0.000 description 8
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 210000000929 nociceptor Anatomy 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 150000001721 carbon Chemical group 0.000 description 7
• 238000004440 column chromatography Methods 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 125000005842 heteroatom Chemical group 0.000 description 7
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 6
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 230000002152 alkylating effect Effects 0.000 description 6
• ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• 229910052801 chlorine Inorganic materials 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000012039 electrophile Substances 0.000 description 6
• 229910052731 fluorine Inorganic materials 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 125000001424 substituent group Chemical group 0.000 description 6
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 208000001294 Nociceptive Pain Diseases 0.000 description 5
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 150000001299 aldehydes Chemical class 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 230000006378 damage Effects 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• 239000011630 iodine Substances 0.000 description 5
• 108091008700 nociceptors Proteins 0.000 description 5
• 229910052760 oxygen Inorganic materials 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 229910052717 sulfur Inorganic materials 0.000 description 5
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 4
• QVUUNTAJJXNRAP-UHFFFAOYSA-N 2-bromo-n-[4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=C(C(F)(F)F)C(F)=CC(C=2N=C(NC(=O)CBr)SC=2)=C1 QVUUNTAJJXNRAP-UHFFFAOYSA-N 0.000 description 4
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
• 108091006146 Channels Proteins 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• 101150095096 TRPM2 gene Proteins 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
• 150000008062 acetophenones Chemical class 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 244000309464 bull Species 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 230000008020 evaporation Effects 0.000 description 4
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
• 125000003944 tolyl group Chemical group 0.000 description 4
• 230000001052 transient effect Effects 0.000 description 4
• OSTDULKDQDIIKB-UHFFFAOYSA-N 1,3,6-trimethyl-5-nitropyrimidine-2,4-dione Chemical compound CC1=C([N+]([O-])=O)C(=O)N(C)C(=O)N1C OSTDULKDQDIIKB-UHFFFAOYSA-N 0.000 description 3
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 3
• GAIZCKXXSFRGOK-UHFFFAOYSA-N 2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetic acid Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(O)=O GAIZCKXXSFRGOK-UHFFFAOYSA-N 0.000 description 3
• LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 3
• BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 3
• QETLJJSSAJXEIO-UHFFFAOYSA-N 4-chloro-1,3-dimethyl-2,6-dioxopyrimidine-5-carbaldehyde Chemical compound CN1C(Cl)=C(C=O)C(=O)N(C)C1=O QETLJJSSAJXEIO-UHFFFAOYSA-N 0.000 description 3
• 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 description 3
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 235000016720 allyl isothiocyanate Nutrition 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 230000002140 halogenating effect Effects 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000003208 petroleum Substances 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• QGLVEAGMVUQOJP-UHFFFAOYSA-N prop-2-enylboronic acid Chemical compound OB(O)CC=C QGLVEAGMVUQOJP-UHFFFAOYSA-N 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
• LSOLGCXAMRBKTJ-UHFFFAOYSA-N 1,3,6-trimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1C=C(C)N2 LSOLGCXAMRBKTJ-UHFFFAOYSA-N 0.000 description 2
• GRYKITFZUYQWCO-UHFFFAOYSA-N 1,3,7-trimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(C)=CN2 GRYKITFZUYQWCO-UHFFFAOYSA-N 0.000 description 2
• XLSXPKZIKMPZHK-UHFFFAOYSA-N 1,3-dimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=C2 XLSXPKZIKMPZHK-UHFFFAOYSA-N 0.000 description 2
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 2
• AACUYXPCLUSFMI-UHFFFAOYSA-N 2-bromo-n-(1,3-thiazol-2-yl)acetamide Chemical compound BrCC(=O)NC1=NC=CS1 AACUYXPCLUSFMI-UHFFFAOYSA-N 0.000 description 2
• RXFZFVUMTSCASN-UHFFFAOYSA-N 2-bromo-n-[4-[3,5-dichloro-4-(2,2-dimethylpropoxy)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=C(Cl)C(OCC(C)(C)C)=C(Cl)C=C1C1=CSC(NC(=O)CBr)=N1 RXFZFVUMTSCASN-UHFFFAOYSA-N 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
• CQTJFQYYLUTDME-UHFFFAOYSA-N 4,6-dimethyl-1h-pyrazolo[4,3-d]pyrimidine-5,7-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NN=C2 CQTJFQYYLUTDME-UHFFFAOYSA-N 0.000 description 2
• UYSJHSJNYGOZHN-UHFFFAOYSA-N 4-[2,4-difluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=C(C(F)=CC=2)C(F)(F)F)F)=C1 UYSJHSJNYGOZHN-UHFFFAOYSA-N 0.000 description 2
• OPHDOIKOSGCXPW-UHFFFAOYSA-N 4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(=CC=2)C(F)(F)F)=C1 OPHDOIKOSGCXPW-UHFFFAOYSA-N 0.000 description 2
• XOCOZIHOJCULLE-UHFFFAOYSA-N 5-(trifluoromethoxy)-1,3-benzothiazol-2-amine Chemical compound FC(F)(F)OC1=CC=C2SC(N)=NC2=C1 XOCOZIHOJCULLE-UHFFFAOYSA-N 0.000 description 2
• FTYAJPZNGIJJNX-UHFFFAOYSA-N 5-[3-fluoro-4-(trifluoromethyl)phenyl]-1h-imidazol-2-amine Chemical compound N1C(N)=NC(C=2C=C(F)C(=CC=2)C(F)(F)F)=C1 FTYAJPZNGIJJNX-UHFFFAOYSA-N 0.000 description 2
• KPADHLBAZFIMTA-UHFFFAOYSA-N 5-amino-1,3-dimethylpyrimidine-2,4-dione Chemical compound CN1C=C(N)C(=O)N(C)C1=O KPADHLBAZFIMTA-UHFFFAOYSA-N 0.000 description 2
• XGIBUCRNAAADNS-UHFFFAOYSA-N 7-[(dimethylamino)methyl]-1,3-dimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(CN(C)C)=CN2 XGIBUCRNAAADNS-UHFFFAOYSA-N 0.000 description 2
• 108010049777 Ankyrins Proteins 0.000 description 2
• 102000008102 Ankyrins Human genes 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• 101800004538 Bradykinin Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
• 101000605625 Homo sapiens Polycystic kidney disease 2-like 1 protein Proteins 0.000 description 2
• 101000605623 Homo sapiens Polycystic kidney disease 2-like 2 protein Proteins 0.000 description 2
• 101001074439 Homo sapiens Polycystin-2 Proteins 0.000 description 2
• 101000844504 Homo sapiens Transient receptor potential cation channel subfamily M member 4 Proteins 0.000 description 2
• 101000844521 Homo sapiens Transient receptor potential cation channel subfamily M member 5 Proteins 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 102100035792 Kininogen-1 Human genes 0.000 description 2
• 102400001335 Mucolipin Human genes 0.000 description 2
• 102100026502 Mucolipin-1 Human genes 0.000 description 2
• 102100030870 Mucolipin-2 Human genes 0.000 description 2
• 102100030868 Mucolipin-3 Human genes 0.000 description 2
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• 102100038330 Polycystic kidney disease 2-like 1 protein Human genes 0.000 description 2
• 102100038335 Polycystic kidney disease 2-like 2 protein Human genes 0.000 description 2
• 102100036142 Polycystin-2 Human genes 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 2
• 108060008646 TRPA Proteins 0.000 description 2
• 102000027549 TRPC Human genes 0.000 description 2
• 108060008648 TRPC Proteins 0.000 description 2
• 102000003564 TRPC7 Human genes 0.000 description 2
• 102000027545 TRPM Human genes 0.000 description 2
• 108091008847 TRPM Proteins 0.000 description 2
• 102000003617 TRPM1 Human genes 0.000 description 2
• 102000003615 TRPM2 Human genes 0.000 description 2
• 102000003620 TRPM3 Human genes 0.000 description 2
• 108060008547 TRPM3 Proteins 0.000 description 2
• 102000003618 TRPM4 Human genes 0.000 description 2
• 102000003611 TRPM7 Human genes 0.000 description 2
• 102000027544 TRPML Human genes 0.000 description 2
• 108091008846 TRPML Proteins 0.000 description 2
• 108060009332 TRPP Proteins 0.000 description 2
• 102000003563 TRPV Human genes 0.000 description 2
• 108060008564 TRPV Proteins 0.000 description 2
• 102000003566 TRPV1 Human genes 0.000 description 2
• 102000003565 TRPV2 Human genes 0.000 description 2
• 102000003568 TRPV3 Human genes 0.000 description 2
• 102000003570 TRPV5 Human genes 0.000 description 2
• 102000003569 TRPV6 Human genes 0.000 description 2
• 101150096736 TRPV6 gene Proteins 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 102100031215 Transient receptor potential cation channel subfamily M member 5 Human genes 0.000 description 2
• 101150033973 Trpc7 gene Proteins 0.000 description 2
• 101150016206 Trpv1 gene Proteins 0.000 description 2
• 101150077905 Trpv2 gene Proteins 0.000 description 2
• 101150043371 Trpv3 gene Proteins 0.000 description 2
• 101150034091 Trpv5 gene Proteins 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 208000005298 acute pain Diseases 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 150000005347 biaryls Chemical group 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 2
• 230000003185 calcium uptake Effects 0.000 description 2
• 235000013877 carbamide Nutrition 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
• IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
• 239000001301 oxygen Chemical group 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Chemical group 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 230000001953 sensory effect Effects 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
• 235000019345 sodium thiosulphate Nutrition 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 208000037816 tissue injury Diseases 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 102000042565 transient receptor (TC 1.A.4) family Human genes 0.000 description 2
• 108091053409 transient receptor (TC 1.A.4) family Proteins 0.000 description 2
• 150000003852 triazoles Chemical group 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
• JVJFIQYAHPMBBX-FNORWQNLSA-N (E)-4-hydroxynon-2-enal Chemical compound CCCCCC(O)\C=C\C=O JVJFIQYAHPMBBX-FNORWQNLSA-N 0.000 description 1
• GRDXZRWCQWDLPG-UHFFFAOYSA-N 1,3,6-trimethylpyrimidine-2,4-dione Chemical compound CC1=CC(=O)N(C)C(=O)N1C GRDXZRWCQWDLPG-UHFFFAOYSA-N 0.000 description 1
• VVSASNKOFCZVES-UHFFFAOYSA-N 1,3-dimethyl-1,3-diazinane-2,4,6-trione Chemical compound CN1C(=O)CC(=O)N(C)C1=O VVSASNKOFCZVES-UHFFFAOYSA-N 0.000 description 1
• LHGAKKLQGHFLPQ-UHFFFAOYSA-N 1,3-dimethyl-2,4-dioxo-5h-pyrrolo[3,2-d]pyrimidine-7-carbaldehyde Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=C2C=O LHGAKKLQGHFLPQ-UHFFFAOYSA-N 0.000 description 1
• IRXHCHDQRVLDGB-UHFFFAOYSA-N 1,3-dimethyl-5-(prop-2-ynylamino)pyrimidine-2,4-dione Chemical compound CN1C=C(NCC#C)C(=O)N(C)C1=O IRXHCHDQRVLDGB-UHFFFAOYSA-N 0.000 description 1
• SDLBIQNBDPOOPJ-UHFFFAOYSA-N 1,3-dimethyl-5-nitropyrimidine-2,4-dione Chemical compound CN1C=C([N+]([O-])=O)C(=O)N(C)C1=O SDLBIQNBDPOOPJ-UHFFFAOYSA-N 0.000 description 1
• SKJJVYVZMFKWBP-UHFFFAOYSA-N 1,3-dimethyl-7h-pyrrolo[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1C=CN2 SKJJVYVZMFKWBP-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
• CFENPPFMNOOCSZ-UHFFFAOYSA-N 1-acetyl-3,5,7-trimethylpyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C(=O)C)N=C2C CFENPPFMNOOCSZ-UHFFFAOYSA-N 0.000 description 1
• 125000006083 1-bromoethyl group Chemical group 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• BDEMHHQEBKKRID-UHFFFAOYSA-N 2,3,5,7-tetramethylpyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C(C)N(C)N=C21 BDEMHHQEBKKRID-UHFFFAOYSA-N 0.000 description 1
• QEQUIPGNNNNDGO-UHFFFAOYSA-N 2-(2,5,7-trimethyl-4,6-dioxopyrazolo[3,4-d]pyrimidin-3-yl)acetic acid Chemical compound CN1C(=O)N(C)C(=O)C2=C(CC(O)=O)N(C)N=C21 QEQUIPGNNNNDGO-UHFFFAOYSA-N 0.000 description 1
• CWKSVOPHDPFOTI-UHFFFAOYSA-N 2-(2h-pyrazolo[3,4-d]pyrimidin-3-yl)acetic acid Chemical compound N1=CN=CC2=C(CC(=O)O)NN=C21 CWKSVOPHDPFOTI-UHFFFAOYSA-N 0.000 description 1
• FLOZQWCOYPLIFQ-UHFFFAOYSA-N 2-bromo-n-[4-[3,5-dichloro-4-(3,3,4,4,4-pentafluorobutoxy)phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound C1=C(Cl)C(OCCC(F)(F)C(F)(F)F)=C(Cl)C=C1C1=CSC(NC(=O)CBr)=N1 FLOZQWCOYPLIFQ-UHFFFAOYSA-N 0.000 description 1
• XOWLWVXAHVAZTM-UHFFFAOYSA-N 2-bromo-n-[4-[3,5-difluoro-4-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound FC1=CC(C=2N=C(NC(=O)CBr)SC=2)=CC(F)=C1OCC1=CC=C(C(F)(F)F)C=C1 XOWLWVXAHVAZTM-UHFFFAOYSA-N 0.000 description 1
• JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• CRZJPEIBPQWDGJ-UHFFFAOYSA-N 2-chloro-1,1-dimethoxyethane Chemical compound COC(CCl)OC CRZJPEIBPQWDGJ-UHFFFAOYSA-N 0.000 description 1
• 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• ALWVPFIPTLPTEV-UHFFFAOYSA-N 2h-pyrazolo[4,3-d]pyrimidine-3,5-dione Chemical compound C1=NC(=O)N=C2C(=O)NN=C21 ALWVPFIPTLPTEV-UHFFFAOYSA-N 0.000 description 1
• DYEIQBYFEXTAAU-UHFFFAOYSA-N 3,4,6-trimethyl-2h-pyrazolo[4,3-d]pyrimidine-5,7-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(C)=NN2 DYEIQBYFEXTAAU-UHFFFAOYSA-N 0.000 description 1
• VSPRBFLKSINHLP-UHFFFAOYSA-N 3,5,7-trimethyl-2h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1NN=C2C VSPRBFLKSINHLP-UHFFFAOYSA-N 0.000 description 1
• HKUPOLYVZQLXKP-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC(F)=CC=2)F)=C1 HKUPOLYVZQLXKP-UHFFFAOYSA-N 0.000 description 1
• NDCSJUJQMRFHEX-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(F)=CC=2)=C1 NDCSJUJQMRFHEX-UHFFFAOYSA-N 0.000 description 1
• DJGBSHUJYGXFQN-UHFFFAOYSA-N 4-(3,5-difluorophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C=C(F)C=2)=C1 DJGBSHUJYGXFQN-UHFFFAOYSA-N 0.000 description 1
• DWGWNNCHJPKZNC-UHFFFAOYSA-N 4-(4-chlorophenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(Cl)=CC=2)=C1 DWGWNNCHJPKZNC-UHFFFAOYSA-N 0.000 description 1
• QFMNMDDKDKCKKW-UHFFFAOYSA-N 4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=C(F)C(=CC=2)C(F)(F)F)F)=C1 QFMNMDDKDKCKKW-UHFFFAOYSA-N 0.000 description 1
• QTFIQKQWACKFHA-UHFFFAOYSA-N 4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=C(C=CC=2)C(F)(F)F)F)=C1 QTFIQKQWACKFHA-UHFFFAOYSA-N 0.000 description 1
• WTMCMRXAHVSYMO-UHFFFAOYSA-N 4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC(=CC=2)C(F)(F)F)F)=C1 WTMCMRXAHVSYMO-UHFFFAOYSA-N 0.000 description 1
• FPIUGVQEXYOXEA-UHFFFAOYSA-N 4-[2-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC=C(C=2)C(F)(F)F)F)=C1 FPIUGVQEXYOXEA-UHFFFAOYSA-N 0.000 description 1
• XVMBKWVKVXOTCS-UHFFFAOYSA-N 4-[3,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(OCC(F)(F)F)=C(F)C=2)=C1 XVMBKWVKVXOTCS-UHFFFAOYSA-N 0.000 description 1
• VYRFEJAFSZHYEI-UHFFFAOYSA-N 4-[3-(trifluoromethoxy)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(OC(F)(F)F)C=CC=2)=C1 VYRFEJAFSZHYEI-UHFFFAOYSA-N 0.000 description 1
• ZZDBATBJNFVJCB-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(C=CC=2)C(F)(F)F)=C1 ZZDBATBJNFVJCB-UHFFFAOYSA-N 0.000 description 1
• VCMSBRUFWBYGNR-UHFFFAOYSA-N 4-[3-fluoro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(OC(F)(F)F)=CC=2)=C1 VCMSBRUFWBYGNR-UHFFFAOYSA-N 0.000 description 1
• UKJQCMKGJGFQFQ-UHFFFAOYSA-N 4-[3-fluoro-5-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(C=C(F)C=2)C(F)(F)F)=C1 UKJQCMKGJGFQFQ-UHFFFAOYSA-N 0.000 description 1
• OFXMYQNRJIWJHK-UHFFFAOYSA-N 4-[4-(2,2-dimethylpropoxy)-3,5-difluorophenyl]-1,3-thiazol-2-amine Chemical compound C1=C(F)C(OCC(C)(C)C)=C(F)C=C1C1=CSC(N)=N1 OFXMYQNRJIWJHK-UHFFFAOYSA-N 0.000 description 1
• QHFXFYBCBXWOGR-UHFFFAOYSA-N 4-[4-(2-methylpropyl)phenyl]-1,3-thiazol-2-amine Chemical compound C1=CC(CC(C)C)=CC=C1C1=CSC(N)=N1 QHFXFYBCBXWOGR-UHFFFAOYSA-N 0.000 description 1
• SDIUFDASQXZLBJ-UHFFFAOYSA-N 4-[4-(difluoromethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(OC(F)F)=C(F)C=2)=C1 SDIUFDASQXZLBJ-UHFFFAOYSA-N 0.000 description 1
• XFGFAEIZTOEDAN-UHFFFAOYSA-N 4-[4-(difluoromethoxy)-3-fluorophenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(F)C(OC(F)F)=CC=2)=C1 XFGFAEIZTOEDAN-UHFFFAOYSA-N 0.000 description 1
• HYAHAIVZFRFEBU-UHFFFAOYSA-N 4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(=CC=2)C(F)(F)F)=C1 HYAHAIVZFRFEBU-UHFFFAOYSA-N 0.000 description 1
• OXROOSXUSPSVNY-UHFFFAOYSA-N 4-[4-fluoro-3-(trifluoromethoxy)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(OC(F)(F)F)C(F)=CC=2)=C1 OXROOSXUSPSVNY-UHFFFAOYSA-N 0.000 description 1
• KGPBNLSPHADRDS-UHFFFAOYSA-N 4-[4-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=C(C(F)=CC=2)C(F)(F)F)=C1 KGPBNLSPHADRDS-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• PZVLJGKJIMBYNP-UHFFFAOYSA-N 5,6-dimethyl-1h-pyrimidine-2,4-dione Chemical compound CC=1NC(=O)NC(=O)C=1C PZVLJGKJIMBYNP-UHFFFAOYSA-N 0.000 description 1
• YINDFUSXBDZGIH-UHFFFAOYSA-N 5-(4-bromophenyl)-1,2-oxazol-3-amine Chemical compound O1N=C(N)C=C1C1=CC=C(Br)C=C1 YINDFUSXBDZGIH-UHFFFAOYSA-N 0.000 description 1
• FDKLGFYAEDLCNA-UHFFFAOYSA-N 5-amino-1,3,6-trimethylpyrimidine-2,4-dione Chemical compound CC1=C(N)C(=O)N(C)C(=O)N1C FDKLGFYAEDLCNA-UHFFFAOYSA-N 0.000 description 1
• ZVFGYVSOABWFCB-UHFFFAOYSA-N 5-prop-2-enyl-1h-pyrazole Chemical compound C=CCC=1C=CNN=1 ZVFGYVSOABWFCB-UHFFFAOYSA-N 0.000 description 1
• RWXJJNUDUCETTI-UHFFFAOYSA-N 6-[2-(dimethylamino)ethenyl]-1,3-dimethyl-5-nitropyrimidine-2,4-dione Chemical compound CN(C)C=CC1=C([N+]([O-])=O)C(=O)N(C)C(=O)N1C RWXJJNUDUCETTI-UHFFFAOYSA-N 0.000 description 1
• VFGRNTYELNYSKJ-UHFFFAOYSA-N 6-amino-1,3-dimethylpyrimidine-2,4-dione Chemical compound CN1C(N)=CC(=O)N(C)C1=O VFGRNTYELNYSKJ-UHFFFAOYSA-N 0.000 description 1
• LNDZXOWGUAIUBG-UHFFFAOYSA-N 6-aminouracil Chemical class NC1=CC(=O)NC(=O)N1 LNDZXOWGUAIUBG-UHFFFAOYSA-N 0.000 description 1
• VATQPUHLFQHDBD-UHFFFAOYSA-N 6-chloro-1,3-dimethylpyrimidine-2,4-dione Chemical compound CN1C(Cl)=CC(=O)N(C)C1=O VATQPUHLFQHDBD-UHFFFAOYSA-N 0.000 description 1
• PKUFNWPSFCOSLU-UHFFFAOYSA-N 6-chloro-1h-pyrimidine-2,4-dione Chemical class ClC1=CC(=O)NC(=O)N1 PKUFNWPSFCOSLU-UHFFFAOYSA-N 0.000 description 1
• YLPPKUCEYSTYSP-UHFFFAOYSA-N 6-ethyl-1,3-dimethyl-5-nitropyrimidine-2,4-dione Chemical compound CCC1=C([N+]([O-])=O)C(=O)N(C)C(=O)N1C YLPPKUCEYSTYSP-UHFFFAOYSA-N 0.000 description 1
• HZJOVZZMDMNJJT-UHFFFAOYSA-N 6-hydrazinyl-1,3-dimethylpyrimidine-2,4-dione Chemical compound CN1C(NN)=CC(=O)N(C)C1=O HZJOVZZMDMNJJT-UHFFFAOYSA-N 0.000 description 1
• ZTWVDTQCEOXUGL-UHFFFAOYSA-N 7-(diethylaminomethyl)-1,3-dimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1C(CN(CC)CC)=CN2 ZTWVDTQCEOXUGL-UHFFFAOYSA-N 0.000 description 1
• DCSPXSBKVLCEGM-UHFFFAOYSA-N 7-bromo-1,3-dimethyl-5h-pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=C2Br DCSPXSBKVLCEGM-UHFFFAOYSA-N 0.000 description 1
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• 240000002234 Allium sativum Species 0.000 description 1
• 102100031366 Ankyrin-1 Human genes 0.000 description 1
• 101710191059 Ankyrin-1 Proteins 0.000 description 1
• 101100350964 Arabidopsis thaliana PANS1 gene Proteins 0.000 description 1
• 244000056139 Brassica cretica Species 0.000 description 1
• 235000003351 Brassica cretica Nutrition 0.000 description 1
• 235000003343 Brassica rupestris Nutrition 0.000 description 1
• OTKUEQRCDCSASO-UHFFFAOYSA-N C1=CC=C(C=C1)NC(=O)C(C2=NC=CS2)Br Chemical compound C1=CC=C(C=C1)NC(=O)C(C2=NC=CS2)Br OTKUEQRCDCSASO-UHFFFAOYSA-N 0.000 description 1
• 101150076566 CMR1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-BKFZFHPZSA-N Calcium-45 Chemical compound [45Ca] OYPRJOBELJOOCE-BKFZFHPZSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 238000005618 Fries rearrangement reaction Methods 0.000 description 1
• JVJFIQYAHPMBBX-UHFFFAOYSA-N HNE Natural products CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 1
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 description 1
• 101000844510 Homo sapiens Transient receptor potential cation channel subfamily M member 1 Proteins 0.000 description 1
• 101000844503 Homo sapiens Transient receptor potential cation channel subfamily M member 3 Proteins 0.000 description 1
• 101000844519 Homo sapiens Transient receptor potential cation channel subfamily M member 6 Proteins 0.000 description 1
• 101000844518 Homo sapiens Transient receptor potential cation channel subfamily M member 7 Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010065390 Inflammatory pain Diseases 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• 101150091161 MCOLN1 gene Proteins 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 101100520164 Mus musculus Pkdrej gene Proteins 0.000 description 1
• 238000007126 N-alkylation reaction Methods 0.000 description 1
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
• 101100426589 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) trp-3 gene Proteins 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 101100047461 Rattus norvegicus Trpm8 gene Proteins 0.000 description 1
• 101100426590 Schizosaccharomyces pombe (strain 972 / ATCC 24843) trp2 gene Proteins 0.000 description 1
• 101100100680 Schizosaccharomyces pombe (strain 972 / ATCC 24843) trp4 gene Proteins 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 102000003627 TRPC1 Human genes 0.000 description 1
• 101150017559 TRPC1 gene Proteins 0.000 description 1
• 102000003629 TRPC3 Human genes 0.000 description 1
• 102000003622 TRPC4 Human genes 0.000 description 1
• 102000003621 TRPC5 Human genes 0.000 description 1
• 101150042815 TRPC5 gene Proteins 0.000 description 1
• 102000003623 TRPC6 Human genes 0.000 description 1
• 102000003609 TRPM5 Human genes 0.000 description 1
• 101150059135 TRPM5 gene Proteins 0.000 description 1
• 102000003608 TRPM6 Human genes 0.000 description 1
• 101150045183 TRPM7 gene Proteins 0.000 description 1
• 108091008849 TRPN Proteins 0.000 description 1
• 108010004408 TRPP Cation Channels Proteins 0.000 description 1
• 102000003567 TRPV4 Human genes 0.000 description 1
• 101150098315 TRPV4 gene Proteins 0.000 description 1
• 102100031229 Transient receptor potential cation channel subfamily M member 3 Human genes 0.000 description 1
• 102100031228 Transient receptor potential cation channel subfamily M member 4 Human genes 0.000 description 1
• 102100031232 Transient receptor potential cation channel subfamily M member 7 Human genes 0.000 description 1
• 101710123694 Transient receptor potential cation channel subfamily M member 7 Proteins 0.000 description 1
• 108050001421 Transient receptor potential channel, canonical 6 Proteins 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 101150037542 Trpc3 gene Proteins 0.000 description 1
• 101150099990 Trpc4 gene Proteins 0.000 description 1
• 101150032671 Trpm1 gene Proteins 0.000 description 1
• 101150111943 Trpm4 gene Proteins 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• QPBNUBJVIBPFJM-UHFFFAOYSA-N acetic acid;1h-pyrimidine-2,4-dione Chemical compound CC(O)=O.OC1=CC=NC(O)=N1 QPBNUBJVIBPFJM-UHFFFAOYSA-N 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 150000003975 aryl alkyl amines Chemical class 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 239000003637 basic solution Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001559 benzoic acids Chemical class 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 239000004305 biphenyl Chemical group 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 235000017803 cinnamon Nutrition 0.000 description 1
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 230000000850 deacetylating effect Effects 0.000 description 1
• 230000006196 deacetylation Effects 0.000 description 1
• 238000003381 deacetylation reaction Methods 0.000 description 1
• 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
• 229940009976 deoxycholate Drugs 0.000 description 1
• KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
• 230000003635 deoxygenating effect Effects 0.000 description 1
• 238000006392 deoxygenation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000006193 diazotization reaction Methods 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 235000004611 garlic Nutrition 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 150000002357 guanidines Chemical class 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• 102000052408 human TRPA1 Human genes 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000001871 ion mobility spectroscopy Methods 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• CKMLAFXRIHREHO-UHFFFAOYSA-N methyl 2-(1,3,7-trimethyl-2,4-dioxopyrrolo[2,3-d]pyrimidin-5-yl)acetate Chemical compound CN1C(=O)N(C)C(=O)C2=C1N(C)C=C2CC(=O)OC CKMLAFXRIHREHO-UHFFFAOYSA-N 0.000 description 1
• YZVMJEWKZHUUSP-UHFFFAOYSA-N methyl 2-(2,5,7-trimethyl-4,6-dioxopyrazolo[3,4-d]pyrimidin-3-yl)acetate Chemical compound CN1C(=O)N(C)C(=O)C2=C(CC(=O)OC)N(C)N=C21 YZVMJEWKZHUUSP-UHFFFAOYSA-N 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 235000010460 mustard Nutrition 0.000 description 1
• NGGXACLSAZXJGM-UHFFFAOYSA-N n-(diaminomethylidene)acetamide Chemical compound CC(=O)N=C(N)N NGGXACLSAZXJGM-UHFFFAOYSA-N 0.000 description 1
• JZJXUDDDTMHSBU-UHFFFAOYSA-N n-[4-[3,5-difluoro-4-(2-methylpropoxy)phenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=C(F)C(OCC(C)C)=C(F)C=C1C1=CSC(NC(=O)CN2C=3C(=O)N(C)C(=O)N(C)C=3C=C2)=N1 JZJXUDDDTMHSBU-UHFFFAOYSA-N 0.000 description 1
• RXOGCQYZCSVOKK-UHFFFAOYSA-N n-[4-[4-(cyclobutylmethoxy)-3,5-difluorophenyl]-1,3-thiazol-2-yl]-2-(1,3-dimethyl-2,4-dioxopyrrolo[3,2-d]pyrimidin-5-yl)acetamide Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2C=CN1CC(=O)NC(SC=1)=NC=1C(C=C1F)=CC(F)=C1OCC1CCC1 RXOGCQYZCSVOKK-UHFFFAOYSA-N 0.000 description 1
• NRPHMVYNJXMSLW-UHFFFAOYSA-N n-[5-[3-fluoro-4-(trifluoromethyl)phenyl]-1h-imidazol-2-yl]acetamide Chemical compound N1C(NC(=O)C)=NC(C=2C=C(F)C(=CC=2)C(F)(F)F)=C1 NRPHMVYNJXMSLW-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 230000001473 noxious effect Effects 0.000 description 1
• 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
• 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000003431 oxalo group Chemical group 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 238000007248 oxidative elimination reaction Methods 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 230000037324 pain perception Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 210000000578 peripheral nerve Anatomy 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 238000005502 peroxidation Methods 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 1
• BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 1
• 150000003233 pyrroles Chemical class 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• LGOOLCMGKKGBHW-UHFFFAOYSA-N pyrrolo[3,2-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C2=NC=CC2=N1 LGOOLCMGKKGBHW-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000006476 reductive cyclization reaction Methods 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 210000001044 sensory neuron Anatomy 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 230000003238 somatosensory effect Effects 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 101150079396 trpC2 gene Proteins 0.000 description 1
• 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1