RU2635564C2 - Композиция для лечения гипертензии и/или фиброза - Google Patents
Композиция для лечения гипертензии и/или фиброза Download PDFInfo
- Publication number
- RU2635564C2 RU2635564C2 RU2016112257A RU2016112257A RU2635564C2 RU 2635564 C2 RU2635564 C2 RU 2635564C2 RU 2016112257 A RU2016112257 A RU 2016112257A RU 2016112257 A RU2016112257 A RU 2016112257A RU 2635564 C2 RU2635564 C2 RU 2635564C2
- Authority
- RU
- Russia
- Prior art keywords
- fibrosis
- compound
- present
- pharmaceutically acceptable
- subject
- Prior art date
Links
- 206010016654 Fibrosis Diseases 0.000 title claims abstract description 58
- 230000004761 fibrosis Effects 0.000 title claims abstract description 58
- 238000011282 treatment Methods 0.000 title claims abstract description 41
- 206010020772 Hypertension Diseases 0.000 title claims abstract description 21
- 239000000203 mixture Substances 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 20
- 206010065918 Prehypertension Diseases 0.000 claims abstract description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 230000003510 anti-fibrotic effect Effects 0.000 claims abstract description 6
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 27
- 206010023421 Kidney fibrosis Diseases 0.000 claims description 11
- 206010028594 Myocardial fibrosis Diseases 0.000 claims description 11
- 230000004531 blood pressure lowering effect Effects 0.000 claims description 3
- 230000036772 blood pressure Effects 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- 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
- 210000001519 tissue Anatomy 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 210000003734 kidney Anatomy 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 210000002216 heart Anatomy 0.000 description 10
- 238000003786 synthesis reaction Methods 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 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000035488 systolic blood pressure Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 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
- 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 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
- QPVCUQOSWAXEOQ-UHFFFAOYSA-N 2-diethoxyphosphorylacetamide Chemical compound CCOP(=O)(CC(N)=O)OCC QPVCUQOSWAXEOQ-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000013256 coordination polymer Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 230000035622 drinking Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001802 infusion Methods 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
- 239000011541 reaction mixture Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent 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
- 239000005541 ACE inhibitor Substances 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 3
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 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
- -1 glidants Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 230000024883 vasodilation 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
- 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
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 102100029143 RNA 3'-terminal phosphate cyclase Human genes 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
- 238000010171 animal model Methods 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent 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
- 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
- 239000007884 disintegrant Substances 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
- 238000001000 micrograph Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 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
- 230000005855 radiation Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 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
- 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
- 229940127291 Calcium channel antagonist Drugs 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
- 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
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 206010020565 Hyperaemia Diseases 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
- 206010023232 Joint swelling Diseases 0.000 description 1
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000005856 abnormality 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
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 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
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000006880 cross-coupling reaction Methods 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
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 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
- 239000011152 fibreglass Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 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
- 238000012750 in vivo screening 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
- 238000002955 isolation Methods 0.000 description 1
- 208000010729 leg swelling Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 208000007106 menorrhagia Diseases 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 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
- 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
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 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
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 208000013846 primary aldosteronism Diseases 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 238000012545 processing Methods 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
- 238000010992 reflux Methods 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 238000011160 research Methods 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
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 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
- 239000003981 vehicle Substances 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 |
|---|---|
| RU2016112257A RU2016112257A (ru) | 2017-10-20 |
| RU2635564C2 true RU2635564C2 (ru) | 2017-11-14 |
Family
ID=52687998
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2016112257A RU2635564C2 (ru) | 2013-09-17 | 2014-09-17 | Композиция для лечения гипертензии и/или фиброза |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9458093B2 (https=) |
| EP (1) | EP3046901B1 (https=) |
| JP (1) | JP6122548B2 (https=) |
| KR (1) | KR101736416B1 (https=) |
| CN (1) | CN105683152B (https=) |
| AP (1) | AP2016009079A0 (https=) |
| AU (1) | AU2014324078B2 (https=) |
| BR (1) | BR112016005601B1 (https=) |
| CA (1) | CA2924356C (https=) |
| DK (1) | DK3046901T3 (https=) |
| ES (1) | ES2655455T3 (https=) |
| IL (1) | IL244621A (https=) |
| MX (1) | MX368865B (https=) |
| MY (1) | MY172557A (https=) |
| NO (1) | NO3046901T3 (https=) |
| NZ (1) | NZ717927A (https=) |
| PH (1) | PH12016500497B1 (https=) |
| PL (1) | PL3046901T3 (https=) |
| RU (1) | RU2635564C2 (https=) |
| SG (1) | SG11201601642WA (https=) |
| UA (1) | UA118111C2 (https=) |
| WO (1) | WO2015039173A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2712140C2 (ru) * | 2015-03-18 | 2020-01-24 | Вектус Байосистемс Лимитед | Композиции для лечения фиброза и связанных с фиброзом состояний |
Families Citing this family (6)
| 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 |
| MX376504B (es) | 2015-03-18 | 2025-03-07 | Vectus Biosystems Ltd | Composiciones para el tratamiento de enfermedades renales y/o hepaticas. |
| EP3353147B1 (en) * | 2015-09-22 | 2021-01-13 | Vectus Biosystems Limited | Synthesis of terphenyl compounds |
| IL298314B2 (en) * | 2016-04-13 | 2025-04-01 | Univ Nebraska | Methods of administration and methods of treating cardiovascular diseases with resiniparatoxin |
| BR112019001510B1 (pt) * | 2016-07-28 | 2022-11-08 | Vectus Biosystems Limited | Composto, e, uso de um composto para manufatura de um medicamento para tratar profilática ou terapeuticamente fibrose pulmonar, ou uma enfermidade relacionada em um indivíduo com fibrose pulmonar ou em risco de desenvolver fibrose pulmonar |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2090552C1 (ru) * | 1992-06-30 | 1997-09-20 | Рон-Пуленк Агрошими | Производные фенилбензамидов, способы их получения, фунгицидная композиция для защиты растений и способ борьбы с фунгицидными заболеваниями |
| WO2005120545A1 (en) * | 2004-06-11 | 2005-12-22 | Vectus Biosystems Limited | Compositions and methods for treatment of cardiovascular disease |
| US20110082109A1 (en) * | 2009-10-02 | 2011-04-07 | Ajinomoto Co., Inc. | Novel acyl guanidine derivatives |
| WO2015039172A1 (en) * | 2013-09-17 | 2015-03-26 | Vectus Biosystems Pty Ltd | Compositions for the treatment of hypertension and/or fibrosis |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ623674A (en) * | 2005-12-09 | 2014-07-25 | Vectus Biosystems Ltd | Vip fragments and methods of use |
-
2014
- 2014-09-17 NO NO14845373A patent/NO3046901T3/no unknown
- 2014-09-17 ES ES14845373.1T patent/ES2655455T3/es active Active
- 2014-09-17 SG SG11201601642WA patent/SG11201601642WA/en unknown
- 2014-09-17 AP AP2016009079A patent/AP2016009079A0/xx unknown
- 2014-09-17 KR KR1020167008664A patent/KR101736416B1/ko active Active
- 2014-09-17 US US15/022,278 patent/US9458093B2/en active Active
- 2014-09-17 RU RU2016112257A patent/RU2635564C2/ru active
- 2014-09-17 DK DK14845373.1T patent/DK3046901T3/en active
- 2014-09-17 CA CA2924356A patent/CA2924356C/en active Active
- 2014-09-17 AU AU2014324078A patent/AU2014324078B2/en active Active
- 2014-09-17 EP EP14845373.1A patent/EP3046901B1/en active Active
- 2014-09-17 UA UAA201602267A patent/UA118111C2/uk unknown
- 2014-09-17 WO PCT/AU2014/000923 patent/WO2015039173A1/en not_active Ceased
- 2014-09-17 PL PL14845373T patent/PL3046901T3/pl unknown
- 2014-09-17 MY MYPI2016000482A patent/MY172557A/en unknown
- 2014-09-17 NZ NZ717927A patent/NZ717927A/en unknown
- 2014-09-17 CN CN201480050979.1A patent/CN105683152B/zh active Active
- 2014-09-17 JP JP2016515425A patent/JP6122548B2/ja active Active
- 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
-
2016
- 2016-03-14 PH PH12016500497A patent/PH12016500497B1/en unknown
- 2016-03-16 IL IL244621A patent/IL244621A/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2090552C1 (ru) * | 1992-06-30 | 1997-09-20 | Рон-Пуленк Агрошими | Производные фенилбензамидов, способы их получения, фунгицидная композиция для защиты растений и способ борьбы с фунгицидными заболеваниями |
| WO2005120545A1 (en) * | 2004-06-11 | 2005-12-22 | Vectus Biosystems Limited | Compositions and methods for treatment of cardiovascular disease |
| US20110082109A1 (en) * | 2009-10-02 | 2011-04-07 | Ajinomoto Co., Inc. | Novel acyl guanidine derivatives |
| WO2015039172A1 (en) * | 2013-09-17 | 2015-03-26 | Vectus Biosystems Pty Ltd | Compositions for the treatment of hypertension and/or fibrosis |
Non-Patent Citations (1)
| Title |
|---|
| MARTIN PETERS et al. "A modular synthesis of teraryl-based α-Helix mimetics, Part 1: Synthesis of core fragments with two electronically differentiated leaving groups", CHEMISTRY-A EUROPEAN JOURNAL, 2013, vol.19, p.2442-2449. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2712140C2 (ru) * | 2015-03-18 | 2020-01-24 | Вектус Байосистемс Лимитед | Композиции для лечения фиброза и связанных с фиброзом состояний |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2635564C2 (ru) | Композиция для лечения гипертензии и/или фиброза | |
| TWI841532B (zh) | 以稠合雙環吡唑治療代謝疾病之方法 | |
| JPWO2008139879A1 (ja) | Ｇ蛋白質共役型レセプター抑制剤および医薬 | |
| US8119839B2 (en) | Carboxylic acid and antidepressant composition containing the same as active ingredient | |
| US10344001B2 (en) | Azolylacryloyl derivatives as therapeutic agents for sickle cell disease | |
| CN104473938A (zh) | 一种治疗慢性心衰药物及其制备方法 | |
| CN105085594A (zh) | N6-(1-(4-甲氧基苯基)乙基)-腺苷的制备及用途 | |
| US20210346331A1 (en) | Trpv4 activity inhibitor | |
| KR20180053032A (ko) | 신규한 피페린 유도체 및 이를 포함하는 약학적 조성물 | |
| CN106866652A (zh) | 具有胰岛素增敏活性的小檗碱12‑位衍生物及其制备方法 | |
| CN106995368B (zh) | 一种非atp竞争性fgfr1抑制剂及其应用 | |
| HK1226324B (en) | Compositions for the treatment of hypertension and/or fibrosis | |
| HK1226324A1 (en) | Compositions for the treatment of hypertension and/or fibrosis | |
| JP2010168290A (ja) | インターロイキン−２産生抑制剤 | |
| KR100903974B1 (ko) | 2,4,5-삼중치환-1,3-티아졸 유도체 및 약제학적으로 허용가능한 그의 염, 그의 제조방법 및 그를 유효성분으로함유하는 ｓｐｃ 수용체 활성으로 유발되는 염증관련 질환치료제 | |
| RU2712624C2 (ru) | Композиции для лечения заболевания почек и/или печени | |
| JPH05503510A (ja) | 光学的に純粋な（ｓ）―アテノロールを含む組成物と方法 | |
| CN103040807A (zh) | 去-o-甲基毛狄泼老素在制备治疗高血压药物中的应用 | |
| CN107235842A (zh) | 一种苯丙酸酯衍生物及其制备方法和应用 | |
| CN118530166A (zh) | 氮杂二苯乙烯类化合物及在代谢综合征防治中的应用 | |
| Seedat | Treatment of hypertension with the aid of beta-adrenergic blocking drugs | |
| KR101051077B1 (ko) | 2-피페라지노-4,5-이중치환-1,3-티아졸 유도체, 그의 제조방법 및 그를 유효성분으로 함유하는 ｓｐｃ 수용체 활성으로 유발되는 염증관련질환 치료제 | |
| CN115770238A (zh) | 大麻素类化合物cbe的制备方法及其医药用途 | |
| CN101829081A (zh) | 色满类化合物hef-05用于舒张血管平滑肌的用途 | |
| CN103027912A (zh) | N-[2-[3-(1-哌嗪基甲基)咪唑并[2,1-b]噻唑-6-基]苯基]-2-喹喔啉甲酰胺在制备防治高血压药物中的应用 |