NO325401B1 - Laktamforbindelser, anvendelse av slike samt farmasoytisk preparat inneholdende nevnte laktamforbindelser - Google Patents

Laktamforbindelser, anvendelse av slike samt farmasoytisk preparat inneholdende nevnte laktamforbindelser Download PDF

Info

Publication number: NO325401B1
Authority: NO; Norway
Prior art keywords: group; substituent; groups; alkyl; ring
Prior art date: 2000-12-01

Application number

NO20032439A

Other languages

English (en)

Norwegian (no)

Other versions

NO20032439D0 (no

NO20032439L (no

Inventor

Akiyo Yamazaki

Yukio Iino

Takao Ikenoue

Nobuo Kondo

Hiroyuki Matsueda

Toshihiro Hatanaka

Ryusuke Hirama

Yoko Masuzawa

Fumio Ohta

Original Assignee

Ajinomoto Kk

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.)

2000-12-01

Filing date

2003-05-28

Publication date

2008-04-21

2003-05-28 Application filed by Ajinomoto Kk filed Critical Ajinomoto Kk

2003-05-28 Publication of NO20032439D0 publication Critical patent/NO20032439D0/no

2003-07-18 Publication of NO20032439L publication Critical patent/NO20032439L/no

2008-04-21 Publication of NO325401B1 publication Critical patent/NO325401B1/no

Links

-1 Lactam Compounds Chemical class 0.000 title claims abstract description 196
239000000825 pharmaceutical preparation Substances 0.000 title description 5
150000003839 salts Chemical class 0.000 claims abstract description 39
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 11
206010063547 Diabetic macroangiopathy Diseases 0.000 claims abstract description 10
206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 10
208000002705 Glucose Intolerance Diseases 0.000 claims abstract description 10
201000009104 prediabetes syndrome Diseases 0.000 claims abstract description 10
208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 9
208000008589 Obesity Diseases 0.000 claims abstract description 9
239000003795 chemical substances by application Substances 0.000 claims abstract description 9
208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 9
239000004480 active ingredient Substances 0.000 claims abstract description 7
125000001424 substituent group Chemical group 0.000 claims description 264
150000001875 compounds Chemical class 0.000 claims description 162
125000003118 aryl group Chemical group 0.000 claims description 84
125000000217 alkyl group Chemical group 0.000 claims description 77
125000002252 acyl group Chemical group 0.000 claims description 62
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 51
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 50
125000005843 halogen group Chemical group 0.000 claims description 47
125000003277 amino group Chemical group 0.000 claims description 45
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 44
125000004423 acyloxy group Chemical group 0.000 claims description 42
125000003282 alkyl amino group Chemical group 0.000 claims description 42
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 41
125000004414 alkyl thio group Chemical group 0.000 claims description 41
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
125000004093 cyano group Chemical group *C#N 0.000 claims description 40
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 40
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
125000004432 carbon atom Chemical group C* 0.000 claims description 39
125000003396 thiol group Chemical group [H]S* 0.000 claims description 39
125000001072 heteroaryl group Chemical group 0.000 claims description 26
125000000623 heterocyclic group Chemical group 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 22
238000002360 preparation method Methods 0.000 claims description 22
125000001931 aliphatic group Chemical group 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
125000001769 aryl amino group Chemical group 0.000 claims description 14
125000003609 aryl vinyl group Chemical group 0.000 claims description 14
125000004104 aryloxy group Chemical group 0.000 claims description 14
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 13
125000005553 heteroaryloxy group Chemical group 0.000 claims description 13
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 12
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 9
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 7
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
125000002723 alicyclic group Chemical group 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
125000006606 n-butoxy group Chemical group 0.000 claims description 2
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 90
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
238000005481 NMR spectroscopy Methods 0.000 description 47
239000000243 solution Substances 0.000 description 42
239000007858 starting material Substances 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
230000015572 biosynthetic process Effects 0.000 description 33
238000000034 method Methods 0.000 description 33
235000000346 sugar Nutrition 0.000 description 33
230000000694 effects Effects 0.000 description 32
238000003786 synthesis reaction Methods 0.000 description 32
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
230000032258 transport Effects 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
150000001299 aldehydes Chemical class 0.000 description 21
235000002639 sodium chloride Nutrition 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
238000010898 silica gel chromatography Methods 0.000 description 18
IUNJCFABHJZSKB-UHFFFAOYSA-N 2,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(O)=C1 IUNJCFABHJZSKB-UHFFFAOYSA-N 0.000 description 16
150000001923 cyclic compounds Chemical class 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
239000007787 solid Substances 0.000 description 14
102000004877 Insulin Human genes 0.000 description 13
108090001061 Insulin Proteins 0.000 description 13
229940125396 insulin Drugs 0.000 description 13
239000002904 solvent Substances 0.000 description 13
239000000126 substance Substances 0.000 description 13
238000005160 1H NMR spectroscopy Methods 0.000 description 12
RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
239000000203 mixture Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
RUXHWBMJNBBYNL-UHFFFAOYSA-N 3-hydroxy-1,2-dihydropyrrol-5-one Chemical compound OC1=CC(=O)NC1 RUXHWBMJNBBYNL-UHFFFAOYSA-N 0.000 description 10
239000008280 blood Substances 0.000 description 10
210000004369 blood Anatomy 0.000 description 10
125000006165 cyclic alkyl group Chemical group 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
238000000605 extraction Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
238000000746 purification Methods 0.000 description 9
238000012360 testing method Methods 0.000 description 9
ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
210000001789 adipocyte Anatomy 0.000 description 8
238000001914 filtration Methods 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000007796 conventional method Methods 0.000 description 7
238000011156 evaluation Methods 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
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 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
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 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000013078 crystal Chemical group 0.000 description 6
239000008103 glucose Substances 0.000 description 6
238000005984 hydrogenation reaction Methods 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
125000004433 nitrogen atom Chemical group N* 0.000 description 5
125000000714 pyrimidinyl group Chemical group 0.000 description 5
DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 5
238000004809 thin layer chromatography Methods 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 4
NRKQMDLBMZFWDM-UHFFFAOYSA-N 4-tert-butyl-2-chlorobenzaldehyde Chemical compound CC(C)(C)C1=CC=C(C=O)C(Cl)=C1 NRKQMDLBMZFWDM-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
238000010511 deprotection reaction Methods 0.000 description 4
230000002708 enhancing effect Effects 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
239000000523 sample Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
238000005406 washing Methods 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
RLPMZMKNIKFKHD-UHFFFAOYSA-N 3-(2-aminoanilino)-1,2-dihydropyrrol-5-one Chemical compound NC1=CC=CC=C1NC1=CC(=O)NC1 RLPMZMKNIKFKHD-UHFFFAOYSA-N 0.000 description 3
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
ZCGUVTAVRMRQOP-RKDXNWHRSA-N 3-[[(1r,2r)-2-aminocyclohexyl]amino]-1,2-dihydropyrrol-5-one Chemical compound N[C@@H]1CCCC[C@H]1NC1=CC(=O)NC1 ZCGUVTAVRMRQOP-RKDXNWHRSA-N 0.000 description 3
MGHIIGWDUVNPPV-UHFFFAOYSA-N 4-(4-nitrophenyl)benzaldehyde Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC=C(C=O)C=C1 MGHIIGWDUVNPPV-UHFFFAOYSA-N 0.000 description 3
SXGZIJOZHSTSAJ-UHFFFAOYSA-N 4-hexoxy-2-hydroxybenzaldehyde Chemical compound CCCCCCOC1=CC=C(C=O)C(O)=C1 SXGZIJOZHSTSAJ-UHFFFAOYSA-N 0.000 description 3
PJAPXLXIEDUVSR-UHFFFAOYSA-N 5-[(2-aminophenyl)methyl]-1,2-dihydropyrazol-3-one Chemical compound NC1=CC=CC=C1CC1=CC(=O)NN1 PJAPXLXIEDUVSR-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000006285 cell suspension Substances 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
230000002218 hypoglycaemic effect Effects 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 3
239000012528 membrane Substances 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 3
230000002093 peripheral effect Effects 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
HQQBZUTZMUSMGR-UHFFFAOYSA-N (4-tert-butyl-2-chlorophenyl) trifluoromethanesulfonate Chemical compound CC(C)(C)C1=CC=C(OS(=O)(=O)C(F)(F)F)C(Cl)=C1 HQQBZUTZMUSMGR-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 2
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239000001103 potassium chloride Substances 0.000 description 1
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159000000001 potassium salts Chemical class 0.000 description 1
239000001294 propane Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
- A61K31/5517—1,4-Benzodiazepines, e.g. diazepam or clozapine condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
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- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Hydrogenated Pyridines (AREA)
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JP (2)	JP3826400B2 (de)
KR (1)	KR100826818B1 (de)
CN (2)	CN100577651C (de)
AT (1)	ATE446297T1 (de)
AU (3)	AU2002218502B2 (de)
BG (1)	BG107857A (de)
BR (1)	BR0115852A (de)
CA (1)	CA2430124C (de)
CZ (1)	CZ20031520A3 (de)
DE (1)	DE60140270D1 (de)
ES (1)	ES2331299T3 (de)
HU (1)	HUP0400806A3 (de)
IL (1)	IL156158A0 (de)
MX (1)	MXPA03004876A (de)
NO (1)	NO325401B1 (de)
NZ (1)	NZ526164A (de)
PL (1)	PL362835A1 (de)
RU (1)	RU2287530C2 (de)
SK (1)	SK6582003A3 (de)
TW (1)	TWI241302B (de)
UA (1)	UA76969C2 (de)
WO (1)	WO2002044180A1 (de)
YU (1)	YU42603A (de)
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CN100577651C (zh) *	2000-12-01	2010-01-06	味之素株式会社	内酰胺化合物及其药物用途
BRPI0407303A (pt) *	2003-02-07	2006-02-07	Ajinomoto Kk	Composição farmacêutica
CA2544310A1 (en)	2003-10-31	2005-05-12	Ajinomoto Co., Inc.	New fused polycyclic compounds having a heterocyclic ring(s) and pharmaceutical use thereof
EP1707567A4 (de) *	2004-01-14	2009-08-19	Ajinomoto Kk	Neue verbindung mit kondensiertem ring
DK1802625T3 (da) *	2004-10-13	2008-09-01	Hoffmann La Roche	Disubstituerede pyrazolobenzodiazepiner der er nyttige som inhibitorer af CDK2 og angiogenese og til behandling af bryst-, tyktarms-, lunge- og prostatacancer
CN101166742B (zh) *	2005-04-28	2011-07-13	味之素株式会社	新型内酰胺化合物
JP5672699B2 (ja)	2007-04-11	2015-02-18	味の素株式会社	血糖降下作用化合物のスクリーニング法
WO2008139574A1 (ja) *	2007-04-27	2008-11-20	Ajinomoto Co., Inc.	ラクタム化合物の結晶形およびその製造方法
WO2008136393A1 (ja) *	2007-04-27	2008-11-13	Ajinomoto Co., Inc.	ラクタム化合物の結晶形およびその製造方法
WO2008139575A1 (ja) *	2007-04-27	2008-11-20	Ajinomoto Co., Inc.	経口投与用製剤
CN101619041B (zh) *	2008-07-02	2012-07-04	重庆华邦制药股份有限公司	一种二酮基含氮环化合物的合成方法及其中间体
JP2012180282A (ja) *	2009-07-02	2012-09-20	Ajinomoto Co Inc	ラクタム化合物の製造方法およびその製造中間体
JP2012180283A (ja) *	2009-07-02	2012-09-20	Ajinomoto Co Inc	ラクタム化合物の製造方法およびその製造中間体
US20170369494A1 (en) *	2014-12-22	2017-12-28	Ea Pharma Co., Ltd.	Drug for treating disorders of corneal epithelium
WO2017127306A1 (en)	2016-01-18	2017-07-27	Arisan Therapeutics	Adamatane derivatives for the treatment of filovirus infection
WO2019018185A1 (en)	2017-07-15	2019-01-24	Arisan Therapeutics Inc.	ENANTIOMERICALLY PURE ADAMATANE DERIVATIVES FOR THE TREATMENT OF FILOVIRUS INFECTIONS
SG11202106694YA (en) *	2019-01-23	2021-07-29	Glycolysis Biomed Co Ltd	Beta-lactam compounds or salts thereof for use in long-acting prevention or treatment of a glucose metabolism disorder

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US189597A (en) *		1877-04-17		Improvement in portable wash-stands
US48847A (en) *		1865-07-18		Improvement in vessels for reception and transportation of night-soil
GB8720414D0 (en) *	1987-08-28	1987-10-07	Roussel Lab Ltd	Chemical compounds
US5719296A (en) *	1995-10-30	1998-02-17	Merck & Co., Inc.	Pseudopeptide lactam inhibitors of peptide binding to MHC class II proteins
JP2001512120A (ja)	1997-07-30	2001-08-21	アメリカン・ホーム・プロダクツ・コーポレイション	三環系バソプレシンアゴニスト
JP4204657B2 (ja)	1997-12-05	2009-01-07	有限会社ケムフィズ	糖尿病の予防・治療剤
CN100577651C (zh) *	2000-12-01	2010-01-06	味之素株式会社	内酰胺化合物及其药物用途
BRPI0407303A (pt)	2003-02-07	2006-02-07	Ajinomoto Kk	Composição farmacêutica

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Publication number	Publication date
US7153850B2 (en)	2006-12-26
ES2331299T3 (es)	2009-12-29
WO2002044180A1 (en)	2002-06-06
CA2430124A1 (en)	2002-06-06
DE60140270D1 (de)	2009-12-03
AU1850202A (en)	2002-06-11
EP1346993A4 (de)	2005-12-21
JPWO2002044180A1 (ja)	2004-04-02
KR100826818B1 (ko)	2008-05-02
JP3826400B2 (ja)	2006-09-27
NZ526164A (en)	2004-09-24
EP1346993A1 (de)	2003-09-24
JP2006213732A (ja)	2006-08-17
EP1346993B1 (de)	2009-10-21
CN1487940A (zh)	2004-04-07
ATE446297T1 (de)	2009-11-15
UA76969C2 (en)	2006-10-16
HUP0400806A3 (en)	2007-11-28
NO20032439D0 (no)	2003-05-28
AU2002218502B2 (en)	2006-09-21
TWI241302B (en)	2005-10-11
US20080096862A1 (en)	2008-04-24
CZ20031520A3 (cs)	2003-10-15
RU2287530C2 (ru)	2006-11-20
US7632830B2 (en)	2009-12-15
AU2006241377A1 (en)	2006-12-14
CA2430124C (en)	2011-01-11
MXPA03004876A (es)	2004-01-27
SK6582003A3 (en)	2003-09-11
BG107857A (bg)	2004-06-30
KR20030051893A (ko)	2003-06-25
NO20032439L (no)	2003-07-18
US7326701B2 (en)	2008-02-05
US20060189597A1 (en)	2006-08-24
PL362835A1 (en)	2004-11-02
YU42603A (sh)	2006-03-03
AU2006241377B2 (en)	2009-01-08
ZA200304100B (en)	2004-08-22
CN1269818C (zh)	2006-08-16
CN1911915A (zh)	2007-02-14
JP4505753B2 (ja)	2010-07-21
CN100577651C (zh)	2010-01-06
IL156158A0 (en)	2003-12-23
BR0115852A (pt)	2003-12-23
US20040048847A1 (en)	2004-03-11
HUP0400806A2 (hu)	2004-07-28

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Publication	Publication Date	Title
US7632830B2 (en)	2009-12-15	Lactam compounds and pharmaceutical use thereof
US11814386B2 (en)	2023-11-14	Fused pyrrolines which act as ubiquitin-specific protease 30 (USP30) inhibitors
TW200303199A (en)	2003-09-01	Novel pyridin-and pyrimidin-derivatives
IL299756A (en)	2023-03-01	Isoquinoline compounds and their use in the treatment of AHR imbalance
EP4021908A1 (de)	2022-07-06	Perk-hemmende pyrrolopyrimidinverbindungen
KR20100087298A (ko)	2010-08-04	피부 질환의 예방 및/또는 치료제
EP2733144B1 (de)	2016-01-06	Neue verbindung mit parp-hemmender wirkung
CN102807575B (zh)	2015-03-25	3-芳基-5-噻吩基-5H-噻唑并[3,2-a]嘧啶类衍生物及其应用
EP4183785A1 (de)	2023-05-24	Neuartiger n-heterocyclischer bet-bromdomäneninhibitor und herstellungsverfahren dafür und medizinische verwendung davon
US7834006B2 (en)	2010-11-16	Fused polycyclic compounds
JP4345097B2 (ja)	2009-10-14	縮合多環式化合物およびその医薬用途
JP2961534B1 (ja)	1999-10-12	縮合ピリダジン誘導体、その製造法および用途
HK40087840A (en)	2023-09-15	Novel n-heterocyclic bet bromodomain inhibitor, and preparation method therefor and medical use thereof
RU2481349C2 (ru)	2013-05-10	Новые тетрациклические ингибиторы цистеиновых протеаз, их фармацевтические композиции и области их терапевтического применения
HK1236935B (zh)	2020-07-10	作为长效dpp-iv抑制剂的取代的氨基六元饱和杂脂环类