OA12296A - Melanocortin receptor ligands. - Google Patents

Info

Publication number

OA12296A

OA12296A OA1200200389A OA1200200389A OA12296A OA 12296 A OA12296 A OA 12296A OA 1200200389 A OA1200200389 A OA 1200200389A OA 1200200389 A OA1200200389 A OA 1200200389A OA 12296 A OA12296 A OA 12296A

Authority

OA

OAPI

Prior art keywords

alkyl

formula

oxo

compound

benzyl

Prior art date

2000-06-28

Links

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• Global Dossier
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• 102000004378 Melanocortin Receptors Human genes 0.000 title abstract description 7
• 108090000950 Melanocortin Receptors Proteins 0.000 title abstract description 7
• 239000003446 ligand Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 201
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
• 201000010099 disease Diseases 0.000 claims abstract description 6
• 230000004913 activation Effects 0.000 claims abstract description 5
• 208000035475 disorder Diseases 0.000 claims abstract description 5
• 125000000217 alkyl group Chemical group 0.000 claims description 115
• 239000001257 hydrogen Substances 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 59
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
• -1 hydroxy, nitro, amino, cyano, phenyl Chemical group 0.000 claims description 47
• 239000002253 acid Substances 0.000 claims description 41
• 150000002148 esters Chemical class 0.000 claims description 39
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
• 229910052757 nitrogen Inorganic materials 0.000 claims description 35
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 229910052760 oxygen Inorganic materials 0.000 claims description 24
• 150000002431 hydrogen Chemical group 0.000 claims description 20
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 150000002367 halogens Chemical class 0.000 claims description 19
• 239000000203 mixture Substances 0.000 claims description 19
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 15
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 14
• 239000001301 oxygen Substances 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• 230000037406 food intake Effects 0.000 claims description 13
• 235000012631 food intake Nutrition 0.000 claims description 13
• SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims description 12
• 229920006395 saturated elastomer Polymers 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 239000000460 chlorine Substances 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 10
• 230000036528 appetite Effects 0.000 claims description 9
• 235000019789 appetite Nutrition 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims description 8
• 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 claims description 8
• 239000000651 prodrug Substances 0.000 claims description 8
• 229940002612 prodrug Drugs 0.000 claims description 8
• 239000011593 sulfur Chemical group 0.000 claims description 8
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 7
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 7
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 229910052740 iodine Inorganic materials 0.000 claims description 7
• 150000003254 radicals Chemical class 0.000 claims description 7
• 208000008589 Obesity Diseases 0.000 claims description 6
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 239000003112 inhibitor Substances 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 235000020824 obesity Nutrition 0.000 claims description 6
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
• 230000037396 body weight Effects 0.000 claims description 5
• 229910052799 carbon Inorganic materials 0.000 claims description 5
• 102000004877 Insulin Human genes 0.000 claims description 4
• 108090001061 Insulin Proteins 0.000 claims description 4
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000001589 carboacyl group Chemical group 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 229940125396 insulin Drugs 0.000 claims description 4
• 244000144972 livestock Species 0.000 claims description 4
• 230000007170 pathology Effects 0.000 claims description 4
• 230000001568 sexual effect Effects 0.000 claims description 4
• 230000004936 stimulating effect Effects 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
• 229940100389 Sulfonylurea Drugs 0.000 claims description 3
• 125000005907 alkyl ester group Chemical group 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 102000005962 receptors Human genes 0.000 claims description 3
• 108020003175 receptors Proteins 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 208000016261 weight loss Diseases 0.000 claims description 3
• 230000004580 weight loss Effects 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 206010006895 Cachexia Diseases 0.000 claims description 2
• 208000007976 Ketosis Diseases 0.000 claims description 2
• 241001296405 Tiso Species 0.000 claims description 2
• 125000004423 acyloxy group Chemical group 0.000 claims description 2
• 239000000048 adrenergic agonist Substances 0.000 claims description 2
• 239000000674 adrenergic antagonist Substances 0.000 claims description 2
• 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 150000007942 carboxylates Chemical class 0.000 claims description 2
• 208000010706 fatty liver disease Diseases 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000005059 halophenyl group Chemical group 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 230000004140 ketosis Effects 0.000 claims description 2
• 239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 230000001850 reproductive effect Effects 0.000 claims description 2
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 3
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
• AHIHSQQZFSNIDT-YKSBVNFPSA-N (3aS)-5-[(2R)-2-amino-3-(4-chlorophenyl)propanoyl]-2-ethyl-3a-[(4-fluorophenyl)methyl]-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-one Chemical compound C([C@]12CN(CCC1=NN(C2=O)CC)C(=O)[C@H](N)CC=1C=CC(Cl)=CC=1)C1=CC=C(F)C=C1 AHIHSQQZFSNIDT-YKSBVNFPSA-N 0.000 claims 1
• 125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
• 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 claims 1
• 230000001856 erectile effect Effects 0.000 claims 1
• FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 claims 1
• 230000002503 metabolic effect Effects 0.000 claims 1
• 230000037323 metabolic rate Effects 0.000 claims 1
• 230000002265 prevention Effects 0.000 abstract description 2
• 239000002904 solvent Substances 0.000 description 66
• 238000010511 deprotection reaction Methods 0.000 description 58
• 239000002585 base Substances 0.000 description 57
• 239000000543 intermediate Substances 0.000 description 52
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
• 238000000034 method Methods 0.000 description 34
• 239000003153 chemical reaction reagent Substances 0.000 description 33
• 239000000243 solution Substances 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• 150000001412 amines Chemical class 0.000 description 32
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 26
• 238000005804 alkylation reaction Methods 0.000 description 24
• 230000029936 alkylation Effects 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• 150000002825 nitriles Chemical class 0.000 description 21
• 239000003795 chemical substances by application Substances 0.000 description 20
• 125000006239 protecting group Chemical group 0.000 description 20
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
• 150000002576 ketones Chemical class 0.000 description 19
• 150000003951 lactams Chemical class 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 229910000104 sodium hydride Inorganic materials 0.000 description 18
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 17
• 150000002596 lactones Chemical class 0.000 description 17
• 239000012312 sodium hydride Substances 0.000 description 17
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 15
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 150000001350 alkyl halides Chemical class 0.000 description 14
• 125000004185 ester group Chemical group 0.000 description 13
• 235000019439 ethyl acetate Nutrition 0.000 description 13
• 238000012360 testing method Methods 0.000 description 13
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 230000009466 transformation Effects 0.000 description 12
• 230000002152 alkylating effect Effects 0.000 description 11
• 230000003197 catalytic effect Effects 0.000 description 11
• 150000004820 halides Chemical class 0.000 description 11
• 239000012948 isocyanate Substances 0.000 description 11
• 150000002513 isocyanates Chemical class 0.000 description 11
• PAQZWJGSJMLPMG-UHFFFAOYSA-N propylphosphonic anhydride Substances CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 11
• 239000012279 sodium borohydride Substances 0.000 description 10
• 229910000033 sodium borohydride Inorganic materials 0.000 description 10
• 241000700159 Rattus Species 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 229940086542 triethylamine Drugs 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• 235000013877 carbamide Nutrition 0.000 description 8
• 239000003638 chemical reducing agent Substances 0.000 description 8
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
• 230000003647 oxidation Effects 0.000 description 8
• 238000007254 oxidation reaction Methods 0.000 description 8
• 230000036284 oxygen consumption Effects 0.000 description 8
• 150000003141 primary amines Chemical class 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• 239000000556 agonist Substances 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 150000002081 enamines Chemical class 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 150000007513 acids Chemical class 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• 230000008878 coupling Effects 0.000 description 6
• 238000010168 coupling process Methods 0.000 description 6
• 238000005859 coupling reaction Methods 0.000 description 6
• 238000011905 homologation Methods 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 150000003839 salts Chemical class 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 241000039077 Copula Species 0.000 description 5
• 206010057671 Female sexual dysfunction Diseases 0.000 description 5
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 150000001413 amino acids Chemical class 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
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• 229940093499 ethyl acetate Drugs 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 0.000 description 5
• 239000012442 inert solvent Substances 0.000 description 5
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 230000011514 reflex Effects 0.000 description 5
• 238000007363 ring formation reaction Methods 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
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• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• 150000003672 ureas Chemical class 0.000 description 5
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 239000007818 Grignard reagent Substances 0.000 description 4
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
• 239000012448 Lithium borohydride Substances 0.000 description 4
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 239000007822 coupling agent Substances 0.000 description 4
• 239000010779 crude oil Substances 0.000 description 4
• 230000005595 deprotonation Effects 0.000 description 4
• 238000010537 deprotonation reaction Methods 0.000 description 4
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• 150000004678 hydrides Chemical class 0.000 description 4
• 150000002466 imines Chemical class 0.000 description 4
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 150000003335 secondary amines Chemical class 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
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