JP2011519343A - Ｔｒｐｖ３モジュレーターとしてのクロマン誘導体 - Google Patents
Ｔｒｐｖ３モジュレーターとしてのクロマン誘導体 Download PDFInfo
- Publication number
- JP2011519343A JP2011519343A JP2010539048A JP2010539048A JP2011519343A JP 2011519343 A JP2011519343 A JP 2011519343A JP 2010539048 A JP2010539048 A JP 2010539048A JP 2010539048 A JP2010539048 A JP 2010539048A JP 2011519343 A JP2011519343 A JP 2011519343A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- compound
- unsubstituted
- dihydrospiro
- chromene
- 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.)
- Pending
Links
- 102000003568 TRPV3 Human genes 0.000 title claims abstract 5
- 101150043371 Trpv3 gene Proteins 0.000 title claims abstract 5
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 412
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 31
- 208000002193 Pain Diseases 0.000 claims abstract description 26
- 208000035475 disorder Diseases 0.000 claims abstract description 22
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 208000004296 neuralgia Diseases 0.000 claims abstract description 8
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 5
- 208000006820 Arthralgia Diseases 0.000 claims abstract description 4
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 4
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 4
- 208000004550 Postoperative Pain Diseases 0.000 claims abstract description 4
- 208000005298 acute pain Diseases 0.000 claims abstract description 4
- 206010003246 arthritis Diseases 0.000 claims abstract description 4
- 230000000302 ischemic effect Effects 0.000 claims abstract description 4
- 206010027599 migraine Diseases 0.000 claims abstract description 4
- 210000004165 myocardium Anatomy 0.000 claims abstract description 4
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 4
- 208000004371 toothache Diseases 0.000 claims abstract description 4
- 206010058019 Cancer Pain Diseases 0.000 claims abstract description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 3
- 206010044652 trigeminal neuralgia Diseases 0.000 claims abstract description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 312
- -1 nitro, cyano, amino Chemical group 0.000 claims description 264
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 126
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 102
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 102
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 96
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 95
- 125000003118 aryl group Chemical group 0.000 claims description 67
- VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 claims description 65
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000001072 heteroaryl group Chemical group 0.000 claims description 47
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 14
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 12
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
- 125000001316 cycloalkyl alkyl 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 230000006870 function Effects 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- QBDKYBYELHDDDG-UHFFFAOYSA-N spiro[3,4-dihydrochromene-2,1'-cyclobutane] Chemical compound C1CCC21OC1=CC=CC=C1CC2 QBDKYBYELHDDDG-UHFFFAOYSA-N 0.000 claims description 4
- UNFGQCCHVMMMRF-UHFFFAOYSA-N 2-phenylbutanamide Chemical compound CCC(C(N)=O)C1=CC=CC=C1 UNFGQCCHVMMMRF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- HCVFGRUKYVWXIF-UHFFFAOYSA-N n-(6-chloro-3,4-dihydro-2h-thiochromen-4-yl)-4-(2-cyclopentyloxy-3-methoxyphenyl)butanamide Chemical compound COC1=CC=CC(CCCC(=O)NC2C3=CC(Cl)=CC=C3SCC2)=C1OC1CCCC1 HCVFGRUKYVWXIF-UHFFFAOYSA-N 0.000 claims description 3
- UIQODYCOSLDHFU-UHFFFAOYSA-N n-(6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-2-pyridin-2-ylacetamide Chemical compound C1C(NC(=O)CC=2N=CC=CC=2)C2=CC(Cl)=CC=C2OC21CCC2 UIQODYCOSLDHFU-UHFFFAOYSA-N 0.000 claims description 3
- UOYBBAUKZUIFAF-UHFFFAOYSA-N n-(6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-3-naphthalen-1-ylpropanamide Chemical compound C1C(NC(=O)CCC=2C3=CC=CC=C3C=CC=2)C2=CC(Cl)=CC=C2OC21CCC2 UOYBBAUKZUIFAF-UHFFFAOYSA-N 0.000 claims description 3
- ABINOOJEFPZEPJ-UHFFFAOYSA-N n-(8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-2-phenylacetamide Chemical compound O1C=2C(Cl)=CC=CC=2C(NC(=O)CC=2C=CC=CC=2)CC21CCC2 ABINOOJEFPZEPJ-UHFFFAOYSA-N 0.000 claims description 3
- YMQJPGZGICKOMX-BVHINDKJSA-N n-[(4r)-6-chloro-3-dibenzofuran-2-yl-3,4-dihydro-2h-chromen-4-yl]acetamide Chemical compound C1=CC=C2C3=CC(C4[C@H](C5=CC(Cl)=CC=C5OC4)NC(=O)C)=CC=C3OC2=C1 YMQJPGZGICKOMX-BVHINDKJSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 claims description 3
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 2
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
- HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 claims description 2
- 201000004384 Alopecia Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
- TUNWYLZLOVAGDE-UHFFFAOYSA-N ClC=1C=C2C(CC3(CCC3)OC2=C(C1)Cl)N(C=1C(=C(C=CC1)C(C)C)OCCC)S(=O)(=O)C Chemical compound ClC=1C=C2C(CC3(CCC3)OC2=C(C1)Cl)N(C=1C(=C(C=CC1)C(C)C)OCCC)S(=O)(=O)C TUNWYLZLOVAGDE-UHFFFAOYSA-N 0.000 claims description 2
- VGWOFVUQTVPGHU-UHFFFAOYSA-N ClC=1C=C2C(CC3(CCC3)OC2=C(C1)Cl)N(C=1C(=C(C=CC1)C(C)C)OCCCC)S(=O)(=O)C Chemical compound ClC=1C=C2C(CC3(CCC3)OC2=C(C1)Cl)N(C=1C(=C(C=CC1)C(C)C)OCCCC)S(=O)(=O)C VGWOFVUQTVPGHU-UHFFFAOYSA-N 0.000 claims description 2
- 208000015943 Coeliac disease Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 208000012661 Dyskinesia Diseases 0.000 claims description 2
- 208000004232 Enteritis Diseases 0.000 claims description 2
- 206010017886 Gastroduodenal ulcer Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000027530 Meniere disease Diseases 0.000 claims description 2
- 208000007101 Muscle Cramp Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000001294 Nociceptive Pain Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 206010038923 Retinopathy Diseases 0.000 claims description 2
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
- 208000005392 Spasm Diseases 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims description 2
- 206010060875 Uraemic pruritus Diseases 0.000 claims description 2
- 206010046543 Urinary incontinence Diseases 0.000 claims description 2
- 208000024780 Urticaria Diseases 0.000 claims description 2
- 206010047700 Vomiting Diseases 0.000 claims description 2
- 208000009621 actinic keratosis Diseases 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 230000000172 allergic effect Effects 0.000 claims description 2
- 201000010105 allergic rhinitis Diseases 0.000 claims description 2
- 231100000360 alopecia Toxicity 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 230000036760 body temperature Effects 0.000 claims description 2
- 230000003925 brain function Effects 0.000 claims description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 210000001508 eye Anatomy 0.000 claims description 2
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 claims description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 2
- 230000009610 hypersensitivity Effects 0.000 claims description 2
- 208000009326 ileitis Diseases 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 230000007794 irritation Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 206010027175 memory impairment Diseases 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 210000004400 mucous membrane Anatomy 0.000 claims description 2
- JTOKVVSQNLAMLI-OAQYLSRUSA-N n-[(4r)-8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl]-2-naphthalen-1-ylacetamide Chemical compound C([C@H](C=1C=CC=C(C=1O1)Cl)NC(=O)CC=2C3=CC=CC=C3C=CC=2)C21CCC2 JTOKVVSQNLAMLI-OAQYLSRUSA-N 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 201000001119 neuropathy Diseases 0.000 claims description 2
- 230000007823 neuropathy Effects 0.000 claims description 2
- 208000037916 non-allergic rhinitis Diseases 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- 230000001823 pruritic effect Effects 0.000 claims description 2
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 claims description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 2
- 231100000886 tinnitus Toxicity 0.000 claims description 2
- 230000008673 vomiting Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 208000011580 syndromic disease Diseases 0.000 claims 4
- 102000011040 TRPV Cation Channels Human genes 0.000 claims 2
- 108010062740 TRPV Cation Channels Proteins 0.000 claims 2
- 125000003418 alkyl amino alkoxy group Chemical group 0.000 claims 2
- 208000019693 Lung disease Diseases 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- KVRXTQZXHGPQAE-OAQYLSRUSA-N n-[(4r)-6,8-difluorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl]-2-naphthalen-1-ylacetamide Chemical compound C1([C@H](NC(=O)CC=2C3=CC=CC=C3C=CC=2)C2)=CC(F)=CC(F)=C1OC12CCC1 KVRXTQZXHGPQAE-OAQYLSRUSA-N 0.000 claims 1
- DWQNFDLYLYBVKF-OAQYLSRUSA-N n-[(4r)-6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl]-2-naphthalen-1-ylacetamide Chemical compound C1([C@H](NC(=O)CC=2C3=CC=CC=C3C=CC=2)C2)=CC(Cl)=CC=C1OC12CCC1 DWQNFDLYLYBVKF-OAQYLSRUSA-N 0.000 claims 1
- 230000000414 obstructive effect Effects 0.000 claims 1
- 208000027753 pain disease Diseases 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 133
- 108020003175 receptors Proteins 0.000 abstract description 7
- 102000005962 receptors Human genes 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 206010065390 Inflammatory pain Diseases 0.000 abstract description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 abstract description 2
- 230000001052 transient effect Effects 0.000 abstract description 2
- 230000006806 disease prevention Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 113
- 239000007787 solid Substances 0.000 description 112
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 66
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 13
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 13
- 235000019260 propionic acid Nutrition 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 9
- 239000005971 1-naphthylacetic acid Substances 0.000 description 9
- RAYZPJVIHSRBQT-UHFFFAOYSA-N 4-(2-cyclopentyloxy-3-methoxyphenyl)butanoic acid Chemical compound COC1=CC=CC(CCCC(O)=O)=C1OC1CCCC1 RAYZPJVIHSRBQT-UHFFFAOYSA-N 0.000 description 9
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 108091006146 Channels Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- QFQGXOGAIJYSFK-UHFFFAOYSA-N spiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical class O1C2=CC=CC=C2C(N)CC21CCC2 QFQGXOGAIJYSFK-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- NKAUNQHFTNOKKK-UHFFFAOYSA-N 3-(2-cyclopentyloxy-3-methoxyphenyl)propanoic acid Chemical compound COC1=CC=CC(CCC(O)=O)=C1OC1CCCC1 NKAUNQHFTNOKKK-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 108091053409 transient receptor (TC 1.A.4) family Proteins 0.000 description 5
- 102000042565 transient receptor (TC 1.A.4) family Human genes 0.000 description 5
- BLZVCIGGICSWIG-UHFFFAOYSA-N 2-aminoethoxydiphenylborane Chemical compound C=1C=CC=CC=1B(OCCN)C1=CC=CC=C1 BLZVCIGGICSWIG-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000011905 homologation Methods 0.000 description 4
- 238000001871 ion mobility spectroscopy Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- UIQLYQPVRAHTIK-UHFFFAOYSA-N 2-(2-cyclopentyloxy-3-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC(CC(O)=O)=C1OC1CCCC1 UIQLYQPVRAHTIK-UHFFFAOYSA-N 0.000 description 3
- AUVKOEHVYGYIKP-UHFFFAOYSA-N 3-(2-methoxynaphthalen-1-yl)propanoic acid Chemical compound C1=CC=CC2=C(CCC(O)=O)C(OC)=CC=C21 AUVKOEHVYGYIKP-UHFFFAOYSA-N 0.000 description 3
- QCVKLQRGFFNQMQ-UHFFFAOYSA-N 3-[3-(methanesulfonamido)-2-propan-2-yloxyphenyl]propanoic acid Chemical compound CC(C)OC1=C(CCC(O)=O)C=CC=C1NS(C)(=O)=O QCVKLQRGFFNQMQ-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 108091005462 Cation channels Proteins 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- VAHPFHDJAVFATB-UHFFFAOYSA-N spiro[3h-chromene-2,1'-cyclobutane]-4-one Chemical compound O1C2=CC=CC=C2C(=O)CC21CCC2 VAHPFHDJAVFATB-UHFFFAOYSA-N 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 2
- CGPHGPCHVUSFFA-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C(O)=O)CCC1 CGPHGPCHVUSFFA-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BVSIAYQIMUUCRW-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=NOC2=C1 BVSIAYQIMUUCRW-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical class OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- ZYDCENGYZQQPSK-UHFFFAOYSA-N 3-(1,3-benzodioxol-4-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC2=C1OCO2 ZYDCENGYZQQPSK-UHFFFAOYSA-N 0.000 description 2
- GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 description 2
- OLBGSNGZJNQJDZ-UHFFFAOYSA-N 3-(2-cyclopentyloxy-3-methylphenyl)propanoic acid Chemical compound CC1=CC=CC(CCC(O)=O)=C1OC1CCCC1 OLBGSNGZJNQJDZ-UHFFFAOYSA-N 0.000 description 2
- OJXLYUHXBOTGIM-UHFFFAOYSA-N 3-(4-methoxynaphthalen-1-yl)propanoic acid Chemical compound C1=CC=C2C(OC)=CC=C(CCC(O)=O)C2=C1 OJXLYUHXBOTGIM-UHFFFAOYSA-N 0.000 description 2
- XRJFAPBYBJAFKS-UHFFFAOYSA-N 3-(4-methoxynaphthalen-2-yl)propanoic acid Chemical compound C1=CC=C2C(OC)=CC(CCC(O)=O)=CC2=C1 XRJFAPBYBJAFKS-UHFFFAOYSA-N 0.000 description 2
- WQQSVTNSLWJMFI-UHFFFAOYSA-N 3-[4-(difluoromethoxy)naphthalen-1-yl]propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CC=C(OC(F)F)C2=C1 WQQSVTNSLWJMFI-UHFFFAOYSA-N 0.000 description 2
- VXIXUWQIVKSKSA-UHFFFAOYSA-N 4-hydroxycoumarin Chemical compound C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 101000633107 Homo sapiens Transient receptor potential cation channel subfamily V member 3 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 108060008564 TRPV Proteins 0.000 description 2
- 102000003563 TRPV Human genes 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
- 102000052198 human TRPV3 Human genes 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 description 2
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 description 2
- DGUWACLYDSWXRZ-UHFFFAOYSA-N (2-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C=O DGUWACLYDSWXRZ-UHFFFAOYSA-N 0.000 description 1
- WMUZDBZPDLHUMW-UHFFFAOYSA-N (2-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1[N+]([O-])=O WMUZDBZPDLHUMW-UHFFFAOYSA-N 0.000 description 1
- PTKPWRCGRXOQEN-SNVBAGLBSA-N (4r)-6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C([C@H](C1=CC(Cl)=CC=C1O1)N)C21CCC2 PTKPWRCGRXOQEN-SNVBAGLBSA-N 0.000 description 1
- BKNLEIBZDPSFFF-SNVBAGLBSA-N (4r)-8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C([C@H](C1=CC=CC(Cl)=C1O1)N)C21CCC2 BKNLEIBZDPSFFF-SNVBAGLBSA-N 0.000 description 1
- PTKPWRCGRXOQEN-JTQLQIEISA-N (4s)-6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C([C@@H](C1=CC(Cl)=CC=C1O1)N)C21CCC2 PTKPWRCGRXOQEN-JTQLQIEISA-N 0.000 description 1
- BKNLEIBZDPSFFF-JTQLQIEISA-N (4s)-8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C([C@@H](C1=CC=CC(Cl)=C1O1)N)C21CCC2 BKNLEIBZDPSFFF-JTQLQIEISA-N 0.000 description 1
- WHCWHBRLHPPUCR-CMDGGOBGSA-N (e)-3-(2-pyridin-2-ylphenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1C1=CC=CC=N1 WHCWHBRLHPPUCR-CMDGGOBGSA-N 0.000 description 1
- UTQNQGGKUKJZSV-ZHACJKMWSA-N (e)-3-(3-methoxy-2-phenylmethoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=CC(\C=C\C(O)=O)=C1OCC1=CC=CC=C1 UTQNQGGKUKJZSV-ZHACJKMWSA-N 0.000 description 1
- NOAVZZTYOVFOTP-BQYQJAHWSA-N (e)-3-[2-(propan-2-ylsulfonylamino)phenyl]prop-2-enoic acid Chemical compound CC(C)S(=O)(=O)NC1=CC=CC=C1\C=C\C(O)=O NOAVZZTYOVFOTP-BQYQJAHWSA-N 0.000 description 1
- QHJIDQGIAPCVMU-BQYQJAHWSA-N (e)-3-quinolin-2-ylprop-2-enoic acid Chemical compound C1=CC=CC2=NC(/C=C/C(=O)O)=CC=C21 QHJIDQGIAPCVMU-BQYQJAHWSA-N 0.000 description 1
- DMMGNAYOWXQFID-PKNBQFBNSA-N (e)-n-(6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-3-quinolin-2-ylprop-2-enamide Chemical compound C1C(NC(=O)\C=C\C=2N=C3C=CC=CC3=CC=2)C2=CC(Cl)=CC=C2OC21CCC2 DMMGNAYOWXQFID-PKNBQFBNSA-N 0.000 description 1
- WDTQEHUEBGDENG-GXDHUFHOSA-N (ne)-n-(6-chlorospiro[3h-chromene-2,1'-cyclobutane]-4-ylidene)hydroxylamine Chemical compound O1C2=CC=C(Cl)C=C2C(=N/O)/CC21CCC2 WDTQEHUEBGDENG-GXDHUFHOSA-N 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
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- YSTIIIRGSQEQNH-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydrochromen-4-amine Chemical compound C1=CC=C2OC(C)(C)CC(N)C2=C1 YSTIIIRGSQEQNH-UHFFFAOYSA-N 0.000 description 1
- NDIOUAVQWJEYHA-UHFFFAOYSA-N 2-(1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid Chemical compound C1=CC=C2CC(CC(=O)O)CCC2=C1 NDIOUAVQWJEYHA-UHFFFAOYSA-N 0.000 description 1
- NXLXDCHSJLNMGU-UHFFFAOYSA-N 2-(1,3-benzodioxol-4-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC2=C1OCO2 NXLXDCHSJLNMGU-UHFFFAOYSA-N 0.000 description 1
- IVEWTCACRDEAOB-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC=C1CC(O)=O IVEWTCACRDEAOB-UHFFFAOYSA-N 0.000 description 1
- HBYIJKKZLCCVML-UHFFFAOYSA-N 2-(5,6,7,8-tetrahydronaphthalen-1-yl)acetic acid Chemical compound C1CCCC2=C1C=CC=C2CC(=O)O HBYIJKKZLCCVML-UHFFFAOYSA-N 0.000 description 1
- VJZAMNBVIWOUJR-UHFFFAOYSA-N 2-(5-fluoro-2-methyl-1h-indol-3-yl)acetic acid Chemical compound C1=C(F)C=C2C(CC(O)=O)=C(C)NC2=C1 VJZAMNBVIWOUJR-UHFFFAOYSA-N 0.000 description 1
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- VKCNNDPZFOVURD-UHFFFAOYSA-N 2-naphthalen-1-ylpropanoic acid Chemical compound C1=CC=C2C(C(C(O)=O)C)=CC=CC2=C1 VKCNNDPZFOVURD-UHFFFAOYSA-N 0.000 description 1
- VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 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
- BPSNETAIJADFTO-UHFFFAOYSA-N 2-pyridinylacetic acid Chemical compound OC(=O)CC1=CC=CC=N1 BPSNETAIJADFTO-UHFFFAOYSA-N 0.000 description 1
- VGCNVPXAIFXIDF-UHFFFAOYSA-N 2h-chromen-4-amine Chemical compound C1=CC=C2C(N)=CCOC2=C1 VGCNVPXAIFXIDF-UHFFFAOYSA-N 0.000 description 1
- GHFKRCCBOMTLMF-UHFFFAOYSA-N 3-(2,3-dihydro-1,4-benzodioxin-5-yl)propanoic acid Chemical compound O1CCOC2=C1C=CC=C2CCC(=O)O GHFKRCCBOMTLMF-UHFFFAOYSA-N 0.000 description 1
- JYAJUMPCPQRKKU-UHFFFAOYSA-N 3-(2,3-dihydro-1,4-benzodioxin-6-yl)propanoic acid Chemical compound O1CCOC2=CC(CCC(=O)O)=CC=C21 JYAJUMPCPQRKKU-UHFFFAOYSA-N 0.000 description 1
- QPHAUUNQQLRYCJ-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)propanoic acid Chemical compound COC1=CC=CC(CCC(O)=O)=C1OC QPHAUUNQQLRYCJ-UHFFFAOYSA-N 0.000 description 1
- APVUXDWUVWZVBU-UHFFFAOYSA-N 3-(2-cyclopentyloxy-3-ethoxyphenyl)propanoic acid Chemical compound CCOC1=CC=CC(CCC(O)=O)=C1OC1CCCC1 APVUXDWUVWZVBU-UHFFFAOYSA-N 0.000 description 1
- DHIVCLLRAFSLCL-UHFFFAOYSA-N 3-(2-cyclopentyloxy-3-methoxyphenyl)butanoic acid Chemical compound COC1=CC=CC(C(C)CC(O)=O)=C1OC1CCCC1 DHIVCLLRAFSLCL-UHFFFAOYSA-N 0.000 description 1
- POCACMYXXDFXNA-UHFFFAOYSA-N 3-(2-cyclopentyloxyphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1OC1CCCC1 POCACMYXXDFXNA-UHFFFAOYSA-N 0.000 description 1
- UMHUEEUKPMGPIL-UHFFFAOYSA-N 3-(2-ethoxy-3-methoxyphenyl)propanoic acid Chemical compound CCOC1=C(CCC(O)=O)C=CC=C1OC UMHUEEUKPMGPIL-UHFFFAOYSA-N 0.000 description 1
- UUZRWWRFDJGLFU-UHFFFAOYSA-N 3-(2-methyl-1-benzofuran-4-yl)propanoic acid Chemical compound C1=CC=C2OC(C)=CC2=C1CCC(O)=O UUZRWWRFDJGLFU-UHFFFAOYSA-N 0.000 description 1
- VKSGMFKOOKXQTN-UHFFFAOYSA-N 3-(2-pyridin-2-ylphenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=CC=C1C1=CC=CC=N1 VKSGMFKOOKXQTN-UHFFFAOYSA-N 0.000 description 1
- MAYOFTZUJPQKET-UHFFFAOYSA-N 3-(3-chloro-4-methoxyphenyl)propanoic acid Chemical compound COC1=CC=C(CCC(O)=O)C=C1Cl MAYOFTZUJPQKET-UHFFFAOYSA-N 0.000 description 1
- STLQLWZRPMBHEJ-UHFFFAOYSA-N 3-(3-methoxy-2-propan-2-yloxyphenyl)propanoic acid Chemical compound COC1=CC=CC(CCC(O)=O)=C1OC(C)C STLQLWZRPMBHEJ-UHFFFAOYSA-N 0.000 description 1
- ZFFYDOYTGRBFKP-UHFFFAOYSA-N 3-(6-cyclopentyloxy-6-methoxycyclohexa-2,4-dien-1-yl)propanoic acid Chemical compound C1CCCC1OC1(OC)C=CC=CC1CCC(O)=O ZFFYDOYTGRBFKP-UHFFFAOYSA-N 0.000 description 1
- GQYRELDXDNXTNU-UHFFFAOYSA-N 3-(7-methoxy-2-methyl-1-benzofuran-4-yl)propanoic acid Chemical compound COC1=CC=C(CCC(O)=O)C2=C1OC(C)=C2 GQYRELDXDNXTNU-UHFFFAOYSA-N 0.000 description 1
- YFGWECQRHVVOBJ-UHFFFAOYSA-N 3-(7-methoxy-2-methyl-1-benzofuran-5-yl)propanoic acid Chemical compound COC1=CC(CCC(O)=O)=CC2=C1OC(C)=C2 YFGWECQRHVVOBJ-UHFFFAOYSA-N 0.000 description 1
- RYNJDYZQIGSAKO-UHFFFAOYSA-N 3-[2-(cyclopropylmethoxy)-3-(methanesulfonamido)phenyl]propanoic acid Chemical compound CS(=O)(=O)NC1=CC=CC(CCC(O)=O)=C1OCC1CC1 RYNJDYZQIGSAKO-UHFFFAOYSA-N 0.000 description 1
- ACNIPTNUWBHPEI-UHFFFAOYSA-N 3-[2-(cyclopropylmethoxy)-3-methoxyphenyl]propanoic acid Chemical compound COC1=CC=CC(CCC(O)=O)=C1OCC1CC1 ACNIPTNUWBHPEI-UHFFFAOYSA-N 0.000 description 1
- PKLPGRUPNYDLEJ-UHFFFAOYSA-N 3-[2-[2-(dimethylazaniumyl)ethoxy]-3-methoxyphenyl]propanoate Chemical compound COC1=CC=CC(CCC(O)=O)=C1OCCN(C)C PKLPGRUPNYDLEJ-UHFFFAOYSA-N 0.000 description 1
- CYHQQGNABKMLSS-UHFFFAOYSA-N 3-[2-butoxy-3-(methanesulfonamido)phenyl]propanoic acid Chemical compound CCCCOC1=C(CCC(O)=O)C=CC=C1NS(C)(=O)=O CYHQQGNABKMLSS-UHFFFAOYSA-N 0.000 description 1
- MRQHRXNQAHEKDR-UHFFFAOYSA-N 3-[3-(methanesulfonamido)-2-propoxyphenyl]propanoic acid Chemical compound CCCOC1=C(CCC(O)=O)C=CC=C1NS(C)(=O)=O MRQHRXNQAHEKDR-UHFFFAOYSA-N 0.000 description 1
- LCTSXADXAPFEDC-UHFFFAOYSA-N 3-[5-(methanesulfonamido)-2-propan-2-yloxyphenyl]propanoic acid Chemical compound CC(C)OC1=CC=C(NS(C)(=O)=O)C=C1CCC(O)=O LCTSXADXAPFEDC-UHFFFAOYSA-N 0.000 description 1
- XODBCXUINWJEKL-UHFFFAOYSA-N 3-dibenzofuran-4-ylpropanoic acid Chemical compound C12=CC=CC=C2OC2=C1C=CC=C2CCC(=O)O XODBCXUINWJEKL-UHFFFAOYSA-N 0.000 description 1
- IZOYTDIICIICBE-UHFFFAOYSA-N 3-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(CCC(=O)O)=CC=C21 IZOYTDIICIICBE-UHFFFAOYSA-N 0.000 description 1
- DWXRALBDWZFUTQ-UHFFFAOYSA-N 4-(2-cyclopentyloxyphenyl)butanoic acid Chemical compound OC(=O)CCCC1=CC=CC=C1OC1CCCC1 DWXRALBDWZFUTQ-UHFFFAOYSA-N 0.000 description 1
- XLMIVOUBVCDUPZ-FZSMXKCYSA-N 4-methylbenzenesulfonic acid;(2r)-pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1.CC1=CC=C(S(O)(=O)=O)C=C1 XLMIVOUBVCDUPZ-FZSMXKCYSA-N 0.000 description 1
- XLMIVOUBVCDUPZ-VWMHFEHESA-N 4-methylbenzenesulfonic acid;(2s)-pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1.CC1=CC=C(S(O)(=O)=O)C=C1 XLMIVOUBVCDUPZ-VWMHFEHESA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- QLRBHLPIQAJKIN-UHFFFAOYSA-N 5-methoxyspiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C1C(N)C=2C(OC)=CC=CC=2OC21CCC2 QLRBHLPIQAJKIN-UHFFFAOYSA-N 0.000 description 1
- XZLOYHHMEYXQEU-UHFFFAOYSA-N 5-phenylmethoxyspiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=CC=CC(OCC=3C=CC=CC=3)=C2C(N)CC21CCC2 XZLOYHHMEYXQEU-UHFFFAOYSA-N 0.000 description 1
- DZGWSEDHIMLGJT-UHFFFAOYSA-N 6,8-dichlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=C(Cl)C=C(Cl)C=C2C(N)CC21CCC2 DZGWSEDHIMLGJT-UHFFFAOYSA-N 0.000 description 1
- FEIHEFQLUXCBGM-UHFFFAOYSA-N 6,8-difluorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=C(F)C=C(F)C=C2C(N)CC21CCC2 FEIHEFQLUXCBGM-UHFFFAOYSA-N 0.000 description 1
- YCHLOTPQPGERAD-UHFFFAOYSA-N 6-chloro-2,2-dimethyl-3,4-dihydrochromen-4-amine Chemical compound ClC1=CC=C2OC(C)(C)CC(N)C2=C1 YCHLOTPQPGERAD-UHFFFAOYSA-N 0.000 description 1
- WVOPBIDNAGCFIJ-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-thiochromen-4-amine Chemical compound C1=C(Cl)C=C2C(N)CCSC2=C1 WVOPBIDNAGCFIJ-UHFFFAOYSA-N 0.000 description 1
- GJCBFBKIFQBKJE-UHFFFAOYSA-N 6-chloro-7-methylspiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound C1C(N)C=2C=C(Cl)C(C)=CC=2OC21CCC2 GJCBFBKIFQBKJE-UHFFFAOYSA-N 0.000 description 1
- PTKPWRCGRXOQEN-UHFFFAOYSA-N 6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=CC=C(Cl)C=C2C(N)CC21CCC2 PTKPWRCGRXOQEN-UHFFFAOYSA-N 0.000 description 1
- WBPJQLVMJUWYDJ-UHFFFAOYSA-N 6-chlorospiro[3,4-dihydrochromene-2,1'-cyclohexane]-4-amine Chemical compound O1C2=CC=C(Cl)C=C2C(N)CC21CCCCC2 WBPJQLVMJUWYDJ-UHFFFAOYSA-N 0.000 description 1
- QXAJODYLQZMLAF-UHFFFAOYSA-N 6-chlorospiro[3,4-dihydrochromene-2,1'-cyclopentane]-4-amine Chemical compound O1C2=CC=C(Cl)C=C2C(N)CC21CCCC2 QXAJODYLQZMLAF-UHFFFAOYSA-N 0.000 description 1
- IIJSMMZDAYZHBP-UHFFFAOYSA-N 6-fluorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=CC=C(F)C=C2C(N)CC21CCC2 IIJSMMZDAYZHBP-UHFFFAOYSA-N 0.000 description 1
- WYQVMRSNNOGTDJ-UHFFFAOYSA-N 7-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=CC(Cl)=CC=C2C(N)CC21CCC2 WYQVMRSNNOGTDJ-UHFFFAOYSA-N 0.000 description 1
- RYGXTDOAPVWESU-UHFFFAOYSA-N 7-phenylmethoxyspiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=CC(OCC=3C=CC=CC=3)=CC=C2C(N)CC21CCC2 RYGXTDOAPVWESU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- ATXJZRUFWUGTFC-UHFFFAOYSA-N 8-chloro-6-fluorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=C(Cl)C=C(F)C=C2C(N)CC21CCC2 ATXJZRUFWUGTFC-UHFFFAOYSA-N 0.000 description 1
- BKNLEIBZDPSFFF-UHFFFAOYSA-N 8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-amine Chemical compound O1C2=C(Cl)C=CC=C2C(N)CC21CCC2 BKNLEIBZDPSFFF-UHFFFAOYSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229920000856 Amylose Polymers 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
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 238000006000 Knoevenagel condensation reaction Methods 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101100208031 Mus musculus Trpv3 gene Proteins 0.000 description 1
- TXWGINUZLBAKDF-UHFFFAOYSA-N N-Deschlorobenzoyl indomethacin Chemical compound COC1=CC=C2NC(C)=C(CC(O)=O)C2=C1 TXWGINUZLBAKDF-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000003728 Vulvodynia Diseases 0.000 description 1
- 206010069055 Vulvovaginal pain Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- BTDFMSBISWEPSZ-UHFFFAOYSA-N acetic acid;1,2,3,4-tetrahydronaphthalene Chemical compound CC(O)=O.C1=CC=C2CCCCC2=C1 BTDFMSBISWEPSZ-UHFFFAOYSA-N 0.000 description 1
- DODXVGQZQIEBHX-UHFFFAOYSA-N acetic acid;1,2-benzoxazole Chemical compound CC(O)=O.C1=CC=C2C=NOC2=C1 DODXVGQZQIEBHX-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229940035676 analgesics Drugs 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
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000003935 benzaldehydes Chemical class 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
- 150000001562 benzopyrans 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
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 150000003997 cyclic ketones Chemical class 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
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 230000003111 delayed effect Effects 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
- 235000019425 dextrin Nutrition 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004721 gamma keto acids Chemical class 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000003617 indole-3-acetic acid Substances 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
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 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
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- FHGJSJFIQNQBCK-UHFFFAOYSA-N menbutone Chemical compound C1=CC=C2C(OC)=CC=C(C(=O)CCC(O)=O)C2=C1 FHGJSJFIQNQBCK-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- PLLMKJLPBLPJAU-UHFFFAOYSA-N methoxymethylidene(triphenyl)-$l^{5}-phosphane;hydrochloride Chemical compound Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)(=COC)C1=CC=CC=C1 PLLMKJLPBLPJAU-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- CQTRCIZQRVOJME-UHFFFAOYSA-N methyl 2-phenylbut-2-enoate Chemical class COC(=O)C(=CC)C1=CC=CC=C1 CQTRCIZQRVOJME-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- OENDOXMVAKXVRG-UHFFFAOYSA-N n-(5-hydroxyspiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-2-naphthalen-1-ylacetamide Chemical compound C1C(NC(=O)CC=2C3=CC=CC=C3C=CC=2)C=2C(O)=CC=CC=2OC21CCC2 OENDOXMVAKXVRG-UHFFFAOYSA-N 0.000 description 1
- RSIMYSZPFUDGCF-UHFFFAOYSA-N n-(6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-2-(2-methoxyphenyl)acetamide Chemical compound COC1=CC=CC=C1CC(=O)NC1C2=CC(Cl)=CC=C2OC2(CCC2)C1 RSIMYSZPFUDGCF-UHFFFAOYSA-N 0.000 description 1
- IQFGZSHORRQUKW-UHFFFAOYSA-N n-(6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl)-3-(1h-indol-3-yl)propanamide Chemical compound C1C(NC(=O)CCC=2C3=CC=CC=C3NC=2)C2=CC(Cl)=CC=C2OC21CCC2 IQFGZSHORRQUKW-UHFFFAOYSA-N 0.000 description 1
- DWQNFDLYLYBVKF-NRFANRHFSA-N n-[(4s)-6-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl]-2-naphthalen-1-ylacetamide Chemical compound C1([C@@H](NC(=O)CC=2C3=CC=CC=C3C=CC=2)C2)=CC(Cl)=CC=C1OC12CCC1 DWQNFDLYLYBVKF-NRFANRHFSA-N 0.000 description 1
- JTOKVVSQNLAMLI-NRFANRHFSA-N n-[(4s)-8-chlorospiro[3,4-dihydrochromene-2,1'-cyclobutane]-4-yl]-2-naphthalen-1-ylacetamide Chemical compound C([C@@H](C=1C=CC=C(C=1O1)Cl)NC(=O)CC=2C3=CC=CC=C3C=CC=2)C21CCC2 JTOKVVSQNLAMLI-NRFANRHFSA-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
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 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
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 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
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical class O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 230000002685 pulmonary effect Effects 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
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 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
- 150000003254 radicals Chemical class 0.000 description 1
- 108700021113 rat TRPV3 Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl 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
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 210000000427 trigeminal ganglion Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/96—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings spiro-condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Otolaryngology (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Psychology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2481MU2007 | 2007-12-18 | ||
| IN2481/MUM/2007 | 2007-12-18 | ||
| IN647MU2008 | 2008-03-26 | ||
| IN647/MUM/2008 | 2008-03-26 | ||
| PCT/IN2008/000838 WO2009084034A2 (en) | 2007-12-18 | 2008-12-16 | Chromane derivatives as trpv3 modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011519343A true JP2011519343A (ja) | 2011-07-07 |
| JP2011519343A5 JP2011519343A5 (enExample) | 2012-01-26 |
Family
ID=40824849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010539048A Pending JP2011519343A (ja) | 2007-12-18 | 2008-12-16 | Ｔｒｐｖ３モジュレーターとしてのクロマン誘導体 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8487121B2 (enExample) |
| EP (1) | EP2254879A4 (enExample) |
| JP (1) | JP2011519343A (enExample) |
| AU (1) | AU2008344922A1 (enExample) |
| CA (1) | CA2706566A1 (enExample) |
| EA (1) | EA201000675A1 (enExample) |
| GE (1) | GEP20125707B (enExample) |
| MX (1) | MX2010005704A (enExample) |
| NZ (1) | NZ595776A (enExample) |
| WO (1) | WO2009084034A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017533277A (ja) * | 2014-10-31 | 2017-11-09 | アッヴィ・エス・ア・エール・エル | 置換テトラヒドロピランおよび使用方法 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GEP20146096B (en) | 2008-12-26 | 2014-05-27 | Glenmark Pharmaceuticals Sa | Fused imidazole derivatives as trpv3 antagonists |
| EP2421980A2 (en) | 2009-04-23 | 2012-02-29 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for cancer |
| US9314005B2 (en) | 2009-07-01 | 2016-04-19 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for severe combined immunodeficiency (SCID) |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| HRP20181746T1 (hr) | 2011-12-16 | 2018-12-28 | Poseida Therapeutics, Inc. | Trpc4 modulatori za uporabu u liječenju ili prevenciji bola |
| EP3558298A4 (en) * | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | ANTIDIABETIC SPIROCHROMAN COMPOUNDS |
| RU2713946C1 (ru) * | 2019-11-13 | 2020-02-11 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | 4,7-диметил-3,4,4a,5,8,8a-гексагидроспиро[хромен-2,1'-циклогексан]-4,8-диол в качестве анальгезирующего средства |
| CN120882726A (zh) * | 2022-12-26 | 2025-10-31 | 阳光安津(南京)生物医药科技有限公司 | 包括杂芳环的化合物及其组合物和方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02223574A (ja) * | 1988-04-26 | 1990-09-05 | Yoshitomi Pharmaceut Ind Ltd | ベンゾピラン化合物 |
| US5276168A (en) * | 1990-06-18 | 1994-01-04 | E. R. Squibb & Sons, Inc. | Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents |
| WO2000003681A2 (en) * | 1998-07-16 | 2000-01-27 | Axys Pharmaceuticals, Inc. | Process for the synthesis of benzopyran derivatives |
| JP2006522835A (ja) * | 2003-04-10 | 2006-10-05 | アムジェン インコーポレイテッド | 環状アミン誘導体およびブラジキニンによって媒介される炎症関連障害の処置におけるそれらの使用 |
| WO2007042906A1 (en) * | 2005-10-07 | 2007-04-19 | Glenmark Pharmaceuticals S.A. | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4537962A (en) | 1982-02-04 | 1985-08-27 | Farmitalia Carlo Erba, S.P.A. | Substituted 1,3,4-thiadiazolo[3,2-A]pyrimidines and compositions containing them |
| US5418245A (en) | 1990-04-16 | 1995-05-23 | Rhone-Poulenc Rorer International (Holdings) Inc. | Styryl-substituted monocyclic and bicyclic heteroaryl compounds which inhibit EGF receptor tyrosine kinase |
| JPH07242666A (ja) | 1994-03-08 | 1995-09-19 | Fujisawa Pharmaceut Co Ltd | 複素環化合物 |
| WO1998046588A2 (en) | 1997-04-11 | 1998-10-22 | Neorx Corporation | Compounds and therapies for the prevention of vascular and non-vascular pathologies |
| US6797819B1 (en) | 1998-06-11 | 2004-09-28 | President And Fellows Of Harvard College | Alkaloids |
| US6610749B2 (en) | 2000-02-18 | 2003-08-26 | Arch Development Corporation | Polyhydroxylated benzene-containing compounds |
| US6559145B2 (en) | 2000-07-12 | 2003-05-06 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| US20040009537A1 (en) | 2002-01-11 | 2004-01-15 | Jack Roos | Methods of modulating and of identifying agents that modulate intracellular calcium |
| CA2473441A1 (en) | 2002-01-18 | 2003-07-24 | The Genetics Company Inc. | Beta-secretase inhibitors |
| AU2004268621C1 (en) | 2003-08-29 | 2011-08-18 | Exelixis, Inc. | c-Kit modulators and methods of use |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| JP4000353B2 (ja) | 2004-11-26 | 2007-10-31 | 国立大学法人 長崎大学 | アミロイド関連疾患診断用組成物 |
| CA2589363A1 (en) | 2004-12-13 | 2006-06-22 | Eli Lilly And Company | Spiro derivatives as lipoxygenase inhibitors |
| EP1954283A2 (en) | 2005-11-04 | 2008-08-13 | Hydra Biosciences, Inc. | Compounds for modulating trpv3 function |
| US7872009B2 (en) * | 2005-11-21 | 2011-01-18 | Amgen Inc. | Beta-Secretase modulators and methods of use |
| DE102006012548A1 (de) * | 2006-03-18 | 2007-09-20 | Bayer Healthcare Ag | Substituierte Chromanol-Derivate und ihre Verwendung |
| US20100101733A1 (en) | 2008-10-24 | 2010-04-29 | Hsiu-Man Yu Chen | Desktop double-sided adhesive tape dispenser |
-
2008
- 2008-12-16 JP JP2010539048A patent/JP2011519343A/ja active Pending
- 2008-12-16 WO PCT/IN2008/000838 patent/WO2009084034A2/en not_active Ceased
- 2008-12-16 EA EA201000675A patent/EA201000675A1/ru unknown
- 2008-12-16 NZ NZ595776A patent/NZ595776A/xx not_active IP Right Cessation
- 2008-12-16 EP EP08868132A patent/EP2254879A4/en not_active Withdrawn
- 2008-12-16 AU AU2008344922A patent/AU2008344922A1/en not_active Abandoned
- 2008-12-16 US US12/808,937 patent/US8487121B2/en not_active Expired - Fee Related
- 2008-12-16 GE GEAP200811876A patent/GEP20125707B/en unknown
- 2008-12-16 CA CA2706566A patent/CA2706566A1/en not_active Abandoned
- 2008-12-16 MX MX2010005704A patent/MX2010005704A/es active IP Right Grant
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02223574A (ja) * | 1988-04-26 | 1990-09-05 | Yoshitomi Pharmaceut Ind Ltd | ベンゾピラン化合物 |
| US5276168A (en) * | 1990-06-18 | 1994-01-04 | E. R. Squibb & Sons, Inc. | Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents |
| WO2000003681A2 (en) * | 1998-07-16 | 2000-01-27 | Axys Pharmaceuticals, Inc. | Process for the synthesis of benzopyran derivatives |
| JP2006522835A (ja) * | 2003-04-10 | 2006-10-05 | アムジェン インコーポレイテッド | 環状アミン誘導体およびブラジキニンによって媒介される炎症関連障害の処置におけるそれらの使用 |
| WO2007042906A1 (en) * | 2005-10-07 | 2007-04-19 | Glenmark Pharmaceuticals S.A. | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017533277A (ja) * | 2014-10-31 | 2017-11-09 | アッヴィ・エス・ア・エール・エル | 置換テトラヒドロピランおよび使用方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009084034A2 (en) | 2009-07-09 |
| AU2008344922A2 (en) | 2012-04-26 |
| US8487121B2 (en) | 2013-07-16 |
| US20100311778A1 (en) | 2010-12-09 |
| GEP20125707B (en) | 2012-12-10 |
| EP2254879A2 (en) | 2010-12-01 |
| NZ595776A (en) | 2013-08-30 |
| EA201000675A1 (ru) | 2011-06-30 |
| MX2010005704A (es) | 2010-08-17 |
| AU2008344922A1 (en) | 2012-01-19 |
| WO2009084034A3 (en) | 2012-01-19 |
| CA2706566A1 (en) | 2009-07-09 |
| EP2254879A4 (en) | 2012-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2011519343A (ja) | Ｔｒｐｖ３モジュレーターとしてのクロマン誘導体 | |
| JP2011519343A5 (enExample) | ||
| JP5368475B2 (ja) | スフィンゴシン−１−ホスフェート（ｓ１ｐ）受容体アンタゴニスト生物活性を有する６−置換インドール−３−カルボン酸アミド化合物 | |
| WO2008059865A1 (en) | Novel 1,2-dihydroquinoline derivative having substituted phenylchalcogeno lower alkyl group and ester-introduced phenyl group as substituents | |
| FR2567885A1 (fr) | Derives 3-aminopropoxyaryliques, leur preparation, leur application comme medicaments et compositions pharmaceutiques les contenant | |
| JPS6242985A (ja) | β―ラクタム系抗生物質中間体の製造方法 | |
| TW201329058A (zh) | 多環類衍生物、其製備方法及其在醫藥上的應用 | |
| JP2010515750A (ja) | スフィンゴシン−１−ホスフェート（ｓ１ｐ）受容体アンタゴニスト生物活性を有する６−置換インドール−３−カルボン酸アミド化合物 | |
| JP4918486B2 (ja) | 苦痛、うつ病及び（又は）不安障害の治療に使用するための飽和及び不飽和３−ピリジル−ベンゾシクロアルキルメチル−アミン類 | |
| FR2681325A1 (fr) | Derives de l'aminomethyl-4 piperidine, leur preparation et leur application en therapeutique. | |
| JPH0433794B2 (enExample) | ||
| EP0398413A1 (en) | "3,4-dehydropiperidine derivatives having psychotropic activity | |
| JP2011529855A (ja) | Ｔｒｐｖ３モジュレーターとしてのクロマン誘導体 | |
| CA2072520A1 (en) | 2-(1-piperidyl) ethanol derivatives, their preparation and their therapeutic application | |
| JP2994459B2 (ja) | 三環［６，５，５］／［６，６，５］―縮合オキサゾリジノン抗菌剤 | |
| Liu et al. | Divergent syntheses of L-733, 060 and CP-122721 from functionalized pieridinones made by one-pot tandem cyclization | |
| FR2782515A1 (fr) | NOUVEAUX DERIVES DE L'INDANE-1-Ol, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT | |
| JP5419894B2 (ja) | Ｔｒｐｖ３モジュレーターとしての縮合ピリミジン誘導体 | |
| CA2047236C (en) | Substituted 3-amino chromans | |
| CN101448503B (zh) | 哌啶和哌嗪衍生物 | |
| US6114549A (en) | Process of making 3-phenyl-1-methylenedioxyphenyl-indane-2-carboxylic acid derivatives | |
| KR20130040284A (ko) | Ｔｒｐｖ3 조절제로서의 크로만 유도체 | |
| TW201329061A (zh) | 做為ｔｒｐｖ３調節劑的色原烷衍生物 | |
| CN103183660A (zh) | 作为trpv3调节剂的色原烷衍生物 | |
| JPH08333338A (ja) | 新規なメラトニン作動性インダニルピペラジン誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111128 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111128 |
|
| RD01 | Notification of change of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7421 Effective date: 20130726 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130919 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131001 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131227 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140110 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140131 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140715 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150106 |