KR20160046693A - 횡격막 기능을 향상시키는 방법들 - Google Patents
횡격막 기능을 향상시키는 방법들 Download PDFInfo
- Publication number
- KR20160046693A KR20160046693A KR1020147027435A KR20147027435A KR20160046693A KR 20160046693 A KR20160046693 A KR 20160046693A KR 1020147027435 A KR1020147027435 A KR 1020147027435A KR 20147027435 A KR20147027435 A KR 20147027435A KR 20160046693 A KR20160046693 A KR 20160046693A
- Authority
- KR
- South Korea
- Prior art keywords
- pyrazin
- imidazo
- alkyl
- enyl
- prop
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 57
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 210000002027 skeletal muscle Anatomy 0.000 claims abstract description 45
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 239000011575 calcium Substances 0.000 claims abstract description 29
- 229940125913 troponin activator Drugs 0.000 claims abstract description 28
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 25
- 230000001965 increasing effect Effects 0.000 claims abstract description 21
- 206010003694 Atrophy Diseases 0.000 claims abstract description 20
- 230000037444 atrophy Effects 0.000 claims abstract description 20
- 230000035945 sensitivity Effects 0.000 claims abstract description 15
- 230000000694 effects Effects 0.000 claims abstract description 13
- 230000002708 enhancing effect Effects 0.000 claims abstract 2
- -1 4-heptyl Chemical group 0.000 claims description 383
- 125000000217 alkyl group Chemical group 0.000 claims description 282
- 150000001875 compounds Chemical class 0.000 claims description 167
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 126
- 125000001424 substituent group Chemical group 0.000 claims description 113
- 125000003118 aryl group Chemical group 0.000 claims description 93
- 229910052799 carbon Inorganic materials 0.000 claims description 89
- 229910052736 halogen Inorganic materials 0.000 claims description 86
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 82
- 125000001072 heteroaryl group Chemical group 0.000 claims description 81
- 150000002367 halogens Chemical class 0.000 claims description 76
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 74
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 72
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 71
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 70
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 67
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 51
- 150000002431 hydrogen Chemical class 0.000 claims description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims description 46
- 239000000835 fiber Substances 0.000 claims description 40
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 38
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 30
- 229910052717 sulfur Chemical group 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 206010019280 Heart failures Diseases 0.000 claims description 24
- 125000001624 naphthyl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 19
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 15
- 201000006938 muscular dystrophy Diseases 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 206010012725 Diaphragmatic paralysis Diseases 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 11
- CHJDFFWYGFUOHU-UHFFFAOYSA-N C(=CC)N1C(=NC=2C1=NC=CN=2)O Chemical compound C(=CC)N1C(=NC=2C1=NC=CN=2)O CHJDFFWYGFUOHU-UHFFFAOYSA-N 0.000 claims description 10
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 10
- 230000004064 dysfunction Effects 0.000 claims description 10
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 9
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 9
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000011593 sulfur Chemical group 0.000 claims description 7
- RSQGZEAXODVTOL-UHFFFAOYSA-N 5-ethynyl-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C#CC1=CN=C2NC(=O)N(C(CC)CC)C2=N1 RSQGZEAXODVTOL-UHFFFAOYSA-N 0.000 claims description 6
- 150000005829 chemical entities Chemical class 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- BUNCDJQSYZGIMV-UHFFFAOYSA-N CCC(CC)C1=CC=COC1N(C1=NC(C#C)=CN=C1N1)C1=O Chemical compound CCC(CC)C1=CC=COC1N(C1=NC(C#C)=CN=C1N1)C1=O BUNCDJQSYZGIMV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 230000002829 reductive effect Effects 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- SBJUQVUTJXSWQG-UHFFFAOYSA-N 5-ethenyl-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C=CC1=CN=C2NC(=O)N(C(CC)CC)C2=N1 SBJUQVUTJXSWQG-UHFFFAOYSA-N 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
- 230000036961 partial effect Effects 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
- 230000001605 fetal effect Effects 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 230000037081 physical activity Effects 0.000 claims description 3
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- SSZGBXHOXMJQIV-NSCUHMNNSA-N 3-(oxan-4-yl)-5-[(e)-prop-1-enyl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(/C=C/C)=CN=C2N=C(O)N1C1CCOCC1 SSZGBXHOXMJQIV-NSCUHMNNSA-N 0.000 claims description 2
- SSZGBXHOXMJQIV-IHWYPQMZSA-N 3-(oxan-4-yl)-5-[(z)-prop-1-enyl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(\C=C/C)=CN=C2NC(=O)N1C1CCOCC1 SSZGBXHOXMJQIV-IHWYPQMZSA-N 0.000 claims description 2
- CWRLTTUDYMJKOH-UHFFFAOYSA-N CCC(CN1CCOCC1)N(C1=NC=CN=C1N1C#C)C1=O Chemical compound CCC(CN1CCOCC1)N(C1=NC=CN=C1N1C#C)C1=O CWRLTTUDYMJKOH-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical group [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 208000002151 Pleural effusion Diseases 0.000 claims description 2
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 2
- 238000005399 mechanical ventilation Methods 0.000 claims description 2
- 231100000572 poisoning Toxicity 0.000 claims description 2
- 230000000607 poisoning effect Effects 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 210000001087 myotubule Anatomy 0.000 abstract description 46
- 210000003205 muscle Anatomy 0.000 description 48
- 206010057190 Respiratory tract infections Diseases 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 125000004043 oxo group Chemical group O=* 0.000 description 37
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 36
- 125000005843 halogen group Chemical group 0.000 description 34
- 241000700159 Rattus Species 0.000 description 32
- 230000006870 function Effects 0.000 description 26
- 125000000753 cycloalkyl group Chemical group 0.000 description 24
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- 230000000638 stimulation Effects 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 description 16
- 229910052731 fluorine Inorganic materials 0.000 description 15
- 239000011737 fluorine Substances 0.000 description 15
- 125000002252 acyl group Chemical group 0.000 description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 13
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 13
- 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 13
- 125000004076 pyridyl group Chemical group 0.000 description 13
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 238000003419 tautomerization reaction Methods 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- CGKLYWOFLUIKCX-UHFFFAOYSA-N 1,3-dihydroimidazo[4,5-b]pyrazin-2-one Chemical compound C1=CN=C2NC(=O)NC2=N1 CGKLYWOFLUIKCX-UHFFFAOYSA-N 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 10
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 125000000547 substituted alkyl group Chemical group 0.000 description 10
- 125000003107 substituted aryl group Chemical group 0.000 description 10
- 125000000335 thiazolyl group Chemical group 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 125000003367 polycyclic group Chemical group 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 125000001113 thiadiazolyl group Chemical group 0.000 description 9
- 102000003505 Myosin Human genes 0.000 description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
- 102000004903 Troponin Human genes 0.000 description 8
- 108090001027 Troponin Proteins 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 230000005684 electric field Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 7
- 206010033799 Paralysis Diseases 0.000 description 7
- 102000013534 Troponin C Human genes 0.000 description 7
- 125000005037 alkyl phenyl group Chemical group 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 125000002883 imidazolyl group Chemical group 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 description 7
- 125000002971 oxazolyl group Chemical group 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 description 7
- 125000006413 ring segment Chemical group 0.000 description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 125000001544 thienyl group Chemical group 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 108060008487 Myosin Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 125000001786 isothiazolyl group Chemical group 0.000 description 6
- 125000000842 isoxazolyl group Chemical group 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 125000005412 pyrazyl group Chemical group 0.000 description 6
- 125000005495 pyridazyl group Chemical group 0.000 description 6
- 125000000168 pyrrolyl group Chemical group 0.000 description 6
- 125000005017 substituted alkenyl group Chemical group 0.000 description 6
- 125000004426 substituted alkynyl group Chemical group 0.000 description 6
- 125000001425 triazolyl group Chemical group 0.000 description 6
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 5
- 229940126062 Compound A Drugs 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 5
- 102000005937 Tropomyosin Human genes 0.000 description 5
- 108010030743 Tropomyosin Proteins 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 230000002146 bilateral effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 230000036461 convulsion Effects 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 5
- 125000003831 tetrazolyl group Chemical group 0.000 description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 description 5
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 208000000059 Dyspnea Diseases 0.000 description 4
- 206010013975 Dyspnoeas Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 108010065729 Troponin I Proteins 0.000 description 4
- 102000013394 Troponin I Human genes 0.000 description 4
- 108090001108 Troponin T Proteins 0.000 description 4
- 102000004987 Troponin T Human genes 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 125000005605 benzo group Chemical group 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000013522 chelant Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 201000004193 respiratory failure Diseases 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000002435 tendon Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- 208000003508 Botulism Diseases 0.000 description 3
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 208000004929 Facial Paralysis Diseases 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 201000006815 congenital muscular dystrophy Diseases 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 230000003274 myotonic effect Effects 0.000 description 3
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 3
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical compound C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 description 3
- 230000004202 respiratory function Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000003313 weakening effect Effects 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- TVYCYSWASMVOMJ-UHFFFAOYSA-N 1,2-dihydropyrazolo[3,4-d][1,3]thiazol-3-one Chemical compound N1=CSC2=C1NNC2=O TVYCYSWASMVOMJ-UHFFFAOYSA-N 0.000 description 2
- MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical compound C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical compound N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 2
- GXTJPCRFZLLAQY-UHFFFAOYSA-N 3-(1-phenylethyl)-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC=CN=C2NC(=O)N1C(C)C1=CC=CC=C1 GXTJPCRFZLLAQY-UHFFFAOYSA-N 0.000 description 2
- JKHDMCILNOHSBK-UHFFFAOYSA-N 3h-quinoxalin-2-one Chemical compound C1=CC=CC2=NC(=O)CN=C21 JKHDMCILNOHSBK-UHFFFAOYSA-N 0.000 description 2
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 2
- WGJUBVJZKNTGRC-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2CNCCC2=C1 WGJUBVJZKNTGRC-UHFFFAOYSA-N 0.000 description 2
- STXKJIIHKFGUCY-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Chemical class C1=NC=C2CNCCC2=N1 STXKJIIHKFGUCY-UHFFFAOYSA-N 0.000 description 2
- OOWPKYXJAWXXJL-UHFFFAOYSA-N 5-(dimethylamino)-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1=C(N(C)C)N=C2N(C(CC)CC)C(O)=NC2=N1 OOWPKYXJAWXXJL-UHFFFAOYSA-N 0.000 description 2
- KNHWRTKKDFEAEB-UHFFFAOYSA-N 5-bromo-1,3-dihydroimidazo[4,5-b]pyrazin-2-one Chemical compound BrC1=CN=C2NC(=O)NC2=N1 KNHWRTKKDFEAEB-UHFFFAOYSA-N 0.000 description 2
- JVUXJJNMSWDQNZ-MRVPVSSYSA-N 5-bromo-3-[(2r)-1-morpholin-4-ylpropan-2-yl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C([C@@H](C)N1C2=NC(Br)=CN=C2N=C1O)N1CCOCC1 JVUXJJNMSWDQNZ-MRVPVSSYSA-N 0.000 description 2
- DLGLLQCQYOSWFA-UHFFFAOYSA-N 5-bromo-3-heptan-4-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1=C(Br)N=C2N(C(CCC)CCC)C(O)=NC2=N1 DLGLLQCQYOSWFA-UHFFFAOYSA-N 0.000 description 2
- WPDKEIHMTHBWTQ-UHFFFAOYSA-N 5-chloro-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound ClC1=CN=C2NC(=O)N(C(CC)CC)C2=N1 WPDKEIHMTHBWTQ-UHFFFAOYSA-N 0.000 description 2
- JPDFKESEFQRCBE-UHFFFAOYSA-N 5-ethyl-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound CCC1=CN=C2NC(=O)N(C(CC)CC)C2=N1 JPDFKESEFQRCBE-UHFFFAOYSA-N 0.000 description 2
- JCLOPOHRCQTTGK-UHFFFAOYSA-N 5-methoxy-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1=C(OC)N=C2N(C(CC)CC)C(O)=NC2=N1 JCLOPOHRCQTTGK-UHFFFAOYSA-N 0.000 description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010003598 Atelectasis Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 2
- FCCNIDZTZOALQQ-UHFFFAOYSA-N CCC(CC)C1=CC=COC1N(C1=NC(OC)=CN=C1N1)C1=O Chemical compound CCC(CC)C1=CC=COC1N(C1=NC(OC)=CN=C1N1)C1=O FCCNIDZTZOALQQ-UHFFFAOYSA-N 0.000 description 2
- HSQWUKOANDMHBB-UHFFFAOYSA-N CCC(CN1CCOCC1)N(C1=NC=CN=C1N1Br)C1=O Chemical compound CCC(CN1CCOCC1)N(C1=NC=CN=C1N1Br)C1=O HSQWUKOANDMHBB-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 102000004420 Creatine Kinase Human genes 0.000 description 2
- 108010042126 Creatine kinase Proteins 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000012839 Krebs-Henseleit buffer Substances 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000010428 Muscle Weakness Diseases 0.000 description 2
- 206010028372 Muscular weakness Diseases 0.000 description 2
- 108030001204 Myosin ATPases Proteins 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010036105 Polyneuropathy Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000007123 Pulmonary Atelectasis Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000004773 chlorofluoromethyl group Chemical group [H]C(F)(Cl)* 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 2
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003434 inspiratory effect Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- WIDYWXVZKVHDEZ-VIFPVBQESA-N methyl 2-oxo-3-[(1s)-1-phenylethyl]-1h-imidazo[4,5-b]pyrazine-5-carboxylate Chemical compound C1([C@H](C)N2C(O)=NC3=NC=C(N=C32)C(=O)OC)=CC=CC=C1 WIDYWXVZKVHDEZ-VIFPVBQESA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000004220 muscle function Effects 0.000 description 2
- 210000003365 myofibril Anatomy 0.000 description 2
- TUNARGMXIPKYIE-UHFFFAOYSA-N n-[[3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl]methyl]pyrimidin-2-amine Chemical compound C1C(F)CC1(C=1C(=CC=CN=1)F)CNC1=NC=CC=N1 TUNARGMXIPKYIE-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 2
- 229960001844 tubocurarine Drugs 0.000 description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
- SWEICGMKXPNXNU-UHFFFAOYSA-N 1,2-dihydroindazol-3-one Chemical compound C1=CC=C2C(O)=NNC2=C1 SWEICGMKXPNXNU-UHFFFAOYSA-N 0.000 description 1
- IUCSHOCKRNTCJS-UHFFFAOYSA-N 1,3-dihydroimidazo[4,5-b]quinoxalin-2-one Chemical compound C1=CC=C2N=C(NC(=O)N3)C3=NC2=C1 IUCSHOCKRNTCJS-UHFFFAOYSA-N 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical compound C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- NLMKTBGFQGKQEV-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hexadecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO NLMKTBGFQGKQEV-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- UPHGKXBLNGRTEU-VIFPVBQESA-N 2-oxo-3-[(1s)-1-phenylethyl]-1h-imidazo[4,5-b]pyrazine-5-carbonitrile Chemical compound C1([C@H](C)N2C3=NC(=CN=C3N=C2O)C#N)=CC=CC=C1 UPHGKXBLNGRTEU-VIFPVBQESA-N 0.000 description 1
- BWMYZRWUZRHUKK-UHFFFAOYSA-N 2-oxo-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazine-5-carbonitrile Chemical compound C1=C(C#N)N=C2N(C(CC)CC)C(O)=NC2=N1 BWMYZRWUZRHUKK-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
- VENKVVKODLVIJV-QBODLPLBSA-N 3-[(1S)-1-phenylethyl]-5-[(E)-prop-1-enyl]imidazo[4,5-b]pyrazine Chemical compound C1(=CC=CC=C1)[C@H](C)N1C=NC=2C1=NC(=CN=2)\C=C\C VENKVVKODLVIJV-QBODLPLBSA-N 0.000 description 1
- SYUYQEHWWBTQJK-KTROKBFUSA-N 3-[(1s)-1-phenylethyl]-5-[(e)-prop-1-enyl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1([C@H](C)N2C(=O)NC3=NC=C(N=C32)/C=C/C)=CC=CC=C1 SYUYQEHWWBTQJK-KTROKBFUSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FMCGTDCYKPWFQL-UHFFFAOYSA-N 3-benzyl-5-bromo-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(Br)=CN=C2NC(=O)N1CC1=CC=CC=C1 FMCGTDCYKPWFQL-UHFFFAOYSA-N 0.000 description 1
- GZESQDDXLPQCPD-UHFFFAOYSA-N 3-benzyl-5-methylsulfanyl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(SC)=CN=C2NC(=O)N1CC1=CC=CC=C1 GZESQDDXLPQCPD-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- PKCQATLNBUPDJX-UHFFFAOYSA-N 3-cyclohexyl-1H-imidazo[4,5-b]pyrazin-2-one Chemical compound O=C1NC2=NC=CN=C2N1C1CCCCC1 PKCQATLNBUPDJX-UHFFFAOYSA-N 0.000 description 1
- QTFTVOGPJMOQQQ-UHFFFAOYSA-N 3-cyclohexyl-5-methylsulfanyl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(SC)=CN=C2N=C(O)N1C1CCCCC1 QTFTVOGPJMOQQQ-UHFFFAOYSA-N 0.000 description 1
- WJOZHHCMYYPKPL-UHFFFAOYSA-N 3-cyclopropyl-5-methylsulfanyl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(SC)=CN=C2NC(=O)N1C1CC1 WJOZHHCMYYPKPL-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- WSZAYYDHFCRVMT-UHFFFAOYSA-N 3-pentan-3-yl-5-(2h-triazol-4-yl)-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C=1N=C2NC(=O)N(C(CC)CC)C2=NC=1C1=CNN=N1 WSZAYYDHFCRVMT-UHFFFAOYSA-N 0.000 description 1
- WYRAXYZTIXGPNA-DAXSKMNVSA-N 3-pentan-3-yl-5-[(z)-prop-1-enyl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C\C=C/C1=CN=C2NC(=O)N(C(CC)CC)C2=N1 WYRAXYZTIXGPNA-DAXSKMNVSA-N 0.000 description 1
- SUIHQCXQVKNRFQ-UHFFFAOYSA-N 3-propan-2-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1=CN=C2NC(=O)N(C(C)C)C2=N1 SUIHQCXQVKNRFQ-UHFFFAOYSA-N 0.000 description 1
- RFAQGXMCMCWSOX-UHFFFAOYSA-N 3H-imidazo[4,5-b]pyrazine-5-carboxylic acid Chemical compound N=1C=NC=2C=1NC(=CN=2)C(=O)O RFAQGXMCMCWSOX-UHFFFAOYSA-N 0.000 description 1
- FPGGLMIYNLQOID-UHFFFAOYSA-N 3h-pyridin-2-one Chemical compound O=C1CC=CC=N1 FPGGLMIYNLQOID-UHFFFAOYSA-N 0.000 description 1
- HETSDWRDICBRSQ-UHFFFAOYSA-N 3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC=NC2=C1 HETSDWRDICBRSQ-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- POILWHVDKZOXJZ-UHFFFAOYSA-N 4-hydroxypent-3-en-2-one Chemical compound CC(O)=CC(C)=O POILWHVDKZOXJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- VRUDHVVJIWFTGM-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[3,2-d]pyrimidine Chemical compound N1=CN=C2CCCNC2=C1 VRUDHVVJIWFTGM-UHFFFAOYSA-N 0.000 description 1
- RIUFVPWKDKPVEE-AWEZNQCLSA-N 5-[(4-methylpiperazin-1-yl)methyl]-3-[(1s)-1-phenylethyl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1([C@H](C)N2C(NC3=NC=C(CN4CCN(C)CC4)N=C32)=O)=CC=CC=C1 RIUFVPWKDKPVEE-AWEZNQCLSA-N 0.000 description 1
- AOLADPNSDQMWQF-UHFFFAOYSA-N 5-bromo-3-[1-(4-methylsulfonylpiperazin-1-yl)butan-2-yl]-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C12=NC(Br)=CN=C2NC(=O)N1C(CC)CN1CCN(S(C)(=O)=O)CC1 AOLADPNSDQMWQF-UHFFFAOYSA-N 0.000 description 1
- JMZLLOCPIPPQSP-UHFFFAOYSA-N 5-bromo-3-pentan-3-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound C1=C(Br)N=C2N(C(CC)CC)C(O)=NC2=N1 JMZLLOCPIPPQSP-UHFFFAOYSA-N 0.000 description 1
- SLZSDVSNSQEZED-UHFFFAOYSA-N 5-bromo-3-pentan-3-ylimidazo[4,5-b]pyrazine Chemical compound C1=C(Br)N=C2N(C(CC)CC)C=NC2=N1 SLZSDVSNSQEZED-UHFFFAOYSA-N 0.000 description 1
- RAGKXJIFFMBPQH-UHFFFAOYSA-N 5-bromo-3-propan-2-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound BrC1=CN=C2NC(=O)N(C(C)C)C2=N1 RAGKXJIFFMBPQH-UHFFFAOYSA-N 0.000 description 1
- SCOUYZQKEZNSSB-UHFFFAOYSA-N 5-bromo-3-tert-butyl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound BrC1=CN=C2NC(=O)N(C(C)(C)C)C2=N1 SCOUYZQKEZNSSB-UHFFFAOYSA-N 0.000 description 1
- BARVETZCMYVZCX-UHFFFAOYSA-N 5-ethyl-1-pentan-3-yl-3h-imidazo[4,5-b]pyrazin-2-one Chemical compound CCC1=CN=C2N(C(CC)CC)C(O)=NC2=N1 BARVETZCMYVZCX-UHFFFAOYSA-N 0.000 description 1
- LCOBPZJLXFSZMI-UHFFFAOYSA-N 5-ethynyl-3-pentan-3-ylimidazo[4,5-b]pyrazine Chemical compound C(#C)C1=CN=C2C(=N1)N(C=N2)C(CC)CC LCOBPZJLXFSZMI-UHFFFAOYSA-N 0.000 description 1
- OWUGKZDHFBKQTR-UHFFFAOYSA-N 5-methylsulfanyl-3-propan-2-yl-1h-imidazo[4,5-b]pyrazin-2-one Chemical compound CSC1=CN=C2N=C(O)N(C(C)C)C2=N1 OWUGKZDHFBKQTR-UHFFFAOYSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- LMAYDNVIKBCSLP-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NCCC2=N1 LMAYDNVIKBCSLP-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- VQFBSVLQPCTMEU-UHFFFAOYSA-N 6-pentan-3-yl-5-(trifluoromethyl)-1,3-dihydroimidazo[4,5-b]pyrazin-2-one Chemical compound CCC(CC)c1nc2[nH]c(=O)[nH]c2nc1C(F)(F)F VQFBSVLQPCTMEU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010003101 Arnold-Chiari Malformation Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- HJCVKUCIQIYIPB-UHFFFAOYSA-N BrC1=CN=C2C(=N1)N(C(N2)=O)C(CNC)CC.N2C(=NC=1C2=NC=CN1)O Chemical compound BrC1=CN=C2C(=N1)N(C(N2)=O)C(CNC)CC.N2C(=NC=1C2=NC=CN1)O HJCVKUCIQIYIPB-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- MHTSMTLREOMUMU-JTQLQIEISA-N C1(=CC=CC=C1)[C@H](C)N1C=NC=2C1=NC=CN2 Chemical compound C1(=CC=CC=C1)[C@H](C)N1C=NC=2C1=NC=CN2 MHTSMTLREOMUMU-JTQLQIEISA-N 0.000 description 1
- SFDROONMRQVZOL-UHFFFAOYSA-N C12=NC(C(=O)N3CCCCC3)=CN=C2NC(=O)N1C(C)C1=CC=CC=C1 Chemical compound C12=NC(C(=O)N3CCCCC3)=CN=C2NC(=O)N1C(C)C1=CC=CC=C1 SFDROONMRQVZOL-UHFFFAOYSA-N 0.000 description 1
- IOZZOWONXXHLLO-UHFFFAOYSA-N C1C(CC1(CNNC(=O)C2=NC=CC=N2)C3=C(C=CC=N3)F)F Chemical compound C1C(CC1(CNNC(=O)C2=NC=CC=N2)C3=C(C=CC=N3)F)F IOZZOWONXXHLLO-UHFFFAOYSA-N 0.000 description 1
- CDTLHOJDFCUEDF-UHFFFAOYSA-N C1NC2=C(S1)C(=O)N=C2 Chemical compound C1NC2=C(S1)C(=O)N=C2 CDTLHOJDFCUEDF-UHFFFAOYSA-N 0.000 description 1
- NGBASDFCSCRANQ-FZNKQFQNSA-N CC(C1=CC=CC=C1)N1C(O)=NC2=NC=C([C@H](CN(C)CC3)N3C(C(N=C3N4[C@@H](C)C5=CC=CC=C5)=CN=C3N=C4O)=O)N=C12 Chemical compound CC(C1=CC=CC=C1)N1C(O)=NC2=NC=C([C@H](CN(C)CC3)N3C(C(N=C3N4[C@@H](C)C5=CC=CC=C5)=CN=C3N=C4O)=O)N=C12 NGBASDFCSCRANQ-FZNKQFQNSA-N 0.000 description 1
- FIEJZSODHRKKFV-UHFFFAOYSA-N CC(CN1CCOCC1)N(C1=NC=CN=C1N1Br)C1=O Chemical compound CC(CN1CCOCC1)N(C1=NC=CN=C1N1Br)C1=O FIEJZSODHRKKFV-UHFFFAOYSA-N 0.000 description 1
- DJAZWDFMUNVKNV-UHFFFAOYSA-N CCC(C)C1=C(N=C2C(=N1)NC(=O)N2)C(C)C Chemical compound CCC(C)C1=C(N=C2C(=N1)NC(=O)N2)C(C)C DJAZWDFMUNVKNV-UHFFFAOYSA-N 0.000 description 1
- DGUBCIOLEVFNJQ-UHFFFAOYSA-N CCC(CC)C1=CC=COC1N(C1=NC(C2CC2)=CN=C1N1)C1=O Chemical compound CCC(CC)C1=CC=COC1N(C1=NC(C2CC2)=CN=C1N1)C1=O DGUBCIOLEVFNJQ-UHFFFAOYSA-N 0.000 description 1
- MDRJNJWFAVAYMS-UHFFFAOYSA-N CCC(CC)N1CN(C2=NC=CN=C21)N3C4=NC=C(N=C4NC3=O)C(=O)NC Chemical compound CCC(CC)N1CN(C2=NC=CN=C21)N3C4=NC=C(N=C4NC3=O)C(=O)NC MDRJNJWFAVAYMS-UHFFFAOYSA-N 0.000 description 1
- IIZBEWZVXMAJBM-VYRBHSGPSA-N CC[C@@H](CN1CCOCC1)C(N=C(C(N1C(CC)CN2CCOCC2)=N2)N=C1O)=C2Br Chemical compound CC[C@@H](CN1CCOCC1)C(N=C(C(N1C(CC)CN2CCOCC2)=N2)N=C1O)=C2Br IIZBEWZVXMAJBM-VYRBHSGPSA-N 0.000 description 1
- NBRUITUGFZAHJK-ZDUSSCGKSA-N C[C@@H](C1=CC=CC=C1)N2C3=C(NC(=O)C(=N3)C(=O)NCC4=CC=CC=C4)NC2=O Chemical compound C[C@@H](C1=CC=CC=C1)N2C3=C(NC(=O)C(=N3)C(=O)NCC4=CC=CC=C4)NC2=O NBRUITUGFZAHJK-ZDUSSCGKSA-N 0.000 description 1
- CETOVFGELVYILH-LBPRGKRZSA-N C[C@@H](C1=CC=CC=C1)N2C=NC3=NC4=CC=CC=C4N=C32 Chemical compound C[C@@H](C1=CC=CC=C1)N2C=NC3=NC4=CC=CC=C4N=C32 CETOVFGELVYILH-LBPRGKRZSA-N 0.000 description 1
- LKOLAMMPARCKRT-LSLKUGRBSA-N C[C@@H](CN1CCOCC1)C(N=C(C(N1C(C)CN2CCOCC2)=N2)N=C1O)=C2Br Chemical compound C[C@@H](CN1CCOCC1)C(N=C(C(N1C(C)CN2CCOCC2)=N2)N=C1O)=C2Br LKOLAMMPARCKRT-LSLKUGRBSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000015321 Chiari malformation Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000693855 Mus musculus Insulin-like growth factor-binding protein complex acid labile subunit Proteins 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- MIECGKLXDWVECI-ILSZIBLNSA-N N,N-diethyl-2-oxo-3-[(1S)-1-phenylethyl]-1H-imidazo[4,5-b]pyrazine-5-carboxamide Chemical compound C(C)N(C(=O)C=1N=C2C(=NC1)NC(N2[C@@H](C)C2=CC=CC=C2)=O)CC.C(C)N(C(=O)C2=CN=C1C(=N2)N(C(=N1)O)[C@@H](C)C1=CC=CC=C1)CC MIECGKLXDWVECI-ILSZIBLNSA-N 0.000 description 1
- RFVUJPUKBYDYJR-UHFFFAOYSA-N N1C(CC=2C1=NC=CC2)=O.N2=CC=CC=C2 Chemical compound N1C(CC=2C1=NC=CC2)=O.N2=CC=CC=C2 RFVUJPUKBYDYJR-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- NVQQFPBCUSSVJA-UHFFFAOYSA-N O1CCC(CC1)N1C(NC=2C1=NC=CN=2)=O Chemical compound O1CCC(CC1)N1C(NC=2C1=NC=CN=2)=O NVQQFPBCUSSVJA-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 208000007964 Organophosphate Poisoning Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 208000027790 Rib fracture Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- AVRWEULSKHQETA-UHFFFAOYSA-N Thiophene-2 Chemical compound S1C=2CCCCCC=2C(C(=O)OC)=C1NC(=O)C1=C(F)C(F)=C(F)C(F)=C1F AVRWEULSKHQETA-UHFFFAOYSA-N 0.000 description 1
- 206010068268 Tumour compression Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- CDGFEINVQHEUQV-UHFFFAOYSA-N [1,3]thiazolo[5,4-d]pyrimidine Chemical compound N1=CN=C2SC=NC2=C1 CDGFEINVQHEUQV-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 102000016679 alpha-Glucosidases Human genes 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- DMSMPAJRVJJAGA-UHFFFAOYSA-N benzo[d]isothiazol-3-one Chemical compound C1=CC=C2C(=O)NSC2=C1 DMSMPAJRVJJAGA-UHFFFAOYSA-N 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000030303 breathing problems Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005514 but-1-yn-3-yl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical group 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000007799 cork Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 206010066336 critical illness polyneuropathy Diseases 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 150000001975 deuterium Chemical group 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 125000006003 dichloroethyl group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 201000009338 distal myopathy Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003948 fast twitch a Anatomy 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- MPWOBEOETVOESI-UHFFFAOYSA-N imidazo[4,5-b]pyrazin-2-one Chemical compound N1=CC=NC2=NC(=O)N=C21 MPWOBEOETVOESI-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 210000000876 intercostal muscle Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 208000002741 leukoplakia Diseases 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- ZEDPIMIYEJBDRX-UHFFFAOYSA-N methyl 2-oxo-1-pentan-3-yl-3h-imidazo[4,5-b]pyrazine-5-carboxylate Chemical compound COC(=O)C1=CN=C2N(C(CC)CC)C(O)=NC2=N1 ZEDPIMIYEJBDRX-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000005996 muscular dysfunction Effects 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- WFUAIWYQPBEHLA-JTQLQIEISA-N n,n-dimethyl-2-oxo-3-[(1s)-1-phenylethyl]-1h-imidazo[4,5-b]pyrazine-5-carboxamide Chemical compound C1([C@H](C)N2C3=NC(=CN=C3N=C2O)C(=O)N(C)C)=CC=CC=C1 WFUAIWYQPBEHLA-JTQLQIEISA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 150000003003 phosphines Chemical group 0.000 description 1
- 150000004857 phospholes Chemical group 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 210000003105 phrenic nerve Anatomy 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000009613 pulmonary function test Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
- PLZDHJUUEGCXJH-UHFFFAOYSA-N pyrido[4,3-d]pyrimidine Chemical compound C1=NC=C2C=NC=CC2=N1 PLZDHJUUEGCXJH-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000036387 respiratory rate Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 210000003875 slow muscle fiber Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- UPCXAARSWVHVLY-UHFFFAOYSA-N tris(2-hydroxyethyl)azanium;acetate Chemical compound CC(O)=O.OCCN(CCO)CCO UPCXAARSWVHVLY-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 108010013477 troponin-tropomyosin complex Proteins 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 150000003672 ureas Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
-
- 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
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261619261P | 2012-04-02 | 2012-04-02 | |
| US61/619,261 | 2012-04-02 | ||
| PCT/US2013/034824 WO2013151938A1 (en) | 2012-04-02 | 2013-04-01 | Methods for improving diaphragm function |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20160046693A true KR20160046693A (ko) | 2016-04-29 |
Family
ID=49300969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147027435A Abandoned KR20160046693A (ko) | 2012-04-02 | 2013-04-01 | 횡격막 기능을 향상시키는 방법들 |
Country Status (15)
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| EP2723746A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| US10272082B2 (en) | 2011-07-13 | 2019-04-30 | Cytokinetics, Inc. | Combination ALS therapy |
| SG10201704166RA (en) * | 2012-04-11 | 2017-06-29 | Cytokinetics Inc | Improving resistance to skeletal muscle fatigue |
| EP4534538A3 (en) | 2012-12-07 | 2025-06-11 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| AU2014229313B2 (en) | 2013-03-14 | 2016-07-28 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH |
| WO2014143240A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Fused pyrazolopyrimidine derivatives useful as inhibitors of atr kinase |
| US8969360B2 (en) | 2013-03-15 | 2015-03-03 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2014143241A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| CA2932757C (en) | 2013-12-06 | 2023-10-31 | Vertex Pharmaceuticals Incorporated | 2-amino-6-fluoro-n-[5-fluoro-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamide compound useful as atr kinase inhibitor, its preparation, different solid forms and radiolabelled derivatives thereof |
| RS63018B1 (sr) | 2014-04-29 | 2022-04-29 | Cytokinetics Inc | Metode za smanjenje opadanja vitalnog kapaciteta |
| RU2719583C2 (ru) | 2014-06-05 | 2020-04-21 | Вертекс Фармасьютикалз Инкорпорейтед | Радиоактивно меченные производные 2-амино-6-фтор-n-[5-фтор-пиридин-3-ил]-пиразоло[1, 5-а]пиримидин-3-карбоксамида, используемые в качестве ингибитора atr киназы, препараты на основе этого соединения и его различные твердые формы |
| SG11201610500WA (en) | 2014-06-17 | 2017-01-27 | Vertex Pharma | Method for treating cancer using a combination of chk1 and atr inhibitors |
| US9987279B2 (en) * | 2014-09-09 | 2018-06-05 | Astellas Pharma Inc. | Pharmaceutical composition for prevention and/or treatment of urinary incontinence |
| JP2018516254A (ja) | 2015-05-29 | 2018-06-21 | ファイザー・インク | バニン１酵素の阻害薬としての新規なヘテロ環化合物 |
| KR102678021B1 (ko) | 2015-09-30 | 2024-06-26 | 버텍스 파마슈티칼스 인코포레이티드 | Dna 손상제와 병용되는, atr 저해제를 포함하는 암 치료용 약제학적 조성물 |
| CN113666938A (zh) | 2016-02-12 | 2021-11-19 | 细胞动力学股份有限公司 | 四氢异喹啉衍生物 |
| EP3484876A1 (en) | 2016-07-14 | 2019-05-22 | Pfizer Inc | Novel pyrimidine carboxamides as inhibitors of vanin-1 enzyme |
| WO2020254343A1 (en) * | 2019-06-19 | 2020-12-24 | F. Hoffmann-La Roche Ag | Digital biomarker |
| CN114007495A (zh) | 2019-06-19 | 2022-02-01 | 豪夫迈·罗氏有限公司 | 数字生物标志物 |
| BR112022000325A2 (pt) | 2019-07-11 | 2022-03-15 | Escape Bio Inc | Indazois e azaindazois como inibidores de lrrk2 |
| US11981644B2 (en) | 2020-11-06 | 2024-05-14 | Cytokinetics, Inc. | Bicyclic 1,4-diazepanones and therapeutic uses thereof |
| WO2023107705A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
| US20240382564A1 (en) * | 2023-04-17 | 2024-11-21 | Allysta Pharmaceuticals, Inc. | Methods and Compositions for Treating Muscular Dystrophy and Memory Impairment |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070173465A9 (en) * | 1995-10-11 | 2007-07-26 | Monahan Sean D | Expression of zeta negative and zeta positive nucleic acids using a dystrophin gene |
| AU2001268149B2 (en) * | 2000-06-01 | 2005-08-18 | University Of North Carolina At Chapel Hill | Methods and compounds for controlled release of recombinant parvovirus vectors |
| CN1283793C (zh) * | 2002-06-03 | 2006-11-08 | 北京大学 | 具有骨骼肌刺激活性和免疫调节作用的趋化素样因子超家族 |
| EP1651638A1 (en) * | 2003-08-08 | 2006-05-03 | Janssen Pharmaceutica N.V. | Pyridyl piperazinyl ureas |
| US8227603B2 (en) * | 2006-08-01 | 2012-07-24 | Cytokinetics, Inc. | Modulating skeletal muscle |
| DK2069352T5 (en) * | 2006-08-02 | 2017-04-03 | Cytokinetics Inc | SPECIFIC CHEMICAL UNITS, COMPOSITIONS AND PROCEDURES |
| US8299248B2 (en) * | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| WO2009023193A1 (en) * | 2007-08-15 | 2009-02-19 | Cytokinetics, Incorporated | Certain chemical entities, compositions, and methods |
| NL2001694C2 (en) * | 2008-06-18 | 2009-12-22 | Nasophlex B V | Ear stimulator for producing a stimulation signal to an ear. |
| AR081331A1 (es) * | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AR081626A1 (es) * | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
-
2013
- 2013-04-01 SG SG11201406270YA patent/SG11201406270YA/en unknown
- 2013-04-01 BR BR112014024552A patent/BR112014024552A2/pt not_active Application Discontinuation
- 2013-04-01 EP EP13773086.7A patent/EP2834269A4/en not_active Withdrawn
- 2013-04-01 EA EA201491605A patent/EA031183B1/ru not_active IP Right Cessation
- 2013-04-01 KR KR1020147027435A patent/KR20160046693A/ko not_active Abandoned
- 2013-04-01 CN CN201810509450.1A patent/CN108553467A/zh active Pending
- 2013-04-01 US US14/389,805 patent/US20150065525A1/en not_active Abandoned
- 2013-04-01 CA CA2868507A patent/CA2868507A1/en not_active Abandoned
- 2013-04-01 MX MX2014011881A patent/MX354965B/es active IP Right Grant
- 2013-04-01 AU AU2013243671A patent/AU2013243671B2/en not_active Ceased
- 2013-04-01 WO PCT/US2013/034824 patent/WO2013151938A1/en not_active Ceased
- 2013-04-01 SG SG10201701101YA patent/SG10201701101YA/en unknown
- 2013-04-01 JP JP2015503681A patent/JP6345645B2/ja not_active Expired - Fee Related
- 2013-04-01 HK HK15106936.7A patent/HK1206364A1/xx unknown
- 2013-04-01 CN CN201380018757.7A patent/CN104379597A/zh active Pending
-
2014
- 2014-09-29 IL IL234885A patent/IL234885A0/en unknown
- 2014-10-01 PH PH12014502217A patent/PH12014502217A1/en unknown
-
2017
- 2017-02-27 US US15/444,063 patent/US20170266192A1/en not_active Abandoned
- 2017-12-07 AU AU2017272286A patent/AU2017272286B2/en not_active Ceased
-
2018
- 2018-05-23 JP JP2018098858A patent/JP2018131460A/ja not_active Ceased
-
2019
- 2019-07-05 IL IL267876A patent/IL267876B/en active IP Right Grant
-
2020
- 2020-06-17 JP JP2020104620A patent/JP2020147607A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| MX354965B (es) | 2018-03-27 |
| HK1206364A1 (en) | 2016-01-08 |
| BR112014024552A2 (pt) | 2017-09-19 |
| AU2013243671B2 (en) | 2017-09-21 |
| JP2015516957A (ja) | 2015-06-18 |
| US20170266192A1 (en) | 2017-09-21 |
| AU2013243671A1 (en) | 2014-10-16 |
| JP2018131460A (ja) | 2018-08-23 |
| JP6345645B2 (ja) | 2018-06-20 |
| IL267876B (en) | 2021-03-25 |
| MX2014011881A (es) | 2016-07-20 |
| SG11201406270YA (en) | 2014-10-30 |
| US20150065525A1 (en) | 2015-03-05 |
| AU2017272286A1 (en) | 2018-01-04 |
| EP2834269A1 (en) | 2015-02-11 |
| PH12014502217A1 (en) | 2015-01-12 |
| JP2020147607A (ja) | 2020-09-17 |
| SG10201701101YA (en) | 2017-04-27 |
| CN108553467A (zh) | 2018-09-21 |
| EP2834269A4 (en) | 2015-12-30 |
| EA031183B1 (ru) | 2018-11-30 |
| CN104379597A (zh) | 2015-02-25 |
| AU2017272286B2 (en) | 2019-05-09 |
| EA201491605A1 (ru) | 2015-03-31 |
| WO2013151938A1 (en) | 2013-10-10 |
| IL267876A (en) | 2019-09-26 |
| IL234885A0 (en) | 2014-12-31 |
| CA2868507A1 (en) | 2013-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20160046693A (ko) | 횡격막 기능을 향상시키는 방법들 | |
| CN105859712B (zh) | 作为nadph氧化酶抑制剂的吡唑并吡啶衍生物 | |
| RU2548022C2 (ru) | Пиразолопиридиновые производные как ингибиторы надфн-оксидазы | |
| JP2022523274A (ja) | Ｊａｋ阻害剤化合物及びその使用 | |
| KR20160046756A (ko) | 브루톤 티로신 키나제 억제제 | |
| CA2971024A1 (en) | Fused ring heteroaryl compounds and their use as trk inhibitors | |
| EP3724194B1 (en) | Substituted azetidine dihydrothienopyrimidines and their use as phosphodiesterase inhibitors | |
| CN119173512A (zh) | 泛素特异性蛋白酶1 (usp1)的小分子抑制剂和其用途 | |
| JP2020512298A (ja) | ポリ−ａｄｐリボースポリメラーゼ（ｐａｒｐ）阻害剤 | |
| EA018803B1 (ru) | Производные триазоло[4,5-d]пирамидина и их применение в качестве антагонистов пуринового рецептора | |
| BR112020005934A2 (pt) | inibidor de pde9 e uso do mesmo | |
| JP5628902B2 (ja) | フェノキシメチル複素環化合物 | |
| KR20160046694A (ko) | 골격근 피로에 대한 저항을 개선 | |
| JP2013520407A (ja) | Ｎａｄｐｈオキシダーゼ阻害剤としてのピラゾロピペリジン誘導体 | |
| JP4616839B2 (ja) | ヒドロキシアルキル置換ピリド−７−ピリミジン−７−オン類 | |
| BR112019025813A2 (pt) | inibidores de pirazolopirimidina pde9 | |
| WO2023086799A1 (en) | Heterocyclic compounds as triggering receptor expressed on myeloid cells 2 agonists | |
| WO2024233848A1 (en) | Heterocyclic compounds as triggering receptor expressed on myeloid cells 2 agonists and methods of use | |
| RU2765868C2 (ru) | Лечение неврологических расстройств | |
| WO2016196417A1 (en) | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors | |
| JP2021535924A (ja) | 新規なチアゾール誘導体及びその薬学的に許容される塩 | |
| KR20130103617A (ko) | 이중 활성 H1 역 효능제/5-HT2A 길항제로서의 치환된 [(5H-피롤로[2,1-c][1,4]벤조디아제핀-11-일)피페라진-1-일]-2,2-디메틸프로판산 화합물 | |
| CN118339149A (zh) | 用于治疗与lpa受体活性相关的病症的化合物和组合物 | |
| HK1261324A1 (en) | Methods for improving diaphragm function | |
| JP7775288B2 (ja) | ピリミジノン化合物およびその使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20140929 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| N231 | Notification of change of applicant | ||
| PN2301 | Change of applicant |
Patent event date: 20160330 Comment text: Notification of Change of Applicant Patent event code: PN23011R01D |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20180328 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: 20190521 Patent event code: PE09021S01D |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20191121 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: 20200728 |
|
| PC1904 | Unpaid initial registration fee |