OA12058A - 5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors. - Google Patents

5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors. Download PDF

Info

Publication number: OA12058A
Authority: OA; OAPI
Prior art keywords: compound; mmol; compounds; dihydro; iower
Prior art date: 1999-10-11

Application number

OA1200200101A

Other languages

English (en)

Inventor

Charlotte Moira Norfo Allerton

Christopher Gordon Barber

Graham Nigel Maw

David James Rawson

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-10-11

Filing date

2000-10-04

Publication date

2006-05-03

1999-10-11 Priority claimed from GBGB9924041.8A external-priority patent/GB9924041D0/en

2000-07-28 Priority claimed from GB0018660A external-priority patent/GB0018660D0/en

2000-10-04 Application filed by Pfizer filed Critical Pfizer

2006-05-03 Publication of OA12058A publication Critical patent/OA12058A/en

Links

229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title 1
239000002571 phosphodiesterase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 526
101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 claims abstract description 9
101150098694 PDE5A gene Proteins 0.000 claims abstract description 9
102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 claims abstract description 9
230000005764 inhibitory process Effects 0.000 claims abstract description 7
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 abstract 3
239000000203 mixture Substances 0.000 claims description 154
238000000034 method Methods 0.000 claims description 114
125000000217 alkyl group Chemical group 0.000 claims description 71
239000002253 acid Substances 0.000 claims description 59
125000003118 aryl group Chemical group 0.000 claims description 47
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
-1 oxadiazol-2-yl Chemical group 0.000 claims description 44
125000005843 halogen group Chemical group 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 36
229910052757 nitrogen Inorganic materials 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 28
229910052799 carbon Inorganic materials 0.000 claims description 22
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
230000008569 process Effects 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
150000001412 amines Chemical class 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 11
238000009472 formulation Methods 0.000 claims description 11
150000001721 carbon Chemical group 0.000 claims description 10
239000003153 chemical reaction reagent Substances 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
239000001301 oxygen Substances 0.000 claims description 8
230000001568 sexual effect Effects 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 7
229920006395 saturated elastomer Polymers 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
229910052740 iodine Inorganic materials 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
206010057671 Female sexual dysfunction Diseases 0.000 claims description 5
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000002346 iodo group Chemical group I* 0.000 claims description 5
125000003107 substituted aryl group Chemical group 0.000 claims description 5
TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
238000006880 cross-coupling reaction Methods 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
230000004064 dysfunction Effects 0.000 claims description 4
201000001881 impotence Diseases 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
208000027520 Somatoform disease Diseases 0.000 claims description 3
150000004703 alkoxides Chemical group 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
235000005152 nicotinamide Nutrition 0.000 claims description 3
239000011570 nicotinamide Substances 0.000 claims description 3
229960003966 nicotinamide Drugs 0.000 claims description 3
208000027753 pain disease Diseases 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
208000030047 Sexual desire disease Diseases 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 2
229910052702 rhenium Inorganic materials 0.000 claims description 2
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 2
208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims 2
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
241000006460 Cyana Species 0.000 claims 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims 1
206010024419 Libido decreased Diseases 0.000 claims 1
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 1
150000001735 carboxylic acids Chemical class 0.000 claims 1
MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims 1
208000017020 hypoactive sexual desire disease Diseases 0.000 claims 1
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims 1
125000000547 substituted alkyl group Chemical group 0.000 claims 1
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 20
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 20
238000009109 curative therapy Methods 0.000 abstract 1
ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 abstract 1
238000011321 prophylaxis Methods 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 258
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 167
239000000243 solution Substances 0.000 description 121
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
238000005160 1H NMR spectroscopy Methods 0.000 description 79
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 57
229940093499 ethyl acetate Drugs 0.000 description 53
235000019439 ethyl acetate Nutrition 0.000 description 53
239000000047 product Substances 0.000 description 53
150000002500 ions Chemical class 0.000 description 50
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 47
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 45
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
239000012267 brine Substances 0.000 description 42
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
239000002904 solvent Substances 0.000 description 41
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
238000004587 chromatography analysis Methods 0.000 description 39
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
238000004458 analytical method Methods 0.000 description 35
238000010992 reflux Methods 0.000 description 35
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
230000002829 reductive effect Effects 0.000 description 32
239000007787 solid Substances 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 30
238000000746 purification Methods 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 18
238000004440 column chromatography Methods 0.000 description 17
239000012043 crude product Substances 0.000 description 17
229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
239000003112 inhibitor Substances 0.000 description 16
150000003839 salts Chemical class 0.000 description 16
235000017557 sodium bicarbonate Nutrition 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
239000003795 chemical substances by application Substances 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
229960001407 sodium bicarbonate Drugs 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 14
229910021529 ammonia Inorganic materials 0.000 description 14
229910052739 hydrogen Inorganic materials 0.000 description 14
239000012071 phase Substances 0.000 description 14
239000000725 suspension Substances 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 13
235000011054 acetic acid Nutrition 0.000 description 13
239000011591 potassium Substances 0.000 description 13
229910052700 potassium Inorganic materials 0.000 description 13
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 12
241000282414 Homo sapiens Species 0.000 description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
238000010828 elution Methods 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
102100024085 Alpha-aminoadipic semialdehyde dehydrogenase Human genes 0.000 description 11
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 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
238000001914 filtration Methods 0.000 description 11
239000011734 sodium Substances 0.000 description 11
229910052708 sodium Inorganic materials 0.000 description 11
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
101710135349 Venom phosphodiesterase Proteins 0.000 description 10
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
238000003756 stirring Methods 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000000304 alkynyl group Chemical group 0.000 description 9
230000000694 effects Effects 0.000 description 9
239000000284 extract Substances 0.000 description 9
238000001665 trituration Methods 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
239000002552 dosage form Substances 0.000 description 8
229940073584 methylene chloride Drugs 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
229920003199 poly(diethylsiloxane) Polymers 0.000 description 8
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
101150085511 PEDS1 gene Proteins 0.000 description 7
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
102100037592 Plasmanylethanolamine desaturase Human genes 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000003814 drug Substances 0.000 description 7
239000001257 hydrogen Substances 0.000 description 7
125000004433 nitrogen atom Chemical group N* 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
125000002877 alkyl aryl group Chemical group 0.000 description 6
239000002585 base Substances 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
239000006071 cream Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000000758 substrate Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
229920002472 Starch Polymers 0.000 description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
229960004132 diethyl ether Drugs 0.000 description 5
239000003480 eluent Substances 0.000 description 5
239000000499 gel Substances 0.000 description 5
125000000623 heterocyclic group Chemical group 0.000 description 5
230000000155 isotopic effect Effects 0.000 description 5
239000010410 layer Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
239000000843 powder Substances 0.000 description 5
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
229940032147 starch Drugs 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
235000011149 sulphuric acid Nutrition 0.000 description 5
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 4
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 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
239000010949 copper Substances 0.000 description 4
239000006260 foam Substances 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
239000008101 lactose Substances 0.000 description 4
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
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 4
235000019271 petrolatum Nutrition 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
239000002590 phosphodiesterase V inhibitor Substances 0.000 description 4
229960005235 piperonyl butoxide Drugs 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
239000000651 prodrug Substances 0.000 description 4
229940002612 prodrug Drugs 0.000 description 4
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 4
229910000080 stannane Inorganic materials 0.000 description 4
239000007858 starting material Substances 0.000 description 4
150000003512 tertiary amines Chemical class 0.000 description 4
DOBUSJIVSSJEDA-UHFFFAOYSA-L 1,3-dioxa-2$l^{6}-thia-4-mercuracyclobutane 2,2-dioxide Chemical compound [Hg+2].[O-]S([O-])(=O)=O DOBUSJIVSSJEDA-UHFFFAOYSA-L 0.000 description 3
108060003345 Adrenergic Receptor Proteins 0.000 description 3
102000017910 Adrenergic receptor Human genes 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
244000089742 Citrus aurantifolia Species 0.000 description 3
235000008733 Citrus aurantifolia Nutrition 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
229910002651 NO3 Inorganic materials 0.000 description 3
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
201000001880 Sexual dysfunction Diseases 0.000 description 3
241000897276 Termes Species 0.000 description 3
235000011941 Tilia x europaea Nutrition 0.000 description 3
239000008186 active pharmaceutical agent Substances 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910002091 carbon monoxide Inorganic materials 0.000 description 3
229940105305 carbon monoxide Drugs 0.000 description 3
230000006315 carbonylation Effects 0.000 description 3
238000005810 carbonylation reaction Methods 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
239000001913 cellulose Substances 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
238000007796 conventional method Methods 0.000 description 3
229910052802 copper Inorganic materials 0.000 description 3
210000005226 corpus cavernosum Anatomy 0.000 description 3
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 3
201000010099 disease Diseases 0.000 description 3
229940088679 drug related substance Drugs 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000004571 lime Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
229910000370 mercury sulfate Inorganic materials 0.000 description 3
229910052759 nickel Inorganic materials 0.000 description 3
235000001968 nicotinic acid Nutrition 0.000 description 3
239000011664 nicotinic acid Substances 0.000 description 3
229960003512 nicotinic acid Drugs 0.000 description 3
229910000069 nitrogen hydride Inorganic materials 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000001294 propane Substances 0.000 description 3
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 3
231100000872 sexual dysfunction Toxicity 0.000 description 3
239000002002 slurry Substances 0.000 description 3
235000017550 sodium carbonate Nutrition 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
229940001593 sodium carbonate Drugs 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
239000007921 spray Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
COIOYMYWGDAQPM-UHFFFAOYSA-N tri(ortho-tolyl)phosphine Substances CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
239000011701 zinc Substances 0.000 description 3
ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
FRDAATYAJDYRNW-UHFFFAOYSA-N 3-methyl-3-pentanol Chemical compound CCC(C)(O)CC FRDAATYAJDYRNW-UHFFFAOYSA-N 0.000 description 2
229930008281 A03AD01 - Papaverine Natural products 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 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
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
241000543381 Cliftonia monophylla Species 0.000 description 2
229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
229920000858 Cyclodextrin Polymers 0.000 description 2
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
208000032131 Diabetic Neuropathies 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
239000001856 Ethyl cellulose Substances 0.000 description 2
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
108090000028 Neprilysin Proteins 0.000 description 2
102000003729 Neprilysin Human genes 0.000 description 2
239000004264 Petrolatum Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
239000000556 agonist Substances 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
230000007815 allergy Effects 0.000 description 2
102000004305 alpha Adrenergic Receptors Human genes 0.000 description 2
108090000861 alpha Adrenergic Receptors Proteins 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
230000001746 atrial effect Effects 0.000 description 2
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
125000002393 azetidinyl group Chemical group 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000011575 calcium Substances 0.000 description 2
150000003857 carboxamides Chemical class 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
IRDLUHRVLVEUHA-UHFFFAOYSA-N diethyl dithiophosphate Chemical compound CCOP(S)(=S)OCC IRDLUHRVLVEUHA-UHFFFAOYSA-N 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 2
229960002986 dinoprostone Drugs 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
235000019325 ethyl cellulose Nutrition 0.000 description 2
229920001249 ethyl cellulose Polymers 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
229940029575 guanosine Drugs 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
208000002551 irritable bowel syndrome Diseases 0.000 description 2
239000006210 lotion Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
ACEONLNNWKIPTM-UHFFFAOYSA-N methyl 2-bromopropanoate Chemical compound COC(=O)C(C)Br ACEONLNNWKIPTM-UHFFFAOYSA-N 0.000 description 2
239000003607 modifier Substances 0.000 description 2
MWMOHAMAKRKDLU-UHFFFAOYSA-N nickel;triethylphosphane Chemical compound [Ni].CCP(CC)CC.CCP(CC)CC MWMOHAMAKRKDLU-UHFFFAOYSA-N 0.000 description 2
239000002840 nitric oxide donor Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
238000005580 one pot reaction Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
125000003431 oxalo group Chemical group 0.000 description 2
229940094443 oxytocics prostaglandins Drugs 0.000 description 2
229960001789 papaverine Drugs 0.000 description 2
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
208000033808 peripheral neuropathy Diseases 0.000 description 2
229940066842 petrolatum Drugs 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
229910000073 phosphorus hydride Inorganic materials 0.000 description 2
125000003386 piperidinyl group Chemical group 0.000 description 2
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
150000003180 prostaglandins Chemical class 0.000 description 2
230000000541 pulsatile effect Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
210000002027 skeletal muscle Anatomy 0.000 description 2
229940080313 sodium starch Drugs 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
SESSOVUNEZQNBV-UHFFFAOYSA-M sodium;2-bromoacetate Chemical compound [Na+].[O-]C(=O)CBr SESSOVUNEZQNBV-UHFFFAOYSA-M 0.000 description 2
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 2
239000001117 sulphuric acid Substances 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 2
229960003991 trazodone Drugs 0.000 description 2
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
239000001993 wax Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
XUKAVPATXGYVKJ-WPKBUWHJSA-N (6ar,9r)-n-[(2s)-1-hydroxypropan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)C)C2)=C3C2=CN(C)C3=C1 XUKAVPATXGYVKJ-WPKBUWHJSA-N 0.000 description 1
YHEIHLVIKSTGJE-YXJHDRRASA-N (6ar,9s,10ar)-9-(diethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(CC)CC)=C3C2=CNC3=C1 YHEIHLVIKSTGJE-YXJHDRRASA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
PYHRZPFZZDCOPH-QXGOIDDHSA-N (S)-amphetamine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C[C@H](N)CC1=CC=CC=C1.C[C@H](N)CC1=CC=CC=C1 PYHRZPFZZDCOPH-QXGOIDDHSA-N 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
BPXVHIRIPLPOPT-UHFFFAOYSA-N 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazinane-2,4,6-trione Chemical compound OCCN1C(=O)N(CCO)C(=O)N(CCO)C1=O BPXVHIRIPLPOPT-UHFFFAOYSA-N 0.000 description 1
RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
WGOBPPNNYVSJTE-UHFFFAOYSA-N 1-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)CP(C=1C=CC=CC=1)C1=CC=CC=C1 WGOBPPNNYVSJTE-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 1
IYUQLJBOKGMHHS-UHFFFAOYSA-N 2-(2-methylpropoxy)pyridine-3-carboxylic acid Chemical compound CC(C)COC1=NC=CC=C1C(O)=O IYUQLJBOKGMHHS-UHFFFAOYSA-N 0.000 description 1
PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
GODXSVXXWPBSEV-UHFFFAOYSA-N 2-butoxy-5-iodopyridine-3-carboxylic acid Chemical compound CCCCOC1=NC=C(I)C=C1C(O)=O GODXSVXXWPBSEV-UHFFFAOYSA-N 0.000 description 1
XCMJQQOMGWGGSI-UHFFFAOYSA-N 2-ethoxypyridine-3-carboxylic acid Chemical compound CCOC1=NC=CC=C1C(O)=O XCMJQQOMGWGGSI-UHFFFAOYSA-N 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-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
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
SBHNNNRQZGYOAU-YVEFUNNKSA-N 3-[(6ar,9s)-5-bromo-7-methyl-6,6a,8,9-tetrahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC(C=2[C@H](N(C)C[C@H](C=2)NC(=O)N(CC)CC)C2)=C3C2=C(Br)NC3=C1 SBHNNNRQZGYOAU-YVEFUNNKSA-N 0.000 description 1
FCRJELOYDVBTGW-ILZDJORESA-N 3-[(6ar,9s,10ar)-7-propyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea Chemical compound C1=CC([C@H]2C[C@@H](CN([C@@H]2C2)CCC)NC(=O)N(CC)CC)=C3C2=CNC3=C1 FCRJELOYDVBTGW-ILZDJORESA-N 0.000 description 1
WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-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
SQNWFKZOFAOCHM-UHFFFAOYSA-N 3-azaniumyl-2-methylprop-2-enoate Chemical compound [NH3+]C=C(C)C([O-])=O SQNWFKZOFAOCHM-UHFFFAOYSA-N 0.000 description 1
NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 1
GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
BMUKKTUHUDJSNZ-UHFFFAOYSA-N 4-[1-hydroxy-2-(1-phenoxypropan-2-ylamino)propyl]phenol Chemical compound C=1C=C(O)C=CC=1C(O)C(C)NC(C)COC1=CC=CC=C1 BMUKKTUHUDJSNZ-UHFFFAOYSA-N 0.000 description 1
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
XIMCGXXYEMOWQP-UHFFFAOYSA-N 5-bromo-n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=C(Br)C=N1 XIMCGXXYEMOWQP-UHFFFAOYSA-N 0.000 description 1
XTPUQGFKKAURLH-UHFFFAOYSA-N 5-ethyl-4-nitro-1h-pyrazole-3-carboxamide Chemical compound CCC=1NN=C(C(N)=O)C=1[N+]([O-])=O XTPUQGFKKAURLH-UHFFFAOYSA-N 0.000 description 1
FHSKGCKRPKPOOW-UHFFFAOYSA-N 5-iodopyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC(I)=C1 FHSKGCKRPKPOOW-UHFFFAOYSA-N 0.000 description 1
VCCNKWWXYVWTLT-CYZBKYQRSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VCCNKWWXYVWTLT-CYZBKYQRSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
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 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 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
239000005695 Ammonium acetate Substances 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
206010002153 Anal fissure Diseases 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
102000008873 Angiotensin II receptor Human genes 0.000 description 1
108050000824 Angiotensin II receptor Proteins 0.000 description 1
208000016583 Anus disease Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
206010071445 Bladder outlet obstruction Diseases 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
108010023798 Charybdotoxin Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
WHIJJQDOKPMDJU-UHFFFAOYSA-N Cl.Cl.B(O)O Chemical compound Cl.Cl.B(O)O WHIJJQDOKPMDJU-UHFFFAOYSA-N 0.000 description 1
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
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 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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 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
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
206010013924 Dyskinesia oesophageal Diseases 0.000 description 1
206010013935 Dysmenorrhoea Diseases 0.000 description 1
102100022404 E3 ubiquitin-protein ligase Midline-1 Human genes 0.000 description 1
101710102210 E3 ubiquitin-protein ligase Midline-1 Proteins 0.000 description 1
101100379080 Emericella variicolor andB gene Proteins 0.000 description 1
101100379081 Emericella variicolor andC gene Proteins 0.000 description 1
102000010180 Endothelin receptor Human genes 0.000 description 1
108050001739 Endothelin receptor Proteins 0.000 description 1
208000010228 Erectile Dysfunction Diseases 0.000 description 1
WVVSZNPYNCNODU-CJBNDPTMSA-N Ergometrine Natural products C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@@H](CO)C)C2)=C3C2=CNC3=C1 WVVSZNPYNCNODU-CJBNDPTMSA-N 0.000 description 1
208000009531 Fissure in Ano Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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 1
239000004471 Glycine Substances 0.000 description 1
239000007821 HATU Substances 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
206010019280 Heart failures Diseases 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
102000007625 Hirudins Human genes 0.000 description 1
108010007267 Hirudins Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
206010021639 Incontinence Diseases 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
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 1
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 1
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
229930064664 L-arginine Natural products 0.000 description 1
235000014852 L-arginine Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 1
WVVSZNPYNCNODU-XTQGRXLLSA-N Lysergic acid propanolamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@H](CO)C)C2)=C3C2=CNC3=C1 WVVSZNPYNCNODU-XTQGRXLLSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
235000006679 Mentha X verticillata Nutrition 0.000 description 1
235000002899 Mentha suaveolens Nutrition 0.000 description 1
235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
HRRBJVNMSRJFHQ-UHFFFAOYSA-N Naftopidil Chemical compound COC1=CC=CC=C1N1CCN(CC(O)COC=2C3=CC=CC=C3C=CC=2)CC1 HRRBJVNMSRJFHQ-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
STJFYCWYHROASW-UHFFFAOYSA-N O-methyl-glaucamine Natural products CN1CCC2=CC(OC)=C(OC)C=C2C2OC(OC)C3=C4OCOC4=CC=C3C12 STJFYCWYHROASW-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
206010061323 Optic neuropathy Diseases 0.000 description 1
BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
244000131316 Panax pseudoginseng Species 0.000 description 1
235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
235000003140 Panax quinquefolius Nutrition 0.000 description 1
101150034459 Parpbp gene Proteins 0.000 description 1
TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 1
239000000026 Pentaerythritol tetranitrate Substances 0.000 description 1
208000018262 Peripheral vascular disease Diseases 0.000 description 1
QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
241000206607 Porphyra umbilicalis Species 0.000 description 1
229940127315 Potassium Channel Openers Drugs 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
206010040893 Skin necrosis Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229920002125 Sokalan® Polymers 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
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
239000005864 Sulphur Substances 0.000 description 1
DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 1
JOAHPSVPXZTVEP-YXJHDRRASA-N Terguride Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NC(=O)N(CC)CC)=C3C2=CNC3=C1 JOAHPSVPXZTVEP-YXJHDRRASA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 1
239000009975 Urodyn Substances 0.000 description 1
206010047139 Vasoconstriction Diseases 0.000 description 1
BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
MMPCMJGFURZYOY-WRWLIDTKSA-N [(6ar,9r,10ar)-5-bromo-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline-9-yl]methyl azepane-1-carboxylate Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4NC(Br)=C(C=34)C2)C1)C)OC(=O)N1CCCCCC1 MMPCMJGFURZYOY-WRWLIDTKSA-N 0.000 description 1
QQPGGBNMTNDKEY-UHFFFAOYSA-N [2-butyl-5-chloro-3-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NN(N=N2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 QQPGGBNMTNDKEY-UHFFFAOYSA-N 0.000 description 1
WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
ANZIISNSHPKVRV-UHFFFAOYSA-N abanoquil Chemical compound C1=C(OC)C(OC)=CC2=NC(N3CCC=4C=C(C(=CC=4C3)OC)OC)=CC(N)=C21 ANZIISNSHPKVRV-UHFFFAOYSA-N 0.000 description 1
229950010137 abanoquil Drugs 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
235000010358 acesulfame potassium Nutrition 0.000 description 1
229960004998 acesulfame potassium Drugs 0.000 description 1
239000000619 acesulfame-K Substances 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
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
206010001053 acute respiratory failure Diseases 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
101150112469 ahcY gene Proteins 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
150000001345 alkine derivatives Chemical group 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
239000004004 anti-anginal agent Substances 0.000 description 1
229940124345 antianginal agent Drugs 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229960004676 antithrombotic agent Drugs 0.000 description 1
229960004046 apomorphine Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000009697 arginine Nutrition 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
239000011324 bead Substances 0.000 description 1
230000008901 benefit Effects 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
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
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 1
BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
229950010062 brazergoline Drugs 0.000 description 1
229950006651 bromerguride Drugs 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
FGNLEIGUMSBZQP-UHFFFAOYSA-N cadaverine dihydrochloride Chemical compound Cl.Cl.NCCCCCN FGNLEIGUMSBZQP-UHFFFAOYSA-N 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000000480 calcium channel blocker Substances 0.000 description 1
BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
239000000292 calcium oxide Substances 0.000 description 1
ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
QTAOMKOIBXZKND-PPHPATTJSA-N carbidopa Chemical compound O.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 QTAOMKOIBXZKND-PPHPATTJSA-N 0.000 description 1
229960004205 carbidopa Drugs 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229960001631 carbomer Drugs 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
UMMADZJLZAPZAW-OVXHCKHTSA-N carboprost tromethamine Chemical compound OCC([NH3+])(CO)CO.CCCCC[C@](C)(O)\C=C\[C@H]1[C@@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC([O-])=O UMMADZJLZAPZAW-OVXHCKHTSA-N 0.000 description 1
229960005296 carboprost tromethamine Drugs 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
HOPSCVCBEOCPJZ-UHFFFAOYSA-N carboxymethyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC(O)=O HOPSCVCBEOCPJZ-UHFFFAOYSA-N 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
208000023819 chronic asthma Diseases 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
229960002896 clonidine Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
238000010668 complexation reaction Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
238000007887 coronary angioplasty Methods 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
229960000913 crospovidone Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
CNVQLPPZGABUCM-LIGYZCPXSA-N ctx toxin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H]3CSSC[C@@H](C(N[C@@H](CC=4C5=CC=CC=C5NC=4)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CO)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3NC=NC=3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N2)C(C)C)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)O)NC1=O)=O)CCSC)C(C)C)[C@@H](C)O)NC(=O)[C@H]1NC(=O)CC1)C1=CC=CC=C1 CNVQLPPZGABUCM-LIGYZCPXSA-N 0.000 description 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
RFWZESUMWJKKRN-UHFFFAOYSA-N dapiprazole Chemical compound CC1=CC=CC=C1N1CCN(CCC=2N3CCCCC3=NN=2)CC1 RFWZESUMWJKKRN-UHFFFAOYSA-N 0.000 description 1
229960002947 dapiprazole Drugs 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
RAABOESOVLLHRU-UHFFFAOYSA-O diazenium Chemical compound [NH2+]=N RAABOESOVLLHRU-UHFFFAOYSA-O 0.000 description 1
JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
AQIXEPGDORPWBJ-UHFFFAOYSA-N diethyl carbinol Natural products CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
229960001342 dinoprost Drugs 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
229940005501 dopaminergic agent Drugs 0.000 description 1
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 1
229960001389 doxazosin Drugs 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000010410 dusting Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
201000009409 embryonal rhabdomyosarcoma Diseases 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000008387 emulsifying waxe Substances 0.000 description 1
OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
229960001405 ergometrine Drugs 0.000 description 1
229960001903 ergotamine tartrate Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
229940052303 ethers for general anesthesia Drugs 0.000 description 1
229950002163 etisulergine Drugs 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
235000008434 ginseng Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 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
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000001631 haemodialysis Methods 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000014617 hemorrhoid Diseases 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
150000004688 heptahydrates Chemical class 0.000 description 1
238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin 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(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](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](C(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)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
229940006607 hirudin Drugs 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
HPMRFMKYPGXPEP-UHFFFAOYSA-N idazoxan Chemical compound N1CCN=C1C1OC2=CC=CC=C2OC1 HPMRFMKYPGXPEP-UHFFFAOYSA-N 0.000 description 1
229950001476 idazoxan Drugs 0.000 description 1
UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
239000012535 impurity Substances 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
229960002056 indoramin Drugs 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940030980 inova Drugs 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
238000005342 ion exchange Methods 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
229960002479 isosorbide 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
229960000201 isosorbide dinitrate Drugs 0.000 description 1
238000002307 isotope ratio mass spectrometry Methods 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
229960004819 isoxsuprine Drugs 0.000 description 1
PRFXRIUZNKLRHM-UHFFFAOYSA-N l-prostaglandin B2 Natural products CCCCCC(O)C=CC1=C(CC=CCCCC(O)=O)C(=O)CC1 PRFXRIUZNKLRHM-UHFFFAOYSA-N 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229950002454 lysergide Drugs 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910000372 mercury(II) sulfate Inorganic materials 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
MXELDPKESKXREN-UHFFFAOYSA-N methyl 5-[3-(4,4-diphenylpiperidin-1-yl)propylcarbamoyl]-2,6-dimethyl-4-(4-nitrophenyl)-1,4-dihydropyridine-3-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1=C(C)NC(C)=C(C(=O)NCCCN2CCC(CC2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=C([N+]([O-])=O)C=C1 MXELDPKESKXREN-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
DUCNHKDCVVSJLG-UHFFFAOYSA-N n-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]-3-methyl-4-oxo-2-phenylchromene-8-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C3=C(C(C(C)=C(O3)C=3C=CC=CC=3)=O)C=CC=2)CC1 DUCNHKDCVVSJLG-UHFFFAOYSA-N 0.000 description 1
229950005705 naftopidil Drugs 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 1
229960002497 nicorandil Drugs 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229960002460 nitroprusside Drugs 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
LVRLSYPNFFBYCZ-VGWMRTNUSA-N omapatrilat Chemical compound C([C@H](S)C(=O)N[C@H]1CCS[C@H]2CCC[C@H](N2C1=O)C(=O)O)C1=CC=CC=C1 LVRLSYPNFFBYCZ-VGWMRTNUSA-N 0.000 description 1
229950000973 omapatrilat Drugs 0.000 description 1
208000020911 optic nerve disease Diseases 0.000 description 1
229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
125000000913 palmityl 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])C([H])([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
239000012188 paraffin wax Substances 0.000 description 1
235000019809 paraffin wax Nutrition 0.000 description 1
229960004321 pentaerithrityl tetranitrate Drugs 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003418 phenoxybenzamine Drugs 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
108091008695 photoreceptors Proteins 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
239000004810 polytetrafluoroethylene Substances 0.000 description 1
229920001343 polytetrafluoroethylene Polymers 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
201000011461 pre-eclampsia Diseases 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000003380 propellant Substances 0.000 description 1
229950004866 propisergide Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
PRFXRIUZNKLRHM-HKVRTXJWSA-N prostaglandin B2 Chemical compound CCCCC[C@H](O)\C=C\C1=C(C\C=C/CCCC(O)=O)C(=O)CC1 PRFXRIUZNKLRHM-HKVRTXJWSA-N 0.000 description 1
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 1
PXGPLTODNUVGFL-YNNPMVKQSA-N prostaglandin F2alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-YNNPMVKQSA-N 0.000 description 1
229950007140 proterguride Drugs 0.000 description 1
208000002815 pulmonary hypertension Diseases 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
201000004193 respiratory failure Diseases 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000004576 sand Substances 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 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
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
235000015096 spirit Nutrition 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229960002613 tamsulosin Drugs 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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
229960004558 terguride Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 1
DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
YNZXWQJZEDLQEG-UHFFFAOYSA-N trimazosin Chemical compound N1=C2C(OC)=C(OC)C(OC)=CC2=C(N)N=C1N1CCN(C(=O)OCC(C)(C)O)CC1 YNZXWQJZEDLQEG-UHFFFAOYSA-N 0.000 description 1
229960002906 trimazosin Drugs 0.000 description 1
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000025033 vasoconstriction Effects 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
238000010792 warming Methods 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 description 1
229960000317 yohimbine Drugs 0.000 description 1
AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1
VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Reproductive Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Endocrinology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

OA1200200101A 1999-10-11 2000-10-04 5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors. OA12058A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9924041.8A GB9924041D0 (en)	1999-10-11	1999-10-11	Pharmaceutically active compounds
GB0018660A GB0018660D0 (en)	2000-07-28	2000-07-28	Pharmaceutically active compounds

Publications (1)

Publication Number	Publication Date
OA12058A true OA12058A (en)	2006-05-03

Family

ID=26244758

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200101A OA12058A (en)	1999-10-11	2000-10-04	5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors.

Country Status (34)

Country	Link
US (1)	US6756373B1 (is)
EP (1)	EP1222190A1 (is)
JP (1)	JP2003511452A (is)
KR (1)	KR20020038941A (is)
CN (1)	CN1378547A (is)
AP (1)	AP2002002455A0 (is)
AR (1)	AR022665A1 (is)
AU (1)	AU7547900A (is)
BG (1)	BG106568A (is)
BR (1)	BR0014695A (is)
CA (1)	CA2387353A1 (is)
CO (1)	CO5261539A1 (is)
CZ (1)	CZ20021151A3 (is)
DZ (1)	DZ3218A1 (is)
EA (1)	EA200200240A1 (is)
EE (1)	EE200200192A (is)
GT (1)	GT200000168A (is)
HK (1)	HK1049834A1 (is)
HU (1)	HUP0203438A3 (is)
IL (1)	IL149025A0 (is)
IS (1)	IS6288A (is)
MA (1)	MA26824A1 (is)
NO (1)	NO20021695L (is)
NZ (1)	NZ517324A (is)
OA (1)	OA12058A (is)
PA (1)	PA8504401A1 (is)
PE (1)	PE20010736A1 (is)
PL (1)	PL357522A1 (is)
SK (1)	SK4562002A3 (is)
SV (1)	SV2002000192A (is)
TN (1)	TNSN00198A1 (is)
TR (1)	TR200200954T2 (is)
UY (1)	UY26383A1 (is)
WO (1)	WO2001027112A1 (is)

Families Citing this family (92)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7235625B2 (en)	1999-06-29	2007-06-26	Palatin Technologies, Inc.	Multiple agent therapy for sexual dysfunction
US6271228B1 (en) *	2000-04-28	2001-08-07	Pfizer Inc.	Blood pressure stabilization during hemodialysis
US6809200B2 (en)	2000-07-28	2004-10-26	Pfizer Inc.	Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-one compounds and intermediates thereof
EP1176147A1 (en) *	2000-07-28	2002-01-30	Pfizer Limited	Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof
US6407259B1 (en)	2000-07-28	2002-06-18	Pfizer Inc.	Process for the preparation of pyrazoles
EP1176142A1 (en) *	2000-07-28	2002-01-30	Pfizer Inc.	Process for the preparation of pyrazoles
GB0025782D0 (en) *	2000-10-20	2000-12-06	Pfizer Ltd	Use of inhibitors
GB0105893D0 (en) *	2001-03-09	2001-04-25	Pfizer Ltd	Pharmaceutically active compounds
US6770645B2 (en)	2001-03-16	2004-08-03	Pfizer Inc.	Pharmaceutically active compounds
GB0106661D0 (en) *	2001-03-16	2001-05-09	Pfizer Ltd	Pharmaceutically active compounds
US6784185B2 (en)	2001-03-16	2004-08-31	Pfizer Inc.	Pharmaceutically active compounds
US20030211040A1 (en)	2001-08-31	2003-11-13	Paul Greengard	Phosphodiesterase activity and regulation of phosphodiesterase 1B-mediated signaling in brain
EP1506015A2 (en) *	2002-05-23	2005-02-16	Pfizer Limited	Pharmaceutical combination of pde5 inhibitors with ace inhibitors
GB0214784D0 (en) *	2002-06-26	2002-08-07	Pfizer Ltd	Novel combination
JP4208512B2 (ja) *	2002-07-23	2009-01-14	株式会社クラレ	５−（２’−ピリジル）−２−ピリドン誘導体の製造方法
GB0219961D0 (en)	2002-08-28	2002-10-02	Pfizer Ltd	Oxytocin inhibitors
US20040067985A1 (en) *	2002-10-04	2004-04-08	Fortuna Haviv	Method of inhibiting angiogenesis
US7323462B2 (en)	2002-12-10	2008-01-29	Pfizer Inc.	Morpholine dopamine agonists
ES2341240T3 (es)	2002-12-13	2010-06-17	Warner-Lambert Company Llc	Ligando alfa-2-delta para tratar los sintomas del tracto urinario inferior.
EP1620437B1 (en)	2003-04-29	2009-06-17	Pfizer Limited	5,7-diaminopyrazolo¬4,3-d pyrimidines useful in the traetment of hypertension
JP2006219373A (ja) *	2003-06-13	2006-08-24	Daiichi Asubio Pharma Co Ltd	Ｐｄｅ７阻害作用を有するピリジニルピラゾロピリミジノン誘導体
US7291640B2 (en)	2003-09-22	2007-11-06	Pfizer Inc.	Substituted triazole derivatives as oxytocin antagonists
US7572799B2 (en)	2003-11-24	2009-08-11	Pfizer Inc	Pyrazolo[4,3-d]pyrimidines as Phosphodiesterase Inhibitors
EP1708718A1 (en)	2004-01-22	2006-10-11	Pfizer Limited	Triazole derivatives which inhibit vasopressin antagonistic activity
US7649002B2 (en)	2004-02-04	2010-01-19	Pfizer Inc	(3,5-dimethylpiperidin-1yl)(4-phenylpyrrolidin-3-yl)methanone derivatives as MCR4 agonists
JP4838792B2 (ja) *	2004-03-05	2011-12-14	ニコメッドゲゼルシャフトミットベシュレンクテルハフツング	Ｐｄｅ５阻害剤のための新規の使用
CA2562251C (en)	2004-04-07	2009-04-28	Pfizer Inc.	Pyrazolo'4,3-d pyrimidines
WO2006100557A1 (en)	2005-03-21	2006-09-28	Pfizer Limited	Substituted triazole derivatives as oxytocin antagonists
EP1881985B1 (en)	2005-05-12	2010-12-29	Pfizer, Inc.	Anhydrous crystalline forms of n-ý1-(2-ethoxyethyl)-5-(n-ethyl-n-methylamino)-7-(4-methylpyridin-2-yl-amino)-1h-pyrazolo[4,3-d]pyrimidine-3-carbonyl¨methanesulfonamide
JP5084725B2 (ja)	2005-06-06	2012-11-28	武田薬品工業株式会社	有機化合物
US20080194592A1 (en) *	2005-08-23	2008-08-14	Intra-Cellular Therapies, Inc.	Organic Compounds
TW200745106A (en) *	2005-10-03	2007-12-16	Astrazeneca Ab	Chemical compounds
WO2007072169A2 (en) *	2005-12-20	2007-06-28	Pfizer Products Inc.	Pharmaceutical combination for the treatment of luts comprising a pde5 inhibitor and a muscarinic antagonist
WO2007143705A2 (en) *	2006-06-06	2007-12-13	Intra-Cellular Therapies, Inc.	Organic compounds
US20090325956A1 (en) *	2006-10-13	2009-12-31	Takahiko Taniguchi	Aromatic amine derivative and use thereof
EP2081431B1 (en) *	2006-11-13	2013-01-16	Intra-Cellular Therapies, Inc.	Organic compounds
JP5837278B2 (ja) *	2006-12-05	2015-12-24	イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−ＣｅｌｌｕｌａｒＴｈｅｒａｐｉｅｓ，Ｉｎｃ．	新規使用
ES2310144B1 (es) *	2007-06-15	2010-01-12	Galenicum Health, S.L.	Intermedios para la preparacion de un inhibidor de la fosfodiesterasa tipo 5.
WO2009045019A2 (en) *	2007-10-02	2009-04-09	Dong-A Pharm.Co., Ltd.	Composition and method for treatment or prevention of benign prostatic hyperplasia and lower urinary tract symptoms
CN104370918A (zh)	2007-12-06	2015-02-25	武田药品工业株式会社	有机化合物
JP5701608B2 (ja) *	2007-12-06	2015-04-15	イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−ＣｅｌｌｕｌａｒＴｈｅｒａｐｉｅｓ，Ｉｎｃ．	有機化合物
EP2367430B1 (en)	2008-12-06	2014-08-13	Intra-Cellular Therapies, Inc.	Organic compounds
BRPI0922808A2 (pt)	2008-12-06	2018-05-29	Intracellular Therapies Inc	compostos orgânicos
BRPI0922809A2 (pt)	2008-12-06	2018-05-29	Intracellular Therapies Inc	compostos orgânicos
BRPI0922131A2 (pt) *	2008-12-06	2015-08-18	Intracellular Therapies Inc	Compostos orgânicos
MX2011005933A (es)	2008-12-06	2011-12-16	Intra Cellular Therapies Inc	Compuestos organicos.
EA201170773A1 (ru)	2008-12-06	2012-01-30	Интра-Селлулар Терапиз, Инк.	Органические соединения
EP2379076B1 (en)	2008-12-23	2014-11-12	The Trustees of Columbia University in the City of New York	Phosphodiesterase inhibitors and uses thereof
US11464781B2 (en)	2009-02-25	2022-10-11	Intra-Cellular Therapies, Inc.	PDE1 inhibitors for ophthalmic disorders
GB0903493D0 (en)	2009-02-27	2009-04-08	Vantia Ltd	New compounds
JP2012526810A (ja)	2009-05-13	2012-11-01	イントラ−セルラー・セラピーズ・インコーポレイテッド	有機化合物
SG10201507362TA (en)	2009-08-05	2015-10-29	Intra Cellular Therapies Inc	Novel Regulatory Proteins And Inhibitors
TW201206937A (en)	2010-05-31	2012-02-16	Intra Cellular Therapies Inc	Organic compounds
WO2011153138A1 (en)	2010-05-31	2011-12-08	Intra-Cellular Therapies, Inc.	Organic compounds
EP2590657A4 (en)	2010-05-31	2014-02-12	Intra Cellular Therapies Inc	ORGANIC CONNECTIONS
US9434730B2 (en)	2010-05-31	2016-09-06	Intra-Cellular Therapies, Inc.	PDE1 inhibitor compounds
WO2012171016A1 (en)	2011-06-10	2012-12-13	Intra-Cellular Therapies, Inc.	Organic compounds
US9402877B2 (en)	2011-11-04	2016-08-02	Xion Pharmaceuticals Corporation	Methods and compositions for oral administration of melanocortin receptor agonist compounds
WO2013109738A1 (en)	2012-01-17	2013-07-25	The Trustees Of Columbia University In The City Of New York	Novel phosphodiesterase inhibitors and uses thereof
EP2956141A4 (en)	2013-02-17	2016-10-26	Intra Cellular Therapies Inc	NEW USES
PL2970279T3 (pl)	2013-03-15	2021-05-31	Intra-Cellular Therapies, Inc.	Związki organiczne
EP2968338B1 (en)	2013-03-15	2019-01-09	Intra-Cellular Therapies, Inc.	Pde1 inhibitors for use in the treatment and/or prevention of cns injuries, and pns diseases, disorders or injuries
WO2015009930A2 (en)	2013-07-17	2015-01-22	The Trustees Of Columbia University In The City Of New York	Novel phosphodiesterase inhibitors and uses thereof
US9849132B2 (en)	2014-01-08	2017-12-26	Intra-Cellular Therapies, Inc.	Products and pharmaceutical compositions
DK3157926T3 (da)	2014-06-20	2019-08-19	Intra Cellular Therapies Inc	Organiske forbindelser
US9546175B2 (en)	2014-08-07	2017-01-17	Intra-Cellular Therapies, Inc.	Organic compounds
US10131671B2 (en)	2014-08-07	2018-11-20	Intra-Cellular Therapies, Inc.	Organic compounds
US10285992B2 (en)	2014-08-07	2019-05-14	Intra-Cellular Therapies, Inc.	Combinations of PDE1 inhibitors and NEP inhibitors and associated methods
RU2711442C2 (ru)	2014-09-17	2020-01-17	Интра-Селлулар Терапиз, Инк.	Соединения и способы
MX371158B (es)	2014-12-06	2020-01-20	Intra Cellular Therapies Inc	Compuestos inhibidores de pde2.
US10105349B2 (en)	2014-12-06	2018-10-23	Intra-Cellular Therapies, Inc.	Organic compounds
US10682354B2 (en)	2016-03-28	2020-06-16	Intra-Cellular Therapies, Inc.	Compositions and methods
WO2018002673A1 (en)	2016-07-01	2018-01-04	N4 Pharma Uk Limited	Novel formulations of angiotensin ii receptor antagonists
TWI771319B (zh)	2016-09-09	2022-07-21	美商英塞特公司	吡唑并吡啶化合物及其用途
WO2018049214A1 (en)	2016-09-09	2018-03-15	Incyte Corporation	Pyrazolopyridine derivatives as hpk1 modulators and uses thereof for the treatment of cancer
AR109595A1 (es)	2016-09-09	2018-12-26	Incyte Corp	Compuestos de pirazolopirimidina y usos de estos como inhibidores de hpk1
EP3509589B1 (en)	2016-09-12	2021-11-17	Intra-Cellular Therapies, Inc.	Novel uses
WO2018152220A1 (en)	2017-02-15	2018-08-23	Incyte Corporation	Pyrazolopyridine compounds and uses thereof
US10722495B2 (en)	2017-09-08	2020-07-28	Incyte Corporation	Cyanoindazole compounds and uses thereof
US11839614B2 (en)	2018-01-31	2023-12-12	Intra-Cellular Therapies, Inc.	Methods for treating or mitigating cardiotoxicity characterized by inhibition of adenosine A2 signaling and/or adenosine A2 receptor expression
US10745388B2 (en)	2018-02-20	2020-08-18	Incyte Corporation	Indazole compounds and uses thereof
WO2019164847A1 (en)	2018-02-20	2019-08-29	Incyte Corporation	Indazole compounds and uses thereof
US10800761B2 (en)	2018-02-20	2020-10-13	Incyte Corporation	Carboxamide compounds and uses thereof
US11299473B2 (en)	2018-04-13	2022-04-12	Incyte Corporation	Benzimidazole and indole compounds and uses thereof
US10899755B2 (en)	2018-08-08	2021-01-26	Incyte Corporation	Benzothiazole compounds and uses thereof
MA53726A (fr)	2018-09-25	2022-05-11	Incyte Corp	Composés pyrazolo[4,3-d]pyrimidine en tant que modulateurs des alk2 et/ou fgfr
PE20221419A1 (es)	2019-08-06	2022-09-20	Incyte Corp	Formas solidas de un inhibidor de hpk1
JP7612672B2 (ja)	2019-09-03	2025-01-14	イントラ－セルラー・セラピーズ・インコーポレイテッド	新規化合物
US11590209B2 (en)	2020-01-21	2023-02-28	Palatin Technologies, Inc.	Use of bremelanotide in patients with controlled hypertension
CN113493459B (zh) *	2020-04-07	2022-12-13	广州白云山医药集团股份有限公司白云山制药总厂	Pde5抑制剂化合物及其制备方法和应用
US12364695B2 (en)	2020-06-02	2025-07-22	Intra-Cellular Therapies, Inc.	Methods of treating inflammatory disease
JP2025513455A (ja)	2022-04-22	2025-04-24	バーテックスファーマシューティカルズインコーポレイテッド	疼痛の治療のためのヘテロアリール化合物

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4871843A (en)	1983-10-18	1989-10-03	Dropic-Societe Civile De Gestion De Droits De Propriete Industrielle	Cyclic benzenesulfonamides, process for their preparation and their use as active substance of pharmaceutical compositions
US4663326A (en)	1985-04-04	1987-05-05	Warner-Lambert Company	Pyrazolo[4,3-d]pyrimidine-5,7-(4H,6H)dione or -5-thione-7-one analogs
US4666908A (en)	1985-04-05	1987-05-19	Warner-Lambert Company	5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use
US5075310A (en)	1988-07-01	1991-12-24	Smith Kline & French Laboratories, Ltd.	Pyrimidone derivatives as bronchodilators
GB8817651D0 (en)	1988-07-25	1988-09-01	Smith Kline French Lab	Chemical compounds
GB9013750D0 (en) *	1990-06-20	1990-08-08	Pfizer Ltd	Therapeutic agents
US5250534A (en)	1990-06-20	1993-10-05	Pfizer Inc.	Pyrazolopyrimidinone antianginal agents
GB9114760D0 (en)	1991-07-09	1991-08-28	Pfizer Ltd	Therapeutic agents
GB9119704D0 (en)	1991-09-14	1991-10-30	Pfizer Ltd	Therapeutic agents
GB9121028D0 (en)	1991-10-03	1991-11-13	Pfizer Ltd	Therapeutic agents
GB9126260D0 (en)	1991-12-11	1992-02-12	Pfizer Ltd	Therapeutic agents
GB9202238D0 (en)	1992-02-03	1992-03-18	Wellcome Found	Compounds
US5294612A (en) *	1992-03-30	1994-03-15	Sterling Winthrop Inc.	6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof
US5734053A (en)	1992-06-26	1998-03-31	Pfizer Inc	Purinone antianginal agents
GB9213623D0 (en)	1992-06-26	1992-08-12	Pfizer Ltd	Therapeutic agents
GB9218322D0 (en)	1992-08-28	1992-10-14	Pfizer Ltd	Therapeutic agents
GB9311920D0 (en) *	1993-06-09	1993-07-28	Pfizer Ltd	Therapeutic agents
GB9315017D0 (en) *	1993-07-20	1993-09-01	Glaxo Lab Sa	Chemical compounds
GB9401090D0 (en)	1994-01-21	1994-03-16	Glaxo Lab Sa	Chemical compounds
GB9514465D0 (en)	1995-07-14	1995-09-13	Glaxo Lab Sa	Chemical compounds
US6143746A (en)	1994-01-21	2000-11-07	Icos Corporation	Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
CA2173493C (en)	1994-08-09	2008-03-25	Nobuhisa Watanabe	Fused pyridazine compounds
GB9423910D0 (en) *	1994-11-26	1995-01-11	Pfizer Ltd	Therapeutic agents
GB9423911D0 (en) *	1994-11-26	1995-01-11	Pfizer Ltd	Therapeutic agents
JP3713783B2 (ja)	1995-01-20	2005-11-09	大正製薬株式会社	１Ｈ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体
JPH11501926A (ja)	1995-03-10	1999-02-16	サノフィファーマシューティカルズインコーポレイティド	６−アリールピラゾロ［３，４−ｄ］ピリミジン−４−オン、並びにその組成物及び使用法
US5656629A (en)	1995-03-10	1997-08-12	Sanofi Winthrop, Inc.	6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof
SI9500173B (sl)	1995-05-19	2002-02-28	Lek,	Trofazna farmacevtska oblika s konstantnim in kontroliranim sproščanjem amorfne učinkovine za enkrat dnevno aplikacijo
IL118778A (en)	1995-07-03	1999-07-14	Sankyo Co	Pharmaceutical compositions for the treatment of arteriosclerosis and xanthoma containing an hmg-coa reductase inhibitor
GB9514464D0 (en)	1995-07-14	1995-09-13	Glaxo Lab Sa	Medicaments
GB9612514D0 (en)	1996-06-14	1996-08-14	Pfizer Ltd	Novel process
CA2288910C (en)	1997-04-25	2003-06-24	Pfizer Inc.	Pyrazolopyrimidinones for sexual dysfunction
GT199800127A (es)	1997-08-29	2000-02-01		Combinaciones terapeuticas.
DE69910368T2 (de) *	1998-04-20	2004-03-25	Pfizer Inc.	Pyrazolopyrimidinone cgmp pde5 inhibitoren zur behandlung von sexualfunktionsstörungen
US6087368A (en)	1998-06-08	2000-07-11	Bristol-Myers Squibb Company	Quinazolinone inhibitors of cGMP phosphodiesterase
EP1123296B1 (en)	1998-10-23	2003-09-17	Pfizer Limited	PYRAZOLOPYRIMIDINONE cGMP PDE5 INHIBITORS FOR THE TREATMENT OF SEXUAL DYSFUNCTION
GB9823101D0 (en) *	1998-10-23	1998-12-16	Pfizer Ltd	Pharmaceutically active compounds
CO5271697A1 (es) *	2000-01-12	2003-04-30	Pfizer Prod Inc	Composiciones y procedimientos para el tratamiento de afecciones que responden a un aumento de testosterona
US20020013327A1 (en) *	2000-04-18	2002-01-31	Lee Andrew G.	Compositions and methods for treating female sexual dysfunction
US6407259B1 (en) *	2000-07-28	2002-06-18	Pfizer Inc.	Process for the preparation of pyrazoles
US6809200B2 (en) *	2000-07-28	2004-10-26	Pfizer Inc.	Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-one compounds and intermediates thereof
US20020165237A1 (en) *	2000-08-11	2002-11-07	Fryburg David Albert	Treatment of the insulin resistance syndrome
US6548508B2 (en) *	2000-10-20	2003-04-15	Pfizer, Inc.	Use of PDE V inhibitors for improved fecundity in mammals
US20020091129A1 (en) *	2000-11-20	2002-07-11	Mitradev Boolell	Treatment of premature ejaculation
US20020173502A1 (en) *	2001-03-09	2002-11-21	Allerton Charlotte Moira Norfor	Pharmaceutically active compounds
US6770645B2 (en) *	2001-03-16	2004-08-03	Pfizer Inc.	Pharmaceutically active compounds
WO2003012095A1 (en)	2001-07-28	2003-02-13	Midwest Research Institute	Thermal tolerant exoglucanase from acidothermus cellulolyticus

2000
- 2000-10-04 KR KR1020027004589A patent/KR20020038941A/ko not_active Ceased
- 2000-10-04 WO PCT/IB2000/001430 patent/WO2001027112A1/en not_active Ceased
- 2000-10-04 SK SK456-2002A patent/SK4562002A3/sk unknown
- 2000-10-04 DZ DZ003218A patent/DZ3218A1/fr active
- 2000-10-04 JP JP2001530330A patent/JP2003511452A/ja not_active Withdrawn
- 2000-10-04 CZ CZ20021151A patent/CZ20021151A3/cs unknown
- 2000-10-04 IL IL14902500A patent/IL149025A0/xx unknown
- 2000-10-04 NZ NZ517324A patent/NZ517324A/en unknown
- 2000-10-04 EA EA200200240A patent/EA200200240A1/ru unknown
- 2000-10-04 CA CA002387353A patent/CA2387353A1/en not_active Abandoned
- 2000-10-04 AU AU75479/00A patent/AU7547900A/en not_active Abandoned
- 2000-10-04 EE EEP200200192A patent/EE200200192A/xx unknown
- 2000-10-04 HK HK03101881.7A patent/HK1049834A1/zh unknown
- 2000-10-04 EP EP00964557A patent/EP1222190A1/en not_active Withdrawn
- 2000-10-04 BR BR0014695-1A patent/BR0014695A/pt not_active IP Right Cessation
- 2000-10-04 CN CN00814083A patent/CN1378547A/zh active Pending
- 2000-10-04 OA OA1200200101A patent/OA12058A/en unknown
- 2000-10-04 TR TR2002/00954T patent/TR200200954T2/xx unknown
- 2000-10-04 AP APAP/P/2002/002455A patent/AP2002002455A0/en unknown
- 2000-10-04 PL PL00357522A patent/PL357522A1/xx not_active Application Discontinuation
- 2000-10-04 HU HU0203438A patent/HUP0203438A3/hu unknown
- 2000-10-06 US US09/684,228 patent/US6756373B1/en not_active Expired - Fee Related
- 2000-10-09 UY UY26383A patent/UY26383A1/es not_active Application Discontinuation
- 2000-10-10 PA PA20008504401A patent/PA8504401A1/es unknown
- 2000-10-10 CO CO00077032A patent/CO5261539A1/es not_active Application Discontinuation
- 2000-10-10 PE PE2000001084A patent/PE20010736A1/es not_active Application Discontinuation
- 2000-10-10 TN TNTNSN00198A patent/TNSN00198A1/fr unknown
- 2000-10-10 AR ARP000105332A patent/AR022665A1/es not_active Application Discontinuation
- 2000-10-10 SV SV2000000192A patent/SV2002000192A/es unknown
- 2000-10-10 GT GT200000168A patent/GT200000168A/es unknown
2002
- 2002-02-26 IS IS6288A patent/IS6288A/is unknown
- 2002-04-02 BG BG106568A patent/BG106568A/bg unknown
- 2002-04-04 MA MA26585A patent/MA26824A1/fr unknown
- 2002-04-10 NO NO20021695A patent/NO20021695L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1378547A (zh)	2002-11-06
CZ20021151A3 (cs)	2003-03-12
BR0014695A (pt)	2002-06-18
BG106568A (bg)	2002-12-29
CA2387353A1 (en)	2001-04-19
TNSN00198A1 (fr)	2002-05-30
US6756373B1 (en)	2004-06-29
HUP0203438A2 (hu)	2003-01-28
PA8504401A1 (es)	2002-04-25
MA26824A1 (fr)	2004-12-20
AU7547900A (en)	2001-04-23
KR20020038941A (ko)	2002-05-24
AR022665A1 (es)	2002-09-04
NZ517324A (en)	2003-09-26
TR200200954T2 (tr)	2002-09-23
DZ3218A1 (fr)	2001-04-19
HK1049834A1 (zh)	2003-05-30
JP2003511452A (ja)	2003-03-25
IS6288A (is)	2002-02-26
HUP0203438A3 (en)	2003-05-28
EE200200192A (et)	2003-06-16
NO20021695D0 (no)	2002-04-10
EA200200240A1 (ru)	2002-10-31
SK4562002A3 (en)	2003-04-01
IL149025A0 (en)	2002-11-10
GT200000168A (es)	2002-04-03
PL357522A1 (en)	2004-07-26
CO5261539A1 (es)	2003-03-31
SV2002000192A (es)	2002-07-16
PE20010736A1 (es)	2001-07-19
AP2002002455A0 (en)	2002-06-30
UY26383A1 (es)	2001-05-31
EP1222190A1 (en)	2002-07-17
NO20021695L (no)	2002-06-07
WO2001027112A1 (en)	2001-04-19

Publication	Publication Date	Title
OA12058A (en)	2006-05-03	5-(2-Substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazoloÄ4,3-DÜpyrimidin-7-ones as phosphodiesterase inhibitors.
US8063048B2 (en)	2011-11-22	Acetylenyl-pyrazolo-pyrimidine derivatives
US10004737B2 (en)	2018-06-26	Fused imidazole and pyrazole derivatives as modulators of TNF activity
IL290341B1 (en)	2024-07-01	Mta-cooperative prmt5 inhibitors
ES2750791T3 (es)	2020-03-27	Derivados de indolizina como inhibidores de fosfoinositido 3-quinasas
EP2001884A1 (en)	2008-12-17	Deazapurines useful as inhibitors of janus kinases
RS50476B (sr)	2010-03-02	Derivati pirazolo (4,3-d) pirimidina
MX2007009429A (es)	2008-03-18	Pirrolopirimidinas utiles como inhibidores de proteinas cinasas.
JP2017522276A (ja)	2017-08-10	ＡＴＲキナーゼ阻害剤として有用な２−アミノ−６−フルオロ−Ｎ−［５−フルオロ−ピリジン−３−イル］ピラゾロ［１，５−ａ］ピリミジン−３−カルボキサミド化合物の放射性標識された誘導体、この化合物およびその異なる固体形態の調製
CA2439528A1 (en)	2002-09-26	Cyclic guanosine 3',5'-monophosphate phosphodiesterase inhibitors
BR112015002262A2 (pt)	2019-12-10	compostos, métodos para os tratamentos de uma condição inflamatória, artrite reumatóide, asma e distúrbio imunológico; composição farmacêutica, utilização do composto e invenção
CZ322192A3 (en)	1993-08-11	Substituted pyrimidine derivatives, process of their preparation and pharmaceutical preparations in which they are comprised
NZ787350A (en)	2022-04-29	Heterocyclic compounds as ret kinase inhibitors
NZ786565A (en)	2022-04-29	Heterocyclic compounds as ret kinase inhibitors