TW202309038A - sGC刺激劑 - Google Patents
sGC刺激劑 Download PDFInfo
- Publication number
- TW202309038A TW202309038A TW111114883A TW111114883A TW202309038A TW 202309038 A TW202309038 A TW 202309038A TW 111114883 A TW111114883 A TW 111114883A TW 111114883 A TW111114883 A TW 111114883A TW 202309038 A TW202309038 A TW 202309038A
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- disease
- substituted
- Prior art date
Links
- 229940127296 soluble guanylate cyclase stimulator Drugs 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 286
- 150000003839 salts Chemical class 0.000 claims abstract description 133
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 67
- 201000010099 disease Diseases 0.000 claims abstract description 60
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims description 65
- 125000001153 fluoro group Chemical group F* 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 229910052731 fluorine Inorganic materials 0.000 claims description 32
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 31
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 26
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 230000008901 benefit Effects 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000002648 combination therapy Methods 0.000 claims description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- 230000000638 stimulation Effects 0.000 claims description 7
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 57
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 abstract description 28
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 abstract description 28
- 230000037361 pathway Effects 0.000 abstract description 6
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- -1 2 H) Chemical compound 0.000 description 56
- 239000000203 mixture Substances 0.000 description 55
- 239000007787 solid Substances 0.000 description 43
- 239000000243 solution Substances 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 28
- ZMCQQCBOZIGNRV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(1,2,4-triazol-1-yl)ethyl]benzamide Chemical compound NCC1=CC(OC2=CC=CC(=C2)C(=O)NCCN2C=NC=N2)=NC(=C1)C(F)(F)F ZMCQQCBOZIGNRV-UHFFFAOYSA-N 0.000 description 26
- 241000700159 Rattus Species 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000011282 treatment Methods 0.000 description 23
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 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 18
- 241001465754 Metazoa Species 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 206010008635 Cholestasis Diseases 0.000 description 15
- 230000035484 reaction time Effects 0.000 description 15
- 239000003981 vehicle Substances 0.000 description 15
- 206010012289 Dementia Diseases 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 208000011580 syndromic disease Diseases 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 239000003995 emulsifying agent Substances 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- 238000004007 reversed phase HPLC Methods 0.000 description 12
- 159000000000 sodium salts Chemical class 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
- 206010016654 Fibrosis Diseases 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 206010007559 Cardiac failure congestive Diseases 0.000 description 10
- 206010019280 Heart failures Diseases 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 208000002193 Pain Diseases 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 239000012981 Hank's balanced salt solution Substances 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 9
- 239000000556 agonist Substances 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 208000010877 cognitive disease Diseases 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- 208000017169 kidney disease Diseases 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 9
- 210000003205 muscle Anatomy 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 208000024827 Alzheimer disease Diseases 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 230000004761 fibrosis Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 231100000252 nontoxic Toxicity 0.000 description 8
- 230000003000 nontoxic effect Effects 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 230000036407 pain Effects 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000036772 blood pressure Effects 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 208000019423 liver disease Diseases 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 208000033808 peripheral neuropathy Diseases 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 208000007056 sickle cell anemia Diseases 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 208000028698 Cognitive impairment Diseases 0.000 description 6
- 201000003883 Cystic fibrosis Diseases 0.000 description 6
- 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 6
- 208000005615 Interstitial Cystitis Diseases 0.000 description 6
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 208000019425 cirrhosis of liver Diseases 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 208000016354 hearing loss disease Diseases 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229960003105 metformin Drugs 0.000 description 6
- 201000001119 neuropathy Diseases 0.000 description 6
- 230000007823 neuropathy Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000002685 pulmonary effect Effects 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 229940083542 sodium Drugs 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 239000002083 C09CA01 - Losartan Substances 0.000 description 5
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 5
- 206010011878 Deafness Diseases 0.000 description 5
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 239000002270 dispersing agent Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 229960003711 glyceryl trinitrate Drugs 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229960002198 irbesartan Drugs 0.000 description 5
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 5
- 239000007937 lozenge Substances 0.000 description 5
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 150000004031 phenylhydrazines Chemical class 0.000 description 5
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 5
- 239000012363 selectfluor Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 239000003765 sweetening agent Substances 0.000 description 5
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 4
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- YJBONAUXKNXNTQ-UHFFFAOYSA-N 2-(4,4,4-trifluorobutyl)guanidine Chemical compound NC(=N)NCCCC(F)(F)F YJBONAUXKNXNTQ-UHFFFAOYSA-N 0.000 description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 4
- 208000012661 Dyskinesia Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 208000019693 Lung disease Diseases 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 239000012901 Milli-Q water Substances 0.000 description 4
- 208000010718 Multiple Organ Failure Diseases 0.000 description 4
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 4
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- ZIIQCSMRQKCOCT-YFKPBYRVSA-N S-nitroso-N-acetyl-D-penicillamine Chemical compound CC(=O)N[C@@H](C(O)=O)C(C)(C)SN=O ZIIQCSMRQKCOCT-YFKPBYRVSA-N 0.000 description 4
- 208000034189 Sclerosis Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 201000004810 Vascular dementia Diseases 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 4
- 229960001770 atorvastatin calcium Drugs 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 238000011260 co-administration Methods 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 231100000895 deafness Toxicity 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 229960003345 empagliflozin Drugs 0.000 description 4
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 229940014259 gelatin Drugs 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 150000003278 haem Chemical class 0.000 description 4
- 230000000004 hemodynamic effect Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 4
- 208000004296 neuralgia Diseases 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 229960003975 potassium Drugs 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- WXXSNCNJFUAIDG-UHFFFAOYSA-N riociguat Chemical compound N1=C(N)C(N(C)C(=O)OC)=C(N)N=C1C(C1=CC=CN=C11)=NN1CC1=CC=CC=C1F WXXSNCNJFUAIDG-UHFFFAOYSA-N 0.000 description 4
- 229960004034 sitagliptin Drugs 0.000 description 4
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 238000000527 sonication Methods 0.000 description 4
- 229960002256 spironolactone Drugs 0.000 description 4
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- 206010065040 AIDS dementia complex Diseases 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 3
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 3
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 3
- 206010007556 Cardiac failure acute Diseases 0.000 description 3
- KJEBULYHNRNJTE-DHZHZOJOSA-N Cinalong Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 KJEBULYHNRNJTE-DHZHZOJOSA-N 0.000 description 3
- 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 3
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 3
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 3
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 3
- 206010013935 Dysmenorrhoea Diseases 0.000 description 3
- 208000005189 Embolism Diseases 0.000 description 3
- 206010014561 Emphysema Diseases 0.000 description 3
- 102000003951 Erythropoietin Human genes 0.000 description 3
- 108090000394 Erythropoietin Proteins 0.000 description 3
- 208000000289 Esophageal Achalasia Diseases 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 description 3
- 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 3
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- FYZPCMFQCNBYCY-WIWKJPBBSA-N Insulin degludec Chemical compound CC[C@H](C)[C@H](NC(=O)CN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc3c[nH]cn3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc3ccccc3)C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC(O)=O)C(O)=O)C(O)=O)NC1=O)[C@@H](C)O)[C@@H](C)CC FYZPCMFQCNBYCY-WIWKJPBBSA-N 0.000 description 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 3
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- 239000000006 Nitroglycerin Substances 0.000 description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- 206010030136 Oesophageal achalasia Diseases 0.000 description 3
- 239000005480 Olmesartan Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 208000001435 Thromboembolism Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 201000000621 achalasia Diseases 0.000 description 3
- 229940083712 aldosterone antagonist Drugs 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 229960004005 amlodipine besylate Drugs 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000009697 arginine Nutrition 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 3
- 229950010993 atrasentan Drugs 0.000 description 3
- 230000001746 atrial effect Effects 0.000 description 3
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 3
- 230000002567 autonomic effect Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 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 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 235000019437 butane-1,3-diol Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 229960003020 cilnidipine Drugs 0.000 description 3
- 230000007882 cirrhosis Effects 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
- 229940126543 compound 14 Drugs 0.000 description 3
- 239000007859 condensation product Substances 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960003834 dapagliflozin Drugs 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 230000001804 emulsifying effect Effects 0.000 description 3
- 229960001208 eplerenone Drugs 0.000 description 3
- JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 description 3
- 229940105423 erythropoietin Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 3
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229960004346 glimepiride Drugs 0.000 description 3
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 3
- 229960002003 hydrochlorothiazide Drugs 0.000 description 3
- 229960001330 hydroxycarbamide Drugs 0.000 description 3
- 201000001881 impotence Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 108010050259 insulin degludec Proteins 0.000 description 3
- 229960004225 insulin degludec Drugs 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 229960004502 levodopa Drugs 0.000 description 3
- 229960002397 linagliptin Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 229960004773 losartan Drugs 0.000 description 3
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 229960004329 metformin hydrochloride Drugs 0.000 description 3
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 230000000414 obstructive effect Effects 0.000 description 3
- 229960005117 olmesartan Drugs 0.000 description 3
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 208000028173 post-traumatic stress disease Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 description 3
- 208000002815 pulmonary hypertension Diseases 0.000 description 3
- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229940044601 receptor agonist Drugs 0.000 description 3
- 239000000018 receptor agonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 201000002793 renal fibrosis Diseases 0.000 description 3
- 229960000529 riociguat Drugs 0.000 description 3
- 229960003953 sacubitril Drugs 0.000 description 3
- PYNXFZCZUAOOQC-UTKZUKDTSA-N sacubitril Chemical compound C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC(O)=O)=CC=C1C1=CC=CC=C1 PYNXFZCZUAOOQC-UTKZUKDTSA-N 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 201000000306 sarcoidosis Diseases 0.000 description 3
- 229960004937 saxagliptin Drugs 0.000 description 3
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 3
- 108010033693 saxagliptin Proteins 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 229940083618 sodium nitroprusside Drugs 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 229960000195 terbutaline Drugs 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 229960004699 valsartan Drugs 0.000 description 3
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 2
- YWQFJNWMWZMXRW-HXUWFJFHSA-N (2r)-3,3,3-trifluoro-2-[[[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]amino]methyl]-2-hydroxypropanamide Chemical compound C1=C(F)C(NC[C@@](O)(C(=O)N)C(F)(F)F)=NC(C2=NN(CC=3C(=CC=CC=3)F)C(C3=NOC=C3)=C2)=N1 YWQFJNWMWZMXRW-HXUWFJFHSA-N 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- YDSGGZZKDUDBMD-UHFFFAOYSA-N 2-[(2-chloro-3,4-dimethoxyphenyl)methylideneamino]-1-hydroxyguanidine Chemical compound COC1=CC=C(C=NNC(=N)NO)C(Cl)=C1OC YDSGGZZKDUDBMD-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- FWCVZAQENIZVMY-UHFFFAOYSA-N 2-hydroxy-6-[[2-(2-propan-2-ylpyrazol-3-yl)pyridin-3-yl]methoxy]benzaldehyde Chemical compound CC(C)N1N=CC=C1C1=NC=CC=C1COC1=CC=CC(O)=C1C=O FWCVZAQENIZVMY-UHFFFAOYSA-N 0.000 description 2
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- PQHLRGARXNPFCF-UHFFFAOYSA-N 5-chloro-2-[(5-chlorothiophen-2-yl)sulfonylamino]-n-(4-morpholin-4-ylsulfonylphenyl)benzamide Chemical compound S1C(Cl)=CC=C1S(=O)(=O)NC1=CC=C(Cl)C=C1C(=O)NC1=CC=C(S(=O)(=O)N2CCOCC2)C=C1 PQHLRGARXNPFCF-UHFFFAOYSA-N 0.000 description 2
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 2
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 description 2
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 2
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 2
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
- 239000005485 Azilsartan Substances 0.000 description 2
- 206010005746 Blood pressure fluctuation Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 description 2
- 208000006029 Cardiomegaly Diseases 0.000 description 2
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 2
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 2
- 208000002330 Congenital Heart Defects Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- 206010011796 Cystitis interstitial Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000019505 Deglutition disease Diseases 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 108050004812 Dopamine receptor Proteins 0.000 description 2
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- 208000005171 Dysmenorrhea Diseases 0.000 description 2
- 208000032274 Encephalopathy Diseases 0.000 description 2
- 206010048554 Endothelial dysfunction Diseases 0.000 description 2
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 description 2
- MCIACXAZCBVDEE-CUUWFGFTSA-N Ertugliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@@]23O[C@@](CO)(CO2)[C@@H](O)[C@H](O)[C@H]3O)=CC=C1Cl MCIACXAZCBVDEE-CUUWFGFTSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- 206010015856 Extrasystoles Diseases 0.000 description 2
- 241000282326 Felis catus Species 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
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010020852 Hypertonia Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000024934 IgG4-related mediastinitis Diseases 0.000 description 2
- 108010073961 Insulin Aspart Proteins 0.000 description 2
- 108010057186 Insulin Glargine Proteins 0.000 description 2
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 description 2
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 2
- 108010019598 Liraglutide Proteins 0.000 description 2
- 108010007859 Lisinopril Proteins 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 208000002805 Mediastinal fibrosis Diseases 0.000 description 2
- 206010027525 Microalbuminuria Diseases 0.000 description 2
- 102100033127 Mitogen-activated protein kinase kinase kinase 5 Human genes 0.000 description 2
- 206010027727 Mitral valve incompetence Diseases 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- 208000034486 Multi-organ failure Diseases 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WFBHRSAKANVBKH-UHFFFAOYSA-N N-hydroxyguanidine Chemical compound NC(=N)NO WFBHRSAKANVBKH-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010063985 Phytosterolaemia Diseases 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 201000001068 Prinzmetal angina Diseases 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 102000007327 Protamines Human genes 0.000 description 2
- 108010007568 Protamines Proteins 0.000 description 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 2
- 208000003782 Raynaud disease Diseases 0.000 description 2
- 208000012322 Raynaud phenomenon Diseases 0.000 description 2
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 206010039163 Right ventricular failure Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- HYHSBSXUHZOYLX-WDSKDSINSA-N S-nitrosoglutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CSN=O)C(=O)NCC(O)=O HYHSBSXUHZOYLX-WDSKDSINSA-N 0.000 description 2
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 2
- 208000002227 Sitosterolemia Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 description 2
- 206010042953 Systemic sclerosis Diseases 0.000 description 2
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
- 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 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 208000012634 Venoocclusive liver disease Diseases 0.000 description 2
- 201000008803 Wolff-Parkinson-white syndrome Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- WGZCUXZFISUUPR-UHFFFAOYSA-N acetonitrile;oxolane Chemical compound CC#N.C1CCOC1 WGZCUXZFISUUPR-UHFFFAOYSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 206010000891 acute myocardial infarction Diseases 0.000 description 2
- 208000012998 acute renal failure Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- QYPPJABKJHAVHS-UHFFFAOYSA-N agmatine Chemical compound NCCCCNC(N)=N QYPPJABKJHAVHS-UHFFFAOYSA-N 0.000 description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 2
- 239000002160 alpha blocker Substances 0.000 description 2
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 2
- 229960000711 alprostadil Drugs 0.000 description 2
- 208000008445 altitude sickness Diseases 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000003173 antianemic agent Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 206010002906 aortic stenosis Diseases 0.000 description 2
- 208000008784 apnea Diseases 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 229950007878 ataciguat Drugs 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 2
- 229960002731 azilsartan Drugs 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 229940124748 beta 2 agonist Drugs 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 229960004436 budesonide Drugs 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229960001713 canagliflozin Drugs 0.000 description 2
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229960004349 candesartan cilexetil Drugs 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229960000830 captopril Drugs 0.000 description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 2
- 229960000623 carbamazepine Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 229940081733 cetearyl alcohol Drugs 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 229960002155 chlorothiazide Drugs 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229960002896 clonidine Drugs 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 235000017471 coenzyme Q10 Nutrition 0.000 description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 208000028831 congenital heart disease Diseases 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229940108928 copper Drugs 0.000 description 2
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 208000017004 dementia pugilistica Diseases 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 229960004166 diltiazem Drugs 0.000 description 2
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 2
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
- 229960002768 dipyridamole Drugs 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 229960001389 doxazosin Drugs 0.000 description 2
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 2
- 229960004242 dronabinol Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 239000003221 ear drop Substances 0.000 description 2
- 229940047652 ear drops Drugs 0.000 description 2
- 239000008387 emulsifying waxe Substances 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 229940095399 enema Drugs 0.000 description 2
- 239000002792 enkephalinase inhibitor Substances 0.000 description 2
- 229950006535 ertugliflozin Drugs 0.000 description 2
- 229940125367 erythropoiesis stimulating agent Drugs 0.000 description 2
- 229950009769 etabonate Drugs 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 2
- 229960003883 furosemide Drugs 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 229940107131 ginseng root Drugs 0.000 description 2
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 208000018645 hepatic veno-occlusive disease Diseases 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 235000014304 histidine Nutrition 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 208000018875 hypoxemia Diseases 0.000 description 2
- WDKXLLJDNUBYCY-UHFFFAOYSA-N ibopamine Chemical compound CNCCC1=CC=C(OC(=O)C(C)C)C(OC(=O)C(C)C)=C1 WDKXLLJDNUBYCY-UHFFFAOYSA-N 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 2
- 229960004717 insulin aspart Drugs 0.000 description 2
- 229960002869 insulin glargine Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 229960002479 isosorbide Drugs 0.000 description 2
- 229960004427 isradipine Drugs 0.000 description 2
- 229960002623 lacosamide Drugs 0.000 description 2
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960001848 lamotrigine Drugs 0.000 description 2
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- OTQCKZUSUGYWBD-BRHMIFOHSA-N lepirudin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 OTQCKZUSUGYWBD-BRHMIFOHSA-N 0.000 description 2
- 229960004408 lepirudin Drugs 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229960002701 liraglutide Drugs 0.000 description 2
- 229960002394 lisinopril Drugs 0.000 description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 229960000519 losartan potassium Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 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
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Chemical class 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 229960002900 methylcellulose Drugs 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 208000027061 mild cognitive impairment Diseases 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000002394 mineralocorticoid antagonist Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 238000011201 multiple comparisons test Methods 0.000 description 2
- 201000006938 muscular dystrophy Diseases 0.000 description 2
- 206010028537 myelofibrosis Diseases 0.000 description 2
- AZNHWXAFPBYFGH-UHFFFAOYSA-N n-[4-(4-fluorophenyl)-2,2-dimethyl-3-oxo-1,4-benzoxazin-7-yl]methanesulfonamide Chemical compound O=C1C(C)(C)OC2=CC(NS(C)(=O)=O)=CC=C2N1C1=CC=C(F)C=C1 AZNHWXAFPBYFGH-UHFFFAOYSA-N 0.000 description 2
- 229960000698 nateglinide Drugs 0.000 description 2
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 2
- FTQHGWIXJSSWOY-UHFFFAOYSA-N nelociguat Chemical compound N1=C(N)C(NC(=O)OC)=C(N)N=C1C(C1=CC=CN=C11)=NN1CC1=CC=CC=C1F FTQHGWIXJSSWOY-UHFFFAOYSA-N 0.000 description 2
- 201000009925 nephrosclerosis Diseases 0.000 description 2
- 229960001267 nesiritide Drugs 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 2
- 229960002497 nicorandil Drugs 0.000 description 2
- 229960001597 nifedipine Drugs 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 150000002826 nitrites Chemical class 0.000 description 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 2
- VOMXSOIBEJBQNF-UTTRGDHVSA-N novorapid Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 VOMXSOIBEJBQNF-UTTRGDHVSA-N 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 235000014593 oils and fats Nutrition 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000001599 osteoclastic effect Effects 0.000 description 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 2
- 229940055726 pantothenic acid Drugs 0.000 description 2
- 235000019161 pantothenic acid Nutrition 0.000 description 2
- 239000011713 pantothenic acid Substances 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 208000008494 pericarditis Diseases 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229950004193 perospirone Drugs 0.000 description 2
- GTAIPSDXDDTGBZ-OYRHEFFESA-N perospirone Chemical compound C1=CC=C2C(N3CCN(CC3)CCCCN3C(=O)[C@@H]4CCCC[C@@H]4C3=O)=NSCC2=C1 GTAIPSDXDDTGBZ-OYRHEFFESA-N 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- CYSJNTQNMDWAJV-UHFFFAOYSA-N praliciguat Chemical compound C1=C(F)C(NCC(O)(C(F)(F)F)C(F)(F)F)=NC(C2=NN(CC=3C(=CC=CC=3)F)C(C3=NOC=C3)=C2)=N1 CYSJNTQNMDWAJV-UHFFFAOYSA-N 0.000 description 2
- 229960001289 prazosin Drugs 0.000 description 2
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 2
- 201000011461 pre-eclampsia Diseases 0.000 description 2
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 2
- 229940048914 protamine Drugs 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229960002052 salbutamol Drugs 0.000 description 2
- 229960004017 salmeterol Drugs 0.000 description 2
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 2
- 229960004617 sapropterin Drugs 0.000 description 2
- 201000004409 schistosomiasis Diseases 0.000 description 2
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 2
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 2
- 229960003946 selegiline Drugs 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 230000007958 sleep Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- QWIHVUUEJBINLC-UHFFFAOYSA-M sodium;3-ethoxy-2-fluoro-3-oxoprop-1-en-1-olate Chemical compound [Na+].CCOC(=O)C(F)=C[O-] QWIHVUUEJBINLC-UHFFFAOYSA-M 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 208000002320 spinal muscular atrophy Diseases 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229960005404 sulfamethoxazole Drugs 0.000 description 2
- 229960001940 sulfasalazine Drugs 0.000 description 2
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 2
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229960001967 tacrolimus Drugs 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 2
- 230000009424 thromboembolic effect Effects 0.000 description 2
- 229960001017 tolmetin Drugs 0.000 description 2
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000007492 two-way ANOVA Methods 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- 208000003663 ventricular fibrillation Diseases 0.000 description 2
- QZFHIXARHDBPBY-UHFFFAOYSA-N vericiguat Chemical compound N1=C(N)C(NC(=O)OC)=C(N)N=C1C(C1=CC(F)=CN=C11)=NN1CC1=CC=CC=C1F QZFHIXARHDBPBY-UHFFFAOYSA-N 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 235000016804 zinc Nutrition 0.000 description 2
- 229960002911 zonisamide Drugs 0.000 description 2
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- DLVAZTPQKCTPLB-PXYINDEMSA-N (2R)-2-amino-3-[1-[3-[3-(2-methoxyethoxy)propylamino]-3-oxopropyl]-2,5-dioxopyrrolidin-3-yl]sulfanylpropanoic acid Chemical compound COCCOCCCNC(=O)CCN1C(=O)CC(SC[C@H](N)C(O)=O)C1=O DLVAZTPQKCTPLB-PXYINDEMSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KRVOJOCLBAAKSJ-RDTXWAMCSA-N (2R,3R)-nemonapride Chemical compound C1=C(Cl)C(NC)=CC(OC)=C1C(=O)N[C@H]1[C@@H](C)N(CC=2C=CC=CC=2)CC1 KRVOJOCLBAAKSJ-RDTXWAMCSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 description 1
- ZEYYDOLCHFETHQ-JOCHJYFZSA-N (2r)-2-cyclopentyl-2-[4-(quinolin-2-ylmethoxy)phenyl]acetic acid Chemical compound C1([C@@H](C(=O)O)C=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CCCC1 ZEYYDOLCHFETHQ-JOCHJYFZSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- BFNXYSZBURSNHS-UVJOBNTFSA-N (2s)-1-[(2s)-6-amino-2-[[(1s)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid;6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 BFNXYSZBURSNHS-UVJOBNTFSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- QKDRXGFQVGOQKS-CRSSMBPESA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](SC)O2)O)=CC=C1Cl QKDRXGFQVGOQKS-CRSSMBPESA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- VQKSCYBKUIDZEI-STQMWFEESA-N (2s,4s)-4-fluoro-1-[2-[(2-methyl-4-oxo-4-pyrrolidin-1-ylbutan-2-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](C[C@H](F)C1)C#N)C(=O)CNC(C)(C)CC(=O)N1CCCC1 VQKSCYBKUIDZEI-STQMWFEESA-N 0.000 description 1
- FEOHYDSNGHIXOM-WLDMJGECSA-N (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)-2-methyloxane-2,4,5-triol Chemical compound CC1(O)[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO FEOHYDSNGHIXOM-WLDMJGECSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 1
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 1
- JDKLPDJLXHXHNV-MFVUMRCOSA-N (3s,6s,9r,12s,15s,23s)-15-[[(2s)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1h-imidazol-5-ylmethyl)-3-(1h-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxamide Chemical compound C([C@@H]1C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCNC(=O)C[C@@H](C(N[C@@H](CC=2NC=NC=2)C(=O)N1)=O)NC(=O)[C@@H](NC(C)=O)CCCC)C(N)=O)C1=CC=CC=C1 JDKLPDJLXHXHNV-MFVUMRCOSA-N 0.000 description 1
- BTBHLEZXCOBLCY-QGZVFWFLSA-N (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide Chemical compound C1([C@@H]2C(=C(C)NC=3C(C)=CN=C(C2=3)OCC)C(N)=O)=CC=C(C#N)C=C1OC BTBHLEZXCOBLCY-QGZVFWFLSA-N 0.000 description 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 1
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- RXZBMPWDPOLZGW-XMRMVWPWSA-N (E)-roxithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 description 1
- RVXKUSLFQCZMJA-NTEUORMPSA-N (e)-3-[2-(4-chlorophenyl)sulfanylphenyl]-n-[4-(dimethylamino)butyl]prop-2-enamide Chemical compound CN(C)CCCCNC(=O)\C=C\C1=CC=CC=C1SC1=CC=C(Cl)C=C1 RVXKUSLFQCZMJA-NTEUORMPSA-N 0.000 description 1
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
- LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 1
- NPMOWVIHURUZDS-UHFFFAOYSA-N 1-hydroxy-2-phenylguanidine Chemical compound ONC(N)=NC1=CC=CC=C1 NPMOWVIHURUZDS-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- MYQXHLQMZLTSDB-UHFFFAOYSA-N 2-(2-ethyl-2,3-dihydro-1-benzofuran-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OC(CC)CC2=C1 MYQXHLQMZLTSDB-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- DEMLYXMVPJAVFU-UHFFFAOYSA-N 2-(chloromethyl)oxirane;2-methyl-1h-imidazole Chemical compound ClCC1CO1.CC1=NC=CN1 DEMLYXMVPJAVFU-UHFFFAOYSA-N 0.000 description 1
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- DCXHLPGLBYHNMU-UHFFFAOYSA-N 2-[1-(4-azidobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(N=[N+]=[N-])C=C1 DCXHLPGLBYHNMU-UHFFFAOYSA-N 0.000 description 1
- APBSKHYXXKHJFK-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(C=2C=CC(Cl)=CC=2)=N1 APBSKHYXXKHJFK-UHFFFAOYSA-N 0.000 description 1
- TYCOFFBAZNSQOJ-UHFFFAOYSA-N 2-[4-(3-fluorophenyl)phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC(F)=C1 TYCOFFBAZNSQOJ-UHFFFAOYSA-N 0.000 description 1
- JIEKMACRVQTPRC-UHFFFAOYSA-N 2-[4-(4-chlorophenyl)-2-phenyl-5-thiazolyl]acetic acid Chemical compound OC(=O)CC=1SC(C=2C=CC=CC=2)=NC=1C1=CC=C(Cl)C=C1 JIEKMACRVQTPRC-UHFFFAOYSA-N 0.000 description 1
- OFCLXUCSWLPMAY-UHFFFAOYSA-N 2-[4-(hydroxyamino)butyl]guanidine Chemical compound NC(=N)NCCCCNO OFCLXUCSWLPMAY-UHFFFAOYSA-N 0.000 description 1
- WRFHGDPIDHPWIQ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(ethoxymethyl)phenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(COCC)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 WRFHGDPIDHPWIQ-UHFFFAOYSA-N 0.000 description 1
- NSVFSAJIGAJDMR-UHFFFAOYSA-N 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCN(CC=2C=CC=CC=2)C=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NSVFSAJIGAJDMR-UHFFFAOYSA-N 0.000 description 1
- XKSAJZSJKURQRX-UHFFFAOYSA-N 2-acetyloxy-5-(4-fluorophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OC(=O)C)=CC=C1C1=CC=C(F)C=C1 XKSAJZSJKURQRX-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical group FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
- IJMQWMFWLFIPIF-UHFFFAOYSA-N 2-cyclopropyl-1-hydroxyguanidine Chemical compound ONC(=N)NC1CC1 IJMQWMFWLFIPIF-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- NMKSAYKQLCHXDK-UHFFFAOYSA-N 3,3-diphenyl-N-(1-phenylethyl)-1-propanamine Chemical compound C=1C=CC=CC=1C(C)NCCC(C=1C=CC=CC=1)C1=CC=CC=C1 NMKSAYKQLCHXDK-UHFFFAOYSA-N 0.000 description 1
- JXZZEXZZKAWDSP-UHFFFAOYSA-N 3-(2-(4-Benzamidopiperid-1-yl)ethyl)indole Chemical compound C1CN(CCC=2C3=CC=CC=C3NC=2)CCC1NC(=O)C1=CC=CC=C1 JXZZEXZZKAWDSP-UHFFFAOYSA-N 0.000 description 1
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 1
- MROVZCRMXJZHCN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxyethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCO)C=CC=1 MROVZCRMXJZHCN-UHFFFAOYSA-N 0.000 description 1
- VTNULXUEOJMRKZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2H-tetrazol-5-ylmethyl)benzamide Chemical compound N=1NN=NC=1CNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O VTNULXUEOJMRKZ-UHFFFAOYSA-N 0.000 description 1
- AJZDHLHTTJRNQJ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(tetrazol-1-yl)ethyl]benzamide Chemical compound N1(N=NN=C1)CCNC(C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)=O AJZDHLHTTJRNQJ-UHFFFAOYSA-N 0.000 description 1
- HAEQAUJYNHQVHV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylbenzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 HAEQAUJYNHQVHV-UHFFFAOYSA-N 0.000 description 1
- OGIYDFVHFQEFKQ-UHFFFAOYSA-N 3-[n-(4,5-dihydro-1h-imidazol-2-ylmethyl)-4-methylanilino]phenol;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 OGIYDFVHFQEFKQ-UHFFFAOYSA-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
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- XTFPDGZNWTZCMF-DHZHZOJOSA-N 3-o-methyl 5-o-[(e)-3-phenylprop-2-enyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 XTFPDGZNWTZCMF-DHZHZOJOSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- PZSMUPGANZGPBF-UHFFFAOYSA-N 4-[5-(dithiolan-3-yl)pentanoylamino]butanoic acid Chemical compound OC(=O)CCCNC(=O)CCCCC1CCSS1 PZSMUPGANZGPBF-UHFFFAOYSA-N 0.000 description 1
- WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-UHFFFAOYSA-N 0.000 description 1
- SYCHUQUJURZQMO-UHFFFAOYSA-N 4-hydroxy-2-methyl-1,1-dioxo-n-(1,3-thiazol-2-yl)-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=CS1 SYCHUQUJURZQMO-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 1
- NEYKRKVLEWKOBI-UHFFFAOYSA-N 5-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-1-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC1=NN(C)C(C(N=2)=O)=C1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CCO)CC1 NEYKRKVLEWKOBI-UHFFFAOYSA-N 0.000 description 1
- YZCSJBGQLATPMH-UHFFFAOYSA-N 5-[3-(dimethylamino)propoxy]-N-(4-methoxyphenyl)-2-(phenylmethyl)-3-pyrazolecarboxamide Chemical compound C1=CC(OC)=CC=C1NC(=O)C1=CC(OCCCN(C)C)=NN1CC1=CC=CC=C1 YZCSJBGQLATPMH-UHFFFAOYSA-N 0.000 description 1
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- UPNQBHMDTPKBDP-UHFFFAOYSA-N 6,8-dibromoimidazo[1,2-a]pyridine Chemical compound C1=C(Br)C=C(Br)C2=NC=CN21 UPNQBHMDTPKBDP-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- DHSSDEDRBUKTQY-UHFFFAOYSA-N 6-prop-2-enyl-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-2-amine Chemical compound C1CN(CC=C)CCC2=C1N=C(N)S2 DHSSDEDRBUKTQY-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- AUNGANRZJHBGPY-MBNYWOFBSA-N 7,8-dimethyl-10-[(2R,3R,4S)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-MBNYWOFBSA-N 0.000 description 1
- KKJUPNGICOCCDW-UHFFFAOYSA-N 7-N,N-Dimethylamino-1,2,3,4,5-pentathiocyclooctane Chemical compound CN(C)C1CSSSSSC1 KKJUPNGICOCCDW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QOYHHIBFXOOADH-UHFFFAOYSA-N 8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 QOYHHIBFXOOADH-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000016089 Acetazolamide-responsive myotonia Diseases 0.000 description 1
- 208000019932 Aciduria Diseases 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- FHHHOYXPRDYHEZ-COXVUDFISA-N Alacepril Chemical compound CC(=O)SC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FHHHOYXPRDYHEZ-COXVUDFISA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 201000010053 Alcoholic Cardiomyopathy Diseases 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 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 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002153 Anal fissure Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- VWVKUNOPTJGDOB-BDHVOXNPSA-N Anhydrous tofogliflozin Chemical compound C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 VWVKUNOPTJGDOB-BDHVOXNPSA-N 0.000 description 1
- 208000016583 Anus disease Diseases 0.000 description 1
- 208000003017 Aortic Valve Stenosis Diseases 0.000 description 1
- 206010002915 Aortic valve incompetence Diseases 0.000 description 1
- 206010002921 Aortitis Diseases 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- NCUCGYYHUFIYNU-UHFFFAOYSA-N Aranidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)=O)C1C1=CC=CC=C1[N+]([O-])=O NCUCGYYHUFIYNU-UHFFFAOYSA-N 0.000 description 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000036640 Asperger disease Diseases 0.000 description 1
- 201000006062 Asperger syndrome Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 208000004746 Atrophic Vaginitis Diseases 0.000 description 1
- 206010003693 Atrophic vulvovaginitis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 206010061666 Autonomic neuropathy Diseases 0.000 description 1
- 208000036154 Autosomal dominant Charcot-Marie-Tooth disease type 2V Diseases 0.000 description 1
- 235000007319 Avena orientalis Nutrition 0.000 description 1
- 244000075850 Avena orientalis Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- ZKFQEACEUNWPMT-UHFFFAOYSA-N Azelnidipine Chemical compound CC(C)OC(=O)C1=C(C)NC(N)=C(C(=O)OC2CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZKFQEACEUNWPMT-UHFFFAOYSA-N 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 229940127280 BAY 41-2272 Drugs 0.000 description 1
- ATOAHNRJAXSBOR-UHFFFAOYSA-N BAY 41-2272 Chemical compound NC1=NC(C=2C3=CC=CN=C3N(CC=3C(=CC=CC=3)F)N=2)=NC=C1C1CC1 ATOAHNRJAXSBOR-UHFFFAOYSA-N 0.000 description 1
- AQYFUZRYBJBAGZ-UHFFFAOYSA-N BAY-41-8543 Chemical compound NC1=NC(C=2C3=CC=CN=C3N(CC=3C(=CC=CC=3)F)N=2)=NC(N)=C1N1CCOCC1 AQYFUZRYBJBAGZ-UHFFFAOYSA-N 0.000 description 1
- TXGZJQLMVSIZEI-UQMAOPSPSA-N Bardoxolone Chemical compound C1=C(C#N)C(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5[C@H]4C(=O)C=C3[C@]21C TXGZJQLMVSIZEI-UQMAOPSPSA-N 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ZBJJDYGJCNTNTH-UHFFFAOYSA-N Betahistine mesilate Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.CNCCC1=CC=CC=N1 ZBJJDYGJCNTNTH-UHFFFAOYSA-N 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010056375 Bile duct obstruction Diseases 0.000 description 1
- 206010004637 Bile duct stone Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 206010071445 Bladder outlet obstruction Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 208000018083 Bone metabolism disease Diseases 0.000 description 1
- 208000002381 Brain Hypoxia Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 1
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- RHLJLALHBZGAFM-UHFFFAOYSA-N Bunazosinum Chemical compound C1CN(C(=O)CCC)CCCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 RHLJLALHBZGAFM-UHFFFAOYSA-N 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- 239000003861 C09CA09 - Azilsartan medoxomil Substances 0.000 description 1
- 208000010482 CADASIL Diseases 0.000 description 1
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical compound CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 1
- 201000002829 CREST Syndrome Diseases 0.000 description 1
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 102000007590 Calpain Human genes 0.000 description 1
- 108010032088 Calpain Proteins 0.000 description 1
- 208000037148 Calpain-3-related limb-girdle muscular dystrophy R1 Diseases 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010007560 Cardiac failure high output Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010007637 Cardiomyopathy alcoholic Diseases 0.000 description 1
- 208000004990 Cardiorenal syndrome Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000003417 Central Sleep Apnea Diseases 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- 208000029812 Cerebral Small Vessel disease Diseases 0.000 description 1
- 208000033221 Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
- 208000033935 Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 208000031976 Channelopathies Diseases 0.000 description 1
- 201000008920 Charcot-Marie-Tooth disease axonal type 2V Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 description 1
- CVKNDPRBJVBDSS-UHFFFAOYSA-N Cicletanine Chemical compound O1CC2=C(O)C(C)=NC=C2C1C1=CC=C(Cl)C=C1 CVKNDPRBJVBDSS-UHFFFAOYSA-N 0.000 description 1
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- OIRAEJWYWSAQNG-UHFFFAOYSA-N Clidanac Chemical compound ClC=1C=C2C(C(=O)O)CCC2=CC=1C1CCCCC1 OIRAEJWYWSAQNG-UHFFFAOYSA-N 0.000 description 1
- BMOVQUBVGICXQN-UHFFFAOYSA-N Clinofibrate Chemical compound C1=CC(OC(C)(CC)C(O)=O)=CC=C1C1(C=2C=CC(OC(C)(CC)C(O)=O)=CC=2)CCCCC1 BMOVQUBVGICXQN-UHFFFAOYSA-N 0.000 description 1
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 229920002905 Colesevelam Polymers 0.000 description 1
- 229920000230 Colestilan Polymers 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000029147 Collagen-vascular disease Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
- 208000004117 Congenital Myasthenic Syndromes Diseases 0.000 description 1
- 208000006509 Congenital Pain Insensitivity Diseases 0.000 description 1
- 208000016305 Congenital insensitivity to pain with severe intellectual disability Diseases 0.000 description 1
- 208000019886 Congenital renal disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 208000026292 Cystic Kidney disease Diseases 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-L D-glucarate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O DSLZVSRJTYRBFB-LLEIAEIESA-L 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- NOQGZXFMHARMLW-UHFFFAOYSA-N Daminozide Chemical compound CN(C)NC(=O)CCC(O)=O NOQGZXFMHARMLW-UHFFFAOYSA-N 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- FMTDIUIBLCQGJB-UHFFFAOYSA-N Demethylchlortetracyclin Natural products C1C2C(O)C3=C(Cl)C=CC(O)=C3C(=O)C2=C(O)C2(O)C1C(N(C)C)C(O)=C(C(N)=O)C2=O FMTDIUIBLCQGJB-UHFFFAOYSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010054044 Diabetic microangiopathy Diseases 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 101100351286 Dictyostelium discoideum pdeE gene Proteins 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical class COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 229940123900 Direct thrombin inhibitor Drugs 0.000 description 1
- ZLVMAMIPILWYHQ-INIZCTEOSA-N Docarpamine Chemical compound CCOC(=O)OC1=CC=C(CCNC(=O)[C@H](CCSC)NC(C)=O)C=C1OC(=O)OCC ZLVMAMIPILWYHQ-INIZCTEOSA-N 0.000 description 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
- 229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 1
- 102000004073 Dopamine D3 Receptors Human genes 0.000 description 1
- 108090000525 Dopamine D3 Receptors Proteins 0.000 description 1
- 229940124243 Dopamine D4 receptor antagonist Drugs 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000001654 Drug Resistant Epilepsy Diseases 0.000 description 1
- 206010073508 Drug reaction with eosinophilia and systemic symptoms Diseases 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 208000001708 Dupuytren contracture Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000004483 Dyspareunia Diseases 0.000 description 1
- 108010024212 E-Selectin Proteins 0.000 description 1
- 102100023471 E-selectin Human genes 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 208000020402 Enthesitis-related juvenile idiopathic arthritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000893536 Epimedium Species 0.000 description 1
- 108010074604 Epoetin Alfa Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 206010057671 Female sexual dysfunction Diseases 0.000 description 1
- CVKUMNRCIJMVAR-UHFFFAOYSA-N Fenoldopam mesylate Chemical compound CS(O)(=O)=O.C1=CC(O)=CC=C1C1C2=CC(O)=C(O)C(Cl)=C2CCNC1 CVKUMNRCIJMVAR-UHFFFAOYSA-N 0.000 description 1
- RBBWCVQDXDFISW-UHFFFAOYSA-N Feprazone Chemical compound O=C1C(CC=C(C)C)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 RBBWCVQDXDFISW-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 239000005475 Fimasartan Substances 0.000 description 1
- 208000009531 Fissure in Ano Diseases 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 208000002339 Frontotemporal Lobar Degeneration Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 206010070538 Gestational hypertension Diseases 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- INJOMKTZOLKMBF-UHFFFAOYSA-N Guanfacine Chemical compound NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl INJOMKTZOLKMBF-UHFFFAOYSA-N 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 206010063629 Hippocampal sclerosis Diseases 0.000 description 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 1
- 101001018196 Homo sapiens Mitogen-activated protein kinase kinase kinase 5 Proteins 0.000 description 1
- 101000780028 Homo sapiens Natriuretic peptides A Proteins 0.000 description 1
- 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 1
- 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020575 Hyperammonaemia Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010048865 Hypoacusis Diseases 0.000 description 1
- 208000008017 Hypohidrosis Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- 206010021036 Hyponatraemia Diseases 0.000 description 1
- 206010058558 Hypoperfusion Diseases 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 1
- FQYQMFCIJNWDQZ-CYDGBPFRSA-N Ile-Pro-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 FQYQMFCIJNWDQZ-CYDGBPFRSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 229940123993 Incretin mimetic Drugs 0.000 description 1
- MADRVGBADLFHMO-UHFFFAOYSA-N Indeloxazine Chemical compound C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 MADRVGBADLFHMO-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 108010089308 Insulin Detemir Proteins 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 238000012695 Interfacial polymerization Methods 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 206010072877 Intestinal fibrosis Diseases 0.000 description 1
- 201000008450 Intracranial aneurysm Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- HUYWAWARQUIQLE-UHFFFAOYSA-N Isoetharine Chemical compound CC(C)NC(CC)C(O)C1=CC=C(O)C(O)=C1 HUYWAWARQUIQLE-UHFFFAOYSA-N 0.000 description 1
- 206010023204 Joint dislocation Diseases 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 208000006264 Korsakoff syndrome Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 125000002059 L-arginyl group Chemical class O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- FSBIGDSBMBYOPN-VKHMYHEASA-N L-canavanine Chemical compound OC(=O)[C@@H](N)CCONC(N)=N FSBIGDSBMBYOPN-VKHMYHEASA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- FEMXZDUTFRTWPE-DZSWIPIPSA-N L-erythro-7,8-dihydrobiopterin Chemical compound N1C(N)=NC(=O)C2=C1NCC([C@@H](O)[C@@H](O)C)=N2 FEMXZDUTFRTWPE-DZSWIPIPSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 208000004552 Lacunar Stroke Diseases 0.000 description 1
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 1
- 240000000759 Lepidium meyenii Species 0.000 description 1
- 235000000421 Lepidium meyenii Nutrition 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 206010024434 Lichen sclerosus Diseases 0.000 description 1
- 201000009342 Limb-girdle muscular dystrophy Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 206010024626 Lipoprotein deficiency Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- XVVOERDUTLJJHN-UHFFFAOYSA-N Lixisenatide Chemical compound C=1NC2=CC=CC=C2C=1CC(C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(CC(N)=O)C(=O)NCC(=O)NCC(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CO)C(=O)NCC(=O)NC(C)C(=O)N1C(CCC1)C(=O)N1C(CCC1)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(CC(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCC(O)=O)NC(=O)C(CCSC)NC(=O)C(CCC(N)=O)NC(=O)C(CCCCN)NC(=O)C(CO)NC(=O)C(CC(C)C)NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC=1C=CC=CC=1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)CNC(=O)C(N)CC=1NC=NC=1)C(C)O)C(C)O)C(C)C)CC1=CC=CC=C1 XVVOERDUTLJJHN-UHFFFAOYSA-N 0.000 description 1
- 208000000185 Localized scleroderma Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 206010025219 Lymphangioma Diseases 0.000 description 1
- 108010075639 MAP Kinase Kinase Kinase 5 Proteins 0.000 description 1
- 101150030891 MRAS gene Proteins 0.000 description 1
- 239000004907 Macro-emulsion Substances 0.000 description 1
- TYMRLRRVMHJFTF-UHFFFAOYSA-N Mafenide Chemical compound NCC1=CC=C(S(N)(=O)=O)C=C1 TYMRLRRVMHJFTF-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 244000097724 Mesua ferrea Species 0.000 description 1
- 235000010931 Mesua ferrea Nutrition 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 1
- 208000004302 Microvascular Angina Diseases 0.000 description 1
- 208000026018 Microvascular coronary artery disease Diseases 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- 208000000996 Mirizzi syndrome Diseases 0.000 description 1
- 208000020128 Mitral stenosis Diseases 0.000 description 1
- 208000011682 Mitral valve disease Diseases 0.000 description 1
- UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 206010027982 Morphoea Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- WPNJAUFVNXKLIM-UHFFFAOYSA-N Moxonidine Chemical compound COC1=NC(C)=NC(Cl)=C1NC1=NCCN1 WPNJAUFVNXKLIM-UHFFFAOYSA-N 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- FQWRAVYMZULPNK-BYPYZUCNSA-N N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)NO FQWRAVYMZULPNK-BYPYZUCNSA-N 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- FSBIGDSBMBYOPN-UHFFFAOYSA-N O-guanidino-DL-homoserine Natural products OC(=O)C(N)CCON=C(N)N FSBIGDSBMBYOPN-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000005704 Olneya tesota Nutrition 0.000 description 1
- 241000283283 Orcinus orca Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 201000000023 Osteosclerosis Diseases 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 108010035766 P-Selectin Proteins 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 229940127355 PCSK9 Inhibitors Drugs 0.000 description 1
- 229940076380 PDE9 inhibitor Drugs 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000000450 Pelvic Pain Diseases 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- 208000004362 Penile Induration Diseases 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 206010061340 Peripheral embolism Diseases 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 208000012202 Pervasive developmental disease Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 208000020758 Peyronie disease Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 description 1
- 229940122353 Phosphodiesterase 11 inhibitor Drugs 0.000 description 1
- 229940121828 Phosphodiesterase 2 inhibitor Drugs 0.000 description 1
- 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- GHUUBYQTCDQWRA-UHFFFAOYSA-N Pioglitazone hydrochloride Chemical compound Cl.N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GHUUBYQTCDQWRA-UHFFFAOYSA-N 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 1
- 239000005477 Pratosartan Substances 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 241001208007 Procas Species 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000008198 Prosopis juliflora Nutrition 0.000 description 1
- 102000009389 Prostaglandin D receptors Human genes 0.000 description 1
- 108050000258 Prostaglandin D receptors Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000340987 Ptychopetalum olacoides Species 0.000 description 1
- 206010037448 Pulmonary valve incompetence Diseases 0.000 description 1
- 208000011191 Pulmonary vascular disease Diseases 0.000 description 1
- 206010037457 Pulmonary vasculitis Diseases 0.000 description 1
- 208000014777 Pulmonary venoocclusive disease Diseases 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 206010067171 Regurgitation Diseases 0.000 description 1
- 206010038423 Renal cyst Diseases 0.000 description 1
- 201000008206 Renpenning syndrome Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 108010001742 S-Nitrosoglutathione Proteins 0.000 description 1
- 108091006277 SLC5A1 Proteins 0.000 description 1
- 208000006117 ST-elevation myocardial infarction Diseases 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 240000006661 Serenoa repens Species 0.000 description 1
- 235000005318 Serenoa repens Nutrition 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 208000029901 Sexual arousal disease Diseases 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010040639 Sick sinus syndrome Diseases 0.000 description 1
- 206010040642 Sickle cell anaemia with crisis Diseases 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010050207 Skin fibrosis Diseases 0.000 description 1
- 201000005847 Sneddon syndrome Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 1
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 1
- 102000058090 Sodium-Glucose Transporter 1 Human genes 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000011963 Substance-induced psychotic disease Diseases 0.000 description 1
- 231100000393 Substance-induced psychotic disorder Toxicity 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
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 206010065342 Supraventricular tachyarrhythmia Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000008253 Systolic Heart Failure Diseases 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 208000001163 Tangier disease Diseases 0.000 description 1
- 208000034799 Tauopathies Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 206010051526 Tolosa-Hunt syndrome Diseases 0.000 description 1
- 208000010641 Tooth disease Diseases 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- 208000018452 Torsade de pointes Diseases 0.000 description 1
- 208000002363 Torsades de Pointes Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical compound NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 1
- 241001521901 Tribulus lanuginosus Species 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 201000001943 Tricuspid Valve Insufficiency Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
- JXNRXNCCROJZFB-RYUDHWBXSA-N Tyr-Arg Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JXNRXNCCROJZFB-RYUDHWBXSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 description 1
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 1
- 208000026723 Urinary tract disease Diseases 0.000 description 1
- 208000012931 Urologic disease Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- DOFAQXCYFQKSHT-SRVKXCTJSA-N Val-Pro-Pro Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DOFAQXCYFQKSHT-SRVKXCTJSA-N 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- 208000009325 Variant Angina Pectoris Diseases 0.000 description 1
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 208000032594 Vascular Remodeling Diseases 0.000 description 1
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 229940116211 Vasopressin antagonist Drugs 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 208000009729 Ventricular Premature Complexes Diseases 0.000 description 1
- 208000033774 Ventricular Remodeling Diseases 0.000 description 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
- 206010065341 Ventricular tachyarrhythmia Diseases 0.000 description 1
- ZVNYJIZDIRKMBF-UHFFFAOYSA-N Vesnarinone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(C=2C=C3CCC(=O)NC3=CC=2)CC1 ZVNYJIZDIRKMBF-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- PFRQBZFETXBLTP-UHFFFAOYSA-N Vitamin K2 Natural products C1=CC=C2C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-UHFFFAOYSA-N 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- 206010049644 Williams syndrome Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 206010048214 Xanthoma Diseases 0.000 description 1
- 206010048215 Xanthomatosis Diseases 0.000 description 1
- PNAMDJVUJCJOIX-IUNFJCKHSA-N [(1s,3r,7s,8s,8ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate;(3r,4s)-1-(4-fluorophenyl)-3-[(3s)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1.N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 PNAMDJVUJCJOIX-IUNFJCKHSA-N 0.000 description 1
- REAYFGLASQTHKB-UHFFFAOYSA-N [2-[3-(1H-pyrazol-4-yl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound N1N=CC(=C1)C=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 REAYFGLASQTHKB-UHFFFAOYSA-N 0.000 description 1
- SAHIZENKTPRYSN-UHFFFAOYSA-N [2-[3-(phenoxymethyl)phenoxy]-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound O(C1=CC=CC=C1)CC=1C=C(OC2=NC(=CC(=C2)CN)C(F)(F)F)C=CC=1 SAHIZENKTPRYSN-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- YQYBUJYBXOVWQW-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3,4-dihydro-1H-isoquinolin-2-yl)methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1CC2=CC=CC=C2CC1 YQYBUJYBXOVWQW-UHFFFAOYSA-N 0.000 description 1
- YKKPYMXANSSQCA-UHFFFAOYSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-(3-pyrazol-1-ylazetidin-1-yl)methanone Chemical compound N1(N=CC=C1)C1CN(C1)C(=O)C1=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F YKKPYMXANSSQCA-UHFFFAOYSA-N 0.000 description 1
- LJHFUFVRZNYVMK-CYBMUJFWSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@@H](CC1)O LJHFUFVRZNYVMK-CYBMUJFWSA-N 0.000 description 1
- LJHFUFVRZNYVMK-ZDUSSCGKSA-N [3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C=CC=1)C(=O)N1C[C@H](CC1)O LJHFUFVRZNYVMK-ZDUSSCGKSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- 229960004892 acemetacin Drugs 0.000 description 1
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 229940068372 acetyl salicylate Drugs 0.000 description 1
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 201000005180 acute myocarditis Diseases 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229940081664 adempas Drugs 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000003043 adrenergic neuron blocking agent Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229960002629 agomelatine Drugs 0.000 description 1
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 description 1
- 229950007884 alacepril Drugs 0.000 description 1
- OGWAVGNOAMXIIM-UHFFFAOYSA-N albiglutide Chemical compound O=C(O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)CNC(=O)C(NC(=O)CNC(=O)C(N)CC=1(N=CNC=1))CCC(=O)O)C(O)C)CC2(=CC=CC=C2))C(O)C)CO)CC(=O)O)C(C)C)CO)CO)CC3(=CC=C(O)C=C3))CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCN)CCC(=O)O)CC4(=CC=CC=C4))C(CC)C)C)CC=6(C5(=C(C=CC=C5)NC=6)))CC(C)C)C(C)C)CCCCN)CCCNC(=N)N OGWAVGNOAMXIIM-UHFFFAOYSA-N 0.000 description 1
- 229960004733 albiglutide Drugs 0.000 description 1
- 229960005142 alclofenac Drugs 0.000 description 1
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000002170 aldosterone antagonist Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229960004539 alirocumab Drugs 0.000 description 1
- 229960004601 aliskiren Drugs 0.000 description 1
- 229960001667 alogliptin Drugs 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
- KEJICOXJTRHYAK-XFULWGLBSA-N alogliptin benzoate Chemical compound OC(=O)C1=CC=CC=C1.C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 KEJICOXJTRHYAK-XFULWGLBSA-N 0.000 description 1
- 229960000447 alogliptin benzoate Drugs 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229960003318 alteplase Drugs 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
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229960002414 ambrisentan Drugs 0.000 description 1
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 description 1
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- 229960000959 amineptine Drugs 0.000 description 1
- ONNOFKFOZAJDHT-UHFFFAOYSA-N amineptine Chemical compound C1CC2=CC=CC=C2C(NCCCCCCC(=O)O)C2=CC=CC=C21 ONNOFKFOZAJDHT-UHFFFAOYSA-N 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 150000005005 aminopyrimidines Chemical class 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 229940022110 amlodipine / atorvastatin Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229960002519 amoxapine Drugs 0.000 description 1
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960002105 amrinone Drugs 0.000 description 1
- RNLQIBCLLYYYFJ-UHFFFAOYSA-N amrinone Chemical compound N1C(=O)C(N)=CC(C=2C=CN=CC=2)=C1 RNLQIBCLLYYYFJ-UHFFFAOYSA-N 0.000 description 1
- 229960003116 amyl nitrite Drugs 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- LDXYBEHACFJIEL-HNNXBMFYSA-N anagliptin Chemical compound C=1N2N=C(C)C=C2N=CC=1C(=O)NCC(C)(C)NCC(=O)N1CCC[C@H]1C#N LDXYBEHACFJIEL-HNNXBMFYSA-N 0.000 description 1
- 229950009977 anagliptin Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940051880 analgesics and antipyretics pyrazolones Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 208000000252 angiomatosis Diseases 0.000 description 1
- 239000000584 angiotensin II type 2 receptor blocker Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003206 anti-remodeling effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 229940124574 antisickling agent Drugs 0.000 description 1
- 239000003939 antisickling agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 201000002064 aortic valve insufficiency Diseases 0.000 description 1
- 229950009097 apararenone Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229950007556 aranidipine Drugs 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 230000001623 arteriogenic effect Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 229940022113 aspirin / pravastatin Drugs 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 1
- 229960002430 atomoxetine Drugs 0.000 description 1
- 229940034406 atorvastatin / ezetimibe Drugs 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 1
- 201000009564 autosomal recessive limb-girdle muscular dystrophy type 2A Diseases 0.000 description 1
- 229960000307 avanafil Drugs 0.000 description 1
- WEAJZXNPAWBCOA-INIZCTEOSA-N avanafil Chemical compound C1=C(Cl)C(OC)=CC=C1CNC1=NC(N2[C@@H](CCC2)CO)=NC=C1C(=O)NCC1=NC=CC=N1 WEAJZXNPAWBCOA-INIZCTEOSA-N 0.000 description 1
- 229950000586 aviptadil Drugs 0.000 description 1
- 108010006060 aviptadil Proteins 0.000 description 1
- 229960001671 azapropazone Drugs 0.000 description 1
- WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 1
- 229950004646 azelnidipine Drugs 0.000 description 1
- 229960001211 azilsartan medoxomil Drugs 0.000 description 1
- QJFSABGVXDWMIW-UHFFFAOYSA-N azilsartan medoxomil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C=3NC(=O)ON=3)C(OCC)=NC2=CC=CC=1C(=O)OCC=1OC(=O)OC=1C QJFSABGVXDWMIW-UHFFFAOYSA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960003623 azlocillin Drugs 0.000 description 1
- JTWOMNBEOCYFNV-NFFDBFGFSA-N azlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCNC1=O JTWOMNBEOCYFNV-NFFDBFGFSA-N 0.000 description 1
- 201000007917 background diabetic retinopathy Diseases 0.000 description 1
- 229950002483 bardoxolone Drugs 0.000 description 1
- 229960002992 barnidipine Drugs 0.000 description 1
- VXMOONUMYLCFJD-DHLKQENFSA-N barnidipine Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@@H]2CN(CC=3C=CC=CC=3)CC2)=CC=CC([N+]([O-])=O)=C1 VXMOONUMYLCFJD-DHLKQENFSA-N 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 229960004916 benidipine Drugs 0.000 description 1
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- MITFXPHMIHQXPI-UHFFFAOYSA-N benzoxaprofen Natural products N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 229960003665 bepridil Drugs 0.000 description 1
- UIEATEWHFDRYRU-UHFFFAOYSA-N bepridil Chemical compound C1CCCN1C(COCC(C)C)CN(C=1C=CC=CC=1)CC1=CC=CC=C1 UIEATEWHFDRYRU-UHFFFAOYSA-N 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 229960004620 bitolterol Drugs 0.000 description 1
- FZGVEKPRDOIXJY-UHFFFAOYSA-N bitolterol Chemical compound C1=CC(C)=CC=C1C(=O)OC1=CC=C(C(O)CNC(C)(C)C)C=C1OC(=O)C1=CC=C(C)C=C1 FZGVEKPRDOIXJY-UHFFFAOYSA-N 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 239000003633 blood substitute Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- FFHBJDQSGDNCIV-MFVUMRCOSA-N bremelanotide Chemical compound C([C@@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCNC(=O)C[C@@H](C(N[C@@H](CC=2NC=NC=2)C(=O)N1)=O)NC(=O)[C@@H](NC(C)=O)CCCC)C(O)=O)C1=CC=CC=C1 FFHBJDQSGDNCIV-MFVUMRCOSA-N 0.000 description 1
- 108010072543 bremelanotide Proteins 0.000 description 1
- 229950000740 bremelanotide Drugs 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
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229960002467 bunazosin Drugs 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 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
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 description 1
- 229960001113 butorphanol Drugs 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 230000003222 cGMP degradation Effects 0.000 description 1
- 229960004596 cabergoline Drugs 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- KIOJIUJTZWEWGA-DJNTWTPDSA-L calcium;benzenesulfonic acid;3-o-ethyl 5-o-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate;(3r,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoate Chemical compound [Ca+2].OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 KIOJIUJTZWEWGA-DJNTWTPDSA-L 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 208000020450 carbohydrate metabolism disease Diseases 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000011128 cardiac conduction Effects 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 206010007625 cardiogenic shock Diseases 0.000 description 1
- 229950008486 carperitide Drugs 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229950011033 cenicriviroc Drugs 0.000 description 1
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003576 central nervous system agent Substances 0.000 description 1
- 229940125693 central nervous system agent Drugs 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 208000016886 cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 1
- 208000011142 cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 Diseases 0.000 description 1
- 230000003788 cerebral perfusion Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- IWXUVYOOUMLUTQ-CZUORRHYSA-N chembl2179105 Chemical compound C([C@H]([C@@H](C1)C=2NC(=O)C=3C=NN(C=3N=2)C2CCOCC2)C)N1CC1=NC=CC=N1 IWXUVYOOUMLUTQ-CZUORRHYSA-N 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 229960001932 cicletanine Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 229950002128 cinaciguat Drugs 0.000 description 1
- WPYWMXNXEZFMAK-UHFFFAOYSA-N cinaciguat Chemical compound C=1C=C(C(O)=O)C=CC=1CN(CCCCC(=O)O)CCC1=CC=CC=C1OCC(C=C1)=CC=C1CCC1=CC=CC=C1 WPYWMXNXEZFMAK-UHFFFAOYSA-N 0.000 description 1
- 229960002174 ciprofibrate Drugs 0.000 description 1
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 229960003324 clavulanic acid Drugs 0.000 description 1
- 229960003597 clevidipine Drugs 0.000 description 1
- KPBZROQVTHLCDU-GOSISDBHSA-N clevidipine Chemical compound CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@H]1C1=CC=CC(Cl)=C1Cl KPBZROQVTHLCDU-GOSISDBHSA-N 0.000 description 1
- 229950010886 clidanac Drugs 0.000 description 1
- 229950003072 clinofibrate Drugs 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960004606 clomipramine Drugs 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960003326 cloxacillin Drugs 0.000 description 1
- LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229940047766 co-trimoxazole Drugs 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 230000009852 coagulant defect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229940110767 coenzyme Q10 Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 229960001152 colesevelam Drugs 0.000 description 1
- 229960004095 colestilan Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- RSOZZQTUMVBTMR-XGUNBQNXSA-N colforsin daropate Chemical compound O[C@H]([C@@]12C)CCC(C)(C)[C@@H]1[C@H](OC(=O)CCN(C)C)[C@H](OC(C)=O)[C@]1(C)[C@]2(O)C(=O)C[C@](C)(C=C)O1 RSOZZQTUMVBTMR-XGUNBQNXSA-N 0.000 description 1
- 229950005198 colforsin daropate Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
- 208000020020 complex sleep apnea Diseases 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 208000016569 congenital mitral valve insufficiency Diseases 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 150000004775 coumarins Chemical class 0.000 description 1
- 229960003624 creatine Drugs 0.000 description 1
- 239000006046 creatine Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 229940109248 cromoglycate Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960003850 dabigatran Drugs 0.000 description 1
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 239000003954 decarboxylase inhibitor Substances 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 229960002398 demeclocycline Drugs 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 description 1
- 229960003461 dezocine Drugs 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 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
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 208000021913 diffuse palmoplantar keratoderma Diseases 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229940042397 direct acting antivirals cyclic amines Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- LJEMFZYMXONDDJ-UHFFFAOYSA-N disodium;[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)pyridin-4-yl]pyrimidin-4-yl]-(5-propan-2-ylpyridin-2-yl)sulfonylazanide Chemical compound [Na+].[Na+].COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C=2[N-]N=NN=2)OCCO)=C1[N-]S(=O)(=O)C1=CC=C(C(C)C)C=N1 LJEMFZYMXONDDJ-UHFFFAOYSA-N 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 201000009338 distal myopathy Diseases 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 229950006045 docarpamine Drugs 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 229940052764 dopaminergic anti-parkinson drug mao b inhibitors Drugs 0.000 description 1
- RYBJORHCUPVNMB-UHFFFAOYSA-N dopexamine Chemical compound C1=C(O)C(O)=CC=C1CCNCCCCCCNCCC1=CC=CC=C1 RYBJORHCUPVNMB-UHFFFAOYSA-N 0.000 description 1
- 229960001857 dopexamine Drugs 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960005426 doxepin Drugs 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 201000002545 drug psychosis Diseases 0.000 description 1
- 229960005175 dulaglutide Drugs 0.000 description 1
- 108010005794 dulaglutide Proteins 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229950003102 efonidipine Drugs 0.000 description 1
- 229950001279 elafibranor Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 229950000234 emricasan Drugs 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 201000010048 endomyocardial fibrosis Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 229950002375 englitazone Drugs 0.000 description 1
- 229960002549 enoxacin Drugs 0.000 description 1
- IDYZIJYBMGIQMJ-UHFFFAOYSA-N enoxacin Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 IDYZIJYBMGIQMJ-UHFFFAOYSA-N 0.000 description 1
- 229960000972 enoximone Drugs 0.000 description 1
- ZJKNESGOIKRXQY-UHFFFAOYSA-N enoximone Chemical compound C1=CC(SC)=CC=C1C(=O)C1=C(C)NC(=O)N1 ZJKNESGOIKRXQY-UHFFFAOYSA-N 0.000 description 1
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 description 1
- 229960003337 entacapone Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 235000018905 epimedium Nutrition 0.000 description 1
- 229960003388 epoetin alfa Drugs 0.000 description 1
- 108010002601 epoetin beta Proteins 0.000 description 1
- 229960004579 epoetin beta Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- DWXKSCKBUSAOKS-UHFFFAOYSA-N ethyl 2-chloro-3-oxopropanoate Chemical compound CCOC(=O)C(Cl)C=O DWXKSCKBUSAOKS-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 229960002027 evolocumab Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 229940054572 ezetimibe / simvastatin Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229950006236 fenclofenac Drugs 0.000 description 1
- IDKAXRLETRCXKS-UHFFFAOYSA-N fenclofenac Chemical compound OC(=O)CC1=CC=CC=C1OC1=CC=C(Cl)C=C1Cl IDKAXRLETRCXKS-UHFFFAOYSA-N 0.000 description 1
- 229950011481 fenclozic acid Drugs 0.000 description 1
- 229960002602 fendiline Drugs 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960002724 fenoldopam Drugs 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 229960001022 fenoterol Drugs 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
- 229960002679 fentiazac Drugs 0.000 description 1
- 229960000489 feprazone Drugs 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960003489 fimasartan Drugs 0.000 description 1
- AMEROGPZOLAFBN-UHFFFAOYSA-N fimasartan Chemical compound CCCCC1=NC(C)=C(CC(=S)N(C)C)C(=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 AMEROGPZOLAFBN-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229950007979 flufenisal Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229950001284 fluprofen Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960003532 fluspirilene Drugs 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
- 229960001318 fondaparinux Drugs 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 0.000 description 1
- 229950010931 furofenac Drugs 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 229960000457 gallopamil Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000001288 gastroparesis Diseases 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- ZRCVYEYHRGVLOC-HYARGMPZSA-N gemifloxacin Chemical compound C1C(CN)C(=N/OC)/CN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1CC1 ZRCVYEYHRGVLOC-HYARGMPZSA-N 0.000 description 1
- 229960003170 gemifloxacin Drugs 0.000 description 1
- 229960002458 gemigliptin Drugs 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 235000021472 generally recognized as safe Nutrition 0.000 description 1
- 229940114119 gentisate Drugs 0.000 description 1
- AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229960003468 gliquidone Drugs 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 231100000852 glomerular disease Toxicity 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- HPBNRIOWIXYZFK-UHFFFAOYSA-N guanadrel Chemical compound O1C(CNC(=N)N)COC11CCCCC1 HPBNRIOWIXYZFK-UHFFFAOYSA-N 0.000 description 1
- 229960003845 guanadrel Drugs 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- 229960002048 guanfacine Drugs 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 210000004024 hepatic stellate cell Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZASXKEGREHRXDL-CAWNUZPDSA-H hexasodium;4-[[(2s,4r)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoate;(2s)-3-methyl-2-[pentanoyl-[[4-[2-(1,2,3-triaza-4-azanidacyclopenta-2,5-dien-5-yl)phenyl]phenyl]methyl]amino]butanoate;pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC([O-])=O)=CC=C1C1=CC=CC=C1.C1=CC(C[C@H](C[C@@H](C)C(=O)OCC)NC(=O)CCC([O-])=O)=CC=C1C1=CC=CC=C1.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C([O-])=O)=CC=C1C1=CC=CC=C1C1=NN=N[N-]1.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C([O-])=O)=CC=C1C1=CC=CC=C1C1=NN=N[N-]1 ZASXKEGREHRXDL-CAWNUZPDSA-H 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
- 208000019271 high output heart failure Diseases 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 1
- 102000044890 human EPO Human genes 0.000 description 1
- 102000056614 human NPPA Human genes 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 208000026621 hypolipoproteinemia Diseases 0.000 description 1
- 229960004370 ibopamine Drugs 0.000 description 1
- 229950009183 ibufenac Drugs 0.000 description 1
- CYWFCPPBTWOZSF-UHFFFAOYSA-N ibufenac Chemical compound CC(C)CC1=CC=C(CC(O)=O)C=C1 CYWFCPPBTWOZSF-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 1
- 229960004135 idebenone Drugs 0.000 description 1
- 229960001195 imidapril Drugs 0.000 description 1
- KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
- 108010070995 imidazoline I1 receptors Proteins 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000017745 inborn carbohydrate metabolic disease Diseases 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- 229960004333 indeloxazine Drugs 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 229960004187 indoprofen Drugs 0.000 description 1
- 229960002056 indoramin Drugs 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910001959 inorganic nitrate Inorganic materials 0.000 description 1
- 229960003948 insulin detemir Drugs 0.000 description 1
- 229960002068 insulin lispro Drugs 0.000 description 1
- UFIPGFMPJACHTH-HXDLXPBZSA-N insulin peglispro Chemical compound C([C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=4C=CC(O)=CC=4)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=4NC=NC=4)NC(=O)[C@H](CO)NC(=O)CNC2=O)C(C)C)C(C)C)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCNC(=O)OCCOC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N1)C(C)C)=O)CSSC[C@@H](C(N3)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C1=CN=CN1 UFIPGFMPJACHTH-HXDLXPBZSA-N 0.000 description 1
- 229950009050 insulin peglispro Drugs 0.000 description 1
- 230000002473 insulinotropic effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 201000002161 intrahepatic cholestasis of pregnancy Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229950000991 ipragliflozin Drugs 0.000 description 1
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960001268 isoetarine Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229960000201 isosorbide dinitrate Drugs 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 229950011455 isoxepac Drugs 0.000 description 1
- QFGMXJOBTNZHEL-UHFFFAOYSA-N isoxepac Chemical compound O1CC2=CC=CC=C2C(=O)C2=CC(CC(=O)O)=CC=C21 QFGMXJOBTNZHEL-UHFFFAOYSA-N 0.000 description 1
- 229950002252 isoxicam Drugs 0.000 description 1
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 1
- IQVRBWUUXZMOPW-PKNBQFBNSA-N istradefylline Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=C(OC)C(OC)=C1 IQVRBWUUXZMOPW-PKNBQFBNSA-N 0.000 description 1
- 229950009028 istradefylline Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 description 1
- 229960005417 ketanserin Drugs 0.000 description 1
- 150000004658 ketimines Chemical class 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 229960004340 lacidipine Drugs 0.000 description 1
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 108010058587 lactokinins Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 229960004294 lercanidipine Drugs 0.000 description 1
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- UGOZVNFCFYTPAZ-IOXYNQHNSA-N levemir Chemical compound CCCCCCCCCCCCCC(=O)NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=2N=CNC=2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=2C=CC=CC=2)C(C)C)CSSC[C@@H]2NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)CSSC[C@H](NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC2=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CC(N)=O)C(O)=O)CC1=CC=C(O)C=C1 UGOZVNFCFYTPAZ-IOXYNQHNSA-N 0.000 description 1
- 229960004002 levetiracetam Drugs 0.000 description 1
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 229960003406 levorphanol Drugs 0.000 description 1
- WHXMKTBCFHIYNQ-SECBINFHSA-N levosimendan Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1 WHXMKTBCFHIYNQ-SECBINFHSA-N 0.000 description 1
- 229960000692 levosimendan Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229960001093 lixisenatide Drugs 0.000 description 1
- 108010004367 lixisenatide Proteins 0.000 description 1
- CHHXEZSCHQVSRE-UHFFFAOYSA-N lobeglitazone Chemical compound C1=CC(OC)=CC=C1OC1=CC(N(C)CCOC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=NC=N1 CHHXEZSCHQVSRE-UHFFFAOYSA-N 0.000 description 1
- 229950007685 lobeglitazone Drugs 0.000 description 1
- 229960002422 lomefloxacin Drugs 0.000 description 1
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 description 1
- 229960003566 lomitapide Drugs 0.000 description 1
- MBBCVAKAJPKAKM-UHFFFAOYSA-N lomitapide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCC1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 MBBCVAKAJPKAKM-UHFFFAOYSA-N 0.000 description 1
- 229940125389 long-acting beta agonist Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229940056203 lovastatin / niacin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 206010025005 lumbar spinal stenosis Diseases 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229960001432 lurasidone Drugs 0.000 description 1
- PQXKDMSYBGKCJA-CVTJIBDQSA-N lurasidone Chemical compound C1=CC=C2C(N3CCN(CC3)C[C@@H]3CCCC[C@H]3CN3C(=O)[C@@H]4[C@H]5CC[C@H](C5)[C@@H]4C3=O)=NSC2=C1 PQXKDMSYBGKCJA-CVTJIBDQSA-N 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- JVGUNCHERKJFCM-UHFFFAOYSA-N mabuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(=O)NCCO)C=C1 JVGUNCHERKJFCM-UHFFFAOYSA-N 0.000 description 1
- 229950001846 mabuprofen Drugs 0.000 description 1
- 229960001039 macitentan Drugs 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 229960003640 mafenide Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229960003963 manidipine Drugs 0.000 description 1
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 description 1
- IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 description 1
- 229960002525 mecamylamine Drugs 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 201000001231 mediastinitis Diseases 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- DKHGMERMDICWDU-GHDNBGIDSA-N menaquinone-4 Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 DKHGMERMDICWDU-GHDNBGIDSA-N 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- IYJMSDVSVHDVGT-PEQKVOOWSA-N metildigoxin Chemical compound O1[C@H](C)[C@@H](OC)[C@@H](O)C[C@@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O IYJMSDVSVHDVGT-PEQKVOOWSA-N 0.000 description 1
- 229960003746 metildigoxin Drugs 0.000 description 1
- AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
- 229960002817 metolazone Drugs 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960004438 mibefradil Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 229960003574 milrinone Drugs 0.000 description 1
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- MIJFNYMSCFYZNY-UHFFFAOYSA-N mirodenafil Chemical compound C1=C(C=2NC=3C(CCC)=CN(CC)C=3C(=O)N=2)C(OCCC)=CC=C1S(=O)(=O)N1CCN(CCO)CC1 MIJFNYMSCFYZNY-UHFFFAOYSA-N 0.000 description 1
- 229950002245 mirodenafil Drugs 0.000 description 1
- 229950006616 miroprofen Drugs 0.000 description 1
- OJGQFYYLKNCIJD-UHFFFAOYSA-N miroprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CN(C=CC=C2)C2=N1 OJGQFYYLKNCIJD-UHFFFAOYSA-N 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
- 208000012268 mitochondrial disease Diseases 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 208000005907 mitral valve insufficiency Diseases 0.000 description 1
- 208000006887 mitral valve stenosis Diseases 0.000 description 1
- 201000006646 mixed sleep apnea Diseases 0.000 description 1
- YHXISWVBGDMDLQ-UHFFFAOYSA-N moclobemide Chemical compound C1=CC(Cl)=CC=C1C(=O)NCCN1CCOCC1 YHXISWVBGDMDLQ-UHFFFAOYSA-N 0.000 description 1
- 229960004644 moclobemide Drugs 0.000 description 1
- 229960005170 moexipril Drugs 0.000 description 1
- 229960005285 mofebutazone Drugs 0.000 description 1
- REOJLIXKJWXUGB-UHFFFAOYSA-N mofebutazone Chemical compound O=C1C(CCCC)C(=O)NN1C1=CC=CC=C1 REOJLIXKJWXUGB-UHFFFAOYSA-N 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960003702 moxifloxacin Drugs 0.000 description 1
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 229940014456 mycophenolate Drugs 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- WIDKTXGNSOORHA-CJHXQPGBSA-N n,n'-dibenzylethane-1,2-diamine;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;tetrahydrate Chemical compound O.O.O.O.C=1C=CC=CC=1CNCCNCC1=CC=CC=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 WIDKTXGNSOORHA-CJHXQPGBSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- ULDDTFAPYWLDGF-UHFFFAOYSA-N n-butyl-n'-hydroxyguanidine Chemical compound CCCCNC(=N)NO ULDDTFAPYWLDGF-UHFFFAOYSA-N 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
- 229960000805 nalbuphine Drugs 0.000 description 1
- 229960000210 nalidixic acid Drugs 0.000 description 1
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 229960003086 naltrexone Drugs 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229960000619 nebivolol Drugs 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000003041 necroinflammatory effect Effects 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- 229950004380 nelociguat Drugs 0.000 description 1
- 229950011108 nemonapride Drugs 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000002988 nephrogenic effect Effects 0.000 description 1
- 230000007372 neural signaling Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000008795 neuromyelitis optica Diseases 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229940110831 niacin / simvastatin Drugs 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229960000916 niflumic acid Drugs 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000004005 nitrosamines Chemical class 0.000 description 1
- 230000008599 nitrosative stress Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- MVPQUSQUURLQKF-MCPDASDXSA-E nonasodium;(2s,3s,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3s,4s,5r,6r)-2-carboxylato-4,5-dimethoxy-6-[(2r,3r,4s,5r,6s)-6-methoxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-di Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S(=O)(=O)O[C@@H]1[C@@H](OS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](OC)[C@H](O[C@@H]4[C@@H]([C@@H](OC)[C@H](OC)[C@@H](COS([O-])(=O)=O)O4)OC)[C@H](O3)C([O-])=O)OC)[C@@H](COS([O-])(=O)=O)O2)OS([O-])(=O)=O)[C@H](C([O-])=O)O1 MVPQUSQUURLQKF-MCPDASDXSA-E 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 229960001601 obeticholic acid Drugs 0.000 description 1
- ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 229950009786 olinciguat Drugs 0.000 description 1
- 229950005421 olprinone Drugs 0.000 description 1
- JPAWFIIYTJQOKW-UHFFFAOYSA-N olprinone Chemical compound N1C(=O)C(C#N)=CC(C2=CN3C=CN=C3C=C2)=C1C JPAWFIIYTJQOKW-UHFFFAOYSA-N 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 229960002657 orciprenaline Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 206010033103 otosclerosis Diseases 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- QPTISOPQFLIZCY-UHFFFAOYSA-N oxatriazol-5-amine Chemical compound NC1=NN=NO1 QPTISOPQFLIZCY-UHFFFAOYSA-N 0.000 description 1
- 229960001816 oxcarbazepine Drugs 0.000 description 1
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000002457 oxidoreductase inhibitor Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000002640 oxygen therapy Methods 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 208000005877 painful neuropathy Diseases 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 229960004662 parecoxib Drugs 0.000 description 1
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 101150037969 pde-6 gene Proteins 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940059411 pegapamodutide Drugs 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229960004851 pergolide Drugs 0.000 description 1
- YEHCICAEULNIGD-MZMPZRCHSA-N pergolide Chemical compound C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 YEHCICAEULNIGD-MZMPZRCHSA-N 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 201000003841 peripheral retinal degeneration Diseases 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 208000030062 persistent idiopathic facial pain Diseases 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229960000280 phenindione Drugs 0.000 description 1
- NFBAXHOPROOJAW-UHFFFAOYSA-N phenindione Chemical compound O=C1C2=CC=CC=C2C(=O)C1C1=CC=CC=C1 NFBAXHOPROOJAW-UHFFFAOYSA-N 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- DQDAYGNAKTZFIW-UHFFFAOYSA-N phenprocoumon Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC)C1=CC=CC=C1 DQDAYGNAKTZFIW-UHFFFAOYSA-N 0.000 description 1
- 229960004923 phenprocoumon Drugs 0.000 description 1
- 229960001999 phentolamine Drugs 0.000 description 1
- FCJSHPDYVMKCHI-UHFFFAOYSA-N phenyl benzoate Chemical class C=1C=CC=CC=1C(=O)OC1=CC=CC=C1 FCJSHPDYVMKCHI-UHFFFAOYSA-N 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229940068065 phytosterols Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002164 pimobendan Drugs 0.000 description 1
- GLBJJMFZWDBELO-UHFFFAOYSA-N pimobendane Chemical compound C1=CC(OC)=CC=C1C1=NC2=CC=C(C=3C(CC(=O)NN=3)C)C=C2N1 GLBJJMFZWDBELO-UHFFFAOYSA-N 0.000 description 1
- 229960002310 pinacidil Drugs 0.000 description 1
- 235000010204 pine bark Nutrition 0.000 description 1
- 229960002827 pioglitazone hydrochloride Drugs 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960000851 pirprofen Drugs 0.000 description 1
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 208000030761 polycystic kidney disease Diseases 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229960005483 polythiazide Drugs 0.000 description 1
- 229920000046 polythiazide Polymers 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 201000010808 postmenopausal atrophic vaginitis Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229960000206 potassium canrenoate Drugs 0.000 description 1
- JTZQCHFUGHIPDF-RYVBEKKQSA-M potassium canrenoate Chemical compound [K+].O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)CCC([O-])=O)[C@@H]4[C@@H]3C=CC2=C1 JTZQCHFUGHIPDF-RYVBEKKQSA-M 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229940070116 praliciguat Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- 229950004891 pranidipine Drugs 0.000 description 1
- 229960003101 pranoprofen Drugs 0.000 description 1
- KCTFTBCZZUBAKN-UHFFFAOYSA-N pratosartan Chemical compound CCCC1=NC=2CCCCC(=O)C=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 KCTFTBCZZUBAKN-UHFFFAOYSA-N 0.000 description 1
- 229950005649 pratosartan Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 150000005599 propionic acid derivatives Chemical class 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 239000011251 protective drug Substances 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229950003776 protoporphyrin Drugs 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 201000010298 pulmonary valve insufficiency Diseases 0.000 description 1
- 208000009138 pulmonary valve stenosis Diseases 0.000 description 1
- 208000037813 pulmonary venous hypertension Diseases 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229930185107 quinolinone Natural products 0.000 description 1
- 108700027806 rGLP-1 Proteins 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- CBQGYUDMJHNJBX-RTBURBONSA-N reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 description 1
- 229960003770 reboxetine Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000015658 resistant hypertension Diseases 0.000 description 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 229960005224 roxithromycin Drugs 0.000 description 1
- 229960003014 rufinamide Drugs 0.000 description 1
- POGQSBRIGCQNEG-UHFFFAOYSA-N rufinamide Chemical compound N1=NC(C(=O)N)=CN1CC1=C(F)C=CC=C1F POGQSBRIGCQNEG-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- NEMGRZFTLSKBAP-LBPRGKRZSA-N safinamide Chemical compound C1=CC(CN[C@@H](C)C(N)=O)=CC=C1OCC1=CC=CC(F)=C1 NEMGRZFTLSKBAP-LBPRGKRZSA-N 0.000 description 1
- 229950002652 safinamide Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229940127100 salmeterol-fluticasone Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000010018 saw palmetto extract Substances 0.000 description 1
- 208000000943 scapulohumeral muscular dystrophy Diseases 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- YIDDLAAKOYYGJG-UHFFFAOYSA-N selonsertib Chemical compound CC(C)N1C=NN=C1C1=CC=CC(NC(=O)C=2C(=CC(C)=C(C=2)N2C=C(N=C2)C2CC2)F)=N1 YIDDLAAKOYYGJG-UHFFFAOYSA-N 0.000 description 1
- 229950003181 selonsertib Drugs 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 description 1
- 229960002639 sildenafil citrate Drugs 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229960003600 silver sulfadiazine Drugs 0.000 description 1
- UEJSSZHHYBHCEL-UHFFFAOYSA-N silver(1+) sulfadiazinate Chemical compound [Ag+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=NC=CC=N1 UEJSSZHHYBHCEL-UHFFFAOYSA-N 0.000 description 1
- 229940084073 simvastatin / sitagliptin Drugs 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960004115 sitagliptin phosphate Drugs 0.000 description 1
- 229960002578 sitaxentan Drugs 0.000 description 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 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
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
- QWIHVUUEJBINLC-LNKPDPKZSA-M sodium;(z)-3-ethoxy-2-fluoro-3-oxoprop-1-en-1-olate Chemical compound [Na+].CCOC(=O)C(\F)=C\[O-] QWIHVUUEJBINLC-LNKPDPKZSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 229950005268 sotagliflozin Drugs 0.000 description 1
- 229950002009 sparsentan Drugs 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 208000005198 spinal stenosis Diseases 0.000 description 1
- 229960002909 spirapril Drugs 0.000 description 1
- HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
- 108700035424 spirapril Proteins 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229950005175 sudoxicam Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229960002673 sulfacetamide Drugs 0.000 description 1
- SKIVFJLNDNKQPD-UHFFFAOYSA-N sulfacetamide Chemical compound CC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 SKIVFJLNDNKQPD-UHFFFAOYSA-N 0.000 description 1
- 229960000654 sulfafurazole Drugs 0.000 description 1
- 229960005158 sulfamethizole Drugs 0.000 description 1
- VACCAVUAMIDAGB-UHFFFAOYSA-N sulfamethizole Chemical compound S1C(C)=NN=C1NS(=O)(=O)C1=CC=C(N)C=C1 VACCAVUAMIDAGB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 208000037905 systemic hypertension Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 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
- 229950008418 talipexole Drugs 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229960004084 temocapril Drugs 0.000 description 1
- FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
- WGRQANOPCQRCME-PMACEKPBSA-N teneligliptin Chemical compound O=C([C@H]1NC[C@H](C1)N1CCN(CC1)C1=CC(=NN1C=1C=CC=CC=1)C)N1CCSC1 WGRQANOPCQRCME-PMACEKPBSA-N 0.000 description 1
- 229950000034 teneligliptin Drugs 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- RTZRUVMEWWPNRR-UHFFFAOYSA-N tert-butyl n-(3-iodo-1h-pyrrolo[2,3-b]pyridin-5-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=C2NC=C(I)C2=C1 RTZRUVMEWWPNRR-UHFFFAOYSA-N 0.000 description 1
- 229960005333 tetrabenazine Drugs 0.000 description 1
- MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 230000000542 thalamic effect Effects 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- ICRHORQIUXBEPA-UHFFFAOYSA-N thionitrous acid Chemical group SN=O ICRHORQIUXBEPA-UHFFFAOYSA-N 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- GUHPRPJDBZHYCJ-UHFFFAOYSA-N tiaprofenic acid Chemical compound S1C(C(C(O)=O)C)=CC=C1C(=O)C1=CC=CC=C1 GUHPRPJDBZHYCJ-UHFFFAOYSA-N 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 229940110309 tiotropium Drugs 0.000 description 1
- BTSOGEDATSQOAF-SMAAHMJQSA-N tirzepatide Chemical compound CC[C@H](C)[C@@H](C(N[C@@H](C)C(N[C@@H](CCC(N)=O)C(N[C@@H](CCCCNC(COCCOCCNC(COCCOCCNC(CC[C@H](C(O)=O)NC(CCCCCCCCCCCCCCCCCCC(O)=O)=O)=O)=O)=O)C(N[C@@H](C)C(N[C@@H](CC1=CC=CC=C1)C(N[C@@H](C(C)C)C(N[C@@H](CCC(N)=O)C(N[C@@H](CC1=CNC2=C1C=CC=C2)C(N[C@@H](CC(C)C)C(N[C@@H]([C@@H](C)CC)C(N[C@@H](C)C(NCC(NCC(N(CCC1)[C@@H]1C(N[C@@H](CO)C(N[C@@H](CO)C(NCC(N[C@@H](C)C(N(CCC1)[C@@H]1C(N(CCC1)[C@@H]1C(N(CCC1)[C@@H]1C(N[C@@H](CO)C(N)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)NC([C@H](CCCCN)NC([C@H](CC(O)=O)NC([C@H](CC(C)C)NC(C(C)(C)NC([C@H]([C@@H](C)CC)NC([C@H](CO)NC([C@H](CC(C=C1)=CC=C1O)NC([C@H](CC(O)=O)NC([C@H](CO)NC([C@H]([C@@H](C)O)NC([C@H](CC1=CC=CC=C1)NC([C@H]([C@@H](C)O)NC(CNC([C@H](CCC(O)=O)NC(C(C)(C)NC([C@H](CC(C=C1)=CC=C1O)N)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O BTSOGEDATSQOAF-SMAAHMJQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229950006667 tofogliflozin Drugs 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 229960002905 tolfenamic acid Drugs 0.000 description 1
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 description 1
- HJQILFPVRNHTIG-UHFFFAOYSA-N tolimidone Chemical compound CC1=CC=CC(OC2=CNC(=O)N=C2)=C1 HJQILFPVRNHTIG-UHFFFAOYSA-N 0.000 description 1
- 229950005012 tolimidone Drugs 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- GYHCTFXIZSNGJT-UHFFFAOYSA-N tolvaptan Chemical compound CC1=CC=CC=C1C(=O)NC(C=C1C)=CC=C1C(=O)N1C2=CC=C(Cl)C=C2C(O)CCC1 GYHCTFXIZSNGJT-UHFFFAOYSA-N 0.000 description 1
- 229960001256 tolvaptan Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 229960003991 trazodone Drugs 0.000 description 1
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960001288 triamterene Drugs 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000009999 tuberous sclerosis Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229960004747 ubidecarenone Drugs 0.000 description 1
- 229960000438 udenafil Drugs 0.000 description 1
- IYFNEFQTYQPVOC-UHFFFAOYSA-N udenafil Chemical compound C1=C(C=2NC=3C(CCC)=NN(C)C=3C(=O)N=2)C(OCCC)=CC=C1S(=O)(=O)NCCC1CCCN1C IYFNEFQTYQPVOC-UHFFFAOYSA-N 0.000 description 1
- 229960001130 urapidil Drugs 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 239000006213 vaginal ring Substances 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 229940102566 valproate Drugs 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 108010015385 valyl-prolyl-proline Proteins 0.000 description 1
- 229960002381 vardenafil Drugs 0.000 description 1
- 208000037820 vascular cognitive impairment Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000003038 vasopressin antagonist Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229950008314 veliflapon Drugs 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229950005018 vericiguat Drugs 0.000 description 1
- 229950005577 vesnarinone Drugs 0.000 description 1
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 1
- 229960005318 vigabatrin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 206010047470 viral myocarditis Diseases 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019143 vitamin K2 Nutrition 0.000 description 1
- 239000011728 vitamin K2 Substances 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 229960002263 vortioxetine Drugs 0.000 description 1
- YQNWZWMKLDQSAC-UHFFFAOYSA-N vortioxetine Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 YQNWZWMKLDQSAC-UHFFFAOYSA-N 0.000 description 1
- 229940070141 voxelotor Drugs 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
- 229960001522 ximelagatran Drugs 0.000 description 1
- 229960000537 xipamide Drugs 0.000 description 1
- MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 1
- 229950007802 zidometacin Drugs 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
- 229960002769 zofenopril Drugs 0.000 description 1
- IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
- WFPIAZLQTJBIFN-DVZOWYKESA-N zuclopenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(Cl)=CC=C2SC2=CC=CC=C2/1 WFPIAZLQTJBIFN-DVZOWYKESA-N 0.000 description 1
- 229960004141 zuclopenthixol Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本發明係關於可溶性鳥苷酸環化酶(sGC)之刺激劑、其醫藥學上可接受之鹽及包含其之醫藥調配物以及其單獨或與一或多種額外藥劑組合用於治療各種疾病之用途,其中一氧化氮(NO)之濃度增加及/或環單磷酸鳥苷(cGMP)之濃度增加或兩者,或NO路徑之上調為適宜的。在一些實施例中,該等化合物為表I之彼等化合物或其醫藥學上可接受之鹽。
Description
本發明係關於作為可溶性鳥苷酸環化酶(sGC)之刺激劑的化合物及其醫藥學上可接受之鹽。其亦係關於包含其之醫藥調配物及劑型以及其單獨或與一或多種額外藥劑組合用於治療各種疾病之用途。其為將得益於sGC刺激或一氧化氮(NO)及/或環單磷酸鳥苷(cGMP)之濃度增加的疾病。
sGC為用於活體內之NO的主要受體。在結合至sGC後,NO活化其催化域且使得鳥苷-5'-三磷酸酯(GTP)轉化成第二傳訊者cGMP。增加量之cGMP又調節包括蛋白激酶、磷酸二酯酶(PDE)及離子通道之下游效應物之活性。在體內,NO藉由各種一氧化氮合成酶(NOS)及藉由無機硝酸鹽之循序還原由精胺酸及氧合成。實驗及臨床跡象指示,NO濃度降低、NO生物可用性降低及/或內源性產生之NO的反應降低促成眾多疾病之發展。sGC刺激劑為sGC酶之血紅素依賴性促效劑,其與不同量之NO協同作用以提高其GTP至cGMP之酶促轉化。sGC刺激劑與已知為sGC活化劑之sGC之另一類別之NO非依賴性、血紅素非依賴性促效劑清楚地相互區分且在結構上不相關。
改良或恢復sGC之功能的療法提供優於現有替代療法之相當大的優點,該等替代療法靶向路徑或以其他方式得益於NO-sGC-cGMP路徑之上調。迫切需要研發出針對具有功能異常NO-sGC-cGMP路徑之患者的新穎且安全的療法。
本發明係基於發現本文所揭示之化合物為sGC刺激劑。具有相關結構特點,特定言之嘧啶環上具有4-OH取代基之化合物先前僅已知為可用於製備嘧啶環上具有4-胺基取代基之sGC刺激劑的合成中間物。出乎意料地發現本發明之化合物具有較強的sGC刺激活性。在一第一態樣中,本發明係關於表I或式I之sGC刺激劑化合物及其醫藥學上可接受之鹽。
表 I. 本發明之例示性 sGC 刺激劑。
在一第二態樣中,本發明係關於醫藥組合物,其包含表I、式I之化合物或其醫藥學上可接受之鹽及至少一種醫藥學上可接受之賦形劑或載劑。
在一第三態樣中,本發明係關於一種治療有需要個體之疾病的方法,其包含單獨或以組合療法形式向該個體投與治療有效量之表I、式I之化合物或其醫藥學上可接受之鹽或其藥物組合物;其中該疾病為將得益於sGC刺激或NO及/或cGMP之濃度增加的疾病。亦提供表I、式I之化合物或其醫藥學上可接受之鹽或其醫藥組合物的用途,其用於製造用於治療有需要個體之疾病的藥劑,其中該疾病為將得益於sGC刺激或NO及/或cGMP之濃度增加的疾病。在某些實施例中,本發明係關於表I之化合物或其醫藥學上可接受之鹽或其醫藥組合物,其用於治療有需要個體之疾病,其中該疾病為將得益於sGC刺激或NO及/或cGMP之濃度增加的疾病。
相關申請案
本申請案主張2021年4月20日申請之美國臨時申請案第63/177,020號及2021年8月4日申請之美國臨時申請案第63/229,248號之優先權益。上文提及之申請案中之每一者的全部內容以引用的方式併入本文中。
現將詳細參考本發明之某些實施例,其實例在隨附結構及式中說明。雖然本發明將結合所列舉之實施例描述,但應瞭解其不欲將本發明限於彼等實施例。相反地,本發明意欲涵蓋所有替代方案、修改及等效物,其可包括在申請專利範圍所界定之本發明範疇內。本發明不限於本文所描述之方法及材料,但包括類似於或等效於可用於本發明之實踐之本文所描述之彼等方法及材料的任何方法及材料。在所併入之文獻參考、專利或類似材料中之一或多者(包括但不限於經定義之術語、術語用法、所描述之技術等)與本申請案不同或抵觸的情況下,以本申請案為準。
定義及通用術語 出於本發明之目的,化學元素係根據元素週期表,CAS版,及Handbook of Chemistry and Physics,第75版,1994來鑑別。另外,有機化學之一般原理描述於「Organic Chemistry」, Thomas Sorrell, University Science Books, Sausalito: 1999及「March's Advanced Organic Chemistry」, 第5版, Smith, M.B.及March, J.編, John Wiley & Sons,New York: 2001中,其全部內容以引用之方式併入本文中。
除非另外陳述,否則本發明化合物之所有互變異構形式亦處於本發明之範疇內。
在一個實施例中,本發明可包括用氘(亦即
2H)置換氫,如此可得到由更大代謝穩定性帶來之某些治療優勢(例如,活體內半衰期延長或劑量需求降低)且因此在一些情況下可為較佳的。經氘標記之本發明化合物大體上可藉由以下類似於下文之流程及/或實例中揭示之彼等程序的程序,藉由用未經氘化之試劑取代經氘化試劑來製備。
如本文中所使用,術語「鹵素」或「鹵基」意謂F(氟)、Cl(氯)、Br(溴)或I(碘)中之任一者。
術語「羥基(hydroxyl/hydroxy)」係指-OH。
如本文中所使用,術語「烷基」係指飽和未分支(例如,直鏈)或分支鏈單價烴基。C
x烷基為含有x個碳原子之烷基鏈,其中x為不同於0之整數。「C
x-y烷基」(其中x及y為兩個不同整數,兩者均不同於0)為含有數目介於x與y之間(包括端點)的碳原子之烷基鏈。舉例而言,C
1-6烷基為如上文所定義之含有介於1與6之間的任何數目之碳原子的烷基。烷基之實例包括(但不限於)甲基(亦即C
1烷基)、乙基(亦即C
2烷基)、正丙基(C
3烷基)、異丙基(不同的C
3烷基)、正丁基、異丁基、二級丁基、三級丁基、戊基、己基、庚基、辛基及其類似者。
如本文中所使用,術語「氟烷基」係指如上文所定義之烷基,其中在烷基之任一個或多個碳原子處,連接至鏈碳原子之氫原子中之一或多者已經氟置換。舉例而言,經1至3個氟原子取代之氟烷基為其中在烷基鏈之同一碳原子或不同碳原子上的任何位置處的1至3個氫原子已經氟原子置換的烷基。
本發明之化合物在本文中藉由其化學結構及/或化學名稱定義。在藉由化學結構與化學名稱提及化合物且化學結構與化學名稱衝突時,化學結構決定化合物之身分。
化合物 / 組合物實施例 本發明之第一實施例為表I之化合物或其醫藥學上可接受之鹽。
在一第七實施例中,本發明之化合物為化合物I-14或其醫藥學上可接受之鹽。在一個實施例中,化合物I-14之醫藥學上可接受之鹽為鈉鹽。在另一實施例中,本發明之化合物為由下式表示之化合物I-14之鈉鹽:
。
在一第八實施例中,本發明之化合物為化合物I-20或其醫藥學上可接受之鹽。在一個實施例中,化合物I-20之醫藥學上可接受之鹽為鈉鹽。在另一實施例中,本發明之化合物為由下式表示之化合物I-20之鈉鹽:
。
在一第九實施例中,本發明之化合物係以式I表示:
;
或其醫藥學上可接受之鹽,其中:
J
C係選自由以下組成之群:氫、鹵素、C
1-6烷基及經1至3個氟原子取代之C
1-6氟烷基;
X為N或C(J
C1);
J
C1係選自由以下組成之群:氫、鹵素、C
1-6烷基及經1至3個氟原子取代之C
1-6氟烷基;
各J
B獨立地選自由以下組成之群:氫、鹵素、C
1-6烷基及經1至3個氟原子取代之C
1-6氟烷基;
J
D係選自由以下組成之群:氫、鹵素、C
1-6烷基及經1至3個氟原子取代之C
1-6氟烷基;及
n為選自0、1、2、3或4之整數,限制條件為該化合物不為以下中之一者:
,
或其醫藥學上可接受之鹽。
在一第十實施例中,對於第九實施例中描述之式I化合物,變數定義如下:
J
C係選自由以下組成之群:氫、鹵素及C
1-6烷基;
X為N或C(J
C1);
J
C1係選自由以下組成之群:氫、鹵素及C
1-6烷基;
各J
B係獨立地選自由以下組成之群:氫、鹵素及C
1-6烷基;
J
D係選自由以下組成之群:氫、鹵素及C
1-6烷基;及
n為選自0、1、2、3或4之整數,限制條件為該化合物不為以下中之一者:
,
或其醫藥學上可接受之鹽。在一些實施例中,各J
B係獨立地選自由鹵素及C
1-6烷基組成之群。
在一第十一實施例中,對於式I化合物,n為選自1、2、3或4之整數,各J
B獨立地選自由以下組成之群:鹵素、C
1-6烷基及經1至3個氟原子取代之C
1-6氟烷基,其中J
B連接之苯環的所有其他碳原子未經取代,且其餘變數如上文在第九實施例中所定義。
在一第十二實施例中,式I化合物係以式IA表示:
,
或其醫藥學上可接受之鹽,其中變數如上文針對第九、第十或第十一實施例中之式I所描述,限制條件為該化合物不為以下中之任一者:
,
或其醫藥學上可接受之鹽。
在一第十三實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為H、F、Cl、C
1-2烷基或經1至3個氟原子取代之C
1-2氟烷基;且其餘變數如第九、第十一或第十二實施例中之任一者所定義。
在一第十四實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為H、F或Cl;且其餘變數如第九至第十二實施例中之任一者所定義。
一第十五實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為H、F、甲基或經1至3個氟原子取代之氟甲基(亦即,-CH
2F、-CHF
2或CF
3);且其餘變數如第九及第十一至第十三實施例中之任一者所定義。
在一第十六實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為H;且其餘變數如第九至第十五實施例中之任一者所定義。
在一第十七實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為F、甲基或經1至3個氟原子取代之氟甲基(亦即,-CH
2F、-CHF
2或CF
3);且其餘變數如第九、第十一至第十三、及第十五實施例中之任一者所定義。
在一第十八實施例中,對於根據第十三、第十五或第十七實施例的式I或式IA之化合物,C
1-2氟烷基或氟甲基經一個氟原子取代。
在一第十九實施例中,對於根據第十三、第十五或第十七實施例之式I或式IA之化合物,C
1-2氟烷基或氟甲基經兩個氟原子取代。
在一第二十實施例中,對於根據第十三、第十五或第十七實施例之式I或式IA之化合物,C
1-2氟烷基或氟甲基經三個氟原子取代。
在一第二十一實施例中,對於式I或式IA之化合物或其醫藥學上可接受之鹽,J
C1為F或H;且其餘變數如第九至第十二實施例中之任一者所定義。
在一第二十三實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2或3,且其餘變數如第九至第二十二實施例中之任一者所描述。在一些實施例中,n為2。在其他實施例中,n為3。
在一第二十四實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為0或1,且其餘變數如第九至第二十二實施例中之任一者所描述。在一些實施例中,n為1。
在一第二十五實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,各J
B獨立地為H、F、C
1-4烷基或經1至3個氟原子取代之C
1-4氟烷基;且其餘變數如第九至第二十四實施例中之任一者所描述。
在一第二十六實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,各J
B獨立地為H、F或C
1-4烷基;且其餘變數如第九至第二十四實施例中之任一者所描述。
在一第二十七實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2或3;各J
B獨立地為F、甲基或經1至3個氟原子取代之氟甲基;且其餘變數如第九至第二十三實施例中之任一者所描述。
在一第二十八實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2或3;各J
B獨立地為F或甲基;且其餘變數如第九至第二十三實施例中之任一者所描述。
在一第二十九實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2或3;各J
B獨立地為F、乙基或經1至3個氟原子取代之氟乙基;且其餘變數如第九至第二十三實施例中之任一者所描述。
在一第三十實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2;J
B均為F或J
B中之一者為F且另一者為甲基或經1至3個氟原子取代之氟甲基;且其餘變數如第九至第二十三實施例中之任一者所描述。在一些實施例中,一個J
B為F且另一者為甲基或經1至3個原子取代之氟甲基。在另其他實施例中,一個J
B為F且另一者為甲基。在又其它實施例中,一個J
B為F且另一者為氟甲基。在一些實施例中,氟甲基經一個氟原子取代(亦即,-CH
2F)。在其他實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。
在一第三十一實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為2;J
B均為F或J
B中之一者為F且另一者為乙基或經1至3個氟原子取代之氟乙基;且其餘變數如第九至第二十三實施例中之任一者所描述。在一些實施例中,一個J
B為F且另一者為乙基或經1至3個原子取代之氟乙基。在另其他實施例中,一個J
B為F且另一者為乙基。在又其它實施例中,一個J
B為F且另一者為氟乙基。在一些實施例中,氟乙基經一個氟原子取代。在其他實施例中,氟乙基經兩個氟原子取代且在其他實施例中,氟乙基經三個氟原子取代。
在一第三十二實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為3;J
B之三個實例為F或J
B中之兩者為F且另一者為甲基或經1至3個氟原子取代之氟甲基;且其餘變數如第九至第二十三實施例中之任一者所描述。在一些實施例中,氟甲基經一個氟原子取代(亦即,-CH
2F)。在其他實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。在一些實施例中,兩個J
B為F且另一者為甲基。
在一第三十三實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為3;J
B之三個實例為F或J
B中之兩者為F且另一者為乙基或經1至3個氟原子取代之氟乙基;且其餘變數如第九至第二十三實施例中之任一者所描述。在一些實施例中,氟乙基經一個氟原子取代。在其他實施例中,氟乙基經兩個氟原子取代且在其他實施例中,氟乙基經三個氟原子取代。
在一第三十四實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為1;J
B為F、甲基、乙基、氟甲基或氟乙基;且其餘變數如第九至第二十二實施例中之任一者所描述。在一些實施例中,氟甲基經一個氟原子取代(亦即,-CH
2F)。在其他實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。在一些實施例中,氟乙基經一個氟原子取代。在其他實施例中,氟乙基經兩個氟原子取代且在其他實施例中,氟乙基經三個氟原子取代。
在一第三十五實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為1;J
B為F;且其餘變數如第九至第二十二實施例中之任一者所描述。
在一第三十六實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,n為0;且其餘變數如第九至第二十二實施例所描述。
在一第三十七實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
D為H、F、Cl、甲基、乙基或氟甲基或氟乙基,其中該氟甲基或氟乙基經1至3個氟原子取代;且其餘變數如第九至第三十六實施例中之任一者所描述。在一些實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。在其他實施例中,氟乙基經一個氟原子取代。在其他實施例中,氟乙基經兩個氟原子取代且在其他實施例中,氟乙基經三個氟原子取代。
在一第三十八實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
D為H或F,且全部其他變數如第九至第三十七實施例中之任一者所定義。在一些實施例中,J
D為F。在一些實施例中,J
D為H。
在一第三十九實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
D為氫;且其餘變數如第九至第三十七實施例中之任一者所描述。
在一第四十實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
D為F;且其餘變數如第九至第三十七實施例中之任一者所描述。
在一第四十一實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
C為H、Cl、F、甲基、乙基、經1至3個氟原子取代之氟乙基或氟甲基;且其餘變數如第九至第四十實施例中之任一者所描述。在一些實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。在其他實施例中,氟乙基經一個氟原子取代。在其他實施例中,氟乙基經兩個氟原子取代且在其他實施例中,氟乙基經三個氟原子取代。
在一第四十二實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
C為H、Cl或F;且其餘變數如第九第四十第四十實施例中之任一者所描述。
在一第四十三實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
C為H、F、甲基或氟甲基;且其餘變數如第九至第四十實施例中之任一者所描述。在一些實施例中,氟甲基經兩個氟原子取代(亦即,-CHF
2)且在其他實施例中,氟甲基經三個氟原子取代(亦即,-CF
3)。
在一第四十四實施例中,對於式I、IA或IB之化合物或其醫藥學上可接受之鹽,J
C為H或F;且其餘變數如第九至第四十實施例中之任一者所描述。在一些實施例中,J
C為H。
在一第四十五實施例中,本發明之化合物為以式IC表示之化合物:
,
或其醫藥學上可接受之鹽,其中X為N或C(J
C1),其中當X為C(J
C1)時,其由下表中之C表示;且變數X、J
C1及J
B之定義描述於下表中;另外其中Me表示甲基且Me-F表示經1至3個氟原子取代之氟化甲基(亦即,-CH
2F、-CHF
2或CF
3):
化合物編號 | J B 於 苯環上之位置及J B 定義 | X | J C1 | ||||
2 | 3 | 4 | 5 | 6 | |||
I-27 | F | C | F | ||||
I-28 | F | C | H | ||||
I-29 | F | N | - | ||||
I-30 | F | C | F | ||||
I-31 | F | F | C | F | |||
I-32 | F | F | C | H | |||
I-33 | F | F | N | - | |||
I-34 | F | F | C | F | |||
I-35 | F | F | C | H | |||
I-36 | F | F | N | - | |||
I-37 | F | F | C | F | |||
I-38 | F | F | C | H | |||
I-39 | F | F | N | - | |||
I-40 | F | F | C | F | |||
I-41 | F | F | C | F | |||
I-42 | F | F | C | H | |||
I-43 | F | F | N | - | |||
I-44 | F | F | C | F | |||
I-45 | F | Me | C | H | |||
I-46 | F | Me | N | - | |||
I-47 | F | Me | C | F | |||
I-48 | Me | F | C | H | |||
I-49 | Me | F | N | - | |||
I-50 | Me | F | C | F | |||
I-51 | F | Me | C | H | |||
I-52 | F | Me | N | - | |||
I-53 | F | Me | C | F | |||
I-54 | Me | F | C | H | |||
I-55 | Me | F | N | - | |||
I-56 | Me | F | C | F | |||
I-57 | F | Me | C | H | |||
I-58 | F | Me | C | F | |||
I-59 | F | Me | N | - | |||
I-60 | Me | F | C | H | |||
I-61 | Me | F | C | F | |||
I-62 | Me | F | N | - | |||
I-63 | F | Me | C | H | |||
I-64 | F | Me | N | - | |||
I-65 | F | Me | C | F | |||
I-66 | Me | F | C | H | |||
I-67 | Me | F | N | - | |||
I-68 | Me | F | C | F | |||
I-69 | F | Me | N | - | |||
I-70 | F | Me | C | F | |||
I-71 | Me | F | C | H | |||
I-72 | Me | F | N | - | |||
I-73 | Me | F | C | F | |||
I-74 | F | Me | C | H | |||
I-75 | F | Me | N | - | |||
I-76 | F | Me | C | F | |||
I-77 | Me | F | C | H | |||
I-78 | Me | F | N | - | |||
I-79 | Me | F | C | F | |||
I-80 | Me | F | C | H | |||
I-81 | Me | F | N | - | |||
I-82 | Me | F | C | F | |||
I-83 | F | Me | C | H | |||
I-84 | F | Me | N | - | |||
I-85 | F | Me | C | F | |||
I-86 | F | F | Me | C | H | ||
I-87 | F | F | Me | N | - | ||
I-88 | F | F | Me | C | F | ||
I-89 | F | F | Me | C | H | ||
I-90 | F | F | Me | N | - | ||
I-91 | F | F | Me | C | F | ||
I-92 | F | F | Me | C | H | ||
I-93 | F | F | Me | N | - | ||
I-94 | F | F | Me | C | F | ||
I-95 | F | Me | F | C | H | ||
I-96 | F | Me | F | N | - | ||
I-97 | F | Me | F | C | F | ||
I-98 | F | F | Me | C | H | ||
I-99 | F | F | Me | N | - | ||
I-100 | F | F | Me | C | F | ||
I-101 | F | F | Me | C | H | ||
I-102 | F | F | Me | N | - | ||
I-103 | F | F | Me | C | F | ||
I-104 | F | Me | F | C | H | ||
I-105 | F | Me | F | C | F | ||
I-106 | F | Me | F | N | - | ||
I-107 | F | F | Me | C | H | ||
I-108 | F | F | Me | C | F | ||
I-109 | F | F | Me | N | - | ||
I-110 | F | Me | F | C | H | ||
I-111 | F | Me | F | N | - | ||
I-112 | F | Me | F | C | F | ||
I-113 | F | Me | F | C | H | ||
I-114 | F | Me | F | N | - | ||
I-115 | F | Me | F | C | F | ||
I-116 | Me | F | F | C | H | ||
I-117 | Me | F | F | N | - | ||
I-118 | Me | F | F | C | F | ||
I-119 | F | F | Me | C | H | ||
I-120 | F | F | Me | N | - | ||
I-121 | F | F | Me | C | F | ||
I-122 | F | F | Me | C | H | ||
I-123 | F | F | Me | N | - | ||
I-124 | F | F | Me | C | F | ||
I-125 | Me | F | F | C | H | ||
I-126 | Me | F | F | N | - | ||
I-127 | Me | F | F | C | F | ||
I-128 | F | Me | F | N | - | ||
I-129 | F | Me | F | C | F | ||
I-130 | F | Me-F | C | H | |||
I-131 | F | Me-F | N | - | |||
I-132 | F | Me-F | C | F | |||
I-133 | Me-F | F | C | H | |||
I-134 | Me-F | F | N | - | |||
I-135 | Me-F | F | C | F | |||
I-136 | F | Me-F | C | H | |||
I-137 | F | Me-F | N | - | |||
I-138 | F | Me-F | C | F | |||
I-139 | Me-F | F | C | H | |||
I-140 | Me-F | F | N | - | |||
I-141 | Me-F | F | C | F | |||
I-142 | F | Me-F | C | H | |||
I-143 | F | Me-F | C | F | |||
I-144 | F | Me-F | N | - | |||
I-145 | Me-F | F | C | H | |||
I-146 | Me-F | F | C | F | |||
I-147 | Me-F | F | N | - | |||
I-148 | F | Me-F | C | H | |||
I-149 | F | Me-F | N | - | |||
I-150 | F | Me-F | C | F | |||
I-151 | Me-F | F | C | H | |||
I-152 | Me-F | F | N | - | |||
I-153 | Me-F | F | C | F | |||
I-154 | F | Me-F | N | - | |||
I-155 | F | Me-F | C | F | |||
I-156 | F | Me-F | C | H | |||
I-157 | Me-F | F | N | - | |||
I-158 | Me-F | F | C | H | |||
I-159 | Me-F | F | C | F | |||
I-160 | F | Me-F | C | H | |||
I-161 | F | Me-F | N | - | |||
I-162 | F | Me-F | C | F | |||
I-163 | Me-F | F | C | H | |||
I-164 | Me-F | F | N | - | |||
I-165 | Me-F | F | C | F | |||
I-166 | Me-F | F | C | H | |||
I-167 | Me-F | F | N | - | |||
I-168 | Me-F | F | C | F | |||
I-169 | F | Me-F | C | H | |||
I-170 | F | Me-F | N | - | |||
I-171 | F | Me-F | C | F | |||
I-172 | F | F | Me-F | C | H | ||
I-173 | F | F | Me-F | N | - | ||
I-174 | F | F | Me-F | C | F | ||
I-175 | F | F | Me-F | C | H | ||
I-176 | F | F | Me-F | N | - | ||
I-177 | F | F | Me-F | C | F | ||
I-178 | F | F | Me-F | C | H | ||
I-179 | F | F | Me-F | N | - | ||
I-180 | F | F | Me-F | C | F | ||
I-181 | F | Me-F | F | C | H | ||
I-182 | F | Me-F | F | N | - | ||
I-183 | F | Me-F | F | C | F | ||
I-184 | F | F | Me-F | C | H | ||
I-185 | F | F | Me-F | N | - | ||
I-186 | F | F | Me-F | C | F | ||
I-187 | F | F | Me-F | C | H | ||
I-188 | F | F | Me-F | N | - | ||
I-189 | F | F | Me-F | C | F | ||
I-190 | F | Me-F | F | C | H | ||
I-191 | F | Me-F | F | C | F | ||
I-192 | F | Me-F | F | N | - | ||
I-193 | F | F | Me-F | C | H | ||
I-194 | F | F | Me-F | C | F | ||
I-195 | F | F | Me-F | N | - | ||
I-196 | F | Me-F | F | C | H | ||
I-197 | F | Me-F | F | N | - | ||
I-198 | F | Me-F | F | C | F | ||
I-199 | F | Me-F | F | C | H | ||
I-200 | F | Me-F | F | N | - | ||
I-201 | F | Me-F | F | C | F | ||
I-202 | Me-F | F | F | C | H | ||
I-203 | Me-F | F | F | N | - | ||
I-204 | Me-F | F | F | C | F | ||
I-205 | F | F | Me-F | C | H | ||
I-206 | F | F | Me-F | N | - | ||
I-207 | F | F | Me-F | C | F | ||
I-208 | F | F | Me-F | C | H | ||
I-209 | F | F | Me-F | N | - | ||
I-210 | F | F | Me-F | C | F | ||
I-211 | Me-F | F | F | C | H | ||
I-212 | Me-F | F | F | N | - | ||
I-213 | Me-F | F | F | C | F | ||
I-214 | F | Me-F | F | N | - | ||
I-215 | F | Me-F | F | C | F | ||
I-216 | F | Me-F | F | C | H |
本發明之醫藥學上可接受之鹽。 本文所描述之化合物之「醫藥學上可接受之鹽」包括由該等化合物與無機酸或有機酸或鹼混合時所得到之彼等鹽。在一些實施例中,該等鹽可在化合物之最終分離及純化期間原位製備。在其他實施例中,可在各別合成步驟中由游離形式之化合物製備鹽。上文所描述之醫藥學上可接受之鹽及其他典型醫藥學上可接受之鹽的製備更充分地描述於以全文引用之方式併入本文中之Berg等人,「Pharmaceutical Salts」,J. Pharm. Sci., 1977:66:1-19中。表I至VI中之任一者或式I之化合物的醫藥學上可接受之鹽為可用於藥品中之彼等鹽。然而,醫藥學上不可接受之鹽可適用於製備表I至VI或式I之化合物或其醫藥學上可接受之鹽。
當本文中所描述之化合物(例如,表I至VI之化合物或以式I表示之化合物)為酸性時,適合之「醫藥學上可接受之鹽」係指由包括無機及有機鹼之醫藥學上可接受之無毒性鹼製備的鹽。衍生自無機鹼之鹽包括鋁鹽、銨鹽、鈣鹽、銅鹽、鐵鹽、亞鐵鹽、鋰鹽、鎂鹽、三價錳鹽、二價錳鹽、鉀鹽、鈉鹽、鋅鹽及類似鹽。特定實施例包括銨鹽、鈣鹽、鎂鹽、鉀鹽及鈉鹽。衍生自醫藥學上可接受之有機無毒性鹼的鹽包括一級、二級及三級胺之鹽,包括天然存在的經取代之胺、環胺、、精胺酸、甜菜鹼、咖啡鹼、膽鹼、N,N
1-二苯甲基乙二胺、二乙胺、2-二乙胺基乙醇、2-二甲胺基乙醇、乙醇胺、乙二胺、N-乙基𠰌啉、N-乙基哌啶、還原葡糖胺、葡糖胺、組胺酸、海卓胺、異丙胺、離胺酸、甲基葡糖胺、𠰌啉、哌𠯤、哌啶、多元胺樹脂、普魯卡因(procaine)、嘌呤、可可豆鹼、三乙胺、三甲胺、三丙胺、緩血酸胺及其類似物。
在一些實施例中,本發明之化合物具有能夠與鹼(例如,醫藥學上可接受之無毒性鹼)反應以形成鹽(例如,醫藥學上可接受之鹽)的酸性OH基團。在一些實施例中,鹽為銨鹽、鈣鹽、鎂鹽、鉀鹽或鈉鹽。在一些實施例中,鹽為鈉鹽。
當本文中所描述之化合物(例如,表I至VI之化合物或以式I表示之化合物)為鹼時,能夠以醫藥學上可接受之無毒性酸(包括無機及有機酸)製備鹽。此類酸包括乙酸根、乙酸、酸式檸檬酸根、酸式磷酸根、抗壞血酸根、苯磺酸、苯磺酸根、苯甲酸、苯甲酸根、溴化物、硫酸氫根、酒石酸氫根、樟腦磺酸、氯離子、檸檬酸根、檸檬酸、乙磺酸根、乙磺酸、甲酸根、反丁烯二酸根、反丁烯二酸、龍膽酸根、葡糖酸根、葡糖酸、葡糖醛酸根、麩胺酸根、麩胺酸、氫溴酸、氫氯酸、碘離子、羥乙基磺酸、異菸鹼酸根、乳酸根、乳酸、順丁烯二酸根、順丁烯二酸、蘋果酸、杏仁酸、甲磺酸、甲磺酸根、黏液酸、硝酸根、硝酸、油酸根、草酸根、撲酸、雙羥萘酸根(亦即,1,1'-亞甲基-雙-(2-羥基-3-萘甲酸根))、泛酸、泛酸根、磷酸根、磷酸、葡糖二酸根、水楊酸根、丁二酸、丁二酸根、硫酸、硫酸根、丹寧酸根、酒石酸根、酒石酸、對甲苯磺酸根、對甲苯磺酸及類似者。特定實施例包括檸檬酸、氫溴酸、鹽酸、順丁烯二酸、磷酸、硫酸及酒石酸。
除了本文所描述之化合物以外,其醫藥學上可接受之鹽亦可用於組合物中以治療或預防本文中所鑑別之疾病。
醫藥組合物及投藥方法。 在一第二態樣中,本發明係關於醫藥組合物,其包含本文中所描述之化合物(例如,表I至VI之化合物或以式I表示之化合物,或其醫藥學上可接受之鹽)及至少一種醫藥學上可接受之賦形劑或載劑。
在一些實施例中,本發明之醫藥組合物包含根據如第一、第二、第三、第四、第五、第六、第七、第八、第九、第十、第十一、第十二、第十三、第十四、第十五、第十六、第十七、第十八、第十九、第二十、第二十一、第二十二、第二十三、第二十四、第二十五、第二十六、第二十七及第二十八實施例中中之任一者所描述的化合物或其醫藥學上可接受之鹽,及至少一種醫藥學上可接受之賦形劑或載劑。
本文所揭示之化合物及其醫藥學上可接受之鹽可調配為醫藥組合物或「調配物」。
藉由將本文中所描述之化合物(例如,表I至VI之化合物或以式I表示之化合物或其醫藥學上可接受之鹽)與載劑、稀釋劑或賦形劑混合來製備典型調配物。適合載劑、稀釋劑及賦形劑為熟習此項技術者所熟知,且包括諸如碳水化合物、蠟、水溶性及/或可膨脹聚合物、親水性或疏水性物質、明膠、油、溶劑、水及其類似物之物質。特定載劑、稀釋劑或賦形劑將視調配本文中所描述之化合物(例如,表I至VI之化合物或以式I表示之化合物或其醫藥學上可接受之鹽)的方式及目的而使用。一般基於熟習此項技術者公認為投與給哺乳動物安全(GRAS-一般視為安全(Generally Regarded as Safe))之溶劑選擇溶劑。一般而言,安全溶劑為無毒水性溶劑,諸如水及可溶於水或可混溶於水之其他無毒溶劑。適合之水性溶劑包括水、乙醇、丙二醇、聚乙二醇(例如PEG400、PEG300)等及其混合物。調配物亦可包括其他類型之賦形劑,諸如一或多種緩衝劑、穩定劑、抗黏劑、界面活性劑、濕潤劑、潤滑劑、乳化劑、黏合劑、懸浮劑、崩解劑、填充劑、吸附劑、包衣(例如腸溶性或緩慢釋放)、防腐劑、抗氧化劑、避光劑、助流劑、加工助劑、著色劑、甜味劑、芳香劑、調味劑及用於提供藥物之精緻呈現(亦即,表I至VI之化合物、以式I表示之化合物或其醫藥組合物)或幫助製造醫藥產物(亦即,藥劑)之其他已知添加劑。
可接受之稀釋劑、載劑、賦形劑及穩定劑為在所採用之劑量及濃度下對接受者無毒待彼等物質,且包括緩衝液,諸如磷酸鹽、檸檬酸鹽及其他有機酸;抗氧化劑,包括抗壞血酸及甲硫胺酸;防腐劑(諸如十八烷基二甲基苯甲基氯化銨;氯化六羥季銨;苯紮氯銨、氯化苯索銨;苯酚、丁醇或苯甲醇;對羥苯甲酸烷酯,諸如對羥基苯甲酸甲酯或對羥基苯甲酸丙酯;兒茶酚;間苯二酚;環己醇;3-戊醇;及間甲酚);蛋白質,諸如血清白蛋白、明膠或免疫球蛋白;親水性聚合物,諸如聚乙烯吡咯啶酮;胺基酸,諸如甘胺酸、麩醯胺酸、天冬醯胺、組胺酸、精胺酸或離胺酸;單醣、雙醣及其他碳水化合物,包括葡萄糖、甘露糖或糊精;螯合劑,諸如EDTA;糖,諸如蔗糖、甘露醇、海藻糖或山梨醇;成鹽相對離子,諸如鈉;金屬錯合物(例如,Zn-蛋白質錯合物);及/或非離子界面活性劑,諸如TWEEN
TM、PLURONICS
TM或聚乙二醇(PEG)。亦可例如藉由凝聚技術或藉由界面聚合將活性醫藥成分包埋於所製備之微膠囊中,例如羥基甲基纖維素或明膠微膠囊及聚-(甲基丙烯酸甲酯)微膠囊分別包埋於膠狀藥物傳遞系統(例如脂質體、白蛋白微球體、微乳液、奈米粒子及奈米囊劑)中或於巨乳液中。此類技術揭示於Remington's: The Science and Practice of Pharmacy,第21版, University of the Sciences in Philadelphia, 2005版(下文之「Remington's」)中。
調配物可使用習知溶解及混合程序製備。
如本文所使用,術語「治療有效量」意謂在組織、系統、動物或人類中引起研究人員、獸醫、醫生或其他臨床醫師所尋求之生物或藥物反應之活性化合物或醫藥劑的量。待投與之化合物之治療有效量將由此類考慮因素決定,且為改善、治癒或治療疾病或其症狀中之一或多者所需的最少量。
關於本發明之化合物、組合物或劑型的術語「投與(administer/administering/administration)」意謂將化合物、組合物或劑型引入至個體或需要治療之患者之系統中。當本發明之化合物與一或多種其他活性劑組合提供時,「投與」及其變化形式各自理解為包括同時及/或依序引入化合物、組合物或劑型及其他活性劑。
視待治療之疾病之嚴重程度及類型而定,本文所描述之組合物可全身性或局部投與,例如經口(包括但不限於固體劑型,包括硬或軟膠囊(例如明膠膠囊)、錠劑、丸劑、粉劑、舌下錠劑、糖衣錠、口含劑及顆粒劑;及液體劑型,包括但不限於醫藥學上可接受之乳液、微乳液、水性或油性溶液、懸浮液、糖漿及酏劑;藉由吸入(例如利用氣溶膠、氣體、吸入器、噴霧器或其類似者);經耳(例如使用滴耳劑);體表(例如使用乳霜、凝膠、吸入劑、擦劑、洗劑、軟膏、貼片、糊劑、粉劑、溶液、噴霧、經皮貼片等);經眼(例如利用滴眼劑、經眼凝膠、經眼軟膏);經直腸(例如使用灌腸劑或栓劑);經鼻;經頰;經陰道(例如使用沖洗劑、子宮內裝置、經陰道栓劑、陰道環或錠劑等);經由滴耳劑;經由植入式貯器或其類似者;或非經腸。如本文所使用,術語「非經腸」包括(但不限於)皮下、靜脈內、肌肉內、關節內、滑液內、胸骨內、鞘內、肝內、病灶內及顱內注射或輸注技術。較佳地,組合物經口、腹膜內或靜脈內投與。
意欲用於經口使用之化合物之調配物可根據此項技術已知用於製造醫藥組合物之任何方法來製備。
在固體劑型中,活性化合物與以下各者混合:至少一種惰性、醫藥學上可接受之賦形劑或載劑,諸如檸檬酸鈉或磷酸二鈣及/或a)填充劑或增量劑,諸如澱粉、乳糖、蔗糖、葡萄糖、甘露醇及矽酸,b)黏合劑,諸如羧甲基纖維素、海藻酸鹽、明膠、聚乙烯吡咯啶酮、蔗糖及阿拉伯膠;c)保濕劑,諸如甘油,d)崩解劑,諸如瓊脂-瓊脂、碳酸鈣、馬鈴薯或木薯澱粉、褐藻酸、某些矽酸鹽及碳酸鈉,e)阻溶劑,諸如石蠟,f)吸收促進劑,諸如四級銨化合物,g)濕潤劑,諸如鯨蠟醇及單硬脂酸甘油酯,h)吸收劑,諸如高嶺土及膨潤土,及/或i)潤滑劑,諸如滑石、硬脂酸鈣、硬脂酸鎂、固態聚乙二醇、月桂基硫酸鈉及其混合物。錠劑可未包覆包衣,或可藉由已知技術經塗佈,包括微囊封裝以掩蔽不適味道或以延緩在胃腸道中之崩解及吸收及/或在更長週期內提供持續作用。舉例而言,可單獨或與蠟一起使用諸如單硬脂酸甘油酯或二硬脂酸甘油酯之延時材料。可採用水溶性味覺掩蔽材料,諸如羥丙基-甲基纖維素或羥丙基-纖維素。
除活性化合物之外,液體劑型可含有此項技術中常用之惰性稀釋劑,諸如水或其他溶劑;增溶劑及乳化劑,諸如乙醇、異丙醇、碳酸乙酯、乙酸乙酯、苯甲醇、苯甲酸苯甲酯、丙二醇、1,3-丁二醇、二甲基甲醯胺、油(尤其棉籽油、花生油、玉米油、胚芽油、橄欖油、蓖麻油及芝麻油)、甘油、四氫糠醇、聚乙二醇及脫水山梨糖醇之脂肪酸酯;及其混合物。除惰性稀釋劑之外,經口組合物亦可包括佐劑,諸如濕潤劑、乳化劑及懸浮劑、甜味劑、調味劑及芳香劑。
經口組合物(固體或液體)亦可包括賦形劑及佐劑,諸如分散劑或濕潤劑,諸如天然存在之磷脂(例如卵磷脂);環氧烷與脂肪酸之縮合產物(例如聚氧乙烯硬脂酸酯)、環氧乙烷與長鏈脂族醇之縮合產物(例如十七伸乙基氧基十六醇)、環氧乙烷與來源於脂肪酸及己醣醇酸酐之部分酯的縮合產物(例如聚氧乙烯脫水山梨糖醇單油酸酯);乳化劑及懸浮劑,諸如羧甲基纖維素鈉、交聯羧甲纖維素、聚維酮、甲基纖維素、羥丙基甲基纖維素、海藻酸鈉、聚乙烯吡咯啶酮、黃蓍膠及阿拉伯膠;甜味劑、調味劑及芳香劑;及/或一或多種防腐劑,諸如對羥基苯甲酸乙酯或對羥基苯甲酸正丙酯;一或多種著色劑;一或多種調味劑;及一或多種甜味劑,諸如蔗糖或糖精。
醫藥組合物亦可藉由經鼻氣溶膠或吸入投與。此類組合物係根據醫藥調配技術中熟知之技術製備,且可使用苯甲醇或其他適合的防腐劑、增強生物可用性之吸收促進劑、碳氟化合物及/或其他習知溶解劑或分散劑製備成於生理食鹽水中之溶液。適用於肺內或經鼻投與之調配物的粒徑例如在0.1微米至500微米範圍內(包括0.1微米至500微米範圍內以諸如0.5微米、1微米、30微米、35微米等微米數遞增之粒子),其藉由經鼻腔快速吸入或藉由經口吸入從而到達肺泡小囊來投與。
本文所描述之醫藥組合物亦可局部投與,尤其當治療目標包括藉由局部施用容易達到之區域或器官(包括眼睛、耳部、皮膚或低位腸道之疾病)時。容易製備適合的局部調配物用於此等區域或器官中之每一者。活性組分係在無菌條件下與醫藥學上可接受之載劑及如可為所需之任何所需防腐劑或緩衝劑摻合。
為了局部塗覆,醫藥組合物可以含有懸浮或溶解於一或多種載劑中之活性組分之適合軟膏形式調配。用於本發明化合物之局部投與的載劑包括(但不限於)礦物油、液體石蠟脂、白石蠟脂、丙二醇、聚氧乙烯、聚氧丙烯化合物、乳化蠟及水。替代地,醫藥組合物可以含有懸浮或溶解於一或多種醫藥學上可接受之載劑中之活性組分之適合乳液或乳膏形式調配。適合之載劑包括但不限於礦物油、脫水山梨糖醇單硬脂酸酯、聚山梨醇酯60、十六基酯蠟、鯨蠟硬脂醇、2-辛基十二醇、苯甲醇及水。
替代地,活性成分可與水包油乳膏基劑一起調配成乳膏。必要時,乳膏基劑之水相可包括多元醇,亦即,具有兩個或更多個羥基之醇,諸如丙二醇、丁烷1,3-二醇、甘露醇、山梨糖醇、丙三醇及聚乙二醇(包括PEG 400)及其混合物。表面調配物宜可包括提高活性成分經由皮膚或其他受影響區域吸收或滲透之化合物。該等經皮滲透增強劑之實例包括二甲亞碸及相關類似物。
使用表I至VI或式I之化合物製備之乳液之油相可以已知方式由已知成分構成。儘管該相可僅包含乳化劑(或稱為利泄劑),但其宜包含至少一種乳化劑與脂肪或油或與脂肪及油兩者之混合物。親水性乳化劑可與充當穩定劑之親脂性乳化劑一起包括在內。在一些實施例中,乳化劑包括油及脂肪兩者。乳化劑與穩定劑一起或不與穩定劑一起構成所謂的乳化蠟,且蠟與油及脂肪一起構成所謂的乳化軟膏基劑,其形成乳膏調配物之油性分散相。適用於表I至VI或式I之化合物之調配物的利泄劑及乳液穩定劑包括Tween
TM-60、Span
TM-80、鯨蠟硬脂醇、苯甲醇、肉豆蔻醇、單硬脂酸甘油酯及月桂基硫酸鈉。
另外,本發明涵蓋使用經皮貼片,其具有向身體提供控制遞送化合物之附加優點。此類劑型可藉由將化合物溶解或分配於適當介質中來製備。亦可使用吸收強化劑來增加化合物之透皮量。可藉由提供速率控制膜或藉由將化合物分散於聚合物基質或凝膠中來控制速率。
對於經眼使用,醫藥組合物可調配為於等張性pH調節無菌生理鹽水中之微米尺寸化懸浮液,或較佳為於等張性pH調節無菌生理鹽水中之溶液,其具有或不具有防腐劑(諸如氯苄烷銨)。替代地,對於經眼使用,醫藥組合物可以軟膏(諸如石蠟脂)形式調配。對於治療眼睛或其他外部組織(例如口部及皮膚),調配物可以含有例如0.075至20% w/w之量的活性成分的局部軟膏或乳膏形式塗覆。當調配成軟膏時,活性成分可與油基石蠟或水可混溶性軟膏基劑一起使用。
用於經直腸或經陰道投與之組合物較佳為栓劑,其可藉由將本文所描述之化合物與適合的無刺激性賦形劑或載劑(諸如可可脂、蜂蠟、聚乙二醇或栓劑蠟,其在環境溫度下為固體,但在體溫下為液體,且因此在直腸或陰道腔室中熔融且釋放活性化合物)混合來製備。適合於經陰道投與之其他調配物可以子宮托、棉塞、乳霜、凝膠、膏體、發泡體或噴霧形式呈現。
本文所描述之組合物之無菌可注射形式(例如用於非經腸投與)可為水性或油性懸浮液。此等懸浮液可根據此項技術中已知之技術,使用適合的分散劑或濕潤劑及懸浮劑(包括先前段落中所描述之彼等者)調配。無菌可注射製劑亦可為於無毒非經腸可接受之稀釋劑或溶劑中之無菌可注射溶液或懸浮液,例如呈1,3-丁二醇中之溶液形式。在該等可接受之媒劑及溶劑中,可採用者為水、林格氏溶液(Ringer's solution)及等張氯化鈉溶液。另外,無菌不揮發性油習用作溶劑或懸浮介質。出於此目的,可採用任何溫和不揮發性油,包括合成單甘油酯或二甘油酯。脂肪酸(諸如油酸及其甘油酯衍生物)適用於製備呈天然醫藥學上可接受之油(諸如植物油,例如花生油、橄欖油、芝麻油或椰子油)形式之可注射劑,尤其呈其聚氧乙烯化形式或於諸如液體石蠟之礦物油中。此等油溶液或懸浮液亦可含有長鏈醇稀釋劑或分散劑,諸如羧甲基纖維素或通常用於調配醫藥學上可接受之劑型(包括乳液及懸浮液)之類似分散劑。其他常用界面活性劑(諸如Tween、Span及其他乳化劑)或常用於製造醫藥學上可接受之固體、液體或其他劑型之生物可用性增強劑亦可用於可注射調配物之目的。油性懸浮液可含有增稠劑,例如蜂蠟、硬石蠟或鯨蠟醇。可添加甜味劑(諸如上述彼等甜味劑)及調味劑,以提供可口之經口製劑。此等組合物可藉由添加抗氧化劑,諸如丁基化羥基大茴香醚或α-生育酚來保存。
在另一態樣中,表I至VI或式I之化合物或其醫藥學上可接受之鹽可調配於包含獸醫用載劑之獸醫用組合物中。獸醫用載劑為適用於投與組合物之目的之材料且可為固體、液體或以其他方式呈惰性之氣態材料。在獸醫學領域中且與活性成份相容。此等獸醫用組合物可以非經腸、經口或藉由任何其他所要途徑投與。
治療方法 在另一態樣中,本發明亦提供一種治療有需要個體之疾病的方法,其包含單獨或以組合形式向該個體投與治療有效量之表I至VI或式I之化合物或其醫藥學上可接受之鹽;其中該疾病為得益於sGC刺激或NO或cGMP或兩者之濃度增加,或NO-sGC-cGMP路徑上調的疾病。本發明亦提供一種治療有需要個體之疾病的方法,其包含單獨或以組合形式向該個體投與包含表I至VI或式I之化合物或其醫藥學上可接受之鹽的醫藥組合物或劑型,其中該疾病為得益於sGC刺激或NO或cGMP或兩者之濃度增加,或NO-sGC-cGMP路徑上調的疾病。
本發明之第十實施例為一種治療需要治療之個體之疾病的方法,其包含向需要治療之個體投與治療有效量之如第一、第二、第三、第四、第五、第六、第七或第八實施例所描述之化合物中之任一者的化合物或其醫藥學上可接受之鹽,或如第九實施例中所描述之醫藥組合物。
在一些實施例中,此處所揭示之化合物為sGC刺激劑,其可適用於預防及/或治療特徵在於NO之生物可用性及/或敏感性不合需要地降低之疾病,諸如與氧化應激或亞硝基化應激之病況相關的彼等疾病。
增加的cGMP濃度導致血管擴張、抑制血小板凝集及黏著、抗高血壓作用、抗重塑作用、抗細胞凋亡作用、抗炎性、抗纖維化作用、代謝作用、神經元信號傳遞作用及線粒體作用。因此,sGC刺激劑可用於治療及/或預防一系列疾病。
可藉由投與本發明之sGC刺激劑(例如,表I至VI或式I之化合物及其醫藥學上可接受之鹽)治療及/或預防的特定疾病或病症包括(但不限於):
β-脂蛋白缺乏症、弛緩不能(例如,食道弛緩不能)、急性呼吸窘迫症候群(ARDS)、黏黏性滑膜囊炎、年齡相關之學習及記憶紊亂、年齡相關之記憶喪失、酒精中毒、禿頭症或脫髮、高原病、阿茲海默症(Alzheimer's disease) (包括前阿茲海默症、輕度至中度阿茲海默症及中度至重度阿茲海默症)、肌萎縮性側索硬化(ALS或葛雷克氏病(Lou Gehrig's disease))、肛裂、動脈瘤、心絞痛(例如,穩定或不穩定型心絞痛、變異型心絞痛(variant angina/Prinzmetal's angina)、微血管心絞痛)、焦慮或焦慮症、精胺基琥珀酸尿症、動脈及靜脈血栓、關節炎、阿斯伯格氏症候群(Asperger's syndrome)、哮喘及哮喘疾病、共濟失調、毛細血管擴張、動脈粥樣硬化(例如,與內皮損傷、血小板及單核球黏附及聚集、平滑肌增殖或遷移相關之動脈粥樣硬化)、萎縮性陰道炎、注意力不足症(ADD)及注意力不足過動症(ADHD)、自閉症及泛自閉症譜系障礙、良性前列腺增生(BPH)或肥大或腫大、躁鬱症、膀胱出口梗阻、膀胱疼痛症候群(BPS)、瞼炎、骨骼及碳水化合物代謝紊亂、骨愈合(例如,破骨重建後之骨癒合、破骨再吸收、新骨形成)、腦動脈瘤、腦缺氧、癌轉移、澱粉狀蛋白腦血管病(CAA)或嗜剛果紅血管病、伴有皮層下梗塞及腦白質病之腦體染色體-顯性動脈病(CADASIL或CADASIL症候群)、腦灌注、腦小血管病、腦血管痙攣、化學腦、兒童崩解症、慢性支氣管炎、慢性疲勞、慢性創傷性腦病(CTE)、纖毛疾病、肝硬化(例如,肝硬化、與慢性肝病相關之肝硬化、原發膽汁性肝硬化)、CNS疾病相關之性功能障礙、CNS疾病相關之睡眠紊亂、與亨廷頓氏病(Huntington's Disease)相關之認知缺陷、認知功能障礙、認知障礙(例如,血管認知障礙、輕度認知障礙、與糖尿病相關之認知障礙、與多發性硬化症相關之認知障礙、與睡眠呼吸暫停相關之認知障礙、與精神分裂症相關之認知障礙(CIAS)、與鐮狀細胞疾病相關之認知障礙)、腦震盪、先天性重肌無力症候群、結締組織病、腦梗塞後果(腦中風)、創傷患者之血液取代物保存、CREST症候群、克羅恩氏病(Crohn's disease)、囊腫纖維化(CF)、妄想症、癡呆症(例如,血管性癡呆、中風後癡呆症、路易體性癡呆、伴有額葉退化之癡呆症、伴有額顳葉型肺葉退化之癡呆症、伴有皮質基底核退化之癡呆症、克羅伊茨費爾特雅各布癡呆症(Creutzfeldt-Jakob dementia)、HIV癡呆症、多梗塞性癡呆、術後癡呆、重要部分單一梗塞性癡呆、HIV相關之癡呆症(包括無症狀的神經認知障礙(ANI)、輕微神經認知障礙(MND))、HIV相關之癡呆症(HAD,亦稱作AIDS癡呆複合[ADC]或HIV腦病)、早老性癡呆(輕度認知障礙,MCI)、混合型癡呆、貝瓦克氏癡呆(Binswanger's dementia) (皮層下動脈硬化腦病)、帕金森氏癡呆症(Parkinson's Dementia))、髓鞘脫失、抑鬱、抑鬱症、皮肌炎、糖尿病血管病變、糖尿病性黃斑水腫、糖尿病微血管病、糖尿病潰瘍或傷口(例如,糖尿病食物潰瘍)、與代謝症候群相關之疾病(例如,肥胖症、糖尿病、胰島素抗性、升高之空腹葡萄糖、升高之空腹胰島素、升高之脂質)、涉及神經傳遞素下調之疾病、涉及腦血流受損之疾病、涉及神經退化受損之疾病、涉及突觸功能減弱之疾病、涉及神經發炎之疾病、涉及神經毒性之疾病、男性及女性泌尿生殖系統之器官疾病(良性及惡性)、伴有學習及記憶問題之兒童的注意力障礙、唐氏症候群(Down syndrome)、藥物成癮、藥物誘發之精神病、乾眼症候群、杜興氏肌肉萎縮症(Duchenne muscular dystrophy)、杜普伊特倫氏攣縮(Dupuytren's contracture)、運動困難(例如,急性運動困難、慢性或遲發性運動不能、非運動性運動困難、左旋多巴誘發之運動困難(LID))、痛經(dysmenhorrea) (例如,原發性痛經、繼發性痛經)、性交困難、吞咽困難、肌肉緊張不足(例如,全身性肌肉緊張不足、局部性肌肉緊張不足、節段性肌肉緊張不足、性肌肉緊張不足、中度肌肉緊張不足、急性肌肉緊張不足反應、遺傳性或原發性肌肉緊張不足)、水腫、電解質紊亂(例如,高鉀血、低鈉血)、肺氣腫、子宮內膜異位、內皮功能障礙或損傷及與內皮功能障礙相關之疾病、勃起功能障礙、食道弛緩不能、法布瑞氏症(Fabry Disease)、女性性功能障礙(例如,女性性喚起功能障礙)、肌肉纖維疼痛、纖維化(例如,心內膜心肌纖維化、心房纖維化、心臟間質纖維化、心臟纖維化、肺纖維化、眼睛纖維化、皮膚纖維化、腸道纖維化、腎或腎臟纖維化、間質性腎纖維化、肺纖維化、特發性肺部纖維化、肺之進展性大型纖維化、肝纖維化、縱隔纖維化、腹膜後纖維化、關節纖維化、骨髓纖維化、骨髓纖維化、骨髓纖維瘤、放射線誘發之纖維化、胰纖維化)、X脆折、機能性消化不良、胃輕癱、高歇氏病(Gaucher Disease)、一般注意力障礙、一般精神病、青光眼、神經膠質母細胞瘤、腎絲球病變(例如,絲球體腎炎、急性絲球體腎炎、腎絲球硬化症、局灶節段性腎絲球硬化)、肉芽腫、頭部損傷、聽力障礙(例如,部分聽力喪失、全部聽力喪失、部分耳聾、全部耳聾、噪音性耳聾)、心臟病(例如,左心室心肌重塑、左心室收縮功能障礙、缺血性心肌症、擴張性心肌病、酒精性心肌病、儲存性心肌病、先天性心臟缺陷、冠狀動脈血流量降低、舒張性或收縮性功能障礙、冠狀動脈功能不全、急性冠狀動脈症候群、冠狀動脈疾病、心律不齊、心室預負荷降低、心臟肥大、右心臟肥大、心房及心室節律紊亂及心臟傳導異常、I至III級房室阻塞(AVB I-III)、室上快速性心律失常、過早心室收縮、心房震顫、心房顫動、心室纖顫、心室顫動、心室快速性心律失常、尖端扭轉型室性心動過速、心房及室性早搏、AV交界面早搏、病態竇房結症候群、AV結折返性心動過速、沃爾弗-帕金森-懷特氏症候群(Wolff-Parkinson-White syndrome)、心肌功能不全、慢性心肌炎、急性心肌炎或病毒性心肌炎、心因性休克、心臟重塑作用)、心衰竭(HF;例如射出分率正常型心臟衰竭(HFPEF)、射出分率降低之心衰竭(HFREF)、急性心衰竭、慢性心衰竭、現有慢性心衰竭之急性期(惡化HF)、短暫性心衰竭、急性心衰竭後、收縮性心衰竭、舒張性心衰竭、充血性心衰竭、急性失代償心衰竭、右心室衰竭、完全性心衰竭、高輸出性心衰竭、伴有瓣膜缺陷之心衰竭、糖尿病心衰竭、心衰竭/心腎症候群、右心臟衰竭)、高濃度之纖維蛋白溶酶原活化抑制劑1 (PA-1)、高含量之血纖維蛋白原及低密度DLD、組織細胞增生症X、亨廷頓氏病或舞蹈病(HD)、高氨血症及相關高血壓(例如,動脈性高血壓、難治性高血壓、糖尿病高血壓、特發性高血壓、原發性高血壓、繼發性高血壓、妊娠期高血壓、門靜脈高血壓、全身性高血壓、子癇前症、急性及慢性冠狀動脈血壓升高)、緊張亢進、肥厚性疤痕、減弱的性喚起病症、灌注不足、陽萎、發炎性腸道疾病(例如,克羅恩氏病、潰瘍性結腸炎)、腦瘧疾引起之發炎、感染性疾病引起之發炎、術前護理中之發炎性反應、血小板凝集、智能障礙、間歇性跛行、間質性膀胱炎(IC)、透析中低血壓、缺血(例如,腦缺血、心肌缺血、血栓栓塞缺血、嚴重肢體缺血)、瘢痕瘤、腎病(例如,慢性腎病、急性及慢性腎衰竭、急性及慢性腎功能衰竭、腎功能衰竭之後遺症、與肺灌腸相關之腎功能不全、與HF相關之腎功能不全、與尿毒症或貧血症相關之腎功能不全、原發性腎病、先天性腎病、多囊性腎病惡化、腎臟移植排斥反應、免疫複合體誘發之腎病、異常降低之肌酐及/或水分泌、異常增加之血液尿、氮濃度、鉀及/或肌酐、改變的腎酶活性(例如,麩胺醯基合成酶)、改變的尿液容積莫耳滲透濃度或尿量、增加之微白蛋白尿、大量白蛋白尿、腎小球及小動脈病變、管狀擴張、高磷酸鹽血症、血管腎病、腎囊腫、因HF所致之腎水腫)、卡薩科夫精神病(Korsakoff psychosis)、白血球活化、左旋多巴誘發之成癮行為、硬化性苔癬、脂質相關病症(例如,過度肥胖、過度皮下脂肪、高脂血、血脂異常、高膽固醇血症、降低之高密度脂蛋白膽固醇(HDL-膽固醇)、中度升高之低密度脂蛋白膽固醇(LDL-膽固醇)含量、高三酸甘油酯血症、高甘油酯血症、低脂蛋白血症、穀固醇血症、脂肪肝病、肝脂肪變性或肝臟之異常脂質累積,心臟、腎臟或肌肉之脂肪變性、穀固醇血症、黃瘤症、丹吉爾病(Tangier disease)、肝臟疾病(例如,血管肝臟疾病、肝星狀細胞活化、肝纖維性膠原蛋白及總膠原蛋白累積、具有壞死性炎症之肝臟疾病及/或免疫血肝臟疾病、與肉芽腫性肝臟疾病相關之膽汁鬱積性肝病、與肝臟惡性腫瘤相關之膽汁鬱積性肝病、與妊娠肝內膽汁鬱積相關之膽汁鬱積性肝病、與肝炎相關之膽汁鬱積性肝病、與敗血症相關之膽汁鬱積性肝病、與藥物或毒素相關之膽汁鬱積性肝病、與移植物抗宿主病相關之膽汁鬱積性肝病、與肝臟移植後相關之膽汁鬱積性肝病、與輸膽管結石相關之膽汁鬱積性肝病、與膽管腫瘤相關之膽汁鬱積性肝病、與胰臟癌相關之膽汁鬱積性肝病、與Mirizzi症候群相關之膽汁鬱積性肝病、與AIDS、膽管病相關之膽汁鬱積性肝病、與寄生物相關之膽汁鬱積性肝病、與血吸蟲病相關之膽汁鬱積性肝病、肝炎、非酒精性脂肪變性肝炎(NASH)、非酒精性脂肪肝病(NAFLD)、肝血管閉塞病(VOD)、肝竇阻塞症候群(SOS)、肝性腦病)、局部血栓形成、下泌尿道症候群(LUTS)、腰脊椎管狹窄、狼瘡性腎炎、狼瘡或全身性紅斑性狼瘡症、微白蛋白尿、微循環異常、偏頭痛、輕微神經認知障礙(MND)、硬斑病、煙霧病(moyamoya)、多發性腔隙性腦梗塞、多器官功能障礙症候群(MODS)、多重器官衰竭(MOF)、多發性硬化症(MS,包括臨床孤立症候群(CIS)、復發緩解型MS(RRMS)、原發性進行性MS(PPMS)、繼發性進行性MS(SPMS))、多發性系統萎縮症(MSA)、心肌梗塞或心臟病發作(例如,ST段抬高型心肌梗塞、非ST段抬高型心肌梗塞、陳舊性心肌梗塞)、近視脈絡膜新生血管、痣、麻醉劑依賴性、腎病變(例如,糖尿病腎病變、非糖尿病腎病變、腎炎、由毒素誘發之腎病變、造影劑誘發之腎病變、糖尿病或非糖尿病腎硬化、腎病症候群、腎盂腎炎、腎源性纖維化)、神經退化性疾病、神經性膀胱及失禁、神經發炎、與一氧化氮產生降低相關之神經病症、肌神經疾病(例如,杜興氏肌肉萎縮症(DMD)、貝氏肌肉萎縮症(BMD)、肢帶型肌肉萎縮症、遠端肌病、I型及II型肌緊張性營養不良、面肩腓肌肉營養不良、體染色體及X性聯埃默里-德雷弗斯氏肌肉萎縮症、眼咽肌肉萎縮症、肌萎縮性側索硬化、脊髓性肌肉萎縮(SMA))、視神經脊髓炎、神經病變(例如,周邊神經病變、自主神經性病變、中樞神經系統神經病變、化學療法誘發之神經病變、糖尿病神經病變疼痛性神經病變、神經痛、非疼痛性神經病變、疼痛性糖尿病神經病變、非疼痛性糖尿病神經病變、與CNS疾病相關聯之神經病(例如,多發性硬化症,MS)、放射線誘發之神經病變)、與帶狀疱疹相關之神經痛、與脊椎手術相關之神經痛)、強迫症(OCD)、阻塞性血栓血管炎、阻塞性尿道疾病、嗜酸性筋膜炎、骨質疏鬆症、膀胱過動症、疼痛(例如,急性疼痛、中樞性疼痛症候群、發炎性疼痛、術後疼痛、強直性疼痛、內臟疼痛、跛行疼痛、孤兒疼痛適應症(例如,乙醯唑胺反應性肌強直、自體紅血球過敏作用症候群、體染色體顯性恰克-馬利-杜斯氏病2V型(Autosomal dominant Charcot - Marie - Tooth disease type 2V)、伴有神經痛之體染色體顯性中度恰克-馬利-杜斯氏病、體染色體隱性肢帶型肌肉萎縮症2A型、離子通道病相關之先天性無痛症、需要脊柱內鎮痛之慢性疼痛、複雜區域疼痛症候群、複雜區域疼痛症候群1型、複雜區域疼痛症候群2型、先天性無痛多汗症、伴有嚴重智能障礙之先天性無痛症、先天性無痛少汗症候群、伴有疼痛性裂紋之彌漫性掌蹠角化病、家族性間歇性疼痛症候群、伴有顯著下肢受累之家族性間歇性疼痛症候群、伴有主要上半身受累之家族性間歇性疼痛症候群、遺傳性疼痛性胼胝、遺傳性感官及自主神經性病變類型4、遺傳性感官及自主神經性病變類型5、遺傳性感官及自主神經性病變類型7、間質性膀胱炎、疼痛性眼眶及全身性神經纖維瘤-馬凡症候群(marfanoid habitus syndrome)、陣發性劇痛症、持久性特發性面部疼痛、定性或定量的鈣蛋白酶缺陷、托洛薩亨特症候群(Tolosa-Hunt syndrome))、胰臟炎、恐慌症、帕金森氏病、帕金森氏疊加症候群、帕金森吞咽困難、病理學飲食障礙、骨盆疼痛、周邊血管疾病(例如,周邊動脈疾病、周邊動脈阻塞疾病周邊栓塞症、周圍灌注紊亂)、腹膜炎、廣泛性發展障礙、佩羅尼氏病(Peyronie's disease)、皮克氏症候群(Picks syndrome)、多軟骨炎、多發性肌炎、疱疹後神經痛、創傷後頭部損傷、創傷後壓力症創傷後應激障礙(PTSD)、早洩、進展性核麻痹、前列腺肥大、肺部疾病(例如,致叢性肺部動脈病、支氣管收縮或肺部支氣管收縮、肺血管疾病、慢性阻塞性肺病(COPD)、肺部毛細管血管瘤病、淋巴管瘤病及壓縮性肺血管(例如,由於淋巴結腫大、腫瘤或纖維化縱隔炎所致)、肺部血管重塑、肺部緊張亢進)、肺高血壓(PH,例如肺動脈高壓(PAH)、原發性PH、繼發性PH、偶發性PH、前毛細管PH、特發性PH、與左心室疾病相關之PH、與HIV相關之PH、與SCD相關之PH、與血栓栓塞相關之PH (慢性血栓栓塞PH或CTEPH)、與類肉瘤病相關之PH、與慢性阻塞性肺病相關之PH、與急性呼吸窘迫症候群(ARDS)相關之PH、與急性肺損傷相關之PH、與α-1-抗胰蛋白酶缺乏症(AATD)相關之PH、與肺部肺氣腫(例如,抽菸誘發之肺氣腫)相關之PH、與肺病相關之PH、與低血氧症相關之PH、與硬皮病相關之PH、與囊腫纖維化(CF)相關之PH、與左心室功能障礙相關之PH、與低血氧症相關之PH、PH (WHO組I、II、III、IV及V)、與二尖瓣膜疾病相關之PH、與心包炎相關之PH、與縮窄性心包炎相關之PH、與主動脈瓣狹窄相關之PH、與擴張型心肌症相關之PH、與肥厚型心肌病相關之PH、與限制型心肌病相關之PH、與縱隔纖維化相關之PH、與肺纖維化相關之PH、與異常肺靜脈引流相關之PH、與肺靜脈閉塞疾病相關之PH、與肺脈管炎相關之PH、與膠原蛋白血管疾病相關之PH、與先天性心臟病相關之PH、與肺靜脈高血壓相關之PH、與間質性肺病相關之PH、與睡眠障礙性呼吸相關之PH、與慢性氣流阻塞相關之PH、與阻塞性睡眠呼吸暫停相關之PH、與中樞性睡眠呼吸暫停相關之PH、與混合型睡眠呼吸暫停相關之PH、與肺泡低通氣症相關之PH、與慢性高原反應相關之PH、與新生兒肺病相關之PH、與肺泡-毛細管發育異常相關之PH、與鐮狀細胞疾病相關之PH、與其他凝血障礙相關之PH、與慢性血栓栓塞相關之PH)、神經根病變、雷諾氏病(Raynaud's disease)、雷諾氏症候群(原發性或繼發性)、難治性癲癇、Renpenning症候群、再灌注損傷(例如,缺血性再灌注損傷、與器官移植相關之缺血性再灌注)、再狹窄(例如,血栓溶解療法後、經皮管內血管成形術(PTA)後、經管腔冠狀動脈血管成形術(PTCA)後、心臟移植後或冠狀動脈旁通手術後出現之再狹窄)、視網膜病(例如,糖尿病性視網膜病變、非糖尿病性視網膜病變、非增生性糖尿病性視網膜病變、增生性玻璃體視網膜病變、周邊視網膜變性、視網膜靜脈阻塞)、瑞特氏症(Rhett's disorder)、類風濕性疾病或風濕疾病(例如,關節炎、類風濕性關節炎)、類肉瘤病、肉瘤病、血吸蟲病、精神分裂情感型障礙、精神分裂症、伴有癡呆症之精神分裂症、硬皮病(例如,局部硬皮病或侷限性硬皮病、全身性硬皮病)、硬化症(例如,腎硬化症、進展性硬化症、肝臟硬化症、原發性硬化性膽管炎、胃腸道硬化症、海馬體硬化症、局部硬化症、原發性側索硬化症、骨硬化症、耳硬化症、動脈粥樣硬化症、結節性硬化症、全身性硬化症、敗血症或敗血性休克或過敏性休克、鐮狀細胞性貧血症、鐮狀細胞疾病、休格倫氏症候群(Sjogren's syndrome)、睡眠清醒障礙、Sneddon症候群、痙攣(例如,冠狀動脈痙攣、血管痙攣、周邊動脈痙攣)、脊髓損傷、脊髓性肌萎縮、脊椎半脫位、脊髓小腦共濟失調、Steel-Richardson-Olszewski疾病(進行性核上麻痹)、中風、蛛膜下出血、皮層下動脈硬化性腦病、暈厥、tau蛋白病、緊張、丘腦退化症、血栓栓塞或形成血栓症、短暫性腦缺血發作(TIA)、創傷性腦損傷、腎小管間質性疾病、潰瘍、子宮肌瘤、陰道萎縮、瓣膜缺損(例如,二尖瓣膜狹窄、二尖瓣反流、功能不全或關閉不全、主動脈瓣膜狹窄、主動脈瓣膜功能不全、三尖瓣膜功能不全、肺瓣膜狹窄、肺瓣膜功能不全、混合型瓣膜缺陷)、腦血管疾病、由心臟及腎併發症引起之血管疾病、血管滲漏或滲透性、脈管炎(例如,血栓性脈管炎、閉塞性血栓性脈管炎、川崎病(Kawasaki disease)、動脈炎、主動脈炎)、血管閉塞性危象、脈移植失敗、濕性年齡相關之黃斑變性及威廉姆斯症候群(Williams syndrome)。
在本發明之一特定實施例中,疾病係選自鐮狀細胞疾病(SCD)、局灶節段性腎小球硬化症(FSGS)、心臟病、非酒精性脂肪變性肝炎(NASH)、非酒精性脂肪肝病(NAFLD)、心衰竭、肺高血壓、肝纖維化及腎纖維化。
如本文所使用,術語「疾病」係指相對於任何身體部分、器官或系統之正常結構或功能的任何偏差或中斷,其藉由症狀及跡象之特徵集合體現,且其病因、病變及預後可為已知的或未知的。術語疾病涵蓋其他相關術語,諸如病症及病況(或醫學病況)以及症候群,其定義為由單一病因導致或因此關於構成不同臨床圖片時通常一起出現的症狀之組合。在一些實施例中,術語疾病係指sGC、cGMP及/或NO介導之醫學或病理學疾病。
關於病症、疾病、病況、症狀或症候群之「治療(Treat/treating/treatment)」係指消除或改善該病症、疾病、病況或症候群之病因及/或影響(亦即,症狀、生理學、身體、精神、情感或任何其他臨床表現、觀測結果或量測,或改善病理學評估)。
如本文中所使用,術語「治療」亦係指延遲或改善或預防疾病之進展(亦即疾病之已知或預期進展)、嚴重程度及/或持續時間或延遲或改善或預防一或多種症狀、臨床表現、觀測結果或量測之進展,或預防或減緩由投與一或多種療法所引起的病理學評估之負發展進展(亦即「控制」而不「治癒」病況)。
如本文所用,術語「個體」及「患者」可互換地使用。術語「個體」及「患者」係指動物(例如,諸如雞、鵪鶉或火雞之鳥類,或哺乳動物),尤其包括非靈長類動物(例如,牛、豬、馬、羊、家兔、天竺鼠、大鼠、貓、狗及小鼠)及靈長類動物(例如,猴、黑猩猩及人類)的「哺乳動物」,且更特定而言人類。在一些實施例中,個體為非人類動物,諸如農場動物(例如馬、牛、豬或綿羊)或伴侶動物或寵物(例如狗、貓、小鼠、大鼠、倉鼠、沙鼠、天竺鼠或家兔)。在一些實施例中,個體為人類。
本發明亦提供一種用於治療個體之以上疾病中之一者的方法,其包含向需要治療之個體投與治療有效量之表I至VI或式I之化合物或其醫藥學上可接受之鹽。替代地,本發明提供表I至VI或式I之化合物或其醫藥學上可接受之鹽的用途,其用於治療需要治療之個體的此等疾病中之一者。本發明亦包括表I至VI或式I之化合物或其醫藥學上可接受之鹽的用途,其用於製造用於治療需要治療之個體的以上疾病中之一者的藥劑。本發明進一步提供一種製造適用於治療此等疾病中之一者之藥劑的方法,其包含使用表I至VI或式I之化合物或其醫藥學上可接受之鹽中之一者。
如本文所使用,術語「生物樣本」係指活體外或離體樣品,且包括(但不限於)細胞培養物或其提取物;獲自哺乳動物或其提取物之活檢材料;血液、唾液、尿液、排泄物、精液、淚液、淋巴液、眼內液、玻璃體液、腦脊髓液(CSF)或其他體液或其提取物。
在其他實施例中,本發明提供一種刺激生物樣本中之sGC活性的方法,其包含使該生物樣本與本發明之化合物或組合物接觸。在生物樣本中使用sGC刺激劑適用於熟習此項技術者已知之多種目的。此類目的之實例包括(但不限於)生物分析及生物樣本儲存。
組合療法 本文所描述之化合物及醫藥組合物可單獨使用或與用於治療藉由sGC、cGMP及/或NO介導、調節或影響之疾病之療法組合使用。
如本文中所使用,術語「組合」(如在語句「組合療法」中)或「共投與」可互換使用以指使用超過一種療法。該等術語之使用不限制向個體投與療法之次序。
本文所描述之化合物及醫藥組合物可用於具有一或多種額外治療劑之組合療法中。對於具有多於一種活性劑之組合治療,在活性劑呈單獨劑型調配物之情況下,活性劑可單獨地或結合投與。另外,投與一個要素可在投與其他藥劑之前、同時或之後進行。
當用於具有其他藥劑之組合療法中時,本文所描述之化合物及醫藥組合物及其他一或多種藥劑之「治療有效量」將視所使用之藥物之類型而定。批准藥劑之適合的劑量為已知的且可由熟習此項技術者根據個體之病狀、所治療病狀之類型及所用之本文所述化合物之量進行調整。在未明確地標註量之情況下,應假設有效量。
在一些實施例中,共投與或組合療法涵蓋以基本上同時的方式(諸如在單一醫藥組合物,例如具有固定比率之第一及第二量之膠囊或錠劑或各自之多次單獨膠囊或錠劑中)投與第一及第二量之化合物。另外,此類共投與亦涵蓋以任一次序,以依序方式使用各化合物。
當共投與涉及分開投與第一量之表I至VI或式I之化合物及第二量之額外治療劑時,化合物在時間上足夠接近地投與以具有所需治療作用。舉例而言,可產生所需治療作用之各投與之間的時間段範圍可在數分鐘與數小時之間,且可考慮到各化合物之特性(諸如效力、溶解度、生物可用性、血漿半衰期及動力學概況)來確定該時間段。舉例而言,表I至VI或式I之化合物及第二治療劑可按任何次序在彼此之約24小時內、彼此之約16小時內、彼此之約8小時內、彼此之約4小時內、彼此之約1小時內或彼此之約30分鐘內投與。
可與表I至VI或式I之化合物或其醫藥學上可接受之鹽組合、分開投與或在同一醫藥組合物中的其他治療劑之實例包括但不限於:
(1) 內皮衍生釋放因子(EDRF)或NO氣體。
(2) NO供體,包括但不限於亞硝基硫醇、亞硝酸鹽、悉尼酮亞胺、NONO鹽、N-亞硝胺、N-羥基亞硝胺、亞硝亞胺、硝基酪胺酸、二氮雜環丁烯二氧化物、㗁三唑5-亞胺、肟、羥胺、N-羥基胍、羥基脲或氧化呋呫。此等類型化合物之一些實例包括:三硝酸甘油酯(亦稱為GTN,硝化甘油、硝酸甘油酯及三硝化甘油)、丙三醇之硝酸酯;硝普鈉(SNP),其中一氧化氮之分子與鐵金屬配位,形成方形雙錐錯合物;3-(N-𠰌啉基)斯德酮亞胺(SIN-1)、藉由𠰌啉及悉尼酮亞胺之組合形成之兩性離子型化合物;S-亞硝基-N-乙醯基青黴胺(SNAP)、具有亞硝基硫醇官能基之N-乙醯化胺基酸衍生物;二伸乙基三胺/NO (DETA/NO)、共價連接至二伸乙基三胺之一氧化氮化合物;乙醯基水楊酸之間硝醯氧基甲基苯基酯。此等類別之NO供體中之一些的更特定實例包括:典型硝基血管舒張劑,諸如有機硝酸酯及亞硝酸酯,包括硝化甘油、亞硝酸戊酯、異山梨醇二硝酸酯、異山梨醇5-單硝酸酯及尼可地爾(nicorandil);異山梨醇;3-(N-𠰌啉基)斯德酮亞胺;林西多明氫氯酸鹽(「SIN-1」);S-亞硝基-N-乙醯基青黴胺(「SNAP」);S-亞硝基穀胱甘肽(GSNO)、硝普鈉、S-亞硝基穀胱甘肽單-乙基-酯(GSNO-酯)、6-(2-羥基-1-甲基-硝基肼基)-
N- 甲基 -1-己胺或二乙胺NONO鹽。
(3) 增強cGMP濃度之其他物質,包括但不限於原卟啉IX、二十碳四烯酸及苯肼衍生物。
(4) 一氧化氮合成酶受質,包括但不限於L-精胺酸、正羥基胍基類似物,諸如N[G]-羥基-L-精胺酸(NOHA)、1-(3,4-二甲氧基-2-氯苯亞甲基胺基)-3-羥基胍及PR5 (1-(3,4-二甲氧基-2-氯苯亞甲基胺基)-3-羥基胍);L-精胺酸衍生物(諸如均Arg、均NOHA、N-三級丁氧基-及N-(3-甲基-2-丁烯基)氧基-L-精胺酸、刀豆胺酸、ε胍-己酸、胍丁胺、羥基-胍丁胺及L-酪胺醯基-L-精胺酸);N-烷基-N'-羥基胍(諸如N-環丙基-N'-羥基胍及正丁基-N'-羥基胍)、N-芳基-N'-羥基胍(諸如N-苯基-N'-羥基胍及其經對位取代之衍生物,其分別攜有-F、-Cl、-甲基、-OH取代基);胍衍生物,諸如3-(三氟甲基)丙基胍。
(5) 增強eNOS轉錄之化合物。
(6) NO非依賴性血紅素非依賴性sGC活化劑,包括但不限於BAY 58-2667 (描述於專利公開案DE19943635中);HMR-1766 (阿他西哌(ataciguat),描述於專利公開案WO2000002851中);S 3448 (2-(4-氯-苯磺醯胺基)-4,5-二甲氧基-N-(4-(硫代𠰌啉-4-磺醯基)-苯基)-苯甲醯胺(描述於專利公開案DE19830430及WO2000002851中);及HMR-1069 (來自Sanofi-Aventis)。
(7) 血紅素依賴性、NO非依賴性sGC刺激劑,包括但不限於YC -1 (參見專利公開案EP667345及DE19744026);瑞司瓜特(riociguat) (BAY 63-2521,Adempas®,描述於DE19834044中);利奧西哌(nelociguat) (BAY 60-4552,描述於WO 2003095451中);維瑞瓜特(vericiguat) (BAY 1021189,描述於US8420656中);BAY 41-2272 (描述於DE19834047及DE19942809中);BAY 41-8543 (描述於DE19834044中);依曲西哌(描述於WO 2003086407中);CFM-1571 (描述於專利公開案WO2000027394中);A-344905,其丙烯醯胺類似物A-350619及胺基嘧啶類似物A-778935;
描述於以下公開案中之一者中的其他sGC刺激劑:US20090209556、US8455638、US20110118282 (WO2009032249)、US20100292192、US20110201621、US7947664、US8053455 (WO2009094242)、US20100216764、US8507512 (WO2010099054)、US20110218202 (WO2010065275)、US20130012511 (WO2011119518)、US20130072492 (WO2011149921)、US20130210798 (WO2012058132)及Tetrahedron Letters(2003), 44(48):8661-8663;及IW1973 (普拉西哌(praliciguat))、IW1701 (奧林西哌(olinciguat))及CY6463 (先前的IW-6463)。
(8) 抑制cGMP及/或cAMP之降解的化合物,包括但不限於:
PDE1抑制劑;PDE2抑制劑;PDE-3抑制劑,諸如氨利酮(amrinone)、米利酮(milrinone)、依諾昔酮(enoximone)、維司力農(vesnarinone)、匹莫苯(pimobendan)及奧普力農(olprinone);PDE4抑制劑,諸如羅路拉斯特(rolumilast);PDE5抑制劑,諸如西地那非(sildenafil)及相關藥劑,諸如阿伐那非(avanafil)、羅地那非(lodenafil)、米羅那非(mirodenafil)、檸檬酸西地那非(sildenafil citrate)、他達拉非(tadalafil)、伐地那非(vardenafil)及烏地那非(udenafil);前列地爾(alprostadil);雙嘧達莫(dipyridamole)及PF-00489791;PDE6抑制劑、PDE9抑制劑,諸如PF-04447943;PDE10抑制劑,諸如PF-02545920 (PF-10);及PDE11抑制劑。
(9) 抗凝血劑,包括但不限於:
香豆素(維生素K拮抗劑),諸如華法林(warfarin)、醋硝香豆醇(cenocoumarol)、苯丙香豆醇(phenprocoumon)及苯茚二酮(phenindione);
肝素及衍生物,諸如低分子量肝素、磺達肝素(fondaparinux)及艾卓肝素(idraparinux);
直接凝血酶抑制劑,諸如阿加曲班(argatroban)、來匹盧定(lepirudin)、比伐盧定(bivalirudin)、達比加群(dabigatran)及希美加群(ximelagatran);及
用於溶解凝塊及解塊動脈之
組織纖維蛋白溶酶原活化劑,諸如阿替普酶(alteplase)。
(10) 抗血小板藥物,包括但不限於托吡格雷(topidogrel)、噻氯匹定(ticlopidine)、雙嘧達莫及阿司匹林。
(11) 補充氧療法。
(12) α-1-腎上腺素受體拮抗劑,包括但不限於哌唑嗪(prazosin)、吲哚拉明(indoramin)、烏拉地爾(urapidil)、布那唑嗪(bunazosin)、特拉唑嗪(terazosin)及多沙唑嗪(doxazosin);心房利尿鈉肽(ANP)、乙醇、組織胺誘導劑、四氫大麻酚(THC)及罌粟鹼。
(13) 支氣管擴張劑,包括但不限於:
短效 β
2 促效劑,諸如沙丁胺醇(albutamol或albuterol)及特布他林(terbutaline);
長效 β
2 促效劑 (LABA),諸如沙美特羅(salmeterol)及福莫特羅(formoterol);
抗膽鹼激導性劑,諸如異丙托銨(pratropium)及噻托銨(tiotropium);及
茶鹼、支氣管擴張劑及磷酸二酯酶抑制劑。
(14) 皮質類固醇,包括但不限於倍氯米松(beclomethasone)、甲基潑尼松龍(methylprednisolone)、倍他米松(betamethasone)、潑尼松(prednisone)、潑尼松龍(prednisolone)、曲安西龍(triamcinolone)、地塞米松(dexamethasone)、氟替卡松(fluticasone)、氟尼縮松(flunisolide)、氫皮質酮(hydrocortisone);及皮質類固醇類似物,諸如布地奈德(budesonide)。
(15) 膳食補充劑,包括但不限於ω-3油;葉酸、菸酸、鋅、銅、韓紅人參根、銀杏、松樹皮、蒺藜(Tribulus terrestris)、精胺酸、燕麥、淫羊藿、秘魯人參根、巴西榥榥木(muira puama)、鋸棕櫚及瑞典花粉;維生素C、維生素E、維生素K2;睪固酮補充劑、睪固酮經皮貼片;克拉維酸(zoraxel)、納曲酮(naltrexone)、佈雷默浪丹(bremelanotide)及美拉諾坦(melanotan) II。
(16) PGD2受體拮抗劑。
(17) 免疫抑止劑,包括但不限於環孢黴素、他克莫司(tacrolimus)、雷帕黴素(rapamycin)及其他FK-506型免疫抑止劑,黴酚酸酯(mycophenolate)、麥考酚酸酯(mycophenolate mofetil)。
(18) 非類固醇抗氣喘劑,包括但不限於:
β2- 促效劑,如特布他林、間羥異丙腎上腺素、非諾特羅(fenoterol)、異他林(isoetharine)、沙丁胺醇、沙美特羅、比托特羅(bitolterol)及吡布特羅(pirbuterol);
β2- 促效劑 - 皮質類固醇組合,諸如沙美特羅-氟替卡松、福莫特羅-布地奈德、茶鹼、色甘酸(cromolyn)、色甘酸鈉、奈多羅米(nedocromil)、阿托品(atropine)、異丙托銨、異丙托溴銨;及
白三烯生物合成抑制劑,諸如齊留通(zileuton)或維夫拉朋(veliflapon)。
(19) 非類固醇抗炎劑(NSAID),包括但不限於:
丙酸衍生物,如阿明洛芬(alminoprofen)、苯惡洛芬(benoxaprofen)、布氯酸、卡洛芬(carprofen)、芬布芬(fenbufen)、非諾洛芬(fenoprofen)、氟洛芬(fluprofen)、氟比洛芬(flurbiprofen)、布洛芬、吲哚洛芬(indoprofen)、酮洛芬(ketoprofen)、咪洛芬(miroprofen)、萘普生(naproxen)、奧沙普嗪、吡洛芬(pirprofen)、普拉洛芬(pranoprofen)、舒洛芬、噻洛芬酸及硫惡洛芬;
乙酸衍生物,諸如吲哚美辛、阿西美辛(acemetacin)、阿氯芬酸(alclofenac)、環氯茚酸(clidanac)、雙氯芬酸(diclofenac)、芬氯酸(fenclofenac)、芬克洛酸(fenclozic acid)、芬替酸(fentiazac)、呋羅芬酸(furofenac)、異丁芬酸(ibufenac)、伊索克酸(isoxepac)、惡平酸(oxpinac)、舒林酸、硫平酸、托美丁(tolmetin)、齊多美辛(zidometacin)及佐美酸(zomepirac);
芬那酸酸衍生物,諸如氟芬那酸(flufenamic acid)、甲氯芬那酸(meclofenamic acid),甲芬那酸(mefenamic acid)、氟尼酸(niflumic acid)及托芬那酸(tolfenamic acid);
二苯基羧酸衍生物,諸如二氟尼柳(diflunisal)及氟苯柳(flufenisal);
昔康(
oxicam),諸如伊索昔康(isoxicam)、吡羅昔康(piroxicam)、舒多昔康(sudoxicam)及替諾昔康(tenoxican);
水楊酸鹽,諸如乙醯基水楊酸及柳氮磺胺吡啶;及
吡唑啉酮,諸如阿帕宗(apazone)、苯哌隆(bezpiperylon)、非普拉宗(feprazone)、莫非布宗(mofebutazone)、羥布宗(oxyphenbutazone)及苯基丁氮酮。
(20) 環加氧酶-2 (COX-2)抑制劑,包括但不限於塞內昔布(celecoxib)、羅非昔布(rofecoxib)、伐地昔布(valdecoxib)、依託昔布(etoricoxib)、帕瑞考昔(parecoxib)及魯米昔布(lumiracoxib);類鴉片鎮痛劑,諸如可待因(codeine)、芬太尼(fentanyl)、氫嗎啡酮(hydromorphone)、左啡諾(levorphanol)、嘜啶(meperidine)、美沙酮(methadone)、嗎啡鹼(morphine)、羥考酮(oxycodone)、羥嗎啡酮(oxymorphone)、丙氧吩(propoxyphene)、丁基原啡因(buprenorphine)、布托啡諾(butorphanol)、地佐辛(dezocine)、納布啡(nalbuphine)及戊唑星(pentazocine);
(21) 腎上腺素神經元阻斷劑,包括但不限於胍乙啶(guanethidine)及胍那決爾(guanadrel)。
(22) 咪唑啉I-1受體促效劑,包括但不限於磷酸二氫利美尼定及氫氯酸莫索尼定水合物。
(23) 鉀通道活化劑,包括但不限於吡那地爾(pinacidil)。
(24) 多巴胺D1促效劑,包括但不限於甲磺酸非諾多泮(fenoldopam mesilate);其他多巴胺促效劑,諸如異波帕胺(ibopamine)、多培沙明(dopexamine)及多卡巴胺(docarpamine)。
(25) 5-HT2拮抗劑,包括但不限於酮色林(ketanserin)。
(26) 血管加壓素拮抗劑,包括但不限於托伐普坦(tolvaptan)。
(27) 鈣通道敏化劑,包括但不限於左西孟旦(levosimendan)或諸如尼可地爾之活化劑。
(28) 腺苷酸環化酶活化劑,包括但不限於達普酸考福辛鹽酸鹽(colforsin dapropate hydrochloride)。
(29) 正性心肌收縮劑,包括但不限於地高辛(digoxin)及甲地高辛(metildigoxin);代謝強心劑,諸如泛癸利酮(ubidecarenone);大腦利尿鈉肽,諸如奈西立肽(nesiritide)。
(30) 用於治療勃起功能障礙之藥物,包括但不限於前列地爾、阿肽地爾(aviptadil)及甲磺酸芬托拉明(phentolamine mesilate)。
(31) 用於治療阿茲海默氏病及癡呆之藥物,包括但不限於:
乙醯基膽鹼酯酶抑制劑,諸如加蘭他敏(galantamine)、雷斯替明(rivastigmine)、多奈哌齊(donepezil)及他可林(tacrine);及
NMDA 受體拮抗劑,諸如美金剛胺(memantine);及
氧化還原酶抑制劑,諸如艾地苯醌(idebenone)。
(32) 精神藥劑,包括但不限於:
齊拉西酮(ziprasidone)、利培酮(risperidone)、奧氮平(olanzapine)、丙戊酸鹽;
多巴胺 D4 受體拮抗劑,諸如氯氮平;
多巴胺 D2 受體拮抗劑,諸如奈莫必利(nemonapride);
混合多巴胺 D1/D2 受體拮抗劑,諸如珠氯噻醇(zuclopenthixol);
GABA A 受體調節劑,諸如卡馬西平(carbamazepine);
鈉離子通道抑制劑,諸如拉莫三嗪(lamotrigine);
單胺氧化酶抑制劑,諸如嗎氯貝胺(moclobemide)及茚氯嗪(indeloxazine);及
匹莫范色林(primavanserin)及哌羅匹隆(perospirone)。
(33) 用於治療運動障礙或症狀之藥物,包括但不限於:
兒茶酚 -O- 甲基轉移酶抑制劑,諸如恩他卡朋(entacapone);
單胺氧化酶 B 抑制劑,諸如司來吉蘭(selegiline);
多巴胺受體調節劑,諸如左旋多巴;
多巴胺 D3 受體促效劑,諸如普拉克索(pramipexole);
去羧酶抑制劑,諸如卡比多巴;
其他多巴胺受體促效劑,諸如培高利特(pergolide)、羅匹尼洛(ropinirole)、卡麥角林(cabergoline);
利提耐德(ritigonide)、伊曲茶鹼(istradefylline)、他利克索(talipexole);唑尼沙胺(zonisamide)及沙芬醯胺(safinamide);及
突觸囊泡胺轉運蛋白抑制劑,諸如丁苯那嗪(tetrabenazine)。
(34)
用於治療情緒或情感障礙或OCD之藥物,諸如以下類型:
三環抗抑鬱劑,諸如阿米曲替林(amitriptyline)、地昔帕明(desipramine)、丙咪嗪(imipramine)、阿莫沙平(amoxapine)、去甲替林(nortriptyline)、多慮平(doxepin)及氯米帕明(clomipramine);
選擇性血清素再吸收抑制劑(SSRI)
,諸如帕羅西汀(paroxetine)、氟西汀(fluoxetine)、舍曲林(sertraline)、曲唑酮(trazodone)及西酞普蘭(citralopram);
非典型抗抑鬱劑,諸如阿戈美拉汀(agomelatine);
選擇性去甲腎上腺素再吸收抑制劑 (SNRI),諸如文拉法辛(venlafaxine)、瑞波西汀(reboxetine)及阿托西汀(atomoxetine);多巴胺激導性抗抑鬱劑,諸如安非他酮(bupropion)及安咪奈丁(amineptine)。
(35) 用於增強突觸可塑性之藥物,包括但不限於:
菸鹼酸受體拮抗劑,諸如美加明(mecamylamine);及
混合 5-HT 、多巴胺及去甲腎上腺素受體促效劑,諸如魯拉西酮(lurasidone)。
(36) 用於治療ADHD之藥物,諸如安非他命(amphetamine);5-HT受體調節劑,諸如沃替西汀(vortioxetine);及α-2腎上腺素受體促效劑,諸如氯壓定。
(37) 一氧化氮合成酶輔因子,包括但不限於四氫生物喋呤、二氫生物蝶呤及沙丙蝶呤(sapropterin)。
(38) 血糖降低藥劑(亦稱作血糖控制藥劑或抗糖尿病藥劑)包括但不限於:
雙胍,諸如二甲雙胍(metformin);
磺醯脲,諸如格列本脲(glyburide)、優降糖(glybenclamide)、格列吡嗪(glipizide)、格列齊特(gliclazide)、格列喹酮(gliquidone)、格列美脲(glimepiride)、與格列美脲組合之阿托伐他汀鈣、美格那肽(meglinatide)、甲苯磺丁脲(tolbutamide)、氯磺丙脲、醋磺環已脲及妥拉磺脲(tolazimide);
α - 葡萄糖苷酶抑制劑,諸如阿卡波糖(acarbose)、依帕司他(epalrestat)、伏格列波糖(voglibose)及米格列醇(miglitol);
胰島素促分泌素,諸如瑞格列奈(repaglinide)、米格列奈(mitiglinide)及那格列奈(nateglinide);
噻唑啶二酮,諸如羅格列酮(rosiglitazone)、曲格列酮(troglitazone)、環格列酮(ciglitazone)、吡格列酮(pioglitazone)、恩格列酮(englitazone)、硫酸洛貝格列酮(lobeglitazone sulfate)及巴拉列酮(balaglitazone);
DPP-4 抑制劑 ( 或 DPP-IV 抑制劑 ),諸如西格列汀(sitagliptin)、維格列汀(vildagliptin)、沙格列汀(saxagliptin)、阿格列汀(alogliptin)、利格列汀(linagliptin)、與二甲雙胍或鹽酸二甲雙胍組合之苯甲酸阿格列汀(alogliptin benzoate)、阿拉格列汀(anagliptin)、替格列汀(teneligliptin)、阿托伐他汀鈣及格列美脲、與利格列汀組合之恩格列淨(empagliflozin)、吉格列汀(gemigliptin)、與吡格列酮鹽酸鹽組合之磷酸西格列汀單水合物、與吡格列酮組合之西格列汀、與阿托伐他汀鈣組合之西格列汀及(2
S,4
S)-1-[2-(1,1-二甲基-3-側氧基-3-吡咯啶-1-基-丙胺基)乙醯基]-4-氟-吡咯啶-2-甲腈(DBPR-108);
GLP-1 受體 促效劑或腸促胰島素模擬物,諸如艾塞那肽(exenatide)、度拉糖肽(dulaglutide)、利拉魯肽(liraglutide)、司美魯肽(semaglutide)、利司那肽(lixisenatide)、與甘精胰島素組合之利司那肽、阿比魯肽(albiglutide)及陪阿帕度肽(pegapamodutide) (TT-401)、LY3298176(雙葡萄糖依賴性促胰島素多肽(GIP)及GLP-1受體促效劑);
SGLT2 抑制劑 (SGLT2i),諸如恩格列淨(empagliflozin)、與利格列汀組合之恩格列淨、與二甲雙胍組合之恩格列淨、伊格列淨(ipragliflozin)、伊格列淨
L- 脯胺酸、托格列淨(tofogliflozin)、依碳酸舍格列淨、依碳酸瑞格列淨、埃格列淨(ertugliflozin)、與西格列汀組合之埃格列淨、與二甲雙胍組合之埃格列淨、索格列淨(sotagliflozin)、卡格列淨(canagliflozin)、與二甲雙胍或鹽酸二甲雙胍組合之卡格列淨、達格列淨(dapagliflozin)、與二甲雙胍或鹽酸二甲雙胍及魯格列淨(luseoglifozin)組合之達格列淨、與沙格列汀組合之達格列淨(dapagliflozin);
SGLT 1 抑制劑或 SGLT1 及 SGLT2 抑制劑之組合,諸如索格列淨;
胰島素療法,諸如許多類型之胰島素中之一者:賴麩胰島素、德穀胰島素、賴脯胰島素、門冬胰島素、甘精胰島素、地特胰島素、魚精蛋白胰島素、混合胰島素(含有快速作用(可溶性)及長效(魚精蛋白)胰島素兩者的人類胰島素、與門冬胰島素組合之德穀胰島素、人類(rDNA來源)吸入粉末胰島素、重組人類胰島素、肝導引囊泡胰島素、特格胰島素(insulin tregopi) (IN-105)、與利拉魯肽組合之德穀胰島素、普賴胰島素(insulin peglispro) (LY-2605541)及諾丁(nodlin);及
托利米酮(
tolimidone)(lyn激酶活化劑)。
(39) 降血壓藥劑(亦稱為抗高血壓藥劑),包括但不限於:
利尿劑,諸如噻嗪利尿劑、氯噻嗪、氯噻酮、氫氯噻嗪、苄氟甲噻嗪、環戊噻嗪、甲氯噻嗪、多噻嗪、喹乙唑酮、希伯胺(xipamide)、美托拉宗(metolazone)、吲達帕胺(indapamide)、西氯他寧(cicletanine)、呋喃苯胺酸(furosemide)、托瑞司胺(toresamide)、胺氯吡脒(amiloride)、螺內酯、坎利酸鉀、依普利酮、、胺苯喋啶(triamterene)、乙醯唑胺及卡培立肽(carperitide);
β 阻斷劑,諸如醋丁洛爾(acebutolol)、阿替洛爾(atenolol)、美托洛爾(metoprolol)及奈必洛爾(nebivolol);
血管收縮素轉化酶 (ACE) 抑制劑,諸如含巰基藥劑(例如,卡托普利(captopril)、佐芬普利(zofenopril))、含二甲酸酯之藥劑(例如,依那普利(enalapril)、喹那普利(quinapril)、雷米普利(ramipril)、培哚普利(perindopril)、賴諾普利及貝那普利(benazepril))、含膦酸酯之藥劑(例如,福辛普利(fosinopril))、天然存在之ACE抑制劑(例如,酪激肽、乳激肽、乳三肽Val-Pro-Pro及Ile-Pro-Pro)、阿拉普利(alacepril)、地拉普利(delapril)、西拉普利(cilazapril)、咪達普利(imidapril)、替莫普利(temocapril)、莫西普利(moexipril)、賴諾普利、賴諾普利與氫氯噻嗪之組合、群多普利(trandolapril)及螺普利(spirapril);
血管收縮素 II 受體阻斷劑 (ARB) ,諸如坎地沙坦(candesartan)、氯沙坦(losartan)、氯沙坦鉀-氫氯噻嗪、纈沙坦(valsartan)、坎地沙坦酯(candesartan cilexetil)、依普沙坦(eprosaran)、依貝沙坦(irbesartan)、替米沙坦(telmisartan)、奧美沙坦美度米(或奧美沙坦)、阿齊沙坦美度米(azilsartan medoxomil)、阿齊沙坦(azilsartan)、與依貝沙坦組合之苯磺酸氨氯地平(amlodipine besylate)、與胺氯地平苯磺組合之阿齊沙坦、與纈沙坦組合之西尼地平(cilnidipine)、非馬沙坦(fimasartan)、與阿托伐他汀組合之依貝沙坦、與三氯甲噻嗪組合之依貝沙坦、與氫氯噻嗪及/或苯磺酸氨氯地平組合之氯沙坦鉀、普特沙坦(pratosartan)、與氯沙坦鉀組合之阿托伐他汀鈣、硝苯地平(nifedipine)及坎地沙坦酯、與纈沙坦或LCZ-696組合之沙庫必曲(sacubitril)、血管緊張素AT2拮抗劑及TAK-591以及奧美沙坦美度米;
內皮素受體拮抗劑 (ERA) ,諸如阿曲生坦(atrasentan)、波生坦(bosentan)、西他塞坦(sitaxentan)、安立生坦(ambrisentan)、愛可泰隆-1 (actelion-1) (馬西替坦(macitentan))、環(D-trp-D-asp-L-pro-D-Val-L-leu) (BQ-123)、斯帕森坦(sparsentan)及替唑生坦二鈉(tezosentan disodium)。
鹽皮質激素受體拮抗劑 (MRA) ,諸如螺內酯、與螺內酯組合之胺氯吡脒鹽酸鹽、阿帕瑞酮(apararenone)或MT-3995、依普利酮及非瑞酮(finerenone) (BAY-94-8862);
鈣通道阻斷劑,諸如胺氯地平、阿雷地平(aranidipine)、阿折地平(azelnidipine)、巴尼地平(barnidipine)、貝尼地平(benidipine)、西尼地平(cilnidipine)、氯維地平(clevidipine)、地爾硫卓(diltiazem)、依福地平(efonidipine)、非洛地平(felodipine)、拉西地平(lacidipine)、樂卡地平(lercanidipine)、馬尼地平(manidipine)、尼卡地平(nicardipine)、硝苯地平、尼伐地平(nilvadipine)、尼莫地平(nimodipine)、尼索地平(nisoldipine)、尼群地平(nitrendipine)、普拉地平(pranidipine)、伊拉地平(isradipine)、維拉帕米(verapamil)、加洛帕米(gallopamil)、地爾硫卓、米貝地爾(mibefradil)、苄普地爾(bepridil)、氟斯必靈(fluspirilene)及芬地林;
腎素抑制劑,諸如阿力克倫(aliskiren);
α 阻斷劑,諸如多沙唑嗪(doxazosin)及哌唑嗪(prazosin);
α - β 阻斷劑,諸如卡維地洛(carvedilol)及拉貝洛爾(labetalol);
中樞神經藥劑,諸如可樂定(clonidine)、胍法新(guanfacine)及甲基多巴(methyldopa);
血管擴張劑,諸如硝酸甘油酯、肼酞嗪及敏樂定(minoxidil);及
醛固酮拮抗劑,諸如非瑞酮、螺內酯及依普利酮。
(40) 抗高脂質血症藥劑,包括但不限於:
士他汀 (s tatins) ,諸如阿托伐他汀(atorvastatin)、氟伐他汀(fluvastatin)、洛伐他汀(lovastatin)、匹伐他汀(pitavastatin)、普伐他汀(pravastatin)、羅素他汀(rosuvastatin)及辛伐他汀(simvastatin);
士他汀與另一藥劑之組合,諸如胺氯地平/阿托伐他汀、阿司匹林/普伐他汀、依澤麥布(ezetimibe)/辛伐他汀、菸酸/辛伐他汀、洛伐他汀/菸酸、辛伐他汀/西格列汀及阿托伐他汀/依澤麥布;
纖維酸酯或纖維酸衍生物。實例包括但不限於非諾貝特(fenofibrate)、吉非羅齊(gemfibrozil)、苯紮貝特(bezafibrate)、環丙貝特(ciprofibrate)、克利貝特(clinofibrate)及氯貝特(clofibrate);
菸酸(或菸鹼酸);
膽酸螯合劑,諸如消膽胺、考來維侖(colesevelam)、考來替蘭(colestilan)及考來替潑(colestipol);
依澤麥布、洛美他哌 (l omitapide) 、 植物固醇或奧利司他 (orlistat) ; 及 PCSK9 抑制劑,諸如阿利庫單抗(alirocumab)及依伏庫單抗(evolocumab);
(41) 腦啡肽酶抑制劑(亦稱為內肽酶抑制劑或NEP抑制劑或腦啡肽酶抑制劑),包括但不限於沙庫必曲(sacubitril)、或沙庫必曲與纈沙坦之組合;腦啡肽酶抑制劑,研發中的TD-1439或TD-0714。
(42) 腎臟保護藥物,包括但不限於:
巴多曲龍(Bardoxolone);
ACE 抑制劑,諸如卡托普利;
ARB ,諸如氯沙坦或依貝沙坦;
SGLT2 抑制劑,諸如卡格列淨,
GLP1 受體促效劑 ; MRA ,諸如非瑞酮;
ERA ,諸如阿曲生坦;及細胞凋亡信號調節激酶1 (ASK1)抑制劑,諸如司隆色替(selonsertib)。
(43) 羥基脲(HU,羥基尿素)。
(44) 抗鐮狀細胞形成藥劑,包括但不限於羥基尿素、沃西洛特(voxelotor)或GBT-440。
(45) 抗黏附療法,包括但不限於阻斷抗體黏附至P-選擇素、E-選擇素、VLA-4、VCAM-1。
(46) 麩醯胺酸。
(47) 紅血球生成素(EPO),亦稱為造血素(hematopoietin/hemopoietin)包括其所有形式,諸如外源性紅血球生成素、重組人類紅血球生成素(rhEPO)或其他紅血球生成刺激劑(ESA),兩個實例為阿法依泊汀(epoetin alfa)及倍他依泊汀(epoetin beta)。
(48) 抗生素,包括但不限於:
青黴素及其衍生物,包括但不限於青黴素、阿莫西林(amoxicillin)、安比西林(ampicillin)、阿洛西林(azlocillin)、氯唑西林(cloxacillin)、青黴素G、青黴素V、普魯卡因青黴素或苄星青黴素等。
頭孢菌素,諸如頭孢力新(cephalexin)、頭孢羥胺苄(cefadroxil)、頭孢克洛(cefaclor)、頭孢呋辛(cefuroxime)及頭孢克肟(cefexime);
巨環內酯,諸如紅黴素、克拉黴素、阿奇黴素及羅紅黴素;
四環素及其衍生物,諸如地美環素(demeclocycline)、多西環素(doxycycline)、二甲胺四環素(minocycline)、土黴素(oxytetracycline)及四環素;
磺醯胺,包括但不限於磺胺米隆(mafenide)、磺胺醋醯胺、磺胺嘧啶、磺胺嘧啶銀、達美磺胺、磺胺甲二唑、磺胺甲異㗁唑、柳氮磺胺吡啶、三甲氧苄二胺嘧啶-磺胺甲異㗁唑(複方新諾明(Co-trimoxazole))及磺胺異㗁唑;及
喹啉酮,包括但不限於環丙沙星(ciprofloxacin)、依諾沙星(enoxacin)、加替沙星(gatifloxacin)、吉米沙星(gemifloxacin)、左氧氟沙星(levofloxacin)、洛美沙星(lomefloxacin)、莫西沙星(moxifloxacin)、氧氟沙星(ofloxacin)及萘啶酸(nalidixic acid)。
(49) FXR促效劑,包括但不限於奧貝膽酸(obeticholic acid)、森尼韋若(cenicriviroc)、恩利卡生(emricasan)、GR-MD-02、司隆色替及艾拉菲諾(elafibranor)。
(50) 甲狀腺受體-β促效劑,包括但不限於MGL-3196。
(51) 乙醯基-CoA羧化酶抑制劑,包括但不限於GS-0976。
(52) 用於粒線體病症之治療劑,包括但不限於維生素及補充劑,包括輔酶Q10;B複合維生素、尤其硫胺(B1)及核黃素(B2);α類脂酸;L-肉鹼(Carnitor);肌酸;瓜胺酸及L-精胺酸。
(53) 用於癲癇或癲癇發作之治療劑,包括但不限於苯妥英(phenytoin)、丙戊酸、苯巴比妥、拉莫三嗪(lamotrigine)、卡馬西平(carbamazepine)、托吡酯、奧卡西平(oxcarbazepine)、唑尼沙胺(zonisamide)、加巴噴汀(gabapentin)、左乙拉西坦(levetiracetam)、普瑞巴林(pregabalin)、可那氮平(clonazepam)、拉科醯胺(lacosamide)、盧非醯胺(rufinamide)及喜保寧(vigabatrin)。
封裝及套組 根據用於投與藥物之方法而定,可以多種方式封裝供使用之醫藥組合物(或調配物)。一般而言,用於經銷之製品包括將醫藥調配物以適當形式存放於其中之容器。適合容器為熟習此項技術者所熟知且包括諸如瓶子(塑膠及玻璃)、藥囊、安瓿、塑膠袋、金屬筒及其類似物之材料。容器亦可包括防開啟裝配件以防止輕易獲取封裝之內含物。另外,容器上附有描述容器內含物之標籤。標籤亦可包括適當警告。
本文所描述之化合物及醫藥調配物可含於套組中。套組可能包括單一或多次劑量之各自單獨封裝或調配之兩種或多於兩種藥劑或單一或多次劑量之組合封裝或調配之兩種或多於兩種藥劑。因此,一或多種藥劑可以存在於第一容器中,且套組可以在第二容器中視情況包括一或多種藥劑。一或多種容器置放於封裝內,且該封裝可視情況包括投與或劑量說明書。套組可以包括額外組件,諸如用於投與藥劑以及稀釋劑之注射器或其他構件或用於調配之其他構件。因此,該套組能夠包含:a)包含本文所描述之化合物及醫藥學上可接受之載劑、媒劑或稀釋劑的醫藥組合物;及b)容器或封裝。該套組可視情況包含描述一種在本文所描述之方法中之一或多者(例如預防或治療本文所描述之疾病及病症中之一或多者)中使用醫藥組合物之方法的說明書。該套組可視情況包含第二醫藥組合物,其包含一或多種本文所描述之用於共療法用途之額外藥劑、醫藥學上可接受之載劑、媒劑或稀釋劑。套組中所含有之包含本文所描述之化合物之醫藥組合物及第二醫藥組合物可視情況組合於相同醫藥組合物中。
實例實例中所提供之所有參考文獻均以引用之方式併入本文中。如本文所使用,所有縮寫、符號及定則均與當代科學文獻中所使用之彼等縮寫、符號及定則一致。參見例如Janet S. Dodd編, The ACS Style Guide: A Manual for Authors and Editors,第2版, Washington, D.C.: American Chemical Society, 1997,其以全文引用之方式併入本文中。
本發明之各種實施例描述於下文中。
實例部分中使用之縮寫之定義提供於下表中。
縮寫 | 字組或片語 |
app. | 明顯 |
Conc. | 濃度 |
DMF | N,N-二甲基甲醯胺 |
DMSO | 二甲亞碸 |
DMSO-d6 | 氘化二甲亞碸 |
dppf | 1.1´-雙(二苯基膦基)二茂鐵 |
dba | 二亞苄基丙酮 |
ES+ | 正電子噴霧電離 |
EtOAc | 乙酸乙酯 |
equiv. | 當量 |
FA | 甲酸 |
h | 小時 |
HEK | 人類胚胎腎 |
HPLC | 高效液相層析 |
i-PrOH | 異丙醇 |
LC-MS | 液相層析質譜法 |
MeOH | 甲醇 |
mL | 毫升 |
MHz | 百萬赫茲 |
MS | 質譜法 |
NMR | 核磁共振 |
No. | 化合物編號 |
Ph | 苯基 |
ppm | 百萬分率 |
RP- HPLC | 逆相高效液相層析 |
TFA | 三氟乙酸 |
THF | 四氫呋喃 |
合成部分 實例 1 : 合成表 I 之化合物本發明亦提供用於合成表I之化合物之方法,其表示本發明之另一實施例。可根據本文所描述之通用及特定合成、化學文獻中報導之合成程序或一般熟習此項技術者已知之方法製備本發明之化合物。如一般熟習此項技術者可理解,可在實驗期間確定之最佳反應條件可基於反應類型及反應中使用之特定試劑而改變。因此,除非特定描述,否則諸如壓力、溫度、試劑之相對比率、溶劑及反應時間的反應條件可由一般熟習此項技術者容易地選擇及改變,而不存在不當實驗。本發明之化合物及中間物可藉由一般熟習此項技術者已知之純化方法來製備。此等方法包括但不限於矽膠層析、再結晶、逆相HPLC (RP-HPLC)及超臨界流體層析(SFC)。RP-HPLC純化可使用選自0%至100%乙腈/含有諸如0.1% TFA或FA之添加劑水的範圍內的適合梯度在適合之逆相管柱(例如,Waters XBridge OBD C18,5 µm,19×150 mm)上實現。非鏡像異構物可藉由矽膠層析、RP-HPLC或對掌性HPLC分離。離散鏡像異構體可藉由使用對掌性HPLC解析由鏡像異構體之混合物獲得。可藉由一般熟習此項技術者已知之方法,諸如薄層層析法、逆相HPLC或串聯逆相HPLC-質譜法(LC-MS)來監測反應進程。
本文所描述之合成中使用之起始材料購自市售來源或可由一般熟習此項技術者使用化學文獻中報導或本文提及之方法來製備。
本文所描述之通用方法可用於製備表I之化合物。本文所描述之通用及特定方法作為實現本發明之說明提供。因此,其並不意欲對本發明之主張化合物之主題及範疇施加任何限制。
實例中所提供之所有參考文獻均以引用之方式併入本文中。如本文所使用,所有縮寫、符號及定則均與當代科學文獻中所使用之彼等縮寫、符號及定則一致。參見例如G. M. Banik, G. Baysinger, P. V. Kamat, N. J. Pienta,編, The ACS Guide to Scholarly Communication, Washington, D.C.: American Chemical Society, 2020 (https;//pub.acs.org/doi/book/10.1021/acsguide),其以全文引用之方式併入本文中。
本文所揭示之化合物可例如使用下文所描繪之通用程序(通用程序C)由對應腈中間物製成:
通用程序 C 本發明之化合物可藉由以下與本文所描述之彼等類似的程序經由其對應腈來製備。具有不同取代模式之腈可藉由以下WO2015187470、WO2016081668、WO2017197555、WO2017200825、WO2018/045276A1及WO2019/126354A1中描述之程序來製備。
以下腈中間物根據WO2018/045276A1及WO2019/126354A1中所描述之文獻程序來製備。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
8-苯甲基咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(3-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(2,3-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(3-氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(3,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(3,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈;
8-(2,5-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-甲腈;
8-(3-氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-甲腈;
8-(3,5-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-甲腈;
8-(2,3-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-甲腈;
8-(2,5-二氟-4-甲基苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-甲腈。
通用程序 A , 例示為適用於合成化合物 I-1以2個步驟合成標題化合物:
步驟 1 :合成8-(3-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
向8-(3-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈(220 mg,0.87 mmol,1.0當量)於甲醇(5.0 mL)中之溶液中添加0.50 N甲醇鈉於甲醇中之溶液(0.17 mL,0.087 mmol,0.10當量) (注意:亦可使用化學計算量或過量之甲醇鈉)。在環境溫度下攪拌6 h之後,添加氯化銨(280 mg,5.2 mmol,6.0當量)且攪拌反應物16 h。將反應混合物在真空中濃縮,用半飽和NaHCO
3溶液(20 mL)稀釋且用2×20 mL之CH
2Cl
2/iPrOH (5:1)萃取。合併之有機相經硫酸鈉乾燥,過濾,且濃縮,得到呈淺棕色泡沫固體狀之粗產物甲脒。其不經進一步純化即用於下一步驟中。LC/MS ES
+m/z = 270.2 [M+H]
+。
步驟 2:合成5-氟-2-(8-(3-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇
向8-(3-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(210 mg,0.79 mmol,1.0當量)於乙醇(7.0 mL)中之懸浮液中添加(Z)-3-乙氧基-2-氟-3-側氧基丙-1-烯-1-醇化鈉(490 mg,3.1 mmol,4.0當量)。在90℃下於密封小瓶中加熱反應物2.5h。在冷卻至環境溫度之後,添加1.0 N HCl水溶液(3.1 mL,3.1 mmol,4.0當量)。將所得物混合物在真空中濃縮,用水(50 mL)稀釋,用飽和NaHCO
3溶液調節至pH 6,且用2×50 mL之CH
2Cl
2/iPrOH (5:1)萃取。合併之有機相經硫酸鈉乾燥,過濾,且濃縮。粗材料經由矽膠層析(0至15%乙腈/甲醇(7:1)於CH
2Cl
2中)純化以得到呈淡褐色固體狀之標題化合物(180 mg,64%產率,歷經2個步驟)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 13.1-12.5 (單峰對, 1 H,互變異構體), 9.46 (s, 1 H), 8.30 (s, 1 H), 8.26-8.00 (單峰對, 1 H,互變異構體), 7.90 (s, 1 H), 7.50 (m, 1 H), 7.41 (m, 1 H), 7.32 (m, 1 H), 7.02 (app. t, 1 H), 4.53 (s, 2 H)。
化合物 I-2 根據通用程序A合成呈白色固體狀之2-(8-苯甲基咪唑并[1,2-a]吡𠯤-6-基)-5-氟嘧啶-4-醇
( 化合物2
)(25 mg,14%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, 甲醇-
d 4) δ (ppm) 9.30 (s, 1 H), 8.09 (s, 1 H), 7.99 (d, 1 H), 7.80 (s, 1 H), 7.40 (d, 2 H), 7.17 (t, 2 H), 7.07 - 7.11 (m, 1 H), 4.52 (s, 2 H)。
化合物 I-4 根據通用程序A合成呈淺褐色固體狀之2-(8-(2,3-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)-5-氟嘧啶-4-醇(化合物4) (150 mg,67%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, 丙酮-
d 6) δ (ppm) 10.6 (s, 1 H), 9.34 (s, 1 H), 8.16 (s, 1 H), 7.92 (s, 1 H), 7.78 (s, 1 H), 7.20 (t, 1 H), 7.09 (q, 1 H), 7.00 (q, 1 H), 4.60 (s, 2 H)。
化合物 I-6 根據通用程序A合成呈淡黃色固體狀之5-氟-2-(8-(3-氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-6) (200 mg,54%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO
-d 6) δ (ppm) 12.9 (br. s, 1 H), 9.44 (s, 1 H), 8.29 (s, 1 H), 8.16 (br. s, 1 H), 7.89 (s, 1 H), 7.39 (d, 1 H), 7.27 (d, 1 H), 7.17 (t, 1 H), 4.48 (s, 2 H), 2.14 (s, 3 H)。
化合物 I-7 根據通用程序A合成呈黃色固體狀之2-(8-(3,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)-5-氟嘧啶-4-醇(
化合物 I-7) (190 mg,57%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO
-d 6) δ (ppm) 13.0 (br. s, 1 H), 9.47 (s, 1 H), 8.31 (s, 1 H), 8.22 (br. s, 1 H), 7.91 (s, 1 H), 7.36 (br. s, 2 H), 7.07 (t, 1 H), 4.53 (s, 2 H)。
化合物 I-3 根據通用程序A合成呈白色固體狀之5-氟-2-(8-(3,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 3) 67 mg,34%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, 氯仿
-d) δ (ppm) 11.1 (br. s, 1 H), 9.14 (s, 1 H), 8.00-7.91 (m, 2 H), 7.87 (s, 1 H), 7.00 (d, 2 H), 4.56 (s, 2 H), 2.14 (s, 3 H)。
化合物 I-14以2個步驟合成標題化合物:
步驟 1 :合成8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
向8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈(2.5 g,8.9 mmol,1.0 當量)於甲醇(44 mL)中之懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(18 mL,8.9 mmol,1.0當量)。在環境溫度下攪拌4 h之後,再添加一份含0.50 N甲醇鈉之甲醇(5.3 mL,2.7 mmol,0.3當量)且再繼續攪拌2 h。接著添加氯化銨(470 mg,8.9 mmol,1.0當量)。16 h之後,將反應混合物在真空中濃縮,懸浮於飽和NaHCO
3水溶液中,且攪拌20 min。藉由過濾收集固體且用3體積之水及2體積之醚洗滌。將粗產物在加熱下再懸浮於100 mL乙腈中,用醚稀釋且過濾。濾餅用3體積之醚洗滌且乾燥,得到淺棕色固體(2.2 g,83%產率)。其不經進一步純化即用於下一步驟中。LC/MS ES
+m/z = 302.1 [M+H]
+。
步驟 2 :合成5-氟-2-(8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇
向含8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(1.9 g,6.2 mmol,1.0當量)之乙醇(31 mL)中添加(Z)-3-乙氧基-2-氟-3-側氧基丙-1-烯-1-醇化鈉(2.9 g,19 mmol,3.0當量)。在90℃下於密封容器中加熱溶液18 h。在冷卻至環境溫度之後,添加2.5 N乙醇HCl溶液(7.4 mL,19 mmol,3.0當量)。將所得物混合物在真空中濃縮,在加熱下懸浮於乙腈(100 mL)中。稍微冷卻之後,添加醚(100 mL)且攪拌混合物10 min。藉由過濾收集固體且用3體積之醚洗滌。將所得固體再懸浮於水中,攪拌1 h且過濾。粗材料經由製備型逆相HPLC (含有0.1%三氟乙酸作為添加劑之10%至70%乙腈/水)純化。不純的溶離份經由製備型逆相HPLC (含有0.1%三氟乙酸作為添加劑之10%至50%乙腈/水)再純化,得到呈灰白色固體狀之標題化合物(840 mg,37%產率)。
1H NMR (500 MHz, 甲醇
-d 4) δ (ppm) 9.43 (s, 1 H), 8.21 (s, 1 H), 8.08 (br. s, 1 H), 7.89 (s, 1 H), 7.09 (m, 1 H), 7.00 (m, 1 H), 4.63 (s, 2 H), 2.23 (s, 3 H)。
化合物 14 之 Na+ 鹽 在氮氣氛圍下向5-氟-2-(8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-14 ,10 g,27 mmol)於450 mL無水MeOH中之灰白色懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(54 mL,27 mmol)。在簡單音波處理之後,將所得淡黃色溶液在環境溫度下攪拌15 min且在真空中濃縮至乾燥。藉助於音波處理將固體再懸浮於250 mL醚且濃縮(兩次)。將所得固體再懸浮於650 mL之醚中且在環境溫度下攪拌3 h。藉由真空過濾收集固體且用醚(3×100 mL)洗滌。在過濾器上乾燥隔夜之後,將產物鹽在真空烘箱中在45℃下乾燥4天,得到呈白色固體狀之5-氟-2-(8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇化鈉(11 g,99% 產率)。
1H NMR (500 MHz, D
2O) δ (ppm) 8.92 (s, 1 H), 7.99 (d, 1 H), 7.97 (d, 1 H), 7.70 (d, 1 H), 6.98 (dd, 1 H), 6.86 (dd, 1 H), 4.48 (s, 2 H), 2.14 (s, 3 H)。
化合物 I-11 根據通用程序A合成呈黃金色固體狀之5-氟-2-(8-(3-氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-11)(61 mg,23%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 13.3 (br. s, 1 H), 9.60 (s, 1 H), 8.86 (s, 1 H), 8.24 - 8.27 (m, 1 H), 7.32 - 7.47 (m, 3 H), 7.03 - 7.06 (m, 1 H), 4.59 (s, 2 H)。
化合物 I-13 根據通用程序A合成呈棕色固體狀之2-(8-(3,5-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-基)-5-氟嘧啶-4-醇(
化合物 I-13) (57 mg,17%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 13.2 (br. s, 1 H), 9.61 (s, 1 H), 8.87 (s, 1 H), 8.25 (s, 1 H), 7.33 (d, 2 H), 7.10 (t, 1 H), 4.60 (s, 2 H)。
化合物 I-10 根據通用程序A合成呈淡黃色固體狀之2-(8-(2,3-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-基)-5-氟嘧啶-4-醇(
化合物 I-10) (85 mg,16%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 13.0 (br. s, 1 H), 9.62 (s, 1 H), 8.85 (s, 1 H), 8.23 (s, 1 H), 7.29 - 7.37 (m, 2 H), 7.09 - 7.16 (m, 1 H), 4.68 (s, 2 H)。
化合物 I-12 根據通用程序A合成呈灰白色固體狀之2-(8-(2,5-二氟苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-基)-5-氟嘧啶-4-醇(
化合物 I-12) (75 mg,57%產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, 甲醇-
d 4) δ (ppm) 9.67 (s, 1 H), 8.69 (s, 1 H), 8.12 (d, 1 H), 7.25 (m, 1 H), 7.13 (m, 1 H), 7.02 (m, 1 H), 4.73 (s, 2 H)。
化合物 I-19 根據通用程序A合成呈淺褐色固體狀之5-氟-2-(8-(2,5-二氟-4-甲基苯甲基)-[1,2,4]三唑并[1,5-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-19) (140 mg,66%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 13.1 (br. s, 1 H), 9.61 (s, 1 H), 8.83 (s, 1 H), 8.26 (br. s, 1 H), 7.35 (br. s, 1 H), 7.17 (m, 1 H), 4.57 (s, 2 H), 2.18 (s, 3 H)。
通用程序 B , 例示為適用於合成化合物 I-16以2個步驟合成標題化合物:
步驟 1:合成8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
向8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈(490 mg,1.8 mmol,1.0當量)於甲醇(5.0 mL)中之懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(3.6 mL,1.8 mmol,1.0當量) (注意:亦可使用催化量或過量之甲醇鈉)。在環境溫度下攪拌3 h 45 min之後,添加氯化銨(970 mg,18 mmol,10當量)且攪拌反應物20 h。將所得混合物在真空中濃縮至約2 mL體積且用EtOAc (20 mL)及10%NaHCO
3水溶液(10 mL)稀釋。在攪拌15 min之後,藉由過濾收集產物,用水(10 mL)洗滌且在真空中乾燥,得到呈灰白色固體狀之標題化合物(420 mg,80%產率)。LC/MS ES
+m/z = 287.9 [M+H]
+。
步驟 2 :合成5-氯-2-(8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇
向8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(100 mg,0.35 mmol)及2-氯-3-側氧基丙酸乙酯(110 mg,0.70 mmol)於甲醇(1.7 mL)中之懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(1.4 mL,0.70 mmol)。在65℃下於密封小瓶中加熱反應物2.5h。在冷卻至環境溫度之後,將所得混合物在真空中濃縮,用水(10 mL)稀釋,用6.0 N HCl水溶液溶液調節至pH 3,且用2×15 mL之CH
2Cl
2/iPrOH (8:1)萃取。合併之有機相經硫酸鈉乾燥,過濾且濃縮。粗材料經由矽膠層析(0%至20%乙腈/甲醇(7:1)於CH
2Cl
2中)純化且經由矽膠層析(20%至100% EtOAc/CH
2Cl
2)再純化,得到呈灰白色固體狀之標題化合物(37 mg,28%產率)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 12.6 (br. s, 1 H), 9.54 (s, 1 H), 8.36 (br. s, 1 H), 8.32 (s, 1 H), 7.89 (s, 1 H), 7.45 (br. s, 1 H), 7.25 (m, 1 H), 7.12 (m, 1 H), 4.58 (s, 2 H)。
化合物 I-17 根據通用程序B合成呈淺棕色固體狀之5-氯-2-(8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-17) (5.2 mg,2.2%總產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。
1H NMR (500 MHz, DMSO
-d 6) δ (ppm) 9.47 (s, 1 H), 8.45 (s, 1 H), 8.22 (d, 1 H), 7.94 (s, 1 H), 7.23 (dd, 1 H), 7.16 (dd, 1 H), 6.72 (d, 1 H), 4.56 (s, 2 H), 2.17 (br s, 3 H). LC/MS ES
+m/z = 388.0 [M+H]
+。
化合物 I-15以2個步驟合成標題化合物:
步驟 1:合成8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
根據通用程序A或B之步驟1合成呈淺棕色固體狀之8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(840 mg,76%產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。LC/MS ES
+m/z = 302.0 [M+H]
+。
步驟 2:合成2-(8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇
向8-(2,5-二氟-4-甲基苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(360 mg,1.2 mmol)及3-甲氧基丙烯酸甲酯(0.39 mL,3.6 mmol)於乙醇(6.0 mL)中之懸浮液中添加休尼格氏鹼(0.63 mL,3.6 mmol)。在90℃下於密封小瓶中加熱反應物3h。在冷卻至環境溫度之後,用2.5 N乙醇HCl溶液(1.4 mL,3.6mmol)處理所得混合物且濃縮至乾燥。粗材料經由矽膠層析(0%至20%乙腈/甲醇(7:1)於CH
2Cl
2中)純化且經由矽膠層析(0至15% MeOH/CH
2Cl
2)再純化,得到呈淺棕色固體狀之標題化合物(120 mg,28%產率)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 11.9 (br. s, 1 H), 9.52 (s, 1 H), 8.31 (s, 1 H), 8.07 (br. d, 1 H), 7.89 (s, 1 H), 7.37 (dd, 1 H), 7.16 (dd, 1 H), 6.38 (br. d, 1 H), 4.54 (s, 2 H), 2.18 (s, 3 H)。
化合物 I-8以2個步驟合成標題化合物:
步驟 1:合成8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
根據通用程序A或B之步驟1合成呈奶黃色固體狀之8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(5.1 g,91%產率)。視需要改變反應條件(諸如試劑比率、溫度及反應時間)及純化方法。LC/MS ES
+m/z = 270.2 [M+H]
+。
步驟 2:合成2-(8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)-5-甲基嘧啶-4-醇
向8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(400 mg,1.5 mmol)及2-甲基-3-側氧基丙酸乙酯(230 mg,1.8 mmol)於
t-BuOH (9.9 mL)中之溶液中添加碳酸氫鉀(220 mg,2.2 mmol)。將反應物加熱至回流2h。在冷卻至環境溫度之後,添加水且藉由過濾收集產物且乾燥,得到呈奶黃色固體狀之標題化合物(410 mg,82%產率)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 11.6 (br. s, 1 H), 9.48 (s, 1 H), 8.30 (s, 1 H), 7.94 (br s, 1 H), 7.88 (s, 1 H), 7.48 (app. t, 1 H), 7.29 (m, 1 H), 7.19 (m, 1 H), 7.11 (app. t, 1 H), 4.60 (s, 2 H), 1.98 (s, 3 H)。
化合物 I-9 含5-氟-2-(8-(2-氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(230 mg,0.67 mmol)之9.0 mL乙腈-THF (2:1)用碳酸氫鈉(84 mg,1.0 mmol)及Selectfluor
TM(350 mg,1.0 mmol)處理且在50℃下加熱。在實驗過程中,再添加額外份碳酸氫鈉(42 + 28 mg)及Selectfluor
TM(180 + 120 mg)。在總共49 h之後,將反應物冷卻至環境溫度且添加20 mL水。所得混合物用1.0 N HCl水溶液酸化至pH 3且用2 × 25 mL之EtOAc萃取。合併之有機相經硫酸鈉乾燥,過濾,且濃縮。粗材料經由矽膠層析(0%至20%乙腈/甲醇(7:1)於CH
2Cl
2中)純化且經由製備型逆相HPLC (含有0.1%甲酸作為添加劑之15%至65%乙腈/水)再純化,得到呈淺棕色固體狀之標題化合物(23 mg,9.7%產率)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 12.6 (br. s, 1 H), 8.98 (s, 1 H), 8.19 (br. s, 1 H), 7.74 (d, 1 H), 7.48 (app. t, 1 H), 7.28 (m, 1 H), 7.19 (m, 1 H), 7.10 (app. t, 1 H), 4.56 (s, 2 H)。
化合物 I-5 含5-氟-2-(8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(200 mg,0.56 mmol)之10 mL乙腈-THF (1:1)用碳酸氫鈉(94 mg,1.1 mmol)及Selectfluor
TM(400 mg,1.1 mmol)處理且在50℃下加熱。在實驗過程中,再添加額外份碳酸氫鈉(3 × 47 mg)及Selectfluor
TM(3 × 200 mg)。在總共74 h之後,將反應物冷卻至環境溫度且添加40 mL水。所得混合物用1.0 N HCl水溶液酸化至pH 3且用2 × 40 mL之CH
2Cl
2/iPrOH (6:1)萃取。合併之有機相經硫酸鈉乾燥,過濾,且濃縮。粗材料藉由矽膠層析(0至20%乙腈/甲醇(7:1)於CH
2Cl
2中)、製備型逆相HPLC (具有0.1% TFA作為添加劑之10%至70%乙腈/水)及最終管柱層析法(20%至100% EtOAc/己烷)純化,得到呈白色固體狀之標題化合物(24 mg,11%產率)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 12.8 (br. s, 1 H), 8.99 (s, 1 H), 8.20 (br. s, 1 H), 7.75 (d, 1 H), 7.42 (m, 1 H), 7.25 (m, 1 H), 7.13 (m, 1 H), 4.54 (s, 2 H)。
化合物 I-18以5個步驟合成標題化合物:
步驟 1:合成6,8 -二溴-3-氟咪唑并[1,2-a]吡𠯤
含6,8-二溴咪唑并[1,2-a]吡𠯤(2.4 g,8.7 mmol)之40 mL乙腈用Selectfluor
TM(4.6 g,13 mmol)處理且在50℃下加熱。在22 h之後,將反應物冷卻至環境溫度,傾入150 mL半飽和NaHCO
3溶液中且用2 × EtOAc (總共400 mL)萃取。合併之有機相經硫酸鈉乾燥,過濾且濃縮。粗材料藉由矽膠層析(0至20% EtOAc/己烷)純化,得到呈橙色固體狀之標題化合物(580 mg,23%產率)。
步驟 2:合成6-溴-8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤
乾燥鋅粉末(240 mg,3.7 mmol)於THF (3.0 mL)中之懸浮液用1,2-二溴乙烷(30 mL,催化劑)處理且在50℃下加熱所得混合物。接著添加氯三甲基矽烷(30 mL,催化劑)。在15 min之後,將混合物冷卻至環境溫度。添加乾燥氯化鋰(170 mg,3.9 mmol),接著逐滴添加1-(溴甲基)-2,5-二氟-3-甲苯(480 mg,2.2 mmol)於THF (2.0 mL)中之溶液(注意:放熱反應)。將混合物在環境溫度下攪拌1 h。同時,6,8-二溴-3-氟咪唑并[1,2-a]吡𠯤(580 mg,2.0 mmol)及Pd(PPh
3)
2Cl
2(41 mg,0.059 mmol)於THF (3.0 mL)中之漿液用氮氣脫氣。經由注射器將新形成之鋅酸鹽溶液轉移至此漿液中且用2×0.5 mL THF沖洗以確保完全轉移。將所得混合物在環境溫度下攪拌1 h 20 min且接著在40℃下攪拌4 h。在冷卻至環境溫度之後,反應物用4 mL飽和NH
4Cl溶液淬滅。有機層經濃縮,用CH
2Cl
2(10 mL)稀釋且經由矽藻土床過濾。濃縮濾液,得到棕色殘餘物,其藉由矽膠層析(負載有CH
2Cl
2之化合物且用0至10% EtOAc/己烷溶離)純化,得到呈黃色固體狀之標題化合物(440 mg,63%產率)。
步驟 3:合成8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤-6-甲腈
由6-溴-8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤(440 mmol,1.2 mmol)、氰化鋅(100 mg,0.87 mmol)、Pd
2(dba)
3(46 mg,0.050 mmol)及1,1'-雙(二苯基膦基)二茂鐵(dppf) (41 mg,0.075 mmol)於無水DMF (5.0 mL)中構成的反應混合物用氮氣脫氣且接著在90℃下加熱6 h。將反應物冷卻至環境溫度且用CH
2Cl
2(50 mL)、水(40 mL)及28%氫氧化銨溶液(4.0 mL)處理。水層用CH
2Cl
2(50 mL)萃取。合併之有機層經Na
2SO
4乾燥,過濾且濃縮,得到棕色油狀物,其藉由管柱層析(0至20% EtOAc/己烷梯度)進行純化,得到呈淺褐色固體狀之標題化合物(310 mg,81%產率)。LC/MS ES
+m/z = 302.8 [M+H]
+。
步驟 4:合成8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤-6-甲脒
向8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤-6-甲腈(150 mg,0.50 mmol)於甲醇(6.0 mL)中之懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(1.0 mL,0.50 mmol)。在環境溫度下攪拌4 h 30 min之後,添加氯化銨(270 mg,5.0 mmol)且攪拌反應物18 h。所得混合物在真空中濃縮,用10%NaHCO
3水溶液(10 mL)處理且進行音波處理,得到懸浮液。在攪拌1 h之後,產物藉由過濾收集,用水(10 mL)洗滌且在真空中乾燥,得到呈淺褐色固體狀之標題化合物(170 mg,>100%產率)。其不經進一步純化即用於下一步驟中。LC/MS ES
+m/z = 319.7 [M+H]
+。
步驟 5:合成2-(8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤-6-氟嘧啶-4-醇
向8-(2,5-二氟-4-甲基苯甲基)-3-氟咪唑并[1,2-a]吡𠯤-6-甲脒(0.50 mmol,來自前一步驟之理論量)於乙醇(5.0 mL)中之懸浮液中添加(Z)-3-乙氧基-2-氟-3-側氧基丙-1-烯-1-醇化鈉(310 mg,2.0 mmol)。在90℃下於密封小瓶中加熱反應物16h。在冷卻至環境溫度之後,混合物用水(7.5 mL)稀釋,用1N HCl水溶液調節至pH 4。所得淺棕色固體藉由過濾收集,用水(50 mL)及乙基醚(30 mL)洗滌,且乾燥,得到呈棕色固體狀之標題化合物(140 mg,71%產率,歷經2個步驟)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 12.8 (br. s, 1 H), 8.98 (s, 1 H), 8.22 (br. s, 1 H), 7.74 (d, 1 H), 7.35 (br. s, 1 H), 7.15 (m, 1 H), 4.50 (s, 2 H), 2.18 (s, 3 H)。
化合物 I-20以2個步驟合成標題化合物:
步驟 1:合成8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒
向8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲腈(500 mg,1.9 mmol)於甲醇(22 mL)中之溶液中添加25 wt%甲醇鈉於甲醇中之溶液(2.1 mL,9.3 mmol)。在環境溫度下攪拌1 h之後,添加氯化銨(1.0 g,19 mmol)且攪拌反應物隔夜。將反應混合物在真空中濃縮,用半飽和NaHCO
3溶液(20 mL)及1.0 N氫氧化鈉溶液(2.0 mL)稀釋,且用2×20 mL之EtOAc萃取。合併之有機相經硫酸鈉乾燥,過濾且濃縮,得到呈棕色固體狀之粗產物。其不經進一步純化即用於下一步驟。LC/MS ES
+m/z = 288.1 [M+H]
+。
步驟 2:合成5-氟-2-(8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇
向8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-甲脒(500 mg,1.7 mmol)於乙醇(9.0 mL)中之懸浮液中添加(Z)-3-乙氧基-2-氟-3-側氧基丙-1-烯-1-醇化鈉(820 mg,5.2 mmol)。在90℃下於密封小瓶中加熱反應物2h。在冷卻至環境溫度之後,逐滴添加濃HCl溶液以將混合物酸化至pH 4。所得混合物在真空中濃縮。藉由製備型逆相HPLC (乙腈-水梯度,具有0.1% TFA作為添加劑)純化,得到呈黃色固體狀之標題化合物(200 mg,28%產率,歷經2個步驟)。
1H NMR (500 MHz, DMSO-
d 6) δ (ppm) 12.6 (br. s, 1 H), 9.49 (s, 1 H), 8.32 (s, 1 H), 8.19 (br. s, 1 H), 7.89 (s, 1 H), 7.43 (s, 1 H), 7.25 (m, 1 H), 7.13 (m, 1 H), 4.58 (s, 2 H)。
化合物 I-20 之 Na+ 鹽 在氮氣氛圍下向5-氟-2-(8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇(
化合物 I-20,10 g,28 mmol)於450 mL無水MeOH中之淺棕色懸浮液中添加0.50 N甲醇鈉於甲醇中之溶液(57 mL,28 mmol)。在簡單音波處理之後,在環境溫度下攪拌所得淺橙色溶液15 min且在真空中濃縮至乾燥。藉助於音波處理將固體再懸浮於200 mL醚且濃縮(兩次)。將所得固體再懸浮於500 mL之醚中且在環境溫度下攪拌3 h。藉由真空過濾收集固體且用醚(3×100 mL)洗滌。在過濾器上乾燥隔夜之後,將產物鹽在真空烘箱中在45℃下乾燥5天,得到呈淺褐色固體狀之5-氟-2-(8-(2,5-二氟苯甲基)咪唑并[1,2-a]吡𠯤-6-基)嘧啶-4-醇化鈉(11 g,99% 產率)。
1H NMR (500 MHz, D
2O) δ (ppm) 8.90 (s, 1 H), 7.98 (d, 1 H), 7.95 (d, 1 H), 7.70 (d, 1 H), 7.10 (m, 1 H), 6.98-6.89 (m, 2 H), 4.53 (s, 2 H)。
生物部分 表I
之化合物之生物特性的評估本發明亦提供對表I之化合物之生物特性的評估。在各種細胞及分析中活體外測試本發明之化合物之代表作為sGC刺激劑的活性且活體內測試其降低動物血壓的能力。血壓降低用作化合物活體內接合目標之能力的指示。此等生物特性表示本發明之另一實施例。
實例 2 : 藉由基於 cGMP GloSensor 細胞之分析 , 384 孔 格式進行生物活性量測表現GloSensor
TM40F cGMP (產品編號:CS182801,Promega)之人類胚胎腎細胞(HEK293)細胞用於評估測試化合物之活性。併入至此等細胞中之發光生物感測器(經工程改造之螢光素酶)偵測由刺激sGC酶之化合物形成之cGMP且發射螢光。
將cGMP GloSensor細胞維持在補充有胎牛血清(FBS,10%最終)及潮黴素(200ug/ml)之達爾伯克改良之伊格爾培養基(Dulbecco's Modification of Eagle's Medium;DMEM)中。分析前一天,將細胞以1.5 × 10
4個細胞/孔之密度接種於聚D-離胺酸塗佈之384孔平坦白底盤(Corning目錄號35661)中之50µL體積的具有10% FBS之DMEM中。在37℃下在具有5% CO
2之潮濕腔室中培養細胞隔夜。次日,移除培養基且用40微升/孔之GloSensor
TM ,2mM (Promega,目錄號E1291)替換細胞。在25℃下處理細胞90分鐘以允許基質在細胞中平衡。將測試化合物及二伸乙基三胺NONO鹽(DETA-NONO鹽)在無血清CO
2非依賴性培養基中稀釋至3mM (20×)且以4×稀釋液連續稀釋以產生5X劑量曲線,將10 ul添加至各孔中(針對測試化合物溶液為x μM濃度且對於DETA-NONO鹽溶液為10 μM濃度;其中x為以下最終濃度中之一者:30 μM、7.5 μM、1.9 μM、469 nM、117 nM、29.3 nM、7.3 nM、1.83 nM、0.46 nM、0.11 nM、0.03 nM)以用於動力學研究,立刻用Envision (Perkin Elmer)以0.2秒/孔量測螢光。對於終點SAR篩選,在室溫下培育55 min之後收集資料。
使用4參數擬合(對數(促效劑)與反應-可變斜率)分析濃度反應資料。EC50係由曲線擬合內推且定義為化合物引發其最大反應之50%時的濃度。當對既定化合物進行多次實驗時,報導所有實驗之幾何平均值。
下表A彙總了本發明之化合物之Glo分析中的EC
50值:
表A.
藉由GloSensor分析測定HEK細胞中之sGC酶活性值。sGC酶活性值(表示為EC
50,其定義為化合物引發其最大反應之50%時的濃度)之代碼定義:EC
50≤ 100 nM = A;100 nM < EC
50≤ 1000 nM = B;1000 nM < EC
50=C。*對於化合物I-20及I-14,使用游離酸及鈉鹽兩者且此處之結果為獨立於形式運行之所有實驗的平均值。
化合物編號 | Glo EC 50(nM) | 化合物編號 | Glo EC 50(nM) |
I-19 | B | I-5 | A |
I-2 | B | I-14* | A |
I-1 | B | I-16 | A |
I-4 | B | I-15 | B |
I-20* | A | I-17 | A |
I-11 | B | I-18 | A |
I-13 | B | I-12 | B |
I-10 | B | I-3 | A |
I-6 | A | I-8 | C |
I-7 | B | I-9 | B |
實例 3. 藉由基於 cGMP 神經元細胞之分析進行生物活性量測自18天妊娠史泊格-多利雌性之胎兒分離出大鼠原代神經元。將胎兒收集在漢克氏平衡鹽溶液(HBSS)中且快速移除大腦。將腦海馬區分離且機械地碎裂。在37℃下在不具有Ca2+及Mg2+之HBSS中用0.25% (wt/vol)胰蛋白酶溶液進行進一步組織消化15 min。胰蛋白酶化之後,將細胞洗滌且再懸浮於補充有0.5 mM L-麩醯胺酸、12.5uM麩胺酸、2% B-27及100 U/mL青黴素及100µg/mL鏈黴素之神經基質培養基中。將細胞以26 × 10
3或4 × 10
4或3 × 10
4個細胞/孔之密度接種於聚D-離胺酸塗佈之384孔平坦透明底盤(Corning目錄號354662)中。在37℃下在具有5% CO
2之潮濕腔室中培育細胞6至7天。移除培養基且用含有Ca2+及Mg2+之HBSS洗滌細胞1×,且用40 uL含有0.5 mM IBMX之HBSS替換,且在37℃下培育15分鐘。添加具有二伸乙基三胺NONO鹽(DETA-NO)之10 uL 5×測試化合物儲備液。DETA-NO之最終濃度為10 μM或30 μM。在37℃下培育細胞20 min。移除培養基,添加50 uL冰冷的10%乙酸,且在4℃下培育60分鐘。在4℃下以1000 ×
g離心5分鐘以使細胞碎片沈澱之後,將上清液抽吸至清潔盤中且分析樣本之cGMP內含物。使用LC-MS/MS自各樣本測定cGMP濃度。
使用4參數擬合(對數(促效劑)與反應-可變斜率)分析濃度反應資料。EC50係由曲線擬合內推且定義為化合物引發其最大反應之50%時的濃度。當對既定化合物進行多次實驗時,報導所有實驗之幾何平均值。
下表B彙總了本發明之化合物之神經元分析中的EC
50值:
表B.
基於神經元之細胞分析。EC
50≤ 100 nM = A;100 nM < EC
50≤ 1000 nM = B;1000 nM < EC
50= C。*對於化合物I-20及I-14,使用游離酸及鈉鹽兩者且此處之結果為獨立於形式運行之所有實驗的平均值。
化合物編號 | sGC 神經元 EC 50(nM) | 化合物編號 | sGC 神經元 EC 50(nM) |
I-5 | A | I-3 | A |
I-2 | B | I-15 | B |
I-1 | B | I-9 | A |
I-4 | A | I-19 | A |
I-20* | A | I-14* | A |
I-16 | A | I-12 | A |
I-6 | A | I-7 | A |
實例 4 : 對 CHO-K1 細胞中 穩定 表現之 人類 a2b1 sGC 同功酶的生物活性量測將sGC刺激劑溶解於DMSO中呈10 mM溶液且儲存於-20℃下。為達成所需測試濃度,將儲備液濃度連續稀釋至DMSO中且接著在分析緩衝液中稀釋至適當濃度。
在37℃下在空氣中含有5% CO
2之95%潮濕氛圍中將穩定轉染有人類α2β1 sGC同功酶(由Ironwood之GenScript產生)之CHO-K1細胞培養在具有10%胎牛血清、4 µg/mL嘌呤黴素(Gibco目錄號A11138-03)及0.4 mg/mL遺傳黴素(Gibco目錄號10131-027)之F-12K培養基(ATCC目錄號30-2004)中。對於GC活性分析,將細胞分別以3 × 10
4個細胞/孔或15 × 10
3之密度接種於384孔聚D-離胺酸塗佈之平底盤(Fisher Scientific #08-774-311)中之50 μL或70 μL培養基中。在37℃下在補充有5% CO
2之潮濕腔室中培養細胞24小時。
對於各測試濃度,將化合物在100% DMSO中稀釋至其最終分析濃度之100倍。緊接在分析之前,將該等溶液20倍稀釋至含有鈣、鎂及50 µM DETA-NONO鹽之HBSS中(5×最終分析濃度)。移除培養基且用40 μL HBSS洗滌細胞一次。接著在37℃下用HBSS中含有0.5 mM IBMX之40 μL溶液培育細胞15 min。將細胞添加至10μL sGC刺激劑/HBSS/DETA-NONO鹽盤中,在37℃下再培育20 min。最終DMSO濃度為1%,最終DETA-NONO鹽濃度為10 µM;且最終化合物濃度為30,000 nM、6000 nM、1200 nM、240 nM、48 nM、9.6 nM、1.92 nM、0.384 nM、0.077 nM、0.015nM或0.003 nM。
在與化合物一起培育後,移除分析緩衝液且向各孔中添加50 μL冰冷的10%乙酸+150 ng/mL內標物(+3 cGMP)。將樣本在冰上培育30至60 min。在4℃下以1000×
g離心5 min以使細胞碎片沈澱後,將上清液轉移至清潔盤中且分析樣本之cGMP內含物。
使用GraphPad Prism軟體v.8以4參數擬合(對數(促效劑)與反應-可變斜率)分析資料。EC50係由曲線擬合內推且定義為化合物引發其最大反應之50%時的濃度。當對既定化合物進行多次實驗時,報導所有實驗之幾何平均值。
下表C彙總了本發明之化合物之CHO分析中的EC
50值:
表C
CHO細胞分析。EC
50≤ 100 nM = A;100 nM < EC
50≤ 1000 nM = B;1000 nM < EC
50= C。*對於化合物I-20及I-14,使用游離酸及鈉鹽兩者且此處之結果為獨立於形式運行之所有實驗的平均值。
化合物編號 | sGC CHO EC 50(nM) | 化合物編號 | sGC CHO EC 50(nM) |
I-14* | A | I-15 | B |
I-2 | B | I-19 | A |
I-17 | A | I-18 | A |
I-4 | A | I-5 | A |
I-20* | A | I-16 | A |
實例
5
:
在本發明之代表性化合物的多個濃度之急性劑量後
,
血壓正常大鼠之血壓影響
a)
化合物
I-14
雄性血壓正常的史泊格多利大白鼠係購自Charles River Laboratories。此等大鼠已安置有留置股動脈導管。將動物拴在繫繩系統且連接至壓力傳感器以監測心臟血管(CV)參數,特定言之平均動脈壓(MAP)及心率(HR)。使動物適應該系統隔夜且收集基線CV參數。隨後向清醒自由移動的大鼠投與1、3、10及30 mg/kg單次口服劑量的含
化合物 I-
14之Milli-Q水(由化合物14之鈉鹽產生的劑量)。在給藥前及給藥後2小時經由導管線自各動物收集血液樣本以用於化合物濃度定量。記錄給藥後十小時內的血液動力學量測。針對此等研究使用五十四隻雄性大鼠且將其在250至275公克之體重範圍內排序以收容。根據方案MIL-110,將其單獨圈養在溫度(21 ± 1℃)、相對濕度(36 ± 1%)之受控條件下且置放於SmartLabs飼養室(21 Erie Street,Cambridge,MA)的12-小時光-暗循環(在6:00AM開燈且在6:00PM關燈)房間內。允許動物隨意獲取食物(LabDiet Prolab Isopro RMH 3000,St.Louis,MO)及水。進行兩組研究。對於第一組研究,
化合物 I -14以0.3及1.0 mg/ml調配於Milli-Q水中且冷凍在-20℃下。對於第二組研究,在Cyclerion Therapeutics稱重
化合物 I-
14之鈉鹽且在SmartLabs復原以提供
化合物 I-
14於Milli-Q水中之0.1、0.3、1.0及3.0 mg/ml 溶液。在給藥前4小時內將製備之調配物解凍且儲存於室溫下,或在給藥前2小時內製成且儲存於室溫下。
歷經6個獨立的階段進行研究。個體之總數目及治療劑分配在下表中列出。動物最初在接收的3天內使用且若導管保持暢通,則在清除6至7天後再使用一次。動物未使用超過兩次。
群組 | 動物數目 | 治療劑 | 劑量體積 | 劑量濃度 |
1 | 13 | 媒劑 | 10 mL/kg | - |
2 | 9 | 1 mg/kg 化合物 I-14 | 10 mL/kg | 0.1 mg/mL |
3 | 6 | 3 mg/kg 化合物 I-14 | 10 mL/kg | 0.3 mg/mL |
4 | 11 | 10 mg/kg 化合物 I-14 | 10 mL/kg | 1.0 mg/mL |
5 | 6 | 30 mg/kg 化合物 I-14 | 10 mL/kg | 30 mg/mL |
血壓之量測 此研究利用ADInstruments LabChart (v8)自繫栓至血壓傳感器(Harvard Apparatus目錄號APT300)的清醒自由移動大鼠收集血液動力學資料。在適應繫繩及壓力傳感器隔夜之後,在1小時基線記錄時間段之後向動物給藥。向動物投與10 mL/kg之劑量體積的
化合物 I-
14之鈉鹽形式或媒劑的單一口服(P.O.)劑量。繼續給藥後10小時內的資料收集。
使用ADInstruments LabChart (v8)監測且輸出血液動力學資料。持續監測血壓及心率,且以1000個資料點/秒收集資料,接著平均至10-分鐘分組中以用於分析。使用Microsoft 365之Microsoft Excel使用在給藥前1小時時間段內平均化的給藥前基線計算相對於基線MAP之變化(ΔBMAP)及相對於基線HR之變化(ΔBHR)。使用此10-分鐘分組資料集測定峰ΔVMAP、峰ΔVMAP之時間、峰ΔVHR及峰ΔVHR之時間。資料集進一步合併至1-小時分組中以用於MAP及HR圖及對ΔBMAP、ΔBMAP及ΔBHR之分析。此等術語/縮寫之定義概述於下文:
Δ BMAP, dMAP | 相對於基線平均動脈壓之變化 |
Δ BHR, dHR | 相對於基線心率之變化 |
Δ VMAP | 經媒劑調整之平均動脈壓 |
Δ VMAP | 經媒劑調整之心率 |
AOC | 曲線上面積 |
在GraphPad Prism (v8)中進行統計分析。藉由雙因子重複量測ANOVA接著鄧尼特多重比較測試來測定與媒劑治療之大鼠相比,ΔBMAP及ΔBHR之顯著性,若存在遺漏資料點,則利用混合效應分析。藉由各劑量組在各時間點之ΔBMAP減去媒劑組之ΔBMAP來計算經媒劑調整之MAP (ΔVMAP)。以類似於ΔVMAP之方式計算經媒劑調整之HR (ΔVHR)。
藉由單因子ANOVA接著鄧尼特多重比較測試來測定與媒劑相比,AOC資料之顯著性。
在分析之前移除一些研究資料。由於2-小時血液樣本收集,移除給藥後130 min及140 min收集之資料。由於在470分鐘開始且持續直至研究結束(600 min)之實驗期間的信號損失,排除一隻大鼠在1 mg/kg下之幾個時間點。出於各種原因,自所有資料集排除5隻動物之全部時程,包括其用於特定分析之離群值或因導致異常結果之信號損失。
血壓變化 MAP相對於基線之變化(ΔBMAP)以圖形方式展示於圖1中。相比於媒劑治療之大鼠,用
化合物 I-
14治療之大鼠的MAP減少更多(如藉由相對於基線MAP之變化ΔBMAP評定)。藉由雙因子ANOVA,ΔBMAP資料集為顯著的(對於治療劑及時間,p<0.0001,且對於治療劑×時間相互作用,p=0.045)。主要治療作用之鄧尼特氏多重比較測試得到:與經媒劑治療之大鼠相比,對於1 mg/kg為p=ns,對於3 mg/kg為p=0.0034且對於10及30 mg/kg劑量為p<0.0001。在各時間點及各劑量對比媒劑治療之大鼠的單一作用之單獨鄧尼特氏多重比較測試展示ΔBMAP在用10及30 mg/kg
化合物 I-
14治療之大鼠中的整個給藥後6-小時時間段內減少更多;在用3 mg/kg
化合物 I-
14治療之大鼠中的給藥後1-小時、2-小時及3-小時減少更多;而在用1 mg/kg
化合物 I-
14治療之大鼠中則沒有減少。
藉由使用10-分鐘分組的資料集計算
化合物 I-14對ΔVMAP之最大作用且展示於下表D中:
表D.
化合物 I-14對經媒劑調整之MAP (ΔVMAP)的最大作用
化合物 14 | 峰 Δ VMAP (mm Hg) | 到達峰之時間 (min) |
1 mg/kg | -6.2 | 90 |
3 mg/kg | -10.1 | 70 |
10 mg/kg | -22.3 | 30 |
30 mg/kg | -24.4 | 30 |
如藉由主效應分析、單一效應分析及藉由AOC評定,對ΔBMAP無作用的劑量為1 mg/kg。
結論 相對於基線且如自媒劑調整,
化合物 I-
14在3、10及30 mg/kg下降低MAP。
b) 化合物 I -20用
化合物 I-
20進行於上文所描述之研究類似的研究。向清醒自由移動的大鼠投與1、3、10及30 mg/kg單次口服劑量的含
化合物 I-
20(由化合物I
-20之鈉鹽製備的劑量)之Milli-Q水。在給藥前及給藥後2小時經由導管線自各動物收集血液樣本以用於化合物濃度定量。記錄給藥後十小時內地血液動力學量測。
血壓變化 相對於基線MAP之變化(ΔBMAP)以圖形方式展示於圖2中。相比於經媒劑治療之大鼠,用
化合物 I-
20治療之大鼠的MAP減少更多(如藉由相對於基線MAP之變化Δ
BMAP評定)。藉由雙因子ANOVA,Δ
BMAP資料集為顯著的(對於治療劑及治療劑×時間相互作用,p<0.0001;且對於時間,p=0.022)。主要治療作用之鄧尼特氏多重比較測試得到:與經媒劑治療之大鼠相比,對於1 mg/kg為p=0.055 (ns),對於3 mg/kg為p=0.0001且對於10及30 mg/kg劑量為p<0.0001。在各時間點及各劑量對比媒劑治療之大鼠的單一作用之單獨鄧尼特氏多重比較測試展示MAP在用3、10及30 mg/kg
化合物 I-
20治療之大鼠中的整個給藥後6-小時時間段內減少更多;在用1 mg/kg
化合物 I-
20治療之大鼠中的給藥後1-小時、2-小時、3-小時、4-小時及5-小時減少更多。
藉由使用10-分鐘分組的資料集計算
化合物 I-20對Δ
VMAP (經媒劑調整之MAP)之最大作用且展示於下表E中:
表E.
化合物 I -20對經媒劑調整之MAP (Δ
VMAP)的最大作用
化合物 20 | 峰 Δ VMAP (mm Hg) | 到達峰之時間 (min) |
1 mg/kg | -14.3 | 20 |
3 mg/kg | -19.2 | 20 |
10 mg/kg | -20.2 | 30 |
30 mg/kg | -38.1 | 30 |
結論 化合物 I-
20在1、3、10及30 mg/kg下降低MAP,相對於基線且如自媒劑調整。
其他 BP 量測在與上文所描述之彼等研究類似的研究中,調配於PEG400中且以10 mg/kg給與之
化合物 I-
4顯示在給藥後50 min,MAP相對於基線之最大減少(Δ
BMAP)為20 mm Hg。在與上文所描述之彼等研究類似的研究中,調配於PEG400中且以10 mg/kg給與之
化合物 I-
20顯示在給藥後42 min,峰Δ
BMAP為-26 mm Hg。在
化合物 I-
20以1、3或10 mg/kg進行測試且調配於甲基纖維素中的另一研究中,化合物在所有測試劑量下均能夠自基線降低MAP。
圖1展示化合物
I-
14對雄性血壓正常大鼠中之MAP相對於基線之變化(Δ
BMAP)的作用。
圖2展示化合物
I-
20對雄性血壓正常大鼠中之Δ
BMAP的作用。
Claims (28)
- 如請求項1或2之化合物或其醫藥學上可接受之鹽,其中J C1為H、F、Cl、C 1-2烷基或經1至3個氟原子取代之C 1-2氟烷基。
- 如請求項3之化合物或其醫藥學上可接受之鹽,其中J C1為H或F。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為2或3。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為0。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為1。
- 如請求項1至8中任一項之化合物或其醫藥學上可接受之鹽,其中各J B獨立地為H、F或C 1-4烷基或經1至3個氟原子取代之C 1-4氟烷基。
- 如請求項9之化合物或其醫藥學上可接受之鹽,其中各J B獨立地為H、F或C 1-4烷基。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為2或3;且各J B獨立地為F、甲基或經1至3個氟原子取代之氟甲基。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為2或3;且各J B獨立地為F或甲基。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為2;且J B均為F或J B中之一者為F且另一者為甲基。
- 如請求項1至5中任一項之化合物或其醫藥學上可接受之鹽,其中n為3;且J B中之兩者為F且另一者為甲基。
- 如請求項1至14中任一項之化合物或其醫藥學上可接受之鹽,其中J D為H、F、Cl、甲基、乙基、氟甲基或氟乙基。
- 如請求項1至14中任一項之化合物或其醫藥學上可接受之鹽,其中J D為H或F。
- 如請求項1至16中任一項之化合物或其醫藥學上可接受之鹽,其中J C為H、Cl、F、甲基、乙基、氟甲基或氟乙基。
- 如請求項17之化合物或其醫藥學上可接受之鹽,其中J C為H或F。
- 如請求項17之化合物或其醫藥學上可接受之鹽,其中J C為H。
- 一種醫藥組合物,其包含如請求項1至25中任一項之化合物或其醫藥學上可接受之鹽,及醫藥學上可接受之賦形劑或載劑。
- 一種治療有需要個體之疾病的方法,其包含單獨或以組合療法形式向該個體投與治療有效量之如請求項1至25中任一項之化合物或其醫藥學上可接受之鹽,或如請求項26之醫藥組合物;其中該疾病或病症為將得益於sGC刺激或NO及/或cGMP之濃度增加的疾病或病症。
- 如請求項27之方法,其中該方法進一步包括向該個體投與額外治療劑。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163177020P | 2021-04-20 | 2021-04-20 | |
US63/177,020 | 2021-04-20 | ||
US202163229248P | 2021-08-04 | 2021-08-04 | |
US63/229,248 | 2021-08-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
TW202309038A true TW202309038A (zh) | 2023-03-01 |
Family
ID=81579984
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW111114883A TW202309038A (zh) | 2021-04-20 | 2022-04-19 | sGC刺激劑 |
Country Status (13)
Country | Link |
---|---|
US (1) | US20240208979A1 (zh) |
EP (1) | EP4326722A1 (zh) |
JP (1) | JP2024515119A (zh) |
KR (1) | KR20240058047A (zh) |
AU (1) | AU2022261862A1 (zh) |
BR (1) | BR112023021851A2 (zh) |
CA (1) | CA3216127A1 (zh) |
CL (1) | CL2023003105A1 (zh) |
CO (1) | CO2023015528A2 (zh) |
CR (1) | CR20230532A (zh) |
IL (1) | IL307865A (zh) |
TW (1) | TW202309038A (zh) |
WO (1) | WO2022225903A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024086179A1 (en) * | 2022-10-18 | 2024-04-25 | Tisento Therapeutics, Inc. | Pyrimidine sgc stimulators |
WO2024086182A1 (en) * | 2022-10-18 | 2024-04-25 | Tisento Therapeutics Inc. | Treatment of mitochondrial diseases with sgc stimulators |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2928079B2 (ja) | 1994-02-14 | 1999-07-28 | 永信薬品工業股▲ふん▼有限公司 | 1−(置換ベンジル)−3−(置換アリール)縮合ピラゾール類、その製造法及びその用途 |
DE19744026A1 (de) | 1997-10-06 | 1999-04-08 | Hoechst Marion Roussel De Gmbh | Pyrazol-Derivate, ihre Herstellung und ihre Verwendung in Arzneimitteln |
DE19830430A1 (de) | 1998-07-08 | 2000-01-13 | Hoechst Marion Roussel De Gmbh | Schwefelsubstituierte Sulfonylamino-carbonsäure-N-arylamide, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
DK1095016T3 (da) | 1998-07-08 | 2006-03-13 | Sanofi Aventis Deutschland | Svovlsubstituerede sulfonylaminocarboxylsyre-N-arylamider, deres fremstilling, deres anvendelse og farmaceutiske præparater omfattende dem |
DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
GB9824310D0 (en) | 1998-11-05 | 1998-12-30 | Univ London | Activators of soluble guanylate cyclase |
DE19942809A1 (de) | 1999-09-08 | 2001-03-15 | Bayer Ag | Verfahren zur Herstellung substituierter Pyrimidinderivate |
DE19943635A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
DE10216145A1 (de) | 2002-04-12 | 2003-10-23 | Bayer Ag | Verwendung von Stimulatoren der löslichen Guanylatcyclase zur Behandlung von Glaukom |
DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
EP2197551B1 (en) | 2007-09-06 | 2016-12-28 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
EP2244575B1 (en) | 2008-01-24 | 2013-07-17 | Merck Sharp & Dohme Corp. | Angiotensin ii receptor antagonists |
US8741910B2 (en) | 2008-11-25 | 2014-06-03 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
JP5411300B2 (ja) | 2009-02-26 | 2014-02-12 | メルク・シャープ・アンド・ドーム・コーポレーション | 可溶性グアニレートシクラーゼ活性化剤 |
US9284301B2 (en) | 2010-03-25 | 2016-03-15 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
ES2564503T3 (es) | 2010-05-27 | 2016-03-23 | Merck Sharp & Dohme Corp. | Activadores de la guanilato-ciclasa soluble |
WO2012058132A1 (en) | 2010-10-28 | 2012-05-03 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
WO2015187470A1 (en) | 2014-06-04 | 2015-12-10 | Merck Sharp & Dohme Corp. | Imidazo-pyrazine derivatives useful as soluble guanylate cyclase activators |
TW201625635A (zh) | 2014-11-21 | 2016-07-16 | 默沙東藥廠 | 作為可溶性鳥苷酸環化酶活化劑之三唑并吡基衍生物 |
US10213429B2 (en) * | 2015-05-28 | 2019-02-26 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
WO2017197555A1 (en) | 2016-05-16 | 2017-11-23 | Merck Sharp & Dohme Corp. | Fused pyrazine derivatives useful as soluble guanylate cyclase stimulators |
DK3507291T3 (da) | 2016-09-02 | 2021-08-30 | Cyclerion Therapeutics Inc | Kondenserede bicykliske sgc-stimulatorer |
WO2019126354A1 (en) | 2017-12-19 | 2019-06-27 | Cyclerion Therapeutics, Inc. | Sgc stimulators |
-
2022
- 2022-04-19 CA CA3216127A patent/CA3216127A1/en active Pending
- 2022-04-19 AU AU2022261862A patent/AU2022261862A1/en active Pending
- 2022-04-19 US US18/287,612 patent/US20240208979A1/en active Pending
- 2022-04-19 BR BR112023021851A patent/BR112023021851A2/pt unknown
- 2022-04-19 CR CR20230532A patent/CR20230532A/es unknown
- 2022-04-19 JP JP2023565192A patent/JP2024515119A/ja active Pending
- 2022-04-19 WO PCT/US2022/025310 patent/WO2022225903A1/en active Application Filing
- 2022-04-19 TW TW111114883A patent/TW202309038A/zh unknown
- 2022-04-19 KR KR1020237039779A patent/KR20240058047A/ko unknown
- 2022-04-19 IL IL307865A patent/IL307865A/en unknown
- 2022-04-19 EP EP22721237.0A patent/EP4326722A1/en active Pending
-
2023
- 2023-10-18 CL CL2023003105A patent/CL2023003105A1/es unknown
- 2023-11-17 CO CONC2023/0015528A patent/CO2023015528A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
CO2023015528A2 (es) | 2024-02-26 |
AU2022261862A2 (en) | 2024-07-18 |
CR20230532A (es) | 2024-03-22 |
JP2024515119A (ja) | 2024-04-04 |
IL307865A (en) | 2023-12-01 |
CL2023003105A1 (es) | 2024-03-22 |
US20240208979A1 (en) | 2024-06-27 |
WO2022225903A1 (en) | 2022-10-27 |
CA3216127A1 (en) | 2022-10-27 |
AU2022261862A1 (en) | 2023-11-30 |
BR112023021851A2 (pt) | 2024-02-06 |
EP4326722A1 (en) | 2024-02-28 |
KR20240058047A (ko) | 2024-05-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI582091B (zh) | 可溶性鳥苷酸環化酶(sGC)刺激物 | |
TWI774683B (zh) | sGC刺激劑之固體形式 | |
AU2022200331B2 (en) | Phosphorus prodrugs of sGC stimulators | |
US20240208979A1 (en) | sGC STIMULATORS | |
KR20200100696A (ko) | sGC 자극제 | |
EP3762389B1 (en) | Crystalline forms of an sgc stimulator | |
US20240207265A1 (en) | TREATMENT OF CNS DISEASES WITH sGC STIMULATORS | |
US20210017160A1 (en) | DEUTERATED sGC STIMULATORS | |
US20210017161A1 (en) | DEUTERATED sGC STIMULATORS | |
CN117957228A (zh) | sGC刺激剂 | |
US20230130739A1 (en) | DEUTERATED sGC STIMULATORS | |
WO2024086179A1 (en) | Pyrimidine sgc stimulators |