ZA200605164B - Heterocyclic derivatives as GPCR receptor agonists - Google Patents

Info

Publication number

ZA200605164B

ZA200605164B ZA200605164A ZA200605164A ZA200605164B ZA 200605164 B ZA200605164 B ZA 200605164B ZA 200605164 A ZA200605164 A ZA 200605164A ZA 200605164 A ZA200605164 A ZA 200605164A ZA 200605164 B ZA200605164 B ZA 200605164B

Authority

ZA

South Africa

Prior art keywords

alkyl

cycloalkyl

pharmaceutically acceptable

formula

compounds

Prior art date

2003-12-24

Links

• Espacenet
• Global Dossier
• Discuss

• 125000000623 heterocyclic group Chemical group 0.000 title claims description 51
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 title description 7
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 title description 7
• 239000000018 receptor agonist Substances 0.000 title description 4
• 229940044601 receptor agonist Drugs 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 285
• 125000000217 alkyl group Chemical group 0.000 claims description 98
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 91
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 76
• 239000000203 mixture Substances 0.000 claims description 62
• 150000003839 salts Chemical class 0.000 claims description 59
• -1 NR® Inorganic materials 0.000 claims description 56
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 48
• 125000003118 aryl group Chemical group 0.000 claims description 45
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 45
• 125000005843 halogen group Chemical group 0.000 claims description 45
• 239000001257 hydrogen Substances 0.000 claims description 45
• 238000011282 treatment Methods 0.000 claims description 41
• 125000001072 heteroaryl group Chemical group 0.000 claims description 40
• 229910052757 nitrogen Inorganic materials 0.000 claims description 39
• 229910052760 oxygen Inorganic materials 0.000 claims description 38
• 125000001424 substituent group Chemical group 0.000 claims description 34
• 150000002431 hydrogen Chemical class 0.000 claims description 33
• 101000775045 Homo sapiens Adhesion G protein-coupled receptor F5 Proteins 0.000 claims description 25
• 102100031933 Adhesion G protein-coupled receptor F5 Human genes 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims description 18
• 125000005842 heteroatom Chemical group 0.000 claims description 18
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 206010012601 diabetes mellitus Diseases 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 125000004122 cyclic group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 7
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 6
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 230000036186 satiety Effects 0.000 claims description 6
• 235000019627 satiety Nutrition 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• 230000033228 biological regulation Effects 0.000 claims description 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
• KEINZLHBRWJPNV-UHFFFAOYSA-N 4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=NC(C=2C=CN=CC=2)=NO1 KEINZLHBRWJPNV-UHFFFAOYSA-N 0.000 claims 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 98
• 239000000243 solution Substances 0.000 description 90
• 238000002360 preparation method Methods 0.000 description 72
• 239000002904 solvent Substances 0.000 description 70
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 49
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 238000000034 method Methods 0.000 description 44
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
• 235000019439 ethyl acetate Nutrition 0.000 description 41
• 238000006243 chemical reaction Methods 0.000 description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
• 239000002253 acid Substances 0.000 description 28
• 238000003818 flash chromatography Methods 0.000 description 25
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 24
• 229920006395 saturated elastomer Polymers 0.000 description 24
• 239000000556 agonist Substances 0.000 description 23
• 239000000460 chlorine Substances 0.000 description 23
• 239000012267 brine Substances 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• 208000008589 Obesity Diseases 0.000 description 18
• 235000020824 obesity Nutrition 0.000 description 18
• 235000019441 ethanol Nutrition 0.000 description 17
• 238000003756 stirring Methods 0.000 description 17
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
• 239000012074 organic phase Substances 0.000 description 15
• 229910052721 tungsten Inorganic materials 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 14
• 238000010992 reflux Methods 0.000 description 14
• 239000007787 solid Substances 0.000 description 14
• 229910052727 yttrium Inorganic materials 0.000 description 14
• 239000000883 anti-obesity agent Substances 0.000 description 13
• 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 13
• 239000011541 reaction mixture Substances 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 12
• 229940125710 antiobesity agent Drugs 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 150000002148 esters Chemical class 0.000 description 12
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
• 238000009833 condensation Methods 0.000 description 11
• 230000005494 condensation Effects 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
• 238000010438 heat treatment Methods 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• 239000012312 sodium hydride Substances 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 238000004440 column chromatography Methods 0.000 description 8
• 239000012634 fragment Substances 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• 210000005253 yeast cell Anatomy 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 150000007513 acids Chemical class 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000000969 carrier Substances 0.000 description 7
• ZUUATXHRJFHSGO-UHFFFAOYSA-N chembl1896408 Chemical compound O/N=C(/N)C1=CC=NC=C1 ZUUATXHRJFHSGO-UHFFFAOYSA-N 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
• 239000002808 molecular sieve Substances 0.000 description 7
• 231100000252 nontoxic Toxicity 0.000 description 7
• 230000003000 nontoxic effect Effects 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 102000005962 receptors Human genes 0.000 description 7
• 108020003175 receptors Proteins 0.000 description 7
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 102000004877 Insulin Human genes 0.000 description 6
• 108090001061 Insulin Proteins 0.000 description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000037396 body weight Effects 0.000 description 6
• 239000011575 calcium Substances 0.000 description 6
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000004615 ingredient Substances 0.000 description 6
• 229940125396 insulin Drugs 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• YHUAHIMRWSVXCN-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]oxyacetic acid Chemical compound CC(C)(C)OC(=O)N1CCC(OCC(O)=O)CC1 YHUAHIMRWSVXCN-UHFFFAOYSA-N 0.000 description 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 5
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 229920001223 polyethylene glycol Polymers 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 238000004007 reversed phase HPLC Methods 0.000 description 5
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• WMQUKDQWMMOHSA-UHFFFAOYSA-N 1-pyridin-4-ylethanone Chemical compound CC(=O)C1=CC=NC=C1 WMQUKDQWMMOHSA-UHFFFAOYSA-N 0.000 description 4
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 4
• 210000000577 adipose tissue Anatomy 0.000 description 4
• 150000001298 alcohols Chemical class 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 229940095074 cyclic amp Drugs 0.000 description 4
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 4
• 235000005911 diet Nutrition 0.000 description 4
• 230000037213 diet Effects 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 4
• ZQWPRMPSCMSAJU-UHFFFAOYSA-N methyl cyclohexanecarboxylate Chemical compound COC(=O)C1CCCCC1 ZQWPRMPSCMSAJU-UHFFFAOYSA-N 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000000376 reactant Substances 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 4
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 4
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
• 229920002554 vinyl polymer Polymers 0.000 description 4
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 3
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical class C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 3
• MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 3
• OAAGDVLVOKMRCQ-UHFFFAOYSA-N 5-piperidin-4-yl-3-pyridin-4-yl-1,2,4-oxadiazole Chemical compound C1CNCCC1C1=NC(C=2C=CN=CC=2)=NO1 OAAGDVLVOKMRCQ-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 3
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 239000004793 Polystyrene Substances 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 150000001409 amidines Chemical class 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 150000001649 bromium compounds Chemical class 0.000 description 3
• 239000000872 buffer 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
• 238000002648 combination therapy Methods 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000003925 fat Substances 0.000 description 3
• 229910052736 halogen Inorganic materials 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
• 150000004866 oxadiazoles Chemical class 0.000 description 3
• CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• AXFHYLRXARSNKA-UHFFFAOYSA-N tert-butyl 4-(2-amino-2-oxoethoxy)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OCC(N)=O)CC1 AXFHYLRXARSNKA-UHFFFAOYSA-N 0.000 description 3
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 3
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 2
• ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical compound ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• 229940124802 CB1 antagonist Drugs 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 108020004414 DNA Proteins 0.000 description 2
• 208000032928 Dyslipidaemia Diseases 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• 102000016267 Leptin Human genes 0.000 description 2
• 108010092277 Leptin Proteins 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• 108050006759 Pancreatic lipases Proteins 0.000 description 2
• 102000019280 Pancreatic lipases Human genes 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 150000001263 acyl chlorides Chemical class 0.000 description 2
• 230000010933 acylation Effects 0.000 description 2
• 238000005917 acylation reaction Methods 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 150000001411 amidrazones Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 230000003579 anti-obesity Effects 0.000 description 2
• 229940125708 antidiabetic agent Drugs 0.000 description 2
• 239000003472 antidiabetic agent Substances 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 235000019577 caloric intake Nutrition 0.000 description 2
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
• VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 2
• ISQVBYGGNVVVHB-UHFFFAOYSA-N cyclopentylmethanol Chemical compound OCC1CCCC1 ISQVBYGGNVVVHB-UHFFFAOYSA-N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 125000005594 diketone group Chemical group 0.000 description 2
• 230000003291 dopaminomimetic effect Effects 0.000 description 2
• FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
• WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 235000019197 fats Nutrition 0.000 description 2
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000005283 haloketone group Chemical group 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 239000012456 homogeneous solution Substances 0.000 description 2
• 102000058189 human ADGRF5 Human genes 0.000 description 2
• 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 239000012948 isocyanate Substances 0.000 description 2
• 150000002513 isocyanates Chemical class 0.000 description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229940039781 leptin Drugs 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 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
• 238000012423 maintenance Methods 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 238000000465 moulding Methods 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 229940116369 pancreatic lipase Drugs 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
• JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 2
• 230000000862 serotonergic effect Effects 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• HTDSYPGJACAFCW-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-4-pyridin-4-ylbutoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OCC(=O)CC(=O)C1=CC=NC=C1 HTDSYPGJACAFCW-UHFFFAOYSA-N 0.000 description 2
• UNVNNPUGYNYGOZ-UHFFFAOYSA-N tert-butyl 4-(3,5-dioxo-5-pyridin-4-ylpentyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC(=O)CC(=O)C1=CC=NC=C1 UNVNNPUGYNYGOZ-UHFFFAOYSA-N 0.000 description 2
• XYDJXFFRMCPJRH-UHFFFAOYSA-N tert-butyl 4-(3-bromo-2-oxopropyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC(=O)CBr)CC1 XYDJXFFRMCPJRH-UHFFFAOYSA-N 0.000 description 2
• QBKIYLAAMXUGDA-UHFFFAOYSA-N tert-butyl 4-(cyanomethoxy)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OCC#N)CC1 QBKIYLAAMXUGDA-UHFFFAOYSA-N 0.000 description 2
• JOMWMDCZYGEZKT-UHFFFAOYSA-N tert-butyl 4-[(2z)-2-amino-2-hydroxyiminoethoxy]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OCC(=N)NO)CC1 JOMWMDCZYGEZKT-UHFFFAOYSA-N 0.000 description 2
• USYCVFFWCMHPPG-UHFFFAOYSA-N tert-butyl 4-sulfanylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(S)CC1 USYCVFFWCMHPPG-UHFFFAOYSA-N 0.000 description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
• HPWSTQITVJEUMH-UHFFFAOYSA-N tert-butyl n-[(2e)-2-amino-2-hydroxyiminoethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC\C(N)=N\O HPWSTQITVJEUMH-UHFFFAOYSA-N 0.000 description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 238000000825 ultraviolet detection Methods 0.000 description 2
• ZINMZWYBMIZQEP-UHFFFAOYSA-N (3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methanol Chemical compound O1C(CO)=NC(C=2C=CN=CC=2)=N1 ZINMZWYBMIZQEP-UHFFFAOYSA-N 0.000 description 1
• PTCDQAKENWVFPK-UHFFFAOYSA-N (3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl methanesulfonate Chemical compound O1C(COS(=O)(=O)C)=NC(C=2C=CN=CC=2)=N1 PTCDQAKENWVFPK-UHFFFAOYSA-N 0.000 description 1
• AXJQVVLKUYCICH-OAQYLSRUSA-N (4s)-5-(4-chlorophenyl)-n-(4-chlorophenyl)sulfonyl-n'-methyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C=1C=C(Cl)C=CC=1C([C@H](C1)C=2C=CC=CC=2)=NN1C(=NC)NS(=O)(=O)C1=CC=C(Cl)C=C1 AXJQVVLKUYCICH-OAQYLSRUSA-N 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• PPVUWDCETZMPLT-UHFFFAOYSA-N 1,3-dihydropyrazole-2-carboxamide Chemical compound NC(=O)N1CC=CN1 PPVUWDCETZMPLT-UHFFFAOYSA-N 0.000 description 1
• VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-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
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
• GXTAADIYVXOPAM-UHFFFAOYSA-N 1-phosphabicyclo[3.3.3]undecane Chemical compound C1CCP2CCCC1CCC2 GXTAADIYVXOPAM-UHFFFAOYSA-N 0.000 description 1
• 229940044613 1-propanol Drugs 0.000 description 1
• VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
• BRGYJZBEPFPCGE-UHFFFAOYSA-N 2-(1,2,4-triazol-1-yl)pyridine Chemical compound N1=CN=CN1C1=CC=CC=N1 BRGYJZBEPFPCGE-UHFFFAOYSA-N 0.000 description 1
• ZXFLMSIMHISJFV-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CC(O)=O)CC1 ZXFLMSIMHISJFV-UHFFFAOYSA-N 0.000 description 1
• 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 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• RGALBQILADNMKA-UHFFFAOYSA-N 2-bromo-1-pyridin-4-ylethanone;hydron;bromide Chemical compound Br.BrCC(=O)C1=CC=NC=C1 RGALBQILADNMKA-UHFFFAOYSA-N 0.000 description 1
• FUSMRNWUUNGSEH-UHFFFAOYSA-N 2-chloro-N'-hydroxypyridine-4-carboximidamide Chemical compound ON=C(N)C1=CC=NC(Cl)=C1 FUSMRNWUUNGSEH-UHFFFAOYSA-N 0.000 description 1
• QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 1
• MPSVJNPESHZCIB-UHFFFAOYSA-N 2-cyanopyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C#N)=C1 MPSVJNPESHZCIB-UHFFFAOYSA-N 0.000 description 1
• NILLIUYSJFTTRH-UHFFFAOYSA-N 2-cyclopentylacetyl chloride Chemical compound ClC(=O)CC1CCCC1 NILLIUYSJFTTRH-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• NPSJHQMIVNJLNN-UHFFFAOYSA-N 2-ethylhexyl 4-nitrobenzoate Chemical compound CCCCC(CC)COC(=O)C1=CC=C([N+]([O-])=O)C=C1 NPSJHQMIVNJLNN-UHFFFAOYSA-N 0.000 description 1
• 239000004808 2-ethylhexylester Substances 0.000 description 1
• MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 1
• IVBBHPTZEFPTFZ-UHFFFAOYSA-N 2-methylpropyl 4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC(C)C)CCC1C1=NC(C=2C=CN=CC=2)=NO1 IVBBHPTZEFPTFZ-UHFFFAOYSA-N 0.000 description 1
• BUTKIHRNYUEGKB-UHFFFAOYSA-N 3,3-dimethylbutanoyl chloride Chemical compound CC(C)(C)CC(Cl)=O BUTKIHRNYUEGKB-UHFFFAOYSA-N 0.000 description 1
• KVAXAKXOSZNECS-UHFFFAOYSA-N 3-(2-cyanopyridin-4-yl)propanoic acid Chemical compound OC(=O)CCC1=CC=NC(C#N)=C1 KVAXAKXOSZNECS-UHFFFAOYSA-N 0.000 description 1
• WMOSOYIGMOXESV-UHFFFAOYSA-N 3-(2-cyanopyridin-4-yl)propyl acetate Chemical compound CC(=O)OCCCC1=CC=NC(C#N)=C1 WMOSOYIGMOXESV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• XWZDPNBLQJCKNC-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CCC(O)=O)CC1 XWZDPNBLQJCKNC-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-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
• PWRBCZZQRRPXAB-UHFFFAOYSA-N 3-chloropyridine Chemical compound ClC1=CC=CN=C1 PWRBCZZQRRPXAB-UHFFFAOYSA-N 0.000 description 1
• FDELGFGAESSHKY-UHFFFAOYSA-N 4-(carboxymethoxy)piperidine-1-carboxylic acid Chemical compound OC(=O)COC1CCN(C(O)=O)CC1 FDELGFGAESSHKY-UHFFFAOYSA-N 0.000 description 1
• RMABHIRQOVJNGI-UHFFFAOYSA-N 4-(methylsulfonyloxymethyl)piperidine-1-carboxylic acid Chemical compound CS(=O)(=O)OCC1CCN(C(O)=O)CC1 RMABHIRQOVJNGI-UHFFFAOYSA-N 0.000 description 1
• ATHDNOVYFBZKGG-UHFFFAOYSA-N 4-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl]piperazine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCN1CC1=NC(C=2C=CN=CC=2)=NO1 ATHDNOVYFBZKGG-UHFFFAOYSA-N 0.000 description 1
• HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
• ZQJNPHCQABYENK-UHFFFAOYSA-N 4-methoxycarbonylcyclohexane-1-carboxylic acid Chemical compound COC(=O)C1CCC(C(O)=O)CC1 ZQJNPHCQABYENK-UHFFFAOYSA-N 0.000 description 1
• RRBBJOSMWARXMG-UHFFFAOYSA-N 4-pentyl-n-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl]cyclohexan-1-amine Chemical compound C1CC(CCCCC)CCC1NCC1=NC(C=2C=CN=CC=2)=NO1 RRBBJOSMWARXMG-UHFFFAOYSA-N 0.000 description 1
• NQEVYZKSODGUEK-UHFFFAOYSA-N 4-pentylcyclohexan-1-amine Chemical compound CCCCCC1CCC(N)CC1 NQEVYZKSODGUEK-UHFFFAOYSA-N 0.000 description 1
• UKLNPJDLSPMJMQ-UHFFFAOYSA-N 4-pentylcyclohexan-1-one Chemical compound CCCCCC1CCC(=O)CC1 UKLNPJDLSPMJMQ-UHFFFAOYSA-N 0.000 description 1
• ZYJCSKAGKUQLQK-UHFFFAOYSA-N 4-pentylcyclohexane-1-carbonitrile Chemical compound CCCCCC1CCC(C#N)CC1 ZYJCSKAGKUQLQK-UHFFFAOYSA-N 0.000 description 1
• QGUCBSXNMDKGML-UHFFFAOYSA-N 5-(4-propylcyclohexyl)-3-(3-pyridinyl)-1,2,4-oxadiazole Chemical compound C1CC(CCC)CCC1C1=NC(C=2C=NC=CC=2)=NO1 QGUCBSXNMDKGML-UHFFFAOYSA-N 0.000 description 1
• YLNMBLHYRUVUBZ-UHFFFAOYSA-N 5-(piperidin-4-yloxymethyl)-3-pyridin-4-yl-1,2,4-oxadiazole Chemical compound N=1C(C=2C=CN=CC=2)=NOC=1COC1CCNCC1 YLNMBLHYRUVUBZ-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• 125000006164 6-membered heteroaryl group Chemical group 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• GGZZISOUXJHYOY-UHFFFAOYSA-N 8-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(N)=CC=CC2=C1O GGZZISOUXJHYOY-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229920001817 Agar Polymers 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
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 101000878595 Arabidopsis thaliana Squalene synthase 1 Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 208000008035 Back Pain Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 229940123208 Biguanide Drugs 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• PUCZYTYGEKDZPK-HDJSIYSDSA-N C1C[C@@H](C(=O)OCCC)CC[C@@H]1C1=NC(C=2C=CN=CC=2)=NO1 Chemical compound C1C[C@@H](C(=O)OCCC)CC[C@@H]1C1=NC(C=2C=CN=CC=2)=NO1 PUCZYTYGEKDZPK-HDJSIYSDSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 208000002177 Cataract Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 102000004859 Cholecystokinin Receptors Human genes 0.000 description 1
• 108090001085 Cholecystokinin Receptors Proteins 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 102100032165 Corticotropin-releasing factor-binding protein Human genes 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 208000002249 Diabetes Complications Diseases 0.000 description 1
• 206010012655 Diabetic complications Diseases 0.000 description 1
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
• 208000030814 Eating disease Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
• 208000019454 Feeding and Eating disease Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 241000027294 Fusi Species 0.000 description 1
• 108091006027 G proteins Proteins 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 102000030782 GTP binding Human genes 0.000 description 1
• 108091000058 GTP-Binding Proteins 0.000 description 1
• 102000011392 Galanin receptor Human genes 0.000 description 1
• 108050001605 Galanin receptor Proteins 0.000 description 1
• 101710198928 Gamma-glutamyl phosphate reductase Proteins 0.000 description 1
• 102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 102400000321 Glucagon Human genes 0.000 description 1
• 108060003199 Glucagon Proteins 0.000 description 1
• 102000030595 Glucokinase Human genes 0.000 description 1
• 108010021582 Glucokinase Proteins 0.000 description 1
• 229940121931 Gluconeogenesis inhibitor Drugs 0.000 description 1
• 208000002705 Glucose Intolerance Diseases 0.000 description 1
• 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
• 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
• 101001133924 Homo sapiens Gamma-glutamyl phosphate reductase Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• 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 1
• 208000015580 Increased body weight Diseases 0.000 description 1
• 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
• 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• 108010009384 L-Iditol 2-Dehydrogenase Proteins 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• 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 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 229910009891 LiAc Inorganic materials 0.000 description 1
• 229940127470 Lipase Inhibitors Drugs 0.000 description 1
• 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 241000252067 Megalops atlanticus Species 0.000 description 1
• 108010008364 Melanocortins Proteins 0.000 description 1
• 101710151321 Melanostatin Proteins 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000019022 Mood disease Diseases 0.000 description 1
• 101001133922 Mus musculus Gamma-glutamyl phosphate reductase Proteins 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 150000001200 N-acyl ethanolamides Chemical class 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• RCLPLCVREXBPCB-SHTZXODSSA-N N1=CC=C(C=C1)C(=O)N(N)C(=O)[C@@H]1CC[C@H](CC1)CCCCC Chemical compound N1=CC=C(C=C1)C(=O)N(N)C(=O)[C@@H]1CC[C@H](CC1)CCCCC RCLPLCVREXBPCB-SHTZXODSSA-N 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 102400000064 Neuropeptide Y Human genes 0.000 description 1
• 108090000189 Neuropeptides Proteins 0.000 description 1
• 102000003797 Neuropeptides Human genes 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 206010033307 Overweight Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 238000006086 Paal-Knorr synthesis reaction Methods 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• 241001474728 Satyrodes eurydice Species 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 239000004133 Sodium thiosulphate Substances 0.000 description 1
• 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 1
• 102100026974 Sorbitol dehydrogenase Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 229940100389 Sulfonylurea Drugs 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• HXJUTPCZVOIRIF-UHFFFAOYSA-N Tetrahydrothiophene-1,1-dioxide, Natural products O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 239000007984 Tris EDTA buffer Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 150000001241 acetals Chemical group 0.000 description 1
• TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 230000001800 adrenalinergic effect Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 239000003288 aldose reductase inhibitor Substances 0.000 description 1
• 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000004703 alkoxides Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 235000012501 ammonium carbonate Nutrition 0.000 description 1
• 238000012440 amplified luminescent proximity homogeneous assay Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 229940125709 anorectic agent Drugs 0.000 description 1
• 239000003524 antilipemic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 235000019789 appetite Nutrition 0.000 description 1
• 230000036528 appetite Effects 0.000 description 1
• 239000002830 appetite depressant Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• TWJVNKMWXNTSAP-UHFFFAOYSA-N azanium;hydroxide;hydrochloride Chemical compound [NH4+].O.[Cl-] TWJVNKMWXNTSAP-UHFFFAOYSA-N 0.000 description 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
• QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 150000004283 biguanides Chemical class 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-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
• 238000013262 cAMP assay Methods 0.000 description 1
• 229910052792 caesium Inorganic materials 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 238000000451 chemical ionisation Methods 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 108010083720 corticotropin releasing factor-binding protein Proteins 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 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
• 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
• OFAUDLLOLVJRBX-UHFFFAOYSA-N cyclopentyl 4-[methyl-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC2CCCC2)CCC1N(C)CC(ON=1)=NC=1C1=CC=NC=C1 OFAUDLLOLVJRBX-UHFFFAOYSA-N 0.000 description 1
• ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 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
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000005595 deprotonation Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 235000014632 disordered eating Nutrition 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000010410 dusting Methods 0.000 description 1
• 201000006549 dyspepsia Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 239000002621 endocannabinoid Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229940088598 enzyme Drugs 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 238000006345 epimerization reaction Methods 0.000 description 1
• IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• KJAWTTRLKLWDGL-UHFFFAOYSA-N ethyl 3-pyridin-4-yl-1,2,4-oxadiazole-5-carboxylate Chemical compound O1C(C(=O)OCC)=NC(C=2C=CN=CC=2)=N1 KJAWTTRLKLWDGL-UHFFFAOYSA-N 0.000 description 1
• MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• LFRXBSFJOBAAMC-UHFFFAOYSA-N ethylbenzene;heptane;oxolane Chemical compound C1CCOC1.CCCCCCC.CCC1=CC=CC=C1 LFRXBSFJOBAAMC-UHFFFAOYSA-N 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013613 expression plasmid Substances 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 208000020694 gallbladder disease Diseases 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000011521 glass 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
• 239000003850 glucocorticoid receptor antagonist Substances 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000000742 histaminergic effect Effects 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 201000001421 hyperglycemia Diseases 0.000 description 1
• 229940126904 hypoglycaemic agent Drugs 0.000 description 1
• 230000002267 hypothalamic effect Effects 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• WRSXUNSJGJUKHE-UHFFFAOYSA-N indazole Chemical compound C1=CC=C[C]2C=NN=C21 WRSXUNSJGJUKHE-UHFFFAOYSA-N 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000037041 intracellular level Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 229940125425 inverse agonist Drugs 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 235000014666 liquid concentrate Nutrition 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 239000002865 melanocortin Substances 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
• JNCPTEDQFZOIHX-SFYZADRCSA-N methyl (1s,3r)-3-(hydroxymethyl)cyclohexane-1-carboxylate Chemical compound COC(=O)[C@H]1CCC[C@@H](CO)C1 JNCPTEDQFZOIHX-SFYZADRCSA-N 0.000 description 1
• QFZTZFHLMOJRBN-RQJHMYQMSA-N methyl (1s,3r)-3-(hydroxymethyl)cyclopentane-1-carboxylate Chemical compound COC(=O)[C@H]1CC[C@@H](CO)C1 QFZTZFHLMOJRBN-RQJHMYQMSA-N 0.000 description 1
• WDUZCDYIJNQXSO-UHFFFAOYSA-N methyl 4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)CCC1C1=NC(C=2C=CN=CC=2)=NO1 WDUZCDYIJNQXSO-UHFFFAOYSA-N 0.000 description 1
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000007932 molded tablet Substances 0.000 description 1
• 230000014925 multi-organism signaling Effects 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• FXPFADBYVRQSQY-UHFFFAOYSA-N n'-(4-pentylcyclohexanecarbonyl)pyridine-4-carbohydrazide Chemical compound C1CC(CCCCC)CCC1C(=O)NNC(=O)C1=CC=NC=C1 FXPFADBYVRQSQY-UHFFFAOYSA-N 0.000 description 1
• SMBOKVZNCISDCP-UHFFFAOYSA-N n'-aminopyridine-4-carboximidamide Chemical compound NN=C(N)C1=CC=NC=C1 SMBOKVZNCISDCP-UHFFFAOYSA-N 0.000 description 1
• ZEONASHSZKLJGT-UHFFFAOYSA-N n'-hydroxy-2-pyridin-3-ylethanimidamide Chemical compound ON=C(N)CC1=CC=CN=C1 ZEONASHSZKLJGT-UHFFFAOYSA-N 0.000 description 1
• VBLBLKXTGWSMPM-UHFFFAOYSA-N n'-hydroxy-2-pyridin-4-ylethanimidamide Chemical compound ON=C(N)CC1=CC=NC=C1 VBLBLKXTGWSMPM-UHFFFAOYSA-N 0.000 description 1
• AQBMQGDKWIPBRF-UHFFFAOYSA-N n'-hydroxypyridine-3-carboximidamide Chemical compound ON=C(N)C1=CC=CN=C1 AQBMQGDKWIPBRF-UHFFFAOYSA-N 0.000 description 1
• OABPOTFGQCRYQD-UHFFFAOYSA-N n-(4-pentylcyclohexyl)-3-pyridin-4-yl-1,2,4-oxadiazole-5-carboxamide Chemical compound C1CC(CCCCC)CCC1NC(=O)C1=NC(C=2C=CN=CC=2)=NO1 OABPOTFGQCRYQD-UHFFFAOYSA-N 0.000 description 1
• NPOPFEQSPOFLAR-UHFFFAOYSA-N n-methyl-n-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methyl]piperidin-4-amine Chemical compound C1CNCCC1N(C)CC(ON=1)=NC=1C1=CC=NC=C1 NPOPFEQSPOFLAR-UHFFFAOYSA-N 0.000 description 1
• QEBGATMRIOQYAX-UHFFFAOYSA-N n-propyl-4-(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxamide Chemical compound C1CN(C(=O)NCCC)CCC1C1=NC(C=2C=CN=CC=2)=NO1 QEBGATMRIOQYAX-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 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 description 1
• RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 230000000406 opioidergic effect Effects 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical compound C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• HZIVRQOIUMAXID-UHFFFAOYSA-N oxocane Chemical compound C1CCCOCCC1 HZIVRQOIUMAXID-UHFFFAOYSA-N 0.000 description 1
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
• FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• RLBIQVVOMOPOHC-UHFFFAOYSA-N parathion-methyl Chemical compound COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1 RLBIQVVOMOPOHC-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000013612 plasmid Substances 0.000 description 1
• 229910003446 platinum oxide Inorganic materials 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
• 235000014483 powder concentrate Nutrition 0.000 description 1
• 201000009104 prediabetes syndrome Diseases 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000003672 processing method Methods 0.000 description 1
• UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
• AFORUYORXZMXKM-UHFFFAOYSA-N propan-2-yl 4-[[5-(2-cyanopyridin-4-yl)-1,2,4-oxadiazol-3-yl]methoxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1OCC1=NOC(C=2C=C(N=CC=2)C#N)=N1 AFORUYORXZMXKM-UHFFFAOYSA-N 0.000 description 1
• IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
• 229960005335 propanol Drugs 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• OAVLEYPTWABFLF-UHFFFAOYSA-N psn-375,963 Chemical compound C1CC(CCCC)CCC1C1=NC(C=2C=CN=CC=2)=NO1 OAVLEYPTWABFLF-UHFFFAOYSA-N 0.000 description 1
• LHZWKWCEAXQUMX-UHFFFAOYSA-N psn-632,408 Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OCC1=NC(C=2C=CN=CC=2)=NO1 LHZWKWCEAXQUMX-UHFFFAOYSA-N 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• KPIIGXWUNXGGCP-UHFFFAOYSA-N pyridine-4-carbothioamide Chemical compound NC(=S)C1=CC=NC=C1 KPIIGXWUNXGGCP-UHFFFAOYSA-N 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 230000009892 regulation of energy homeostasis Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229960003015 rimonabant Drugs 0.000 description 1
• 235000002020 sage Nutrition 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
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000020374 simple syrup Nutrition 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 238000000935 solvent evaporation Methods 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 230000006103 sulfonylation Effects 0.000 description 1
• 238000005694 sulfonylation reaction Methods 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 238000004416 surface enhanced Raman spectroscopy Methods 0.000 description 1
• 208000011580 syndromic disease Diseases 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
• 235000020679 tap water Nutrition 0.000 description 1
• 239000008399 tap water Substances 0.000 description 1
• OEMSQFKGRVHKSM-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-4-pyridin-4-ylbutyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CC(=O)CC(=O)C1=CC=NC=C1 OEMSQFKGRVHKSM-UHFFFAOYSA-N 0.000 description 1
• MOGMUOIYZGUJBY-UHFFFAOYSA-N tert-butyl 4-(2-amino-2-sulfanylideneethoxy)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OCC(N)=S)CC1 MOGMUOIYZGUJBY-UHFFFAOYSA-N 0.000 description 1
• HZUQPWAZDQXMBI-UHFFFAOYSA-N tert-butyl 4-[(3-pyridin-4-yl-1,2,4-oxadiazol-5-yl)methoxymethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COCC1=NC(C=2C=CN=CC=2)=NO1 HZUQPWAZDQXMBI-UHFFFAOYSA-N 0.000 description 1
• FDRHMAIJPIXWBZ-UHFFFAOYSA-N tert-butyl 4-[(5-pyridin-4-yl-1,2-oxazol-3-yl)methoxy]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OCC1=NOC(C=2C=CN=CC=2)=C1 FDRHMAIJPIXWBZ-UHFFFAOYSA-N 0.000 description 1
• OKPNANBGMBXLNA-UHFFFAOYSA-N tert-butyl 4-[(5-pyridin-4-yl-1,2-oxazol-3-yl)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CC1=NOC(C=2C=CN=CC=2)=C1 OKPNANBGMBXLNA-UHFFFAOYSA-N 0.000 description 1
• BHOGBIUUVFUONZ-UHFFFAOYSA-N tert-butyl 4-[2-(5-pyridin-4-yl-1,2-oxazol-3-yl)ethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCC1=NOC(C=2C=CN=CC=2)=C1 BHOGBIUUVFUONZ-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
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 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
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 description 1
• NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
• XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 230000000929 thyromimetic effect Effects 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 239000012137 tryptone Substances 0.000 description 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 239000013585 weight reducing agent Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1