UA109140C2 - Гетероциклічні сполуки бензодіоксолу або бензодіоксепіну як інгібітори фосфодіестераз - Google Patents

Гетероциклічні сполуки бензодіоксолу або бензодіоксепіну як інгібітори фосфодіестераз Download PDF

Info

Publication number: UA109140C2
Authority: UA; Ukraine
Prior art keywords: compound; compound according; difluoromethoxy; dichloro; skin
Prior art date: 2010-06-24

Application number

UAA201300812A

Other languages

English (en)

Ukrainian (uk)

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.)

2010-06-24

Filing date

2011-06-24

Publication date

2015-07-27

2011-06-24 Application filed filed Critical

2015-07-27 Publication of UA109140C2 publication Critical patent/UA109140C2/uk

Links

125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 11
239000002571 phosphodiesterase inhibitor Substances 0.000 title description 3
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 title 1
WITJHZRCLVXYCA-UHFFFAOYSA-N 3h-1,2-benzodioxepine Chemical class C1=CCOOC2=CC=CC=C21 WITJHZRCLVXYCA-UHFFFAOYSA-N 0.000 title 1
229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 120
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 31
125000005842 heteroatom Chemical group 0.000 claims abstract description 26
-1 amino, thioxo Chemical group 0.000 claims abstract description 22
238000011282 treatment Methods 0.000 claims abstract description 18
125000000217 alkyl group Chemical group 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 12
208000027866 inflammatory disease Diseases 0.000 claims abstract description 10
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 8
125000003118 aryl group Chemical group 0.000 claims abstract description 7
125000001424 substituent group Chemical group 0.000 claims abstract description 7
125000004366 heterocycloalkenyl group Chemical group 0.000 claims abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
239000012453 solvate Substances 0.000 claims abstract description 6
125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
229910052736 halogen Inorganic materials 0.000 claims abstract description 5
150000002367 halogens Chemical group 0.000 claims abstract description 5
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 5
239000001257 hydrogen Substances 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 4
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 4
239000011593 sulfur Chemical group 0.000 claims abstract description 4
229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 47
238000000034 method Methods 0.000 claims description 28
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 27
239000004480 active ingredient Substances 0.000 claims description 16
201000004624 Dermatitis Diseases 0.000 claims description 8
206010012438 Dermatitis atopic Diseases 0.000 claims description 8
206010040799 Skin atrophy Diseases 0.000 claims description 8
201000008937 atopic dermatitis Diseases 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
YCRGMNXARTVRLB-UHFFFAOYSA-N 2h-1,5-benzodioxepine Chemical compound O1C=CCOC2=CC=CC=C21 YCRGMNXARTVRLB-UHFFFAOYSA-N 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
230000002757 inflammatory effect Effects 0.000 claims description 6
210000003491 skin Anatomy 0.000 claims description 6
208000017520 skin disease Diseases 0.000 claims description 6
WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 claims description 5
206010061218 Inflammation Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
230000004054 inflammatory process Effects 0.000 claims description 5
208000002874 Acne Vulgaris Diseases 0.000 claims description 4
201000004384 Alopecia Diseases 0.000 claims description 4
208000011231 Crohn disease Diseases 0.000 claims description 4
206010012442 Dermatitis contact Diseases 0.000 claims description 4
206010051246 Photodermatosis Diseases 0.000 claims description 4
208000003251 Pruritus Diseases 0.000 claims description 4
206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 4
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 4
208000024780 Urticaria Diseases 0.000 claims description 4
206010000496 acne Diseases 0.000 claims description 4
231100000360 alopecia Toxicity 0.000 claims description 4
208000010668 atopic eczema Diseases 0.000 claims description 4
239000011230 binding agent Substances 0.000 claims description 4
239000004202 carbamide Substances 0.000 claims description 4
208000010247 contact dermatitis Diseases 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
230000008845 photoaging Effects 0.000 claims description 4
230000002062 proliferating effect Effects 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
208000008742 seborrheic dermatitis Diseases 0.000 claims description 4
230000009759 skin aging Effects 0.000 claims description 4
150000003431 steroids Chemical class 0.000 claims description 4
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 4
XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 claims description 4
GINSRDSEEGBTJO-UHFFFAOYSA-N thietane 1-oxide Chemical compound O=S1CCC1 GINSRDSEEGBTJO-UHFFFAOYSA-N 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 3
208000031091 Amnestic disease Diseases 0.000 claims description 3
208000023275 Autoimmune disease Diseases 0.000 claims description 3
206010012289 Dementia Diseases 0.000 claims description 3
206010019280 Heart failures Diseases 0.000 claims description 3
206010022491 Insulin resistant diabetes Diseases 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 3
206010039085 Rhinitis allergic Diseases 0.000 claims description 3
241000534944 Thia Species 0.000 claims description 3
201000010105 allergic rhinitis Diseases 0.000 claims description 3
230000006986 amnesia Effects 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
210000003169 central nervous system Anatomy 0.000 claims description 3
208000026106 cerebrovascular disease Diseases 0.000 claims description 3
230000006378 damage Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
210000002615 epidermis Anatomy 0.000 claims description 3
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
230000000302 ischemic effect Effects 0.000 claims description 3
201000006417 multiple sclerosis Diseases 0.000 claims description 3
201000008383 nephritis Diseases 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 3
230000007170 pathology Effects 0.000 claims description 3
238000010992 reflux Methods 0.000 claims description 3
230000035939 shock Effects 0.000 claims description 3
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 claims description 3
239000000126 substance Substances 0.000 claims description 3
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 2
FCFMKFHUNDYKEG-UHFFFAOYSA-N thietane 1,1-dioxide Chemical compound O=S1(=O)CCC1 FCFMKFHUNDYKEG-UHFFFAOYSA-N 0.000 claims description 2
101100534115 Drosophila melanogaster Snup gene Proteins 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 abstract description 4
150000004677 hydrates Chemical class 0.000 abstract description 2
101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 abstract 1
101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 abstract 1
125000004438 haloalkoxy group Chemical group 0.000 abstract 1
125000000446 sulfanediyl group Chemical group *S* 0.000 abstract 1
238000002360 preparation method Methods 0.000 description 29
238000005481 NMR spectroscopy Methods 0.000 description 28
239000000243 solution Substances 0.000 description 23
238000004587 chromatography analysis Methods 0.000 description 19
239000000047 product Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
238000003756 stirring Methods 0.000 description 18
230000002829 reductive effect Effects 0.000 description 17
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
MRTAVLDNYYEJHK-UHFFFAOYSA-M sodium;2-chloro-2,2-difluoroacetate Chemical compound [Na+].[O-]C(=O)C(F)(F)Cl MRTAVLDNYYEJHK-UHFFFAOYSA-M 0.000 description 12
239000003112 inhibitor Substances 0.000 description 11
235000002639 sodium chloride Nutrition 0.000 description 11
125000003003 spiro group Chemical group 0.000 description 11
210000002966 serum Anatomy 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
239000003814 drug Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
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 8
235000019253 formic acid Nutrition 0.000 description 8
239000000843 powder Substances 0.000 description 8
YAJYJWXEWKRTPO-UHFFFAOYSA-N 2,3,3,4,4,5-hexamethylhexane-2-thiol Chemical compound CC(C)C(C)(C)C(C)(C)C(C)(C)S YAJYJWXEWKRTPO-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
229940079593 drug Drugs 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000007788 liquid Substances 0.000 description 7
150000003254 radicals Chemical class 0.000 description 7
239000012266 salt solution Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 6
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 6
125000002619 bicyclic group Chemical group 0.000 description 6
ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
238000006386 neutralization reaction Methods 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000012300 argon atmosphere Substances 0.000 description 4
125000002837 carbocyclic group Chemical group 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000003921 oil Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
239000002207 metabolite Substances 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
235000010981 methylcellulose Nutrition 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000002245 particle Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
239000003826 tablet Substances 0.000 description 3
229960000278 theophylline Drugs 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
WPGHPGAUFIJVJF-UHFFFAOYSA-N 3,5-dichloropyridine Chemical compound ClC1=CN=CC(Cl)=C1 WPGHPGAUFIJVJF-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
235000006491 Acacia senegal Nutrition 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
230000005526 G1 to G0 transition Effects 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
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 2
229920000084 Gum arabic Polymers 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
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 2
239000002253 acid Substances 0.000 description 2
230000002411 adverse Effects 0.000 description 2
150000003973 alkyl amines Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
239000011324 bead Substances 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
210000003710 cerebral cortex Anatomy 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
SNQXJPARXFUULZ-UHFFFAOYSA-N dioxolane Chemical compound C1COOC1 SNQXJPARXFUULZ-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
238000007429 general method Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
150000002430 hydrocarbons Chemical class 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
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
210000004969 inflammatory cell Anatomy 0.000 description 2
230000028709 inflammatory response Effects 0.000 description 2
230000003993 interaction Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
238000002955 isolation Methods 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229960002900 methylcellulose Drugs 0.000 description 2
238000000465 moulding Methods 0.000 description 2
210000000440 neutrophil Anatomy 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
238000003825 pressing Methods 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000700 radioactive tracer Substances 0.000 description 2
230000007017 scission Effects 0.000 description 2
238000010956 selective crystallization Methods 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000008107 starch Substances 0.000 description 2
229940032147 starch Drugs 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
230000000707 stereoselective effect Effects 0.000 description 2
239000000758 substrate Substances 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
239000011782 vitamin Substances 0.000 description 2
229940088594 vitamin Drugs 0.000 description 2
229930003231 vitamin Natural products 0.000 description 2
235000013343 vitamin Nutrition 0.000 description 2
150000003722 vitamin derivatives Chemical class 0.000 description 2
LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
BVRDQVRQVGRNHG-UHFFFAOYSA-N 2-morpholin-4-ylpyrimido[2,1-a]isoquinolin-4-one Chemical compound N1=C2C3=CC=CC=C3C=CN2C(=O)C=C1N1CCOCC1 BVRDQVRQVGRNHG-UHFFFAOYSA-N 0.000 description 1
CBXMULHQEVXJDI-UHFFFAOYSA-N 3,4-dihydro-2h-1,5-benzodioxepine Chemical compound O1CCCOC2=CC=CC=C21 CBXMULHQEVXJDI-UHFFFAOYSA-N 0.000 description 1
ISIQAMHROGZHOV-UHFFFAOYSA-N 3,5-dichloropyridin-4-amine Chemical compound NC1=C(Cl)C=NC=C1Cl ISIQAMHROGZHOV-UHFFFAOYSA-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
XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
RJBSTXIIQYFNPX-UHFFFAOYSA-N 4-methoxy-6-phenyl-1,3,5-triazin-2-amine Chemical compound COC1=NC(N)=NC(C=2C=CC=CC=2)=N1 RJBSTXIIQYFNPX-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
STBGWNRZMPCVTG-UHFFFAOYSA-N 4h-thiopyran Chemical compound C1C=CSC=C1 STBGWNRZMPCVTG-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
RTAPDZBZLSXHQQ-UHFFFAOYSA-N 8-methyl-3,7-dihydropurine-2,6-dione Chemical class N1C(=O)NC(=O)C2=C1N=C(C)N2 RTAPDZBZLSXHQQ-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar 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
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
239000004381 Choline salt Substances 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
206010010904 Convulsion Diseases 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
208000012895 Gastric disease Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical class CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
UULYVBBLIYLRCU-UHFFFAOYSA-N Palmitinsaeure-n-tetradecylester Natural products CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC UULYVBBLIYLRCU-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
241001377010 Pila Species 0.000 description 1
108010003541 Platelet Activating Factor Proteins 0.000 description 1
229910052777 Praseodymium Inorganic materials 0.000 description 1
241000549435 Pria Species 0.000 description 1
229910052774 Proactinium Inorganic materials 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
241000282887 Suidae Species 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
241001189642 Theroa Species 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000011149 active material Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
239000000464 adrenergic agent Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
229940023476 agar Drugs 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
239000012491 analyte Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
238000011861 anti-inflammatory therapy Methods 0.000 description 1
229940125715 antihistaminic agent Drugs 0.000 description 1
239000000739 antihistaminic agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
239000000440 bentonite Substances 0.000 description 1
229910000278 bentonite Inorganic materials 0.000 description 1
229940092782 bentonite Drugs 0.000 description 1
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
YOUGRGFIHBUKRS-UHFFFAOYSA-N benzyl(trimethyl)azanium Chemical class C[N+](C)(C)CC1=CC=CC=C1 YOUGRGFIHBUKRS-UHFFFAOYSA-N 0.000 description 1
150000003939 benzylamines Chemical class 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
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
229940046731 calcineurin inhibitors Drugs 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
229940105329 carboxymethylcellulose Drugs 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000009134 cell regulation Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical class CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
235000019417 choline salt Nutrition 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
238000010411 cooking Methods 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000006071 cream 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
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229940095074 cyclic amp Drugs 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000009849 deactivation Effects 0.000 description 1
230000020335 dealkylation Effects 0.000 description 1
238000006900 dealkylation reaction Methods 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
SIYLLGKDQZGJHK-UHFFFAOYSA-N dimethyl-(phenylmethyl)-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]ammonium Chemical class C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 description 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
150000002169 ethanolamines Chemical class 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000008172 hydrogenated vegetable oil Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
229960000905 indomethacin Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
230000001678 irradiating effect Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000865 liniment Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
239000000025 natural resin Substances 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
229960001639 penicillamine Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
108091008695 photoreceptors Proteins 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000011002 quantification Methods 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000002994 raw material Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
238000012552 review Methods 0.000 description 1
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
229950005741 rolipram Drugs 0.000 description 1
150000003902 salicylic acid esters Chemical class 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
UKHWJBVVWVYFEY-UHFFFAOYSA-M silver;hydroxide Chemical compound [OH-].[Ag+] UKHWJBVVWVYFEY-UHFFFAOYSA-M 0.000 description 1
230000037380 skin damage Effects 0.000 description 1
206010040882 skin lesion Diseases 0.000 description 1
231100000444 skin lesion Toxicity 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
229960001940 sulfasalazine Drugs 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000057 synthetic resin Substances 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
230000002123 temporal effect Effects 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
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical class CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
239000007762 w/o emulsion Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems

UAA201300812A 2010-06-24 2011-06-24 Гетероциклічні сполуки бензодіоксолу або бензодіоксепіну як інгібітори фосфодіестераз UA109140C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US35820910P	2010-06-24	2010-06-24
PCT/DK2011/000069 WO2011160632A1 (en)	2010-06-24	2011-06-24	Benzodioxole or benzodioxepine heterocyclic compounds phosphodiesterase inhibitors

Publications (1)

Publication Number	Publication Date
UA109140C2 true UA109140C2 (uk)	2015-07-27

Family

ID=44351701

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UAA201300812A UA109140C2 (uk)	2010-06-24	2011-06-24	Гетероциклічні сполуки бензодіоксолу або бензодіоксепіну як інгібітори фосфодіестераз

Country Status (30)

Country	Link
US (3)	US8980905B2 (ru)
EP (2)	EP3070091B1 (ru)
JP (2)	JP6174997B2 (ru)
KR (1)	KR101864578B1 (ru)
CN (1)	CN102958937B (ru)
AU (1)	AU2011269429B2 (ru)
BR (1)	BR112012032813B1 (ru)
CA (1)	CA2802895C (ru)
CY (2)	CY1117862T1 (ru)
DK (2)	DK3070091T3 (ru)
ES (2)	ES2584055T3 (ru)
HK (1)	HK1182699A1 (ru)
HR (2)	HRP20160919T1 (ru)
HU (2)	HUE030081T2 (ru)
IL (1)	IL223329A (ru)
LT (2)	LT3070091T (ru)
MX (1)	MX2012014131A (ru)
MY (1)	MY157481A (ru)
NZ (1)	NZ603895A (ru)
PL (2)	PL2585469T3 (ru)
PT (2)	PT2585469T (ru)
RS (2)	RS58945B1 (ru)
RU (1)	RU2583787C2 (ru)
SG (1)	SG186140A1 (ru)
SI (2)	SI2585469T1 (ru)
TR (1)	TR201909709T4 (ru)
TW (1)	TWI507410B (ru)
UA (1)	UA109140C2 (ru)
WO (1)	WO2011160632A1 (ru)
ZA (1)	ZA201209031B (ru)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2663448C2 (ru) *	2012-11-30	2018-08-06	Лео Фарма А/С	Способ ингибирования экспрессии ил-22 активированными т-клетками
JP6785666B2 (ja) *	2014-06-23	2020-11-18	レオファーマアクティーゼルスカブ	１，３−ベンゾジオキソール複素環化合物の調製方法
WO2017089347A1 (en)	2015-11-25	2017-06-01	Inserm (Institut National De La Sante Et De La Recherche Medicale)	Methods and pharmaceutical compositions for the treatment of braf inhibitor resistant melanomas
CA3007432A1 (en)	2015-12-18	2017-06-22	Leo Pharma A/S	Methods for the preparation of 1,3-benzodioxole heterocyclic compounds
AU2018286964B2 (en) *	2017-06-20	2022-04-14	UNION therapeutics A/S	Methods for the preparation of 1,3-benzodioxole heterocyclic compounds
CN112262143A (zh)	2018-05-21	2021-01-22	星座制药公司	甲基修饰酶的调节剂、其组合物和用途
EA202191955A1 (ru) *	2019-01-15	2021-10-07	Юнион Терапьютикс А/С	Таблетированные составы с модифицированным высвобождением, содержащие ингибиторы фосфодиэстеразы
PE20230253A1 (es) *	2019-07-24	2023-02-07	Constellation Pharmaceuticals Inc	Inhibicion de ezh2 en tratamientos combinados para el tratamiento del cancer
CN112552276B (zh) *	2019-09-25	2023-03-21	中国科学院上海药物研究所	苯并氧杂卓-5-酮类化合物及其制备方法和用途
WO2022200339A1 (en)	2021-03-22	2022-09-29	UNION therapeutics A/S	Treatment of hidradenitis suppurativa with orismilast
GB202205715D0 (en)	2022-04-19	2022-06-01	Union Therapeutics As	Treatment of neutrophilic dermatoses

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ290266B6 (cs)	1993-07-02	2002-06-12	Byk Gulden Lomberg Chemische Fabrik Gmbh	Substituované benzamidy, způsob jejich výroby a farmaceutické prostředky s jejich obsahem
GB9507297D0 (en)	1995-04-07	1995-05-31	Rh Ne Poulenc Rorer Limited	New composition of matter
JP4172817B2 (ja)	1995-05-19	2008-10-29	協和醗酵工業株式会社	含酸素複素環化合物
NZ332340A (en) *	1996-05-20	2000-04-28	Darwin Discovery Ltd	4-(aryl or heteroaryl) substituted benzofurancarboxamide derivatives and medicaments
EP0943613A4 (en) *	1996-11-19	2002-07-10	Kyowa Hakko Kogyo Kk	HETEROCYCLIC COMPOUNDS CONTAINING OXYGEN
JP2005060375A (ja) *	2003-07-28	2005-03-10	Kyowa Hakko Kogyo Co Ltd	含酸素複素環化合物
DE10360792A1 (de) *	2003-12-23	2005-07-28	Grünenthal GmbH	Spirocyclische Cyclohexan-Derivate
MX2007007345A (es) *	2004-12-17	2007-09-07	Glenmark Pharmaceuticals Sa	Compuestos heterociclicos novedosos utiles para el tratamiento de trastornos inflamatorios y alergicos.
ES2478670T3 (es) *	2007-02-28	2014-07-22	Leo Pharma A/S	Nuevos inhibidores de la fosfodiesterasa
ZA200905371B (en) *	2007-02-28	2010-10-27	Leo Pharma As	Novel phosphodiesterase Inhibitors
EP2794603B1 (en) *	2011-12-21	2016-06-15	Leo Pharma A/S	[1,2,4]triazolopyridines and their use as phospodiesterase inhibitors

2011
- 2011-06-24 PT PT117298893T patent/PT2585469T/pt unknown
- 2011-06-24 US US13/806,659 patent/US8980905B2/en active Active
- 2011-06-24 HU HUE11729889A patent/HUE030081T2/en unknown
- 2011-06-24 RS RS20190851A patent/RS58945B1/sr unknown
- 2011-06-24 SG SG2012088761A patent/SG186140A1/en unknown
- 2011-06-24 DK DK16020112.5T patent/DK3070091T3/da active
- 2011-06-24 TW TW100122303A patent/TWI507410B/zh active
- 2011-06-24 WO PCT/DK2011/000069 patent/WO2011160632A1/en active Application Filing
- 2011-06-24 CN CN201180031069.5A patent/CN102958937B/zh active Active
- 2011-06-24 UA UAA201300812A patent/UA109140C2/uk unknown
- 2011-06-24 HU HUE16020112 patent/HUE044301T2/hu unknown
- 2011-06-24 MX MX2012014131A patent/MX2012014131A/es active IP Right Grant
- 2011-06-24 LT LTEP16020112.5T patent/LT3070091T/lt unknown
- 2011-06-24 NZ NZ603895A patent/NZ603895A/en unknown
- 2011-06-24 DK DK11729889.3T patent/DK2585469T3/en active
- 2011-06-24 PT PT16020112T patent/PT3070091T/pt unknown
- 2011-06-24 CA CA2802895A patent/CA2802895C/en active Active
- 2011-06-24 PL PL11729889T patent/PL2585469T3/pl unknown
- 2011-06-24 LT LTEP11729889.3T patent/LT2585469T/lt unknown
- 2011-06-24 JP JP2013515698A patent/JP6174997B2/ja active Active
- 2011-06-24 RU RU2013103079/04A patent/RU2583787C2/ru active
- 2011-06-24 RS RS20160581A patent/RS55104B1/sr unknown
- 2011-06-24 MY MYPI2012005553A patent/MY157481A/en unknown
- 2011-06-24 SI SI201130896A patent/SI2585469T1/sl unknown
- 2011-06-24 EP EP16020112.5A patent/EP3070091B1/en active Active
- 2011-06-24 SI SI201131743T patent/SI3070091T1/sl unknown
- 2011-06-24 EP EP11729889.3A patent/EP2585469B1/en active Active
- 2011-06-24 TR TR2019/09709T patent/TR201909709T4/tr unknown
- 2011-06-24 KR KR1020137001855A patent/KR101864578B1/ko not_active Application Discontinuation
- 2011-06-24 ES ES11729889.3T patent/ES2584055T3/es active Active
- 2011-06-24 ES ES16020112T patent/ES2733092T3/es active Active
- 2011-06-24 PL PL16020112T patent/PL3070091T3/pl unknown
- 2011-06-24 BR BR112012032813-1A patent/BR112012032813B1/pt active IP Right Grant
- 2011-06-24 AU AU2011269429A patent/AU2011269429B2/en active Active
2012
- 2012-11-28 IL IL223329A patent/IL223329A/en active IP Right Grant
- 2012-11-29 ZA ZA2012/09031A patent/ZA201209031B/en unknown
2013
- 2013-08-26 HK HK13109964.8A patent/HK1182699A1/zh unknown
2014
- 2014-12-30 US US14/586,681 patent/US9273064B2/en active Active
2015
- 2015-10-01 US US14/872,487 patent/US9637499B2/en active Active
2016
- 2016-03-16 JP JP2016052707A patent/JP2016164168A/ja active Pending
- 2016-07-21 HR HRP20160919TT patent/HRP20160919T1/hr unknown
- 2016-07-28 CY CY20161100745T patent/CY1117862T1/el unknown
2019
- 2019-06-21 HR HRP20191136TT patent/HRP20191136T1/hr unknown
- 2019-06-28 CY CY20191100679T patent/CY1122201T1/el unknown

Also Published As

Publication number	Publication date
CA2802895A1 (en)	2011-12-29
ES2733092T3 (es)	2019-11-27
EP3070091B1 (en)	2019-04-17
RU2583787C2 (ru)	2016-05-10
ES2584055T3 (es)	2016-09-23
KR101864578B1 (ko)	2018-06-07
TWI507410B (zh)	2015-11-11
HUE030081T2 (en)	2017-04-28
PL2585469T3 (pl)	2017-07-31
US20130123291A1 (en)	2013-05-16
IL223329A (en)	2017-01-31
HRP20160919T1 (hr)	2016-10-07
SG186140A1 (en)	2013-01-30
TW201206940A (en)	2012-02-16
WO2011160632A1 (en)	2011-12-29
DK2585469T3 (en)	2016-08-29
MX2012014131A (es)	2013-01-29
HK1182699A1 (zh)	2013-12-06
TR201909709T4 (tr)	2019-07-22
JP2016164168A (ja)	2016-09-08
KR20130038341A (ko)	2013-04-17
DK3070091T3 (da)	2019-07-08
EP2585469A1 (en)	2013-05-01
BR112012032813B1 (pt)	2022-02-01
LT2585469T (lt)	2016-10-10
JP2013529602A (ja)	2013-07-22
US9273064B2 (en)	2016-03-01
HUE044301T2 (hu)	2019-10-28
RU2013103079A (ru)	2014-07-27
PT3070091T (pt)	2019-07-22
LT3070091T (lt)	2019-07-25
PT2585469T (pt)	2016-08-29
RS55104B1 (sr)	2016-12-30
JP6174997B2 (ja)	2017-08-02
SI3070091T1 (sl)	2019-08-30
BR112012032813A2 (pt)	2016-11-08
US20150111915A1 (en)	2015-04-23
CA2802895C (en)	2019-05-21
EP2585469B1 (en)	2016-05-25
MY157481A (en)	2016-06-15
RS58945B1 (sr)	2019-08-30
AU2011269429A1 (en)	2012-12-20
CN102958937A (zh)	2013-03-06
ZA201209031B (en)	2014-02-26
CY1117862T1 (el)	2017-05-17
HRP20191136T1 (hr)	2019-09-20
PL3070091T3 (pl)	2019-09-30
EP3070091A1 (en)	2016-09-21
US20160022657A1 (en)	2016-01-28
AU2011269429B2 (en)	2015-07-09
CY1122201T1 (el)	2020-11-25
IL223329A0 (en)	2013-02-03
NZ603895A (en)	2014-10-31
US8980905B2 (en)	2015-03-17
CN102958937B (zh)	2016-03-30
US9637499B2 (en)	2017-05-02
SI2585469T1 (sl)	2016-11-30

Publication	Publication Date	Title
UA109140C2 (uk)	2015-07-27	Гетероциклічні сполуки бензодіоксолу або бензодіоксепіну як інгібітори фосфодіестераз
US8338431B2 (en)	2012-12-25	Phosphodiesterase inhibitors
CN101631792A (zh)	2010-01-20	新的磷酸二酯酶抑制剂
CN110372665A (zh)	2019-10-25	一种阿哌沙班吡啶酮杂质的制备方法
TWI432439B (zh)	2014-04-01	新穎磷酸二酯酶抑制劑