JP5184536B2 - チオフェンピラゾロピリミジン化合物 - Google Patents
チオフェンピラゾロピリミジン化合物 Download PDFInfo
- Publication number
- JP5184536B2 JP5184536B2 JP2009529307A JP2009529307A JP5184536B2 JP 5184536 B2 JP5184536 B2 JP 5184536B2 JP 2009529307 A JP2009529307 A JP 2009529307A JP 2009529307 A JP2009529307 A JP 2009529307A JP 5184536 B2 JP5184536 B2 JP 5184536B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- reaction
- hexane
- added
- ethyl acetate
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 79
- 150000003839 salts Chemical class 0.000 claims description 26
- -1 nitro, methoxy, methoxymethyl Chemical group 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 242
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 184
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
- 238000006243 chemical reaction Methods 0.000 description 91
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 31
- 239000012298 atmosphere Substances 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000010410 layer Substances 0.000 description 26
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 25
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 25
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 25
- 238000002360 preparation method Methods 0.000 description 24
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 22
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 description 21
- 101000878678 Homo sapiens Corticotropin-releasing factor receptor 1 Proteins 0.000 description 21
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 21
- 101000948733 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Probable phospholipid translocase non-catalytic subunit CRF1 Proteins 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- 238000009739 binding Methods 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 230000027455 binding Effects 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 102100038019 Corticotropin-releasing factor receptor 2 Human genes 0.000 description 12
- 101000878664 Homo sapiens Corticotropin-releasing factor receptor 2 Proteins 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 229910052725 zinc Inorganic materials 0.000 description 12
- 239000011701 zinc Substances 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
- 229910052786 argon Inorganic materials 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 10
- 238000009826 distribution Methods 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 10
- 108091005471 CRHR1 Proteins 0.000 description 9
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 108091005470 CRHR2 Proteins 0.000 description 7
- 0 Cc1n[n]2c(C(*)*)cc(C)nc2c1* Chemical compound Cc1n[n]2c(C(*)*)cc(C)nc2c1* 0.000 description 7
- BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 229930192474 thiophene Natural products 0.000 description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 description 6
- 206010036618 Premenstrual syndrome Diseases 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- KQJDDNCSNLUGAK-UHFFFAOYSA-N 3-iodo-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CCC(CC)C1=CC(C)=NC2=C(I)C(C)=NN12 KQJDDNCSNLUGAK-UHFFFAOYSA-N 0.000 description 5
- QTEPSNRIXHMSKM-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[4,3-d]pyrimidine Chemical compound N1=CN=C2C(I)=NNC2=C1 QTEPSNRIXHMSKM-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000008589 Obesity Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000009871 nonspecific binding Effects 0.000 description 5
- 235000020824 obesity Nutrition 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 230000001817 pituitary effect Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 239000011592 zinc chloride Substances 0.000 description 5
- 235000005074 zinc chloride Nutrition 0.000 description 5
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 4
- 208000005676 Adrenogenital syndrome Diseases 0.000 description 4
- 208000007848 Alcoholism Diseases 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 4
- 208000008448 Congenital adrenal hyperplasia Diseases 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- 206010013654 Drug abuse Diseases 0.000 description 4
- 208000001640 Fibromyalgia Diseases 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 4
- 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 4
- 208000005107 Premature Birth Diseases 0.000 description 4
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 4
- 239000000683 Pro-Opiomelanocortin Substances 0.000 description 4
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 208000007107 Stomach Ulcer Diseases 0.000 description 4
- 230000008484 agonism Effects 0.000 description 4
- 206010001584 alcohol abuse Diseases 0.000 description 4
- 208000025746 alcohol use disease Diseases 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 201000005917 gastric ulcer Diseases 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 208000019116 sleep disease Diseases 0.000 description 4
- 208000011117 substance-related disease Diseases 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 208000009935 visceral pain Diseases 0.000 description 4
- MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 3
- YTETWZNORTXMFJ-UHFFFAOYSA-N 2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CCC(CC)C1=CC(C)=NC2=CC(C)=NN12 YTETWZNORTXMFJ-UHFFFAOYSA-N 0.000 description 3
- CRVNUZXQVCHLQW-UHFFFAOYSA-N 3-(5-bromo-3-chlorothiophen-2-yl)-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(Br)=CC=1Cl CRVNUZXQVCHLQW-UHFFFAOYSA-N 0.000 description 3
- ANNRUWYFVIGKHA-UHFFFAOYSA-N 3-[6-(dimethylamino)-4-methylpyridin-3-yl]-2,5-dimethyl-n,n-dipropylpyrazolo[1,5-a]pyrimidin-7-amine Chemical compound CC1=NN2C(N(CCC)CCC)=CC(C)=NC2=C1C1=CN=C(N(C)C)C=C1C ANNRUWYFVIGKHA-UHFFFAOYSA-N 0.000 description 3
- 208000033054 Cushing disease Diseases 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 3
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 3
- 206010036590 Premature baby Diseases 0.000 description 3
- 201000001880 Sexual dysfunction Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000000509 infertility Diseases 0.000 description 3
- 230000036512 infertility Effects 0.000 description 3
- 231100000535 infertility Toxicity 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 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 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 231100000872 sexual dysfunction Toxicity 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- LGQMDCIHBYTQJU-UHFFFAOYSA-N 2,5-dimethyl-1h-pyrazolo[1,5-a]pyrimidin-7-one Chemical compound CC1=CC(=O)N2NC(C)=CC2=N1 LGQMDCIHBYTQJU-UHFFFAOYSA-N 0.000 description 2
- JIZRGGUCOQKGQD-UHFFFAOYSA-N 2-nitrothiophene Chemical compound [O-][N+](=O)C1=CC=CS1 JIZRGGUCOQKGQD-UHFFFAOYSA-N 0.000 description 2
- OXYAOCAGZMYLDI-UHFFFAOYSA-N 3-(3-chlorothiophen-2-yl)-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC=CC=1Cl OXYAOCAGZMYLDI-UHFFFAOYSA-N 0.000 description 2
- RHSSAEZVCVVURO-UHFFFAOYSA-N 3-methylthieno[3,2-b]pyridine Chemical compound C1=CN=C2C(C)=CSC2=C1 RHSSAEZVCVVURO-UHFFFAOYSA-N 0.000 description 2
- PBFWFPWWCJABJD-UHFFFAOYSA-N 4-chloro-n-(dimethylaminomethylidene)thiophene-2-carboxamide Chemical compound CN(C)C=NC(=O)C1=CC(Cl)=CS1 PBFWFPWWCJABJD-UHFFFAOYSA-N 0.000 description 2
- ZYSQCHVJVZREAZ-UHFFFAOYSA-N 4-chlorothiophene-2-carbonitrile Chemical compound ClC1=CSC(C#N)=C1 ZYSQCHVJVZREAZ-UHFFFAOYSA-N 0.000 description 2
- JXZMYXSGIKGEJA-UHFFFAOYSA-N 4-chlorothiophene-2-carboxamide Chemical compound NC(=O)C1=CC(Cl)=CS1 JXZMYXSGIKGEJA-UHFFFAOYSA-N 0.000 description 2
- KURDJOFACNOXMV-UHFFFAOYSA-N 5-(4-chlorothiophen-2-yl)-1-methyl-1,2,4-triazole Chemical compound CN1N=CN=C1C1=CC(Cl)=CS1 KURDJOFACNOXMV-UHFFFAOYSA-N 0.000 description 2
- BXCOJAQBVASMAR-UHFFFAOYSA-N 5-(5-bromo-4-chlorothiophen-2-yl)-1-methyl-1,2,4-triazole Chemical compound CN1N=CN=C1C1=CC(Cl)=C(Br)S1 BXCOJAQBVASMAR-UHFFFAOYSA-N 0.000 description 2
- FYTLHYRDGXRYEY-UHFFFAOYSA-N 5-Methyl-3-pyrazolamine Chemical compound CC=1C=C(N)NN=1 FYTLHYRDGXRYEY-UHFFFAOYSA-N 0.000 description 2
- ARYSXQXKEJNADL-UHFFFAOYSA-N 5-fluoro-3-methyl-1-benzothiophene Chemical compound C1=C(F)C=C2C(C)=CSC2=C1 ARYSXQXKEJNADL-UHFFFAOYSA-N 0.000 description 2
- LTGAWNSZFPWASH-UHFFFAOYSA-N 7-butyl-3-iodo-2,5-dimethylpyrazolo[1,5-a]pyrimidine Chemical compound CCCCC1=CC(C)=NC2=C(I)C(C)=NN12 LTGAWNSZFPWASH-UHFFFAOYSA-N 0.000 description 2
- QGROGNQUPBOMJQ-UHFFFAOYSA-N 7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidine Chemical compound N1=C(C)C=C(Cl)N2N=C(C)C=C21 QGROGNQUPBOMJQ-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 101150105710 CRF1 gene Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FRAKGJKEMLMXMD-UHFFFAOYSA-N Cc1ncn[n]1C Chemical compound Cc1ncn[n]1C FRAKGJKEMLMXMD-UHFFFAOYSA-N 0.000 description 2
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 2
- 239000005751 Copper oxide Substances 0.000 description 2
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 2
- 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 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108090000189 Neuropeptides Proteins 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 241000233805 Phoenix Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 210000004198 anterior pituitary gland Anatomy 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 230000007529 anxiety like behavior Effects 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000002567 autonomic effect Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 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 2
- 229910000431 copper oxide Inorganic materials 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 2
- 238000012224 gene deletion Methods 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- UUSXSNJAQDJKCG-UHFFFAOYSA-N iodo(methoxy)methane Chemical compound COCI UUSXSNJAQDJKCG-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 208000015706 neuroendocrine disease Diseases 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 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 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000002821 scintillation proximity assay Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 150000003577 thiophenes Chemical class 0.000 description 2
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-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
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- BUEFDJQUUGMUJO-UHFFFAOYSA-N 1h-pyrazolo[1,5-a]pyrimidin-7-one Chemical compound O=C1C=CN=C2C=CNN12 BUEFDJQUUGMUJO-UHFFFAOYSA-N 0.000 description 1
- UIVVICIYVFEGIH-UHFFFAOYSA-N 1h-pyrazolo[4,3-d]pyrimidine;thiophene Chemical class C=1C=CSC=1.N1=CN=C2C=NNC2=C1 UIVVICIYVFEGIH-UHFFFAOYSA-N 0.000 description 1
- KFBXUKHERGLHLG-UHFFFAOYSA-N 2,4-Nonanedione Chemical compound CCCCCC(=O)CC(C)=O KFBXUKHERGLHLG-UHFFFAOYSA-N 0.000 description 1
- UOTNZJKQUNSKJN-UHFFFAOYSA-N 2,5-dimethyl-3-(3-methyl-5-nitrothiophen-2-yl)-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC([N+]([O-])=O)=CC=1C UOTNZJKQUNSKJN-UHFFFAOYSA-N 0.000 description 1
- OJFVVINIATZCQO-UHFFFAOYSA-N 2,5-dimethyl-3-[3-methyl-5-(2-methyl-1,2,4-triazol-3-yl)thiophen-2-yl]-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=C(SC(=C1)C=1N(N=CN1)C)C=1C(=NN2C1N=C(C=C2C(CC)CC)C)C OJFVVINIATZCQO-UHFFFAOYSA-N 0.000 description 1
- FEOWWVIFEQBZSE-UHFFFAOYSA-N 2,5-dimethyl-3-[3-methyl-5-(6-methylpyridin-2-yl)thiophen-2-yl]-6-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound C=12N=C(C)C(C(CC)CC)=CN2N=C(C)C=1C(=C(C=1)C)SC=1C1=CC=CC(C)=N1 FEOWWVIFEQBZSE-UHFFFAOYSA-N 0.000 description 1
- DAHVYXLODIKJMN-UHFFFAOYSA-N 2-(2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methylthieno[3,2-b]pyridine Chemical compound S1C2=CC=CN=C2C(C)=C1C1=C2N=C(C)C=C(C(CC)CC)N2N=C1C DAHVYXLODIKJMN-UHFFFAOYSA-N 0.000 description 1
- NWNJULSUNJLBCO-UHFFFAOYSA-N 2-(5-bromo-4-methylthiophen-2-yl)-6-methylpyridine Chemical compound S1C(Br)=C(C)C=C1C1=CC=CC(C)=N1 NWNJULSUNJLBCO-UHFFFAOYSA-N 0.000 description 1
- MHRHSJIWGVBMLY-UHFFFAOYSA-N 2-bromo-3-chlorothiophene Chemical compound ClC=1C=CSC=1Br MHRHSJIWGVBMLY-UHFFFAOYSA-N 0.000 description 1
- YYJBWYBULYUKMR-UHFFFAOYSA-N 2-bromo-3-methylthiophene Chemical compound CC=1C=CSC=1Br YYJBWYBULYUKMR-UHFFFAOYSA-N 0.000 description 1
- ZADAEJSZAKGTSD-UHFFFAOYSA-N 2-bromo-5-fluoro-3-methyl-1-benzothiophene Chemical compound C1=C(F)C=C2C(C)=C(Br)SC2=C1 ZADAEJSZAKGTSD-UHFFFAOYSA-N 0.000 description 1
- SOHDPICLICFSOP-UHFFFAOYSA-N 2-bromo-6-methylpyridine Chemical compound CC1=CC=CC(Br)=N1 SOHDPICLICFSOP-UHFFFAOYSA-N 0.000 description 1
- OKEHURCMYKPVFW-UHFFFAOYSA-N 2-methoxythiophene Chemical compound COC1=CC=CS1 OKEHURCMYKPVFW-UHFFFAOYSA-N 0.000 description 1
- BTLCCDKAGUEKJH-UHFFFAOYSA-N 3-(3-chloro-5-methoxythiophen-2-yl)-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(OC)=CC=1Cl BTLCCDKAGUEKJH-UHFFFAOYSA-N 0.000 description 1
- GIVHMSPFUPSFMQ-UHFFFAOYSA-N 3-(5-bromo-3-methylthiophen-2-yl)-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(Br)=CC=1C GIVHMSPFUPSFMQ-UHFFFAOYSA-N 0.000 description 1
- XFUSDMUJIHKDGB-UHFFFAOYSA-N 3-(5-fluoro-3-methyl-1-benzothiophen-2-yl)-2,5-dimethyl-7-propan-2-ylpyrazolo[1,5-a]pyrimidine Chemical compound S1C2=CC=C(F)C=C2C(C)=C1C1=C2N=C(C)C=C(C(C)C)N2N=C1C XFUSDMUJIHKDGB-UHFFFAOYSA-N 0.000 description 1
- LOIAVWHRSTUMHR-UHFFFAOYSA-N 3-[3-chloro-5-(2-methyl-1,2,4-triazol-3-yl)thiophen-2-yl]-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C(=C(C=1)Cl)SC=1C1=NC=NN1C LOIAVWHRSTUMHR-UHFFFAOYSA-N 0.000 description 1
- MXBCMYBZQGVRFL-UHFFFAOYSA-N 3-[3-chloro-5-(2-methyl-1,2,4-triazol-3-yl)thiophen-2-yl]-7-heptan-4-yl-2,5-dimethylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CCC)CCC)=CC(C)=NC2=C1C(=C(C=1)Cl)SC=1C1=NC=NN1C MXBCMYBZQGVRFL-UHFFFAOYSA-N 0.000 description 1
- KWZOULBKHIQNLK-UHFFFAOYSA-N 3-[3-chloro-5-(methoxymethyl)thiophen-2-yl]-2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(COC)=CC=1Cl KWZOULBKHIQNLK-UHFFFAOYSA-N 0.000 description 1
- VTOQFOCYBTVOJZ-UHFFFAOYSA-N 3-bromopentane Chemical compound CCC(Br)CC VTOQFOCYBTVOJZ-UHFFFAOYSA-N 0.000 description 1
- AACVULYSNJAKEQ-UHFFFAOYSA-N 4h-thieno[3,2-b]pyridin-7-one Chemical compound OC1=CC=NC2=C1SC=C2 AACVULYSNJAKEQ-UHFFFAOYSA-N 0.000 description 1
- HPFAKXCQLPTCQH-UHFFFAOYSA-N 5-(2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)-n,n,4-trimethylthiophen-2-amine;hydrochloride Chemical compound Cl.CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(N(C)C)=CC=1C HPFAKXCQLPTCQH-UHFFFAOYSA-N 0.000 description 1
- ZYLIOXAULQKGII-UHFFFAOYSA-N 5-bromo-1-methyl-1,2,4-triazole Chemical compound CN1N=CN=C1Br ZYLIOXAULQKGII-UHFFFAOYSA-N 0.000 description 1
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1h-pyrazole Chemical group CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 description 1
- VQJUPRDWOZCCOH-UHFFFAOYSA-N 7-butyl-3-[3-chloro-5-(2-methyl-1,2,4-triazol-3-yl)thiophen-2-yl]-2,5-dimethylpyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(CCCC)=CC(C)=NC2=C1C(=C(C=1)Cl)SC=1C1=NC=NN1C VQJUPRDWOZCCOH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- PKHPFHKLOCQQJU-UHFFFAOYSA-N BrC1=C(C=C(S1)C1=NC(=CC=C1)C)C.CC1=C(SC(=C1)C1=NC(=CC=C1)C)B(O)O Chemical compound BrC1=C(C=C(S1)C1=NC(=CC=C1)C)C.CC1=C(SC(=C1)C1=NC(=CC=C1)C)B(O)O PKHPFHKLOCQQJU-UHFFFAOYSA-N 0.000 description 1
- RZEHJYZHYUGQFC-UHFFFAOYSA-N BrC1=C2C(=NC=C1)C=CS2.S2C=CC1=NC=CC=C12 Chemical compound BrC1=C2C(=NC=C1)C=CS2.S2C=CC1=NC=CC=C12 RZEHJYZHYUGQFC-UHFFFAOYSA-N 0.000 description 1
- ZYXZEIYETAMGFG-UHFFFAOYSA-N BrC1=CSC=2C1=NC=CC2.CC2=CSC=1C2=NC=CC1 Chemical compound BrC1=CSC=2C1=NC=CC2.CC2=CSC=1C2=NC=CC1 ZYXZEIYETAMGFG-UHFFFAOYSA-N 0.000 description 1
- SMWIARQADJXVSS-UHFFFAOYSA-N C(C)#N.BrC1=C(C2=C(S1)C=CC(=C2)F)C Chemical compound C(C)#N.BrC1=C(C2=C(S1)C=CC(=C2)F)C SMWIARQADJXVSS-UHFFFAOYSA-N 0.000 description 1
- BHGHFUZAQISFDJ-UHFFFAOYSA-N C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(CCC)C1=CC(=NC=2N1N=C(C2C2=C(C1=C(S2)C=CC(=C1)F)C)C)C Chemical compound C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(CCC)C1=CC(=NC=2N1N=C(C2C2=C(C1=C(S2)C=CC(=C1)F)C)C)C BHGHFUZAQISFDJ-UHFFFAOYSA-N 0.000 description 1
- VTYQUQCXXKMTON-UHFFFAOYSA-N CC1=C(SC=C1)C=1C(=NN2C1N=C(C=C2C(CC)CC)C)C.[N+](=O)([O-])C2=CC(=C(S2)C=2C(=NN1C2N=C(C=C1C(CC)CC)C)C)C Chemical compound CC1=C(SC=C1)C=1C(=NN2C1N=C(C=C2C(CC)CC)C)C.[N+](=O)([O-])C2=CC(=C(S2)C=2C(=NN1C2N=C(C=C1C(CC)CC)C)C)C VTYQUQCXXKMTON-UHFFFAOYSA-N 0.000 description 1
- YTNWQXDAOVDOMS-UHFFFAOYSA-N CC1=NN2C(NC(=CC2=O)C)=C1.ClC1=CC(=NC=2N1N=C(C2)C)C Chemical compound CC1=NN2C(NC(=CC2=O)C)=C1.ClC1=CC(=NC=2N1N=C(C2)C)C YTNWQXDAOVDOMS-UHFFFAOYSA-N 0.000 description 1
- SZEVOUMVBLSWDF-UHFFFAOYSA-N CC=1C=C(NN1)N.C(CCC)C1=CC(=NC=2N1N=C(C2)C)C Chemical compound CC=1C=C(NN1)N.C(CCC)C1=CC(=NC=2N1N=C(C2)C)C SZEVOUMVBLSWDF-UHFFFAOYSA-N 0.000 description 1
- GFTMSEKTZHIVHD-UHFFFAOYSA-N CCCCc([n]1nc2C)cc(C)nc1c2-c([s]c(/C(/NC)=N/C=N)c1)c1Cl Chemical compound CCCCc([n]1nc2C)cc(C)nc1c2-c([s]c(/C(/NC)=N/C=N)c1)c1Cl GFTMSEKTZHIVHD-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 101000957724 Catostomus commersonii Corticoliberin-1 Proteins 0.000 description 1
- OISVCGZHLKNMSJ-UHFFFAOYSA-N Cc1nc(C)ccc1 Chemical compound Cc1nc(C)ccc1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 208000012895 Gastric disease Diseases 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- KCTZOTUQSGYWLV-UHFFFAOYSA-N N1C=NC=C2N=CC=C21 Chemical class N1C=NC=C2N=CC=C21 KCTZOTUQSGYWLV-UHFFFAOYSA-N 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- XYRGBBBLMDZIMD-UHFFFAOYSA-N S1C=CC2=NC=CC(=C21)O.BrC2=C1C(=NC=C2)C=CS1 Chemical compound S1C=CC2=NC=CC(=C21)O.BrC2=C1C(=NC=C2)C=CS1 XYRGBBBLMDZIMD-UHFFFAOYSA-N 0.000 description 1
- GYICGFQVLGTLNO-UHFFFAOYSA-N S1C=CC2=NC=CC=C21.BrC2=CSC=1C2=NC=CC1 Chemical compound S1C=CC2=NC=CC=C21.BrC2=CSC=1C2=NC=CC1 GYICGFQVLGTLNO-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- GRGKXCGLSXDCHZ-UHFFFAOYSA-M [Br-].CC1=C(SC=C1)[Zn+].CC1=C(SC=C1)C=1C(=NN2C1N=C(C=C2C(CC)CC)C)C Chemical compound [Br-].CC1=C(SC=C1)[Zn+].CC1=C(SC=C1)C=1C(=NN2C1N=C(C=C2C(CC)CC)C)C GRGKXCGLSXDCHZ-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 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
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- JMFBYAYYTCYQTP-UHFFFAOYSA-N ethyl 4-chloro-5-(2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OCC)=CC(Cl)=C1C1=C2N=C(C)C=C(C(CC)CC)N2N=C1C JMFBYAYYTCYQTP-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- KUJOABUXCGVGIY-UHFFFAOYSA-N lithium zinc Chemical compound [Li].[Zn] KUJOABUXCGVGIY-UHFFFAOYSA-N 0.000 description 1
- SNHOZPMHMQQMNI-UHFFFAOYSA-N lithium;2h-thiophen-2-ide Chemical compound [Li+].C=1C=[C-]SC=1 SNHOZPMHMQQMNI-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 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
- MSDSXFCUICNRPU-UHFFFAOYSA-N n-[5-(2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)-4-methylthiophen-2-yl]acetamide Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C=1SC(NC(C)=O)=CC=1C MSDSXFCUICNRPU-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000003186 pharmaceutical solution Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JUXWUYWPUDKPSD-UHFFFAOYSA-N pyrazolo[1,5-a][1,3,5]triazine Chemical compound N1=CN=CN2N=CC=C21 JUXWUYWPUDKPSD-UHFFFAOYSA-N 0.000 description 1
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- JSTYQZIXEXOPBT-UHFFFAOYSA-M zinc;6-methyl-2h-pyridin-2-ide;bromide Chemical compound Br[Zn+].CC1=CC=C[C-]=N1 JSTYQZIXEXOPBT-UHFFFAOYSA-M 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Gynecology & Obstetrics (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Rheumatology (AREA)
- Anesthesiology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Pregnancy & Childbirth (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82627306P | 2006-09-20 | 2006-09-20 | |
| US60/826,273 | 2006-09-20 | ||
| PCT/US2007/078352 WO2008036541A1 (en) | 2006-09-20 | 2007-09-13 | Thiophene pyrazolopyrimidine compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010504343A JP2010504343A (ja) | 2010-02-12 |
| JP2010504343A5 JP2010504343A5 (https=) | 2010-11-04 |
| JP5184536B2 true JP5184536B2 (ja) | 2013-04-17 |
Family
ID=38988344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009529307A Expired - Fee Related JP5184536B2 (ja) | 2006-09-20 | 2007-09-13 | チオフェンピラゾロピリミジン化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8110580B2 (https=) |
| EP (1) | EP2076515B1 (https=) |
| JP (1) | JP5184536B2 (https=) |
| KR (1) | KR101088196B1 (https=) |
| CN (1) | CN101516886B (https=) |
| AU (1) | AU2007297481B2 (https=) |
| BR (1) | BRPI0717070A2 (https=) |
| CA (1) | CA2662000C (https=) |
| EA (1) | EA016056B1 (https=) |
| ES (1) | ES2428543T3 (https=) |
| MX (1) | MX2009003098A (https=) |
| WO (1) | WO2008036541A1 (https=) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US9029411B2 (en) | 2008-01-25 | 2015-05-12 | Millennium Pharmaceuticals, Inc. | Thiophenes and uses thereof |
| WO2010090716A1 (en) | 2009-01-30 | 2010-08-12 | Millennium Pharmaceuticals, Inc. | Heteroaryls and their use as pi3k inhibitors |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| WO2012021611A1 (en) | 2010-08-11 | 2012-02-16 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| US8859768B2 (en) | 2010-08-11 | 2014-10-14 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| TW201217365A (en) | 2010-08-11 | 2012-05-01 | Millennium Pharm Inc | Heteroaryls and uses thereof |
| TW201307309A (zh) | 2010-10-13 | 2013-02-16 | Millennium Pharm Inc | 雜芳基化合物及其用途 |
| EP2729455B1 (en) | 2011-07-05 | 2016-09-14 | Lupin Limited | Biaryl derivatives as nachr modulators |
| 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 |
| RS65839B1 (sr) | 2014-01-21 | 2024-09-30 | Neurocrine Biosciences Inc | Crf1 receptor antagonisti za tretman kongenitalne adrenalne hiperplazije |
| JP6364967B2 (ja) * | 2014-05-30 | 2018-08-01 | 東ソー株式会社 | ジチエノベンゾジチオフェンの製造方法 |
| EP3238676B1 (en) | 2016-04-29 | 2019-01-02 | The Procter and Gamble Company | Absorbent core with profiled distribution of absorbent material |
| WO2019036503A1 (en) | 2017-08-14 | 2019-02-21 | Spruce Biosciences, Inc. | CORTICOTROPIN RELEASE FACTOR RECEPTOR ANTAGONISTS |
| JP7285222B2 (ja) * | 2017-08-14 | 2023-06-01 | スプルース バイオサイエンシズ インコーポレイテッド | 副腎皮質刺激ホルモン放出因子受容体拮抗薬 |
| EP4643950A3 (en) | 2018-04-27 | 2026-01-14 | Spruce Biosciences, Inc. | Methods for treating testicular and ovarian adrenal rest tumors |
| US20220023266A1 (en) | 2018-12-07 | 2022-01-27 | Neurocrine Biosciences, Inc. | Crf1 receptor antagonist, pharmaceutical formulations and solid forms thereof for the treatment of congenital adrenal hyperplasia |
| JP7623365B2 (ja) | 2019-09-27 | 2025-01-28 | ニューロクライン バイオサイエンシーズ，インコーポレイテッド | Ｃｒｆ受容体アンタゴニストおよび使用方法 |
| TW202134241A (zh) * | 2019-12-04 | 2021-09-16 | 美商紐羅克里生物科學有限公司 | Ｃｒｆ受體拮抗劑及使用方法 |
| KR20240023691A (ko) | 2020-08-12 | 2024-02-22 | 스프루스 바이오사이언시스 인코포레이티드 | 다낭성 난소 증후군을 치료하기 위한 방법 및 조성물 |
| US11708372B2 (en) | 2021-11-19 | 2023-07-25 | Spruce Biosciences, Inc. | Crystalline composition of tildacerfont and methods of use and preparation thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR19990067704A (ko) | 1992-12-17 | 1999-08-25 | 디. 제이. 우드, 스피겔 알렌 제이 | 부신피질자극호르몬 유리인자 길항제로서의 피롤로피리미딘을함유하는 약학 조성물 |
| AU713673B2 (en) * | 1996-02-07 | 1999-12-09 | Neurocrine Biosciences Inc. | Pyrazolopyrimidines as crf receptor antagonists |
| HU229024B1 (en) | 1996-07-24 | 2013-07-29 | Bristol Myers Squibb Pharma Co | Azolo-pyridimidines, pharmaceutical compositions containing the same and use thereof |
| JP3621706B2 (ja) | 1996-08-28 | 2005-02-16 | ファイザー・インク | 置換された６，５―ヘテロ―二環式誘導体 |
| ES2277855T3 (es) * | 1999-09-30 | 2007-08-01 | Neurogen Corporation | Pirazolo-(1,5-a)-1,5-pirimidinas y pirazolo-(1,5-a)-1,3,5-triazinas amino sustituidas. |
| MY143499A (en) * | 2003-12-22 | 2011-05-31 | Sb Pharmco Inc | Crf receptor antagonist and methods relating thereto |
| EP1869049B1 (en) * | 2005-03-21 | 2009-03-04 | Eli Lilly And Company | Imidazopyridazine compounds |
-
2007
- 2007-09-13 JP JP2009529307A patent/JP5184536B2/ja not_active Expired - Fee Related
- 2007-09-13 KR KR1020097005694A patent/KR101088196B1/ko not_active Expired - Fee Related
- 2007-09-13 EA EA200970302A patent/EA016056B1/ru not_active IP Right Cessation
- 2007-09-13 WO PCT/US2007/078352 patent/WO2008036541A1/en not_active Ceased
- 2007-09-13 AU AU2007297481A patent/AU2007297481B2/en not_active Ceased
- 2007-09-13 ES ES07814842T patent/ES2428543T3/es active Active
- 2007-09-13 US US12/438,953 patent/US8110580B2/en active Active
- 2007-09-13 BR BRPI0717070-0A2A patent/BRPI0717070A2/pt not_active IP Right Cessation
- 2007-09-13 CN CN2007800349472A patent/CN101516886B/zh not_active Expired - Fee Related
- 2007-09-13 CA CA2662000A patent/CA2662000C/en not_active Expired - Fee Related
- 2007-09-13 MX MX2009003098A patent/MX2009003098A/es active IP Right Grant
- 2007-09-13 EP EP07814842.6A patent/EP2076515B1/en not_active Not-in-force
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010504343A (ja) | 2010-02-12 |
| CN101516886B (zh) | 2012-02-29 |
| MX2009003098A (es) | 2009-04-01 |
| US8110580B2 (en) | 2012-02-07 |
| ES2428543T3 (es) | 2013-11-08 |
| CN101516886A (zh) | 2009-08-26 |
| AU2007297481A1 (en) | 2008-03-27 |
| KR101088196B1 (ko) | 2011-11-30 |
| EA200970302A1 (ru) | 2009-10-30 |
| CA2662000C (en) | 2013-01-08 |
| CA2662000A1 (en) | 2008-03-27 |
| KR20090053921A (ko) | 2009-05-28 |
| EP2076515A1 (en) | 2009-07-08 |
| BRPI0717070A2 (pt) | 2013-09-24 |
| WO2008036541A1 (en) | 2008-03-27 |
| EA016056B1 (ru) | 2012-01-30 |
| AU2007297481B2 (en) | 2012-03-08 |
| EP2076515B1 (en) | 2013-07-17 |
| US20100022560A1 (en) | 2010-01-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5184536B2 (ja) | チオフェンピラゾロピリミジン化合物 | |
| JP5161226B2 (ja) | Ｃｒｆ１受容体アンタゴニストとしてのチアゾールピラゾロピリミジン | |
| JP5926727B2 (ja) | 置換イミダゾ［１，２−ｂ］ピリダジン | |
| TWI439272B (zh) | 稠合雙環嘧啶 | |
| EP1140946A2 (en) | Quinoline derivatives | |
| CA2691866A1 (fr) | Derives de 6-cycloamino-3-(pyridin-4-yl)imidazo[1, 2-b]-pyridazine, leur preparation et leur application en therapeutique | |
| EP2331546B1 (fr) | Derives de 2-alkyl-6-cycloamino-3-(pyridin-4-yl)imidazo[1,2-ib]-pyridazine, leur preparation et leur application en therapeutique | |
| US7557103B2 (en) | Imidazopyridazine compounds | |
| CN1938309B (zh) | Crf受体拮抗剂及其相关方法 | |
| Abe et al. | The chemistry of azaazulenes | |
| HK1132505B (en) | Thiazole pyrazolopyrimidines as crf1 receptor antagonists | |
| TW201002713A (en) | Pyrrolo[2,3-d]pyrimidin-2-yl-amine derivatives as PKC-theta inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100907 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100907 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20121218 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130116 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160125 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |