CN103539785B - 大麻素受体调节剂 - Google Patents
大麻素受体调节剂 Download PDFInfo
- Publication number
- CN103539785B CN103539785B CN201310463585.6A CN201310463585A CN103539785B CN 103539785 B CN103539785 B CN 103539785B CN 201310463585 A CN201310463585 A CN 201310463585A CN 103539785 B CN103539785 B CN 103539785B
- Authority
- CN
- China
- Prior art keywords
- pyridin
- methyl
- ethyl
- phenyl
- group
- 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.)
- Active
Links
- 239000003520 cannabinoid receptor affecting agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 278
- 238000000034 method Methods 0.000 claims abstract description 112
- 238000011282 treatment Methods 0.000 claims abstract description 94
- 230000000694 effects Effects 0.000 claims abstract description 27
- 208000004454 Hyperalgesia Diseases 0.000 claims abstract description 25
- 208000002193 Pain Diseases 0.000 claims abstract description 25
- 230000036407 pain Effects 0.000 claims abstract description 25
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 19
- 208000035154 Hyperesthesia Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 206010061218 Inflammation Diseases 0.000 claims abstract description 17
- 230000004054 inflammatory process Effects 0.000 claims abstract description 17
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 claims abstract description 16
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 claims abstract description 16
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 16
- 208000026935 allergic disease Diseases 0.000 claims abstract description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 11
- 206010012289 Dementia Diseases 0.000 claims abstract description 11
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 11
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 11
- 208000006820 Arthralgia Diseases 0.000 claims abstract description 9
- 206010006002 Bone pain Diseases 0.000 claims abstract description 9
- 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 7
- 206010053552 allodynia Diseases 0.000 claims abstract description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 6
- 206010011224 Cough Diseases 0.000 claims abstract description 6
- 206010019233 Headaches Diseases 0.000 claims abstract description 6
- 206010025323 Lymphomas Diseases 0.000 claims abstract description 6
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 208000008238 Muscle Spasticity Diseases 0.000 claims abstract description 6
- 208000000112 Myalgia Diseases 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 6
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 6
- 230000001154 acute effect Effects 0.000 claims abstract description 6
- 230000002411 adverse Effects 0.000 claims abstract description 6
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 6
- 208000025997 central nervous system neoplasm Diseases 0.000 claims abstract description 6
- 230000006378 damage Effects 0.000 claims abstract description 6
- 231100000869 headache Toxicity 0.000 claims abstract description 6
- 210000002865 immune cell Anatomy 0.000 claims abstract description 6
- 208000032839 leukemia Diseases 0.000 claims abstract description 6
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 6
- 206010027599 migraine Diseases 0.000 claims abstract description 6
- 208000004296 neuralgia Diseases 0.000 claims abstract description 6
- 230000002981 neuropathic effect Effects 0.000 claims abstract description 6
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 6
- 230000020341 sensory perception of pain Effects 0.000 claims abstract description 6
- 208000018198 spasticity Diseases 0.000 claims abstract description 6
- 208000004371 toothache Diseases 0.000 claims abstract description 6
- 208000013465 muscle pain Diseases 0.000 claims abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 61
- 239000003814 drug Substances 0.000 claims description 58
- 201000010099 disease Diseases 0.000 claims description 54
- 238000004519 manufacturing process Methods 0.000 claims description 52
- 239000012453 solvate Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 20
- 150000004677 hydrates Chemical class 0.000 claims description 15
- 208000023275 Autoimmune disease Diseases 0.000 claims description 14
- 208000006011 Stroke Diseases 0.000 claims description 10
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 9
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
- 206010003267 Arthritis reactive Diseases 0.000 claims description 5
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 5
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 208000009137 Behcet syndrome Diseases 0.000 claims description 5
- 206010010741 Conjunctivitis Diseases 0.000 claims description 5
- 208000016192 Demyelinating disease Diseases 0.000 claims description 5
- 206010012305 Demyelination Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
- 201000005569 Gout Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 206010065673 Nephritic syndrome Diseases 0.000 claims description 5
- 208000003251 Pruritus Diseases 0.000 claims description 5
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 5
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 5
- 208000008765 Sciatica Diseases 0.000 claims description 5
- 206010039710 Scleroderma Diseases 0.000 claims description 5
- 206010052779 Transplant rejections Diseases 0.000 claims description 5
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
- 208000024780 Urticaria Diseases 0.000 claims description 5
- 206010047115 Vasculitis Diseases 0.000 claims description 5
- 230000036783 anaphylactic response Effects 0.000 claims description 5
- 208000003455 anaphylaxis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 206010025135 lupus erythematosus Diseases 0.000 claims description 5
- 201000001119 neuropathy Diseases 0.000 claims description 5
- 230000007823 neuropathy Effects 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 208000000813 polyradiculoneuropathy Diseases 0.000 claims description 5
- 208000002574 reactive arthritis Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims description 5
- 208000001640 Fibromyalgia Diseases 0.000 claims description 4
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 4
- 201000002661 Spondylitis Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- CPXGJSHIYISOMS-SNVBAGLBSA-N N-[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]cyclopenta-1,3-diene-1-carboxamide Chemical compound OC[C@H](C(C)(C)C)NC(=O)C1=CC=CC1 CPXGJSHIYISOMS-SNVBAGLBSA-N 0.000 claims description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 208000030961 allergic reaction Diseases 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims 1
- 210000001685 thyroid gland Anatomy 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 5
- 229930003827 cannabinoid Natural products 0.000 abstract description 5
- 239000003557 cannabinoid Substances 0.000 abstract description 5
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 abstract description 2
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 abstract description 2
- 208000027418 Wounds and injury Diseases 0.000 abstract description 2
- 208000014674 injury Diseases 0.000 abstract description 2
- 208000026278 immune system disease Diseases 0.000 abstract 1
- -1 ureido, amino Chemical group 0.000 description 4045
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 191
- 125000003118 aryl group Chemical group 0.000 description 151
- 125000001072 heteroaryl group Chemical group 0.000 description 128
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 120
- 125000000753 cycloalkyl group Chemical group 0.000 description 98
- 125000000623 heterocyclic group Chemical group 0.000 description 98
- 239000002585 base Substances 0.000 description 97
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 93
- 125000001424 substituent group Chemical group 0.000 description 92
- 229910052799 carbon Inorganic materials 0.000 description 84
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 67
- 229910052736 halogen Inorganic materials 0.000 description 59
- 150000002367 halogens Chemical class 0.000 description 59
- 229910052757 nitrogen Inorganic materials 0.000 description 58
- 229910052739 hydrogen Inorganic materials 0.000 description 55
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 54
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 52
- 125000004433 nitrogen atom Chemical group N* 0.000 description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 48
- 125000004093 cyano group Chemical group *C#N 0.000 description 46
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 45
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 44
- 125000005549 heteroarylene group Chemical group 0.000 description 42
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 40
- 125000002993 cycloalkylene group Chemical group 0.000 description 36
- 125000004663 dialkyl amino group Chemical group 0.000 description 36
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 34
- 125000001769 aryl amino group Chemical group 0.000 description 33
- 125000004104 aryloxy group Chemical group 0.000 description 33
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 33
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 32
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 32
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 30
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 28
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 28
- 125000005553 heteroaryloxy group Chemical group 0.000 description 27
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 26
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 25
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 24
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 24
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 23
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 22
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 22
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 21
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 21
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 20
- 150000001204 N-oxides Chemical class 0.000 description 19
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 18
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 18
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 18
- 150000001602 bicycloalkyls Chemical group 0.000 description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 18
- 125000005363 dialkylsulfonamide group Chemical group 0.000 description 18
- 125000003277 amino group Chemical group 0.000 description 17
- 125000005129 aryl carbonyl group Chemical group 0.000 description 17
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 17
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 16
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 16
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 229910052760 oxygen Inorganic materials 0.000 description 16
- 125000005724 cycloalkenylene group Chemical group 0.000 description 15
- 239000005977 Ethylene Substances 0.000 description 14
- 239000000460 chlorine Chemical group 0.000 description 14
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 14
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 14
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 13
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 12
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 12
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 12
- 125000006413 ring segment Chemical group 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 11
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 11
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 11
- 239000001301 oxygen Substances 0.000 description 11
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 11
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 10
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- 229910052731 fluorine Inorganic materials 0.000 description 9
- 125000001153 fluoro group Chemical group F* 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 210000003169 central nervous system Anatomy 0.000 description 8
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 8
- 125000004076 pyridyl group Chemical group 0.000 description 8
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 8
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 7
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 7
- 108050007331 Cannabinoid receptor Proteins 0.000 description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 6
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 6
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 6
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 6
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 6
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
- 125000003636 chemical group Chemical group 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 6
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 6
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 6
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 6
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 6
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 6
- 125000003070 2-(2-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 5
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 5
- 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 description 5
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 5
- 125000006500 3-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC(F)(F)F)=C1[H])C([H])([H])* 0.000 description 5
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 5
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000001188 haloalkyl group Chemical group 0.000 description 5
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000000634 powder X-ray diffraction Methods 0.000 description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 5
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 5
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 4
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 4
- OHCLSNSCCQEQTA-UHFFFAOYSA-N 3-methyl-2-methylidenebutan-1-ol Chemical group CC(C)C(=C)CO OHCLSNSCCQEQTA-UHFFFAOYSA-N 0.000 description 4
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 4
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- 230000037081 physical activity Effects 0.000 description 4
- 206010043778 thyroiditis Diseases 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- 125000004814 1,1-dimethylethylene group Chemical group [H]C([H])([H])C([*:1])(C([H])([H])[H])C([H])([H])[*:2] 0.000 description 3
- VPUAYOJTHRDUTK-UHFFFAOYSA-N 1-ethylpyrrole Chemical compound CCN1C=CC=C1 VPUAYOJTHRDUTK-UHFFFAOYSA-N 0.000 description 3
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- 125000006184 2,5-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])*)C([H])([H])[H] 0.000 description 3
- AKAQDSCODRVUDP-UHFFFAOYSA-N 3-fluoro-2-(fluoromethyl)prop-1-ene Chemical group FCC(=C)CF AKAQDSCODRVUDP-UHFFFAOYSA-N 0.000 description 3
- KFDVPJUYSDEJTH-UHFFFAOYSA-N 4-ethenylpyridine Chemical group C=CC1=CC=NC=C1 KFDVPJUYSDEJTH-UHFFFAOYSA-N 0.000 description 3
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 229940065144 cannabinoids Drugs 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- WCASXYBKJHWFMY-UHFFFAOYSA-N crotyl alcohol Chemical group CC=CCO WCASXYBKJHWFMY-UHFFFAOYSA-N 0.000 description 3
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- YIWFBNMYFYINAD-UHFFFAOYSA-N ethenylcyclopropane Chemical group C=CC1CC1 YIWFBNMYFYINAD-UHFFFAOYSA-N 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229940125425 inverse agonist Drugs 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 239000004031 partial agonist Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 150000003217 pyrazoles Chemical class 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000005551 pyridylene group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- CDSYXCIQYSQOKF-UHFFFAOYSA-N 1-(2-methylpropyl)pyrrole Chemical compound CC(C)CN1C=CC=C1 CDSYXCIQYSQOKF-UHFFFAOYSA-N 0.000 description 2
- BKYALEQPNMLLSD-UHFFFAOYSA-N 1-cyclobutyl-3-methoxybenzene Chemical compound COC1=CC=CC(C2CCC2)=C1 BKYALEQPNMLLSD-UHFFFAOYSA-N 0.000 description 2
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical group C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 2
- NARVIWMVBMUEOG-UHFFFAOYSA-N 2-Hydroxy-propylene Natural products CC(O)=C NARVIWMVBMUEOG-UHFFFAOYSA-N 0.000 description 2
- KGJASVTXXHUNTA-UHFFFAOYSA-N 2-fluorocyclohexa-1,3-diene Chemical compound FC1=CCCC=C1 KGJASVTXXHUNTA-UHFFFAOYSA-N 0.000 description 2
- ZMLHBBXPXZXTSP-UHFFFAOYSA-N 2-fluoropropane Chemical group C[C](C)F ZMLHBBXPXZXTSP-UHFFFAOYSA-N 0.000 description 2
- VEFUEZBNYXOTDQ-UHFFFAOYSA-N 3-fluoro-3-methylbut-1-ene Chemical group CC(C)(F)C=C VEFUEZBNYXOTDQ-UHFFFAOYSA-N 0.000 description 2
- YHQXBTXEYZIYOV-UHFFFAOYSA-N 3-methylbut-1-ene Chemical group CC(C)C=C YHQXBTXEYZIYOV-UHFFFAOYSA-N 0.000 description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- WCNKHTIPPVQEQW-UHFFFAOYSA-N 4,4,4-trifluorobut-1-ene Chemical group FC(F)(F)CC=C WCNKHTIPPVQEQW-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- UGOCVMXQVPANMP-UHFFFAOYSA-N CC(C)(F)C(=C=C)C(C(F)(F)F)C(F)(F)F Chemical group CC(C)(F)C(=C=C)C(C(F)(F)F)C(F)(F)F UGOCVMXQVPANMP-UHFFFAOYSA-N 0.000 description 2
- MJLVOLJVYWOLAV-UHFFFAOYSA-N FCC(CF)=C=CCC(F)(F)F Chemical group FCC(CF)=C=CCC(F)(F)F MJLVOLJVYWOLAV-UHFFFAOYSA-N 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- YNZYKPIVVIWDGU-CYBMUJFWSA-N N-[(2S)-1-hydroxy-3,3-dimethylbutan-2-yl]pentalene-1-carboxamide Chemical compound OC[C@H](C(C)(C)C)NC(=O)C=1C2=CC=CC2=CC1 YNZYKPIVVIWDGU-CYBMUJFWSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- ITQTTZVARXURQS-UHFFFAOYSA-N beta-methylpyridine Chemical group CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001924 cycloalkanes Chemical class 0.000 description 2
- 125000004976 cyclobutylene group Chemical group 0.000 description 2
- 125000004956 cyclohexylene group Chemical group 0.000 description 2
- PWAPCRSSMCLZHG-UHFFFAOYSA-N cyclopentylidene Chemical group [C]1CCCC1 PWAPCRSSMCLZHG-UHFFFAOYSA-N 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- MHNNAWXXUZQSNM-UHFFFAOYSA-N methylethylethylene Natural products CCC(C)=C MHNNAWXXUZQSNM-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 150000003901 oxalic acid esters Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- 125000005710 tetrahydropyranylene group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- OBMKZINZPBARIK-UHFFFAOYSA-N (1-aminocyclopropyl)methanol Chemical compound OCC1(N)CC1 OBMKZINZPBARIK-UHFFFAOYSA-N 0.000 description 1
- YFBWGBFWVFEGEZ-UHFFFAOYSA-N 1,1,1-trifluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)C(F)(F)F YFBWGBFWVFEGEZ-UHFFFAOYSA-N 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000004822 1,1-dimethylpropylene group Chemical group [H]C([H])([H])C([*:1])(C([H])([H])[H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 1
- NYZGXIKOABSJGA-UHFFFAOYSA-N 1-(2-methoxyethyl)azetidine Chemical compound COCCN1CCC1 NYZGXIKOABSJGA-UHFFFAOYSA-N 0.000 description 1
- UYHQDFQKVUGCAQ-UHFFFAOYSA-N 1-(trifluoromethyl)cyclobutan-1-amine Chemical compound FC(F)(F)C1(N)CCC1 UYHQDFQKVUGCAQ-UHFFFAOYSA-N 0.000 description 1
- FBWOFVFUKXZXKT-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropan-1-amine Chemical compound FC(F)(F)C1(N)CC1 FBWOFVFUKXZXKT-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical group FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- 125000004812 1-ethylethylene group Chemical group [H]C([H])([H])C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- CHODSSFYKUSDHG-UHFFFAOYSA-N 1-fluoro-2-methylpropan-2-amine Chemical compound CC(C)(N)CF CHODSSFYKUSDHG-UHFFFAOYSA-N 0.000 description 1
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
- 125000004806 1-methylethylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- DFIFVMZOFMQSAG-UHFFFAOYSA-N 1-tert-butyl-3-methylurea Chemical group CNC(=O)NC(C)(C)C DFIFVMZOFMQSAG-UHFFFAOYSA-N 0.000 description 1
- KORIJXKQGMTQTO-UHFFFAOYSA-N 1h-pyrrol-2-ylmethanol Chemical compound OCC1=CC=CN1 KORIJXKQGMTQTO-UHFFFAOYSA-N 0.000 description 1
- HNRMPXKDFBEGFZ-UHFFFAOYSA-N 2,2-dimethylbutane Chemical compound CCC(C)(C)C HNRMPXKDFBEGFZ-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- KCRPBTDUKFYBMV-UHFFFAOYSA-N 2,3-dihydro-1H-inden-1-amine Chemical compound NC1CCC2=CC=CC=C12.NC1CCC2=CC=CC=C12 KCRPBTDUKFYBMV-UHFFFAOYSA-N 0.000 description 1
- XIXAOYUNUKDINI-UHFFFAOYSA-N 2,5,5-trimethylhexa-2,3-diene Chemical group CC(C)=C=CC(C)(C)C XIXAOYUNUKDINI-UHFFFAOYSA-N 0.000 description 1
- JKLUVCHKXQJGIG-UHFFFAOYSA-N 2-Methylenebutan-1-ol Chemical group CCC(=C)CO JKLUVCHKXQJGIG-UHFFFAOYSA-N 0.000 description 1
- JQULXIOYDDCNGR-UHFFFAOYSA-N 2-amino-2-methylpropanenitrile Chemical compound CC(C)(N)C#N JQULXIOYDDCNGR-UHFFFAOYSA-N 0.000 description 1
- LPEUUBBXMBUTCQ-UHFFFAOYSA-N 2-amino-3-fluoro-2-(fluoromethyl)propan-1-ol Chemical compound OCC(N)(CF)CF LPEUUBBXMBUTCQ-UHFFFAOYSA-N 0.000 description 1
- BPKJNEIOHOEWLO-RXMQYKEDSA-N 2-amino-n,3,3-trimethylbutanamide Chemical compound CNC(=O)[C@@H](N)C(C)(C)C BPKJNEIOHOEWLO-RXMQYKEDSA-N 0.000 description 1
- MUUOUUYKIVSIAR-UHFFFAOYSA-N 2-but-3-enyloxirane Chemical class C=CCCC1CO1 MUUOUUYKIVSIAR-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000004819 2-methylbutylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:1])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- BYDRTKVGBRTTIT-UHFFFAOYSA-N 2-methylprop-2-en-1-ol Chemical group CC(=C)CO BYDRTKVGBRTTIT-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical group C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- PKXHXOTZMFCXSH-UHFFFAOYSA-N 3,3-dimethylbut-1-ene Chemical group CC(C)(C)C=C PKXHXOTZMFCXSH-UHFFFAOYSA-N 0.000 description 1
- GXZIKGUOPZOGHM-UHFFFAOYSA-N 3-ethenyloxolane Chemical group C=CC1CCOC1 GXZIKGUOPZOGHM-UHFFFAOYSA-N 0.000 description 1
- DPZYLEIWHTWHCU-UHFFFAOYSA-N 3-ethenylpyridine Chemical group C=CC1=CC=CN=C1 DPZYLEIWHTWHCU-UHFFFAOYSA-N 0.000 description 1
- FASUFOTUSHAIHG-UHFFFAOYSA-N 3-methoxyprop-1-ene Chemical group COCC=C FASUFOTUSHAIHG-UHFFFAOYSA-N 0.000 description 1
- LDTAOIUHUHHCMU-UHFFFAOYSA-N 3-methylpent-1-ene Chemical group CCC(C)C=C LDTAOIUHUHHCMU-UHFFFAOYSA-N 0.000 description 1
- PYOXIJHTSXVKMZ-UHFFFAOYSA-N 4-(3,3-dimethylbutyl)morpholine Chemical compound CC(C)(C)CCN1CCOCC1 PYOXIJHTSXVKMZ-UHFFFAOYSA-N 0.000 description 1
- IXLAHJAJWGJIMY-UHFFFAOYSA-N 4-ethenyloxane Chemical group C=CC1CCOCC1 IXLAHJAJWGJIMY-UHFFFAOYSA-N 0.000 description 1
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical group OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 1
- FUGYGGDSWSUORM-UHFFFAOYSA-N 4-hydroxystyrene Chemical group OC1=CC=C(C=C)C=C1 FUGYGGDSWSUORM-UHFFFAOYSA-N 0.000 description 1
- PJCTVLGNVGGVJR-UHFFFAOYSA-N 5-prop-2-enyl-1h-imidazole Chemical group C=CCC1=CN=CN1 PJCTVLGNVGGVJR-UHFFFAOYSA-N 0.000 description 1
- VBEVDXSKWIIPKQ-UHFFFAOYSA-N 7-(2,4-difluorophenyl)-N-(1-hydroxy-2-methylpropan-2-yl)-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-diene-9-carboxamide Chemical compound C1=2CC3CC3C=2C(C(=O)NC(C)(CO)C)=NN1C1=CC=C(F)C=C1F VBEVDXSKWIIPKQ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- TYTKDUWAVIKPRD-SNVBAGLBSA-N CC([C@@H](C(NC)=O)NC(=O)C1=CC=CC1)(C)C Chemical compound CC([C@@H](C(NC)=O)NC(=O)C1=CC=CC1)(C)C TYTKDUWAVIKPRD-SNVBAGLBSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JMKBKBSFRWVYOZ-UHFFFAOYSA-N N-(1,1,1-trifluoro-2-methylpropan-2-yl)pentalene-1-carboxamide Chemical compound FC(C(C)(C)NC(=O)C=1C2=CC=CC2=CC1)(F)F JMKBKBSFRWVYOZ-UHFFFAOYSA-N 0.000 description 1
- ILDSZHWFGJDPGJ-UHFFFAOYSA-N N-(1-hydroxy-2-methylpropan-2-yl)cyclopenta-1,3-diene-1-carboxamide Chemical compound OCC(C)(C)NC(=O)C1=CC=CC1 ILDSZHWFGJDPGJ-UHFFFAOYSA-N 0.000 description 1
- QQGNLKJAIVSNCO-UHFFFAOYSA-N N-butylformamide Chemical group CCCCNC=O QQGNLKJAIVSNCO-UHFFFAOYSA-N 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical group OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=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
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- YKXMZSYOSBDLMM-UHFFFAOYSA-N bicyclo[3.1.0]hexan-3-ol Chemical class C1C(O)CC2CC21 YKXMZSYOSBDLMM-UHFFFAOYSA-N 0.000 description 1
- MKUWVMRNQOOSAT-UHFFFAOYSA-N but-3-en-2-ol Chemical group CC(O)C=C MKUWVMRNQOOSAT-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- 230000002950 deficient Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- SMVBADCAMQOTOV-UHFFFAOYSA-N ethyl cyclobutanecarboxylate Chemical compound CCOC(=O)C1CCC1 SMVBADCAMQOTOV-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000008622 extracellular signaling Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000001634 furandiyl group Chemical group O1C(=C(C=C1)*)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000000917 hyperalgesic effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000005945 imidazopyridyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005932 isopentyloxycarbonyl group Chemical group 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- XCTTVNSXEHWZBI-UHFFFAOYSA-N n-(2-methylpropyl)formamide Chemical group CC(C)CNC=O XCTTVNSXEHWZBI-UHFFFAOYSA-N 0.000 description 1
- NRMJMIGWXUCEEW-UHFFFAOYSA-N n-butan-2-ylformamide Chemical group CCC(C)NC=O NRMJMIGWXUCEEW-UHFFFAOYSA-N 0.000 description 1
- 125000006126 n-butyl sulfonyl group Chemical group 0.000 description 1
- KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical group CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- ATHHXGZTWNVVOU-VQEHIDDOSA-N n-methylformamide Chemical group CN[13CH]=O ATHHXGZTWNVVOU-VQEHIDDOSA-N 0.000 description 1
- KVTGAKFJRLBHLU-UHFFFAOYSA-N n-propan-2-ylformamide Chemical group CC(C)NC=O KVTGAKFJRLBHLU-UHFFFAOYSA-N 0.000 description 1
- 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
- SUUDTPGCUKBECW-UHFFFAOYSA-N n-propylformamide Chemical group CCCNC=O SUUDTPGCUKBECW-UHFFFAOYSA-N 0.000 description 1
- SDLAKRCBYGZJRW-UHFFFAOYSA-N n-tert-butylformamide Chemical group CC(C)(C)NC=O SDLAKRCBYGZJRW-UHFFFAOYSA-N 0.000 description 1
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 125000005933 neopentyloxycarbonyl group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000002276 neurotropic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 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
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- HJWLCRVIBGQPNF-UHFFFAOYSA-N prop-2-enylbenzene Chemical group C=CCC1=CC=CC=C1 HJWLCRVIBGQPNF-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000000197 pyrolysis Methods 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
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AGDSCTQQXMDDCV-UHFFFAOYSA-M sodium;2-iodoacetate Chemical compound [Na+].[O-]C(=O)CI AGDSCTQQXMDDCV-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27550609P | 2009-08-28 | 2009-08-28 | |
| US61/275,506 | 2009-08-28 | ||
| US39658810P | 2010-05-28 | 2010-05-28 | |
| US61/396,588 | 2010-05-28 | ||
| US40014610P | 2010-07-22 | 2010-07-22 | |
| US61/400,146 | 2010-07-22 | ||
| CN201080049159.2A CN102596913B (zh) | 2009-08-28 | 2010-08-27 | 大麻素受体调节剂 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080049159.2A Division CN102596913B (zh) | 2009-08-28 | 2010-08-27 | 大麻素受体调节剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103539785A CN103539785A (zh) | 2014-01-29 |
| CN103539785B true CN103539785B (zh) | 2015-09-23 |
Family
ID=43127457
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310463585.6A Active CN103539785B (zh) | 2009-08-28 | 2010-08-27 | 大麻素受体调节剂 |
| CN201080049159.2A Active CN102596913B (zh) | 2009-08-28 | 2010-08-27 | 大麻素受体调节剂 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080049159.2A Active CN102596913B (zh) | 2009-08-28 | 2010-08-27 | 大麻素受体调节剂 |
Country Status (19)
| Country | Link |
|---|---|
| US (6) | US8778950B2 (https=) |
| EP (4) | EP3363788A1 (https=) |
| JP (5) | JP5746698B2 (https=) |
| KR (6) | KR102682216B1 (https=) |
| CN (2) | CN103539785B (https=) |
| AR (1) | AR077991A1 (https=) |
| AU (1) | AU2010286988B2 (https=) |
| BR (1) | BR112012008159A2 (https=) |
| CA (1) | CA2770866C (https=) |
| EA (1) | EA023586B1 (https=) |
| HK (1) | HK1259082A1 (https=) |
| IL (1) | IL218130A (https=) |
| IN (1) | IN2012DN02474A (https=) |
| MX (1) | MX2012002499A (https=) |
| NZ (1) | NZ598288A (https=) |
| SG (3) | SG178907A1 (https=) |
| TW (1) | TWI503316B (https=) |
| WO (1) | WO2011025541A1 (https=) |
| ZA (1) | ZA202205142B (https=) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN2012DN02474A (https=) * | 2009-08-28 | 2015-08-21 | Arena Pharm Inc | |
| AU2012222149B2 (en) | 2011-02-25 | 2017-06-29 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| US9597340B2 (en) * | 2011-02-25 | 2017-03-21 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| EP2678330A1 (en) | 2011-02-25 | 2014-01-01 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of condensed azacycles ( cannabinoid receptor modulators) |
| ITMI20122221A1 (it) | 2012-12-21 | 2014-06-22 | C4T S C A R L | Nuovi composti del 2,3-diidro-4h-1,3-benzossazin-4-one, metodo per prepararli e forma farmaceutica che li comprende |
| EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
| JP5983714B2 (ja) * | 2013-11-29 | 2016-09-06 | 大正製薬株式会社 | 含フッ素アミノ酸プロドラッグの結晶形とその製造方法 |
| WO2015095953A1 (en) | 2013-12-27 | 2015-07-02 | The Centre For Drug Research And Development | Sulfonamide-containing linkage systems for drug conjugates |
| ES2905569T3 (es) | 2014-09-17 | 2022-04-11 | Zymeworks Inc | Compuestos citotóxicos y antimitóticos y métodos para utilizarlos |
| WO2016085941A1 (en) * | 2014-11-25 | 2016-06-02 | Arena Pharmaceuticals, Inc. | Processes for the preparation of cannabinoid receptor modulators |
| US10172786B2 (en) | 2014-12-16 | 2019-01-08 | Axim Biotechnologies, Inc. | Oral care composition comprising cannabinoids |
| AU2017249211A1 (en) * | 2016-04-10 | 2018-11-22 | Arena Pharmaceuticals, Inc. | Methods of treatment with selective CB2 receptor agonists |
| CN109689045A (zh) | 2016-05-04 | 2019-04-26 | 因美制药公司 | 大麻素的局部制剂在治疗大疱性表皮松解症和相关结缔组织病症中的用途 |
| WO2018208847A1 (en) | 2017-05-08 | 2018-11-15 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of pain from inflammatory bowel disease |
| US20200078358A1 (en) | 2017-05-08 | 2020-03-12 | Arena Pharmaceuticals, Inc. | Compounds and Methods for Treatment of Visceral Pain |
| WO2019043635A1 (en) | 2017-09-01 | 2019-03-07 | Richter Gedeon Nyrt. | COMPOUNDS INHIBITING THE ACTIVITY OF D-AMINO ACID OXIDASE |
| US12357604B2 (en) | 2017-09-22 | 2025-07-15 | Inmed Pharmaceuticals Inc. | Topical formulations of cannabinoids and use thereof in the treatment of pain |
| EP3886845B1 (en) | 2018-11-28 | 2024-09-04 | Merck Sharp & Dohme LLC | Novel substituted piperazine amide compounds as indoleamine 2, 3-dioxygenase (ido) inhibitors |
| WO2021047583A1 (zh) * | 2019-09-12 | 2021-03-18 | 四川海思科制药有限公司 | 一种三环吡唑衍生物及其制备 |
| WO2021047581A1 (zh) * | 2019-09-12 | 2021-03-18 | 四川海思科制药有限公司 | 一种六氢化苯并吡唑衍生物及其制备 |
| JP7620024B2 (ja) | 2020-09-24 | 2025-01-22 | 富士フイルム株式会社 | 複合パターンの製造方法、樹脂組成物、積層体の製造方法、及び、半導体デバイスの製造方法 |
| CN115536648B (zh) * | 2021-06-29 | 2024-09-17 | 深圳开悦生命科技有限公司 | 一类抑制rna解旋酶dhx33的多环化合物及其应用 |
| CN114736173B (zh) * | 2022-05-24 | 2024-06-11 | 无锡捷化医药科技有限公司 | 一种3-（二氟甲基）氧杂环丁烷-3-胺盐酸盐的制备方法 |
| WO2025090133A1 (en) | 2023-10-23 | 2025-05-01 | Inmed Pharmaceuticals Inc. | Compositions and methods for use of cannabinol compounds in neuroprotection |
| WO2025090587A1 (en) | 2023-10-23 | 2025-05-01 | Inmed Pharmaceuticals Inc. | Cannabinoids compounds and their use in the treatment of neuronal disorders |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006129178A1 (en) * | 2005-06-02 | 2006-12-07 | Glenmark Pharmaceuticals S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3964478B2 (ja) | 1995-06-30 | 2007-08-22 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘテロ環含有カルボン酸誘導体及びそれを含有する医薬 |
| YU72201A (sh) | 1999-04-28 | 2005-07-19 | Aventis Pharma Deutschland Gmbh. | Derivati di-aril kiseline kao ppar receptorski ligandi |
| EP1461027A4 (en) | 2001-12-07 | 2005-09-07 | Univ Virginia Commonwealth | TREATMENT OF NEOPLASIA |
| SE0300010D0 (sv) | 2003-01-07 | 2003-01-07 | Astrazeneca Ab | Novel Compounds |
| ITMI20041033A1 (it) * | 2004-05-24 | 2004-08-24 | Neuroscienze S C A R L | Composti farmaceutici |
| EP2343302A1 (en) | 2004-07-12 | 2011-07-13 | Cadila Healthcare Limited | Tricyclic pyrazole derivatives as cannabinoid receptor modulators |
| WO2006010379A1 (en) * | 2004-07-29 | 2006-02-02 | Actelion Pharmaceuticals Ltd. | Novel thiophene derivatives as immunosuppressive agents |
| FR2875230A1 (fr) * | 2004-09-13 | 2006-03-17 | Sanofi Aventis Sa | Derives de pyrazole condense, leur preparation et leur application en therapeutique |
| DE102004054666A1 (de) | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte Pyrazol-3-carboxamide, Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| PE20060949A1 (es) * | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| ATE459352T1 (de) | 2006-07-04 | 2010-03-15 | Janssen Pharmaceutica Nv | Benzimidazol-cannabinoid-agonisten mit einer substituierten heterocyclischen gruppe |
| US7928123B2 (en) | 2006-09-25 | 2011-04-19 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| US8481574B2 (en) | 2006-10-12 | 2013-07-09 | Abbott Laboratories | Compounds as cannabinoid receptor ligands |
| WO2008048914A1 (en) | 2006-10-17 | 2008-04-24 | Boehringer Ingelheim International Gmbh | Polycyclic compounds which modulate the cb2 receptor |
| EP2091921A2 (en) | 2006-11-03 | 2009-08-26 | Glenmark Pharmaceuticals S.A. | Bridged bicyclic indazoles as cannabinoid receptor ligands |
| US8173638B2 (en) | 2006-11-21 | 2012-05-08 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| US20080161340A1 (en) | 2006-12-20 | 2008-07-03 | Cara Therapeutics, Inc. | Tetrahydroquinilinones, tetrahydronaphthyridones and derivatives thereof |
| WO2008085302A1 (en) | 2006-12-20 | 2008-07-17 | Merck & Co., Inc. | Imidazopyridine analogs as cb2 receptor modulators, useful in the treatment of pain, respiratory and non-respiratory diseases |
| US20080214537A1 (en) | 2007-03-02 | 2008-09-04 | Cara Therapeutics, Inc. | Bridged phenanthridines |
| US8193369B2 (en) | 2007-03-30 | 2012-06-05 | Janssen Pharmaceutica Nv | Benzimidazole cannabinoid agonists |
| WO2008157500A1 (en) | 2007-06-17 | 2008-12-24 | Kalypsys, Inc. | Aminoquinazoline cannabinoid receptor modulators for treatment of disease |
| CN101686989B (zh) | 2007-06-21 | 2016-10-19 | 卡拉治疗学股份有限公司 | 取代的咪唑并杂环 |
| US8338623B2 (en) | 2007-07-09 | 2012-12-25 | Abbvie Inc. | Compounds as cannabinoid receptor ligands |
| US7943658B2 (en) | 2007-07-23 | 2011-05-17 | Bristol-Myers Squibb Company | Indole indane amide compounds useful as CB2 agonists and method |
| EP2203171A2 (en) | 2007-08-21 | 2010-07-07 | Merck Sharp & Dohme Corp. | Cb2 receptor ligands for the treatment of pain |
| UA104010C2 (en) | 2008-12-18 | 2013-12-25 | Эли Лилли Энд Компани | Purine compounds |
| US7741350B1 (en) | 2009-01-28 | 2010-06-22 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| WO2010088050A2 (en) | 2009-01-28 | 2010-08-05 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| IN2012DN02474A (https=) | 2009-08-28 | 2015-08-21 | Arena Pharm Inc | |
| AU2012222149B2 (en) * | 2011-02-25 | 2017-06-29 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| US9597340B2 (en) * | 2011-02-25 | 2017-03-21 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| EP2678330A1 (en) * | 2011-02-25 | 2014-01-01 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of condensed azacycles ( cannabinoid receptor modulators) |
-
2010
- 2010-08-27 IN IN2474DEN2012 patent/IN2012DN02474A/en unknown
- 2010-08-27 TW TW099128986A patent/TWI503316B/zh active
- 2010-08-27 KR KR1020227032376A patent/KR102682216B1/ko active Active
- 2010-08-27 AU AU2010286988A patent/AU2010286988B2/en not_active Ceased
- 2010-08-27 EP EP18150186.7A patent/EP3363788A1/en not_active Withdrawn
- 2010-08-27 KR KR1020207001281A patent/KR20200008045A/ko not_active Ceased
- 2010-08-27 EP EP22159802.2A patent/EP4036082A1/en active Pending
- 2010-08-27 CA CA2770866A patent/CA2770866C/en active Active
- 2010-08-27 SG SG2012013967A patent/SG178907A1/en unknown
- 2010-08-27 SG SG10201901293RA patent/SG10201901293RA/en unknown
- 2010-08-27 CN CN201310463585.6A patent/CN103539785B/zh active Active
- 2010-08-27 EP EP22160034.9A patent/EP4036089A1/en not_active Withdrawn
- 2010-08-27 US US13/392,074 patent/US8778950B2/en active Active
- 2010-08-27 EP EP10757325A patent/EP2470508A1/en not_active Withdrawn
- 2010-08-27 AR ARP100103145A patent/AR077991A1/es active IP Right Grant
- 2010-08-27 KR KR1020187029637A patent/KR20180115807A/ko not_active Ceased
- 2010-08-27 EA EA201270336A patent/EA023586B1/ru unknown
- 2010-08-27 JP JP2012526732A patent/JP5746698B2/ja not_active Expired - Fee Related
- 2010-08-27 KR KR1020217014027A patent/KR20210057213A/ko not_active Ceased
- 2010-08-27 KR KR1020177016103A patent/KR20170072358A/ko not_active Ceased
- 2010-08-27 WO PCT/US2010/002360 patent/WO2011025541A1/en not_active Ceased
- 2010-08-27 KR KR1020127007857A patent/KR101749778B1/ko not_active Expired - Fee Related
- 2010-08-27 SG SG10201404925TA patent/SG10201404925TA/en unknown
- 2010-08-27 BR BR112012008159A patent/BR112012008159A2/pt not_active Application Discontinuation
- 2010-08-27 NZ NZ598288A patent/NZ598288A/en not_active IP Right Cessation
- 2010-08-27 MX MX2012002499A patent/MX2012002499A/es active IP Right Grant
- 2010-08-27 CN CN201080049159.2A patent/CN102596913B/zh active Active
-
2012
- 2012-02-15 IL IL218130A patent/IL218130A/en active IP Right Grant
- 2012-09-14 US US13/616,918 patent/US9944606B2/en active Active
-
2015
- 2015-05-08 JP JP2015095753A patent/JP2015145423A/ja not_active Withdrawn
-
2017
- 2017-10-26 JP JP2017207036A patent/JP2018021074A/ja not_active Withdrawn
-
2018
- 2018-03-06 US US15/912,700 patent/US20180354907A1/en not_active Abandoned
-
2019
- 2019-01-29 HK HK19101582.1A patent/HK1259082A1/en unknown
- 2019-09-24 US US16/580,697 patent/US11214548B2/en active Active
- 2019-12-06 JP JP2019221000A patent/JP2020033387A/ja not_active Withdrawn
-
2020
- 2020-09-18 US US17/024,752 patent/US11746091B2/en active Active
-
2021
- 2021-10-22 JP JP2021173078A patent/JP2022009408A/ja not_active Withdrawn
- 2021-11-08 US US17/520,952 patent/US20220306586A1/en not_active Abandoned
-
2022
- 2022-05-10 ZA ZA2022/05142A patent/ZA202205142B/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006129178A1 (en) * | 2005-06-02 | 2006-12-07 | Glenmark Pharmaceuticals S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103539785B (zh) | 大麻素受体调节剂 | |
| TWI789381B (zh) | 雜環化合物 | |
| JP5427321B2 (ja) | ２−（２，４，５−置換−アニリノ）ピリミジン化合物 | |
| WO2015091426A1 (de) | Neue indazolcarboxamide, verfahren zu ihrer herstellung, pharmazeutische präparate die diese enthalten, sowie deren verwendung zur herstellung von arzneimitteln | |
| CN110003178A (zh) | 二杂芳基化合物及其用途 | |
| DE102017005091A1 (de) | Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one | |
| HK40078299A (en) | Cannabinoid receptor modulators | |
| HK40011011A (en) | Cannabinoid receptor modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |