KR20080009112A - Npy 길항제, 제법 및 용도 - Google Patents
Npy 길항제, 제법 및 용도Info
- Publication number
- KR20080009112A KR20080009112A KR1020077026216A KR20077026216A KR20080009112A KR 20080009112 A KR20080009112 A KR 20080009112A KR 1020077026216 A KR1020077026216 A KR 1020077026216A KR 20077026216 A KR20077026216 A KR 20077026216A KR 20080009112 A KR20080009112 A KR 20080009112A
- Authority
- KR
- South Korea
- Prior art keywords
- ethyl
- propyl
- phenoxy
- phenyl
- ureido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000002360 preparation method Methods 0.000 title abstract description 55
- 239000005557 antagonist Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 355
- 238000000034 method Methods 0.000 claims abstract description 99
- 238000011282 treatment Methods 0.000 claims abstract description 38
- 101710151321 Melanostatin Proteins 0.000 claims abstract description 23
- 102400000064 Neuropeptide Y Human genes 0.000 claims abstract description 23
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- -1 (C1-C6) alkyl radical Chemical class 0.000 claims description 403
- 239000000203 mixture Substances 0.000 claims description 143
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 109
- 229910052757 nitrogen Inorganic materials 0.000 claims description 86
- 238000004519 manufacturing process Methods 0.000 claims description 77
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 62
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 44
- 229910052760 oxygen Inorganic materials 0.000 claims description 44
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
- 239000001301 oxygen Substances 0.000 claims description 42
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 40
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 37
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 36
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 33
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 33
- 125000002947 alkylene group Chemical group 0.000 claims description 31
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 27
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 22
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 19
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 19
- 239000004202 carbamide Substances 0.000 claims description 19
- 150000003254 radicals Chemical class 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 19
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 15
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 11
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 11
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 11
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 10
- 125000001118 alkylidene group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 125000004434 sulfur atom Chemical group 0.000 claims description 9
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 8
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims description 8
- IBSOMGOYPZGUCQ-UHFFFAOYSA-N C(C)C(CC)NC(NC1=CC(=C(OC2=C(C=CC=C2)C2=CC=C(C(=O)N)C=C2)C=C1)OC)=O Chemical compound C(C)C(CC)NC(NC1=CC(=C(OC2=C(C=CC=C2)C2=CC=C(C(=O)N)C=C2)C=C1)OC)=O IBSOMGOYPZGUCQ-UHFFFAOYSA-N 0.000 claims description 8
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 150000004677 hydrates Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 239000012453 solvate Substances 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- HYLJXJSMGIOVIK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1,5-benzoxazepine Chemical compound O1CCCNC2=CC=CC=C21 HYLJXJSMGIOVIK-UHFFFAOYSA-N 0.000 claims description 7
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical compound C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 claims description 7
- 208000008589 Obesity Diseases 0.000 claims description 7
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 7
- 235000020824 obesity Nutrition 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- GLUABPSZMHYCNO-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,2-b]pyrrole Chemical compound N1CCC2NCCC21 GLUABPSZMHYCNO-UHFFFAOYSA-N 0.000 claims description 6
- QFCMBRXRVQRSSF-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropyrrolo[3,4-c]pyrrole Chemical compound C1NCC2CNCC21 QFCMBRXRVQRSSF-UHFFFAOYSA-N 0.000 claims description 6
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 6
- RDIPQDIDALDHGW-UHFFFAOYSA-N 1-[3-(4-hydroxypiperidin-1-yl)propyl]indole-5-carboxylic acid Chemical compound C1CC(O)CCN1CCCN1C2=CC=C(C(O)=O)C=C2C=C1 RDIPQDIDALDHGW-UHFFFAOYSA-N 0.000 claims description 6
- DDVRNOMZDQTUNS-UHFFFAOYSA-N 2,7-diazaspiro[4.4]nonane Chemical compound C1NCCC11CNCC1 DDVRNOMZDQTUNS-UHFFFAOYSA-N 0.000 claims description 6
- XADZUYKKOYGAMH-UHFFFAOYSA-N 2-(2-piperidin-1-ylethyl)-1-propan-2-ylbenzimidazole-5-carboxylic acid Chemical compound N=1C2=CC(C(O)=O)=CC=C2N(C(C)C)C=1CCN1CCCCC1 XADZUYKKOYGAMH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 6
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- KKRILSBRRMZZLD-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 KKRILSBRRMZZLD-UHFFFAOYSA-N 0.000 claims description 6
- GJKVQTRICWNJOP-UHFFFAOYSA-N 1,2,3,5-tetrahydro-4,1-benzoxazepine Chemical compound N1CCOCC2=CC=CC=C21 GJKVQTRICWNJOP-UHFFFAOYSA-N 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 235000021061 dietary behavior Nutrition 0.000 claims description 5
- 235000006694 eating habits Nutrition 0.000 claims description 5
- 230000037406 food intake Effects 0.000 claims description 5
- 235000012631 food intake Nutrition 0.000 claims description 5
- 230000036407 pain Effects 0.000 claims description 5
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 5
- 230000009329 sexual behaviour Effects 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- JDEZRZYTYBRIFB-UHFFFAOYSA-N 1,2,3,4,4a,9b-hexahydro-[1]benzofuro[3,2-c]pyridine Chemical compound O1C2=CC=CC=C2C2C1CCNC2 JDEZRZYTYBRIFB-UHFFFAOYSA-N 0.000 claims description 4
- OGOWMVYFFWEWQT-UHFFFAOYSA-N 1,2,3,4-tetrahydro-[1]benzofuro[3,2-c]pyridine Chemical compound O1C2=CC=CC=C2C2=C1CCNC2 OGOWMVYFFWEWQT-UHFFFAOYSA-N 0.000 claims description 4
- VCQFYVAPWWWLIA-UHFFFAOYSA-N 1-(2-piperidin-1-ylethyl)indole-5-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2N1CCN1CCCCC1 VCQFYVAPWWWLIA-UHFFFAOYSA-N 0.000 claims description 4
- XKWZJHHJLVEHAW-UHFFFAOYSA-N 1-(3-piperidin-1-ylpropyl)indole-5-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2N1CCCN1CCCCC1 XKWZJHHJLVEHAW-UHFFFAOYSA-N 0.000 claims description 4
- MGZGPQCRWVOGFE-UHFFFAOYSA-N 2,4-dihydro-1h-isoquinolin-3-one Chemical compound C1=CC=C2CNC(=O)CC2=C1 MGZGPQCRWVOGFE-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- IJSHKABSUHCROO-UHFFFAOYSA-N 3-[(4-hydroxypiperidin-1-yl)methyl]-1-propan-2-ylindole-6-carboxylic acid Chemical compound C12=CC=C(C(O)=O)C=C2N(C(C)C)C=C1CN1CCC(O)CC1 IJSHKABSUHCROO-UHFFFAOYSA-N 0.000 claims description 4
- GYLMCBOAXJVARF-UHFFFAOYSA-N 3-azabicyclo[2.2.1]heptane Chemical compound C1C2CCC1NC2 GYLMCBOAXJVARF-UHFFFAOYSA-N 0.000 claims description 4
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 claims description 4
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- GHRJRUVRNORWDI-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropanoyl)amino]-n-[5-[4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CC)C(=O)CCN2CCCCC2)C=C1 GHRJRUVRNORWDI-UHFFFAOYSA-N 0.000 claims description 4
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 4
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 claims description 4
- DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 206010003225 Arteriospasm coronary Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 208000003782 Raynaud disease Diseases 0.000 claims description 4
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 201000007930 alcohol dependence Diseases 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 208000022531 anorexia Diseases 0.000 claims description 4
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
- 206010061428 decreased appetite Diseases 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000001286 intracranial vasospasm Diseases 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 4
- 210000002540 macrophage Anatomy 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- MFORUHUIMUWKNB-UHFFFAOYSA-N n-[3-methyl-4-[3-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-3-yl)oxybenzamide Chemical compound CCC(CC)NC(=O)NC1=CC=CC(OC=2C(=CC(NC(=O)C=3C=CC(OC4CN(CCC4)C(C)C)=CC=3)=CC=2)C)=C1 MFORUHUIMUWKNB-UHFFFAOYSA-N 0.000 claims description 4
- HIGBOGGHQOEOCC-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-1-(3-piperidin-1-ylpropyl)indole-5-carboxamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCCN2CCCCC2)C=C2)C2=C1 HIGBOGGHQOEOCC-UHFFFAOYSA-N 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 208000020016 psychiatric disease Diseases 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- 208000019553 vascular disease Diseases 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 3
- XNZPEHYZTCDIGW-UHFFFAOYSA-N 1,5-diazocan-2-one Chemical compound O=C1CCNCCCN1 XNZPEHYZTCDIGW-UHFFFAOYSA-N 0.000 claims description 3
- BVAOHDFTSCLRPU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2-fluoro-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC(C=C1F)=CC=C1C(=O)NC(C=C1)=CC=C1OC1=CC=C(NC(=O)NC(CC)CC)C=C1OC BVAOHDFTSCLRPU-UHFFFAOYSA-N 0.000 claims description 3
- VZAJUPUWKRLYEB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)F)C=C1C VZAJUPUWKRLYEB-UHFFFAOYSA-N 0.000 claims description 3
- NUYRPDAMJXPRCO-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 NUYRPDAMJXPRCO-UHFFFAOYSA-N 0.000 claims description 3
- XZIGELPPZXBTCH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[5-[2-(ethoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2SC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COCC)=CN=2)C=C1 XZIGELPPZXBTCH-UHFFFAOYSA-N 0.000 claims description 3
- PRVNOWRLOOUYAG-UHFFFAOYSA-N 4-(4-ethylpiperazine-1-carbonyl)-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(C(=O)N2CCN(CC)CC2)C=C1 PRVNOWRLOOUYAG-UHFFFAOYSA-N 0.000 claims description 3
- RSXVQPOXROWBNT-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)acetyl]-3,6-dihydro-2h-pyridin-4-yl]-n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=2CCN(CC=2)C(=O)CN(C)C)C=C1 RSXVQPOXROWBNT-UHFFFAOYSA-N 0.000 claims description 3
- LMUQMCCBEHURNA-UHFFFAOYSA-N 4-[acetyl(2-piperidin-1-ylethyl)amino]-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C(C)=O)C=C1 LMUQMCCBEHURNA-UHFFFAOYSA-N 0.000 claims description 3
- CEVGGCCDBXMNPS-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropanoyl)amino]-n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CC)C(=O)CCN2CCCCC2)C=C1 CEVGGCCDBXMNPS-UHFFFAOYSA-N 0.000 claims description 3
- FFSPNGQIEQLZPT-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropyl)amino]-n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CC)CCCN2CCCCC2)C=C1 FFSPNGQIEQLZPT-UHFFFAOYSA-N 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 3
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 3
- 230000000977 initiatory effect Effects 0.000 claims description 3
- HHBSROCTANUBIR-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(2-piperidin-1-ylethyl)indole-5-carboxamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C=C2)C2=C1 HHBSROCTANUBIR-UHFFFAOYSA-N 0.000 claims description 3
- YBEAOMIQGSAFOX-UHFFFAOYSA-N n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 YBEAOMIQGSAFOX-UHFFFAOYSA-N 0.000 claims description 3
- KQCZQUSMZFKEET-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(3-piperidin-1-ylpropanoylamino)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1NC(=O)CCN1CCCCC1 KQCZQUSMZFKEET-UHFFFAOYSA-N 0.000 claims description 3
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 3
- WXLCDTBTIVJDCE-UHFFFAOYSA-N 1,4-oxazepine Chemical compound O1C=CC=NC=C1 WXLCDTBTIVJDCE-UHFFFAOYSA-N 0.000 claims description 2
- DOUXDVJGQDOJQO-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[2-fluoro-4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C(=CC(OC=4C=C(F)C(NC(=O)NC(CC)CC)=CC=4)=CC=3)F)C=C2C=C1 DOUXDVJGQDOJQO-UHFFFAOYSA-N 0.000 claims description 2
- ZNZQHUJVFBGGSS-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=C(C)C(OC=4C=CC(NC(=O)NC(CC)CC)=CC=4)=CC=3)C=C2C=C1 ZNZQHUJVFBGGSS-UHFFFAOYSA-N 0.000 claims description 2
- RNZACGFFOMPGMO-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C(=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OCC)=CC=3)F)C=C2C=C1 RNZACGFFOMPGMO-UHFFFAOYSA-N 0.000 claims description 2
- CYKXUGCWXCBBTL-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2,3-dihydroindole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OCC)=CC=3)C=C2CC1 CYKXUGCWXCBBTL-UHFFFAOYSA-N 0.000 claims description 2
- FZOJKYLOVHTPFT-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OCC)=CC=3)C=C2C=C1 FZOJKYLOVHTPFT-UHFFFAOYSA-N 0.000 claims description 2
- VLBAKMLLPHOSLB-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=CC(OC=4C=CC(NC(=O)NC(CC)CC)=CC=4)=CC=3)C=C2C=C1 VLBAKMLLPHOSLB-UHFFFAOYSA-N 0.000 claims description 2
- KJHLAFQGWOZULA-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=C(F)C=4)OC)=CC=3)C=C2C=C1 KJHLAFQGWOZULA-UHFFFAOYSA-N 0.000 claims description 2
- XYLYLOGJHZTKOJ-UHFFFAOYSA-N 1-[4-[2-[4-(1-butylpiperidin-4-yl)oxyphenyl]-1-ethylindol-5-yl]oxy-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C=2N(C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3C=2)CC)C=C1 XYLYLOGJHZTKOJ-UHFFFAOYSA-N 0.000 claims description 2
- LXSJTVFHEQRNRV-UHFFFAOYSA-N 1-[4-[2-[4-(1-butylpiperidin-4-yl)oxyphenyl]-1-methylbenzimidazol-5-yl]oxy-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C=2N(C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3N=2)C)C=C1 LXSJTVFHEQRNRV-UHFFFAOYSA-N 0.000 claims description 2
- FWRBJTIVZRKTOR-UHFFFAOYSA-N 1-[4-[2-[4-(1-butylpiperidin-4-yl)oxyphenyl]-1-propylbenzimidazol-5-yl]oxy-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C=2N(C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3N=2)CCC)C=C1 FWRBJTIVZRKTOR-UHFFFAOYSA-N 0.000 claims description 2
- UQNPEVBBZSZTTD-UHFFFAOYSA-N 1-[4-[4-[6-(1-butylpiperidin-4-yl)oxy-1,3-benzoxazol-2-yl]phenoxy]-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(N=C(O2)C=3C=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)=CC=3)C2=C1 UQNPEVBBZSZTTD-UHFFFAOYSA-N 0.000 claims description 2
- RJMPIGWZUXXIET-UHFFFAOYSA-N 1-[4-[4-[6-(1-butylpiperidin-4-yl)oxy-1,3-benzoxazol-2-yl]phenoxy]phenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(N=C(O2)C=3C=CC(OC=4C=CC(NC(=O)NC(CC)CC)=CC=4)=CC=3)C2=C1 RJMPIGWZUXXIET-UHFFFAOYSA-N 0.000 claims description 2
- ZDSPRGPTRLSDRN-UHFFFAOYSA-N 1-[4-[[1-[4-(1-butylpiperidin-4-yl)oxy-3-methylbenzoyl]-2,3-dihydroindol-5-yl]oxy]-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N2C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3CC2)C=C1C ZDSPRGPTRLSDRN-UHFFFAOYSA-N 0.000 claims description 2
- QZZWVJVJJNKWEA-UHFFFAOYSA-N 1-[4-[[1-[4-(1-butylpiperidin-4-yl)oxybenzoyl]-2,3-dihydroindol-5-yl]oxy]-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N2C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3CC2)C=C1 QZZWVJVJJNKWEA-UHFFFAOYSA-N 0.000 claims description 2
- WPDNYXYSBFGQCI-UHFFFAOYSA-N 1-[4-[[5-[4-(1-butylpiperidin-4-yl)oxybenzoyl]-3,4-dihydro-2h-1,5-benzoxazepin-8-yl]oxy]-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N2C3=CC=C(OC=4C(=CC(NC(=O)NC(CC)CC)=CC=4)OC)C=C3OCCC2)C=C1 WPDNYXYSBFGQCI-UHFFFAOYSA-N 0.000 claims description 2
- CZDNSYLCKAIQMT-UHFFFAOYSA-N 2-[2-(4-hydroxypiperidin-1-yl)ethyl]-n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-1-benzofuran-6-carboxamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=C(CCN2CCC(O)CC2)O2)C2=C1 CZDNSYLCKAIQMT-UHFFFAOYSA-N 0.000 claims description 2
- NQARMZXRWIQPJW-UHFFFAOYSA-N 2-[4-[4-[[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]carbamoyl]phenoxy]piperidin-1-yl]acetic acid Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC(O)=O)CC1 NQARMZXRWIQPJW-UHFFFAOYSA-N 0.000 claims description 2
- PMOMKMLZKFOSNP-UHFFFAOYSA-N 2-[4-[4-[[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]carbamoyl]phenoxy]piperidin-1-yl]ethyl acetate Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCOC(C)=O)CC1 PMOMKMLZKFOSNP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- WYXDGYXAOVFBDC-UHFFFAOYSA-N 3-acetyl-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(2-piperidin-1-ylethyl)indole-5-carboxamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C=C2C(C)=O)C2=C1 WYXDGYXAOVFBDC-UHFFFAOYSA-N 0.000 claims description 2
- CJQGAUMARIXBTE-UHFFFAOYSA-N 3-methyl-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(2-piperidin-1-ylethyl)indole-5-carboxamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C=C2C)C2=C1 CJQGAUMARIXBTE-UHFFFAOYSA-N 0.000 claims description 2
- FGVGVIASMFIXPC-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxy-n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 FGVGVIASMFIXPC-UHFFFAOYSA-N 0.000 claims description 2
- CPZUCPGMFKUONU-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 CPZUCPGMFKUONU-UHFFFAOYSA-N 0.000 claims description 2
- AVUFIEPQKCEWMR-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 AVUFIEPQKCEWMR-UHFFFAOYSA-N 0.000 claims description 2
- LYQVLHHKKUORGT-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC(OC)=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 LYQVLHHKKUORGT-UHFFFAOYSA-N 0.000 claims description 2
- DGRBQWCUACUGPB-UHFFFAOYSA-N 4-(1-butan-2-ylpiperidin-4-yl)oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)CC)CC1 DGRBQWCUACUGPB-UHFFFAOYSA-N 0.000 claims description 2
- VONGLEDCGUVQBY-UHFFFAOYSA-N 4-(1-butan-2-ylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)CC)CC1 VONGLEDCGUVQBY-UHFFFAOYSA-N 0.000 claims description 2
- ASUZZLAVJYBLMU-UHFFFAOYSA-N 4-(1-butyl-3,6-dihydro-2h-pyridin-4-yl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound C1N(CCCC)CCC(C=2C=CC(=CC=2)C(=O)NC=2C=C(C)C(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)=C1 ASUZZLAVJYBLMU-UHFFFAOYSA-N 0.000 claims description 2
- HJCTZAFCCZTIOB-UHFFFAOYSA-N 4-(1-butyl-3,6-dihydro-2h-pyridin-4-yl)-n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound C1N(CCCC)CCC(C=2C=CC(=CC=2)C(=O)NC=2SC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COC)=CN=2)=C1 HJCTZAFCCZTIOB-UHFFFAOYSA-N 0.000 claims description 2
- BSHDFAUKDMXMPG-UHFFFAOYSA-N 4-(1-butyl-3-fluoropiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound FC1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 BSHDFAUKDMXMPG-UHFFFAOYSA-N 0.000 claims description 2
- BYPMIYVSLZWOMH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2,5-difluoro-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1F BYPMIYVSLZWOMH-UHFFFAOYSA-N 0.000 claims description 2
- MUMPCRJXXWNRSH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2,5-difluoro-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1F MUMPCRJXXWNRSH-UHFFFAOYSA-N 0.000 claims description 2
- DUNXKCVUAFDENW-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2-fluoro-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-5-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1C DUNXKCVUAFDENW-UHFFFAOYSA-N 0.000 claims description 2
- HDUXAQCADSTRBE-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-chloro-n-ethyl-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1Cl HDUXAQCADSTRBE-UHFFFAOYSA-N 0.000 claims description 2
- PBNMSNJIVZUMLK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-fluoro-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1F PBNMSNJIVZUMLK-UHFFFAOYSA-N 0.000 claims description 2
- JXLBXYNZQJKPFL-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methoxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1OC JXLBXYNZQJKPFL-UHFFFAOYSA-N 0.000 claims description 2
- YEHQJXDUMFUVPZ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methyl-n-[4-[4-(pentan-3-ylcarbamoylamino)-2-propoxyphenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCCC)=CC=2)C=C1C YEHQJXDUMFUVPZ-UHFFFAOYSA-N 0.000 claims description 2
- JQRUDBOTMKGVMF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-(2-ethoxyethyl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOCC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 JQRUDBOTMKGVMF-UHFFFAOYSA-N 0.000 claims description 2
- PEIYXBRLIJUPPQ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-(2-hydroxyethyl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCO)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 PEIYXBRLIJUPPQ-UHFFFAOYSA-N 0.000 claims description 2
- VGCBWKYEOUETMG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-(2-methoxyethyl)-3-methyl-n-[4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOC)C=2C=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1C VGCBWKYEOUETMG-UHFFFAOYSA-N 0.000 claims description 2
- ROSFHFSMFJXVJP-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-(2-methoxyethyl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1C ROSFHFSMFJXVJP-UHFFFAOYSA-N 0.000 claims description 2
- URBVEYNMNJJTBB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-(2-methoxyethyl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 URBVEYNMNJJTBB-UHFFFAOYSA-N 0.000 claims description 2
- DGRSCDJBQWNMDJ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2,5-dimethyl-4-[4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(C)C)=CC=3)=C(C)C=2)C)C=C1 DGRSCDJBQWNMDJ-UHFFFAOYSA-N 0.000 claims description 2
- VDZKSQXTWRAGMT-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)F)C=C1C VDZKSQXTWRAGMT-UHFFFAOYSA-N 0.000 claims description 2
- CJVNDRDZYCWROM-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)F)C=C1 CJVNDRDZYCWROM-UHFFFAOYSA-N 0.000 claims description 2
- QBWDWTXHNPLVDX-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)F)C=C1C QBWDWTXHNPLVDX-UHFFFAOYSA-N 0.000 claims description 2
- KAFSOBPQEKCJFZ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methoxybenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)F)C=C1OC KAFSOBPQEKCJFZ-UHFFFAOYSA-N 0.000 claims description 2
- XIUCAZURIYIENF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-fluoro-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)F)C=C1 XIUCAZURIYIENF-UHFFFAOYSA-N 0.000 claims description 2
- ZOFIUQCOSMJWNK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-methoxy-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)OC)C=C1C ZOFIUQCOSMJWNK-UHFFFAOYSA-N 0.000 claims description 2
- RVWMTBJXYDRHEG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[2-methoxy-4-[4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C=CC(NC(=O)NC(C)C)=CC=3)=CC=2)OC)C=C1 RVWMTBJXYDRHEG-UHFFFAOYSA-N 0.000 claims description 2
- ZNGOWSQAUVDYBB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[3,5-dimethyl-4-[4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=CC(NC(=O)NC(C)C)=CC=3)=C(C)C=2)C=C1 ZNGOWSQAUVDYBB-UHFFFAOYSA-N 0.000 claims description 2
- MVURYMBQJCLHGO-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[3-(pentan-3-ylcarbamoylamino)-5,6-dihydrobenzo[b][1]benzoxepin-8-yl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C3CCC4=CC(NC(=O)NC(CC)CC)=CC=C4OC3=CC=2)C=C1 MVURYMBQJCLHGO-UHFFFAOYSA-N 0.000 claims description 2
- TYVCJXCHLUBQKV-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[3-[4-(dimethylaminocarbamoylamino)-2-methoxyphenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(OC=3C(=CC(NC(=O)NN(C)C)=CC=3)OC)C=CC=2)C=C1 TYVCJXCHLUBQKV-UHFFFAOYSA-N 0.000 claims description 2
- XYHGYDPZHXJOOB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2,5-difluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2,5-difluorobenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)F)=CC=2)C=C1F XYHGYDPZHXJOOB-UHFFFAOYSA-N 0.000 claims description 2
- KAPQDAUTXKVGMY-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2,5-difluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)F)=CC=2)C=C1C KAPQDAUTXKVGMY-UHFFFAOYSA-N 0.000 claims description 2
- XQOCZYXKNRQHKJ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2,5-difluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)F)=CC=2)C=C1 XQOCZYXKNRQHKJ-UHFFFAOYSA-N 0.000 claims description 2
- XBCRLYKCQSGRQZ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COC)=CC=2)C=C1 XBCRLYKCQSGRQZ-UHFFFAOYSA-N 0.000 claims description 2
- WKRPNMCZPQXZGK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COC)=CC=2)C=C1 WKRPNMCZPQXZGK-UHFFFAOYSA-N 0.000 claims description 2
- UJMUSNNVNLRABQ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-[2-(dimethylamino)ethoxy]-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCCN(C)C)=CC=2)F)C=C1 UJMUSNNVNLRABQ-UHFFFAOYSA-N 0.000 claims description 2
- QNJKKYYVDBABIS-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-chloro-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)Cl)=CC=2)F)C=C1C QNJKKYYVDBABIS-UHFFFAOYSA-N 0.000 claims description 2
- SGKQKEFQSTUMLM-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-chloro-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)Cl)=CC=2)F)C=C1 SGKQKEFQSTUMLM-UHFFFAOYSA-N 0.000 claims description 2
- SFJIPJBWVWUCPV-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)F)C=C1C SFJIPJBWVWUCPV-UHFFFAOYSA-N 0.000 claims description 2
- PBRFSLVRILTYLA-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C(=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)F)C=C1 PBRFSLVRILTYLA-UHFFFAOYSA-N 0.000 claims description 2
- XLYWSAPGKJDXSR-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-fluoro-5-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1C XLYWSAPGKJDXSR-UHFFFAOYSA-N 0.000 claims description 2
- YTRNZICPYNKYTG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methoxybenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1OC YTRNZICPYNKYTG-UHFFFAOYSA-N 0.000 claims description 2
- XBNFPGMXYCGPQM-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1C XBNFPGMXYCGPQM-UHFFFAOYSA-N 0.000 claims description 2
- HRBDBNTXQXWBDW-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2-methoxyethyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 HRBDBNTXQXWBDW-UHFFFAOYSA-N 0.000 claims description 2
- LIWMLJKBXFYZNK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]piperidine-1-carboxamide Chemical compound C1CN(CCCC)CCC1OC1CCN(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)CC1 LIWMLJKBXFYZNK-UHFFFAOYSA-N 0.000 claims description 2
- GJFMRAHCTNFZFA-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-5-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-fluoro-5-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OCC)=CC=2)C=C1C GJFMRAHCTNFZFA-UHFFFAOYSA-N 0.000 claims description 2
- SYLHZIKXOVLLLU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-5-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OCC)=CC=2)C=C1C SYLHZIKXOVLLLU-UHFFFAOYSA-N 0.000 claims description 2
- WRFYOAWVHWMNHE-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)F)=CC=2)C=C1 WRFYOAWVHWMNHE-UHFFFAOYSA-N 0.000 claims description 2
- XCJIASCWKCMONP-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 XCJIASCWKCMONP-UHFFFAOYSA-N 0.000 claims description 2
- AYBMFMXAZSHUDU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC(C=C1C)=CC=C1C(=O)NC(C=C1)=CC=C1OC1=CC=C(NC(=O)NC(CC)CC)C=C1OC AYBMFMXAZSHUDU-UHFFFAOYSA-N 0.000 claims description 2
- HPNYZHCLCOXJSH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3,5-dimethylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=C(C)C=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1C HPNYZHCLCOXJSH-UHFFFAOYSA-N 0.000 claims description 2
- AMTWDLWXLBUIBE-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1C(F)(F)F AMTWDLWXLBUIBE-UHFFFAOYSA-N 0.000 claims description 2
- GDSJVUOGBDCTTR-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(1-methoxypropan-2-yl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(C(C)COC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 GDSJVUOGBDCTTR-UHFFFAOYSA-N 0.000 claims description 2
- NUZMEPMIHGYXAY-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2,2,2-trifluoroethyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC(F)(F)F)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 NUZMEPMIHGYXAY-UHFFFAOYSA-N 0.000 claims description 2
- OKXBJPFVXDWQCK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2-methoxypropyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC(C)OC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 OKXBJPFVXDWQCK-UHFFFAOYSA-N 0.000 claims description 2
- NYGQODCRDUNUGG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2-methylpropyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC(C)C)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 NYGQODCRDUNUGG-UHFFFAOYSA-N 0.000 claims description 2
- TYEVBPSOPPXZDA-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(3,3,3-trifluoropropyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCC(F)(F)F)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 TYEVBPSOPPXZDA-UHFFFAOYSA-N 0.000 claims description 2
- VUEMEAXRNCMQPZ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(3-methoxypropyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCCOC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 VUEMEAXRNCMQPZ-UHFFFAOYSA-N 0.000 claims description 2
- KWVNECGFOSSAOY-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(4,4,4-trifluorobutyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCCC(F)(F)F)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 KWVNECGFOSSAOY-UHFFFAOYSA-N 0.000 claims description 2
- ORLRWXZFNSLLHL-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(oxan-4-yl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(C2CCOCC2)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 ORLRWXZFNSLLHL-UHFFFAOYSA-N 0.000 claims description 2
- IXWINLQGPUSAHW-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(oxolan-2-ylmethyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC2OCCC2)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 IXWINLQGPUSAHW-UHFFFAOYSA-N 0.000 claims description 2
- VLPZKEGLHGCFEO-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(oxolan-3-yl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(C2COCC2)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 VLPZKEGLHGCFEO-UHFFFAOYSA-N 0.000 claims description 2
- DQGMBEYKYZNIHM-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 DQGMBEYKYZNIHM-UHFFFAOYSA-N 0.000 claims description 2
- LMVMNKSCSCGTJG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(C)C)=CC=3)OC)=CC=2)C=C1 LMVMNKSCSCGTJG-UHFFFAOYSA-N 0.000 claims description 2
- SYXMEFWBGVPEFH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-(hydroxymethyl)-4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=C(CO)C(NC(=O)NC(C)C)=CC=3)=CC=2)C=C1 SYXMEFWBGVPEFH-UHFFFAOYSA-N 0.000 claims description 2
- JACMHNLBYPGUDI-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-3-(2-hydroxyethyl)benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1CCO JACMHNLBYPGUDI-UHFFFAOYSA-N 0.000 claims description 2
- ITMLVJFERQQABL-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 ITMLVJFERQQABL-UHFFFAOYSA-N 0.000 claims description 2
- QGZVEFXYTCOMDN-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methoxybenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1OC QGZVEFXYTCOMDN-UHFFFAOYSA-N 0.000 claims description 2
- ITZCLHXHZFYJHX-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1C ITZCLHXHZFYJHX-UHFFFAOYSA-N 0.000 claims description 2
- DYPGHHCNOSMWBU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 DYPGHHCNOSMWBU-UHFFFAOYSA-N 0.000 claims description 2
- MOPXYSCFOKGEEF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[3-methoxy-4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=C(OC)C(NC(=O)NC(C)C)=CC=3)=CC=2)C=C1 MOPXYSCFOKGEEF-UHFFFAOYSA-N 0.000 claims description 2
- DIFLHHSBHKYWKB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(dimethylaminocarbamoylamino)phenoxy]-3-(methoxymethyl)phenyl]-3-methoxybenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(COC)C(OC=3C=CC(NC(=O)NN(C)C)=CC=3)=CC=2)C=C1OC DIFLHHSBHKYWKB-UHFFFAOYSA-N 0.000 claims description 2
- YVXJZLNZIMCTQW-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(dimethylaminocarbamoylamino)phenoxy]-3-(methoxymethyl)phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(COC)C(OC=3C=CC(NC(=O)NN(C)C)=CC=3)=CC=2)C=C1C YVXJZLNZIMCTQW-UHFFFAOYSA-N 0.000 claims description 2
- YPHCLYRKHGYOLI-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(pentan-3-ylcarbamoylamino)-2-propan-2-ylphenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)C(C)C)=CC=2)C=C1 YPHCLYRKHGYOLI-UHFFFAOYSA-N 0.000 claims description 2
- UGNHMNFKESEJNK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(pentan-3-ylcarbamoylamino)phenoxy]-3-(trifluoromethyl)phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C(F)(F)F)C=C1 UGNHMNFKESEJNK-UHFFFAOYSA-N 0.000 claims description 2
- JYIOAPYSALPRKD-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 JYIOAPYSALPRKD-UHFFFAOYSA-N 0.000 claims description 2
- PQFHFEWCALHXSU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C=CC(NC(=O)NC(C)C)=CC=3)=CC=2)C=C1 PQFHFEWCALHXSU-UHFFFAOYSA-N 0.000 claims description 2
- YHFPOBGSSUURGF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-(propan-2-ylcarbamoylamino)phenyl]sulfanylphenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(SC=3C=CC(NC(=O)NC(C)C)=CC=3)=CC=2)C=C1 YHFPOBGSSUURGF-UHFFFAOYSA-N 0.000 claims description 2
- AISSVXAWLNLHDD-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[4-[[2-(dimethylamino)acetyl]amino]-2-methoxyphenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)CN(C)C)=CC=3)OC)=CC=2)C=C1 AISSVXAWLNLHDD-UHFFFAOYSA-N 0.000 claims description 2
- MGWAUTHWSRRJPC-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(1-methoxybutan-2-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)COC)=C(F)C=3)OC)=CC=2)C=C1C MGWAUTHWSRRJPC-UHFFFAOYSA-N 0.000 claims description 2
- PKKWHNHOIOWDPB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1C PKKWHNHOIOWDPB-UHFFFAOYSA-N 0.000 claims description 2
- OOZLXYXTLVYKIS-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2-methoxyethyl)-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CCOC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1C OOZLXYXTLVYKIS-UHFFFAOYSA-N 0.000 claims description 2
- JLHARIGFOPCLNN-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1 JLHARIGFOPCLNN-UHFFFAOYSA-N 0.000 claims description 2
- BXPVDHIZGWYUSG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[5-fluoro-2-methoxy-4-(propan-2-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(C)C)=C(F)C=3)OC)=CC=2)C=C1C BXPVDHIZGWYUSG-UHFFFAOYSA-N 0.000 claims description 2
- NVZVPFAQDXKTHJ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[[4-(propan-2-ylcarbamoylamino)phenyl]methyl]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(CC=3C=CC(NC(=O)NC(C)C)=CC=3)=CC=2)C=C1 NVZVPFAQDXKTHJ-UHFFFAOYSA-N 0.000 claims description 2
- MLYFBLSRMGYQRK-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2SC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COC)=CN=2)C=C1 MLYFBLSRMGYQRK-UHFFFAOYSA-N 0.000 claims description 2
- LFZNLWCIOZNFFI-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-ethyl-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)N(CC)C=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1C LFZNLWCIOZNFFI-UHFFFAOYSA-N 0.000 claims description 2
- VPXFIZRTCFCHTR-UHFFFAOYSA-N 4-(1-butylpyrrolidin-3-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1N(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 VPXFIZRTCFCHTR-UHFFFAOYSA-N 0.000 claims description 2
- BZBRUIVBZMJZLQ-UHFFFAOYSA-N 4-(1-cyclobutylpiperidin-4-yl)oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C2CCC2)CC1 BZBRUIVBZMJZLQ-UHFFFAOYSA-N 0.000 claims description 2
- OBSQBSQXEXXZTL-UHFFFAOYSA-N 4-(1-cyclopentylpiperidin-4-yl)oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C2CCCC2)CC1 OBSQBSQXEXXZTL-UHFFFAOYSA-N 0.000 claims description 2
- LWNUGHZZTYVNCS-UHFFFAOYSA-N 4-(1-cyclopropylpiperidin-4-yl)oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C2CC2)CC1 LWNUGHZZTYVNCS-UHFFFAOYSA-N 0.000 claims description 2
- GADZXRRNUDZPOU-UHFFFAOYSA-N 4-(1-ethyl-3,6-dihydro-2h-pyridin-4-yl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(C=2CCN(CC)CC=2)C=C1 GADZXRRNUDZPOU-UHFFFAOYSA-N 0.000 claims description 2
- UCIJFSQLGXOPTA-UHFFFAOYSA-N 4-(4-butyl-1,4-diazepan-1-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2,5-difluorobenzamide Chemical compound C1CN(CCCC)CCCN1C1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1F UCIJFSQLGXOPTA-UHFFFAOYSA-N 0.000 claims description 2
- CFWSGLDWVOEREG-UHFFFAOYSA-N 4-(4-butyl-1,4-diazepan-1-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCCN1C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 CFWSGLDWVOEREG-UHFFFAOYSA-N 0.000 claims description 2
- ZRJUHKOPGLUHEH-UHFFFAOYSA-N 4-(4-butyl-1,4-diazepan-1-yl)-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCCN1C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 ZRJUHKOPGLUHEH-UHFFFAOYSA-N 0.000 claims description 2
- JMCKGBWZTNUCHV-UHFFFAOYSA-N 4-(4-butyl-1,4-diazepan-1-yl)-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCCN1C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1 JMCKGBWZTNUCHV-UHFFFAOYSA-N 0.000 claims description 2
- BQSHOHKYTKCXPT-UHFFFAOYSA-N 4-(4-butylpiperazin-1-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-fluoro-5-methylbenzamide Chemical compound C1CN(CCCC)CCN1C1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1C BQSHOHKYTKCXPT-UHFFFAOYSA-N 0.000 claims description 2
- IKHRUXPEYUBTBU-UHFFFAOYSA-N 4-(4-butylpiperazin-1-yl)-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCN1C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 IKHRUXPEYUBTBU-UHFFFAOYSA-N 0.000 claims description 2
- UOZHOXNBJUWQER-UHFFFAOYSA-N 4-[(1-benzylpiperidin-4-yl)-methylamino]-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(N(C)C2CCN(CC=3C=CC=CC=3)CC2)C=C1 UOZHOXNBJUWQER-UHFFFAOYSA-N 0.000 claims description 2
- SONUAIKJYBKLAG-UHFFFAOYSA-N 4-[(1-benzylpiperidin-4-yl)amino]-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1NC1CCN(CC=2C=CC=CC=2)CC1 SONUAIKJYBKLAG-UHFFFAOYSA-N 0.000 claims description 2
- YQYJFFXGCJHPLR-UHFFFAOYSA-N 4-[(1-butylpiperidin-4-yl)-methylamino]-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1N(C)C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 YQYJFFXGCJHPLR-UHFFFAOYSA-N 0.000 claims description 2
- QASRHWVUQZXSBK-UHFFFAOYSA-N 4-[(1-butylpiperidin-4-yl)-methylamino]-n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1N(C)C1=CC=C(C(=O)NC=2C=CC(OC=3C=C(F)C(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 QASRHWVUQZXSBK-UHFFFAOYSA-N 0.000 claims description 2
- CEKINWILKSPEMJ-UHFFFAOYSA-N 4-[(1-butylpiperidin-4-yl)-methylamino]-n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1N(C)C1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=C(F)C=3)OC)=CC=2)C=C1 CEKINWILKSPEMJ-UHFFFAOYSA-N 0.000 claims description 2
- JQSALQCXJMNEMX-UHFFFAOYSA-N 4-[(1-butylpiperidin-4-yl)amino]-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCCC)CCC1NC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1 JQSALQCXJMNEMX-UHFFFAOYSA-N 0.000 claims description 2
- CTUIAOGXUAIYJC-UHFFFAOYSA-N 4-[1-(2-ethoxyethyl)piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CCOCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 CTUIAOGXUAIYJC-UHFFFAOYSA-N 0.000 claims description 2
- WSQSGEBZRQLGEX-UHFFFAOYSA-N 4-[1-(2-ethylbutyl)piperidin-4-yl]oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1CN(CC(CC)CC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 WSQSGEBZRQLGEX-UHFFFAOYSA-N 0.000 claims description 2
- VZAMIYXUENHJJZ-UHFFFAOYSA-N 4-[1-(2-hydroxyethyl)piperidin-4-yl]oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCO)CC1 VZAMIYXUENHJJZ-UHFFFAOYSA-N 0.000 claims description 2
- CYCQYHSYFMABRB-UHFFFAOYSA-N 4-[1-(2-methoxyethyl)piperidin-4-yl]oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCOC)CC1 CYCQYHSYFMABRB-UHFFFAOYSA-N 0.000 claims description 2
- NUKKOFPCEDTWJX-UHFFFAOYSA-N 4-[1-(3-hydroxypropyl)piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCCO)CC1 NUKKOFPCEDTWJX-UHFFFAOYSA-N 0.000 claims description 2
- YQGXAEMZSRXDCE-UHFFFAOYSA-N 4-[1-(3-methylbutyl)piperidin-4-yl]oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCC(C)C)CC1 YQGXAEMZSRXDCE-UHFFFAOYSA-N 0.000 claims description 2
- LJNUJNKEYXDJQN-UHFFFAOYSA-N 4-[1-(cyclohexylmethyl)piperidin-4-yl]oxy-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC2CCCCC2)CC1 LJNUJNKEYXDJQN-UHFFFAOYSA-N 0.000 claims description 2
- NKTYUBKNUYCOQN-UHFFFAOYSA-N 4-[1-(dimethylamino)piperidin-4-yl]oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(N(C)C)CC1 NKTYUBKNUYCOQN-UHFFFAOYSA-N 0.000 claims description 2
- GWUVTEQQVVYCGA-UHFFFAOYSA-N 4-[1-[2-(diethylamino)ethyl]piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCN(CC)CC)CC1 GWUVTEQQVVYCGA-UHFFFAOYSA-N 0.000 claims description 2
- LJRIYXMHCSFTDJ-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(=O)CN(C)C)CC1 LJRIYXMHCSFTDJ-UHFFFAOYSA-N 0.000 claims description 2
- XYJXOEVTTSWJOB-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)ethyl]piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCN(C)C)CC1 XYJXOEVTTSWJOB-UHFFFAOYSA-N 0.000 claims description 2
- NPJQXBZYUCFXTD-UHFFFAOYSA-N 4-[1-[3-(dimethylamino)propyl]piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCCN(C)C)CC1 NPJQXBZYUCFXTD-UHFFFAOYSA-N 0.000 claims description 2
- OMCFOYXMSVOVJT-UHFFFAOYSA-N 4-[4-[4-[[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]carbamoyl]phenoxy]piperidin-1-yl]butyl acetate Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCCCOC(C)=O)CC1 OMCFOYXMSVOVJT-UHFFFAOYSA-N 0.000 claims description 2
- PBKFGZGHLBONGJ-UHFFFAOYSA-N 4-[acetyl(2-piperidin-1-ylethyl)amino]-n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C(C)=O)C=C1 PBKFGZGHLBONGJ-UHFFFAOYSA-N 0.000 claims description 2
- OPBUYQCPRSTPBK-UHFFFAOYSA-N 4-[acetyl(3-piperidin-1-ylpropyl)amino]-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCCN2CCCCC2)C(C)=O)C=C1 OPBUYQCPRSTPBK-UHFFFAOYSA-N 0.000 claims description 2
- DYBNNRCMDWRMEK-UHFFFAOYSA-N 4-[acetyl(3-piperidin-1-ylpropyl)amino]-n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CCCN2CCCCC2)C(C)=O)C=C1 DYBNNRCMDWRMEK-UHFFFAOYSA-N 0.000 claims description 2
- SZGVFJITCITDPB-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropanoyl)amino]-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CC)C(=O)CCN2CCCCC2)C=C1 SZGVFJITCITDPB-UHFFFAOYSA-N 0.000 claims description 2
- SXHYZJRXGJDFOB-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropyl)amino]-n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CC)CCCN2CCCCC2)C=C1 SXHYZJRXGJDFOB-UHFFFAOYSA-N 0.000 claims description 2
- FJIQDFXENHYODP-UHFFFAOYSA-N C(C)C(CC)NC(NC1=CC(=C(OC2=C(C=CC=C2)C2=C(C=C(C(=O)N)C=C2)C)C=C1)OC)=O Chemical compound C(C)C(CC)NC(NC1=CC(=C(OC2=C(C=CC=C2)C2=C(C=C(C(=O)N)C=C2)C)C=C1)OC)=O FJIQDFXENHYODP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 2
- 108010045501 diazocan Proteins 0.000 claims description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 claims description 2
- 229940127554 medical product Drugs 0.000 claims description 2
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 claims description 2
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 2
- AZFTXEMSLJQSLJ-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(N(CCN(C)C)C(=O)C=2C=CC(OC3CCN(C)CC3)=CC=2)C=C1 AZFTXEMSLJQSLJ-UHFFFAOYSA-N 0.000 claims description 2
- KDGXTXHYIFNACT-UHFFFAOYSA-N n-[2-fluoro-4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC=C1OC(C=C1F)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C)CC1 KDGXTXHYIFNACT-UHFFFAOYSA-N 0.000 claims description 2
- TWQIKVLHSIDKQS-UHFFFAOYSA-N n-[2-fluoro-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methyl-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1F)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(C)CC1 TWQIKVLHSIDKQS-UHFFFAOYSA-N 0.000 claims description 2
- MDPPYDGPKLGMML-UHFFFAOYSA-N n-[3-(methoxymethyl)-4-[3-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound CCC(CC)NC(=O)NC1=CC=CC(OC=2C(=CC(NC(=O)C=3C=C(OC4CCN(CC4)C(C)C)C=CC=3)=CC=2)COC)=C1 MDPPYDGPKLGMML-UHFFFAOYSA-N 0.000 claims description 2
- PNNJRGXDAIREBH-UHFFFAOYSA-N n-[3-(methoxymethyl)-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(1-methylpiperidin-4-yl)indole-5-carboxamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)COC)=CC=C1NC(=O)C1=CC=C(N(C=C2)C3CCN(C)CC3)C2=C1 PNNJRGXDAIREBH-UHFFFAOYSA-N 0.000 claims description 2
- JQEUUEWGKBGBNL-UHFFFAOYSA-N n-[3-(methoxymethyl)-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)COC)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 JQEUUEWGKBGBNL-UHFFFAOYSA-N 0.000 claims description 2
- HSZWWMXUGRRLJA-UHFFFAOYSA-N n-[3-[4-(dimethylaminocarbamoylamino)-2-methoxyphenoxy]phenyl]-4-(1-propan-2-ylpiperidin-3-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NN(C)C)=CC=C1OC1=CC=CC(NC(=O)C=2C=CC(OC3CN(CCC3)C(C)C)=CC=2)=C1 HSZWWMXUGRRLJA-UHFFFAOYSA-N 0.000 claims description 2
- ZDHYVMHTZXOZKV-UHFFFAOYSA-N n-[3-methyl-4-[3-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound CCC(CC)NC(=O)NC1=CC=CC(OC=2C(=CC(NC(=O)C=3C=C(OC4CCN(CC4)C(C)C)C=CC=3)=CC=2)C)=C1 ZDHYVMHTZXOZKV-UHFFFAOYSA-N 0.000 claims description 2
- VYNJNPGQNQQBEI-UHFFFAOYSA-N n-[3-methyl-4-[3-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound CCC(CC)NC(=O)NC1=CC=CC(OC=2C(=CC(NC(=O)C=3C=CC(OC4CCN(CC4)C(C)C)=CC=3)=CC=2)C)=C1 VYNJNPGQNQQBEI-UHFFFAOYSA-N 0.000 claims description 2
- YFGLOPRBXCOJSZ-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(3-piperidin-1-ylpropyl)indole-5-carboxamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(N(CCCN2CCCCC2)C=C2)C2=C1 YFGLOPRBXCOJSZ-UHFFFAOYSA-N 0.000 claims description 2
- BBQBXLHVMBLJHI-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-pentan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound C1CN(C(C)CCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 BBQBXLHVMBLJHI-UHFFFAOYSA-N 0.000 claims description 2
- GQDJQARCUREFJN-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-pentan-3-ylpiperidin-4-yl)oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(CC)CC)CC1 GQDJQARCUREFJN-UHFFFAOYSA-N 0.000 claims description 2
- ZGRKHNXEKDCESX-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 ZGRKHNXEKDCESX-UHFFFAOYSA-N 0.000 claims description 2
- SVAZIBFKQYVKJN-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propylpiperidin-4-yl)oxybenzamide Chemical compound C1CN(CCC)CCC1OC1=CC=C(C(=O)NC=2C=C(C)C(OC=3C=CC(NC(=O)NC(CC)CC)=CC=3)=CC=2)C=C1 SVAZIBFKQYVKJN-UHFFFAOYSA-N 0.000 claims description 2
- VKLJKIJKZQHIMG-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(3-piperidin-1-ylpropanoylamino)benzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1NC(=O)CCN1CCCCC1 VKLJKIJKZQHIMG-UHFFFAOYSA-N 0.000 claims description 2
- PRYHOQMBRWLRNC-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(2-methylpropyl)piperidin-4-yl]oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CC(C)C)CC1 PRYHOQMBRWLRNC-UHFFFAOYSA-N 0.000 claims description 2
- DEVJMMLCOOQENK-UHFFFAOYSA-N n-[3-methyl-4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-piperidin-4-yloxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCNCC1 DEVJMMLCOOQENK-UHFFFAOYSA-N 0.000 claims description 2
- CCJPAXUKPDHEQV-UHFFFAOYSA-N n-[4-(1-butylpiperidin-4-yl)oxyphenyl]-4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]benzamide Chemical compound C1CN(CCCC)CCC1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1=CC=C(NC(=O)NC(CC)CC)C=C1OC CCJPAXUKPDHEQV-UHFFFAOYSA-N 0.000 claims description 2
- NXFLADOIBVGMBU-UHFFFAOYSA-N n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-yl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2CCN(CC=2)C(C)C)C=C1 NXFLADOIBVGMBU-UHFFFAOYSA-N 0.000 claims description 2
- MLDACWQKXJKQIE-UHFFFAOYSA-N n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 MLDACWQKXJKQIE-UHFFFAOYSA-N 0.000 claims description 2
- QYIGTPVHHKTJFI-UHFFFAOYSA-N n-[4-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-piperidin-4-yloxybenzamide Chemical class COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCNCC1 QYIGTPVHHKTJFI-UHFFFAOYSA-N 0.000 claims description 2
- HRPGMDVLGQWGIF-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-2-fluorophenyl]-3-methyl-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1F)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(C)CC1 HRPGMDVLGQWGIF-UHFFFAOYSA-N 0.000 claims description 2
- XGNARZWLEYPJOD-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methyl-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(C)CC1 XGNARZWLEYPJOD-UHFFFAOYSA-N 0.000 claims description 2
- XLYAVFFQVWIUMN-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(4-ethylpiperazin-1-yl)benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(N2CCN(CC)CC2)C=C1 XLYAVFFQVWIUMN-UHFFFAOYSA-N 0.000 claims description 2
- CPQHIJUNQASEAE-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(4-methyl-1,4-diazepan-1-yl)benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(N2CCN(C)CCC2)C=C1 CPQHIJUNQASEAE-UHFFFAOYSA-N 0.000 claims description 2
- VLNZAFKUNMPMPZ-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(piperidin-4-ylamino)benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1NC1CCNCC1 VLNZAFKUNMPMPZ-UHFFFAOYSA-N 0.000 claims description 2
- CQHURGMMHVEBCX-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[(1-ethylpiperidin-4-yl)-methylamino]benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(N(C)C2CCN(CC)CC2)C=C1 CQHURGMMHVEBCX-UHFFFAOYSA-N 0.000 claims description 2
- OLXHZWLRTSFQEX-UHFFFAOYSA-N n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[(1-ethylpiperidin-4-yl)amino]benzamide Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1NC1CCN(CC)CC1 OLXHZWLRTSFQEX-UHFFFAOYSA-N 0.000 claims description 2
- CRAANLVBDXZIQF-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(C=2CCN(C)CC=2)C=C1 CRAANLVBDXZIQF-UHFFFAOYSA-N 0.000 claims description 2
- UJQWYFMKZCMXTE-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-(1-propan-2-yl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C1=CC=C(C=2CCN(CC=2)C(C)C)C=C1 UJQWYFMKZCMXTE-UHFFFAOYSA-N 0.000 claims description 2
- CMOBCYPQCNOJBR-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 CMOBCYPQCNOJBR-UHFFFAOYSA-N 0.000 claims description 2
- SOFWHSCYZUFARG-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-(1-propyl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound C1N(CCC)CCC(C=2C=CC(=CC=2)C(=O)NC=2C=C(C)C(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)=C1 SOFWHSCYZUFARG-UHFFFAOYSA-N 0.000 claims description 2
- GJWFHXUDTZLXLG-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-[1-(3-methylbutyl)piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCC(C)C)CC1 GJWFHXUDTZLXLG-UHFFFAOYSA-N 0.000 claims description 2
- CZYWVVHGZBXOSA-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-4-piperidin-4-yloxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCNCC1 CZYWVVHGZBXOSA-UHFFFAOYSA-N 0.000 claims description 2
- OFNBITKXJXTFJC-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-1-(1-methylpiperidin-4-yl)indole-5-carboxamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(N(C=C2)C3CCN(C)CC3)C2=C1 OFNBITKXJXTFJC-UHFFFAOYSA-N 0.000 claims description 2
- NYDAXKWANOEOBM-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-methyl-3,4-dihydro-1h-[1]benzofuro[3,2-c]pyridine-8-carboxamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(OC2=C3CN(C)CC2)C3=C1 NYDAXKWANOEOBM-UHFFFAOYSA-N 0.000 claims description 2
- LDYUCFCZAIDKHK-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1,2,2,6,6-pentamethylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CC(C)(C)N(C)C(C)(C)C1 LDYUCFCZAIDKHK-UHFFFAOYSA-N 0.000 claims description 2
- AJOOEGXVGUAQIJ-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2CCN(C)CC=2)C=C1 AJOOEGXVGUAQIJ-UHFFFAOYSA-N 0.000 claims description 2
- SZCFYBRQLBKLOG-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-pentan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound C1CN(C(C)CCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 SZCFYBRQLBKLOG-UHFFFAOYSA-N 0.000 claims description 2
- ADGSGHPJXPAZKO-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-yl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2CCN(CC=2)C(C)C)C=C1 ADGSGHPJXPAZKO-UHFFFAOYSA-N 0.000 claims description 2
- KWBIFKAECWJVQX-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propylpiperidin-4-yl)oxybenzamide Chemical compound C1CN(CCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1 KWBIFKAECWJVQX-UHFFFAOYSA-N 0.000 claims description 2
- RNVRNNXSRMWEEF-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[(8-propyl-8-azabicyclo[3.2.1]octan-3-yl)oxy]benzamide Chemical compound CCCN1C(C2)CCC1CC2OC(C=C1)=CC=C1C(=O)NC(C=C1)=CC=C1OC1=CC=C(NC(=O)NC(CC)CC)C=C1OC RNVRNNXSRMWEEF-UHFFFAOYSA-N 0.000 claims description 2
- BRWORHLCJQQOHY-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(3,3,3-trifluoropropyl)piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCC(F)(F)F)CC1 BRWORHLCJQQOHY-UHFFFAOYSA-N 0.000 claims description 2
- NZMYQNHXZNUJBG-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(3-methylbutyl)piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCC(C)C)CC1 NZMYQNHXZNUJBG-UHFFFAOYSA-N 0.000 claims description 2
- VVDCHGRDXKJTHJ-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(4,4,4-trifluorobutyl)piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCCC(F)(F)F)CC1 VVDCHGRDXKJTHJ-UHFFFAOYSA-N 0.000 claims description 2
- KZKXDGASENDEHL-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-[3-(oxan-4-ylamino)propyl]piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(CCCNC2CCOCC2)CC1 KZKXDGASENDEHL-UHFFFAOYSA-N 0.000 claims description 2
- IIWLFZWJOMBKEU-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-piperidin-4-yloxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCNCC1 IIWLFZWJOMBKEU-UHFFFAOYSA-N 0.000 claims description 2
- BZFFVDAPUMEUNY-UHFFFAOYSA-N n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]-3-methylphenyl]-3-(2-hydroxyethyl)-4-piperidin-4-yloxybenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC=C1OC(C(=C1)C)=CC=C1NC(=O)C(C=C1CCO)=CC=C1OC1CCNCC1 BZFFVDAPUMEUNY-UHFFFAOYSA-N 0.000 claims description 2
- PZBPINODIVAYPS-UHFFFAOYSA-N n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methyl-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(C)CC1 PZBPINODIVAYPS-UHFFFAOYSA-N 0.000 claims description 2
- BLDRNKYYLFKXGL-UHFFFAOYSA-N n-[4-[3-fluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C1=CC=C(C=2CCN(C)CC=2)C=C1 BLDRNKYYLFKXGL-UHFFFAOYSA-N 0.000 claims description 2
- RJHVXXCFMVVXTD-UHFFFAOYSA-N n-[4-[4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 RJHVXXCFMVVXTD-UHFFFAOYSA-N 0.000 claims description 2
- BVKKFUYJOXKDLQ-UHFFFAOYSA-N n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methyl-4-piperidin-4-yloxybenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC(OC)=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCNCC1 BVKKFUYJOXKDLQ-UHFFFAOYSA-N 0.000 claims description 2
- KONRUKIKLIBOEO-UHFFFAOYSA-N n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(3-methoxypropyl)piperidin-4-yl]oxy-3-methylbenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC(OC)=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(CCCOC)CC1 KONRUKIKLIBOEO-UHFFFAOYSA-N 0.000 claims description 2
- VREPQVXICUMGMC-UHFFFAOYSA-N n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(1-propan-2-yl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=2CCN(CC=2)C(C)C)C=C1 VREPQVXICUMGMC-UHFFFAOYSA-N 0.000 claims description 2
- KPYHLDXGNUNPSE-UHFFFAOYSA-N n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(1-propyl-3,6-dihydro-2h-pyridin-4-yl)benzamide Chemical compound C1N(CCC)CCC(C=2C=CC(=CC=2)C(=O)NC=2SC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)COC)=CN=2)=C1 KPYHLDXGNUNPSE-UHFFFAOYSA-N 0.000 claims description 2
- VQDUUVROHKWCNK-UHFFFAOYSA-N n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-[1-(2-methylpropyl)-3,6-dihydro-2h-pyridin-4-yl]benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=2CCN(CC(C)C)CC=2)C=C1 VQDUUVROHKWCNK-UHFFFAOYSA-N 0.000 claims description 2
- VBSVBVIUPCHCGE-UHFFFAOYSA-N n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-[1-(3-methylbutyl)-3,6-dihydro-2h-pyridin-4-yl]benzamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=2CCN(CCC(C)C)CC=2)C=C1 VBSVBVIUPCHCGE-UHFFFAOYSA-N 0.000 claims description 2
- PBYPZUCHLJABPH-UHFFFAOYSA-N n-[5-[2-[2-(methylamino)-2-oxoethyl]-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound CNC(=O)CC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 PBYPZUCHLJABPH-UHFFFAOYSA-N 0.000 claims description 2
- NWTLYGSKNDTPMO-UHFFFAOYSA-N n-[5-[2-[2-(methylamino)-2-oxoethyl]-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-[1-(2-methylpropyl)-3,6-dihydro-2h-pyridin-4-yl]benzamide Chemical compound CNC(=O)CC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(C=2CCN(CC(C)C)CC=2)C=C1 NWTLYGSKNDTPMO-UHFFFAOYSA-N 0.000 claims description 2
- HIPVWNLDIROBHV-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-1-(2-piperidin-1-ylethyl)indole-5-carboxamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C1=CC=C(N(CCN2CCCCC2)C=C2)C2=C1 HIPVWNLDIROBHV-UHFFFAOYSA-N 0.000 claims description 2
- TUTZHFDRKCRPNK-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C)CC1 TUTZHFDRKCRPNK-UHFFFAOYSA-N 0.000 claims description 2
- BKUSKBZVKGZKBV-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-(3-piperidin-1-ylpropoxy)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OCCCN1CCCCC1 BKUSKBZVKGZKBV-UHFFFAOYSA-N 0.000 claims description 2
- HDYYTPBLXMNEAP-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-[(1-propan-2-ylpiperidin-4-yl)methoxy]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OCC1CCN(C(C)C)CC1 HDYYTPBLXMNEAP-UHFFFAOYSA-N 0.000 claims description 2
- WNNJKZIMJHMIGW-UHFFFAOYSA-N n-[5-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]-4-[(1-propan-2-ylpiperidin-4-yl)oxymethyl]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1COC1CCN(C(C)C)CC1 WNNJKZIMJHMIGW-UHFFFAOYSA-N 0.000 claims description 2
- OHVNNYYCXSZMRM-UHFFFAOYSA-N n-[5-[4-(dimethylaminocarbamoylamino)-2-[2-(methylamino)-2-oxoethyl]phenoxy]-1,3-thiazol-2-yl]-4-(1-propan-2-ylpiperidin-4-yl)oxybenzamide Chemical compound CNC(=O)CC1=CC(NC(=O)NN(C)C)=CC=C1OC(S1)=CN=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C(C)C)CC1 OHVNNYYCXSZMRM-UHFFFAOYSA-N 0.000 claims description 2
- DLHJFHSTADOJAO-UHFFFAOYSA-N n-methyl-5-(pentan-3-ylcarbamoylamino)-2-[4-[[4-(3-piperidin-1-ylpropoxy)benzoyl]amino]phenoxy]benzamide Chemical compound CNC(=O)C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OCCCN1CCCCC1 DLHJFHSTADOJAO-UHFFFAOYSA-N 0.000 claims description 2
- ZNARRPWDMYHQIE-UHFFFAOYSA-N pentan-3-ylcarbamic acid Chemical compound CCC(CC)NC(O)=O ZNARRPWDMYHQIE-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- LRTVIXSGIOJJGY-UHFFFAOYSA-N 1-[4-(4-aminophenoxy)-2,5-difluorophenyl]-3-pentan-3-ylurea Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC(F)=C1OC1=CC=C(N)C=C1 LRTVIXSGIOJJGY-UHFFFAOYSA-N 0.000 claims 1
- NIFBNIANYCOETB-UHFFFAOYSA-N 8-methyl-n-(2-phenylethyl)-8-azabicyclo[3.2.1]octan-3-amine Chemical compound CN1C(C2)CCC1CC2NCCC1=CC=CC=C1 NIFBNIANYCOETB-UHFFFAOYSA-N 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- BPGXUIVWLQTVLZ-OFGSCBOVSA-N neuropeptide y(npy) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 BPGXUIVWLQTVLZ-OFGSCBOVSA-N 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 4
- 230000036541 health Effects 0.000 abstract description 2
- 210000001428 peripheral nervous system Anatomy 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 295
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 235
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 234
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 147
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 146
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 132
- 238000007429 general method Methods 0.000 description 118
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
- 239000012044 organic layer Substances 0.000 description 95
- 239000002904 solvent Substances 0.000 description 80
- 150000001412 amines Chemical class 0.000 description 79
- 239000012429 reaction media Substances 0.000 description 77
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000000377 silicon dioxide Substances 0.000 description 66
- 238000004587 chromatography analysis Methods 0.000 description 65
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 239000000543 intermediate Substances 0.000 description 53
- 229910000104 sodium hydride Inorganic materials 0.000 description 53
- 239000000843 powder Substances 0.000 description 52
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 46
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 45
- 239000002244 precipitate Substances 0.000 description 45
- 238000010992 reflux Methods 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 40
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 36
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 35
- 239000002253 acid Substances 0.000 description 35
- 239000007864 aqueous solution Substances 0.000 description 32
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 31
- 150000002148 esters Chemical class 0.000 description 31
- 239000011734 sodium Substances 0.000 description 31
- 239000000725 suspension Substances 0.000 description 31
- 229960004132 diethyl ether Drugs 0.000 description 30
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 29
- 239000002609 medium Substances 0.000 description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 27
- 229960000583 acetic acid Drugs 0.000 description 25
- 150000001735 carboxylic acids Chemical class 0.000 description 25
- 230000008569 process Effects 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
- 235000011054 acetic acid Nutrition 0.000 description 23
- 239000005711 Benzoic acid Substances 0.000 description 22
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 21
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 21
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 230000002378 acidificating effect Effects 0.000 description 19
- 229910052801 chlorine Inorganic materials 0.000 description 19
- 230000007062 hydrolysis Effects 0.000 description 19
- 238000006460 hydrolysis reaction Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 238000000746 purification Methods 0.000 description 18
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 17
- 150000001408 amides Chemical class 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 239000011780 sodium chloride Substances 0.000 description 17
- 150000001414 amino alcohols Chemical class 0.000 description 16
- 125000003277 amino group Chemical group 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 14
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 239000012948 isocyanate Substances 0.000 description 14
- 150000002825 nitriles Chemical class 0.000 description 14
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 13
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- XFDCNXIWKCIBAE-UHFFFAOYSA-N 5-bromo-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.NC1=NC=C(Br)S1 XFDCNXIWKCIBAE-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 241000219098 Parthenocissus Species 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 10
- LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- 150000002513 isocyanates Chemical class 0.000 description 10
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 10
- 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 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RLKMOPWWGZKHOP-UHFFFAOYSA-N 1-butylpiperidin-4-ol Chemical compound CCCCN1CCC(O)CC1 RLKMOPWWGZKHOP-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- 238000007126 N-alkylation reaction Methods 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 238000006268 reductive amination reaction Methods 0.000 description 8
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 8
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 7
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 150000003840 hydrochlorides Chemical group 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000006751 Mitsunobu reaction Methods 0.000 description 6
- XMLNCADGRIEXPK-KUMOIWDRSA-M chembl2146143 Chemical compound [Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N+]2(C)C)C(=O)C(CO)C1=CC=CC=C1 XMLNCADGRIEXPK-KUMOIWDRSA-M 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 6
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 239000012317 TBTU Substances 0.000 description 5
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000004985 diamines Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000002198 insoluble material Substances 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 150000003573 thiols Chemical class 0.000 description 5
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- LORCRQGJKOFOAW-UHFFFAOYSA-N 4-(1-propan-2-yl-3,6-dihydro-2h-pyridin-4-yl)benzoic acid Chemical compound C1N(C(C)C)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 LORCRQGJKOFOAW-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- RCGAINRPVXLUMU-UHFFFAOYSA-N 4-[1-(2-methylpropyl)-3,6-dihydro-2h-pyridin-4-yl]benzoic acid Chemical compound C1N(CC(C)C)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 RCGAINRPVXLUMU-UHFFFAOYSA-N 0.000 description 4
- 125000006847 BOC protecting group Chemical group 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 229940095102 methyl benzoate Drugs 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- VBEGHXKAFSLLGE-UHFFFAOYSA-N n-phenylnitramide Chemical compound [O-][N+](=O)NC1=CC=CC=C1 VBEGHXKAFSLLGE-UHFFFAOYSA-N 0.000 description 4
- 108010043412 neuropeptide Y-Y1 receptor Proteins 0.000 description 4
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- OOQAIRKHRAVJTC-UHFFFAOYSA-N 1-[4-(4-aminophenoxy)-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(N)C=C1 OOQAIRKHRAVJTC-UHFFFAOYSA-N 0.000 description 3
- HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 3
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- NLWMCEWGWBQMGO-UHFFFAOYSA-N 4-(3-piperidin-1-ylpropanoylamino)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)CCN1CCCCC1 NLWMCEWGWBQMGO-UHFFFAOYSA-N 0.000 description 3
- ALOPORHTRKLOQZ-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropanoyl)amino]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(CC)C(=O)CCN1CCCCC1 ALOPORHTRKLOQZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 102000016267 Leptin Human genes 0.000 description 3
- 108010092277 Leptin Proteins 0.000 description 3
- 108090000189 Neuropeptides Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 3
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 3
- 229940039781 leptin Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- ITTMCTUWHMLWKK-UHFFFAOYSA-N n-pentan-3-ylimidazole-1-carboxamide Chemical compound CCC(CC)NC(=O)N1C=CN=C1 ITTMCTUWHMLWKK-UHFFFAOYSA-N 0.000 description 3
- RBXVOQPAMPBADW-UHFFFAOYSA-N nitrous acid;phenol Chemical class ON=O.OC1=CC=CC=C1 RBXVOQPAMPBADW-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- CCVYRRGZDBSHFU-UHFFFAOYSA-N (2-hydroxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1O CCVYRRGZDBSHFU-UHFFFAOYSA-N 0.000 description 2
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- DRRVROVYLJHJIV-UHFFFAOYSA-N 1,4-diazepan-2-one Chemical compound O=C1CNCCCN1 DRRVROVYLJHJIV-UHFFFAOYSA-N 0.000 description 2
- QPPLBCQXWDBQFS-UHFFFAOYSA-N 1,4-diazepan-5-one Chemical compound O=C1CCNCCN1 QPPLBCQXWDBQFS-UHFFFAOYSA-N 0.000 description 2
- WNRWEBKEQARBKV-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine Chemical compound ClCCN1CCCCC1 WNRWEBKEQARBKV-UHFFFAOYSA-N 0.000 description 2
- UQRFAQXJVKHIQU-UHFFFAOYSA-N 1-[3-(methoxymethyl)-4-[[2-(methylamino)-1,3-thiazol-5-yl]oxy]phenyl]-3-pentan-3-ylurea Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(NC)S1 UQRFAQXJVKHIQU-UHFFFAOYSA-N 0.000 description 2
- ZLDAZBBIBPTRSY-UHFFFAOYSA-N 1-[4-(4-aminophenoxy)-3-ethoxyphenyl]-3-pentan-3-ylurea Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(N)C=C1 ZLDAZBBIBPTRSY-UHFFFAOYSA-N 0.000 description 2
- VKDJDQIOQWQWNQ-UHFFFAOYSA-N 1-[4-[(2-amino-1,3-thiazol-5-yl)oxy]-3-(ethoxymethyl)phenyl]-3-pentan-3-ylurea Chemical compound CCOCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 VKDJDQIOQWQWNQ-UHFFFAOYSA-N 0.000 description 2
- PXUHTAAKWRBEMY-UHFFFAOYSA-N 1-[4-[(2-amino-1,3-thiazol-5-yl)oxy]-3-(methoxymethyl)phenyl]-3-pentan-3-ylurea Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 PXUHTAAKWRBEMY-UHFFFAOYSA-N 0.000 description 2
- FGNDVVPJJQQZNP-UHFFFAOYSA-N 1-[4-[(2-amino-1,3-thiazol-5-yl)oxy]-3-fluorophenyl]-3-pentan-3-ylurea Chemical compound FC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 FGNDVVPJJQQZNP-UHFFFAOYSA-N 0.000 description 2
- OWIPHPMLCHOHHX-UHFFFAOYSA-N 1-[4-[(2-amino-1,3-thiazol-5-yl)oxy]-3-methoxyphenyl]-3-pentan-3-ylurea Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 OWIPHPMLCHOHHX-UHFFFAOYSA-N 0.000 description 2
- KSWJYZMVIAXPHC-UHFFFAOYSA-N 1-[4-[(2-amino-1,3-thiazol-5-yl)oxy]phenyl]-3-pentan-3-ylurea Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 KSWJYZMVIAXPHC-UHFFFAOYSA-N 0.000 description 2
- QVUNMWQRCFABKL-UHFFFAOYSA-N 1-propan-2-ylpiperidin-3-ol Chemical compound CC(C)N1CCCC(O)C1 QVUNMWQRCFABKL-UHFFFAOYSA-N 0.000 description 2
- UZRXHHMTKCJKTQ-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-ol Chemical compound CC(C)N1CCC(O)CC1 UZRXHHMTKCJKTQ-UHFFFAOYSA-N 0.000 description 2
- VDVUCLWJZJHFAV-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidin-4-ol Chemical compound CC1(C)CC(O)CC(C)(C)N1 VDVUCLWJZJHFAV-UHFFFAOYSA-N 0.000 description 2
- LJFDXXUKKMEQKE-UHFFFAOYSA-N 2,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C(F)=C1 LJFDXXUKKMEQKE-UHFFFAOYSA-N 0.000 description 2
- IZLVFLOBTPURLP-UHFFFAOYSA-N 2-Methoxy-4-nitrophenol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1O IZLVFLOBTPURLP-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- HIFCFBDBBPTLHZ-UHFFFAOYSA-N 2-[2-[(2-amino-1,3-thiazol-5-yl)oxy]-5-(dimethylaminocarbamoylamino)phenyl]-n-methylacetamide Chemical compound CNC(=O)CC1=CC(NC(=O)NN(C)C)=CC=C1OC1=CN=C(N)S1 HIFCFBDBBPTLHZ-UHFFFAOYSA-N 0.000 description 2
- LXTKXPZKNACKNN-UHFFFAOYSA-N 2-[2-[(2-amino-1,3-thiazol-5-yl)oxy]-5-(pentan-3-ylcarbamoylamino)phenyl]-n-methylacetamide Chemical compound CNC(=O)CC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(N)S1 LXTKXPZKNACKNN-UHFFFAOYSA-N 0.000 description 2
- SJWOKHWEUNAYEB-UHFFFAOYSA-N 2-[5-amino-2-[(2-amino-1,3-thiazol-5-yl)oxy]phenyl]-n-methylacetamide Chemical compound CNC(=O)CC1=CC(N)=CC=C1OC1=CN=C(N)S1 SJWOKHWEUNAYEB-UHFFFAOYSA-N 0.000 description 2
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 2
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 2
- BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 description 2
- LGXRMVZWNFRXKU-UHFFFAOYSA-N 3-(1-propan-2-ylpiperidin-3-yl)oxybenzoic acid Chemical compound C1N(C(C)C)CCCC1OC1=CC=CC(C(O)=O)=C1 LGXRMVZWNFRXKU-UHFFFAOYSA-N 0.000 description 2
- XLNPWNBHHIYBJZ-UHFFFAOYSA-N 3-(1-propan-2-ylpiperidin-4-yl)oxybenzoic acid Chemical compound C1CN(C(C)C)CCC1OC1=CC=CC(C(O)=O)=C1 XLNPWNBHHIYBJZ-UHFFFAOYSA-N 0.000 description 2
- MMXLEHHVXPFOLC-UHFFFAOYSA-N 3-acetyl-1-(2-piperidin-1-ylethyl)indole-5-carboxylic acid Chemical compound C12=CC=C(C(O)=O)C=C2C(C(=O)C)=CN1CCN1CCCCC1 MMXLEHHVXPFOLC-UHFFFAOYSA-N 0.000 description 2
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 2
- JZTPKAROPNTQQV-UHFFFAOYSA-N 3-fluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1 JZTPKAROPNTQQV-UHFFFAOYSA-N 0.000 description 2
- PYCPZTVDHIIFOK-UHFFFAOYSA-N 3-methyl-1-(2-piperidin-1-ylethyl)indole-5-carboxylic acid Chemical compound C12=CC=C(C(O)=O)C=C2C(C)=CN1CCN1CCCCC1 PYCPZTVDHIIFOK-UHFFFAOYSA-N 0.000 description 2
- JMUCXULQKPWSTJ-UHFFFAOYSA-N 3-piperidin-1-ylpropan-1-amine Chemical compound NCCCN1CCCCC1 JMUCXULQKPWSTJ-UHFFFAOYSA-N 0.000 description 2
- CZJKSRMVKZIVJL-UHFFFAOYSA-N 4-(1,2,2,6,6-pentamethylpiperidin-4-yl)oxybenzoic acid Chemical compound C1C(C)(C)N(C)C(C)(C)CC1OC1=CC=C(C(O)=O)C=C1 CZJKSRMVKZIVJL-UHFFFAOYSA-N 0.000 description 2
- WGZBIAAOXBTSNA-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 WGZBIAAOXBTSNA-UHFFFAOYSA-N 0.000 description 2
- SWXJPLGPVKMHOA-UHFFFAOYSA-N 4-(1-butyl-3,6-dihydro-2h-pyridin-4-yl)benzoic acid Chemical compound C1N(CCCC)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 SWXJPLGPVKMHOA-UHFFFAOYSA-N 0.000 description 2
- CXXKSSZINLHORZ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2-fluorobenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C(F)=C1 CXXKSSZINLHORZ-UHFFFAOYSA-N 0.000 description 2
- OXETXZTTXHAKRF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3,5-dimethylbenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=C(C)C=C(C(O)=O)C=C1C OXETXZTTXHAKRF-UHFFFAOYSA-N 0.000 description 2
- YJMSTQGSNFDZDT-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-(trifluoromethyl)benzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1C(F)(F)F YJMSTQGSNFDZDT-UHFFFAOYSA-N 0.000 description 2
- FHYTWXCSETVTPH-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-chlorobenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1Cl FHYTWXCSETVTPH-UHFFFAOYSA-N 0.000 description 2
- YUGQUABPVKZCCT-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-fluorobenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1F YUGQUABPVKZCCT-UHFFFAOYSA-N 0.000 description 2
- VRSLOTGXAWCYTJ-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methoxybenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1OC VRSLOTGXAWCYTJ-UHFFFAOYSA-N 0.000 description 2
- HOCNOHDJIGWLEV-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methylbenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1C HOCNOHDJIGWLEV-UHFFFAOYSA-N 0.000 description 2
- IMZLQNNTPYFSKP-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxybenzoic acid Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(O)=O)C=C1 IMZLQNNTPYFSKP-UHFFFAOYSA-N 0.000 description 2
- OXRWDFFTZLWACC-UHFFFAOYSA-N 4-(1-ethyl-3,6-dihydro-2h-pyridin-4-yl)benzoic acid Chemical compound C1N(CC)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 OXRWDFFTZLWACC-UHFFFAOYSA-N 0.000 description 2
- BRAPKFOBEYNFNC-UHFFFAOYSA-N 4-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)benzoic acid Chemical compound C1N(C)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 BRAPKFOBEYNFNC-UHFFFAOYSA-N 0.000 description 2
- YBVIJDLPKKTZBO-UHFFFAOYSA-N 4-(1-methylpiperidin-1-ium-4-yl)oxybenzoate Chemical compound C1CN(C)CCC1OC1=CC=C(C(O)=O)C=C1 YBVIJDLPKKTZBO-UHFFFAOYSA-N 0.000 description 2
- CNJCLJDNQQCZOT-UHFFFAOYSA-N 4-(1-propan-2-ylpiperidin-3-yl)oxybenzoic acid Chemical compound C1N(C(C)C)CCCC1OC1=CC=C(C(O)=O)C=C1 CNJCLJDNQQCZOT-UHFFFAOYSA-N 0.000 description 2
- NATRHQIYBAERJK-UHFFFAOYSA-N 4-(1-propan-2-ylpiperidin-4-yl)benzoic acid Chemical compound C1CN(C(C)C)CCC1C1=CC=C(C(O)=O)C=C1 NATRHQIYBAERJK-UHFFFAOYSA-N 0.000 description 2
- JLCNNCNFTBWQKK-UHFFFAOYSA-N 4-(1-propan-2-ylpiperidin-4-yl)oxybenzoic acid Chemical compound C1CN(C(C)C)CCC1OC1=CC=C(C(O)=O)C=C1 JLCNNCNFTBWQKK-UHFFFAOYSA-N 0.000 description 2
- CPLAWFIYLZIJLR-UHFFFAOYSA-N 4-(1-propan-2-ylpyrrolidin-3-yl)oxybenzoic acid Chemical compound C1N(C(C)C)CCC1OC1=CC=C(C(O)=O)C=C1 CPLAWFIYLZIJLR-UHFFFAOYSA-N 0.000 description 2
- CJSMVZJPUIFLFV-UHFFFAOYSA-N 4-(1-propyl-3,6-dihydro-2h-pyridin-4-yl)benzoic acid Chemical compound C1N(CCC)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 CJSMVZJPUIFLFV-UHFFFAOYSA-N 0.000 description 2
- DVQVEWCHSJTLSQ-UHFFFAOYSA-N 4-(2,2,6,6-tetramethylpiperidin-4-yl)oxybenzoic acid Chemical compound C1C(C)(C)NC(C)(C)CC1OC1=CC=C(C(O)=O)C=C1 DVQVEWCHSJTLSQ-UHFFFAOYSA-N 0.000 description 2
- ONYUPIAZASQLKZ-UHFFFAOYSA-N 4-(3-piperidin-1-ium-1-ylpropoxy)benzoate Chemical compound C1=CC(C(=O)O)=CC=C1OCCCN1CCCCC1 ONYUPIAZASQLKZ-UHFFFAOYSA-N 0.000 description 2
- RMQIMIMWZXIZRT-UHFFFAOYSA-N 4-(4-ethylpiperazine-1-carbonyl)benzoic acid Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(C(O)=O)C=C1 RMQIMIMWZXIZRT-UHFFFAOYSA-N 0.000 description 2
- CZGCEKJOLUNIFY-UHFFFAOYSA-N 4-Chloronitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1 CZGCEKJOLUNIFY-UHFFFAOYSA-N 0.000 description 2
- HNUZJZKETFHTIR-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-3-yl)methoxy]benzoic acid Chemical compound C1N(C(C)C)CCCC1COC1=CC=C(C(O)=O)C=C1 HNUZJZKETFHTIR-UHFFFAOYSA-N 0.000 description 2
- QZZBQZCRXXTZGK-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-4-yl)methoxy]benzoic acid Chemical compound C1CN(C(C)C)CCC1COC1=CC=C(C(O)=O)C=C1 QZZBQZCRXXTZGK-UHFFFAOYSA-N 0.000 description 2
- FBANHWICHLHWGJ-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-4-yl)oxymethyl]benzoic acid Chemical compound C1CN(C(C)C)CCC1OCC1=CC=C(C(O)=O)C=C1 FBANHWICHLHWGJ-UHFFFAOYSA-N 0.000 description 2
- RFBDIXRPZGZLIP-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-4-ylidene)methyl]benzoic acid Chemical compound C1CN(C(C)C)CCC1=CC1=CC=C(C(O)=O)C=C1 RFBDIXRPZGZLIP-UHFFFAOYSA-N 0.000 description 2
- UXIRSUMMKWNXPA-UHFFFAOYSA-N 4-[(8-methyl-8-azabicyclo[3.2.1]octan-6-yl)oxy]benzoic acid Chemical compound C1CCC2N(C)C1CC2OC1=CC=C(C(O)=O)C=C1 UXIRSUMMKWNXPA-UHFFFAOYSA-N 0.000 description 2
- UTSBREMSFADHKZ-UHFFFAOYSA-N 4-[1-(3-methylbutyl)-3,6-dihydro-2h-pyridin-4-yl]benzoic acid Chemical compound C1N(CCC(C)C)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 UTSBREMSFADHKZ-UHFFFAOYSA-N 0.000 description 2
- AOAMBGASPANNJI-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)acetyl]-3,6-dihydro-2h-pyridin-4-yl]benzoic acid Chemical compound C1N(C(=O)CN(C)C)CCC(C=2C=CC(=CC=2)C(O)=O)=C1 AOAMBGASPANNJI-UHFFFAOYSA-N 0.000 description 2
- NYQKDWXYXIDQRS-UHFFFAOYSA-N 4-[3-(4-hydroxypiperidin-1-yl)propoxy]benzoic acid Chemical compound C1CC(O)CCN1CCCOC1=CC=C(C(O)=O)C=C1 NYQKDWXYXIDQRS-UHFFFAOYSA-N 0.000 description 2
- HIRAZRRAGLIWHK-UHFFFAOYSA-N 4-[4-(4,4-dimethyl-5h-1,3-oxazol-2-yl)phenyl]-1-propan-2-ylpiperidin-4-ol Chemical compound C1CN(C(C)C)CCC1(O)C1=CC=C(C=2OCC(C)(C)N=2)C=C1 HIRAZRRAGLIWHK-UHFFFAOYSA-N 0.000 description 2
- KHIMSQFYYIIJFX-UHFFFAOYSA-N 4-[acetyl(2-piperidin-1-ylethyl)amino]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(C(=O)C)CCN1CCCCC1 KHIMSQFYYIIJFX-UHFFFAOYSA-N 0.000 description 2
- KMOHDMVHQUKABT-UHFFFAOYSA-N 4-[acetyl(3-piperidin-1-ylpropyl)amino]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(C(=O)C)CCCN1CCCCC1 KMOHDMVHQUKABT-UHFFFAOYSA-N 0.000 description 2
- WDIWLOIPGJBQGH-UHFFFAOYSA-N 4-[acetyl-[3-(diethylamino)propyl]amino]benzoic acid Chemical compound CCN(CC)CCCN(C(C)=O)C1=CC=C(C(O)=O)C=C1 WDIWLOIPGJBQGH-UHFFFAOYSA-N 0.000 description 2
- XWEFLVRUYVCAIK-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropyl)amino]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(CC)CCCN1CCCCC1 XWEFLVRUYVCAIK-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 2
- 206010059109 Cerebral vasoconstriction Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 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
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 102100029549 Neuropeptide Y receptor type 5 Human genes 0.000 description 2
- 101710198055 Neuropeptide Y receptor type 5 Proteins 0.000 description 2
- 102000029748 Neuropeptide Y2 receptor Human genes 0.000 description 2
- 108010002245 Neuropeptide Y4 receptor Proteins 0.000 description 2
- 102000028435 Neuropeptide Y4 receptor Human genes 0.000 description 2
- 102000003797 Neuropeptides Human genes 0.000 description 2
- 102100029909 Peptide YY Human genes 0.000 description 2
- 108010088847 Peptide YY Proteins 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000004130 lipolysis Effects 0.000 description 2
- 239000007788 liquid Substances 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
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- AZXBCGCDZNGESQ-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-(1-methylpiperidin-4-yl)oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C)CC1 AZXBCGCDZNGESQ-UHFFFAOYSA-N 0.000 description 2
- 108010089579 neuropeptide Y2 receptor Proteins 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- RPVOKBZITVQZPD-UHFFFAOYSA-N phenol;hydroiodide Chemical compound I.OC1=CC=CC=C1 RPVOKBZITVQZPD-UHFFFAOYSA-N 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- VBSNVDGIHSXRKJ-UHFFFAOYSA-N pyrrolidine-2,5-dione;hydroiodide Chemical compound I.O=C1CCC(=O)N1 VBSNVDGIHSXRKJ-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000011894 semi-preparative HPLC Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000012799 strong cation exchange Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 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 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- HCPNCTDXIJYEEV-UHFFFAOYSA-N (2-hydroxy-5-nitrophenyl)methyl acetate Chemical compound CC(=O)OCC1=CC([N+]([O-])=O)=CC=C1O HCPNCTDXIJYEEV-UHFFFAOYSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical class C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NWHNXXMYEICZAT-UHFFFAOYSA-N 1,2,2,6,6-pentamethylpiperidin-4-ol Chemical compound CN1C(C)(C)CC(O)CC1(C)C NWHNXXMYEICZAT-UHFFFAOYSA-N 0.000 description 1
- RNYCGIOXRWNPLF-UHFFFAOYSA-N 1,2,6-trimethylpiperidin-4-ol Chemical compound CC1CC(O)CC(C)N1C RNYCGIOXRWNPLF-UHFFFAOYSA-N 0.000 description 1
- KXVUMEAPZKTOCS-UHFFFAOYSA-N 1,2,6-trimethylpyridin-4-one Chemical compound CC1=CC(=O)C=C(C)N1C KXVUMEAPZKTOCS-UHFFFAOYSA-N 0.000 description 1
- DTYUTSMRCQYVNW-UHFFFAOYSA-N 1,2-diethoxy-4-nitrobenzene Chemical compound CCOC1=CC=C([N+]([O-])=O)C=C1OCC DTYUTSMRCQYVNW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- JYGFTBXVXVMTGB-HOSYLAQJSA-N 1,3-dihydroindol-2-one Chemical group N1C([13CH2]C2=CC=CC=C12)=O JYGFTBXVXVMTGB-HOSYLAQJSA-N 0.000 description 1
- QDVBKXJMLILLLB-UHFFFAOYSA-N 1,4'-bipiperidine Chemical compound C1CCCCN1C1CCNCC1 QDVBKXJMLILLLB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IRVWBMPPWDTJQQ-UHFFFAOYSA-N 1-(1-butylpiperidin-4-yl)-n-[4-[2,5-difluoro-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]indole-5-carboxamide Chemical compound C1CN(CCCC)CCC1N1C2=CC=C(C(=O)NC=3C=CC(OC=4C(=CC(NC(=O)NC(CC)CC)=C(F)C=4)F)=CC=3)C=C2C=C1 IRVWBMPPWDTJQQ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- CKEUUGMTHYIYHY-UHFFFAOYSA-N 1-[3-ethoxy-4-(4-nitrophenoxy)phenyl]-3-pentan-3-ylurea Chemical compound CCOC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 CKEUUGMTHYIYHY-UHFFFAOYSA-N 0.000 description 1
- IGPVIMKZOZZMFB-UHFFFAOYSA-N 1-[3-methoxy-4-(4-nitrophenoxy)phenyl]-3-pentan-3-ylurea Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 IGPVIMKZOZZMFB-UHFFFAOYSA-N 0.000 description 1
- NHRLTNXCRHLTGB-UHFFFAOYSA-N 1-[3-methyl-4-(4-nitrophenoxy)phenyl]-3-pentan-3-ylurea Chemical compound CC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 NHRLTNXCRHLTGB-UHFFFAOYSA-N 0.000 description 1
- UHCIQEQHWXDUDG-UHFFFAOYSA-N 1-[4-(4-aminophenoxy)-3-methylphenyl]-3-pentan-3-ylurea Chemical compound CC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(N)C=C1 UHCIQEQHWXDUDG-UHFFFAOYSA-N 0.000 description 1
- OKFKZFOGPOJHJK-UHFFFAOYSA-N 1-benzyl-4-[4-(4,4-dimethyl-5h-1,3-oxazol-2-yl)phenyl]piperidin-4-ol Chemical compound CC1(C)COC(C=2C=CC(=CC=2)C2(O)CCN(CC=3C=CC=CC=3)CC2)=N1 OKFKZFOGPOJHJK-UHFFFAOYSA-N 0.000 description 1
- MLEGMEBCXGDFQT-UHFFFAOYSA-N 1-benzylpiperidin-2-one Chemical compound O=C1CCCCN1CC1=CC=CC=C1 MLEGMEBCXGDFQT-UHFFFAOYSA-N 0.000 description 1
- BPPZXJZYCOETDA-UHFFFAOYSA-N 1-benzylpiperidin-4-ol Chemical compound C1CC(O)CCN1CC1=CC=CC=C1 BPPZXJZYCOETDA-UHFFFAOYSA-N 0.000 description 1
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- NXLYPGKGCCBVFW-UHFFFAOYSA-N 1-but-3-ynylpiperidin-4-ol Chemical compound OC1CCN(CCC#C)CC1 NXLYPGKGCCBVFW-UHFFFAOYSA-N 0.000 description 1
- JXIJUAWSDBACEB-UHFFFAOYSA-N 1-chloro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1Cl JXIJUAWSDBACEB-UHFFFAOYSA-N 0.000 description 1
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
- GVDQKJQFVPXADH-UHFFFAOYSA-N 1-propan-2-ylpiperidin-2-one Chemical compound CC(C)N1CCCCC1=O GVDQKJQFVPXADH-UHFFFAOYSA-N 0.000 description 1
- MYFPIRLHESHOGR-UHFFFAOYSA-N 1-propan-2-ylpyrrolidin-3-ol Chemical compound CC(C)N1CCC(O)C1 MYFPIRLHESHOGR-UHFFFAOYSA-N 0.000 description 1
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 1
- GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- WXFWXFIWDGJRSC-UHFFFAOYSA-N 2,5-dimethoxy-2,5-dihydrofuran Chemical compound COC1OC(OC)C=C1 WXFWXFIWDGJRSC-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- PFCAGOJIMITPRX-UHFFFAOYSA-N 2-(2-hydroxy-5-nitrophenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC([N+]([O-])=O)=CC=C1O PFCAGOJIMITPRX-UHFFFAOYSA-N 0.000 description 1
- ORXCFNAIXBBSJC-UHFFFAOYSA-N 2-(2-hydroxy-5-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC([N+]([O-])=O)=CC=C1O ORXCFNAIXBBSJC-UHFFFAOYSA-N 0.000 description 1
- GXWMQSSSRSHOBL-UHFFFAOYSA-N 2-(4-bromophenyl)-4,4-dimethyl-5h-1,3-oxazole Chemical compound CC1(C)COC(C=2C=CC(Br)=CC=2)=N1 GXWMQSSSRSHOBL-UHFFFAOYSA-N 0.000 description 1
- YLHCMDNAKVPTIO-UHFFFAOYSA-N 2-(4-hydroxycyclohexyl)isoindole-1,3-dione Chemical compound C1CC(O)CCC1N1C(=O)C2=CC=CC=C2C1=O YLHCMDNAKVPTIO-UHFFFAOYSA-N 0.000 description 1
- KFDPCYZHENQOBV-UHFFFAOYSA-N 2-(bromomethyl)-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1CBr KFDPCYZHENQOBV-UHFFFAOYSA-N 0.000 description 1
- PJNPZIYGODMAQE-UHFFFAOYSA-N 2-(chloromethyl)-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1CCl PJNPZIYGODMAQE-UHFFFAOYSA-N 0.000 description 1
- UIOXRCWGBSZXPM-UHFFFAOYSA-N 2-(ethoxymethyl)-4-nitrophenol Chemical compound CCOCC1=CC([N+]([O-])=O)=CC=C1O UIOXRCWGBSZXPM-UHFFFAOYSA-N 0.000 description 1
- LDKUCBVEAIZHKZ-UHFFFAOYSA-N 2-(methoxymethyl)-4-nitrophenol Chemical compound COCC1=CC([N+]([O-])=O)=CC=C1O LDKUCBVEAIZHKZ-UHFFFAOYSA-N 0.000 description 1
- CHTTVRGLIODMMD-UHFFFAOYSA-N 2-[2-[(2-amino-1,3-thiazol-5-yl)oxy]-5-nitrophenyl]-n-methylacetamide Chemical compound CNC(=O)CC1=CC([N+]([O-])=O)=CC=C1OC1=CN=C(N)S1 CHTTVRGLIODMMD-UHFFFAOYSA-N 0.000 description 1
- ZNJRONVKWRHYBF-UHFFFAOYSA-N 2-[2-[2-(1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-7-yl)ethenyl]-6-methylpyran-4-ylidene]propanedinitrile Chemical compound O1C(C)=CC(=C(C#N)C#N)C=C1C=CC1=CC(CCCN2CCC3)=C2C3=C1 ZNJRONVKWRHYBF-UHFFFAOYSA-N 0.000 description 1
- JYGPQAFNYZAXJL-UHFFFAOYSA-N 2-[4-[[4-[3-(4-hydroxypiperidin-1-yl)propoxy]benzoyl]amino]phenoxy]-n-methyl-5-(pentan-3-ylcarbamoylamino)benzamide Chemical compound CNC(=O)C1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OCCCN1CCC(O)CC1 JYGPQAFNYZAXJL-UHFFFAOYSA-N 0.000 description 1
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- GIHYKBDWFSOKNN-UHFFFAOYSA-N 2-ethoxy-4-nitrophenol Chemical compound CCOC1=CC([N+]([O-])=O)=CC=C1O GIHYKBDWFSOKNN-UHFFFAOYSA-N 0.000 description 1
- MIOLIKNCVCJTTE-UHFFFAOYSA-N 2-ethyl-4-(1,2,3,6-tetrahydropyridin-4-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C=2CCNCC=2)=C1 MIOLIKNCVCJTTE-UHFFFAOYSA-N 0.000 description 1
- BODCKVXOVCWXJR-UHFFFAOYSA-N 2-ethyl-4-(1-ethyl-4-hydroxypiperidin-4-yl)benzoic acid Chemical compound CCC1=C(C=CC(=C1)C2(CCN(CC2)CC)O)C(=O)O BODCKVXOVCWXJR-UHFFFAOYSA-N 0.000 description 1
- XFVXDBONXISSMP-UHFFFAOYSA-N 2-ethyl-4-(4-hydroxy-1-methylpiperidin-4-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C2(O)CCN(C)CC2)=C1 XFVXDBONXISSMP-UHFFFAOYSA-N 0.000 description 1
- XRJGJQKNHUDKBO-UHFFFAOYSA-N 2-ethyl-4-(4-hydroxy-1-propan-2-ylpiperidin-4-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C2(O)CCN(CC2)C(C)C)=C1 XRJGJQKNHUDKBO-UHFFFAOYSA-N 0.000 description 1
- GMSVYAWPFIZJMF-UHFFFAOYSA-N 2-ethyl-4-(4-hydroxypiperidin-4-yl)benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C2(O)CCNCC2)=C1 GMSVYAWPFIZJMF-UHFFFAOYSA-N 0.000 description 1
- VEOTZKTWFCTBEW-UHFFFAOYSA-N 2-ethyl-4-[1-(2-methylpropyl)-3,6-dihydro-2H-pyridin-4-yl]benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C=2CCN(CC(C)C)CC=2)=C1 VEOTZKTWFCTBEW-UHFFFAOYSA-N 0.000 description 1
- MBDQWOPRTRRDLE-UHFFFAOYSA-N 2-ethyl-4-[1-(3-methylbutyl)-3,6-dihydro-2H-pyridin-4-yl]benzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C=2CCN(CCC(C)C)CC=2)=C1 MBDQWOPRTRRDLE-UHFFFAOYSA-N 0.000 description 1
- KDQPMQNHVQVVMR-UHFFFAOYSA-N 2-methyl-4-nitrophenol Chemical compound CC1=CC([N+]([O-])=O)=CC=C1O KDQPMQNHVQVVMR-UHFFFAOYSA-N 0.000 description 1
- HKHXJOJUZSYKAJ-UHFFFAOYSA-N 2-phenoxy-1,3-thiazole Chemical compound C=1C=CC=CC=1OC1=NC=CS1 HKHXJOJUZSYKAJ-UHFFFAOYSA-N 0.000 description 1
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- BTBFCBQZFMQBNT-UHFFFAOYSA-N 3,4-difluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1F BTBFCBQZFMQBNT-UHFFFAOYSA-N 0.000 description 1
- YWPMKTWUFVOFPL-UHFFFAOYSA-N 3,4-dihydro-2h-isoquinolin-1-one Chemical group C1=CC=C2C(=O)NCCC2=C1 YWPMKTWUFVOFPL-UHFFFAOYSA-N 0.000 description 1
- OUYYUXLTWUIDBX-UHFFFAOYSA-N 3-(1-propan-2-ylpiperidin-3-yl)oxybenzonitrile Chemical compound C1N(C(C)C)CCCC1OC1=CC=CC(C#N)=C1 OUYYUXLTWUIDBX-UHFFFAOYSA-N 0.000 description 1
- ZYGAEJAKOZAGLN-UHFFFAOYSA-N 3-(1-propan-2-ylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(C(C)C)CCC1OC1=CC=CC(C#N)=C1 ZYGAEJAKOZAGLN-UHFFFAOYSA-N 0.000 description 1
- KHEMQWDCWVUZOJ-UHFFFAOYSA-N 3-(3-piperidin-1-ylpropanoylamino)-4-(propan-2-ylamino)benzoic acid Chemical compound CC(C)NC1=CC=C(C(O)=O)C=C1NC(=O)CCN1CCCCC1 KHEMQWDCWVUZOJ-UHFFFAOYSA-N 0.000 description 1
- OXTNCQMOKLOUAM-UHFFFAOYSA-N 3-Oxoglutaric acid Chemical compound OC(=O)CC(=O)CC(O)=O OXTNCQMOKLOUAM-UHFFFAOYSA-N 0.000 description 1
- KLAIOABSDQUNSA-WUKNDPDISA-N 3-[(e)-octadec-2-enyl]oxolane-2,5-dione Chemical compound CCCCCCCCCCCCCCC\C=C\CC1CC(=O)OC1=O KLAIOABSDQUNSA-WUKNDPDISA-N 0.000 description 1
- VGFRRQNUXQDJFF-UHFFFAOYSA-N 3-amino-4-(propan-2-ylamino)benzoic acid Chemical compound CC(C)NC1=CC=C(C(O)=O)C=C1N VGFRRQNUXQDJFF-UHFFFAOYSA-N 0.000 description 1
- VAHXXQJJZKBZDX-UHFFFAOYSA-N 3-chloro-4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1Cl VAHXXQJJZKBZDX-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- SRHBVRTYOXWHLO-UHFFFAOYSA-N 3-ethoxy-4-(4-nitrophenoxy)aniline Chemical compound CCOC1=CC(N)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 SRHBVRTYOXWHLO-UHFFFAOYSA-N 0.000 description 1
- REOVJSWOIBTTBR-UHFFFAOYSA-N 3-methoxy-4-(4-nitrophenoxy)aniline Chemical compound COC1=CC(N)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 REOVJSWOIBTTBR-UHFFFAOYSA-N 0.000 description 1
- SSKRKOBNIFWNDT-UHFFFAOYSA-N 3-methyl-4-(4-nitrophenoxy)aniline Chemical compound CC1=CC(N)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 SSKRKOBNIFWNDT-UHFFFAOYSA-N 0.000 description 1
- YHKWFDPEASWKFQ-UHFFFAOYSA-N 3-nitrobenzene-1,2-diol Chemical compound OC1=CC=CC([N+]([O-])=O)=C1O YHKWFDPEASWKFQ-UHFFFAOYSA-N 0.000 description 1
- LPDGWMLCUHULJF-UHFFFAOYSA-N 3-piperidin-1-ylpropanoic acid Chemical compound OC(=O)CCN1CCCCC1 LPDGWMLCUHULJF-UHFFFAOYSA-N 0.000 description 1
- UCKPDEJTQRIACH-UHFFFAOYSA-N 3-piperidin-1-ylpropanoyl chloride Chemical compound ClC(=O)CCN1CCCCC1 UCKPDEJTQRIACH-UHFFFAOYSA-N 0.000 description 1
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 1
- YBRVSVVVWCFQMG-UHFFFAOYSA-N 4,4'-diaminodiphenylmethane Chemical compound C1=CC(N)=CC=C1CC1=CC=C(N)C=C1 YBRVSVVVWCFQMG-UHFFFAOYSA-N 0.000 description 1
- ARFXPEOGQYPXLK-UHFFFAOYSA-N 4-(1,2,2,6,6-pentamethylpiperidin-4-yl)oxybenzonitrile Chemical compound C1C(C)(C)N(C)C(C)(C)CC1OC1=CC=C(C#N)C=C1 ARFXPEOGQYPXLK-UHFFFAOYSA-N 0.000 description 1
- QVBKFHQRUZULHH-UHFFFAOYSA-N 4-(1-benzyl-4-hydroxypiperidin-4-yl)-2-ethylbenzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C2(O)CCN(CC=3C=CC=CC=3)CC2)=C1 QVBKFHQRUZULHH-UHFFFAOYSA-N 0.000 description 1
- IEEZVCRNLGJRHW-UHFFFAOYSA-N 4-(1-benzylpiperidin-4-yl)oxybenzonitrile Chemical compound C1=CC(C#N)=CC=C1OC1CCN(CC=2C=CC=CC=2)CC1 IEEZVCRNLGJRHW-UHFFFAOYSA-N 0.000 description 1
- QTGOIJPVQRGVSU-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-2-fluorobenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C(F)=C1 QTGOIJPVQRGVSU-UHFFFAOYSA-N 0.000 description 1
- MUIKFPDCYJHKJP-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3,5-dimethylbenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=C(C)C=C(C#N)C=C1C MUIKFPDCYJHKJP-UHFFFAOYSA-N 0.000 description 1
- XLZVNLMZRCRARW-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-(trifluoromethyl)benzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1C(F)(F)F XLZVNLMZRCRARW-UHFFFAOYSA-N 0.000 description 1
- WUUXMMAPNXJEEG-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-chlorobenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1Cl WUUXMMAPNXJEEG-UHFFFAOYSA-N 0.000 description 1
- FNSWQNBGIVBAGD-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-fluorobenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1F FNSWQNBGIVBAGD-UHFFFAOYSA-N 0.000 description 1
- QWWDUHVHSNUGTF-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methoxybenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1OC QWWDUHVHSNUGTF-UHFFFAOYSA-N 0.000 description 1
- ZSXFHGDWTIQMJB-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-3-methylbenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1C ZSXFHGDWTIQMJB-UHFFFAOYSA-N 0.000 description 1
- SYTLJAXMLIVHAI-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-ethoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2,5-difluorobenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC(F)=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OCC)=CC=2)C=C1F SYTLJAXMLIVHAI-UHFFFAOYSA-N 0.000 description 1
- SBGDIVSDVGWZPD-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-3-methylbenzamide Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C(=O)NC=2C=CC(OC=3C(=CC(NC(=O)NC(CC)CC)=CC=3)OC)=CC=2)C=C1C SBGDIVSDVGWZPD-UHFFFAOYSA-N 0.000 description 1
- SVJQSDHWRHYVNM-UHFFFAOYSA-N 4-(1-butylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(CCCC)CCC1OC1=CC=C(C#N)C=C1 SVJQSDHWRHYVNM-UHFFFAOYSA-N 0.000 description 1
- WJSCWKSMRWKRDF-UHFFFAOYSA-N 4-(1-methylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(C)CCC1OC1=CC=C(C#N)C=C1 WJSCWKSMRWKRDF-UHFFFAOYSA-N 0.000 description 1
- BAGPMTKLZXXGBA-UHFFFAOYSA-N 4-(1-propan-2-ylpiperidin-3-yl)oxybenzonitrile Chemical compound C1N(C(C)C)CCCC1OC1=CC=C(C#N)C=C1 BAGPMTKLZXXGBA-UHFFFAOYSA-N 0.000 description 1
- YUULAACUMPOSJE-UHFFFAOYSA-N 4-(1-propan-2-ylpiperidin-4-yl)oxybenzonitrile Chemical compound C1CN(C(C)C)CCC1OC1=CC=C(C#N)C=C1 YUULAACUMPOSJE-UHFFFAOYSA-N 0.000 description 1
- ZPUUCOXERGOOBF-UHFFFAOYSA-N 4-(1-propan-2-ylpyrrolidin-3-yl)oxybenzonitrile Chemical compound C1N(C(C)C)CCC1OC1=CC=C(C#N)C=C1 ZPUUCOXERGOOBF-UHFFFAOYSA-N 0.000 description 1
- OBSXMBPBRLMART-UHFFFAOYSA-N 4-(2,2,6,6-tetramethylpiperidin-4-yl)oxybenzonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1OC1=CC=C(C#N)C=C1 OBSXMBPBRLMART-UHFFFAOYSA-N 0.000 description 1
- MRBFWTDIRYEDBQ-UHFFFAOYSA-N 4-(2-aminoethyl)benzoic acid Chemical compound NCCC1=CC=C(C(O)=O)C=C1 MRBFWTDIRYEDBQ-UHFFFAOYSA-N 0.000 description 1
- YWOJPBOOGGYTTG-UHFFFAOYSA-N 4-(2-piperidin-1-ylethylamino)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NCCN1CCCCC1 YWOJPBOOGGYTTG-UHFFFAOYSA-N 0.000 description 1
- UNUFUEPIZVLMRL-UHFFFAOYSA-N 4-(2-piperidin-1-ylethylamino)benzonitrile Chemical compound C1=CC(C#N)=CC=C1NCCN1CCCCC1 UNUFUEPIZVLMRL-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- NUPCSJZDHMGMBF-UHFFFAOYSA-N 4-(isopropylamino)-3-nitrobenzoic acid Chemical compound CC(C)NC1=CC=C(C(O)=O)C=C1[N+]([O-])=O NUPCSJZDHMGMBF-UHFFFAOYSA-N 0.000 description 1
- WXOIBAGAYFVXRW-UHFFFAOYSA-N 4-(piperidin-3-ylmethoxy)benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCC1CNCCC1 WXOIBAGAYFVXRW-UHFFFAOYSA-N 0.000 description 1
- GOQBRNAQGBAZJE-UHFFFAOYSA-N 4-(piperidin-4-yloxymethyl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1COC1CCNCC1 GOQBRNAQGBAZJE-UHFFFAOYSA-N 0.000 description 1
- ZCQUGRWGTNKYSN-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-3-yl)methoxy]benzonitrile Chemical compound C1N(C(C)C)CCCC1COC1=CC=C(C#N)C=C1 ZCQUGRWGTNKYSN-UHFFFAOYSA-N 0.000 description 1
- LPXJONAKOJTMGH-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-4-yl)methyl]benzoic acid Chemical compound C1CN(C(C)C)CCC1CC1=CC=C(C(O)=O)C=C1 LPXJONAKOJTMGH-UHFFFAOYSA-N 0.000 description 1
- XVCJIKKPNKTUHK-UHFFFAOYSA-N 4-[(1-propan-2-ylpiperidin-4-yl)oxymethyl]benzonitrile Chemical compound C1CN(C(C)C)CCC1OCC1=CC=C(C#N)C=C1 XVCJIKKPNKTUHK-UHFFFAOYSA-N 0.000 description 1
- WJHAOCHDCDWEJY-UHFFFAOYSA-N 4-[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy]benzoic acid Chemical compound CN1C(C2)CCC1CC2OC1=CC=C(C(O)=O)C=C1 WJHAOCHDCDWEJY-UHFFFAOYSA-N 0.000 description 1
- HVAYSUJTZZHPMX-UHFFFAOYSA-N 4-[(8-methyl-8-azabicyclo[3.2.1]octan-6-yl)oxy]benzonitrile Chemical compound C1CCC2N(C)C1CC2OC1=CC=C(C#N)C=C1 HVAYSUJTZZHPMX-UHFFFAOYSA-N 0.000 description 1
- LKYYVFJXHLPLHZ-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)acetyl]-4-hydroxypiperidin-4-yl]-2-ethylbenzoic acid Chemical compound C1=C(C(O)=O)C(CC)=CC(C2(O)CCN(CC2)C(=O)CN(C)C)=C1 LKYYVFJXHLPLHZ-UHFFFAOYSA-N 0.000 description 1
- MAMZBEOJOJVWFU-UHFFFAOYSA-N 4-[1-[3-(dimethylamino)propyl]piperidin-4-yl]oxy-n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-n-(2-methylpropyl)benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(N(CC(C)C)C(=O)C=2C=CC(OC3CCN(CCCN(C)C)CC3)=CC=2)C=C1 MAMZBEOJOJVWFU-UHFFFAOYSA-N 0.000 description 1
- KNGJKKYCJDYVLF-UHFFFAOYSA-N 4-[3-(diethylamino)propylamino]benzoic acid Chemical compound CCN(CC)CCCNC1=CC=C(C(O)=O)C=C1 KNGJKKYCJDYVLF-UHFFFAOYSA-N 0.000 description 1
- DVUPTJCJSARFLV-UHFFFAOYSA-N 4-[3-(diethylamino)propylamino]benzonitrile Chemical compound CCN(CC)CCCNC1=CC=C(C#N)C=C1 DVUPTJCJSARFLV-UHFFFAOYSA-N 0.000 description 1
- PVSUMHGSPSIZBC-UHFFFAOYSA-N 4-[4-(4,4-dimethyl-5h-1,3-oxazol-2-yl)phenyl]-1-(2-methylpropyl)piperidin-4-ol Chemical compound C1CN(CC(C)C)CCC1(O)C1=CC=C(C=2OCC(C)(C)N=2)C=C1 PVSUMHGSPSIZBC-UHFFFAOYSA-N 0.000 description 1
- UNPBISIHDFZSDG-UHFFFAOYSA-N 4-[4-(4,4-dimethyl-5h-1,3-oxazol-2-yl)phenyl]piperidin-4-ol Chemical compound CC1(C)COC(C=2C=CC(=CC=2)C2(O)CCNCC2)=N1 UNPBISIHDFZSDG-UHFFFAOYSA-N 0.000 description 1
- DHQSKHOLUOJDRL-UHFFFAOYSA-N 4-[ethyl(3-piperidin-1-ylpropyl)amino]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1N(CC)CCCN1CCCCC1 DHQSKHOLUOJDRL-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- QTPXHZCTCJPRCZ-UHFFFAOYSA-N 4-bromo-n-(1-hydroxy-2-methylpropan-2-yl)benzamide Chemical compound OCC(C)(C)NC(=O)C1=CC=C(Br)C=C1 QTPXHZCTCJPRCZ-UHFFFAOYSA-N 0.000 description 1
- DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
- SQISNVXBYZWWBC-UHFFFAOYSA-N 4-chloro-3-methylbenzonitrile Chemical compound CC1=CC(C#N)=CC=C1Cl SQISNVXBYZWWBC-UHFFFAOYSA-N 0.000 description 1
- CQZQCORFYSSCFY-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(C#N)C=C1C(F)(F)F CQZQCORFYSSCFY-UHFFFAOYSA-N 0.000 description 1
- BOJWTAQWPVBIPG-UHFFFAOYSA-N 4-fluoro-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C([N+]([O-])=O)=C1 BOJWTAQWPVBIPG-UHFFFAOYSA-N 0.000 description 1
- WFYGXOWFEIOHCZ-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzonitrile Chemical compound CC1=CC(C#N)=CC(C)=C1O WFYGXOWFEIOHCZ-UHFFFAOYSA-N 0.000 description 1
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical group COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
- REIDAMBAPLIATC-UHFFFAOYSA-M 4-methoxycarbonylbenzoate Chemical compound COC(=O)C1=CC=C(C([O-])=O)C=C1 REIDAMBAPLIATC-UHFFFAOYSA-M 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- ORPHLVJBJOCHBR-UHFFFAOYSA-N 403-19-0 Chemical compound OC1=CC=C([N+]([O-])=O)C=C1F ORPHLVJBJOCHBR-UHFFFAOYSA-N 0.000 description 1
- KDTABHQJJRRBEO-UHFFFAOYSA-N 5-(2-fluoro-4-nitrophenoxy)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1OC1=CC=C([N+]([O-])=O)C=C1F KDTABHQJJRRBEO-UHFFFAOYSA-N 0.000 description 1
- ZZBATNJCLZZTFL-UHFFFAOYSA-N 5-(2-methoxy-4-nitrophenoxy)-1,3-thiazol-2-amine Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OC1=CN=C(N)S1 ZZBATNJCLZZTFL-UHFFFAOYSA-N 0.000 description 1
- AWOBOJCFKRCCHW-UHFFFAOYSA-N 5-(4-amino-2-fluorophenoxy)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1OC1=CC=C(N)C=C1F AWOBOJCFKRCCHW-UHFFFAOYSA-N 0.000 description 1
- ROVXUUUTDJCWKA-UHFFFAOYSA-N 5-(4-amino-2-methoxyphenoxy)-1,3-thiazol-2-amine Chemical compound COC1=CC(N)=CC=C1OC1=CN=C(N)S1 ROVXUUUTDJCWKA-UHFFFAOYSA-N 0.000 description 1
- WMIAFRVYUOABKK-UHFFFAOYSA-N 5-(4-nitrophenoxy)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC=C1OC1=CC=C([N+]([O-])=O)C=C1 WMIAFRVYUOABKK-UHFFFAOYSA-N 0.000 description 1
- DRYFQDDXZXPPHH-UHFFFAOYSA-N 5-[2-(ethoxymethyl)-4-nitrophenoxy]-1,3-thiazol-2-amine Chemical compound CCOCC1=CC([N+]([O-])=O)=CC=C1OC1=CN=C(N)S1 DRYFQDDXZXPPHH-UHFFFAOYSA-N 0.000 description 1
- IHELMIVNQXOODO-UHFFFAOYSA-N 5-[2-(methoxymethyl)-4-nitrophenoxy]-1,3-thiazol-2-amine Chemical compound COCC1=CC([N+]([O-])=O)=CC=C1OC1=CN=C(N)S1 IHELMIVNQXOODO-UHFFFAOYSA-N 0.000 description 1
- KPTUGLYLELCKSX-UHFFFAOYSA-N 5-[4-amino-2-(ethoxymethyl)phenoxy]-1,3-thiazol-2-amine Chemical compound CCOCC1=CC(N)=CC=C1OC1=CN=C(N)S1 KPTUGLYLELCKSX-UHFFFAOYSA-N 0.000 description 1
- PJYYTPQUADEGPC-UHFFFAOYSA-N 5-[4-amino-2-(methoxymethyl)phenoxy]-1,3-thiazol-2-amine Chemical compound COCC1=CC(N)=CC=C1OC1=CN=C(N)S1 PJYYTPQUADEGPC-UHFFFAOYSA-N 0.000 description 1
- UOHSTKWPZWFYTF-UHFFFAOYSA-N 6-hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-one Chemical compound C1C(=O)CC2C(O)CC1N2C UOHSTKWPZWFYTF-UHFFFAOYSA-N 0.000 description 1
- PZPVPVJLCPBGRW-UHFFFAOYSA-N 8-methyl-8-azabicyclo[3.2.1]octan-6-ol Chemical compound C1CCC2C(O)CC1N2C PZPVPVJLCPBGRW-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010001605 Alcohol poisoning Diseases 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
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- WYIBBUOGOBWZPY-UHFFFAOYSA-N C(N)(OC(CC1=CC(=C(C=C1)O)OCC)(C)C)=O Chemical compound C(N)(OC(CC1=CC(=C(C=C1)O)OCC)(C)C)=O WYIBBUOGOBWZPY-UHFFFAOYSA-N 0.000 description 1
- WTXIUIRBPPEJHN-UHFFFAOYSA-N CCC1=C(C=CC(=C1)C2(CCN(CC2)CC(C)C)O)C(=O)O Chemical compound CCC1=C(C=CC(=C1)C2(CCN(CC2)CC(C)C)O)C(=O)O WTXIUIRBPPEJHN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical class O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical class 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 1
- 241000282898 Sus scrofa Species 0.000 description 1
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-N 0.000 description 1
- ANIKAPXDMYFXMF-UHFFFAOYSA-N [1-(4-hydroxy-3-methoxyphenyl)-2-methylpropan-2-yl] carbamate Chemical compound COC1=CC(CC(C)(C)OC(N)=O)=CC=C1O ANIKAPXDMYFXMF-UHFFFAOYSA-N 0.000 description 1
- KBZURSYZWJIXOK-UHFFFAOYSA-N [1-(4-hydroxy-3-methylphenyl)-2-methylpropan-2-yl] carbamate Chemical compound CC1=CC(CC(C)(C)OC(N)=O)=CC=C1O KBZURSYZWJIXOK-UHFFFAOYSA-N 0.000 description 1
- VSNIYERMPSQYIY-UHFFFAOYSA-N [1-[3-ethoxy-4-(4-nitrophenoxy)phenyl]-2-methylpropan-2-yl] carbamate Chemical compound CCOC1=CC(CC(C)(C)OC(N)=O)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 VSNIYERMPSQYIY-UHFFFAOYSA-N 0.000 description 1
- SRFSIESZOQLZSQ-UHFFFAOYSA-N [1-[3-methoxy-4-(4-nitrophenoxy)phenyl]-2-methylpropan-2-yl] carbamate Chemical compound COC1=CC(CC(C)(C)OC(N)=O)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 SRFSIESZOQLZSQ-UHFFFAOYSA-N 0.000 description 1
- YRGSFBOAVTXXJF-UHFFFAOYSA-N [1-[4-(2-methoxy-4-nitrophenoxy)phenyl]-2-methylpropan-2-yl] carbamate Chemical compound COC1=CC([N+]([O-])=O)=CC=C1OC1=CC=C(CC(C)(C)OC(N)=O)C=C1 YRGSFBOAVTXXJF-UHFFFAOYSA-N 0.000 description 1
- HIOWOFIRWNEMIW-UHFFFAOYSA-N [1-[4-(4-amino-2-methoxyphenoxy)phenyl]-2-methylpropan-2-yl] carbamate Chemical compound COC1=CC(N)=CC=C1OC1=CC=C(CC(C)(C)OC(N)=O)C=C1 HIOWOFIRWNEMIW-UHFFFAOYSA-N 0.000 description 1
- TZMUEHZAKCIZHE-UHFFFAOYSA-N [1-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-2-methylpropan-2-yl] carbamate Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CC=C(CC(C)(C)OC(N)=O)C=C1 TZMUEHZAKCIZHE-UHFFFAOYSA-N 0.000 description 1
- UNUIDWFCDRUUFQ-UHFFFAOYSA-N [1-[5-(4-aminophenoxy)-1,3-thiazol-2-yl]-2-methylpropan-2-yl] carbamate Chemical compound S1C(CC(C)(C)OC(N)=O)=NC=C1OC1=CC=C(N)C=C1 UNUIDWFCDRUUFQ-UHFFFAOYSA-N 0.000 description 1
- DHVYMPXPAADVGK-UHFFFAOYSA-N [2-methyl-1-[3-methyl-4-(4-nitrophenoxy)phenyl]propan-2-yl] carbamate Chemical compound CC1=CC(CC(C)(C)OC(N)=O)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 DHVYMPXPAADVGK-UHFFFAOYSA-N 0.000 description 1
- QOIXJJUNKWADSY-UHFFFAOYSA-N [2-methyl-1-[5-(4-nitrophenoxy)-1,3-thiazol-2-yl]propan-2-yl] carbamate Chemical compound S1C(CC(C)(C)OC(N)=O)=NC=C1OC1=CC=C([N+]([O-])=O)C=C1 QOIXJJUNKWADSY-UHFFFAOYSA-N 0.000 description 1
- NTQQEOWVXJLDPA-UHFFFAOYSA-N [2-methyl-1-[5-[4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]propan-2-yl] carbamate Chemical compound C1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(CC(C)(C)OC(N)=O)S1 NTQQEOWVXJLDPA-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- BOIZHGCLUSQNLD-UHFFFAOYSA-N acetic acid;1h-indole Chemical compound CC(O)=O.C1=CC=C2NC=CC2=C1 BOIZHGCLUSQNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- ZWNUQDJANZGVFO-YHSALVGYSA-N acyline Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(C)=O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(C)=O)C=C1 ZWNUQDJANZGVFO-YHSALVGYSA-N 0.000 description 1
- 108010070822 acyline Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000004079 adrenergic fiber Anatomy 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 description 1
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- SQISUZWPWJHTEP-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1.NC1=CC=CC=C1 SQISUZWPWJHTEP-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001262 anti-secretory effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- OTJZCIYGRUNXTP-UHFFFAOYSA-N but-3-yn-1-ol Chemical compound OCCC#C OTJZCIYGRUNXTP-UHFFFAOYSA-N 0.000 description 1
- APJYYFNGGGLDJF-UHFFFAOYSA-N but-3-ynyl methanesulfonate Chemical compound CS(=O)(=O)OCCC#C APJYYFNGGGLDJF-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical class CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- UMPRJGKLMUDRHL-UHFFFAOYSA-N ethyl 4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C=C1 UMPRJGKLMUDRHL-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- QSPOJWMZYOMAEI-UHFFFAOYSA-N ethyl n-[(ethoxycarbonylamino)methyl]carbamate Chemical compound CCOC(=O)NCNC(=O)OCC QSPOJWMZYOMAEI-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- QOHMWDJIBGVPIF-UHFFFAOYSA-N n',n'-diethylpropane-1,3-diamine Chemical compound CCN(CC)CCCN QOHMWDJIBGVPIF-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- VVZCEZKXELLKSX-UHFFFAOYSA-N n-(1-hydroxy-2-methylpropan-2-yl)-4-(4-hydroxy-1-propan-2-ylpiperidin-4-yl)benzamide Chemical compound C1CN(C(C)C)CCC1(O)C1=CC=C(C(=O)NC(C)(C)CO)C=C1 VVZCEZKXELLKSX-UHFFFAOYSA-N 0.000 description 1
- HVCGOOUZQACZBJ-UHFFFAOYSA-N n-(1-hydroxy-2-methylpropan-2-yl)-4-[4-hydroxy-1-(2-methylpropyl)piperidin-4-yl]benzamide Chemical compound C1CN(CC(C)C)CCC1(O)C1=CC=C(C(=O)NC(C)(C)CO)C=C1 HVCGOOUZQACZBJ-UHFFFAOYSA-N 0.000 description 1
- MVNDRBDXSKYHGG-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[(8-methyl-8-azabicyclo[3.2.1]octan-6-yl)oxy]benzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1C(N2C)CCCC2C1 MVNDRBDXSKYHGG-UHFFFAOYSA-N 0.000 description 1
- TXSVHIPGMJQCHW-UHFFFAOYSA-N n-[4-[2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(oxan-4-yl)piperidin-4-yl]oxybenzamide Chemical compound COC1=CC(NC(=O)NC(CC)CC)=CC=C1OC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1CCN(C2CCOCC2)CC1 TXSVHIPGMJQCHW-UHFFFAOYSA-N 0.000 description 1
- FYWXECIQFBXPOK-UHFFFAOYSA-N n-[4-[5-fluoro-2-methoxy-4-(pentan-3-ylcarbamoylamino)phenoxy]phenyl]-4-[1-(2-methoxyethyl)piperidin-4-yl]oxy-3-methylbenzamide Chemical compound C1=C(F)C(NC(=O)NC(CC)CC)=CC(OC)=C1OC(C=C1)=CC=C1NC(=O)C(C=C1C)=CC=C1OC1CCN(CCOC)CC1 FYWXECIQFBXPOK-UHFFFAOYSA-N 0.000 description 1
- BIYGMNWBZWALSA-UHFFFAOYSA-N n-[5-[2-(methoxymethyl)-4-(pentan-3-ylcarbamoylamino)phenoxy]-1,3-thiazol-2-yl]formamide Chemical compound COCC1=CC(NC(=O)NC(CC)CC)=CC=C1OC1=CN=C(NC=O)S1 BIYGMNWBZWALSA-UHFFFAOYSA-N 0.000 description 1
- XTQKRXXERDFDLH-UHFFFAOYSA-N n-ethyl-n-propylpiperidin-1-amine Chemical compound CCCN(CC)N1CCCCC1 XTQKRXXERDFDLH-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000005702 oxyalkylene group Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 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
- 238000002638 palliative care Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000001175 peptic effect Effects 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- OJCLHERKFHHUTB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)C1 OJCLHERKFHHUTB-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YRQMBQUMJFVZLF-UHFFFAOYSA-N tert-butyl n-(4-hydroxyphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(O)C=C1 YRQMBQUMJFVZLF-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 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
- 239000008096 xylene Substances 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/452—Piperidinium derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/42—Oxygen atoms attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Reproductive Health (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0503795A FR2884516B1 (fr) | 2005-04-15 | 2005-04-15 | Antagonistes npy, preparation et utilisations |
| FR0503795 | 2005-04-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080009112A true KR20080009112A (ko) | 2008-01-24 |
Family
ID=35447654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020077026216A Withdrawn KR20080009112A (ko) | 2005-04-15 | 2006-04-14 | Npy 길항제, 제법 및 용도 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US20090233910A1 (https=) |
| EP (1) | EP1879887A2 (https=) |
| JP (1) | JP2008538749A (https=) |
| KR (1) | KR20080009112A (https=) |
| CN (1) | CN101198604A (https=) |
| AP (1) | AP2007004218A0 (https=) |
| AU (1) | AU2006234413A1 (https=) |
| CA (1) | CA2604773A1 (https=) |
| CR (1) | CR9514A (https=) |
| EA (1) | EA200800157A1 (https=) |
| EC (1) | ECSP077894A (https=) |
| FR (1) | FR2884516B1 (https=) |
| IL (1) | IL186601A0 (https=) |
| MA (1) | MA29444B1 (https=) |
| MX (1) | MX2007012847A (https=) |
| NI (1) | NI200700260A (https=) |
| NO (1) | NO20075322L (https=) |
| TN (1) | TNSN07376A1 (https=) |
| WO (1) | WO2006108965A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102234530B1 (ko) * | 2020-09-01 | 2021-03-31 | 대한민국 | 신규 톨트라주릴 유도체 및 이를 포함하는 쿠도아충 예방·치료를 위한 약학 조성물 |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR051780A1 (es) * | 2004-11-29 | 2007-02-07 | Japan Tobacco Inc | Compuestos en anillo fusionados que contienen nitrogeno y utilizacion de los mismos |
| GB0512091D0 (en) * | 2005-06-14 | 2005-07-20 | Novartis Ag | Organic compounds |
| JP5301999B2 (ja) * | 2005-10-31 | 2013-09-25 | メルク・シャープ・アンド・ドーム・コーポレーション | Cetp阻害薬 |
| US7816535B2 (en) | 2006-01-25 | 2010-10-19 | Synta Pharmaceuticals Corp. | Vinyl-phenyl derivatives for inflammation and immune-related uses |
| US8012955B2 (en) | 2006-12-28 | 2011-09-06 | Rigel Pharmaceuticals, Inc. | N-substituted-heterocycloalkyloxybenzamide compounds and methods of use |
| EP2141994A4 (en) * | 2007-04-26 | 2011-05-18 | Avalon Pharmaceuticals | POLYCYCLIC COMPOUNDS AND USES THEREOF |
| CA2685266C (en) | 2007-04-27 | 2014-01-28 | Purdue Pharma L.P. | Trpv1 antagonists and uses thereof for the treatment of prevention of pain, ui and ulcer, ibd, or ibs in an animal |
| JP2008303155A (ja) * | 2007-06-06 | 2008-12-18 | Ube Ind Ltd | N−(ω−フルオロアルキル)環状アミン化合物の製法、並びに新規なN−(4−フルオロブチル)環状アミン化合物及びその製法 |
| JP2009035537A (ja) * | 2007-07-10 | 2009-02-19 | Nippon Synthetic Chem Ind Co Ltd:The | N−置換アニリン誘導体及び1−置換インドール誘導体の製造方法 |
| BRPI0919816A2 (pt) * | 2008-09-26 | 2019-09-24 | Eisai R&D Man Co Ltd | uso compostos benzoxazólicos no tratamento de malária |
| WO2010053861A2 (en) * | 2008-11-07 | 2010-05-14 | H. Lundbeck A/S | Biologically active amides |
| JP5642661B2 (ja) * | 2009-03-05 | 2014-12-17 | 塩野義製薬株式会社 | Npyy5受容体拮抗作用を有するピペリジンおよびピロリジン誘導体 |
| WO2011090738A2 (en) | 2009-12-29 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Type ii raf kinase inhibitors |
| PE20141531A1 (es) | 2011-06-22 | 2014-10-23 | Purdue Pharma Lp | Antagonistas de trpv1 que incluyen sustituyentes dihidroxi y sus usos |
| JP6263469B2 (ja) | 2011-07-15 | 2018-01-17 | ノバルティス アーゲー | アザ二環式ジ−アリールエーテルの塩およびその製造方法またはその前駆体の製造方法 |
| KR20140117380A (ko) * | 2012-01-25 | 2014-10-07 | 데메알엑스, 인크. | (1r,4r) 7-옥소-2-아자바이사이클로[2.2.2]옥트-5-엔 및 그의 유도체 |
| WO2015177193A1 (en) * | 2014-05-21 | 2015-11-26 | Solvay Specialty Polymers Usa, Llc | Stabilizer compounds |
| JP6854762B2 (ja) | 2014-12-23 | 2021-04-07 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼ7(cdk7)の阻害剤 |
| USRE50776E1 (en) | 2015-03-27 | 2026-02-03 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| TW201710251A (zh) * | 2015-05-27 | 2017-03-16 | 諾福根有限公司 | 作為抗癌藥劑之經官能化及取代之吲哚 |
| AU2016319125B2 (en) * | 2015-09-09 | 2021-04-08 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
| JP2017137259A (ja) * | 2016-02-03 | 2017-08-10 | 株式会社Ihi | 有機化合物の製造方法 |
| MX376974B (es) | 2016-02-19 | 2025-03-07 | Phoenix Molecular Designs | Derivados de carboxamida útiles como inhibidores de rsk. |
| CN106543089A (zh) * | 2016-11-04 | 2017-03-29 | 山东铂源药业有限公司 | 一种达沙替尼中间体的合成方法 |
| CN107892656A (zh) * | 2017-10-27 | 2018-04-10 | 苏州盖德精细材料有限公司 | 一种2,5‑二氨基苯乙醇的制备方法 |
| EP3810132A4 (en) | 2018-06-25 | 2022-06-22 | Dana-Farber Cancer Institute, Inc. | TAIRE FAMILY KINASE INHIBITORS AND RELATED USES |
| CA3129722A1 (en) | 2019-02-11 | 2020-08-20 | Phoenix Molecular Designs | Crystalline forms of an rsk inhibitor |
| BR112022004791A2 (pt) * | 2019-09-17 | 2022-06-21 | Bial R&D Invest S A | Carboxamidas de imidazol substituídas e seu uso no tratamento de distúrbios médicos |
| JP2023525757A (ja) * | 2020-05-08 | 2023-06-19 | ジョージアミューン・インコーポレイテッド | Akt3モジュレーター |
| CN115215787A (zh) * | 2021-04-19 | 2022-10-21 | 中国科学院上海药物研究所 | 生长抑素受体5拮抗剂及其用途 |
| CN118206542B (zh) * | 2023-03-22 | 2025-06-27 | 沈阳药科大学 | 一种化合物及其制备方法和在制备sEH抑制剂与PPARs激动剂中的应用 |
| CN117003672B (zh) * | 2023-08-09 | 2024-05-28 | 湖南正量工程技术有限公司 | 一种boc-4,4’-二硝基二苯胺的制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06248153A (ja) * | 1993-03-01 | 1994-09-06 | Shin Etsu Chem Co Ltd | 難燃樹脂組成物 |
| SE9703414D0 (sv) * | 1997-09-23 | 1997-09-23 | Astra Ab | New compounds |
| EP1086078B1 (en) * | 1998-06-08 | 2003-02-05 | Schering Corporation | Neuropeptide y5 receptor antagonists |
| JP2000287697A (ja) * | 1999-02-05 | 2000-10-17 | Shionogi & Co Ltd | Npy受容体親和性を有するラクトン誘導体 |
| GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| DE10038007A1 (de) * | 2000-08-04 | 2002-02-14 | Bayer Ag | Neue Amino-und Amido-Diphenylether für Arzneimittel |
| CA2422013A1 (en) * | 2000-09-14 | 2002-03-21 | Schering Corporation | Substituted urea neuropeptide y y5 receptor antagonists |
| PL368201A1 (en) * | 2001-07-26 | 2005-03-21 | Schering Corporation | Substituted urea neuropeptide y y5 receptor antagonists |
| MXPA04008379A (es) * | 2002-02-28 | 2004-11-26 | Hoffmann La Roche | Derivados de tiazol como antagonistas del receptor de neuropeptido y (npy). |
| BR0312593A (pt) * | 2002-07-11 | 2005-04-12 | Aventis Pharma Gmbh | Aciluréias substituìdas por uréia e uretano, processo para a sua produção e sua aplicação |
| EP1635773A2 (en) * | 2003-06-06 | 2006-03-22 | Merck & Co., Inc. (a New Jersey corp.) | Combination therapy for the treatment of hypertension |
-
2005
- 2005-04-15 FR FR0503795A patent/FR2884516B1/fr not_active Expired - Fee Related
-
2006
- 2006-04-14 JP JP2008505929A patent/JP2008538749A/ja active Pending
- 2006-04-14 EP EP06743700A patent/EP1879887A2/fr not_active Withdrawn
- 2006-04-14 NI NI200700260A patent/NI200700260A/es unknown
- 2006-04-14 AP AP2007004218A patent/AP2007004218A0/xx unknown
- 2006-04-14 CN CNA2006800212757A patent/CN101198604A/zh active Pending
- 2006-04-14 CA CA002604773A patent/CA2604773A1/fr not_active Abandoned
- 2006-04-14 AU AU2006234413A patent/AU2006234413A1/en not_active Abandoned
- 2006-04-14 WO PCT/FR2006/000829 patent/WO2006108965A2/fr not_active Ceased
- 2006-04-14 US US11/918,470 patent/US20090233910A1/en not_active Abandoned
- 2006-04-14 MX MX2007012847A patent/MX2007012847A/es unknown
- 2006-04-14 KR KR1020077026216A patent/KR20080009112A/ko not_active Withdrawn
- 2006-04-14 EA EA200800157A patent/EA200800157A1/ru unknown
-
2007
- 2007-10-05 TN TNP2007000376A patent/TNSN07376A1/en unknown
- 2007-10-11 IL IL186601A patent/IL186601A0/en unknown
- 2007-10-17 NO NO20075322A patent/NO20075322L/no not_active Application Discontinuation
- 2007-11-07 MA MA30359A patent/MA29444B1/fr unknown
- 2007-11-13 EC EC2007007894A patent/ECSP077894A/es unknown
- 2007-11-13 CR CR9514A patent/CR9514A/es not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102234530B1 (ko) * | 2020-09-01 | 2021-03-31 | 대한민국 | 신규 톨트라주릴 유도체 및 이를 포함하는 쿠도아충 예방·치료를 위한 약학 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| AP2007004218A0 (en) | 2007-10-31 |
| FR2884516A1 (fr) | 2006-10-20 |
| EA200800157A1 (ru) | 2008-04-28 |
| AU2006234413A1 (en) | 2006-10-19 |
| MA29444B1 (fr) | 2008-05-02 |
| US20090233910A1 (en) | 2009-09-17 |
| CA2604773A1 (fr) | 2006-10-19 |
| WO2006108965A3 (fr) | 2007-03-29 |
| MX2007012847A (es) | 2008-03-25 |
| FR2884516B1 (fr) | 2007-06-22 |
| CR9514A (es) | 2008-08-26 |
| WO2006108965A2 (fr) | 2006-10-19 |
| TNSN07376A1 (en) | 2009-03-17 |
| JP2008538749A (ja) | 2008-11-06 |
| EP1879887A2 (fr) | 2008-01-23 |
| IL186601A0 (en) | 2008-01-20 |
| NI200700260A (es) | 2009-03-03 |
| NO20075322L (no) | 2008-01-11 |
| ECSP077894A (es) | 2008-03-26 |
| CN101198604A (zh) | 2008-06-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20080009112A (ko) | Npy 길항제, 제법 및 용도 | |
| US20070197530A1 (en) | Amido compounds and their use as pharmaceuticals | |
| ES2356815T3 (es) | Derivados de benzoxazinona, su preparación y su aplicación como medicamentos. | |
| TWI469979B (zh) | 脂肪酸醯胺水解酶(faah)抑制劑、以及其藥學組成物與用途 | |
| AU746406B2 (en) | 1-((1-substituted-4-piperidinyl)methyl)-4-piperidine derivatives, process for producing the same, medicinal compositions containing the same and intermediates of these compounds | |
| US20080004312A1 (en) | Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-II receptor antagonists | |
| MX2010010241A (es) | Derivados de piperidina novedosos como inhibidores de estearoil-coa desaturasa. | |
| WO2007069053A1 (en) | Benzimidazole antagonists of the h-3 receptor | |
| WO2006019020A1 (ja) | 置換されたウレア化合物 | |
| KR920003980B1 (ko) | 축합 디아제핀온의 제조방법 | |
| JP2009537542A (ja) | ヒスタミン−3アンタゴニストとしてのn−ベンゾイルピロリジン−3−イルアミンおよびn−ベンジルピロリジン−3−イルアミン | |
| EA014498B1 (ru) | Производные бензамидов в качестве антагонистов брадикининовых рецепторов | |
| PT1828172E (pt) | Derivados de pirrol com a actividade antagonista de receptor crth2 | |
| WO2007039781A2 (en) | New compounds | |
| ZA200700321B (en) | Kynurenic acid amide derivatives as NR2B receptor antagonists | |
| WO2011001931A1 (ja) | 新規オキサジアゾール誘導体 | |
| CA2688110A1 (en) | Azacyclylbenzamide derivatives as histamine-3 antagonists | |
| BRPI0722156A2 (pt) | Derivados não-peptidicos como antagonistas de bradicinina b1 | |
| JP5091138B2 (ja) | 機能性5−ht6リガンドとしてのアミノアリールスルホンアミド誘導体 | |
| JP2007533715A (ja) | GlyT1阻害剤として用いるためのモルホリニルおよびピペリジニル基を有する化合物 | |
| ZA200703668B (en) | 4-biarylyl-1-phenylazetidin-2-ones | |
| JP2007533713A (ja) | N−[4−4(4−モルホリニル)フェニル]−[(4−ピペリジニル)メチル]カルボキシアミド誘導体、およびグリシントランスポーター阻害薬としてのその使用 | |
| CN101405265A (zh) | 酰氨基化合物及其作为药物的应用 | |
| FR2894964A1 (fr) | Composes a base de quatre cycles aromatiques, preparation et utilisations | |
| KR20060127157A (ko) | 인다놀 유도체 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20071112 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |