NZ749202A - Modulators of the beta-3 adrenergic receptor useful for the treatment or prevention of disorders related thereto - Google Patents

Info

Publication number

NZ749202A

NZ749202A NZ749202A NZ74920217A NZ749202A NZ 749202 A NZ749202 A NZ 749202A NZ 749202 A NZ749202 A NZ 749202A NZ 74920217 A NZ74920217 A NZ 74920217A NZ 749202 A NZ749202 A NZ 749202A

Authority

NZ

New Zealand

Prior art keywords

compound

phenoxy

pyridinyl

methyl

phenyl

Prior art date

2016-06-06

Links

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• Global Dossier
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• 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 title claims abstract description 66
• 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 title claims abstract description 66
• 238000011282 treatment Methods 0.000 title abstract description 32
• 230000002265 prevention Effects 0.000 title description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 677
• 238000000034 method Methods 0.000 claims abstract description 104
• 206010019280 Heart failures Diseases 0.000 claims abstract description 102
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 91
• 208000035475 disorder Diseases 0.000 claims abstract description 80
• 230000001404 mediated effect Effects 0.000 claims abstract description 56
• 210000002216 heart Anatomy 0.000 claims abstract description 55
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 50
• 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims abstract description 23
• 206010007556 Cardiac failure acute Diseases 0.000 claims abstract description 21
• 230000002861 ventricular Effects 0.000 claims abstract description 17
• 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 16
• 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 15
• 206010024119 Left ventricular failure Diseases 0.000 claims abstract description 14
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 14
• 230000000747 cardiac effect Effects 0.000 claims abstract description 11
• 230000006378 damage Effects 0.000 claims abstract description 9
• 238000002592 echocardiography Methods 0.000 claims abstract description 9
• 210000003709 heart valve Anatomy 0.000 claims abstract description 9
• 210000003734 kidney Anatomy 0.000 claims abstract description 9
• 230000008816 organ damage Effects 0.000 claims abstract description 9
• 230000033764 rhythmic process Effects 0.000 claims abstract description 9
• 206010067125 Liver injury Diseases 0.000 claims abstract description 8
• 238000002583 angiography Methods 0.000 claims abstract description 8
• 231100000234 hepatic damage Toxicity 0.000 claims abstract description 8
• 230000008818 liver damage Effects 0.000 claims abstract description 8
• -1 C1-C6 kylamino Chemical group 0.000 claims description 1552
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 333
• 125000004076 pyridyl group Chemical group 0.000 claims description 177
• 238000002360 preparation method Methods 0.000 claims description 137
• 239000000203 mixture Substances 0.000 claims description 102
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 96
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 96
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 88
• 125000001424 substituent group Chemical group 0.000 claims description 78
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 65
• 150000003839 salts Chemical class 0.000 claims description 60
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 52
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 49
• PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 claims description 47
• 239000012453 solvate Substances 0.000 claims description 44
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
• 125000006308 propyl amino group Chemical group 0.000 claims description 41
• 150000004677 hydrates Chemical class 0.000 claims description 40
• 229910052736 halogen Inorganic materials 0.000 claims description 39
• 150000002367 halogens Chemical class 0.000 claims description 39
• 125000004043 oxo group Chemical group O=* 0.000 claims description 37
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 37
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 32
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 31
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 29
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 29
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 28
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 26
• 239000003814 drug Substances 0.000 claims description 26
• 239000000543 intermediate Substances 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 239000004305 biphenyl Substances 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000001153 fluoro group Chemical group F* 0.000 claims description 22
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 22
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 21
• 229940127557 pharmaceutical product Drugs 0.000 claims description 21
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• 239000002904 solvent Substances 0.000 claims description 19
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
• 235000010290 biphenyl Nutrition 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
• 238000004519 manufacturing process Methods 0.000 claims description 18
• 125000001624 naphthyl group Chemical group 0.000 claims description 18
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 18
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 claims description 17
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 15
• 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 claims description 13
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
• 125000000335 thiazolyl group Chemical group 0.000 claims description 13
• 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 12
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 12
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 11
• 239000002552 dosage form Substances 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 11
• 125000001041 indolyl group Chemical group 0.000 claims description 11
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 11
• XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 claims description 10
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 9
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 9
• XWQVQSXLXAXOPJ-QNGMFEMESA-N 4-[[[6-[5-chloro-2-[[4-[[(2r)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]pyridin-4-yl]pyridin-2-yl]amino]methyl]oxane-4-carbonitrile Chemical compound C1CC(N[C@H](C)COC)CCC1NC1=CC(C=2N=C(NCC3(CCOCC3)C#N)C=CC=2)=C(Cl)C=N1 XWQVQSXLXAXOPJ-QNGMFEMESA-N 0.000 claims description 9
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 9
• 238000009472 formulation Methods 0.000 claims description 9
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 9
• 125000006002 1,1-difluoroethyl group Chemical group 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 125000003566 oxetanyl group Chemical group 0.000 claims description 8
• 229920002554 vinyl polymer Polymers 0.000 claims description 8
• 230000001800 adrenalinergic effect Effects 0.000 claims description 7
• 125000002947 alkylene group Chemical group 0.000 claims description 7
• 125000002393 azetidinyl group Chemical group 0.000 claims description 7
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• FRFSUUWVTVDAJG-UHFFFAOYSA-N 3-fluoro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)C(F)=CC2=C1 FRFSUUWVTVDAJG-UHFFFAOYSA-N 0.000 claims description 6
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 6
• 125000005347 halocycloalkyl group Chemical group 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 5
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 241001024304 Mino Species 0.000 claims description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 3
• GVCLNACSYKYUHP-UHFFFAOYSA-N 4-amino-7-(2-hydroxyethoxymethyl)pyrrolo[2,3-d]pyrimidine-5-carbothioamide Chemical compound C1=NC(N)=C2C(C(=S)N)=CN(COCCO)C2=N1 GVCLNACSYKYUHP-UHFFFAOYSA-N 0.000 claims description 3
• NJIAKNWTIVDSDA-FQEVSTJZSA-N 7-[4-(1-methylsulfonylpiperidin-4-yl)phenyl]-n-[[(2s)-morpholin-2-yl]methyl]pyrido[3,4-b]pyrazin-5-amine Chemical compound C1CN(S(=O)(=O)C)CCC1C1=CC=C(C=2N=C(NC[C@H]3OCCNC3)C3=NC=CN=C3C=2)C=C1 NJIAKNWTIVDSDA-FQEVSTJZSA-N 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 2
• 229940125898 compound 5 Drugs 0.000 claims description 2
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 11
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 7
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 7
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 4
• 125000005955 1H-indazolyl group Chemical group 0.000 claims 4
• 125000005899 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl group Chemical group 0.000 claims 3
• 238000013329 compounding Methods 0.000 claims 3
• 125000006798 (C1-C6) haloalkylamino group Chemical group 0.000 claims 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 25
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 239000000243 solution Substances 0.000 description 88
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 84
• 238000006243 chemical reaction Methods 0.000 description 80
• 238000005481 NMR spectroscopy Methods 0.000 description 79
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
• 229910001868 water Inorganic materials 0.000 description 64
• 239000007787 solid Substances 0.000 description 62
• 125000000217 alkyl group Chemical group 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 239000012267 brine Substances 0.000 description 46
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 46
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
• 238000010898 silica gel chromatography Methods 0.000 description 39
• 239000000126 substance Substances 0.000 description 36
• 235000019439 ethyl acetate Nutrition 0.000 description 32
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• 125000003545 alkoxy group Chemical group 0.000 description 30
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
• 239000010410 layer Substances 0.000 description 26
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 25
• 239000012044 organic layer Substances 0.000 description 25
• 239000011541 reaction mixture Substances 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 24
• 125000001188 haloalkyl group Chemical group 0.000 description 24
• 238000000746 purification Methods 0.000 description 24
• 239000000706 filtrate Substances 0.000 description 23
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 20
• 239000000843 powder Substances 0.000 description 20
• 239000000725 suspension Substances 0.000 description 20
• 239000007864 aqueous solution Substances 0.000 description 19
• 150000002500 ions Chemical class 0.000 description 19
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 17
• 239000007788 liquid Substances 0.000 description 17
• 238000001816 cooling Methods 0.000 description 16
• 125000003373 pyrazinyl group Chemical group 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• 239000004480 active ingredient Substances 0.000 description 15
• 125000003282 alkyl amino group Chemical group 0.000 description 14
• 125000004429 atom Chemical group 0.000 description 14
• 208000024891 symptom Diseases 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 13
• 239000000460 chlorine Substances 0.000 description 13
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 13
• 125000001715 oxadiazolyl group Chemical group 0.000 description 13
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 125000004992 haloalkylamino group Chemical group 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 125000006413 ring segment Chemical group 0.000 description 12
• 239000003826 tablet Substances 0.000 description 12
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• 150000003254 radicals Chemical class 0.000 description 10
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• 208000001953 Hypotension Diseases 0.000 description 9
• 241000700159 Rattus Species 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
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• 208000021822 hypotensive Diseases 0.000 description 9
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• 125000006239 protecting group Chemical group 0.000 description 9
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• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000012071 phase Substances 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• 125000005605 benzo group Chemical group 0.000 description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 description 6
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 125000003636 chemical group Chemical group 0.000 description 6
• 230000009977 dual effect Effects 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• 229910052760 oxygen Inorganic materials 0.000 description 6
• 230000037081 physical activity Effects 0.000 description 6
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