CA2537916A1 - 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds - Google Patents
5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds Download PDFInfo
- Publication number
- CA2537916A1 CA2537916A1 CA002537916A CA2537916A CA2537916A1 CA 2537916 A1 CA2537916 A1 CA 2537916A1 CA 002537916 A CA002537916 A CA 002537916A CA 2537916 A CA2537916 A CA 2537916A CA 2537916 A1 CA2537916 A1 CA 2537916A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- c6alkyl
- substituted
- mono
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 371
- 150000003230 pyrimidines Chemical class 0.000 title abstract description 6
- 150000003216 pyrazines Chemical class 0.000 title 1
- 150000003222 pyridines Chemical class 0.000 title 1
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 claims abstract description 57
- 238000000034 method Methods 0.000 claims abstract description 48
- 230000027455 binding Effects 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 239000000523 sample Substances 0.000 claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 108091005471 CRHR1 Proteins 0.000 claims abstract description 13
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 11
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 9
- 208000030814 Eating disease Diseases 0.000 claims abstract description 7
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 7
- -1 hydroxy, cyano, amino Chemical group 0.000 claims description 422
- 229910052736 halogen Inorganic materials 0.000 claims description 194
- 150000002367 halogens Chemical class 0.000 claims description 193
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 173
- 150000003839 salts Chemical class 0.000 claims description 151
- 125000000217 alkyl group Chemical group 0.000 claims description 138
- 125000005843 halogen group Chemical group 0.000 claims description 133
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 126
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 124
- 125000001424 substituent group Chemical group 0.000 claims description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims description 103
- 239000001257 hydrogen Substances 0.000 claims description 103
- 229910020008 S(O) Inorganic materials 0.000 claims description 86
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 86
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 83
- 239000000203 mixture Substances 0.000 claims description 78
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 66
- 125000003282 alkyl amino group Chemical group 0.000 claims description 63
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 59
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 59
- 229910052760 oxygen Inorganic materials 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 54
- 125000001072 heteroaryl group Chemical class 0.000 claims description 52
- 125000004043 oxo group Chemical group O=* 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 48
- 210000004027 cell Anatomy 0.000 claims description 45
- 125000004076 pyridyl group Chemical group 0.000 claims description 43
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 43
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 42
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 36
- 229910052717 sulfur Inorganic materials 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 34
- 230000000694 effects Effects 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 26
- 238000000338 in vitro Methods 0.000 claims description 26
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 24
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 24
- 125000002757 morpholinyl group Chemical group 0.000 claims description 24
- 125000004193 piperazinyl group Chemical group 0.000 claims description 24
- 125000003386 piperidinyl group Chemical group 0.000 claims description 24
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 229920006395 saturated elastomer Polymers 0.000 claims description 23
- 238000012360 testing method Methods 0.000 claims description 23
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 22
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000002393 azetidinyl group Chemical group 0.000 claims description 21
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 18
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 17
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 17
- 125000002971 oxazolyl group Chemical group 0.000 claims description 17
- 125000000335 thiazolyl group Chemical group 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000001425 triazolyl group Chemical group 0.000 claims description 15
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 12
- 150000003462 sulfoxides Chemical class 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 241001465754 Metazoa Species 0.000 claims description 10
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 10
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 10
- 238000001727 in vivo Methods 0.000 claims description 10
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 10
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 10
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 239000013068 control sample Substances 0.000 claims description 9
- 238000001525 receptor binding assay Methods 0.000 claims description 9
- 150000003457 sulfones Chemical class 0.000 claims description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000005432 dialkylcarboxamide group Chemical group 0.000 claims description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
- BRZNXTNBNXQMGU-UHFFFAOYSA-N 6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC BRZNXTNBNXQMGU-UHFFFAOYSA-N 0.000 claims description 5
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- CFUVRYWPAMHGFL-UHFFFAOYSA-N 1-(1,3-dimethoxypropan-2-yl)-6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(COC)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC CFUVRYWPAMHGFL-UHFFFAOYSA-N 0.000 claims description 4
- AVJYVWPFLPYXRZ-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n,n-dimethyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N(C)C AVJYVWPFLPYXRZ-UHFFFAOYSA-N 0.000 claims description 4
- MIPUGSKUPXSXRI-UHFFFAOYSA-N 5-(2,4-dichlorophenyl)-3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(Cl)C=C1Cl MIPUGSKUPXSXRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 238000000159 protein binding assay Methods 0.000 claims description 4
- BUDHDLJHCYFGNX-UHFFFAOYSA-N 3-(1-benzyl-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl)-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound N1=C(C)C=2N=C(C=3C(=NC(=CC=3)C(C)C)NC)C(CC)=NC=2N1CC1=CC=CC=C1 BUDHDLJHCYFGNX-UHFFFAOYSA-N 0.000 claims description 3
- GOWITECUMJBDPL-UHFFFAOYSA-N 6-ethyl-1-(1-methoxypropan-2-yl)-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(C)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC GOWITECUMJBDPL-UHFFFAOYSA-N 0.000 claims description 3
- JJKBWXRWTUZNRD-UHFFFAOYSA-N 6-ethyl-5-(2-ethyl-6-propan-2-ylpyridin-3-yl)-1-(1-methoxypropan-2-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC(C(C)C)=CC=C1C(C(=N1)CC)=NC2=C1N(C(C)COC)N=C2C JJKBWXRWTUZNRD-UHFFFAOYSA-N 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 238000001514 detection method Methods 0.000 claims description 3
- JIFOURNCJACCCO-UHFFFAOYSA-N 1-(1,3-dimethoxypropan-2-yl)-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3,6-dimethylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(COC)COC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC JIFOURNCJACCCO-UHFFFAOYSA-N 0.000 claims description 2
- CFKOUPLOBHRGEF-UHFFFAOYSA-N 1-(1,3-dimethoxypropan-2-yl)-6-ethyl-5-(2-ethyl-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC(C(C)C)=CC=C1C(C(=N1)CC)=NC2=C1N(C(COC)COC)N=C2C CFKOUPLOBHRGEF-UHFFFAOYSA-N 0.000 claims description 2
- JMMZEWGMUIBGDU-UHFFFAOYSA-N 1-benzyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3,6-dimethylpyrazolo[3,4-b]pyrazine Chemical compound COC1=NC(C(C)C)=CC=C1C(C(=N1)C)=NC2=C1N(CC=1C=CC=CC=1)N=C2C JMMZEWGMUIBGDU-UHFFFAOYSA-N 0.000 claims description 2
- OBPRWDDPOKYOCQ-UHFFFAOYSA-N 2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-phenylmethoxypropan-1-ol Chemical compound CCC1=NC=2N(C(CO)COCC=3C=CC=CC=3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC OBPRWDDPOKYOCQ-UHFFFAOYSA-N 0.000 claims description 2
- FMFYWKOPCWUTJP-UHFFFAOYSA-N 3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-(2-methoxyethyl)-6-propan-2-ylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCOC FMFYWKOPCWUTJP-UHFFFAOYSA-N 0.000 claims description 2
- KKPHSQPAGFZWBS-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NC KKPHSQPAGFZWBS-UHFFFAOYSA-N 0.000 claims description 2
- XWAOLOLIBVUZCF-UHFFFAOYSA-N 3-[1-(1,1-diethoxybutan-2-yl)-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)C(OCC)OCC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NC XWAOLOLIBVUZCF-UHFFFAOYSA-N 0.000 claims description 2
- RSVRQSRFOBRMHK-UHFFFAOYSA-N 3-[1-(1,3-dimethoxypropan-2-yl)-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-n,n-dimethyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC1=NC=2N(C(COC)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1N(C)C RSVRQSRFOBRMHK-UHFFFAOYSA-N 0.000 claims description 2
- PZJJWCLPVPMFRF-UHFFFAOYSA-N 3-[1-(1,3-dimethoxypropan-2-yl)-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC1=NC=2N(C(COC)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1NC PZJJWCLPVPMFRF-UHFFFAOYSA-N 0.000 claims description 2
- FFCKMZDPHGHDRN-UHFFFAOYSA-N 3-[6-ethyl-1-(1-methoxypropan-2-yl)-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC1=NC=2N(C(C)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1NC FFCKMZDPHGHDRN-UHFFFAOYSA-N 0.000 claims description 2
- YLWZRYDNZWRUQD-UHFFFAOYSA-N 3-[6-ethyl-3-methyl-1-(1-morpholin-4-ylbutan-2-yl)pyrazolo[3,4-b]pyrazin-5-yl]-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound N1=C(C)C2=NC(C=3C(=NC(=CC=3)C(C)C)NC)=C(CC)N=C2N1C(CC)CN1CCOCC1 YLWZRYDNZWRUQD-UHFFFAOYSA-N 0.000 claims description 2
- HDZKUCFRNUGBIZ-UHFFFAOYSA-N 5-(1,5-dimethyl-3-pentan-3-ylpyrazolo[3,4-b]pyridin-6-yl)-n,n,4-triethylpyridin-2-amine Chemical compound CC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC HDZKUCFRNUGBIZ-UHFFFAOYSA-N 0.000 claims description 2
- NYQIDMBKPDTHQM-UHFFFAOYSA-N 5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC NYQIDMBKPDTHQM-UHFFFAOYSA-N 0.000 claims description 2
- AULRDTJMIJDNIP-UHFFFAOYSA-N 5-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n,n,4-triethylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC AULRDTJMIJDNIP-UHFFFAOYSA-N 0.000 claims description 2
- QWNWRFNUXKHGAA-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC QWNWRFNUXKHGAA-UHFFFAOYSA-N 0.000 claims description 2
- HAMCWMIJNZEOPE-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-3-[5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-3-yl]-6-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound C12=NC(C=3C(=CC(OC(F)(F)F)=CC=3)OC)=C(C)N=C2N(C(CC)CC)N=C1C(C1=N2)=NN(C(CC)CC)C1=NC(C)=C2C1=CC=C(OC(F)(F)F)C=C1OC HAMCWMIJNZEOPE-UHFFFAOYSA-N 0.000 claims description 2
- CBEVHLYINAIDCI-UHFFFAOYSA-N 5-[6-(diethylamino)-4-ethylpyridin-3-yl]-3-methyl-1-pentan-3-yl-7H-pyrazolo[3,4-b]pyrazin-6-one Chemical compound OC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC CBEVHLYINAIDCI-UHFFFAOYSA-N 0.000 claims description 2
- YTCLZHORLMANMB-UHFFFAOYSA-N 5-ethyl-6-[2-methoxy-4-(trifluoromethoxy)phenyl]-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound CCC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC YTCLZHORLMANMB-UHFFFAOYSA-N 0.000 claims description 2
- CCFIIBGXUPOABC-UHFFFAOYSA-N 6-(2-chloro-4-methoxyphenyl)-1,5-dimethyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound CC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC=C(OC)C=C1Cl CCFIIBGXUPOABC-UHFFFAOYSA-N 0.000 claims description 2
- OTYGIDMUHGEFFF-UHFFFAOYSA-N 6-[2-methoxy-4-(trifluoromethoxy)phenyl]-1,5-dimethyl-3-pentan-3-yloxypyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2C(OC(CC)CC)=NN(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC OTYGIDMUHGEFFF-UHFFFAOYSA-N 0.000 claims description 2
- NSHMTIFFJMNCGC-UHFFFAOYSA-N 6-[2-methoxy-4-(trifluoromethoxy)phenyl]-1,5-dimethyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound CC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC NSHMTIFFJMNCGC-UHFFFAOYSA-N 0.000 claims description 2
- HPUUTSPLWGLQQY-UHFFFAOYSA-N 6-ethyl-1-(1-methoxy-3-phenylmethoxypropan-2-yl)-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(COC)COCC=3C=CC=CC=3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC HPUUTSPLWGLQQY-UHFFFAOYSA-N 0.000 claims description 2
- CHEDQUJEAKPKCQ-UHFFFAOYSA-N 6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(C)C)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC CHEDQUJEAKPKCQ-UHFFFAOYSA-N 0.000 claims description 2
- HYURDKIHMQOXOZ-UHFFFAOYSA-N 6-methoxy-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound COC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC HYURDKIHMQOXOZ-UHFFFAOYSA-N 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 210000001124 body fluid Anatomy 0.000 claims description 2
- 239000010839 body fluid Substances 0.000 claims description 2
- 238000002825 functional assay Methods 0.000 claims description 2
- WLLSQZZWMORSQO-UHFFFAOYSA-N n,n,4-triethyl-5-(6-methoxy-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)pyridin-2-amine Chemical compound COC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC WLLSQZZWMORSQO-UHFFFAOYSA-N 0.000 claims description 2
- UGPBBCNSDNHARL-UHFFFAOYSA-N n-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methoxypropyl]cyclobutanamine Chemical compound CCC1=NC=2N(C(CNC3CCC3)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC UGPBBCNSDNHARL-UHFFFAOYSA-N 0.000 claims description 2
- SPVZHHINVCWERL-UHFFFAOYSA-N n-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]propyl]cyclobutanamine Chemical compound CCC1=NC=2N(C(C)CNC3CCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC SPVZHHINVCWERL-UHFFFAOYSA-N 0.000 claims description 2
- 210000002569 neuron Anatomy 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 57
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 54
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 25
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 25
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 3
- 238000005406 washing Methods 0.000 claims 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- OBFRJIYJGOMGEP-UHFFFAOYSA-N 1-[3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]-n,n-dimethylpyrrolidin-3-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N1CCC(N(C)C)C1 OBFRJIYJGOMGEP-UHFFFAOYSA-N 0.000 claims 1
- UJUUEMRBCIYWNS-UHFFFAOYSA-N 1-[3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]pyrrolidin-3-ol Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N1CCC(O)C1 UJUUEMRBCIYWNS-UHFFFAOYSA-N 0.000 claims 1
- WJJMQBQGTHXSJX-UHFFFAOYSA-N 2-[[3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]-methylamino]ethanol Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N(C)CCO WJJMQBQGTHXSJX-UHFFFAOYSA-N 0.000 claims 1
- FTYWNDYCCNDEFZ-UHFFFAOYSA-N 3-(1-butan-2-yl-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl)-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(C)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NC FTYWNDYCCNDEFZ-UHFFFAOYSA-N 0.000 claims 1
- ZMZJUIOHRNZPIQ-UHFFFAOYSA-N 3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n,n-dimethyl-6-propan-2-ylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N(C)C ZMZJUIOHRNZPIQ-UHFFFAOYSA-N 0.000 claims 1
- SJZWROGPGFGEPU-UHFFFAOYSA-N 3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-[2-(1h-imidazol-5-yl)ethyl]-6-propan-2-ylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCC1=CNC=N1 SJZWROGPGFGEPU-UHFFFAOYSA-N 0.000 claims 1
- DRTUJIXMLFTIHD-UHFFFAOYSA-N 3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NC DRTUJIXMLFTIHD-UHFFFAOYSA-N 0.000 claims 1
- OZMVZEAPSPBOTR-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-(2-methoxyethyl)-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCOC OZMVZEAPSPBOTR-UHFFFAOYSA-N 0.000 claims 1
- PUNCRTBOJKCWFC-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-(3-piperidin-1-ylpropyl)-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCCN1CCCCC1 PUNCRTBOJKCWFC-UHFFFAOYSA-N 0.000 claims 1
- TWVVREXPWXIGFH-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n-(oxolan-2-ylmethyl)-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCC1CCCO1 TWVVREXPWXIGFH-UHFFFAOYSA-N 0.000 claims 1
- CIMAAIMUGNKMAO-UHFFFAOYSA-N 3-[6-ethyl-1-(1-methoxybutan-2-yl)-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC=1N=C2N(C(COC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NC CIMAAIMUGNKMAO-UHFFFAOYSA-N 0.000 claims 1
- SAQMOSWKTMUTJQ-UHFFFAOYSA-N 4-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methoxypropyl]morpholine Chemical compound CCC1=NC=2N(C(COC)CN3CCOCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC SAQMOSWKTMUTJQ-UHFFFAOYSA-N 0.000 claims 1
- LYTCHMQOAULXTL-UHFFFAOYSA-N 4-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]propyl]morpholine Chemical compound CCC1=NC=2N(C(C)CN3CCOCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC LYTCHMQOAULXTL-UHFFFAOYSA-N 0.000 claims 1
- KPRZMBJIBABYFU-UHFFFAOYSA-N 4-[3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]morpholine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N1CCOCC1 KPRZMBJIBABYFU-UHFFFAOYSA-N 0.000 claims 1
- FYNJTFSJMRNADD-UHFFFAOYSA-N 5-(1,5-dimethyl-3-pentan-3-ylpyrazolo[3,4-b]pyridin-6-yl)-3-methoxy-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(OC)C(NC(CC)CC)=NC(C)=C1C(C(=C1)C)=NC2=C1C(C(CC)CC)=NN2C FYNJTFSJMRNADD-UHFFFAOYSA-N 0.000 claims 1
- UOPJLQPVWYXERQ-UHFFFAOYSA-N 5-(2-chloro-4-methoxyphenyl)-6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(OC)C=C1Cl UOPJLQPVWYXERQ-UHFFFAOYSA-N 0.000 claims 1
- LOMFKMCPDJJTGM-UHFFFAOYSA-N 5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-n,3-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-6-amine Chemical compound CNC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC LOMFKMCPDJJTGM-UHFFFAOYSA-N 0.000 claims 1
- CSROFRAFISMKIB-UHFFFAOYSA-N 5-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-4-methoxy-n,n-dimethylpyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(C)C)C=C1OC CSROFRAFISMKIB-UHFFFAOYSA-N 0.000 claims 1
- DYRLLDGYNJSVQQ-UHFFFAOYSA-N 5-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n,n-dimethyl-4-propan-2-yloxypyridin-2-amine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(C)C)C=C1OC(C)C DYRLLDGYNJSVQQ-UHFFFAOYSA-N 0.000 claims 1
- IDTORXIZLZZSAQ-UHFFFAOYSA-N 5-(5-ethyl-1-methyl-3-propan-2-ylpyrazolo[3,4-b]pyridin-6-yl)-3-methoxy-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical compound N1=C(OC)C(NC(CC)CC)=NC(C)=C1C(C(=C1)CC)=NC2=C1C(C(C)C)=NN2C IDTORXIZLZZSAQ-UHFFFAOYSA-N 0.000 claims 1
- CTPZWLJHXYJILO-UHFFFAOYSA-N 5-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-n,n-dimethyl-4-propan-2-yloxypyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(C)C)C=C1OC(C)C CTPZWLJHXYJILO-UHFFFAOYSA-N 0.000 claims 1
- RITBHLKMBVDJPA-UHFFFAOYSA-N 5-[2-(azetidin-1-yl)-6-propan-2-ylpyridin-3-yl]-3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N1CCC1 RITBHLKMBVDJPA-UHFFFAOYSA-N 0.000 claims 1
- SCFLYACWYMJURL-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=CC2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC SCFLYACWYMJURL-UHFFFAOYSA-N 0.000 claims 1
- OMSIJNHIKWBCMY-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-1-pentan-3-yltriazolo[4,5-b]pyrazine Chemical compound CC=1N=C2N(C(CC)CC)N=NC2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC OMSIJNHIKWBCMY-UHFFFAOYSA-N 0.000 claims 1
- MKEJHPYHBBYWOR-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-n,3-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-6-amine Chemical compound CNC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC MKEJHPYHBBYWOR-UHFFFAOYSA-N 0.000 claims 1
- SBBHSVQVITYIJQ-UHFFFAOYSA-N 5-[6-(diethylamino)-4-ethylpyridin-3-yl]-n,3-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-6-amine Chemical compound CNC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC SBBHSVQVITYIJQ-UHFFFAOYSA-N 0.000 claims 1
- AFHIYJBAZCYQTK-UHFFFAOYSA-N 5-chloro-6-[2-methoxy-4-(trifluoromethoxy)phenyl]-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC AFHIYJBAZCYQTK-UHFFFAOYSA-N 0.000 claims 1
- KZZGCCYXKRZWOZ-UHFFFAOYSA-N 5-chloro-6-[5-chloro-2-methoxy-4-(trifluoromethoxy)phenyl]-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC(Cl)=C(OC(F)(F)F)C=C1OC KZZGCCYXKRZWOZ-UHFFFAOYSA-N 0.000 claims 1
- WQJYSZHVDDRSBZ-UHFFFAOYSA-N 6-ethyl-3-methyl-1-pentan-3-yl-5-(2-piperidin-1-yl-6-propan-2-ylpyridin-3-yl)pyrazolo[3,4-b]pyrazine Chemical group CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1N1CCCCC1 WQJYSZHVDDRSBZ-UHFFFAOYSA-N 0.000 claims 1
- HDQUFKCTVFFUOW-UHFFFAOYSA-N 6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-1-(1-methoxy-3-pyrrolidin-1-ylpropan-2-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(COC)CN3CCCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC HDQUFKCTVFFUOW-UHFFFAOYSA-N 0.000 claims 1
- KPQLNBAMNKFYBM-UHFFFAOYSA-N 6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methyl-1-(1-pyrrolidin-1-ylpropan-2-yl)pyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(C)CN3CCCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC KPQLNBAMNKFYBM-UHFFFAOYSA-N 0.000 claims 1
- YFGOPMUEQFLLMK-UHFFFAOYSA-N 6-ethyl-5-[2-methoxy-4-(trifluoromethoxy)phenyl]-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(OC(F)(F)F)C=C1OC YFGOPMUEQFLLMK-UHFFFAOYSA-N 0.000 claims 1
- ISRBTWYLOCNAOM-UHFFFAOYSA-N 6-methoxy-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound COC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC ISRBTWYLOCNAOM-UHFFFAOYSA-N 0.000 claims 1
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 1
- WGCNPGFFNZXZAZ-UHFFFAOYSA-N n,n,4-triethyl-5-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)pyridin-2-amine Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC WGCNPGFFNZXZAZ-UHFFFAOYSA-N 0.000 claims 1
- IZGAZOXGYOLPLW-UHFFFAOYSA-N n-[2-[[3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]amino]ethyl]acetamide Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCNC(C)=O IZGAZOXGYOLPLW-UHFFFAOYSA-N 0.000 claims 1
- CGGOILLSGCZWTQ-UHFFFAOYSA-N n-[3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]-n',n'-dimethylethane-1,2-diamine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCN(C)C CGGOILLSGCZWTQ-UHFFFAOYSA-N 0.000 claims 1
- KKFSZFWTLAYLOS-UHFFFAOYSA-N n-[3-(3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl]-n',n'-dimethylpentane-1,5-diamine Chemical compound CC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1NCCCCCN(C)C KKFSZFWTLAYLOS-UHFFFAOYSA-N 0.000 claims 1
- NQKOHCQQLARPBE-UHFFFAOYSA-N n-[5-[6-(diethylamino)-4-ethylpyridin-3-yl]-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-6-yl]-1,1,1-trifluoro-n-methylmethanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(C)C=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CN=C(N(CC)CC)C=C1CC NQKOHCQQLARPBE-UHFFFAOYSA-N 0.000 claims 1
- ILEYULZAFIYLAS-UHFFFAOYSA-N n-ethyl-2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methoxy-n-methylpropan-1-amine Chemical compound CCC=1N=C2N(C(COC)CN(C)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC ILEYULZAFIYLAS-UHFFFAOYSA-N 0.000 claims 1
- CUTJPUIYWMRMSR-UHFFFAOYSA-N n-ethyl-2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-n-methylpropan-1-amine Chemical compound CCC=1N=C2N(C(C)CN(C)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OC CUTJPUIYWMRMSR-UHFFFAOYSA-N 0.000 claims 1
- 102000005962 receptors Human genes 0.000 abstract description 23
- 108020003175 receptors Proteins 0.000 abstract description 23
- 238000003556 assay Methods 0.000 abstract description 21
- 230000036506 anxiety Effects 0.000 abstract description 6
- 230000004807 localization Effects 0.000 abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 80
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
- 239000000741 silica gel Substances 0.000 description 52
- 229910002027 silica gel Inorganic materials 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 230000015572 biosynthetic process Effects 0.000 description 44
- 238000003786 synthesis reaction Methods 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
- 238000000746 purification Methods 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 39
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 37
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 150000002431 hydrogen Chemical class 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 23
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 208000035475 disorder Diseases 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 16
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000007872 degassing Methods 0.000 description 12
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- USDIRSJFHPHMAS-UHFFFAOYSA-N ClC1=NC=C(C=2C1=NC=CN=2)F Chemical compound ClC1=NC=C(C=2C1=NC=CN=2)F USDIRSJFHPHMAS-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 231100000252 nontoxic Toxicity 0.000 description 10
- 230000003000 nontoxic effect Effects 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 125000000068 chlorophenyl group Chemical group 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
- 108010052164 Sodium Channels Proteins 0.000 description 8
- 102000018674 Sodium Channels Human genes 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 229940086542 triethylamine Drugs 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- DOTPSQVYOBAWPQ-UHFFFAOYSA-N pyrazolo[4,3-d]pyrimidin-3-one Chemical class N1=CN=C2C(=O)N=NC2=C1 DOTPSQVYOBAWPQ-UHFFFAOYSA-N 0.000 description 7
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 150000001543 aryl boronic acids Chemical class 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 6
- 125000005805 dimethoxy phenyl group Chemical group 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 239000012038 nucleophile Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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 5
- 208000019022 Mood disease Diseases 0.000 description 5
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 5
- AJCQJELUJDPGEY-UHFFFAOYSA-N [2-methoxy-4-(trifluoromethoxy)phenyl]boronic acid Chemical compound COC1=CC(OC(F)(F)F)=CC=C1B(O)O AJCQJELUJDPGEY-UHFFFAOYSA-N 0.000 description 5
- 230000000949 anxiolytic effect Effects 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 229940049706 benzodiazepine Drugs 0.000 description 5
- 125000005620 boronic acid group Chemical class 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 238000004020 luminiscence type Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 150000003141 primary amines Chemical class 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- IBQVYGGCPFGFCM-UHFFFAOYSA-N 1-benzyl-5-bromo-3,6-dimethylpyrazolo[3,4-b]pyrazine Chemical compound C12=NC(C)=C(Br)N=C2C(C)=NN1CC1=CC=CC=C1 IBQVYGGCPFGFCM-UHFFFAOYSA-N 0.000 description 4
- DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical compound C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 description 4
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 241000282326 Felis catus Species 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 238000005660 chlorination reaction Methods 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- ZBQUMMFUJLOTQC-UHFFFAOYSA-L dichloronickel;3-diphenylphosphanylpropyl(diphenyl)phosphane Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 ZBQUMMFUJLOTQC-UHFFFAOYSA-L 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
- 229910001629 magnesium chloride Inorganic materials 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- CJFLBOKQFSMRMF-UHFFFAOYSA-N pentan-3-ylhydrazine;hydrochloride Chemical compound Cl.CCC(CC)NN CJFLBOKQFSMRMF-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 4
- 229910052722 tritium Inorganic materials 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- VUIJGYPRRJGNPI-UHFFFAOYSA-N (2-methoxy-6-propan-2-ylpyridin-3-yl)boronic acid Chemical compound COC1=NC(C(C)C)=CC=C1B(O)O VUIJGYPRRJGNPI-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- UVYBHEMEDUQKQI-UHFFFAOYSA-N 2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]propane-1,3-diol Chemical compound CCC1=NC=2N(C(CO)CO)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC UVYBHEMEDUQKQI-UHFFFAOYSA-N 0.000 description 3
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
- LAGLBZHHFADKIZ-UHFFFAOYSA-N 5-bromo-4-methoxy-n,n-dimethylpyridin-2-amine Chemical compound COC1=CC(N(C)C)=NC=C1Br LAGLBZHHFADKIZ-UHFFFAOYSA-N 0.000 description 3
- XAJICICTVFDDQB-UHFFFAOYSA-N 5-methyl-2-pentan-3-ylpyrazole-3,4-diamine;sulfuric acid Chemical compound OS(O)(=O)=O.CCC(CC)N1N=C(C)C(N)=C1N XAJICICTVFDDQB-UHFFFAOYSA-N 0.000 description 3
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 206010013883 Dwarfism Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- 208000025966 Neurological disease Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- YYKBBFZVNQTPHA-UHFFFAOYSA-N [6-(dimethylamino)-4-ethylpyridin-3-yl]boronic acid Chemical compound CCC1=CC(N(C)C)=NC=C1B(O)O YYKBBFZVNQTPHA-UHFFFAOYSA-N 0.000 description 3
- NEKJUWAYMREFEB-UHFFFAOYSA-N [6-(dimethylamino)-4-methoxypyridin-3-yl]boronic acid Chemical compound COC1=CC(N(C)C)=NC=C1B(O)O NEKJUWAYMREFEB-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000003556 anti-epileptic effect Effects 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 229940005530 anxiolytics Drugs 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 238000000211 autoradiogram Methods 0.000 description 3
- 238000000376 autoradiography Methods 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 230000000112 colonic effect Effects 0.000 description 3
- 239000002769 corticotropin releasing factor antagonist Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 125000003963 dichloro group Chemical group Cl* 0.000 description 3
- XXECWTBMGGXMKP-UHFFFAOYSA-L dichloronickel;2-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 XXECWTBMGGXMKP-UHFFFAOYSA-L 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 210000001853 liver microsome Anatomy 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 230000003228 microsomal effect Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 229910052759 nickel Inorganic materials 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- AKNWFQAMENPERB-UHFFFAOYSA-N (3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=C(C)N=C2N(C(CC)CC)N=C(C)C2=N1 AKNWFQAMENPERB-UHFFFAOYSA-N 0.000 description 2
- FRHPAXDEWMMDAP-UHFFFAOYSA-N (4-methoxypyridin-2-yl) trifluoromethanesulfonate Chemical compound COC1=CC=NC(OS(=O)(=O)C(F)(F)F)=C1 FRHPAXDEWMMDAP-UHFFFAOYSA-N 0.000 description 2
- QDJPBFLSWVIGQY-UHFFFAOYSA-N (6-methoxy-2-propan-2-ylpyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(C(C)C)=N1 QDJPBFLSWVIGQY-UHFFFAOYSA-N 0.000 description 2
- RQMDBLHDKKQYNP-UHFFFAOYSA-N (6-methoxy-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=C(OC)N=C2N(C(CC)CC)N=C(C)C2=N1 RQMDBLHDKKQYNP-UHFFFAOYSA-N 0.000 description 2
- PXESPODEHHFYOV-UHFFFAOYSA-N 1-(2,6-dichloropyridin-3-yl)-2-ethylbutan-1-one Chemical compound CCC(CC)C(=O)C1=CC=C(Cl)N=C1Cl PXESPODEHHFYOV-UHFFFAOYSA-N 0.000 description 2
- BIGVOTVNQHHJRO-UHFFFAOYSA-N 1-[2-methoxy-4-(trifluoromethoxy)phenyl]propane-1,2-dione Chemical compound COC1=CC(OC(F)(F)F)=CC=C1C(=O)C(C)=O BIGVOTVNQHHJRO-UHFFFAOYSA-N 0.000 description 2
- PGEUKADUXYXSNV-UHFFFAOYSA-N 1-benzyl-3,6-dimethylpyrazolo[3,4-b]pyrazine Chemical compound C12=NC(C)=CN=C2C(C)=NN1CC1=CC=CC=C1 PGEUKADUXYXSNV-UHFFFAOYSA-N 0.000 description 2
- XUQRLMCZVKFXFX-UHFFFAOYSA-N 1-bromo-2-methoxy-4-(trifluoromethoxy)benzene Chemical compound COC1=CC(OC(F)(F)F)=CC=C1Br XUQRLMCZVKFXFX-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- GWFWEAWYOQCHFX-UHFFFAOYSA-N 1-methoxypropan-2-ylhydrazine;hydrochloride Chemical group Cl.COCC(C)NN GWFWEAWYOQCHFX-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- QUKPALAWEPMWOS-UHFFFAOYSA-N 1h-pyrazolo[3,4-d]pyrimidine Chemical class C1=NC=C2C=NNC2=N1 QUKPALAWEPMWOS-UHFFFAOYSA-N 0.000 description 2
- RHRRKORKKIVAGJ-UHFFFAOYSA-N 2-bromo-5-(trifluoromethoxy)phenol Chemical compound OC1=CC(OC(F)(F)F)=CC=C1Br RHRRKORKKIVAGJ-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- GZSXIWDPTFEOFF-UHFFFAOYSA-N 2-methoxy-4-(trifluoromethoxy)benzoic acid Chemical compound COC1=CC(OC(F)(F)F)=CC=C1C(O)=O GZSXIWDPTFEOFF-UHFFFAOYSA-N 0.000 description 2
- PPYRIPJLBOJUNH-UHFFFAOYSA-N 2-methoxy-6-propan-2-ylpyridine Chemical compound COC1=CC=CC(C(C)C)=N1 PPYRIPJLBOJUNH-UHFFFAOYSA-N 0.000 description 2
- UOFCIZJNXQPVRA-UHFFFAOYSA-N 3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound C1=C(C)N=C2N(C(CC)CC)N=C(C)C2=N1 UOFCIZJNXQPVRA-UHFFFAOYSA-N 0.000 description 2
- DBHANEQBGVDWRC-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-yl-1h-pyridin-2-one Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1O DBHANEQBGVDWRC-UHFFFAOYSA-N 0.000 description 2
- DLTUCKVHMFCQNU-UHFFFAOYSA-N 3-(6-ethyl-3-methyl-2h-pyrazolo[3,4-b]pyrazin-5-yl)-n-methyl-6-propan-2-ylpyridin-2-amine Chemical compound CCC1=NC=2NN=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1NC DLTUCKVHMFCQNU-UHFFFAOYSA-N 0.000 description 2
- VTOQFOCYBTVOJZ-UHFFFAOYSA-N 3-bromopentane Chemical compound CCC(Br)CC VTOQFOCYBTVOJZ-UHFFFAOYSA-N 0.000 description 2
- AGVPSBDCZREIHN-UHFFFAOYSA-N 4-methoxy-n,n-dimethylpyridin-2-amine Chemical compound COC1=CC=NC(N(C)C)=C1 AGVPSBDCZREIHN-UHFFFAOYSA-N 0.000 description 2
- ZYNJFZHNKQWCAC-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-3-pentan-3-yloxy-1h-pyrazolo[3,4-b]pyrazine Chemical compound N1=C2C(OC(CC)CC)=NNC2=NC(C)=C1C1=CC=C(OC(F)(F)F)C=C1OC ZYNJFZHNKQWCAC-UHFFFAOYSA-N 0.000 description 2
- NWGJICLFCFVMBE-UHFFFAOYSA-N 5-bromo-2-(dimethylamino)-1h-pyridin-4-one Chemical compound CN(C)C1=CC(=O)C(Br)=CN1 NWGJICLFCFVMBE-UHFFFAOYSA-N 0.000 description 2
- FJCGQINRDIQYQT-UHFFFAOYSA-N 5-bromo-3,6-dimethyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazine Chemical compound BrC1=C(C)N=C2N(C(CC)CC)N=C(C)C2=N1 FJCGQINRDIQYQT-UHFFFAOYSA-N 0.000 description 2
- LTBJXVMZGBOLDO-UHFFFAOYSA-N 5-bromo-3,6-dimethyl-1-propan-2-ylpyrazolo[3,4-b]pyrazine Chemical compound BrC1=C(C)N=C2N(C(C)C)N=C(C)C2=N1 LTBJXVMZGBOLDO-UHFFFAOYSA-N 0.000 description 2
- ITUPSXMFKJKMHR-UHFFFAOYSA-N 5-bromo-3,6-dimethyl-2h-pyrazolo[3,4-b]pyrazine Chemical compound CC1=C(Br)N=C2C(C)=NNC2=N1 ITUPSXMFKJKMHR-UHFFFAOYSA-N 0.000 description 2
- VAYXTSQDQDZGAI-UHFFFAOYSA-N 5-bromo-6-chloro-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC1=C(Br)C=C2C(C(CC)CC)=NN(C)C2=N1 VAYXTSQDQDZGAI-UHFFFAOYSA-N 0.000 description 2
- VSSNLTKVCYNFLL-UHFFFAOYSA-N 5-methyl-4-nitro-2-pentan-3-ylpyrazol-3-amine Chemical compound CCC(CC)N1N=C(C)C([N+]([O-])=O)=C1N VSSNLTKVCYNFLL-UHFFFAOYSA-N 0.000 description 2
- ZVTXHIWYGDMTAH-UHFFFAOYSA-N 6-chloro-1,5-dimethyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC1=C(C)C=C2C(C(CC)CC)=NN(C)C2=N1 ZVTXHIWYGDMTAH-UHFFFAOYSA-N 0.000 description 2
- XNBKAGPINFMZHL-UHFFFAOYSA-N 6-chloro-5-ethyl-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC1=C(CC)C=C2C(C(CC)CC)=NN(C)C2=N1 XNBKAGPINFMZHL-UHFFFAOYSA-N 0.000 description 2
- UJERPVCVLGCVQW-UHFFFAOYSA-N 6-chloro-n-pentan-3-ylpyrazin-2-amine Chemical compound CCC(CC)NC1=CN=CC(Cl)=N1 UJERPVCVLGCVQW-UHFFFAOYSA-N 0.000 description 2
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 2
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 2
- 230000002407 ATP formation Effects 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000017194 Affective disease Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108091005470 CRHR2 Proteins 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 description 2
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 2
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 206010019842 Hepatomegaly Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010029260 Neuroblastoma Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 2
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000006619 Stille reaction Methods 0.000 description 2
- 208000013200 Stress disease Diseases 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 206010048327 Supranuclear palsy Diseases 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 208000001871 Tachycardia Diseases 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- IVPOYDDYTQIIET-UHFFFAOYSA-N [2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methoxypropyl] methanesulfonate Chemical compound CCC1=NC=2N(C(COC)COS(C)(=O)=O)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC IVPOYDDYTQIIET-UHFFFAOYSA-N 0.000 description 2
- TVGOHIHUIYNARL-UHFFFAOYSA-N [3-(1-benzyl-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl] trifluoromethanesulfonate Chemical compound N1=C(C)C=2N=C(C=3C(=NC(=CC=3)C(C)C)OS(=O)(=O)C(F)(F)F)C(CC)=NC=2N1CC1=CC=CC=C1 TVGOHIHUIYNARL-UHFFFAOYSA-N 0.000 description 2
- CLTNZMGTZFJQMX-UHFFFAOYSA-N [3-(6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-ylpyridin-2-yl] trifluoromethanesulfonate Chemical compound CCC=1N=C2N(C(CC)CC)N=C(C)C2=NC=1C1=CC=C(C(C)C)N=C1OS(=O)(=O)C(F)(F)F CLTNZMGTZFJQMX-UHFFFAOYSA-N 0.000 description 2
- BNQNMTSAFNTECK-UHFFFAOYSA-N [3-methyl-6-(methylamino)-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl] trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=C(NC)N=C2N(C(CC)CC)N=C(C)C2=N1 BNQNMTSAFNTECK-UHFFFAOYSA-N 0.000 description 2
- WYYLIOQAOKRRPK-UHFFFAOYSA-N [3-methyl-6-[methyl(trifluoromethylsulfonyl)amino]-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl] trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=C(N(C)S(=O)(=O)C(F)(F)F)N=C2N(C(CC)CC)N=C(C)C2=N1 WYYLIOQAOKRRPK-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000000338 anxiogenic effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-M benzenecarboximidate Chemical compound [NH-]C(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-M 0.000 description 2
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 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 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
- 108091008039 hormone receptors Proteins 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 210000003141 lower extremity Anatomy 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
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 210000001589 microsome Anatomy 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- WWZGQUNHUVWALX-UHFFFAOYSA-N n,2-dimethoxy-n-methyl-4-(trifluoromethoxy)benzamide Chemical compound CON(C)C(=O)C1=CC=C(OC(F)(F)F)C=C1OC WWZGQUNHUVWALX-UHFFFAOYSA-N 0.000 description 2
- JRFDLYLIEQPIES-UHFFFAOYSA-N n-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]prop-2-enyl]cyclobutanamine Chemical compound CCC1=NC=2N(C(=C)CNC3CCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC JRFDLYLIEQPIES-UHFFFAOYSA-N 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000006794 tachycardia Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YHLYZSRYRWSHMP-UHFFFAOYSA-N tert-butyl n-(1-methoxypropan-2-ylideneamino)carbamate Chemical compound COCC(C)=NNC(=O)OC(C)(C)C YHLYZSRYRWSHMP-UHFFFAOYSA-N 0.000 description 2
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 150000003738 xylenes Chemical class 0.000 description 2
- XUWAHAVKQUELEK-UHFFFAOYSA-N (1-methoxypropan-2-ylamino)carbamic acid Chemical compound COCC(C)NNC(=O)O XUWAHAVKQUELEK-UHFFFAOYSA-N 0.000 description 1
- QNEGDGPAXKYZHZ-UHFFFAOYSA-N (2,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1Cl QNEGDGPAXKYZHZ-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- PQWHYMIYFPATGG-UHFFFAOYSA-N (4-amino-5-oxo-1,2-dihydropyrazol-3-yl)azanium;hydrogen sulfate Chemical compound OS(O)(=O)=O.NC=1NNC(=O)C=1N PQWHYMIYFPATGG-UHFFFAOYSA-N 0.000 description 1
- MCYVNNPUSZWZPI-UHFFFAOYSA-N (6-ethyl-3-methyl-1-pentan-3-ylpyrazolo[3,4-b]pyrazin-5-yl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=C(CC)N=C2N(C(CC)CC)N=C(C)C2=N1 MCYVNNPUSZWZPI-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- XCNCWUWFKBPSNJ-UHFFFAOYSA-N 1,3-bis(phenylmethoxy)propan-2-ylhydrazine Chemical group C=1C=CC=CC=1COCC(NN)COCC1=CC=CC=C1 XCNCWUWFKBPSNJ-UHFFFAOYSA-N 0.000 description 1
- LHBQVBVCWLHKAL-UHFFFAOYSA-N 1-(2,6-dichloro-5-ethylpyridin-3-yl)-2-ethylbutan-1-one Chemical compound CCC(CC)C(=O)C1=CC(CC)=C(Cl)N=C1Cl LHBQVBVCWLHKAL-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 description 1
- JQZZTIHLYMCNCM-UHFFFAOYSA-N 1-[1,3-bis(phenylmethoxy)propan-2-yl]-6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound CCC1=NC=2N(C(COCC=3C=CC=CC=3)COCC=3C=CC=CC=3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC JQZZTIHLYMCNCM-UHFFFAOYSA-N 0.000 description 1
- OMSIMDVDKGSNMR-UHFFFAOYSA-N 1-benzyl-6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazine Chemical compound N1=C(C)C=2N=C(C=3C(=NC(=CC=3)C(C)C)OC)C(CC)=NC=2N1CC1=CC=CC=C1 OMSIMDVDKGSNMR-UHFFFAOYSA-N 0.000 description 1
- OKSRAPDSZKICKZ-UHFFFAOYSA-N 1-methoxy-3-(trifluoromethoxy)benzene Chemical compound COC1=CC=CC(OC(F)(F)F)=C1 OKSRAPDSZKICKZ-UHFFFAOYSA-N 0.000 description 1
- CUZLJOLBIRPEFB-UHFFFAOYSA-N 1-methoxypropan-2-one Chemical compound COCC(C)=O CUZLJOLBIRPEFB-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- RRRIVLVAFKDWCH-UHFFFAOYSA-N 1-methylpyrazolo[3,4-b]pyrazine Chemical compound C1=CN=C2N(C)N=CC2=N1 RRRIVLVAFKDWCH-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical compound C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 description 1
- LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 1
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 description 1
- UNNGUFMVYQJGTD-UHFFFAOYSA-N 2-Ethylbutanal Chemical compound CCC(CC)C=O UNNGUFMVYQJGTD-UHFFFAOYSA-N 0.000 description 1
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- RBTPVZTVPXWBCF-UHFFFAOYSA-N 2-[1,3-bis(phenylmethoxy)propan-2-yl]-5-methyl-4-nitropyrazol-3-amine Chemical compound NC1=C([N+]([O-])=O)C(C)=NN1C(COCC=1C=CC=CC=1)COCC1=CC=CC=C1 RBTPVZTVPXWBCF-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- KVGGSTUZMLEFFK-UHFFFAOYSA-N 2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methoxypropan-1-ol Chemical compound CCC1=NC=2N(C(CO)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC KVGGSTUZMLEFFK-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- JQLOELYADIUZLD-UHFFFAOYSA-N 2-bromo-1,1-diethoxybutane Chemical compound CCOC(OCC)C(Br)CC JQLOELYADIUZLD-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- VAVGOGHLNAJECD-UHFFFAOYSA-N 2-chloro-6-methoxypyridine Chemical compound COC1=CC=CC(Cl)=N1 VAVGOGHLNAJECD-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- VFNDYQPYYFGVBB-UHFFFAOYSA-N 2-nitro-3-oxobutanenitrile pyridine Chemical compound C1=CC=NC=C1.CC(=O)C(C#N)[N+]([O-])=O VFNDYQPYYFGVBB-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- BNKWTZXQHJHKCI-UHFFFAOYSA-N 3,5-dichloro-6-ethyl-1,4-oxazin-2-one Chemical compound CCC=1OC(=O)C(Cl)=NC=1Cl BNKWTZXQHJHKCI-UHFFFAOYSA-N 0.000 description 1
- IAXMLNUCJZEOBP-UHFFFAOYSA-N 3,6-dimethyl-1-pentan-3-yl-4h-pyrazolo[3,4-b]pyrazin-5-one Chemical compound OC1=C(C)N=C2N(C(CC)CC)N=C(C)C2=N1 IAXMLNUCJZEOBP-UHFFFAOYSA-N 0.000 description 1
- ALZQJEBUDFPVRL-UHFFFAOYSA-N 3-(1-benzyl-6-ethyl-3-methylpyrazolo[3,4-b]pyrazin-5-yl)-6-propan-2-yl-1h-pyridin-2-one Chemical compound N1=C(C)C=2N=C(C=3C(=NC(=CC=3)C(C)C)O)C(CC)=NC=2N1CC1=CC=CC=C1 ALZQJEBUDFPVRL-UHFFFAOYSA-N 0.000 description 1
- UWLJERQTLRORJN-UHFFFAOYSA-N 3-(trifluoromethoxy)phenol Chemical compound OC1=CC=CC(OC(F)(F)F)=C1 UWLJERQTLRORJN-UHFFFAOYSA-N 0.000 description 1
- VEKFTKILCNXLJQ-UHFFFAOYSA-N 3-methyl-6-(methylamino)-1-pentan-3-yl-4h-pyrazolo[3,4-b]pyrazin-5-one Chemical compound OC1=C(NC)N=C2N(C(CC)CC)N=C(C)C2=N1 VEKFTKILCNXLJQ-UHFFFAOYSA-N 0.000 description 1
- 125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- RJNUXEDAPIKMDE-UHFFFAOYSA-M 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium;chloride;hydrate Chemical compound O.[Cl-].COC1=NC(OC)=NC([N+]2(C)CCOCC2)=N1 RJNUXEDAPIKMDE-UHFFFAOYSA-M 0.000 description 1
- JAOUWTBETOTCHL-UHFFFAOYSA-N 4-[2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]prop-2-enyl]morpholine Chemical compound CCC1=NC=2N(C(=C)CN3CCOCC3)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC JAOUWTBETOTCHL-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
- OLXSSIGLMQHXHR-UHFFFAOYSA-N 4-ethylhex-1-yn-3-ol Chemical compound CCC(CC)C(O)C#C OLXSSIGLMQHXHR-UHFFFAOYSA-N 0.000 description 1
- SJWHILBZPGQBJE-UHFFFAOYSA-N 4-ethylpyridin-2-amine Chemical compound CCC1=CC=NC(N)=C1 SJWHILBZPGQBJE-UHFFFAOYSA-N 0.000 description 1
- BZIUQZRSHNDQTH-UHFFFAOYSA-N 4-methoxy-1h-pyridin-2-one Chemical compound COC1=CC=NC(O)=C1 BZIUQZRSHNDQTH-UHFFFAOYSA-N 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- XDWUNABFOGIJOS-UHFFFAOYSA-N 5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3,6-dimethyl-1-propan-2-ylpyrazolo[3,4-b]pyrazine Chemical compound COC1=NC(C(C)C)=CC=C1C(C(=N1)C)=NC2=C1N(C(C)C)N=C2C XDWUNABFOGIJOS-UHFFFAOYSA-N 0.000 description 1
- FETKQSKTSRJILW-UHFFFAOYSA-N 5-[2-methoxy-4-(trifluoromethoxy)phenyl]-6-methyl-3-pentan-3-yloxy-1-(trifluoromethylsulfonyl)pyrazolo[3,4-b]pyrazine Chemical compound N1=C2C(OC(CC)CC)=NN(S(=O)(=O)C(F)(F)F)C2=NC(C)=C1C1=CC=C(OC(F)(F)F)C=C1OC FETKQSKTSRJILW-UHFFFAOYSA-N 0.000 description 1
- RSWILCOQDPKRNL-UHFFFAOYSA-N 5-bromo-3-methoxy-6-methyl-n-pentan-3-ylpyrazin-2-amine Chemical compound CCC(CC)NC1=NC(C)=C(Br)N=C1OC RSWILCOQDPKRNL-UHFFFAOYSA-N 0.000 description 1
- KAPUAWKCOGEFDJ-UHFFFAOYSA-N 5-methyl-2-pentan-3-ylpyrazole-3,4-diamine Chemical compound CCC(CC)N1N=C(C)C(N)=C1N KAPUAWKCOGEFDJ-UHFFFAOYSA-N 0.000 description 1
- SGEGQQKYIUKFDF-UHFFFAOYSA-N 6-(2-methoxy-4-methylphenyl)-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound C=1C=C2C(C(CC)CC)=NN(C)C2=NC=1C1=CC=C(C)C=C1OC SGEGQQKYIUKFDF-UHFFFAOYSA-N 0.000 description 1
- VEXXUWVRCYCTBV-UHFFFAOYSA-N 6-[2-methoxy-4-(trifluoromethoxy)phenyl]-1,5-dimethyl-2h-pyrazolo[3,4-b]pyrazin-3-one Chemical compound COC1=CC(OC(F)(F)F)=CC=C1C(C(=N1)C)=NC2=C1C(O)=NN2C VEXXUWVRCYCTBV-UHFFFAOYSA-N 0.000 description 1
- DVSIDMYFFQEEPZ-UHFFFAOYSA-N 6-chloro-1-methyl-3-pentan-3-ylpyrazolo[3,4-b]pyridine Chemical compound ClC1=CC=C2C(C(CC)CC)=NN(C)C2=N1 DVSIDMYFFQEEPZ-UHFFFAOYSA-N 0.000 description 1
- UTYNORZQSVPJGF-UHFFFAOYSA-N 6-methoxy-3-methyl-1-pentan-3-yl-4h-pyrazolo[3,4-b]pyrazin-5-one Chemical compound OC1=C(OC)N=C2N(C(CC)CC)N=C(C)C2=N1 UTYNORZQSVPJGF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000017916 BDKRB1 Human genes 0.000 description 1
- 108060003359 BDKRB1 Proteins 0.000 description 1
- 102000017915 BDKRB2 Human genes 0.000 description 1
- 101150022344 BDKRB2 gene Proteins 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 229940110385 Benzodiazepine receptor antagonist Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000010183 Bradykinin receptor Human genes 0.000 description 1
- 108050001736 Bradykinin receptor Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000511343 Chondrostoma nasus Species 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 206010015549 Euthyroid sick syndrome Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 102000027484 GABAA receptors Human genes 0.000 description 1
- 108091008681 GABAA receptors Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 102100034223 Golgi apparatus protein 1 Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 101000895481 Homo sapiens Corticoliberin Proteins 0.000 description 1
- 101000878678 Homo sapiens Corticotropin-releasing factor receptor 1 Proteins 0.000 description 1
- 101100449731 Homo sapiens GLG1 gene Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 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
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 1
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 102000009493 Neurokinin receptors Human genes 0.000 description 1
- 108050000302 Neurokinin receptors Proteins 0.000 description 1
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 1
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 101150085511 PEDS1 gene Proteins 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 101150024701 PPH3 gene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 102100037592 Plasmanylethanolamine desaturase Human genes 0.000 description 1
- 208000008939 Pneumonic Pasteurellosis Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 206010054048 Postoperative ileus Diseases 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 101000948733 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Probable phospholipid translocase non-catalytic subunit CRF1 Proteins 0.000 description 1
- 101100439271 Schizosaccharomyces pombe (strain 972 / ATCC 24843) cfr1 gene Proteins 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 108090001094 Thyrotropin-releasing hormone receptors Proteins 0.000 description 1
- 102000004852 Thyrotropin-releasing hormone receptors Human genes 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 235000004240 Triticum spelta Nutrition 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 102000012088 Vasoactive Intestinal Peptide Receptors Human genes 0.000 description 1
- 108010075974 Vasoactive Intestinal Peptide Receptors Proteins 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- ITCQYRWOWPXOBQ-UHFFFAOYSA-N [2-[6-ethyl-5-(2-methoxy-6-propan-2-ylpyridin-3-yl)-3-methylpyrazolo[3,4-b]pyrazin-1-yl]-3-methylsulfonyloxypropyl] methanesulfonate Chemical compound CCC1=NC=2N(C(COS(C)(=O)=O)COS(C)(=O)=O)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OC ITCQYRWOWPXOBQ-UHFFFAOYSA-N 0.000 description 1
- MXBNGFBEIHOJFL-UHFFFAOYSA-N [3-[6-ethyl-1-(1-methoxypropan-2-yl)-3-methylpyrazolo[3,4-b]pyrazin-5-yl]-6-propan-2-ylpyridin-2-yl] trifluoromethanesulfonate Chemical compound CCC1=NC=2N(C(C)COC)N=C(C)C=2N=C1C1=CC=C(C(C)C)N=C1OS(=O)(=O)C(F)(F)F MXBNGFBEIHOJFL-UHFFFAOYSA-N 0.000 description 1
- LJJGMQKIIMYIGL-UHFFFAOYSA-N [6-(diethylamino)-4-ethylpyridin-3-yl]boronic acid Chemical compound CCN(CC)C1=CC(CC)=C(B(O)O)C=N1 LJJGMQKIIMYIGL-UHFFFAOYSA-N 0.000 description 1
- OBUIBLXEKZAWEA-UHFFFAOYSA-N [6-(dimethylamino)-4-propan-2-yloxypyridin-3-yl]boronic acid Chemical compound CC(C)OC1=CC(N(C)C)=NC=C1B(O)O OBUIBLXEKZAWEA-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 231100000131 acute cytotoxicity Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 1
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 210000004198 anterior pituitary gland Anatomy 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001262 anti-secretory effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 239000000749 benzodiazepine receptor blocking agent Substances 0.000 description 1
- 239000000755 benzodiazepine receptor inverse stimulating agent Substances 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000005512 benztetrazolyl group Chemical group 0.000 description 1
- PRBLRLQZOKOQCQ-UHFFFAOYSA-N benzylhydrazine;hydron;chloride Chemical group Cl.NNCC1=CC=CC=C1 PRBLRLQZOKOQCQ-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 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
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229960004782 chlordiazepoxide Drugs 0.000 description 1
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 108010050742 corticotropin releasing hormone (9-41) Proteins 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 238000002565 electrocardiography Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 229940126904 hypoglycaemic agent Drugs 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 102000010681 interleukin-8 receptors Human genes 0.000 description 1
- 108010038415 interleukin-8 receptors Proteins 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000005438 isoindazolyl group Chemical group 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 244000309715 mini pig Species 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 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
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- QEEJLLNYQOBRRM-KSHGRFHLSA-N ovine crf Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](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](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C1=CN=CN1 QEEJLLNYQOBRRM-KSHGRFHLSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920003199 poly(diethylsiloxane) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 229940076788 pyruvate Drugs 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229940075993 receptor modulator Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 1
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000004722 stifle Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- NCMWLXIQNKUWEU-UHFFFAOYSA-N tert-butyl n-(1-methoxypropan-2-ylamino)carbamate Chemical compound COCC(C)NNC(=O)OC(C)(C)C NCMWLXIQNKUWEU-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical group 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000006032 tissue transformation Effects 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50003303P | 2003-09-03 | 2003-09-03 | |
| US60/500,033 | 2003-09-03 | ||
| PCT/US2004/028663 WO2005028480A2 (en) | 2003-09-03 | 2004-09-03 | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2537916A1 true CA2537916A1 (en) | 2005-03-31 |
Family
ID=34375241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002537916A Abandoned CA2537916A1 (en) | 2003-09-03 | 2004-09-03 | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20050070542A1 (https=) |
| EP (1) | EP1675858A2 (https=) |
| JP (1) | JP2007504243A (https=) |
| AU (1) | AU2004274403A1 (https=) |
| CA (1) | CA2537916A1 (https=) |
| WO (1) | WO2005028480A2 (https=) |
Families Citing this family (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101312736B1 (ko) * | 2003-02-27 | 2013-09-27 | 팔라우 파르마 에스에이 | 피라졸로피리딘 유도체 |
| US20090008238A1 (en) * | 2004-04-09 | 2009-01-08 | The Arizona Bd Of Reg On Behalf Of The Univ Of Az | Transportable gas sterilization unit, disposable gas generator, light activated anti-infective coating and method of disinfection and sterilization using chlorine dioxide |
| TW200618800A (en) * | 2004-08-03 | 2006-06-16 | Uriach Y Compania S A J | Heterocyclic compounds |
| RU2008110941A (ru) * | 2005-08-25 | 2009-09-27 | Ф.Хоффманн-Ля Рош Аг (Ch) | ИНГИБИТОРЫ КИНАЗЫ p38 МАР И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| GB0525068D0 (en) | 2005-12-08 | 2006-01-18 | Novartis Ag | Organic compounds |
| EP1961754A4 (en) | 2005-12-15 | 2009-11-11 | Ono Pharmaceutical Co | BICYCLIC HETEROCYCLIC COMPOUND |
| NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
| WO2008076446A1 (en) * | 2006-12-18 | 2008-06-26 | Coleman Peter R | Accelerated opiate dependence detoxification process |
| JP2010513370A (ja) * | 2006-12-19 | 2010-04-30 | エフ．ホフマン−ラ ロシュ アーゲー | ピラゾロ［３，４−ｄ］ピリミジンｐ３８ＭＡＰキナーゼインヒビター |
| US20100298557A1 (en) | 2006-12-28 | 2010-11-25 | Taisho Pharmaceutical Co., Ltd | Pyrazolopyrimidine compound |
| WO2010016846A1 (en) * | 2008-08-08 | 2010-02-11 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 for treatment of disease |
| JP2010077067A (ja) * | 2008-09-25 | 2010-04-08 | Fujifilm Corp | ピラゾール誘導体類の製造方法 |
| US8349852B2 (en) | 2009-01-13 | 2013-01-08 | Novartis Ag | Quinazolinone derivatives useful as vanilloid antagonists |
| JP5781510B2 (ja) | 2009-08-12 | 2015-09-24 | ノバルティス アーゲー | ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用 |
| JP5775871B2 (ja) | 2009-08-20 | 2015-09-09 | ノバルティス アーゲー | ヘテロ環式オキシム化合物 |
| EP3795573B1 (en) | 2009-12-31 | 2022-07-06 | Hutchison Medipharma Limited | Certain triazolopyrazines, compositions thereof and methods of use therefor |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| WO2011092290A1 (en) | 2010-02-01 | 2011-08-04 | Novartis Ag | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
| EP2531490B1 (en) | 2010-02-02 | 2014-10-15 | Novartis AG | Cyclohexyl amide derivatives as crf receptor antagonists |
| US8754114B2 (en) | 2010-12-22 | 2014-06-17 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3 |
| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| AR086554A1 (es) | 2011-05-27 | 2014-01-08 | Novartis Ag | Derivados de la piperidina 3-espirociclica como agonistas de receptores de la ghrelina |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US8846712B2 (en) | 2011-09-12 | 2014-09-30 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2570415B1 (en) | 2011-09-19 | 2015-08-26 | Sanofi | N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides and their use as pharmaceuticals |
| US20130072493A1 (en) | 2011-09-19 | 2013-03-21 | Sanofi | N-[4-(1H-PYRAZOLO[3,4-b]PYRAZIN-6-YL)-PHENYL]-SULFONAMIDES AND THEIR USE AS PHARMACEUTICALS |
| AU2011377409B2 (en) | 2011-09-19 | 2017-05-25 | Sanofi | N-[4-(1H-pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides and their use as pharmaceuticals |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US9199975B2 (en) | 2011-09-30 | 2015-12-01 | Asana Biosciences, Llc | Biaryl imidazole derivatives for regulating CYP17 |
| JP2015525202A (ja) | 2012-05-03 | 2015-09-03 | ノバルティス アーゲー | グレリン受容体アゴニストとしての２，７−ジアザ−スピロ［４，５］デカ−７−イル誘導体のｌ−リンゴ酸塩およびその結晶形態 |
| EP2847191B1 (en) | 2012-05-09 | 2016-06-15 | Sanofi | Substituted 6-(4-hydroxy-phenyl)-1h-pyrazolo[3,4-b]pyridine derivatives as kinase inhibitors |
| ES2704744T3 (es) | 2012-06-13 | 2019-03-19 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| EP2884978B1 (en) * | 2012-08-16 | 2019-07-17 | The Scripps Research Institute | Novel kappa opioid ligands |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| ES2717757T3 (es) | 2014-01-29 | 2019-06-25 | Glaxosmithkline Ip Dev Ltd | Compuestos |
| KR20160106622A (ko) | 2014-01-29 | 2016-09-12 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 화합물 |
| EP3102576B8 (en) | 2014-02-03 | 2019-06-19 | Vitae Pharmaceuticals, LLC | Dihydropyrrolopyridine inhibitors of ror-gamma |
| PT3207043T (pt) | 2014-10-14 | 2019-03-25 | Vitae Pharmaceuticals Llc | Inibidores de di-hidropirrolopiridina de ror-gama |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| US9845308B2 (en) | 2014-11-05 | 2017-12-19 | Vitae Pharmaceuticals, Inc. | Isoindoline inhibitors of ROR-gamma |
| US9663515B2 (en) | 2014-11-05 | 2017-05-30 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| MX373169B (es) | 2015-02-20 | 2020-04-24 | Incyte Holdings Corp | Heterociclos bicíclicos como inhibidores de receptores del factor de crecimiento fibroblástico (fgfr). |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| WO2017024018A1 (en) | 2015-08-05 | 2017-02-09 | Vitae Pharmaceuticals, Inc. | Modulators of ror-gamma |
| US11008340B2 (en) | 2015-11-20 | 2021-05-18 | Vitae Pharmaceuticals, Llc | Modulators of ROR-gamma |
| TW202220968A (zh) | 2016-01-29 | 2022-06-01 | 美商維它藥物有限責任公司 | ＲＯＲ－γ調節劑 |
| AU2017274199B2 (en) | 2016-05-31 | 2021-09-23 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| US9481674B1 (en) | 2016-06-10 | 2016-11-01 | Vitae Pharmaceuticals, Inc. | Dihydropyrrolopyridine inhibitors of ROR-gamma |
| KR102598895B1 (ko) | 2016-07-12 | 2023-11-07 | 레볼루션 메디슨즈, 인크. | 다른자리 입체성 shp2 억제제로서의 2,5-이치환 3-메틸 피라진 및 2,5,6-3치환 3-메틸 피라진 |
| MX2019008695A (es) | 2017-01-23 | 2019-09-11 | Revolution Medicines Inc | Compuestos biciclicos como inhibidores alostericos de shp2. |
| MX2019008696A (es) | 2017-01-23 | 2019-09-13 | Revolution Medicines Inc | Compuestos de piridina como inhibidores de shp2 alostericos. |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| JP2020528904A (ja) | 2017-07-24 | 2020-10-01 | ヴァイティー ファーマシューティカルズ，エルエルシー | ＲＯＲγの阻害剤 |
| WO2019018975A1 (en) | 2017-07-24 | 2019-01-31 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF ROR GAMMA |
| MX2020003579A (es) | 2017-10-12 | 2020-07-22 | Revolution Medicines Inc | Compuestos de piridina, pirazina, y triazina como inhibidores de shp2 alostericos. |
| AR113926A1 (es) | 2017-12-14 | 2020-07-01 | H Lundbeck As | Derivados de 1h-pirazolo[4,3-b]piridinas |
| BR112020009757A2 (pt) | 2017-12-15 | 2020-11-03 | Revolution Medicines, Inc. | compostos policíclicos como inibidores alostéricos de shp2 |
| US10766893B2 (en) * | 2017-12-20 | 2020-09-08 | H. Lundbeck A/S | 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors |
| CA3098988A1 (en) | 2018-05-02 | 2019-11-07 | Jw Pharmaceutical Corporation | Heterocycle derivative |
| KR102611661B1 (ko) | 2018-05-02 | 2023-12-08 | 나비레 파르마, 인코퍼레이티드 | Ptpn11의 치환된 헤테로사이클릭 억제제 |
| CR20200590A (es) | 2018-05-04 | 2021-04-26 | Incyte Corp | Formas sólidas de un inhibidor de fgfr y procesos para prepararlas |
| MA52493A (fr) | 2018-05-04 | 2021-03-10 | Incyte Corp | Sels d'un inhibiteur de fgfr |
| LT3833670T (lt) | 2018-08-10 | 2024-06-25 | Navire Pharma, Inc. | 6-(4-amino-3-metil-2-oksa-8-azaspiro[4.5]dekan-8-il)-3-(2,3-dichlorfenil)-2-metilpirimidin-4(3h)-ono dariniai ir susiję junginiai kaip ptpn11 (shp2) inhibitoriai, skirti vėžiui gydyti |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| KR20220024403A (ko) | 2019-06-14 | 2022-03-03 | 얀센 파마슈티카 엔.브이. | 치환된 피라졸로-피라진 및 이들의 glun2b 수용체 조절제로서의 용도 |
| JP7667097B2 (ja) | 2019-06-14 | 2025-04-22 | ヤンセン ファーマシューティカ エヌ．ベー． | 置換ピラゾロ－ピリジンアミド及びｇｌｕｎ２ｂ受容体調節因子としてのその使用 |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TWI891666B (zh) | 2019-10-14 | 2025-08-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之雙環雜環 |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| BR112022010664A2 (pt) | 2019-12-04 | 2022-08-16 | Incyte Corp | Derivados de um inibidor de fgfr |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含ｆｇｆｒ抑制劑及ｎｅｃｔｉｎ－４靶向劑之組合療法 |
| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3957785A (en) * | 1971-12-02 | 1976-05-18 | Societa' Farmaceutici Italia S.P.A. | Bβ-Pyrimidino-aminomethyl-10α-ergoline and 10α-methoxyergoline derivatives |
| US3957782A (en) * | 1974-12-16 | 1976-05-18 | E. R. Squibb & Sons, Inc. | Pyrazolo [3,4-b]pyrazine-5-carboxylic acids, esters, nitriles and amides |
| US4303658A (en) * | 1980-05-12 | 1981-12-01 | Abbott Laboratories | Antiviral pyrazolopyrazines |
| US4666908A (en) * | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| GB9013750D0 (en) * | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| TW370529B (en) * | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| CZ280697A3 (cs) * | 1995-03-10 | 1998-04-15 | Sanofi Pharmaceuticals, Inc. | 6 aryl-pyrazolo(3,4-d)pyrimidin-4-ony a kompozice je obsahující, a způsob jejich použití |
| EP1012151B1 (en) * | 1997-09-02 | 2002-08-07 | Bristol-Myers Squibb Pharma Company | Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin releasing hormone (crh) antagonists, useful for treating cns and stress-related disorders |
| GB9722520D0 (en) * | 1997-10-24 | 1997-12-24 | Pfizer Ltd | Compounds |
| ATE264861T1 (de) * | 1998-09-04 | 2004-05-15 | Ortho Mcneil Pharm Inc | 5-heterozyklyl-pyrazolo(4,3-d)pyrimidin-7-one für die behandlung von männlichen erectilen dysfunktionen |
| GB9823103D0 (en) * | 1998-10-23 | 1998-12-16 | Pfizer Ltd | Pharmaceutically active compounds |
| EP1002798A1 (en) * | 1998-11-20 | 2000-05-24 | Orchid Chemicals & Pharmaceuticals Ltd. | An improved process for preparing a therapeutically active pyrazolopyrimidinone derivative |
| GB0106661D0 (en) * | 2001-03-16 | 2001-05-09 | Pfizer Ltd | Pharmaceutically active compounds |
| EP1372656B1 (en) * | 2001-03-16 | 2005-06-22 | Pfizer Limited | Pyrazolo[4,3-d]pyrimidinone compounds as cgmp pde inhibitors |
| EP1336602A1 (en) * | 2002-02-13 | 2003-08-20 | Giovanni Scaramuzzino | Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases |
| JP2006521398A (ja) * | 2003-03-28 | 2006-09-21 | サイオス・インコーポレーテツド | ＴＧＦβの二−環式ピリミジン阻害剤 |
| US20050113379A1 (en) * | 2003-09-05 | 2005-05-26 | Ping Ge | Heteroaryl fused pyridines, pyrazines and pyrimidines as CRF1 receptor ligands |
| AU2005219517A1 (en) * | 2004-02-27 | 2005-09-15 | F.Hoffmann-La Roche Ag | Heteroaryl-fused pyrazolo derivatives |
-
2004
- 2004-09-03 WO PCT/US2004/028663 patent/WO2005028480A2/en not_active Ceased
- 2004-09-03 CA CA002537916A patent/CA2537916A1/en not_active Abandoned
- 2004-09-03 US US10/933,700 patent/US20050070542A1/en not_active Abandoned
- 2004-09-03 AU AU2004274403A patent/AU2004274403A1/en not_active Abandoned
- 2004-09-03 JP JP2006525454A patent/JP2007504243A/ja active Pending
- 2004-09-03 EP EP04788563A patent/EP1675858A2/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005028480A3 (en) | 2005-06-02 |
| WO2005028480A2 (en) | 2005-03-31 |
| AU2004274403A1 (en) | 2005-03-31 |
| JP2007504243A (ja) | 2007-03-01 |
| US20050070542A1 (en) | 2005-03-31 |
| EP1675858A2 (en) | 2006-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2537916A1 (en) | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds | |
| TWI380987B (zh) | 吡咯并吡激酶抑制劑 | |
| WO2005115399A2 (en) | Imidazopyrazines, imidazopyridines, ans imidazopyrimidines as crf1 receptor ligands | |
| EP1255740B1 (en) | Substituted arylpyrazines | |
| KR100574313B1 (ko) | 아졸로 트리아진 및 피리미딘 | |
| US6310063B1 (en) | Aminoalkyl substituted pyrrolo [3,2-E]pyridine and pyrollo [2,3-b]pyrimidine derivatives: modulators of CRF1 receptors | |
| WO2005023806A2 (en) | Heteroaryl fused pyridines, pyrazines and pyrimidines as crf1 receptor ligands | |
| JP2002507996A (ja) | 神経学的障害を治療するためのイミダゾピリミジン類およびイミダゾピリジン類 | |
| EP2448941A2 (en) | Pyrazolopyrimidine jak inhibitor compounds and methods | |
| JP2000511183A (ja) | 神経学的疾患治療のためのテトラヒドロプテリジンおよびピリジルピペラジン | |
| EP1322620A1 (en) | Benzimidazole and indole derivatives as crf receptor modulators | |
| US7297708B2 (en) | Heteroaromatic substituted cyclopropane as corticotropin releasing hormone ligands | |
| CA2478715A1 (en) | Novel pyrazolo [1,5-a]pyridine derivatives and their use as neurotransmitter modulators | |
| CA2416248A1 (en) | 5-substituted 2-aryl-4-pyrimidinones | |
| WO2004099213A2 (en) | Pyrrolo (1,2-b) pyridazine compounds and their use as crf-1 receptor antagonists | |
| WO2001068614A2 (en) | 5-substituted arylpyrimidines | |
| RS51244B (sr) | Derivati 3-heteroaril-3,5-dihidro-4-okso-4h-piridazino(4,5- b)-indol-1-acetamida, njihovo dobijanje i primena u terapiji | |
| CN100457756C (zh) | 咪唑-嘧啶类及三唑-嘧啶类:苯并二氮平受体配体 | |
| MXPA00009575A (en) | Aminoalkyl substituted pyrrolo[2,3-b]pyridine and pyrrolo[2,3-d]pyrimidine derivatives:modulators of crf1 receptors | |
| MXPA06002556A (en) | Heteroaryl fused pyridines, pyrazines and pyrimidines as crf1 receptor ligands |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |