KR102332957B1 - 화합물 및 방법 - Google Patents
화합물 및 방법 Download PDFInfo
- Publication number
- KR102332957B1 KR102332957B1 KR1020177010409A KR20177010409A KR102332957B1 KR 102332957 B1 KR102332957 B1 KR 102332957B1 KR 1020177010409 A KR1020177010409 A KR 1020177010409A KR 20177010409 A KR20177010409 A KR 20177010409A KR 102332957 B1 KR102332957 B1 KR 102332957B1
- Authority
- KR
- South Korea
- Prior art keywords
- injury
- disease
- compound
- pharmaceutically acceptable
- acceptable salt
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 177
- 238000000034 method Methods 0.000 title claims abstract description 118
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 81
- 230000006378 damage Effects 0.000 claims abstract description 54
- 208000035475 disorder Diseases 0.000 claims abstract description 34
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 23
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 claims description 87
- 208000014674 injury Diseases 0.000 claims description 62
- 230000003834 intracellular effect Effects 0.000 claims description 49
- 150000003839 salts Chemical group 0.000 claims description 49
- 208000027418 Wounds and injury Diseases 0.000 claims description 48
- 201000010099 disease Diseases 0.000 claims description 47
- 239000011575 calcium Substances 0.000 claims description 36
- 229910052791 calcium Inorganic materials 0.000 claims description 36
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 35
- 210000003169 central nervous system Anatomy 0.000 claims description 28
- 208000020431 spinal cord injury Diseases 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 208000029028 brain injury Diseases 0.000 claims description 14
- 230000008733 trauma Effects 0.000 claims description 14
- 208000010412 Glaucoma Diseases 0.000 claims description 12
- 230000001684 chronic effect Effects 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- 208000027232 peripheral nervous system disease Diseases 0.000 claims description 8
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 210000004556 brain Anatomy 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 231100000317 environmental toxin Toxicity 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 210000002161 motor neuron Anatomy 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 2
- 208000024412 Friedreich ataxia Diseases 0.000 claims description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 2
- 208000024777 Prion disease Diseases 0.000 claims description 2
- 206010057430 Retinal injury Diseases 0.000 claims description 2
- 206010002022 amyloidosis Diseases 0.000 claims description 2
- 208000025434 cerebellar degeneration Diseases 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 208000008675 hereditary spastic paraplegia Diseases 0.000 claims description 2
- 230000002503 metabolic effect Effects 0.000 claims description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
- 239000003053 toxin Substances 0.000 claims description 2
- 231100000765 toxin Toxicity 0.000 claims description 2
- 230000000926 neurological effect Effects 0.000 claims 1
- 101001117086 Dictyostelium discoideum cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase A Proteins 0.000 abstract description 28
- 239000003795 chemical substances by application Substances 0.000 abstract description 19
- 239000003112 inhibitor Substances 0.000 abstract description 7
- 210000005036 nerve Anatomy 0.000 abstract description 6
- 238000011321 prophylaxis Methods 0.000 abstract description 6
- 230000000324 neuroprotective effect Effects 0.000 abstract description 5
- 230000001172 regenerating effect Effects 0.000 abstract description 3
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 31
- 230000000694 effects Effects 0.000 description 29
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 238000001819 mass spectrum Methods 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000003814 drug Substances 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- -1 5-fluoropyrid-2-yl Chemical group 0.000 description 17
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 17
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 17
- 125000000217 alkyl group Chemical group 0.000 description 17
- 208000028017 Psychotic disease Diseases 0.000 description 15
- 229910052736 halogen Inorganic materials 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 15
- 230000008929 regeneration Effects 0.000 description 15
- 238000011069 regeneration method Methods 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- 239000013543 active substance Substances 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 201000000980 schizophrenia Diseases 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000000651 prodrug Chemical group 0.000 description 13
- 229940002612 prodrug Drugs 0.000 description 13
- 239000000186 progesterone Substances 0.000 description 13
- 229960003387 progesterone Drugs 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 230000011664 signaling Effects 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 9
- 230000003376 axonal effect Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 230000004766 neurogenesis Effects 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 8
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 208000006011 Stroke Diseases 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 210000001428 peripheral nervous system Anatomy 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical compound O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 206010026749 Mania Diseases 0.000 description 7
- 208000030886 Traumatic Brain injury Diseases 0.000 description 7
- 108010037572 Type 1 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 210000003050 axon Anatomy 0.000 description 7
- 208000010877 cognitive disease Diseases 0.000 description 7
- 239000003085 diluting agent Substances 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 230000000155 isotopic effect Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000019491 signal transduction Effects 0.000 description 7
- 208000011580 syndromic disease Diseases 0.000 description 7
- 230000009529 traumatic brain injury Effects 0.000 description 7
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 102000010856 Type 1 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 230000004406 elevated intraocular pressure Effects 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 201000003631 narcolepsy Diseases 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- ICISSZBYTVZMRU-UHFFFAOYSA-N 2-[4-(chloromethyl)phenyl]pyridine Chemical compound C1=CC(CCl)=CC=C1C1=CC=CC=N1 ICISSZBYTVZMRU-UHFFFAOYSA-N 0.000 description 5
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 5
- 208000020925 Bipolar disease Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 102000012749 Dopamine and cAMP-Regulated Phosphoprotein 32 Human genes 0.000 description 5
- 108010090047 Dopamine and cAMP-Regulated Phosphoprotein 32 Proteins 0.000 description 5
- 206010057671 Female sexual dysfunction Diseases 0.000 description 5
- 101001117044 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Proteins 0.000 description 5
- 101001117099 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Proteins 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 210000001742 aqueous humor Anatomy 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 229960002470 bimatoprost Drugs 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000003889 eye drop Substances 0.000 description 5
- 229940012356 eye drops Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000031146 intracellular signal transduction Effects 0.000 description 5
- 230000004410 intraocular pressure Effects 0.000 description 5
- 210000001577 neostriatum Anatomy 0.000 description 5
- 210000004126 nerve fiber Anatomy 0.000 description 5
- 210000002241 neurite Anatomy 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 4
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 4
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 4
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 4
- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 208000024254 Delusional disease Diseases 0.000 description 4
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 4
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108010083674 Myelin Proteins Proteins 0.000 description 4
- 102000006386 Myelin Proteins Human genes 0.000 description 4
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 4
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 4
- 102000003923 Protein Kinase C Human genes 0.000 description 4
- 108090000315 Protein Kinase C Proteins 0.000 description 4
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 4
- 239000012472 biological sample Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229960003679 brimonidine Drugs 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 230000009245 menopause Effects 0.000 description 4
- 210000005012 myelin Anatomy 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 208000002851 paranoid schizophrenia Diseases 0.000 description 4
- 229960001416 pilocarpine Drugs 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 208000022610 schizoaffective disease Diseases 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 229960004605 timolol Drugs 0.000 description 4
- RHNXMQLPXJSMON-UHFFFAOYSA-N 2-[4-(chloromethyl)phenyl]-6-fluoropyridine Chemical compound FC1=CC=CC(C=2C=CC(CCl)=CC=2)=N1 RHNXMQLPXJSMON-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 102000003678 AMPA Receptors Human genes 0.000 description 3
- 108090000078 AMPA Receptors Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 201000000736 Amenorrhea Diseases 0.000 description 3
- 206010001928 Amenorrhoea Diseases 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 102100024317 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Human genes 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001117094 Homo sapiens Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Proteins 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 206010033799 Paralysis Diseases 0.000 description 3
- 208000005793 Restless legs syndrome Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 3
- 230000001668 ameliorated effect Effects 0.000 description 3
- 231100000540 amenorrhea Toxicity 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001627 detrimental effect Effects 0.000 description 3
- 238000002875 fluorescence polarization Methods 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 208000003532 hypothyroidism Diseases 0.000 description 3
- 230000002989 hypothyroidism Effects 0.000 description 3
- 208000000509 infertility Diseases 0.000 description 3
- 230000036512 infertility Effects 0.000 description 3
- 231100000535 infertility Toxicity 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000003998 progesterone receptors Human genes 0.000 description 3
- 108090000468 progesterone receptors Proteins 0.000 description 3
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000007781 signaling event Effects 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 208000002320 spinal muscular atrophy Diseases 0.000 description 3
- 208000011117 substance-related disease Diseases 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- 0 *N(C(c(c(N1c2ccccc2)n2)c[n]2[Fl])=O)C1=O Chemical compound *N(C(c(c(N1c2ccccc2)n2)c[n]2[Fl])=O)C1=O 0.000 description 2
- IWEGDQUCWQFKHS-UHFFFAOYSA-N 1-(1,3-dioxolan-2-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC2OCCO2)N=C1 IWEGDQUCWQFKHS-UHFFFAOYSA-N 0.000 description 2
- YRAJNWYBUCUFBD-UHFFFAOYSA-N 2,2,6,6-tetramethylheptane-3,5-dione Chemical compound CC(C)(C)C(=O)CC(=O)C(C)(C)C YRAJNWYBUCUFBD-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 2
- QWVQDAMZVZLFPB-UHFFFAOYSA-N 4-[(4-bromophenyl)methyl]-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one Chemical compound C1=C2C(=O)N(C)C3=NC(C)(C)CN3C2=NN1CC1=CC=C(Br)C=C1 QWVQDAMZVZLFPB-UHFFFAOYSA-N 0.000 description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 2
- XNFGIXXZGYPLNJ-UHFFFAOYSA-N 5-methyl-2-[(4-pyridin-2-ylphenyl)methyl]-7H-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound CN1C(NC=2C(C1=O)=CN(N=2)CC1=CC=C(C=C1)C1=NC=CC=C1)=O XNFGIXXZGYPLNJ-UHFFFAOYSA-N 0.000 description 2
- AEOBEOJCBAYXBA-UHFFFAOYSA-N A2P5P Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1OP(O)(O)=O AEOBEOJCBAYXBA-UHFFFAOYSA-N 0.000 description 2
- 208000037853 Abnormal uterine bleeding Diseases 0.000 description 2
- 101150051188 Adora2a gene Proteins 0.000 description 2
- 201000005670 Anovulation Diseases 0.000 description 2
- 206010002659 Anovulatory cycle Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010003805 Autism Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 description 2
- 102000003846 Carbonic anhydrases Human genes 0.000 description 2
- 108090000209 Carbonic anhydrases Proteins 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- HQRBEOJBYYXEGA-UHFFFAOYSA-N ClC=1N(C(C=2C(N=1)=NN(C=2)CC1=CC=C(C=C1)C1=NC=CC=C1)=O)C Chemical compound ClC=1N(C(C=2C(N=1)=NN(C=2)CC1=CC=C(C=C1)C1=NC=CC=C1)=O)C HQRBEOJBYYXEGA-UHFFFAOYSA-N 0.000 description 2
- VKXDBZLEZCBSHR-UHFFFAOYSA-N ClCC1=CC=C(C=C1)C1=NC=C(C=C1)F Chemical compound ClCC1=CC=C(C=C1)C1=NC=C(C=C1)F VKXDBZLEZCBSHR-UHFFFAOYSA-N 0.000 description 2
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 2
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 2
- 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 description 2
- 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 description 2
- 206010012239 Delusion Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- 102000009025 Endorphins Human genes 0.000 description 2
- 108010049140 Endorphins Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JZWGOJWFNRWYJY-UHFFFAOYSA-N FC=1C=CC(=NC=1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CC)C=C1 Chemical compound FC=1C=CC(=NC=1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CC)C=C1 JZWGOJWFNRWYJY-UHFFFAOYSA-N 0.000 description 2
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 2
- 208000001914 Fragile X syndrome Diseases 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 206010027339 Menstruation irregular Diseases 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- CMFFRXAKDHYJMI-UHFFFAOYSA-N N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2)C=C1 Chemical compound N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2)C=C1 CMFFRXAKDHYJMI-UHFFFAOYSA-N 0.000 description 2
- HNHZSUMYHHGAQL-UHFFFAOYSA-N N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2Cl)C=C1 Chemical compound N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2Cl)C=C1 HNHZSUMYHHGAQL-UHFFFAOYSA-N 0.000 description 2
- UUDPSRGKDVVMSG-UHFFFAOYSA-N N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC(=C(C=C2)F)F)C=C1 Chemical compound N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC(=C(C=C2)F)F)C=C1 UUDPSRGKDVVMSG-UHFFFAOYSA-N 0.000 description 2
- UHBXCVVEFDTTRT-UHFFFAOYSA-N N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC=C(C=C2)F)C=C1 Chemical compound N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC=C(C=C2)F)C=C1 UHBXCVVEFDTTRT-UHFFFAOYSA-N 0.000 description 2
- 108020001621 Natriuretic Peptide Proteins 0.000 description 2
- 102000004571 Natriuretic peptide Human genes 0.000 description 2
- 102400001103 Neurotensin Human genes 0.000 description 2
- 101800001814 Neurotensin Proteins 0.000 description 2
- 108010005298 Oligodendrocyte-Myelin Glycoprotein Proteins 0.000 description 2
- 102100026746 Oligodendrocyte-myelin glycoprotein Human genes 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 206010033864 Paranoia Diseases 0.000 description 2
- 208000027099 Paranoid disease Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- ZGUGWUXLJSTTMA-UHFFFAOYSA-N Promazinum Chemical group C1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZGUGWUXLJSTTMA-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 206010051482 Prostatomegaly Diseases 0.000 description 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 201000001880 Sexual dysfunction Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 229960000571 acetazolamide Drugs 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 2
- 239000000674 adrenergic antagonist Substances 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 231100000552 anovulation Toxicity 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 2
- 125000001769 aryl amino group Chemical group 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 description 2
- 229940127236 atypical antipsychotics Drugs 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000028600 axonogenesis Effects 0.000 description 2
- FZIZEIAMIREUTN-UHFFFAOYSA-N azane;cerium(3+) Chemical compound N.[Ce+3] FZIZEIAMIREUTN-UHFFFAOYSA-N 0.000 description 2
- 210000004227 basal ganglia Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000012148 binding buffer Substances 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 229960001724 brimonidine tartrate Drugs 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
- 229960001076 chlorpromazine Drugs 0.000 description 2
- 210000004240 ciliary body Anatomy 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 231100000868 delusion Toxicity 0.000 description 2
- 210000001947 dentate gyrus Anatomy 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000003028 elevating effect Effects 0.000 description 2
- 201000003914 endometrial carcinoma Diseases 0.000 description 2
- 201000006828 endometrial hyperplasia Diseases 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 210000000720 eyelash Anatomy 0.000 description 2
- 229960000556 fingolimod Drugs 0.000 description 2
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000002657 hormone replacement therapy Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 229960001160 latanoprost Drugs 0.000 description 2
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 239000000472 muscarinic agonist Substances 0.000 description 2
- 239000000692 natriuretic peptide Substances 0.000 description 2
- 210000005155 neural progenitor cell Anatomy 0.000 description 2
- 230000001272 neurogenic effect Effects 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000003018 neuroregenerative effect Effects 0.000 description 2
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000002474 noradrenergic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000006461 physiological response Effects 0.000 description 2
- 229960001697 physostigmine Drugs 0.000 description 2
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000583 progesterone congener Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 208000002815 pulmonary hypertension Diseases 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 231100000872 sexual dysfunction Toxicity 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000009121 systemic therapy Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 229960002368 travoprost Drugs 0.000 description 2
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YUSCRGFYKCAQHE-HQFNMCNFSA-N (8r,9s,13s,14s,17s)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol;(8r,9s,13s,14s,16r,17r)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,16,17-triol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1.OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 YUSCRGFYKCAQHE-HQFNMCNFSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- PMXMIIMHBWHSKN-LJQANCHMSA-N (R)-paliperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCC[C@@H](O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-LJQANCHMSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- WSPOMRSOLSGNFJ-AUWJEWJLSA-N (Z)-chlorprothixene Chemical compound C1=C(Cl)C=C2C(=C/CCN(C)C)\C3=CC=CC=C3SC2=C1 WSPOMRSOLSGNFJ-AUWJEWJLSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
- FCLQGHNSQXFQEG-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]pyridine Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=N1 FCLQGHNSQXFQEG-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- NYMDPDNETOLVBS-UHFFFAOYSA-N 4-fluoro-3-methylaniline Chemical compound CC1=CC(N)=CC=C1F NYMDPDNETOLVBS-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- MKLSFWUVWIXENK-UHFFFAOYSA-N 5-chloro-4-[[4-(5-fluoropyridin-2-yl)phenyl]methyl]-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one Chemical compound ClC1=C2C(=O)N(C)C3=NC(C)(C)CN3C2=NN1CC(C=C1)=CC=C1C1=CC=C(F)C=N1 MKLSFWUVWIXENK-UHFFFAOYSA-N 0.000 description 1
- JVYBHXSIAJRNGN-UHFFFAOYSA-N 7-[(4-methoxyphenyl)methyl]-5-methyl-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N(C)C(=O)C2=C1NN=C2 JVYBHXSIAJRNGN-UHFFFAOYSA-N 0.000 description 1
- BUFOYCZRAQRAJP-UHFFFAOYSA-N 8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2(6),4,9-trien-7-one Chemical compound O=C1N(C)C2=NC(C)(C)CN2C2=NNC=C21 BUFOYCZRAQRAJP-UHFFFAOYSA-N 0.000 description 1
- SIQHHHARVVFAQQ-UHFFFAOYSA-N 8,11,11-trimethyl-4-[(4-phenoxyphenyl)methyl]-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one Chemical compound C1=C2C(=O)N(C)C3=NC(C)(C)CN3C2=NN1CC(C=C1)=CC=C1OC1=CC=CC=C1 SIQHHHARVVFAQQ-UHFFFAOYSA-N 0.000 description 1
- UNGDGQYONLTNJZ-UHFFFAOYSA-N 9-methoxy-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2OC UNGDGQYONLTNJZ-UHFFFAOYSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 208000006373 Bell palsy Diseases 0.000 description 1
- CYGODHVAJQTCBG-UHFFFAOYSA-N Bifeprunox Chemical compound C=12OC(=O)NC2=CC=CC=1N(CC1)CCN1CC(C=1)=CC=CC=1C1=CC=CC=C1 CYGODHVAJQTCBG-UHFFFAOYSA-N 0.000 description 1
- HASSSWFIYBIFLI-UHFFFAOYSA-N C(C)C=1N(N=C2C=1C(N(C=1N2CC(N=1)(C)C)C)=O)CC1=CC=C(C=C1)C1=NC(=CC=C1)F Chemical compound C(C)C=1N(N=C2C=1C(N(C=1N2CC(N=1)(C)C)C)=O)CC1=CC=C(C=C1)C1=NC(=CC=C1)F HASSSWFIYBIFLI-UHFFFAOYSA-N 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- HFNMIXCYCKYLAO-UHFFFAOYSA-N ClC1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC=C(C=C2)F)C=C1 Chemical compound ClC1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC=C(C=C2)F)C=C1 HFNMIXCYCKYLAO-UHFFFAOYSA-N 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 208000019743 Cranial nerve injury Diseases 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- NOGNXFISZULWKY-UHFFFAOYSA-N FC1=CC=CC(=N1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CCC)C=C1 Chemical compound FC1=CC=CC(=N1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CCC)C=C1 NOGNXFISZULWKY-UHFFFAOYSA-N 0.000 description 1
- JLZVVIDQMULSIM-UHFFFAOYSA-N FC=1C=CC(=NC=1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CCC)C=C1 Chemical compound FC=1C=CC(=NC=1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2CCC)C=C1 JLZVVIDQMULSIM-UHFFFAOYSA-N 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 1
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010048462 Growth of eyelashes Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000008899 Habitual abortion Diseases 0.000 description 1
- 206010019468 Hemiplegia Diseases 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- 201000008450 Intracranial aneurysm Diseases 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- 208000007623 Lordosis Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000019430 Motor disease Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 1
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- IUEKCYIGTAOMHJ-UHFFFAOYSA-N N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC(=C(C=C2)F)C)C=C1 Chemical compound N1=C(C=CC=C1)C1=CC=C(CN2N=C3C(C(N(C=4N3CC(N=4)(C)C)C)=O)=C2NC2=CC(=C(C=C2)F)C)C=C1 IUEKCYIGTAOMHJ-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ZNYOOJSUSHOBEK-UHFFFAOYSA-N OCC(C)(C)NC=1N(C(C=2C(N=1)=NN(C=2)CC1=CC=C(C=C1)C1=NC=CC=C1)=O)C Chemical compound OCC(C)(C)NC=1N(C(C=2C(N=1)=NN(C=2)CC1=CC=C(C=C1)C1=NC=CC=C1)=O)C ZNYOOJSUSHOBEK-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 208000006399 Premature Obstetric Labor Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 206010037714 Quadriplegia Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
- GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 1
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- 229940003677 alphagan Drugs 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 229960003036 amisulpride Drugs 0.000 description 1
- NTJOBXMMWNYJFB-UHFFFAOYSA-N amisulpride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(N)C=C1OC NTJOBXMMWNYJFB-UHFFFAOYSA-N 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
- 229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical compound ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 description 1
- 229960002610 apraclonidine Drugs 0.000 description 1
- 230000004509 aqueous humor production Effects 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 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
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 229940098085 betagan Drugs 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 229950009087 bifeprunox Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229960000722 brinzolamide Drugs 0.000 description 1
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 210000000782 cerebellar granule cell Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000036319 cervical spondylosis Diseases 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 229960001552 chlorprothixene Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 229940088505 compazine Drugs 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 229960000632 dexamfetamine Drugs 0.000 description 1
- 229940099238 diamox Drugs 0.000 description 1
- 150000001987 diarylethers Chemical class 0.000 description 1
- VKFAUCPBMAGVRG-UHFFFAOYSA-N dipivefrin hydrochloride Chemical compound [Cl-].C[NH2+]CC(O)C1=CC=C(OC(=O)C(C)(C)C)C(OC(=O)C(C)(C)C)=C1 VKFAUCPBMAGVRG-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229960000394 droperidol Drugs 0.000 description 1
- RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229960002017 echothiophate Drugs 0.000 description 1
- BJOLKYGKSZKIGU-UHFFFAOYSA-N ecothiopate Chemical compound CCOP(=O)(OCC)SCC[N+](C)(C)C BJOLKYGKSZKIGU-UHFFFAOYSA-N 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000009585 enzyme analysis Methods 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 229940008359 estradiol / estriol Drugs 0.000 description 1
- 239000003687 estradiol congener Substances 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 229960001348 estriol Drugs 0.000 description 1
- 230000012173 estrus Effects 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960002690 fluphenazine Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940003380 geodon Drugs 0.000 description 1
- 229960003776 glatiramer acetate Drugs 0.000 description 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 description 1
- 235000013928 guanylic acid Nutrition 0.000 description 1
- 229940095895 haldol Drugs 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000009808 hippocampal neurogenesis Effects 0.000 description 1
- 102000055551 human PDE1A Human genes 0.000 description 1
- 102000055462 human PDE1B Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003140 lateral ventricle Anatomy 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- 229960000831 levobunolol Drugs 0.000 description 1
- DNTDOBSIBZKFCP-YDALLXLXSA-N levobunolol hydrochloride Chemical compound [Cl-].O=C1CCCC2=C1C=CC=C2OC[C@@H](O)C[NH2+]C(C)(C)C DNTDOBSIBZKFCP-YDALLXLXSA-N 0.000 description 1
- 229940112534 lumigan Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 210000001767 medulla oblongata Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- SLVMESMUVMCQIY-UHFFFAOYSA-N mesoridazine Chemical compound CN1CCCCC1CCN1C2=CC(S(C)=O)=CC=C2SC2=CC=CC=C21 SLVMESMUVMCQIY-UHFFFAOYSA-N 0.000 description 1
- 229960000300 mesoridazine Drugs 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- VRQVVMDWGGWHTJ-CQSZACIVSA-N methotrimeprazine Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1 VRQVVMDWGGWHTJ-CQSZACIVSA-N 0.000 description 1
- 229940042053 methotrimeprazine Drugs 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229960001344 methylphenidate Drugs 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 229960001165 modafinil Drugs 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 201000005518 mononeuropathy Diseases 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 230000017997 negative regulation of axon regeneration Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000000734 parasympathomimetic agent Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960000761 pemoline Drugs 0.000 description 1
- NRNCYVBFPDDJNE-UHFFFAOYSA-N pemoline Chemical compound O1C(N)=NC(=O)C1C1=CC=CC=C1 NRNCYVBFPDDJNE-UHFFFAOYSA-N 0.000 description 1
- 229960000762 perphenazine Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000007084 physiological dysfunction Effects 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000004911 positive regulation of CREB transcription factor activity Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- DSKIOWHQLUWFLG-SPIKMXEPSA-N prochlorperazine maleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 DSKIOWHQLUWFLG-SPIKMXEPSA-N 0.000 description 1
- 150000003146 progesterones Chemical class 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 201000008752 progressive muscular atrophy Diseases 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 229960003598 promazine Drugs 0.000 description 1
- 229960003910 promethazine Drugs 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical class 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 229960002601 protriptyline Drugs 0.000 description 1
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 208000034213 recurrent susceptibility to 1 pregnancy loss Diseases 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000005801 spondylosis Diseases 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 150000005075 thioxanthenes Chemical class 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 206010048627 thoracic outlet syndrome Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229960005013 tiotixene Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 1
- 229960002324 trifluoperazine Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- XSCGXQMFQXDFCW-UHFFFAOYSA-N triflupromazine Chemical compound C1=C(C(F)(F)F)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 XSCGXQMFQXDFCW-UHFFFAOYSA-N 0.000 description 1
- 229960003904 triflupromazine Drugs 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 229960004317 unoprostone Drugs 0.000 description 1
- TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 229940002639 xalatan Drugs 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- WFPIAZLQTJBIFN-DVZOWYKESA-N zuclopenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(Cl)=CC=C2SC2=CC=CC=C2/1 WFPIAZLQTJBIFN-DVZOWYKESA-N 0.000 description 1
- 229960004141 zuclopenthixol Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D347/00—Heterocyclic compounds containing rings having halogen atoms as ring hetero atoms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/84—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/50—Determining the risk of developing a disease
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- General Physics & Mathematics (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462051735P | 2014-09-17 | 2014-09-17 | |
| US62/051,735 | 2014-09-17 | ||
| US201462052283P | 2014-09-18 | 2014-09-18 | |
| US62/052,283 | 2014-09-18 | ||
| PCT/US2015/050814 WO2016044667A1 (en) | 2014-09-17 | 2015-09-17 | Compounds and methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20170058406A KR20170058406A (ko) | 2017-05-26 |
| KR102332957B1 true KR102332957B1 (ko) | 2021-11-29 |
Family
ID=55533880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020177010409A Active KR102332957B1 (ko) | 2014-09-17 | 2015-09-17 | 화합물 및 방법 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10150774B2 (enExample) |
| EP (2) | EP3193878B1 (enExample) |
| JP (1) | JP6596080B2 (enExample) |
| KR (1) | KR102332957B1 (enExample) |
| CN (1) | CN107106563B (enExample) |
| AU (1) | AU2015317527B2 (enExample) |
| BR (1) | BR112017005533B1 (enExample) |
| CA (1) | CA2961212C (enExample) |
| ES (2) | ES2915200T3 (enExample) |
| HK (1) | HK1243342A1 (enExample) |
| IL (2) | IL292225B2 (enExample) |
| MX (1) | MX385382B (enExample) |
| RU (1) | RU2711442C2 (enExample) |
| WO (1) | WO2016044667A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3193878B1 (en) | 2014-09-17 | 2021-01-06 | Intra-Cellular Therapies, Inc. | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) |
| EP3746081A4 (en) | 2018-01-31 | 2021-10-27 | Intra-Cellular Therapies, Inc. | Novel uses |
| CN112189013A (zh) * | 2018-05-25 | 2021-01-05 | 细胞内治疗公司 | 有机化合物 |
| US12194042B2 (en) | 2018-10-21 | 2025-01-14 | Intra-Cellular Therapies, Inc. | Uses |
| WO2020146384A1 (en) | 2019-01-07 | 2020-07-16 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP3953358A4 (en) * | 2019-04-12 | 2023-01-04 | Intra-Cellular Therapies, Inc. | ORGANIC COMPOUNDS |
| CN114340636A (zh) * | 2019-09-03 | 2022-04-12 | 细胞内治疗公司 | 治疗方法 |
| EP4413980A3 (en) | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel compounds |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Family Cites Families (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6032638B2 (ja) | 1976-09-01 | 1985-07-29 | 武田薬品工業株式会社 | ３−アミノピラゾロ〔３，４−ｄ〕ピリミジン誘導体 |
| EP0077372A1 (de) | 1981-04-22 | 1983-04-27 | Byk Gulden Lomberg Chemische Fabrik GmbH | NEUE PYRAZOLO(3,4-d)PYRIMIDINE, VERFAHREN ZU DEREN HERSTELLUNG UND SIE ENTHALTENDE ARZNEIMITTEL |
| US4469868A (en) | 1982-05-24 | 1984-09-04 | Warner-Lambert Company | Alkylimidazo[1,2-c]pyrazolo[3,4-e]pyrimidines |
| US4603203A (en) | 1983-12-14 | 1986-07-29 | Takeda Chemical Industries, Ltd. | 3-aminopyrazolo[3,4-d]pyrimidine derivatives and production thereof |
| US4666908A (en) | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| NZ238609A (en) | 1990-06-21 | 1993-12-23 | Schering Corp | Polycyclic guanine derivatives; preparation, pharmaceutical compositions, |
| US5202328A (en) | 1991-03-06 | 1993-04-13 | Merck & Co., Inc. | Substituted fused pyrimidinones |
| US5294612A (en) | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| CA2156918A1 (en) | 1993-02-26 | 1994-09-01 | Deen Tulshian | 2-benzyl-polycyclic guanine derivatives and process for preparing them |
| GB9304919D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9315017D0 (en) | 1993-07-20 | 1993-09-01 | Glaxo Lab Sa | Chemical compounds |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| US5824683A (en) | 1995-11-28 | 1998-10-20 | Schering Corporation | 2'- 4'-halo- 1,1'-biphenyl!-4-yl!methyl!-5'-methyl-spiro cyclopentane-1,7' (8'H)- 3H! imidazo 2,1-b!purin!-4' (5'H)-ones |
| GB9526245D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2001507349A (ja) | 1996-12-23 | 2001-06-05 | セルテック セラピューティックス リミテッド | 縮合多環式２−アミノピリミジン誘導体、それらの製造およびたんぱく質チロシンキナーゼ抑制因子としてのそれらの使用 |
| SE9701398D0 (sv) | 1997-04-15 | 1997-04-15 | Astra Pharma Prod | Novel compounds |
| CZ299633B6 (cs) * | 1997-04-25 | 2008-09-24 | Pfizer Inc. | Pyrazolopyrimidinony, meziprodukty pro jejich výrobu a farmaceutické a veterinární kompozice na jejich bázi |
| IT1291372B1 (it) | 1997-05-21 | 1999-01-07 | Schering Plough S P A | Uso di analoghi eterociclici di 1,2,4-triazolo (1,5-c) pirimidine per la preparazione di medicamenti utili per il trattamento delle malattie |
| US6013621A (en) | 1997-10-17 | 2000-01-11 | The Rockfeller University | Method of treating psychosis and/or hyperactivity |
| GB9722520D0 (en) | 1997-10-24 | 1997-12-24 | Pfizer Ltd | Compounds |
| ES2356886T3 (es) | 1998-03-31 | 2011-04-14 | Kyowa Hakko Kirin Co., Ltd. | Compuestos heterocíclicos nitrogenados. |
| US6133273A (en) | 1998-05-08 | 2000-10-17 | American Home Products Corporation | Pyrazolopyrimidine-2,4-dione sulfonamides |
| GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
| EP1206265B1 (en) | 1999-06-30 | 2003-11-12 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| EP1194152A4 (en) | 1999-06-30 | 2002-11-06 | Merck & Co Inc | Links to SRC kinase inhibition |
| DE19931206A1 (de) | 1999-07-07 | 2001-01-11 | Stief Christian | Arzneimittel zur Erhöhung des cAMP-Spiegels und deren Verwendung |
| ATE309241T1 (de) | 1999-09-10 | 2005-11-15 | Merck & Co Inc | Tyrosin kinase inhibitoren |
| AU7738100A (en) | 1999-09-30 | 2001-04-30 | Neurogen Corporation | Certain alkylene diamine-substituted pyrazolo(1,5,-a)-1,5-pyrimidines and pyrazolo(1,5-a)-1,3,5-triazines |
| JP2003511452A (ja) | 1999-10-11 | 2003-03-25 | ファイザー・インク | ホスホジエステラーゼ阻害剤としての５−（２−置換−５−ヘテロシクリルスルホニルピリド−３−イル）−ジヒドロピラゾロ［４，３−ｄ］ピリミジン−７−オン |
| TWI265925B (en) | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
| IL139073A0 (en) | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| AU2001255849B8 (en) | 2000-04-19 | 2006-04-27 | Lilly Icos, Llc. | PDE-V inhibitors for treatment of Parkinson's Disease |
| US6693099B2 (en) | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| ES2241994T3 (es) | 2001-03-16 | 2005-11-01 | Pfizer Inc. | Compuestos pirazolo(4,3-d)pirimidinona como inhibidores de gmpc. |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| SE0102315D0 (sv) | 2001-06-28 | 2001-06-28 | Astrazeneca Ab | Compounds |
| CN1315835C (zh) | 2001-08-28 | 2007-05-16 | 先灵公司 | 多环鸟嘌呤磷酸二酯酶v抑制剂 |
| CA2459161A1 (en) | 2001-08-31 | 2003-03-13 | The Rockefeller University | Phosphodiesterase activity and regulation of phosphodiesterase 1b-mediated signaling in brain |
| US6943171B2 (en) | 2001-11-09 | 2005-09-13 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase V inhibitors |
| HRP20040850A2 (en) | 2002-02-15 | 2005-08-31 | Synovo Gmbh | Conjugates of biologically active compounds, methods for their preparation and use formulation and pharmaceutical applications thereof |
| US20050153372A1 (en) | 2002-02-21 | 2005-07-14 | Paul Greengard | Compositions and method for regulation of calcium-dependent signaling in brain |
| GB0230045D0 (en) | 2002-12-23 | 2003-01-29 | Glaxo Group Ltd | Compounds |
| EP1613747A1 (en) | 2003-03-31 | 2006-01-11 | Pfizer Products Inc. | Crystal structure of 3 ,5 -cyclic nucleotide phosphodiesterase 1b (pde1b) and uses thereof |
| BRPI0409229A (pt) | 2003-04-01 | 2006-03-28 | Applied Research Systems | inibidores das fosfodiesterases na infertilidade |
| CN1878773A (zh) | 2003-09-05 | 2006-12-13 | 神经能质公司 | 作为crf1受体配位体的杂芳基稠合的吡啶,吡嗪及嘧啶 |
| CN101248050B (zh) | 2005-06-06 | 2013-07-17 | 武田药品工业株式会社 | 有机化合物 |
| EP1919287A4 (en) | 2005-08-23 | 2010-04-28 | Intra Cellular Therapies Inc | ORGANIC COMPOUNDS FOR TREATING A REDUCED DOPAMINE RECEPTOR SIGNALING ACTIVITY |
| KR20090042227A (ko) | 2006-06-06 | 2009-04-29 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| US20070286890A1 (en) | 2006-06-07 | 2007-12-13 | John Garnett Walt | Eyelash applicator and method |
| WO2008063505A1 (en) * | 2006-11-13 | 2008-05-29 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9006258B2 (en) | 2006-12-05 | 2015-04-14 | Intra-Cellular Therapies, Inc. | Method of treating female sexual dysfunction with a PDE1 inhibitor |
| DK2152712T3 (da) * | 2007-05-11 | 2012-03-26 | Pfizer | Aminoheterocykliske fobindelser |
| WO2009075784A1 (en) | 2007-12-06 | 2009-06-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| AU2008331833A1 (en) | 2007-12-06 | 2009-06-11 | Intra-Cellular Therapies, Inc | Organic compounds |
| WO2010065147A1 (en) | 2008-12-06 | 2010-06-10 | Intra-Cellular Therapies, Inc. | Organic compounds |
| CN102232077A (zh) | 2008-12-06 | 2011-11-02 | 细胞内治疗公司 | 有机化合物 |
| CN102223799A (zh) * | 2008-12-06 | 2011-10-19 | 细胞内治疗公司 | 有机化合物 |
| EP2367429B1 (en) | 2008-12-06 | 2017-06-07 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2358204B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| KR20110098731A (ko) | 2008-12-06 | 2011-09-01 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| EP2400970A4 (en) | 2009-02-25 | 2012-07-18 | Intra Cellular Therapies Inc | PDE-1-HEMMER FOR EYE DRESSING |
| US9468637B2 (en) | 2009-05-13 | 2016-10-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP2013507360A (ja) | 2009-10-08 | 2013-03-04 | イントラ−セルラー・セラピーズ・インコーポレイテッド | ホスホジエステラーゼ１−標的トレーサーおよび方法 |
| MX339805B (es) | 2010-04-22 | 2016-06-10 | Intra Cellular Therapies Inc | Compuestos organicos. |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP5911854B2 (ja) | 2010-05-31 | 2016-04-27 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| JP5879336B2 (ja) | 2010-05-31 | 2016-03-08 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| US10561656B2 (en) | 2011-06-10 | 2020-02-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| AR091507A1 (es) | 2012-06-21 | 2015-02-11 | Intra Cellular Therapies Inc | SALES DE (6aR,9aS)-5,6a,7,8,9,9a-HEXAHIDRO-5-METIL-3-(FENILAMINO)-2-((4-(6-FLUOROPIRIDIN-2-IL)FENIL)METIL)-CICLOPENT[4,5]IMIDAZO[1,2-a]PIRAZOLO[4,3-e]PIRIMIDIN-4(2H)-ONA |
| ES2836129T3 (es) | 2013-03-15 | 2021-06-24 | Intra Cellular Therapies Inc | Compuestos orgánicos |
| ES2745819T3 (es) * | 2014-08-07 | 2020-03-03 | Intra Cellular Therapies Inc | Derivados de imidazo[1,2-a]-pirazolo[4,3-e]-pirimidin-4-ona con actividad inhibidora de la PDE1 |
| EP3193878B1 (en) | 2014-09-17 | 2021-01-06 | Intra-Cellular Therapies, Inc. | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) |
| CN104570148B (zh) * | 2014-12-29 | 2015-09-02 | 河海大学 | 涉水结构物渗漏无热源光纤定位定向系统及监测方法 |
-
2015
- 2015-09-17 EP EP15841777.4A patent/EP3193878B1/en active Active
- 2015-09-17 JP JP2017514842A patent/JP6596080B2/ja active Active
- 2015-09-17 ES ES20178873T patent/ES2915200T3/es active Active
- 2015-09-17 EP EP20178873.4A patent/EP3725789B1/en active Active
- 2015-09-17 WO PCT/US2015/050814 patent/WO2016044667A1/en not_active Ceased
- 2015-09-17 AU AU2015317527A patent/AU2015317527B2/en active Active
- 2015-09-17 MX MX2017003646A patent/MX385382B/es unknown
- 2015-09-17 BR BR112017005533-3A patent/BR112017005533B1/pt active IP Right Grant
- 2015-09-17 ES ES15841777T patent/ES2857567T3/es active Active
- 2015-09-17 IL IL292225A patent/IL292225B2/en unknown
- 2015-09-17 RU RU2017112989A patent/RU2711442C2/ru active
- 2015-09-17 CA CA2961212A patent/CA2961212C/en active Active
- 2015-09-17 US US15/512,005 patent/US10150774B2/en active Active
- 2015-09-17 KR KR1020177010409A patent/KR102332957B1/ko active Active
- 2015-09-17 HK HK18102919.4A patent/HK1243342A1/zh unknown
- 2015-09-17 CN CN201580062061.3A patent/CN107106563B/zh active Active
-
2017
- 2017-03-12 IL IL251107A patent/IL251107B/en unknown
-
2018
- 2018-11-09 US US16/186,272 patent/US20190144460A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016044667A1 (en) | 2016-03-24 |
| US10150774B2 (en) | 2018-12-11 |
| EP3193878A1 (en) | 2017-07-26 |
| CN107106563B (zh) | 2021-05-25 |
| CA2961212A1 (en) | 2016-03-24 |
| CA2961212C (en) | 2024-02-06 |
| BR112017005533A2 (pt) | 2017-12-05 |
| RU2017112989A3 (enExample) | 2019-04-23 |
| BR112017005533B1 (pt) | 2023-10-10 |
| HK1243342A1 (zh) | 2018-07-13 |
| CN107106563A (zh) | 2017-08-29 |
| EP3725789A1 (en) | 2020-10-21 |
| EP3725789B1 (en) | 2022-03-09 |
| AU2015317527B2 (en) | 2020-08-20 |
| RU2017112989A (ru) | 2018-10-17 |
| IL292225B2 (en) | 2024-12-01 |
| AU2015317527A1 (en) | 2017-04-13 |
| JP6596080B2 (ja) | 2019-10-23 |
| JP2017527598A (ja) | 2017-09-21 |
| EP3193878A4 (en) | 2018-03-21 |
| MX2017003646A (es) | 2017-07-13 |
| RU2711442C2 (ru) | 2020-01-17 |
| IL292225B1 (en) | 2024-08-01 |
| ES2857567T3 (es) | 2021-09-29 |
| IL251107B (en) | 2022-05-01 |
| ES2915200T3 (es) | 2022-06-21 |
| IL292225A (en) | 2022-06-01 |
| US20190144460A1 (en) | 2019-05-16 |
| KR20170058406A (ko) | 2017-05-26 |
| IL251107A0 (en) | 2017-04-30 |
| MX385382B (es) | 2025-03-18 |
| US20170291904A1 (en) | 2017-10-12 |
| EP3193878B1 (en) | 2021-01-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102332957B1 (ko) | 화합물 및 방법 | |
| JP5911854B2 (ja) | 有機化合物 | |
| JP5710492B2 (ja) | 有機化合物 | |
| JP5879335B2 (ja) | 有機化合物 | |
| JP5894148B2 (ja) | 有機化合物 | |
| JP5784501B2 (ja) | 有機化合物 | |
| CA2906640C (en) | Substituted imidazo-[1,2-a]pyrazolo[4.3-e]pyrimidin-4[5h]-one compounds and pharmaceutical compositions and use therof as pde1 inhibitors | |
| KR20110096032A (ko) | 유기 화합물 | |
| HK1241719B (en) | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) | |
| HK1241719A1 (en) | 7,8-dihydro-[2h]-imidazo-[1,2-a]pyrazolo[4,3-e]pyrimidin-4(5h)-one derivatives as phosphodiesterase 1 (pde1) inhibitors for treating diseases, disorders or injuries of the central nervous system (cns) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20170417 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20191015 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20210324 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20210826 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20211125 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20211125 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20241028 Start annual number: 4 End annual number: 4 |