PT100491A - Acidos n-(heteroaril)-imidazolil-alcenoicos, composicoes farmaceuticas que os contem e seu uso - Google Patents
Acidos n-(heteroaril)-imidazolil-alcenoicos, composicoes farmaceuticas que os contem e seu uso Download PDFInfo
- Publication number
- PT100491A PT100491A PT100491A PT10049192A PT100491A PT 100491 A PT100491 A PT 100491A PT 100491 A PT100491 A PT 100491A PT 10049192 A PT10049192 A PT 10049192A PT 100491 A PT100491 A PT 100491A
- Authority
- PT
- Portugal
- Prior art keywords
- alkyl
- thienyl
- compound according
- methyl
- alcoalkyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 97
- -1 -CH 2 O-CH 2 - Chemical group 0.000 claims description 45
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 206010019280 Heart failures Diseases 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 10
- 206010020772 Hypertension Diseases 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 102000008873 Angiotensin II receptor Human genes 0.000 claims description 8
- 108050000824 Angiotensin II receptor Proteins 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 201000006370 kidney failure Diseases 0.000 claims description 6
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- FUTADZHZXRWZMC-UYRXBGFRSA-N 5-[[2-butyl-5-[(E)-1-carboxy-1-thiophen-2-ylprop-1-en-2-yl]imidazol-1-yl]methyl]thiophene-2-carboxylic acid Chemical group C(CCC)C=1N(C(=CN=1)/C(=C(\C(=O)O)/C=1SC=CC=1)/C)CC=1SC(=CC=1)C(=O)O FUTADZHZXRWZMC-UYRXBGFRSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 230000003042 antagnostic effect Effects 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 3
- 125000006088 2-oxoazepinyl group Chemical group 0.000 claims description 2
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 claims description 2
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
- 108020001305 NR1 subfamily Proteins 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- RGZJTVWECAEHHO-OQLLNIDSSA-N 4-[[2-butyl-5-[(e)-2-carboxy-3-thiophen-2-ylprop-1-enyl]imidazol-1-yl]methyl]thiophene-2-carboxylic acid Chemical compound C=1SC(C(O)=O)=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 RGZJTVWECAEHHO-OQLLNIDSSA-N 0.000 claims 1
- 101150009274 nhr-1 gene Proteins 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 230000001052 transient effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 239000002904 solvent Substances 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 238000000034 method Methods 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 239000002253 acid Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 229950006323 angiotensin ii Drugs 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 19
- 102000005862 Angiotensin II Human genes 0.000 description 19
- 101800000733 Angiotensin-2 Proteins 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Chemical class CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 239000000460 chlorine Chemical group 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- GFOPHLFSDVVYGB-UHFFFAOYSA-N methyl 5-(bromomethyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CBr)S1 GFOPHLFSDVVYGB-UHFFFAOYSA-N 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000036454 renin-angiotensin system Effects 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- SPCCQBFOGATTOR-UHFFFAOYSA-N methyl 5-[(2-butyl-5-formylimidazol-1-yl)methyl]thiophene-2-carboxylate Chemical compound CCCCC1=NC=C(C=O)N1CC1=CC=C(C(=O)OC)S1 SPCCQBFOGATTOR-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- DXSZKDOOHOBZMT-UHFFFAOYSA-N (2-butyl-4-chloro-1h-imidazol-5-yl)methanol Chemical compound CCCCC1=NC(Cl)=C(CO)N1 DXSZKDOOHOBZMT-UHFFFAOYSA-N 0.000 description 3
- YAXGIWYFMQQCIB-UHFFFAOYSA-N (2-butyl-5-formylimidazol-1-yl)methyl 2,2-dimethylpropanoate Chemical compound CCCCC1=NC=C(C=O)N1COC(=O)C(C)(C)C YAXGIWYFMQQCIB-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000008485 antagonism Effects 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000002641 lithium Chemical class 0.000 description 3
- WRCWTABCFWQYKG-UHFFFAOYSA-N methyl 6-[(2-butyl-4-chloro-5-formylimidazol-1-yl)methyl]pyridine-3-carboxylate Chemical compound CCCCC1=NC(Cl)=C(C=O)N1CC1=CC=C(C(=O)OC)C=N1 WRCWTABCFWQYKG-UHFFFAOYSA-N 0.000 description 3
- YMEHWISYYMKMFO-WOMRJYOTSA-N methyl N-[(12E,15S)-15-[(4S)-4-(3-chlorophenyl)-2-oxopiperidin-1-yl]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate Chemical compound COC(=O)Nc1ccc2-c3cnc([nH]3)[C@H](C\C=C\CCC(=O)Nc2c1)N1CC[C@@H](CC1=O)c1cccc(Cl)c1 YMEHWISYYMKMFO-WOMRJYOTSA-N 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 210000002254 renal artery Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- UZKBZGAMRJRWLR-UHFFFAOYSA-N (2-butyl-1H-imidazol-4-yl)methanol Chemical compound CCCCC1=NC=C(CO)N1 UZKBZGAMRJRWLR-UHFFFAOYSA-N 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- OJRJAEIZNDZTIP-UHFFFAOYSA-N 2-(thiophen-2-ylmethyl)prop-2-enoic acid Chemical compound OC(=O)C(=C)CC1=CC=CS1 OJRJAEIZNDZTIP-UHFFFAOYSA-N 0.000 description 2
- PTHGVOCFAZSNNA-UHFFFAOYSA-N 2-butyl-1h-imidazole-5-carbaldehyde Chemical compound CCCCC1=NC=C(C=O)N1 PTHGVOCFAZSNNA-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- PMJNEQWWZRSFCE-UHFFFAOYSA-N 3-ethoxy-3-oxo-2-(thiophen-2-ylmethyl)propanoic acid Chemical compound CCOC(=O)C(C(O)=O)CC1=CC=CS1 PMJNEQWWZRSFCE-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- ONSJNCYARNJTNG-ZHZULCJRSA-N 6-[[2-butyl-5-[(E)-1-carboxy-1-thiophen-2-ylprop-1-en-2-yl]imidazol-1-yl]methyl]pyridine-3-carboxylic acid Chemical compound C(CCC)C=1N(C(=CN1)/C(=C(C(=O)O)/C=1SC=CC1)/C)CC1=NC=C(C=C1)C(=O)O ONSJNCYARNJTNG-ZHZULCJRSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 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 2
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102100028255 Renin Human genes 0.000 description 2
- 108090000783 Renin Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ACIAHEMYLLBZOI-ZZXKWVIFSA-N Unsaturated alcohol Chemical class CC\C(CO)=C/C ACIAHEMYLLBZOI-ZZXKWVIFSA-N 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229940120503 dihydroxyacetone Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- PRJKNHOMHKJCEJ-UHFFFAOYSA-N imidazol-4-ylacetic acid Chemical class OC(=O)CC1=CN=CN1 PRJKNHOMHKJCEJ-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000003446 ligand Substances 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
- 230000033001 locomotion Effects 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
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- SLCONNVOXPHHSC-UHFFFAOYSA-N methyl 6-[(2-butyl-5-formylimidazol-1-yl)methyl]pyridine-3-carboxylate Chemical compound CCCCC1=NC=C(C=O)N1CC1=CC=C(C(=O)OC)C=N1 SLCONNVOXPHHSC-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229920003169 water-soluble polymer Polymers 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- WMRVFHHQZRFRCH-UHFFFAOYSA-N 1,1-diphenylpropoxybenzene Chemical compound C1(=CC=CC=C1)OC(C1=CC=CC=C1)(C1=CC=CC=C1)CC WMRVFHHQZRFRCH-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GMVXCWQXIVFUHX-UHFFFAOYSA-N 1h-imidazol-2-yl prop-2-enoate Chemical class C=CC(=O)OC1=NC=CN1 GMVXCWQXIVFUHX-UHFFFAOYSA-N 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical class O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
- FIGYYXIYTVBRJV-UHFFFAOYSA-N 1h-imidazole;lithium Chemical class [Li].C1=CNC=N1 FIGYYXIYTVBRJV-UHFFFAOYSA-N 0.000 description 1
- TWWVIBZNLDTRON-UHFFFAOYSA-N 2-(1-benzyl-2-butyl-5-chloroimidazol-4-yl)acetic acid Chemical compound CCCCC1=NC(CC(O)=O)=C(Cl)N1CC1=CC=CC=C1 TWWVIBZNLDTRON-UHFFFAOYSA-N 0.000 description 1
- ZLSNPZVGNMESDB-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)prop-2-enoic acid Chemical class OC(=O)C(=C)C1=NC=CN1 ZLSNPZVGNMESDB-UHFFFAOYSA-N 0.000 description 1
- OWZRRFCGWTXNTM-UHFFFAOYSA-N 2-(1h-imidazol-5-yl)propanoic acid Chemical class OC(=O)C(C)C1=CN=CN1 OWZRRFCGWTXNTM-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- PQRKWOSQTRDIPE-UHFFFAOYSA-N 2-[2-butyl-5-chloro-3-[(2-chlorophenyl)methyl]imidazol-4-yl]acetic acid Chemical compound CCCCC1=NC(Cl)=C(CC(O)=O)N1CC1=CC=CC=C1Cl PQRKWOSQTRDIPE-UHFFFAOYSA-N 0.000 description 1
- SLLDUURXGMDOCY-UHFFFAOYSA-N 2-butyl-1h-imidazole Chemical compound CCCCC1=NC=CN1 SLLDUURXGMDOCY-UHFFFAOYSA-N 0.000 description 1
- JLVIHQCWASNXCK-UHFFFAOYSA-N 2-butyl-5-chloro-1h-imidazole-4-carbaldehyde Chemical compound CCCCC1=NC(C=O)=C(Cl)N1 JLVIHQCWASNXCK-UHFFFAOYSA-N 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- XYWDNESIXGLWDB-UHFFFAOYSA-N 3-(1-benzyl-5-chloro-2-phenylimidazol-4-yl)propanoic acid Chemical compound C=1C=CC=CC=1CN1C(Cl)=C(CCC(=O)O)N=C1C1=CC=CC=C1 XYWDNESIXGLWDB-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BNYKZFOZWZMEJD-UHFFFAOYSA-N 3-methylimidazole-4-carbaldehyde Chemical compound CN1C=NC=C1C=O BNYKZFOZWZMEJD-UHFFFAOYSA-N 0.000 description 1
- IFLKEBSJTZGCJG-UHFFFAOYSA-N 5-methyl-2-thiophenecarboxylic acid Natural products CC=1C=CSC=1C(O)=O IFLKEBSJTZGCJG-UHFFFAOYSA-N 0.000 description 1
- VCNGNQLPFHVODE-UHFFFAOYSA-N 5-methylthiophene-2-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)S1 VCNGNQLPFHVODE-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JJHRPTXPOATRCQ-UHFFFAOYSA-N OC(=O)C(P(O)(O)=O)CC1=CC=CS1 Chemical compound OC(=O)C(P(O)(O)=O)CC1=CC=CS1 JJHRPTXPOATRCQ-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010041277 Sodium retention Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001514 alkali metal chloride Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- YDPLDMLRERBXAV-UHFFFAOYSA-N aluminum;triazide Chemical compound [Al+3].[N-]=[N+]=[N-].[N-]=[N+]=[N-].[N-]=[N+]=[N-] YDPLDMLRERBXAV-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- QWLWTXHDWKWZFB-UHFFFAOYSA-N diethyl 2-thiophen-2-ylpropanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC=CS1 QWLWTXHDWKWZFB-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 229940057307 dihydrate calcium sulfate Drugs 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000004406 elevated intraocular pressure Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- CYPPHOGCEHKEHQ-UHFFFAOYSA-N ethyl 3-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]prop-2-enoate Chemical compound C=1C=C(F)C=CC=1N1C(C=CC(=O)OCC)=C(C(C)C)N=C1C1=CC=CC=C1 CYPPHOGCEHKEHQ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- IPJKJLXEVHOKSE-UHFFFAOYSA-L manganese dihydroxide Chemical compound [OH-].[OH-].[Mn+2] IPJKJLXEVHOKSE-UHFFFAOYSA-L 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 210000003975 mesenteric artery Anatomy 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- SWVMLNPDTIFDDY-FVGYRXGTSA-N methyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CC=C1 SWVMLNPDTIFDDY-FVGYRXGTSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- USTRJLXKHMURIF-UHFFFAOYSA-N methyl 3-thiophen-2-ylpropanoate Chemical compound COC(=O)CCC1=CC=CS1 USTRJLXKHMURIF-UHFFFAOYSA-N 0.000 description 1
- BICIWERKUIGGMD-UHFFFAOYSA-N methyl 5-[(2-butyl-5-formylimidazol-1-yl)methyl]furan-2-carboxylate Chemical compound CCCCC1=NC=C(C=O)N1CC1=CC=C(C(=O)OC)O1 BICIWERKUIGGMD-UHFFFAOYSA-N 0.000 description 1
- NEPZGUGQLAOODR-UHFFFAOYSA-N methyl 5-methylthiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(C)S1 NEPZGUGQLAOODR-UHFFFAOYSA-N 0.000 description 1
- IRQSKJQDKUAART-UHFFFAOYSA-N methyl 6-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CBr)N=C1 IRQSKJQDKUAART-UHFFFAOYSA-N 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-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
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 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
- 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 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical class [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical class OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000036584 pressor response Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- LOIYMIARKYCTBW-UHFFFAOYSA-N urocanic acid Chemical compound OC(=O)C=CC1=CNC=N1 LOIYMIARKYCTBW-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919110532A GB9110532D0 (en) | 1991-05-15 | 1991-05-15 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT100491A true PT100491A (pt) | 1993-09-30 |
Family
ID=10695047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT100491A PT100491A (pt) | 1991-05-15 | 1992-05-15 | Acidos n-(heteroaril)-imidazolil-alcenoicos, composicoes farmaceuticas que os contem e seu uso |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0585383A4 (enExample) |
| JP (1) | JPH06507899A (enExample) |
| AU (1) | AU2156192A (enExample) |
| GB (1) | GB9110532D0 (enExample) |
| IE (1) | IE921539A1 (enExample) |
| MX (1) | MX9202262A (enExample) |
| NZ (1) | NZ242734A (enExample) |
| PT (1) | PT100491A (enExample) |
| TW (1) | TW211010B (enExample) |
| WO (1) | WO1992020651A2 (enExample) |
| ZA (1) | ZA923496B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5395847A (en) * | 1993-12-02 | 1995-03-07 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids |
| KR100587187B1 (ko) * | 1997-10-29 | 2006-10-24 | 론자 아게 | 포르밀이미다졸의제조방법 |
| KR100567183B1 (ko) * | 1997-11-14 | 2006-06-13 | 론자 아게 | 포르밀이미다졸의제조방법 |
| JP2000053651A (ja) * | 1998-06-18 | 2000-02-22 | Lonza Ag | ホルミルイミダゾ―ル類の製造方法 |
| SE9903028D0 (sv) | 1999-08-27 | 1999-08-27 | Astra Ab | New use |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| KR20100074288A (ko) * | 2007-10-22 | 2010-07-01 | 오키드 리서치 레버라토리즈 리미티드 | 히스톤 디아세틸라제 억제제 |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE190051T1 (de) * | 1989-06-14 | 2000-03-15 | Smithkline Beecham Corp | Imidazoalkensäure |
| CA2027937A1 (en) * | 1989-10-25 | 1991-04-26 | Richard M. Keenan | Substituted 5-¬ (tetrazolyl)alkenyl|imidazoles |
-
1991
- 1991-05-15 GB GB919110532A patent/GB9110532D0/en active Pending
-
1992
- 1992-05-14 NZ NZ242734A patent/NZ242734A/en unknown
- 1992-05-14 AU AU21561/92A patent/AU2156192A/en not_active Abandoned
- 1992-05-14 ZA ZA923496A patent/ZA923496B/xx unknown
- 1992-05-14 EP EP9292913103A patent/EP0585383A4/en not_active Withdrawn
- 1992-05-14 JP JP5500202A patent/JPH06507899A/ja active Pending
- 1992-05-14 WO PCT/US1992/004071 patent/WO1992020651A2/en not_active Ceased
- 1992-05-14 MX MX9202262A patent/MX9202262A/es unknown
- 1992-05-15 PT PT100491A patent/PT100491A/pt not_active Application Discontinuation
- 1992-05-15 TW TW081103799A patent/TW211010B/zh active
- 1992-07-01 IE IE153992A patent/IE921539A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB9110532D0 (en) | 1991-07-03 |
| ZA923496B (en) | 1993-04-28 |
| JPH06507899A (ja) | 1994-09-08 |
| MX9202262A (es) | 1992-11-01 |
| EP0585383A1 (en) | 1994-03-09 |
| AU2156192A (en) | 1992-12-30 |
| WO1992020651A2 (en) | 1992-11-26 |
| IE921539A1 (en) | 1992-11-18 |
| TW211010B (enExample) | 1993-08-11 |
| NZ242734A (en) | 1995-04-27 |
| EP0585383A4 (en) | 1994-08-17 |
| WO1992020651A3 (en) | 1993-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2207091T3 (es) | Acido imidazolil-alquenoico. | |
| EP0641203B1 (en) | Pharmaceutical compositions of an imidazolyl-akenoic acid salt and their use as angiotensin ii antagonists | |
| EP0425211B1 (en) | Substituted 5-((tetrazolyl)alkenyl)-imidazoles | |
| PT94374A (pt) | Processo de preparacao de acidos imidazolilalcenoicos e de composicooes farmaceuticas que os contem | |
| US5312828A (en) | Substituted imidazoles having angiotensin II receptor blocking activity | |
| PT98143A (pt) | Processo de preparacao de histidinas substituidas e de composicoes farmaceuticas | |
| PT96399A (pt) | Processo de preparacao de derivados de imidazol e de composicoes farmaceuticas que os contem | |
| PT100491A (pt) | Acidos n-(heteroaril)-imidazolil-alcenoicos, composicoes farmaceuticas que os contem e seu uso | |
| EP0427463B1 (en) | Substituted N-(imidazolyl)alkyl alanine derivatives | |
| US5444080A (en) | Substituted [1H-imidazol-5-ylialkanoic acids having angiotension II receptor antagonist activity | |
| EP0563238B1 (en) | Imidazolyl-alkenoic acids | |
| US5234917A (en) | Substituted 5-(alkyl)carboxamide imidazoles | |
| US5248689A (en) | Substituted N-(imidazolyl)alkyl alanine derivatives | |
| US5447949A (en) | N-(heteroaryl) imidazolyl-alkenoic acids having angiotension II receptor antagonist activity | |
| US5177096A (en) | Substituted 5-((tetrazolyl)alkenyl)imidazoles and pharmaceutical methods of use thereof | |
| HK1012384B (en) | Imidazolyl-alkenoic acids | |
| HK1012246B (en) | Pharmaceutical compositions of an imidazolyl-akenoic acid salt and their use as angiotensin ii antagonists | |
| SI9200228A (sl) | Imidazolil-alkenojske kisline | |
| HK1025315B (en) | Imidazolyl-alkenoic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB1A | Laying open of patent application |
Effective date: 19930427 |
|
| FC3A | Refusal |
Effective date: 19990406 |