NO311977B1 - (Azetidin-1-ylalkyl) laktamer som tachykinin-antagonister - Google Patents

(Azetidin-1-ylalkyl) laktamer som tachykinin-antagonister Download PDF

Info

Publication number: NO311977B1
Authority: NO; Norway
Prior art keywords: compound; formula; vol; preparation; solution
Prior art date: 1994-08-09

Application number

NO19970566A

Other languages

English (en)

Norwegian (no)

Other versions

NO970566D0 (no

NO970566L (no

Inventor

Alexander Roderick Mackenzie

Allan Patrick Marchington

Sandra Dora Meadows

Donald Stuart Middleton

Original Assignee

Pfizer Res And Dev Co Nv Sa

Priority date (The priority date 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 date listed.)

1994-08-09

Filing date

1997-02-07

Publication date

2002-02-25

1994-08-09 Priority claimed from GB9416084A external-priority patent/GB9416084D0/en

1997-02-07 Application filed by Pfizer Res And Dev Co Nv Sa filed Critical Pfizer Res And Dev Co Nv Sa

1997-02-07 Publication of NO970566D0 publication Critical patent/NO970566D0/no

1997-02-07 Publication of NO970566L publication Critical patent/NO970566L/no

2002-02-25 Publication of NO311977B1 publication Critical patent/NO311977B1/no

Links

102000003141 Tachykinin Human genes 0.000 title claims abstract description 6
108060008037 tachykinin Proteins 0.000 title claims abstract description 6
150000003951 lactams Chemical class 0.000 title claims description 9
239000005557 antagonist Substances 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 313
239000000203 mixture Substances 0.000 claims abstract description 115
150000003839 salts Chemical class 0.000 claims abstract description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
125000001424 substituent group Chemical group 0.000 claims abstract description 5
125000000217 alkyl group Chemical group 0.000 claims abstract description 4
125000002947 alkylene group Chemical group 0.000 claims abstract description 3
125000005843 halogen group Chemical group 0.000 claims abstract description 3
-1 2-methylcyclohexylmethyl Chemical group 0.000 claims description 45
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
208000035475 disorder Diseases 0.000 claims description 18
201000010099 disease Diseases 0.000 claims description 13
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 11
239000000460 chlorine Substances 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
208000004296 neuralgia Diseases 0.000 claims description 9
206010020751 Hypersensitivity Diseases 0.000 claims description 8
208000002193 Pain Diseases 0.000 claims description 8
210000003169 central nervous system Anatomy 0.000 claims description 8
230000002496 gastric effect Effects 0.000 claims description 8
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
208000026935 allergic disease Diseases 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
108010040722 Neurokinin-2 Receptors Proteins 0.000 claims description 5
102100037342 Substance-K receptor Human genes 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
208000019901 Anxiety disease Diseases 0.000 claims description 4
208000001387 Causalgia Diseases 0.000 claims description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
208000000094 Chronic Pain Diseases 0.000 claims description 4
208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 4
206010011224 Cough Diseases 0.000 claims description 4
208000011231 Crohn disease Diseases 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 4
201000004624 Dermatitis Diseases 0.000 claims description 4
206010012442 Dermatitis contact Diseases 0.000 claims description 4
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
239000005977 Ethylene Substances 0.000 claims description 4
208000034347 Faecal incontinence Diseases 0.000 claims description 4
101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 claims description 4
206010021639 Incontinence Diseases 0.000 claims description 4
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
208000019693 Lung disease Diseases 0.000 claims description 4
102100029409 Neuromedin-K receptor Human genes 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
208000028017 Psychotic disease Diseases 0.000 claims description 4
208000024780 Urticaria Diseases 0.000 claims description 4
230000001154 acute effect Effects 0.000 claims description 4
208000005298 acute pain Diseases 0.000 claims description 4
230000007815 allergy Effects 0.000 claims description 4
230000036506 anxiety Effects 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
208000010668 atopic eczema Diseases 0.000 claims description 4
206010009887 colitis Diseases 0.000 claims description 4
208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims description 4
208000010247 contact dermatitis Diseases 0.000 claims description 4
125000006622 cycloheptylmethyl group Chemical group 0.000 claims description 4
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 claims description 4
201000003146 cystitis Diseases 0.000 claims description 4
230000000694 effects Effects 0.000 claims description 4
208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 4
230000009610 hypersensitivity Effects 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
210000000056 organ Anatomy 0.000 claims description 4
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
208000005877 painful neuropathy Diseases 0.000 claims description 4
208000033808 peripheral neuropathy Diseases 0.000 claims description 4
206010039083 rhinitis Diseases 0.000 claims description 4
208000000187 Abnormal Reflex Diseases 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
206010020745 hyperreflexia Diseases 0.000 claims description 3
230000035859 hyperreflexia Effects 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
230000001939 inductive effect Effects 0.000 claims 1
229940126601 medicinal product Drugs 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 232
239000000543 intermediate Substances 0.000 abstract description 10
125000003118 aryl group Chemical group 0.000 abstract description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 2
125000001153 fluoro group Chemical group F* 0.000 abstract 2
125000003161 (C1-C6) alkylene group Chemical group 0.000 abstract 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 abstract 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 abstract 1
125000001589 carboacyl group Chemical group 0.000 abstract 1
125000001041 indolyl group Chemical group 0.000 abstract 1
125000001624 naphthyl group Chemical group 0.000 abstract 1
125000001544 thienyl group Chemical group 0.000 abstract 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 407
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 300
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
239000000243 solution Substances 0.000 description 178
230000002829 reductive effect Effects 0.000 description 129
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 111
239000002904 solvent Substances 0.000 description 111
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
239000000741 silica gel Substances 0.000 description 95
229910002027 silica gel Inorganic materials 0.000 description 95
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 92
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 78
239000011541 reaction mixture Substances 0.000 description 78
238000005160 1H NMR spectroscopy Methods 0.000 description 74
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
238000000034 method Methods 0.000 description 69
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
239000000706 filtrate Substances 0.000 description 54
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 49
229910052757 nitrogen Inorganic materials 0.000 description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
239000007787 solid Substances 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 36
239000012044 organic layer Substances 0.000 description 34
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000007858 starting material Substances 0.000 description 32
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
239000003921 oil Substances 0.000 description 29
239000002253 acid Substances 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
229910052943 magnesium sulfate Inorganic materials 0.000 description 25
235000019341 magnesium sulphate Nutrition 0.000 description 25
238000010992 reflux Methods 0.000 description 25
229920006395 saturated elastomer Polymers 0.000 description 24
229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
235000017557 sodium bicarbonate Nutrition 0.000 description 23
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
238000003818 flash chromatography Methods 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
238000001914 filtration Methods 0.000 description 14
239000012312 sodium hydride Substances 0.000 description 14
229910000104 sodium hydride Inorganic materials 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
239000000284 extract Substances 0.000 description 13
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
238000011065 in-situ storage Methods 0.000 description 12
239000010410 layer Substances 0.000 description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
229910052739 hydrogen Inorganic materials 0.000 description 11
239000001257 hydrogen Substances 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
150000001412 amines Chemical class 0.000 description 10
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 10
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 10
238000000746 purification Methods 0.000 description 10
239000000126 substance Substances 0.000 description 10
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000012298 atmosphere Substances 0.000 description 9
239000012267 brine Substances 0.000 description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
229910052794 bromium Inorganic materials 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
238000007796 conventional method Methods 0.000 description 9
239000006185 dispersion Substances 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
239000003960 organic solvent Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
239000012359 Methanesulfonyl chloride Substances 0.000 description 8
235000011114 ammonium hydroxide Nutrition 0.000 description 8
239000012043 crude product Substances 0.000 description 8
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 7
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 7
239000003480 eluent Substances 0.000 description 7
125000005948 methanesulfonyloxy group Chemical group 0.000 description 7
239000000725 suspension Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
MSVZMUILYMLJCF-UHFFFAOYSA-N (1-benzhydrylazetidin-3-yl) methanesulfonate Chemical compound C1C(OS(=O)(=O)C)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 MSVZMUILYMLJCF-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
150000002466 imines Chemical class 0.000 description 6
238000003756 stirring Methods 0.000 description 6
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 5
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
150000007975 iminium salts Chemical class 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
101000600912 Homo sapiens Substance-K receptor Proteins 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
150000001539 azetidines Chemical class 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000006071 cream Substances 0.000 description 4
238000010511 deprotection reaction Methods 0.000 description 4
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
238000010828 elution Methods 0.000 description 4
239000006260 foam Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000007800 oxidant agent Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
XXBDTKYKFFIAEY-UHFFFAOYSA-N tert-butyl 3-methylsulfonyloxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)C1 XXBDTKYKFFIAEY-UHFFFAOYSA-N 0.000 description 4
229910052721 tungsten Inorganic materials 0.000 description 4
BRSCYENHLCPOAU-UHFFFAOYSA-N 1-benzhydrylazetidin-1-ium-3-carboxylate Chemical compound C1C(C(=O)O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BRSCYENHLCPOAU-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
230000001595 contractor effect Effects 0.000 description 3
230000018044 dehydration Effects 0.000 description 3
238000006297 dehydration reaction Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
238000001640 fractional crystallisation Methods 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
FTNFEHXDETWERN-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-2,6-dimethyl-5-[(4-propan-2-yloxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 FTNFEHXDETWERN-UHFFFAOYSA-N 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000002265 prevention Effects 0.000 description 3
239000002464 receptor antagonist Substances 0.000 description 3
229940044551 receptor antagonist Drugs 0.000 description 3
238000006268 reductive amination reaction Methods 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical class C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
ZZAKLGGGMWORRT-UHFFFAOYSA-N 1-methylsulfonylpiperazine Chemical compound CS(=O)(=O)N1CCNCC1 ZZAKLGGGMWORRT-UHFFFAOYSA-N 0.000 description 2
QWZNCAFWRZZJMA-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetonitrile Chemical compound ClC1=CC=C(CC#N)C=C1Cl QWZNCAFWRZZJMA-UHFFFAOYSA-N 0.000 description 2
CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
WESDDKGEBHTDKM-UHFFFAOYSA-N 4-(1-benzhydrylazetidin-3-yl)morpholine Chemical compound C1C(N2CCOCC2)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 WESDDKGEBHTDKM-UHFFFAOYSA-N 0.000 description 2
OJONYYKAHHNFOW-UHFFFAOYSA-N 4-(azetidin-3-yl)piperazine-1-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1CN(S(=O)(=O)N)CCN1C1CNC1 OJONYYKAHHNFOW-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
150000007960 acetonitrile Chemical class 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
ZXVOCOLRQJZVBW-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO ZXVOCOLRQJZVBW-UHFFFAOYSA-N 0.000 description 2
FDPKMJDUXJFKOI-UHFFFAOYSA-N azetidin-3-amine Chemical class NC1CNC1 FDPKMJDUXJFKOI-UHFFFAOYSA-N 0.000 description 2
GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical class OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
NYUVWFKXXNINGH-UHFFFAOYSA-N benzyl thiomorpholine-4-carboxylate Chemical compound C1CSCCN1C(=O)OCC1=CC=CC=C1 NYUVWFKXXNINGH-UHFFFAOYSA-N 0.000 description 2
230000027455 binding Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
SBBZAZOOOJEDAR-UHFFFAOYSA-N cycloheptylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCCCC1 SBBZAZOOOJEDAR-UHFFFAOYSA-N 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000003456 ion exchange resin Substances 0.000 description 2
229920003303 ion-exchange polymer Polymers 0.000 description 2
238000002955 isolation Methods 0.000 description 2
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-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
CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 2
IAOYPKQGBTUDIZ-UHFFFAOYSA-N n-pyran-4-ylidenehydroxylamine Chemical compound ON=C1C=COC=C1 IAOYPKQGBTUDIZ-UHFFFAOYSA-N 0.000 description 2
XITQUSLLOSKDTB-UHFFFAOYSA-N nitrofen Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C(Cl)C=C1Cl XITQUSLLOSKDTB-UHFFFAOYSA-N 0.000 description 2
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000002674 ointment Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
208000027232 peripheral nervous system disease Diseases 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
210000001147 pulmonary artery Anatomy 0.000 description 2
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
238000006476 reductive cyclization reaction Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
150000003527 tetrahydropyrans Chemical group 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
230000007306 turnover Effects 0.000 description 2
HMHYXLVEFVGOPM-QKUYTOGTSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(3-carboxypropanoylamino)-4-oxobutan Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)N(C)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)CCC(O)=O)C1=CC=CC=C1 HMHYXLVEFVGOPM-QKUYTOGTSA-N 0.000 description 1
XJZNZSLOHZLFQP-UHFFFAOYSA-N (4,4-difluorocyclohexyl)methanol Chemical compound OCC1CCC(F)(F)CC1 XJZNZSLOHZLFQP-UHFFFAOYSA-N 0.000 description 1
OCWUKOKBIIRNFC-UHFFFAOYSA-N (4,4-difluorocyclohexyl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCC(F)(F)CC1 OCWUKOKBIIRNFC-UHFFFAOYSA-N 0.000 description 1
125000006833 (C1-C5) alkylene group Chemical group 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
OXDIYMHNQAWSCL-UHFFFAOYSA-N 1,4-oxazepan-5-one Chemical compound O=C1CCOCCN1 OXDIYMHNQAWSCL-UHFFFAOYSA-N 0.000 description 1
LJRCWNIWOVZLKS-UHFFFAOYSA-N 1,4-oxazepane;hydrochloride Chemical compound Cl.C1CNCCOC1 LJRCWNIWOVZLKS-UHFFFAOYSA-N 0.000 description 1
YSDYOQPAFHYREM-UHFFFAOYSA-N 1-(1-benzhydrylazetidin-3-yl)-2,6-dimethylpiperidine Chemical compound CC1CCCC(C)N1C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 YSDYOQPAFHYREM-UHFFFAOYSA-N 0.000 description 1
ZKHIWSTVWAUZOC-UHFFFAOYSA-N 1-(1-benzhydrylazetidin-3-yl)-4-methylsulfonylpiperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 ZKHIWSTVWAUZOC-UHFFFAOYSA-N 0.000 description 1
YPCUFKPCUHJUIH-UHFFFAOYSA-N 1-(1-benzhydrylazetidin-3-yl)piperidine Chemical compound C1C(N2CCCCC2)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YPCUFKPCUHJUIH-UHFFFAOYSA-N 0.000 description 1
KADKULLDXOYFNH-UHFFFAOYSA-N 1-(azetidin-3-yl)-4-methylsulfonylpiperazine;dihydrochloride Chemical compound Cl.Cl.C1CN(S(=O)(=O)C)CCN1C1CNC1 KADKULLDXOYFNH-UHFFFAOYSA-N 0.000 description 1
UTXSJCMAGHSVIE-UHFFFAOYSA-N 1-(azetidin-3-yl)imidazole;dihydrochloride Chemical compound Cl.Cl.C1NCC1N1C=NC=C1 UTXSJCMAGHSVIE-UHFFFAOYSA-N 0.000 description 1
CEWHASUCOPRVLA-UHFFFAOYSA-N 1-(azetidin-3-yl)piperidin-3-ol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1C(O)CCCN1C1CNC1 CEWHASUCOPRVLA-UHFFFAOYSA-N 0.000 description 1
IGPSPBNOEVKQBV-UHFFFAOYSA-N 1-(azetidin-3-yl)piperidine;dihydrochloride Chemical compound Cl.Cl.C1NCC1N1CCCCC1 IGPSPBNOEVKQBV-UHFFFAOYSA-N 0.000 description 1
ATLQGZVLWOURFU-UHFFFAOYSA-N 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(CBr)=CC(C(F)(F)F)=C1 ATLQGZVLWOURFU-UHFFFAOYSA-N 0.000 description 1
HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical compound C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 1
VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 1
DXMZDPITFJVMNT-UHFFFAOYSA-N 1-(cycloheptylmethyl)-5-(3,4-dichlorophenyl)-5-[2-(3-morpholin-4-ylazetidin-1-yl)ethyl]piperidin-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(CCN2CC(C2)N2CCOCC2)CN(CC2CCCCCC2)C(=O)CC1 DXMZDPITFJVMNT-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
VVWJFRAKLGCWQV-UHFFFAOYSA-N 1-benzhydryl-n-(2-hydroxyethyl)-n-methylazetidine-3-carboxamide Chemical compound C1C(C(=O)N(CCO)C)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 VVWJFRAKLGCWQV-UHFFFAOYSA-N 0.000 description 1
MMAJXKGUZYDTHV-UHFFFAOYSA-N 1-benzhydrylazetidin-3-ol Chemical compound C1C(O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 MMAJXKGUZYDTHV-UHFFFAOYSA-N 0.000 description 1
IXMOEAHDRKNAAG-UHFFFAOYSA-N 1-benzhydrylazetidine-3-carbonitrile Chemical compound C1C(C#N)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 IXMOEAHDRKNAAG-UHFFFAOYSA-N 0.000 description 1
POVNTWJCRHSIPG-UHFFFAOYSA-N 1-benzyl-5-(3,4-dichlorophenyl)-5-[2-[3-(1-oxo-1,4-thiazinan-4-yl)azetidin-1-yl]ethyl]piperidin-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(CCN2CC(C2)N2CCS(=O)CC2)CN(CC=2C=CC=CC=2)C(=O)CC1 POVNTWJCRHSIPG-UHFFFAOYSA-N 0.000 description 1
YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
RTCUCQWIICFPOD-UHFFFAOYSA-N 1-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C(C(N)C)=CC=CC2=C1 RTCUCQWIICFPOD-UHFFFAOYSA-N 0.000 description 1
MNOKGEXWJSNZBJ-UHFFFAOYSA-N 1-piperazin-1-ylethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC(=O)N1CCNCC1 MNOKGEXWJSNZBJ-UHFFFAOYSA-N 0.000 description 1
SDGKUVSVPIIUCF-UHFFFAOYSA-N 2,6-dimethylpiperidine Chemical compound CC1CCCC(C)N1 SDGKUVSVPIIUCF-UHFFFAOYSA-N 0.000 description 1
GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
MGBNNXFLAFERSO-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)pent-4-enenitrile Chemical compound ClC1=CC=C(C(CC=C)C#N)C=C1Cl MGBNNXFLAFERSO-UHFFFAOYSA-N 0.000 description 1
QGIVNHURAZETRF-UHFFFAOYSA-N 2-cyclopropylethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1CC1 QGIVNHURAZETRF-UHFFFAOYSA-N 0.000 description 1
YHVZEPIEDXIJJT-UHFFFAOYSA-N 2-piperidin-4-yl-1,3-benzoxazole Chemical compound C1CNCCC1C1=NC2=CC=CC=C2O1 YHVZEPIEDXIJJT-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
IBKYGUVSELLWPP-UHFFFAOYSA-N 3-azidoazetidine Chemical class [N-]=[N+]=NC1CNC1 IBKYGUVSELLWPP-UHFFFAOYSA-N 0.000 description 1
DHXNZYCXMFBMHE-UHFFFAOYSA-N 3-bromopropanoic acid Chemical compound OC(=O)CCBr DHXNZYCXMFBMHE-UHFFFAOYSA-N 0.000 description 1
XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 1
KTTHNJILQSHJHQ-UHFFFAOYSA-N 4-(azetidin-3-yl)morpholine;dihydrochloride Chemical compound Cl.Cl.C1NCC1N1CCOCC1 KTTHNJILQSHJHQ-UHFFFAOYSA-N 0.000 description 1
AEGZLYNAJWQQTO-UHFFFAOYSA-N 4-(azetidin-3-yl)morpholine;hydrochloride Chemical compound Cl.C1NCC1N1CCOCC1 AEGZLYNAJWQQTO-UHFFFAOYSA-N 0.000 description 1
FOANNJQFHJONSC-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxy]piperidine Chemical compound CC(C)(C)OC1CCNCC1 FOANNJQFHJONSC-UHFFFAOYSA-N 0.000 description 1
PGLDEHWCFNSWPM-UHFFFAOYSA-N 4-cyano-4-(3,4-dichlorophenyl)hept-6-enoic acid Chemical compound OC(=O)CCC(CC=C)(C#N)C1=CC=C(Cl)C(Cl)=C1 PGLDEHWCFNSWPM-UHFFFAOYSA-N 0.000 description 1
OADCYGWXGFTBDD-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)-1-[(4,4-difluorocyclohexyl)methyl]-5-[2-(oxan-2-yloxy)ethyl]piperidin-2-one Chemical compound C1CC(F)(F)CCC1CN1C(=O)CCC(CCOC2OCCCC2)(C=2C=C(Cl)C(Cl)=CC=2)C1 OADCYGWXGFTBDD-UHFFFAOYSA-N 0.000 description 1
FAZLJDFLFSDGOT-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(cyclohexylmethyl)-5-(2-hydroxyethyl)piperidin-2-one Chemical compound C1C(CCO)(C=2C=CC(Cl)=CC=2)CCC(=O)N1CC1CCCCC1 FAZLJDFLFSDGOT-UHFFFAOYSA-N 0.000 description 1
NVRVNSHHLPQGCU-UHFFFAOYSA-N 6-bromohexanoic acid Chemical compound OC(=O)CCCCCBr NVRVNSHHLPQGCU-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000007848 Alcoholism Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
206010008334 Cervicobrachial syndrome Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
241000699802 Cricetulus griseus Species 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
AWEAIAAIUSUENX-UHFFFAOYSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.N1CCC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.N1CCC1 AWEAIAAIUSUENX-UHFFFAOYSA-N 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000600903 Homo sapiens Substance-P receptor Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010062016 Immunosuppression Diseases 0.000 description 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 1
CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 description 1
201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
206010047700 Vomiting Diseases 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
CDAWGRSDYGQLOI-UHFFFAOYSA-N [4-(azetidin-3-yl)piperazin-1-yl]-phenylmethanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C=1C=CC=CC=1C(=O)N(CC1)CCN1C1CNC1 CDAWGRSDYGQLOI-UHFFFAOYSA-N 0.000 description 1
UOWHCAKKYIRMSX-UHFFFAOYSA-N [N].C1CNC1 Chemical group [N].C1CNC1 UOWHCAKKYIRMSX-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
201000007930 alcohol dependence Diseases 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
150000001347 alkyl bromides Chemical class 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
XFVKLOGLCAUHPR-UHFFFAOYSA-N benzyl 1,1-dioxo-1,4-thiazinane-4-carboxylate Chemical compound C1CS(=O)(=O)CCN1C(=O)OCC1=CC=CC=C1 XFVKLOGLCAUHPR-UHFFFAOYSA-N 0.000 description 1
JKIUUDJOCYHIGY-UHFFFAOYSA-N benzyl 4-hydroxypiperidine-1-carboxylate Chemical compound C1CC(O)CCN1C(=O)OCC1=CC=CC=C1 JKIUUDJOCYHIGY-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
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 1
230000007885 bronchoconstriction Effects 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
150000004648 butanoic acid derivatives Chemical class 0.000 description 1
KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical class CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
BMCQFFXPECPDPS-UHFFFAOYSA-N cycloheptylmethanol Chemical compound OCC1CCCCCC1 BMCQFFXPECPDPS-UHFFFAOYSA-N 0.000 description 1
KVGWLBBNYLXXSJ-UHFFFAOYSA-N cyclopropylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CC1 KVGWLBBNYLXXSJ-UHFFFAOYSA-N 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
BIPUHAHGLJKIPK-UHFFFAOYSA-N dicyclopropylmethanone Chemical compound C1CC1C(=O)C1CC1 BIPUHAHGLJKIPK-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
150000004862 dioxolanes Chemical class 0.000 description 1
MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
HZZDWLBBNSDYQM-UHFFFAOYSA-N ethyl 4,4-difluorocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(F)(F)CC1 HZZDWLBBNSDYQM-UHFFFAOYSA-N 0.000 description 1
ZXYAWONOWHSQRU-UHFFFAOYSA-N ethyl 4-oxocyclohexanecarboxylate Chemical compound CCOC(=O)C1CCC(=O)CC1 ZXYAWONOWHSQRU-UHFFFAOYSA-N 0.000 description 1
VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
229910003480 inorganic solid Inorganic materials 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000155 melt Substances 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
JWBMVCUFNLHJGN-UHFFFAOYSA-N methyl 1-(azetidin-3-yl)piperidine-4-carboxylate;dihydrochloride Chemical compound Cl.Cl.C1CC(C(=O)OC)CCN1C1CNC1 JWBMVCUFNLHJGN-UHFFFAOYSA-N 0.000 description 1
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
UJJUEJRWNWVHCM-UHFFFAOYSA-N n-methylsulfamoyl chloride Chemical compound CNS(Cl)(=O)=O UJJUEJRWNWVHCM-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 1
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000003410 quininyl group Chemical group 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
108010016070 senktide Proteins 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
PCVKFNSNKBXJFZ-UHFFFAOYSA-M sodium;3-bromopropanoate Chemical compound [Na+].[O-]C(=O)CCBr PCVKFNSNKBXJFZ-UHFFFAOYSA-M 0.000 description 1
230000000392 somatic effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical class NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
FZCNTSBMDUNXQL-UHFFFAOYSA-N tert-butyl 1,4-oxazepane-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCOCC1 FZCNTSBMDUNXQL-UHFFFAOYSA-N 0.000 description 1
CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 description 1
DRYSGWPVVVBDNA-UHFFFAOYSA-N tert-butyl 3-(3-hydroxypiperidin-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1CC(O)CCC1 DRYSGWPVVVBDNA-UHFFFAOYSA-N 0.000 description 1
HMLGUHMEAMBSPE-UHFFFAOYSA-N tert-butyl 3-(4-benzoylpiperazin-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1CCN(C(=O)C=2C=CC=CC=2)CC1 HMLGUHMEAMBSPE-UHFFFAOYSA-N 0.000 description 1
CTUKTUNUHJCMGX-UHFFFAOYSA-N tert-butyl 3-(4-methoxypiperidin-1-yl)azetidine-1-carboxylate Chemical compound C1CC(OC)CCN1C1CN(C(=O)OC(C)(C)C)C1 CTUKTUNUHJCMGX-UHFFFAOYSA-N 0.000 description 1
KQHMCDLKYDJVSB-UHFFFAOYSA-N tert-butyl 3-(4-methylsulfonylpiperazin-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1CCN(S(C)(=O)=O)CC1 KQHMCDLKYDJVSB-UHFFFAOYSA-N 0.000 description 1
GHCSIFASLFMJDZ-UHFFFAOYSA-N tert-butyl 3-(4-sulfamoylpiperazin-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1CCN(S(N)(=O)=O)CC1 GHCSIFASLFMJDZ-UHFFFAOYSA-N 0.000 description 1
PFRGSZXMESNWFD-UHFFFAOYSA-N tert-butyl 3-[4-(methylcarbamoyl)piperazin-1-yl]azetidine-1-carboxylate Chemical compound C1CN(C(=O)NC)CCN1C1CN(C(=O)OC(C)(C)C)C1 PFRGSZXMESNWFD-UHFFFAOYSA-N 0.000 description 1
UEZIEASDVIMTDW-UHFFFAOYSA-N tert-butyl 3-[4-(methylsulfamoyl)piperazin-1-yl]azetidine-1-carboxylate Chemical compound C1CN(S(=O)(=O)NC)CCN1C1CN(C(=O)OC(C)(C)C)C1 UEZIEASDVIMTDW-UHFFFAOYSA-N 0.000 description 1
DLRAZCARRIYDOF-UHFFFAOYSA-N tert-butyl 3-imidazol-1-ylazetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1C=NC=C1 DLRAZCARRIYDOF-UHFFFAOYSA-N 0.000 description 1
KEQBTRKQDYXHTO-UHFFFAOYSA-N tert-butyl 3-piperazin-1-ylazetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1CCNCC1 KEQBTRKQDYXHTO-UHFFFAOYSA-N 0.000 description 1
GYWVYUMNHDRQEC-UHFFFAOYSA-N tert-butyl 4-(azetidin-3-yl)piperazine-1-carboxylate;hydrochloride Chemical compound Cl.C1CN(C(=O)OC(C)(C)C)CCN1C1CNC1 GYWVYUMNHDRQEC-UHFFFAOYSA-N 0.000 description 1
QQFDVJXNIXQJGW-UHFFFAOYSA-N tert-butyl 4-acetylpiperazine-1-carboxylate Chemical compound CC(=O)N1CCN(C(=O)OC(C)(C)C)CC1 QQFDVJXNIXQJGW-UHFFFAOYSA-N 0.000 description 1
KEVJRVHXORTWTR-UHFFFAOYSA-N tert-butyl 4-methylsulfonylpiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(S(C)(=O)=O)CC1 KEVJRVHXORTWTR-UHFFFAOYSA-N 0.000 description 1
PSELCIMQRLODQE-UHFFFAOYSA-N tert-butyl 6-bromohexanoate Chemical compound CC(C)(C)OC(=O)CCCCCBr PSELCIMQRLODQE-UHFFFAOYSA-N 0.000 description 1
CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
FODWRUPJCKASBN-UHFFFAOYSA-M tetrabutylazanium;chloride;hydrate Chemical compound O.[Cl-].CCCC[N+](CCCC)(CCCC)CCCC FODWRUPJCKASBN-UHFFFAOYSA-M 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 1
230000002455 vasospastic effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Urology & Nephrology (AREA)
Immunology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Liquid Crystal (AREA)

NO19970566A 1994-08-09 1997-02-07 (Azetidin-1-ylalkyl) laktamer som tachykinin-antagonister NO311977B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB9416084A GB9416084D0 (en)	1994-08-09	1994-08-09	Lactams
GB9417898A GB9417898D0 (en)	1994-08-09	1994-09-06	Lactams
PCT/EP1995/003054 WO1996005193A1 (fr)	1994-08-09	1995-07-29	(azetidin-1-ylalkyl) lactames utilises comme antagonistes de la tachykinine

Publications (3)

Publication Number	Publication Date
NO970566D0 NO970566D0 (no)	1997-02-07
NO970566L NO970566L (no)	1997-02-07
NO311977B1 true NO311977B1 (no)	2002-02-25

Family

ID=26305431

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19970566A NO311977B1 (no)	1994-08-09	1997-02-07	(Azetidin-1-ylalkyl) laktamer som tachykinin-antagonister

Country Status (24)

Country	Link
US (1)	US5968923A (fr)
EP (1)	EP0775132B1 (fr)
JP (1)	JP3159389B2 (fr)
CN (1)	CN1072666C (fr)
AT (1)	ATE200083T1 (fr)
AU (1)	AU689303B2 (fr)
BR (1)	BR9503582A (fr)
CA (1)	CA2197086C (fr)
CZ (1)	CZ291544B6 (fr)
DE (1)	DE69520502T2 (fr)
DK (1)	DK0775132T3 (fr)
ES (1)	ES2155894T3 (fr)
FI (1)	FI970523A7 (fr)
GR (1)	GR3035726T3 (fr)
HU (1)	HUT77771A (fr)
IL (1)	IL114826A (fr)
MY (1)	MY115975A (fr)
NO (1)	NO311977B1 (fr)
NZ (1)	NZ291423A (fr)
PT (1)	PT775132E (fr)
RU (1)	RU2150468C1 (fr)
TR (1)	TR199500981A2 (fr)
TW (1)	TW432061B (fr)
WO (1)	WO1996005193A1 (fr)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9524157D0 (en) *	1995-11-25	1996-01-24	Pfizer Ltd	Therapeutic agents
GB9600235D0 (en) *	1996-01-05	1996-03-06	Pfizer Ltd	Therapeutic agents
GB9601202D0 (en) *	1996-01-22	1996-03-20	Pfizer Ltd	Piperidones
GB9601680D0 (en) *	1996-01-27	1996-03-27	Pfizer Ltd	Therapeutic agents
GB9601697D0 (en) *	1996-01-27	1996-03-27	Pfizer Ltd	Therapeutic agents
GB9714129D0 (en)	1997-07-04	1997-09-10	Pfizer Ltd	Azetidines
WO1999019297A1 (fr) *	1997-10-15	1999-04-22	Coelacanth Chemical Corporation	Synthese de derives d'azetidine
IL136510A (en)	1997-12-04	2005-09-25	Sankyo Co	Acylated hetero-alicyclic derivatives and pharmaceutical compositions containing the same
GB9812037D0 (en) *	1998-06-04	1998-07-29	Pfizer Ltd	Piperidones
AU3565999A (en) *	1999-04-16	2000-11-02	Coelacanth Chemical Corporation	Synthesis of azetidine derivatives
MXPA02004330A (es)	1999-11-03	2004-07-30	Albany Molecular Res Inc	Tetrahidroisoquinolinas aril-y heteroaril-sustituidas y uso de las mismas para bloquear la recaptacion de norepinefrina, dopamina y serotonina..
US7163949B1 (en)	1999-11-03	2007-01-16	Amr Technology, Inc.	4-phenyl substituted tetrahydroisoquinolines and use thereof
CA2412355A1 (fr) *	2000-06-12	2001-12-20	University Of Rochester	Methode de traitement de symptomes de la variation hormonale, tels que les bouffees de chaleur, au moyen d'un antagoniste du recepteur de la tachykinine
KR100821410B1 (ko)	2000-07-11	2008-04-10	에이엠알 테크놀로지, 인크.	4-페닐 치환된 테트라하이드로이소퀴놀린 및 이의치료학적 용도
GB0130261D0 (en)	2001-12-18	2002-02-06	Pfizer Ltd	Lactams as tachykinin antagonists
JP4430941B2 (ja)	2002-01-18	2010-03-10	メルクエンドカムパニーインコーポレーテッド	Ｅｄｇ受容体作動薬
RU2311409C2 (ru) *	2003-01-10	2007-11-27	Ф.Хоффманн-Ля Рош Аг	Производные 2-пиперидона в качестве агонистов простагландина
TW200508221A (en)	2003-06-13	2005-03-01	Astrazeneca Ab	New azetidine compounds
EP1698375B1 (fr)	2003-12-25	2014-04-02	Ono Pharmaceutical Co., Ltd.	Composés cycliques d'azetidine et médicaments les renfermant
NZ552397A (en)	2004-07-15	2011-04-29	Amr Technology Inc	Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
ES2382814T3 (es)	2005-05-17	2012-06-13	Merck Sharp & Dohme Ltd.	Ácido cis-4-[(4-clorofenil)sulfonil]-4-(2,5-difluorofenil)ciclohexanopropanoico para el tratamiento del cáncer
KR101594898B1 (ko)	2005-07-15	2016-02-18	알바니 몰레큘라 리써치, 인크.	아릴- 및 헤테로아릴-치환된 테트라히드로벤자제핀, 및 노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기 위한 용도
EP1940842B1 (fr)	2005-09-29	2012-05-30	Merck Sharp & Dohme Corp.	Dérivés acylés de spiropipéridine en tant que modulateurs du récepteur de la mélanocortine-4
AR057828A1 (es)	2005-09-29	2007-12-19	Astrazeneca Ab	Compuestos derivados de azetidina, su preparacion y composicion farmaceuutica
GB0603041D0 (en)	2006-02-15	2006-03-29	Angeletti P Ist Richerche Bio	Therapeutic compounds
US8106208B2 (en)	2006-05-18	2012-01-31	Albireo Ab	Benzamide compounds that act as NK receptor antagonists
US8173629B2 (en)	2006-09-22	2012-05-08	Merck Sharp & Dohme Corp.	Method of treatment using fatty acid synthesis inhibitors
US20110218176A1 (en)	2006-11-01	2011-09-08	Barbara Brooke Jennings-Spring	Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
CN101190330A (zh)	2006-11-30	2008-06-04	深圳市鼎兴生物医药技术开发有限公司	胆碱酯酶在拮抗速激肽药物中的应用
WO2008076042A1 (fr) *	2006-12-19	2008-06-26	Astrazeneca Ab	Dérivés d'azétidinepipérazine qui sont des antagonistes du récepteur de neurokinine (nk), et leur utilisation
JP4611444B2 (ja)	2007-01-10	2011-01-12	イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー	ポリ（ａｄｐ−リボース）ポリメラーゼ（ｐａｒｐ）阻害剤としてのアミド置換インダゾール
JP5319518B2 (ja)	2007-04-02	2013-10-16	Ｍｓｄ株式会社	インドールジオン誘導体
AU2008269154B2 (en)	2007-06-27	2014-06-12	Merck Sharp & Dohme Llc	4-carboxybenzylamino derivatives as histone deacetylase inhibitors
AU2009222122A1 (en)	2008-03-03	2009-09-11	Tiger Pharmatech	Tyrosine kinase inhibitors
US9156812B2 (en)	2008-06-04	2015-10-13	Bristol-Myers Squibb Company	Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
DE102008063992A1 (de)	2008-12-19	2010-09-02	Lerner, Zinoviy, Dipl.-Ing.	Neue aliphatisch substituierte Pyrazolopyridine und ihre Verwendung
WO2010114780A1 (fr)	2009-04-01	2010-10-07	Merck Sharp & Dohme Corp.	Inhibiteurs de l'activité akt
AU2010247763B2 (en)	2009-05-12	2015-12-24	Albany Molecular Research, Inc.	7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof
WO2010132437A1 (fr)	2009-05-12	2010-11-18	Albany Molecular Research, Inc.	Aryle, hétéroaryle et tétrahydroisoquinolines à hétérocycle substitué et leur utilisation
AU2010247735B2 (en)	2009-05-12	2015-07-16	Albany Molecular Research, Inc.	Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)- 1,2,3,4-tetrahydroisoquinoline and use thereof
US8399451B2 (en)	2009-08-07	2013-03-19	Bristol-Myers Squibb Company	Heterocyclic compounds
PE20121172A1 (es)	2009-10-14	2012-09-05	Merck Sharp & Dohme	Piperidinas sustituidas con actividad en la hdm2
WO2011163330A1 (fr)	2010-06-24	2011-12-29	Merck Sharp & Dohme Corp.	Nouveaux composés hétérocycliques utilisés comme inhibiteurs de erk
ES2550939T3 (es)	2010-07-16	2015-11-13	Nivalis Therapeutics, Inc.	Nuevos compuestos de dihidropiridin-2-(1H)-ona como inhibidores de la S-nitrosoglutatión reductasa y antagonistas del receptor de la neurocinina-3
EP3330377A1 (fr)	2010-08-02	2018-06-06	Sirna Therapeutics, Inc.	Inhibition à médiation par interférence arn de caténine (protéine associée à cadhérine), expression du gène bêta 1 (ctnnb1) à l'aide de petit acide nucléique interférent (sian)
US9029341B2 (en)	2010-08-17	2015-05-12	Sirna Therapeutics, Inc.	RNA interference mediated inhibition of hepatitis B virus (HBV) gene expression using short interfering nucleic acid (siNA)
US8883801B2 (en)	2010-08-23	2014-11-11	Merck Sharp & Dohme Corp.	Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors
EP2613782B1 (fr)	2010-09-01	2016-11-02	Merck Sharp & Dohme Corp.	Dérivés d'indazole utilisables en tant qu'inhibiteurs de la voie erk
US9242981B2 (en)	2010-09-16	2016-01-26	Merck Sharp & Dohme Corp.	Fused pyrazole derivatives as novel ERK inhibitors
WO2012058210A1 (fr)	2010-10-29	2012-05-03	Merck Sharp & Dohme Corp.	INHIBITION FACILITÉE PAR L'INTERFÉRENCE D'ARN DE L'EXPRESSION D'UN GÈNE AU MOYEN D'ACIDES NUCLÉIQUES INTERFÉRENTS COURTS (siNA)
WO2012087772A1 (fr)	2010-12-21	2012-06-28	Schering Corporation	Dérivés d'indazole utiles en tant qu'inhibiteurs de erk
AU2012245971A1 (en)	2011-04-21	2013-10-17	Piramal Enterprises Limited	A crystalline form of a salt of a morpholino sulfonyl indole derivative and a process for its preparation
CN102321045B (zh) *	2011-06-13	2013-07-17	陕西瑞科新材料股份有限公司	一种制备高吗啉盐酸盐的方法
EP2770987B1 (fr)	2011-10-27	2018-04-04	Merck Sharp & Dohme Corp.	Nouveaux composés qui sont des inhibiteurs d'erk
US20150299696A1 (en)	2012-05-02	2015-10-22	Sirna Therapeutics, Inc.	SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
RU2660429C2 (ru)	2012-09-28	2018-07-06	Мерк Шарп И Доум Корп.	Новые соединения, которые являются ингибиторами erk
RS56680B1 (sr)	2012-11-28	2018-03-30	Merck Sharp & Dohme	Kompozicije i postupci za lečenje kancera
KR102196882B1 (ko)	2012-12-20	2020-12-30	머크 샤프 앤드 돔 코포레이션	Hdm2 억제제로서의 치환된 이미다조피리딘
WO2014120748A1 (fr)	2013-01-30	2014-08-07	Merck Sharp & Dohme Corp.	Purines 2,6,7,8-substituées utilisées en tant qu'inhibiteurs de hdm2
WO2015034925A1 (fr)	2013-09-03	2015-03-12	Moderna Therapeutics, Inc.	Polynucléotides circulaires
EP3525785B1 (fr)	2016-10-12	2025-08-27	Merck Sharp & Dohme LLC	Inhibiteurs de kdm5
CN107176917A (zh) *	2017-05-11	2017-09-19	蚌埠中实化学技术有限公司	一种制备二甲胺基磺酰氯的方法
US10947234B2 (en)	2017-11-08	2021-03-16	Merck Sharp & Dohme Corp.	PRMT5 inhibitors
EP3706747B1 (fr)	2017-11-08	2025-09-03	Merck Sharp & Dohme LLC	Inhibiteurs de prmt5
US12173026B2 (en)	2018-08-07	2024-12-24	Merck Sharp & Dohme Llc	PRMT5 inhibitors
US11981701B2 (en)	2018-08-07	2024-05-14	Merck Sharp & Dohme Llc	PRMT5 inhibitors
EP3833668B1 (fr)	2018-08-07	2025-03-19	Merck Sharp & Dohme LLC	Inhibiteurs de prmt5

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1383619A (en) *	1972-07-26	1974-02-12	Lepetit Spa	3-azetidinylethyl-1-phenyl-2-midazolidinone derivatives
US5187156A (en) *	1988-03-16	1993-02-16	Fujisawa Pharmaceutical Co., Ltd.	Peptide compounds, processes for preparation thereof and pharmaceutical composition comprising the same
FR2663329B1 (fr) *	1990-06-15	1992-10-16	Sanofi Sa	Composes aromatiques amines, procede pour leur preparation et compositions pharmaceutiques les contenant.
IL99320A (en) *	1990-09-05	1995-07-31	Sanofi Sa	Arylalkylamines, their preparation and pharmaceutical compositions containing them
FR2676054B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
FR2676055B1 (fr) *	1991-05-03	1993-09-03	Sanofi Elf	Composes polycycliques amines et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant.
CA2106840A1 (fr) *	1992-09-25	1994-03-26	Marco Baroni	Heteroarylazetidines et -pyrrolidines, methode pour les preparer et compositions pharmaceutiques les renfermant
GB9321557D0 (en) *	1992-11-03	1993-12-08	Zeneca Ltd	Carboxamide derivatives
CA2154569A1 (fr) *	1993-01-28	1994-08-04	Jeffrey J. Hale	Derives de substitution spiro d'azacycles, antagonistes du recepteur de la tachykinine
GB9305718D0 (en) *	1993-03-19	1993-05-05	Glaxo Group Ltd	Medicaments
FR2703679B1 (fr) *	1993-04-05	1995-06-23	Rhone Poulenc Rorer Sa	Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent.
GB9310066D0 (en) *	1993-05-17	1993-06-30	Zeneca Ltd	Alkyl substituted heterocycles
GB9310713D0 (en) *	1993-05-24	1993-07-07	Zeneca Ltd	Aryl substituted heterocycles
JPH08511522A (ja) *	1993-06-07	1996-12-03	メルクエンドカンパニーインコーポレーテッド	ニューロキニンアンタゴニストとしてのスピロ置換アザ環
AU682510B2 (en) *	1993-07-01	1997-10-09	Pfizer Japan Inc.	2-(1-(1,3-thiazolin-2-yl)azetidin-3-yl)thio-carbapenem derivatives
GB9317104D0 (en) *	1993-08-17	1993-09-29	Zeneca Ltd	Therapeutic heterocycles
GB9322643D0 (en) *	1993-11-03	1993-12-22	Zeneca Ltd	Lactam derivatives
US5472958A (en) *	1994-08-29	1995-12-05	Abbott Laboratories	2-((nitro)phenoxymethyl) heterocyclic compounds that enhance cognitive function

1995
- 1995-07-17 TW TW084107375A patent/TW432061B/zh not_active IP Right Cessation
- 1995-07-29 AT AT95929036T patent/ATE200083T1/de not_active IP Right Cessation
- 1995-07-29 AU AU32549/95A patent/AU689303B2/en not_active Ceased
- 1995-07-29 RU RU97104032/04A patent/RU2150468C1/ru not_active IP Right Cessation
- 1995-07-29 PT PT95929036T patent/PT775132E/pt unknown
- 1995-07-29 US US08/798,534 patent/US5968923A/en not_active Expired - Fee Related
- 1995-07-29 EP EP95929036A patent/EP0775132B1/fr not_active Expired - Lifetime
- 1995-07-29 NZ NZ291423A patent/NZ291423A/en unknown
- 1995-07-29 WO PCT/EP1995/003054 patent/WO1996005193A1/fr not_active Ceased
- 1995-07-29 DE DE69520502T patent/DE69520502T2/de not_active Expired - Fee Related
- 1995-07-29 CA CA002197086A patent/CA2197086C/fr not_active Expired - Fee Related
- 1995-07-29 DK DK95929036T patent/DK0775132T3/da active
- 1995-07-29 ES ES95929036T patent/ES2155894T3/es not_active Expired - Lifetime
- 1995-07-29 HU HU9700373A patent/HUT77771A/hu unknown
- 1995-07-29 JP JP50697496A patent/JP3159389B2/ja not_active Expired - Fee Related
- 1995-07-29 CN CN95194416A patent/CN1072666C/zh not_active Expired - Fee Related
- 1995-07-29 CZ CZ1997381A patent/CZ291544B6/cs not_active IP Right Cessation
- 1995-08-02 MY MYPI95002252A patent/MY115975A/en unknown
- 1995-08-03 IL IL11482695A patent/IL114826A/xx not_active IP Right Cessation
- 1995-08-08 BR BR9503582A patent/BR9503582A/pt not_active IP Right Cessation
- 1995-08-09 TR TR95/00981A patent/TR199500981A2/xx unknown
1997
- 1997-02-07 NO NO19970566A patent/NO311977B1/no unknown
- 1997-02-07 FI FI970523A patent/FI970523A7/fi not_active Application Discontinuation
2001
- 2001-04-06 GR GR20010400578T patent/GR3035726T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
MY115975A (en)	2003-10-31
NO970566D0 (no)	1997-02-07
HUT77771A (hu)	1998-08-28
IL114826A0 (en)	1995-12-08
WO1996005193A1 (fr)	1996-02-22
TR199500981A2 (tr)	1996-06-21
CA2197086A1 (fr)	1996-02-22
FI970523A0 (fi)	1997-02-07
NO970566L (no)	1997-02-07
CN1072666C (zh)	2001-10-10
EP0775132B1 (fr)	2001-03-28
JPH09508646A (ja)	1997-09-02
DE69520502D1 (de)	2001-05-03
CN1154699A (zh)	1997-07-16
DE69520502T2 (de)	2001-07-12
ATE200083T1 (de)	2001-04-15
ES2155894T3 (es)	2001-06-01
DK0775132T3 (da)	2001-04-30
IL114826A (en)	1999-12-31
EP0775132A1 (fr)	1997-05-28
FI970523A7 (fi)	1997-02-07
US5968923A (en)	1999-10-19
AU3254995A (en)	1996-03-07
RU2150468C1 (ru)	2000-06-10
GR3035726T3 (en)	2001-07-31
MX9701006A (es)	1998-05-31
BR9503582A (pt)	1996-04-30
PT775132E (pt)	2001-07-31
AU689303B2 (en)	1998-03-26
CA2197086C (fr)	2000-07-25
JP3159389B2 (ja)	2001-04-23
NZ291423A (en)	1998-03-25
CZ291544B6 (cs)	2003-04-16
TW432061B (en)	2001-05-01
CZ38197A3 (cs)	1998-01-14

Publication	Publication Date	Title
NO311977B1 (no)	2002-02-25	(Azetidin-1-ylalkyl) laktamer som tachykinin-antagonister
US6242438B1 (en)	2001-06-05	3-Azetidinylalkylpiperidines or -pyrrolidines as tachykinin antagonists
EP0862567A1 (fr)	1998-09-09	5-azabicyclo(3,1,0)hexylalkyl-2-piperidones et -glutarimides en tant qu'antagonistes du recepteur des neurokinines
EA002773B1 (ru)	2002-08-29	Производные азетидинилпропилпиперидина, промежуточные соединения и применение в качестве антагонистов тахикинина
CA2240964C (fr)	2002-06-25	Piperidones, antagonistes de la tachykinine
US5846965A (en)	1998-12-08	3-aza and 3-oxa piperidone tachykinin antagonists
EP0791592B1 (fr)	2003-05-21	Azétidines
JP3091844B2 (ja)	2000-09-25	複素環式化合物
KR100218626B1 (ko)	1999-09-01	타키키닌 길항물질로서의 (아제티딘-1-일알킬)락탐
MXPA99005176A (en)	2000-11-01	Piperidones as tachykinin antagonists