BR112016005601B1 - composto, composição farmacêutica, e usos de um composto - Google Patents
composto, composição farmacêutica, e usos de um composto Download PDFInfo
- Publication number
- BR112016005601B1 BR112016005601B1 BR112016005601-9A BR112016005601A BR112016005601B1 BR 112016005601 B1 BR112016005601 B1 BR 112016005601B1 BR 112016005601 A BR112016005601 A BR 112016005601A BR 112016005601 B1 BR112016005601 B1 BR 112016005601B1
- Authority
- BR
- Brazil
- Prior art keywords
- fibrosis
- compound
- present
- pharmaceutically acceptable
- weeks
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 60
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 46
- 230000004761 fibrosis Effects 0.000 claims abstract description 46
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 20
- 206010020772 Hypertension Diseases 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 13
- 206010065918 Prehypertension Diseases 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 206010028594 Myocardial fibrosis Diseases 0.000 claims description 5
- 201000002793 renal fibrosis Diseases 0.000 claims description 5
- 239000002131 composite material Substances 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 abstract description 4
- -1 terphenyl compound Chemical class 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 235000005911 diet Nutrition 0.000 description 18
- 230000037213 diet Effects 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 230000036772 blood pressure Effects 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 210000002216 heart Anatomy 0.000 description 11
- 230000035488 systolic blood pressure Effects 0.000 description 11
- 210000003734 kidney Anatomy 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- NAUBSKHQFFCEMQ-UHFFFAOYSA-N 2-hydroxy-5-phenylbenzaldehyde Chemical compound C1=C(C=O)C(O)=CC=C1C1=CC=CC=C1 NAUBSKHQFFCEMQ-UHFFFAOYSA-N 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- QPVCUQOSWAXEOQ-UHFFFAOYSA-N 2-diethoxyphosphorylacetamide Chemical compound CCOP(=O)(CC(N)=O)OCC QPVCUQOSWAXEOQ-UHFFFAOYSA-N 0.000 description 4
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- XJKSTNDFUHDPQJ-UHFFFAOYSA-N 1,4-diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 XJKSTNDFUHDPQJ-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000002682 Hyperkalemia Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 3
- 230000003510 anti-fibrotic effect Effects 0.000 description 3
- 210000002403 aortic endothelial cell Anatomy 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000024883 vasodilation Effects 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- WIJNYNBSPQMJGO-UHFFFAOYSA-N (3-phenylmethoxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(OCC=2C=CC=CC=2)=C1 WIJNYNBSPQMJGO-UHFFFAOYSA-N 0.000 description 2
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 2
- MKKSTJKBKNCMRV-UHFFFAOYSA-N 5-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C=C1C=O MKKSTJKBKNCMRV-UHFFFAOYSA-N 0.000 description 2
- 208000028185 Angioedema Diseases 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000025047 Non-histaminic angioedema Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 206010030124 Oedema peripheral Diseases 0.000 description 2
- 102100029143 RNA 3'-terminal phosphate cyclase Human genes 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002170 aldosterone antagonist Substances 0.000 description 2
- 229940083712 aldosterone antagonist Drugs 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004531 blood pressure lowering effect Effects 0.000 description 2
- FGNLEIGUMSBZQP-UHFFFAOYSA-N cadaverine dihydrochloride Chemical compound Cl.Cl.NCCCCCN FGNLEIGUMSBZQP-UHFFFAOYSA-N 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- CZRCFAOMWRAFIC-UHFFFAOYSA-N 5-(tetradecyloxy)-2-furoic acid Chemical compound CCCCCCCCCCCCCCOC1=CC=C(C(O)=O)O1 CZRCFAOMWRAFIC-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 208000016998 Conn syndrome Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 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
- 201000005569 Gout Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000699762 Homo sapiens RNA 3'-terminal phosphate cyclase Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020571 Hyperaldosteronism Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021036 Hyponatraemia Diseases 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000000079 gynecomastia Diseases 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 210000003111 iliac vein Anatomy 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 208000007106 menorrhagia Diseases 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-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
- 238000012544 monitoring process Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 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
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000013846 primary aldosteronism Diseases 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011273 tar residue Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2013903573 | 2013-09-17 | ||
| AU2013903573A AU2013903573A0 (en) | 2013-09-17 | Compositions for the treatment of hypertension and/or fibrosis | |
| PCT/AU2014/000923 WO2015039173A1 (en) | 2013-09-17 | 2014-09-17 | Compositions for the treatment of hypertension and/or fibrosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BR112016005601A8 BR112016005601A8 (pt) | 2020-02-18 |
| BR112016005601B1 true BR112016005601B1 (pt) | 2021-02-02 |
Family
ID=52687998
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112016005601-9A BR112016005601B1 (pt) | 2013-09-17 | 2014-09-17 | composto, composição farmacêutica, e usos de um composto |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9458093B2 (enExample) |
| EP (1) | EP3046901B1 (enExample) |
| JP (1) | JP6122548B2 (enExample) |
| KR (1) | KR101736416B1 (enExample) |
| CN (1) | CN105683152B (enExample) |
| AP (1) | AP2016009079A0 (enExample) |
| AU (1) | AU2014324078B2 (enExample) |
| BR (1) | BR112016005601B1 (enExample) |
| CA (1) | CA2924356C (enExample) |
| DK (1) | DK3046901T3 (enExample) |
| ES (1) | ES2655455T3 (enExample) |
| IL (1) | IL244621A (enExample) |
| MX (1) | MX368865B (enExample) |
| MY (1) | MY172557A (enExample) |
| NO (1) | NO3046901T3 (enExample) |
| NZ (1) | NZ717927A (enExample) |
| PH (1) | PH12016500497B1 (enExample) |
| PL (1) | PL3046901T3 (enExample) |
| RU (1) | RU2635564C2 (enExample) |
| SG (1) | SG11201601642WA (enExample) |
| UA (1) | UA118111C2 (enExample) |
| WO (1) | WO2015039173A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3284981B2 (ja) | 1998-11-02 | 2002-05-27 | 株式会社デンソー | 車両用交流発電機およびそのステータの製造方法 |
| US9956166B2 (en) | 2013-09-18 | 2018-05-01 | Sorrento Therapeutics, Inc. | Methods for administration and methods for treating cardiovascular diseases with resiniferatoxin |
| RU2712140C2 (ru) * | 2015-03-18 | 2020-01-24 | Вектус Байосистемс Лимитед | Композиции для лечения фиброза и связанных с фиброзом состояний |
| RU2712624C9 (ru) * | 2015-03-18 | 2020-04-28 | Вектус Байосистемс Лимитед | Композиции для лечения заболевания почек и/или печени |
| EP3353147B1 (en) * | 2015-09-22 | 2021-01-13 | Vectus Biosystems Limited | Synthesis of terphenyl compounds |
| KR102395342B1 (ko) * | 2016-04-13 | 2022-05-10 | 보드 오브 리젠츠 오브 디 유니버시티 오브 네브라스카 | 레시니페라톡신을 사용한 투여 방법 및 심혈관 질환을 치료하는 방법 |
| RU2747801C2 (ru) * | 2016-07-28 | 2021-05-14 | Вектус Байосистемс Лимитед | Композиции для лечения легочного фиброза |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2694288B1 (fr) * | 1992-06-30 | 1994-09-09 | Rhone Poulenc Agrochimie | Phenylbenzamides fongicides et procédés pour les préparer. |
| KR20140057411A (ko) * | 2004-06-11 | 2014-05-12 | 벡투스 바이오시스템즈 피티와이 리미티드 | 심혈관 질환의 치료를 위한 조성물 및 방법 |
| PT1976548E (pt) * | 2005-12-09 | 2014-10-13 | Vectus Biosystems Ltd | Fragmentos de vip e suas composições |
| US20120088737A2 (en) * | 2009-10-02 | 2012-04-12 | Ajinomoto Co., Inc | Novel acyl guanidine derivatives |
| ES2694375T3 (es) * | 2013-09-17 | 2018-12-20 | Vectus Biosystems Limited | Composiciones para el tratamiento de la hipertensión y/o de la fibrosis |
-
2014
- 2014-09-17 CN CN201480050979.1A patent/CN105683152B/zh active Active
- 2014-09-17 SG SG11201601642WA patent/SG11201601642WA/en unknown
- 2014-09-17 AU AU2014324078A patent/AU2014324078B2/en active Active
- 2014-09-17 NO NO14845373A patent/NO3046901T3/no unknown
- 2014-09-17 MX MX2016003371A patent/MX368865B/es active IP Right Grant
- 2014-09-17 BR BR112016005601-9A patent/BR112016005601B1/pt active IP Right Grant
- 2014-09-17 PL PL14845373T patent/PL3046901T3/pl unknown
- 2014-09-17 DK DK14845373.1T patent/DK3046901T3/en active
- 2014-09-17 RU RU2016112257A patent/RU2635564C2/ru active
- 2014-09-17 US US15/022,278 patent/US9458093B2/en active Active
- 2014-09-17 MY MYPI2016000482A patent/MY172557A/en unknown
- 2014-09-17 JP JP2016515425A patent/JP6122548B2/ja active Active
- 2014-09-17 ES ES14845373.1T patent/ES2655455T3/es active Active
- 2014-09-17 NZ NZ717927A patent/NZ717927A/en unknown
- 2014-09-17 WO PCT/AU2014/000923 patent/WO2015039173A1/en not_active Ceased
- 2014-09-17 KR KR1020167008664A patent/KR101736416B1/ko active Active
- 2014-09-17 UA UAA201602267A patent/UA118111C2/uk unknown
- 2014-09-17 AP AP2016009079A patent/AP2016009079A0/xx unknown
- 2014-09-17 CA CA2924356A patent/CA2924356C/en active Active
- 2014-09-17 EP EP14845373.1A patent/EP3046901B1/en active Active
-
2016
- 2016-03-14 PH PH12016500497A patent/PH12016500497B1/en unknown
- 2016-03-16 IL IL244621A patent/IL244621A/en active IP Right Grant
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR112016005601B1 (pt) | composto, composição farmacêutica, e usos de um composto | |
| ES2791539T3 (es) | Compuestos para el tratamiento de enfermedades relacionadas con la expresión de DUX4 | |
| KR20240021884A (ko) | 암을 치료하기 위한 parp 억제제와 조합된 atr 억제제의 용도 | |
| JP2004525179A (ja) | ジペプチジルペプチダーゼｉｖ阻害剤でのｉｉ型糖尿病の処置 | |
| JPH11502199A (ja) | 大腸ガンの治療のための防護組成物中のｒ−ｎｓａｉｄの使用 | |
| JPH10236978A (ja) | 中枢カンナビノイドレセプターｃｂ１の既知の作用薬の利用 | |
| BR112020003865A2 (pt) | composições farmacêuticas compreendendo sepiapterina e seus usos | |
| EP2999691A1 (en) | Cryopyrin inhibitors for preventing and treating inflammation | |
| ES2253810T3 (es) | Uso de r-aines para la prevencion de la enfermedad de alzheimer. | |
| BR112016005606B1 (pt) | Composto, composição farmacêutica, e usos de um composto | |
| WO2015176539A1 (zh) | 异喹啉生物碱衍生物用于制备促进ampk活性的药物的用途 | |
| TWI472519B (zh) | 含正－亞丁基苯酞之醫藥組成物用於治療肝損傷及改善肝功能 | |
| HK1226324B (en) | Compositions for the treatment of hypertension and/or fibrosis | |
| HK1226324A1 (en) | Compositions for the treatment of hypertension and/or fibrosis | |
| TW200302091A (en) | Methods of treating sepsis | |
| WO2012000306A1 (zh) | 含二苯乙烯片段的苯基硝酮类化合物及其用途 | |
| EP3753559A1 (en) | Colitis improving agent | |
| CN104288145B (zh) | 斯诺普利在制备预防肿瘤转移或肿瘤治疗药物中的应用 | |
| WO2021196884A1 (zh) | 邻苯二酚及衍生物在制备用于治疗睡眠障碍药物中的用途 | |
| EP4284352A1 (en) | Enhanced anti-proliferative and antitumor immune effects of mitochondria-targeted hydroxyurea | |
| CN120284970A (zh) | Cb-839在制备治疗糖尿病肾脏病药物中的应用 | |
| JP2025079327A (ja) | Ｓｍａｄ非依存的ＴＧＦ－βシグナル伝達経路阻害剤、及びそれを含むがん浸潤及び／又は転移抑制組成物 | |
| JP2019182845A (ja) | キヌレニンアミノトランスフェラーゼ２（ｋａｔ２）阻害剤 | |
| WO2021203779A1 (zh) | 治疗肺动脉高压的化合物及其应用 | |
| ITFI20120170A1 (it) | Nuovi composti ad azione anti-allodinica ed anti-iperalgesica. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B07D | Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette] | ||
| B07E | Notification of approval relating to section 229 industrial property law [chapter 7.5 patent gazette] |
Free format text: NOTIFICACAO DE ANUENCIA RELACIONADA COM O ART 229 DA LPI |
|
| B06U | Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 17/09/2014, OBSERVADAS AS CONDICOES LEGAIS. |