SK18052000A3 - Amidínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents

Amidínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie Download PDF

Info

Publication number: SK18052000A3
Authority: SK; Slovakia
Prior art keywords: tert; formula; cysteine; iminoethylamino; butyl
Prior art date: 1998-05-30

Application number

SK1805-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Paul John Beswick

Savvas Kleanthous

Robert John Young

Original Assignee

Glaxo Group Limited

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.)

1998-05-30

Filing date

1999-05-27

Publication date

2001-06-11

1999-05-27 Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited

2001-06-11 Publication of SK18052000A3 publication Critical patent/SK18052000A3/sk

Links

239000000236 nitric oxide synthase inhibitor Substances 0.000 title claims 3
CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 48
239000012453 solvate Substances 0.000 claims abstract description 32
238000000034 method Methods 0.000 claims abstract description 24
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
238000004519 manufacturing process Methods 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 4
238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 3
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims abstract description 3
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 65
-1 1-Iminoethylamino Chemical group 0.000 claims description 64
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
239000004201 L-cysteine Substances 0.000 claims description 17
150000001409 amidines Chemical class 0.000 claims description 16
239000004480 active ingredient Substances 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 14
239000000203 mixture Substances 0.000 claims description 12
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
238000011321 prophylaxis Methods 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 8
239000000543 intermediate Substances 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
208000019695 Migraine disease Diseases 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
206010027599 migraine Diseases 0.000 claims description 6
230000003287 optical effect Effects 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
235000018417 cysteine Nutrition 0.000 claims description 4
208000008384 ileus Diseases 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
KAXFOSOXUNYWRV-CAHLUQPWSA-N (2s)-2-amino-3-[(2s)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-CAHLUQPWSA-N 0.000 claims description 3
125000004414 alkyl thio group Chemical group 0.000 claims description 3
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
229940124639 Selective inhibitor Drugs 0.000 abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
102000011779 Nitric Oxide Synthase Type II Human genes 0.000 abstract 1
108010076864 Nitric Oxide Synthase Type II Proteins 0.000 abstract 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 abstract 1
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Natural products SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 13
239000003112 inhibitor Substances 0.000 description 13
239000000243 solution Substances 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 12
239000000047 product Substances 0.000 description 12
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 10
229910052799 carbon Inorganic materials 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
238000004949 mass spectrometry Methods 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
150000001721 carbon Chemical group 0.000 description 8
235000013878 L-cysteine Nutrition 0.000 description 7
208000002193 Pain Diseases 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
102000008299 Nitric Oxide Synthase Human genes 0.000 description 6
108010021487 Nitric Oxide Synthase Proteins 0.000 description 6
241000700159 Rattus Species 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
239000007788 liquid Substances 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
239000002585 base Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
208000027866 inflammatory disease Diseases 0.000 description 5
239000003826 tablet Substances 0.000 description 5
229950004288 tosilate Drugs 0.000 description 5
208000035143 Bacterial infection Diseases 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
101710111444 Nitric oxide synthase, brain Proteins 0.000 description 4
102100022397 Nitric oxide synthase, brain Human genes 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
208000022362 bacterial infectious disease Diseases 0.000 description 4
208000026278 immune system disease Diseases 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000035939 shock Effects 0.000 description 4
238000001228 spectrum Methods 0.000 description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 description 3
102000003960 Ligases Human genes 0.000 description 3
108090000364 Ligases Proteins 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
125000002252 acyl group Chemical class 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
238000002983 circular dichroism Methods 0.000 description 3
239000008187 granular material Substances 0.000 description 3
102000055708 human NOS2 Human genes 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
238000012261 overproduction Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
ATVFTGTXIUDKIZ-YFKPBYRVSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-sulfanylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CS)C(O)=O ATVFTGTXIUDKIZ-YFKPBYRVSA-N 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical class CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 2
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
208000000094 Chronic Pain Diseases 0.000 description 2
XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
229930195710 D‐cysteine Natural products 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
208000005298 acute pain Diseases 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
150000001370 alpha-amino acid derivatives Chemical group 0.000 description 2
235000008206 alpha-amino acids Nutrition 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
230000001186 cumulative effect Effects 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
230000004968 inflammatory condition Effects 0.000 description 2
208000014674 injury Diseases 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
238000002156 mixing Methods 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
WZOXMZCQBCMNOR-UHFFFAOYSA-N naphthalen-1-ylmethyl ethanimidothioate;hydrochloride Chemical compound Cl.C1=CC=C2C(CSC(=N)C)=CC=CC2=C1 WZOXMZCQBCMNOR-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
229960001802 phenylephrine Drugs 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
230000036303 septic shock Effects 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
KAXFOSOXUNYWRV-IYSWYEEDSA-N (2s)-2-amino-3-[(2r)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-IYSWYEEDSA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
208000007788 Acute Liver Failure Diseases 0.000 description 1
206010000804 Acute hepatic failure Diseases 0.000 description 1
206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
206010006002 Bone pain Diseases 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
206010008479 Chest Pain Diseases 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
208000010412 Glaucoma Diseases 0.000 description 1
206010018364 Glomerulonephritis Diseases 0.000 description 1
108010078321 Guanylate Cyclase Proteins 0.000 description 1
102000014469 Guanylate cyclase Human genes 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000037357 HIV infectious disease Diseases 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
206010020710 Hyperphagia Diseases 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
206010065390 Inflammatory pain Diseases 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
108010044467 Isoenzymes Proteins 0.000 description 1
208000012659 Joint disease Diseases 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
235000014852 L-arginine Nutrition 0.000 description 1
229930064664 L-arginine Natural products 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
208000019693 Lung disease Diseases 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
206010049816 Muscle tightness Diseases 0.000 description 1
208000000112 Myalgia Diseases 0.000 description 1
201000002481 Myositis Diseases 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
208000016222 Pancreatic disease Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
206010058046 Post procedural complication Diseases 0.000 description 1
208000035965 Postoperative Complications Diseases 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
208000026062 Tissue disease Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
231100000836 acute liver failure Toxicity 0.000 description 1
208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000004419 alkynylene group Chemical group 0.000 description 1
230000001668 ameliorated effect Effects 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
210000002376 aorta thoracic Anatomy 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
229960002173 citrulline Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
206010009887 colitis Diseases 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
230000016396 cytokine production Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical group CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
208000010643 digestive system disease Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000003821 enantio-separation Methods 0.000 description 1
208000037902 enteropathy Diseases 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
208000030533 eye disease Diseases 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
230000001146 hypoxic effect Effects 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
208000028774 intestinal disease Diseases 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
238000000465 moulding Methods 0.000 description 1
210000002200 mouth mucosa Anatomy 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
208000013465 muscle pain Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
210000000944 nerve tissue Anatomy 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
230000001129 nonadrenergic effect Effects 0.000 description 1
230000002536 noncholinergic effect Effects 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
201000011264 priapism Diseases 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
239000002151 riboflavin Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000008733 trauma Effects 0.000 description 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (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)
Neurology (AREA)
Rheumatology (AREA)
Neurosurgery (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Heart & Thoracic Surgery (AREA)
Oncology (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK1805-2000A 1998-05-30 1999-05-27 Amidínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie SK18052000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9811599.1A GB9811599D0 (en)	1998-05-30	1998-05-30	Nitric oxide synthase inhibitors
PCT/EP1999/003583 WO1999062875A1 (en)	1998-05-30	1999-05-27	Nitric oxide synthase inhibitors

Publications (1)

Publication Number	Publication Date
SK18052000A3 true SK18052000A3 (sk)	2001-06-11

Family

ID=10832929

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1805-2000A SK18052000A3 (sk)	1998-05-30	1999-05-27	Amidínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie

Country Status (30)

Country	Link
US (2)	US6355689B1 (sr)
EP (1)	EP1084104B1 (sr)
JP (1)	JP3839256B2 (sr)
KR (1)	KR20010043920A (sr)
CN (1)	CN1218940C (sr)
AP (1)	AP1382A (sr)
AT (1)	ATE245142T1 (sr)
AU (1)	AU757042B2 (sr)
BR (1)	BR9910849A (sr)
CA (1)	CA2333322C (sr)
CZ (1)	CZ297473B6 (sr)
DE (1)	DE69909625T2 (sr)
DK (1)	DK1084104T3 (sr)
EA (1)	EA003026B1 (sr)
EE (1)	EE04149B1 (sr)
ES (1)	ES2203147T3 (sr)
GB (1)	GB9811599D0 (sr)
HU (1)	HUP0102472A3 (sr)
ID (1)	ID26790A (sr)
IL (1)	IL139697A (sr)
IS (1)	IS2442B (sr)
NO (1)	NO20006044L (sr)
NZ (1)	NZ508222A (sr)
PL (1)	PL194784B1 (sr)
PT (1)	PT1084104E (sr)
RS (1)	RS49984B (sr)
SK (1)	SK18052000A3 (sr)
TR (1)	TR200003539T2 (sr)
WO (1)	WO1999062875A1 (sr)
ZA (1)	ZA200006847B (sr)

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK1265859T3 (da) *	2000-03-24	2006-05-01	Pharmacia Corp	Amidinoforbindelser der er nyttige som nitrogenoxidsyntaseinhibitorer
US7012098B2 (en)	2001-03-23	2006-03-14	Pharmacia Corporation	Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers
JPWO2003022309A1 (ja) *	2001-09-10	2004-12-24	小野薬品工業株式会社	アレルギー疾患治療剤
US20030109522A1 (en) *	2001-09-24	2003-06-12	Manning Pamela T.	Ophthalmologic treatment methods using selective iNOS inhibitors
CN1652843A (zh) *	2002-05-16	2005-08-10	法玛西雅公司	使用选择性iNOS抑制剂治疗呼吸系统疾病和病症
US20040087653A1 (en) *	2002-05-16	2004-05-06	Manning Pamela T.	Methods for the treatment of respiratory diseases and conditions with a selective iNOS inhibitor and a PDE inhibitor and compositions therefor
MXPA05001255A (es) *	2002-08-02	2005-06-08	Pharmacia Corp	Metodos para el tratamiento y prevencion de condiciones gastrointestinales.
US20060247216A1 (en) *	2002-10-25	2006-11-02	Haj-Yehia Abdullah I	Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments
EP1578413A2 (en) *	2002-11-29	2005-09-28	Yissum Research Development Company of The Hebrew University of Jerusalem	Ace-inhibitors having antioxidant and no-donor activity
TWI328009B (en)	2003-05-21	2010-08-01	Glaxo Group Ltd	Quinoline derivatives as phosphodiesterase inhibitors
GB0316212D0 (en) *	2003-07-10	2003-08-13	Glaxo Group Ltd	Novel compounds
GB0316290D0 (en)	2003-07-11	2003-08-13	Glaxo Group Ltd	Novel compounds
WO2005025620A2 (en) *	2003-08-13	2005-03-24	Pharmacia Corporation	Combination therapy with inhibitors of inducible nitric oxide synthase and alkylating agents
AR049384A1 (es)	2004-05-24	2006-07-26	Glaxo Group Ltd	Derivados de purina
TWI307630B (en)	2004-07-01	2009-03-21	Glaxo Group Ltd	Immunoglobulins
GB0418045D0 (en)	2004-08-12	2004-09-15	Glaxo Group Ltd	Compounds
EP1841780B1 (en)	2005-01-10	2011-07-27	Glaxo Group Limited	Androstane 17-alpha-carbonate derivatives for use in the treatment of allergic and inflammatory conditions
PE20061193A1 (es)	2005-03-25	2006-12-02	Glaxo Group Ltd	DERIVADOS DE 3,4-DIHIDROPIRIMIDO[4,5-d]PIRIMIDIN-2-[1H]-0NA COMO INHIBIDORES DE QUINASA p38
MY145343A (en)	2005-03-25	2012-01-31	Glaxo Group Ltd	Novel compounds
JPWO2007000884A1 (ja) *	2005-06-29	2009-01-22	国立大学法人金沢大学	骨・関節疾患の予防・治療剤およびそのスクリーニング方法
GB0514809D0 (en)	2005-07-19	2005-08-24	Glaxo Group Ltd	Compounds
TW200730498A (en)	2005-12-20	2007-08-16	Glaxo Group Ltd	Compounds
KR20090003349A (ko)	2006-04-20	2009-01-09	글락소 그룹 리미티드	화합물
GB0611587D0 (en)	2006-06-12	2006-07-19	Glaxo Group Ltd	Novel compounds
CA2659539A1 (en)	2006-08-01	2008-02-07	Glaxo Group Limited	Pyrazolo[3,4-b]pyridine compounds, and their use as pde4 inhibitors
CA2669138A1 (en) *	2006-11-09	2008-12-04	University Of Maryland, Baltimore	Use of 5,6-dimethylxanthenone-4-acetic acid as an antimicrobial agent
PE20081889A1 (es)	2007-03-23	2009-03-05	Smithkline Beecham Corp	Indol carboxamidas como inhibidores de ikk2
BRPI0912267A2 (pt)	2008-05-23	2015-10-13	Amira Pharmaceuticals Inc	sal farmaceuticamente aceitável, composição farmacêutica, artigo de fabricação, métodos para tratar asma, rinite alérgica, doença, lesões gástricas e dor, métodos para prevenir broncoconstrição e rinite alérgica, uso de um sal farmaceuticamente aceitável, e, processo para a preparação de um sal farmaceuticamente aceitável.
ES2566339T3 (es)	2008-06-05	2016-04-12	Glaxo Group Limited	Derivados de 4-carboxamida indazol útiles como inhibidores de PI3-quinasas
JP5502077B2 (ja)	2008-06-05	2014-05-28	グラクソグループリミテッド	新規な化合物
WO2010094643A1 (en)	2009-02-17	2010-08-26	Glaxo Group Limited	Quinoline derivatives and their uses for rhinitis and urticaria
US8524751B2 (en)	2009-03-09	2013-09-03	GlaxoSmithKline Intellecutual Property Development	4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases
JP2012520257A (ja)	2009-03-10	2012-09-06	グラクソグループリミテッド	Ｉｋｋ２阻害剤としてのインドール誘導体
EP2408769A1 (en)	2009-03-17	2012-01-25	Glaxo Group Limited	Pyrimidine derivatives used as itk inhibitors
WO2010107958A1 (en)	2009-03-19	2010-09-23	Merck Sharp & Dohme Corp.	RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 6 (STAT6) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
EA201171144A1 (ru)	2009-03-19	2012-04-30	Мерк Шарп Энд Домэ Корп.	ОПОСРЕДОВАННОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНА ГОМОЛОГА 1 BTB И CNC, ОСНОВНОГО ФАКТОРА ТРАНСКРИПЦИИ С ЛЕЙЦИНОВОЙ МОЛНИЕЙ 1 (Bach1) С ИСПОЛЬЗОВАНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК)
EP2408916A2 (en)	2009-03-19	2012-01-25	Merck Sharp&Dohme Corp.	RNA INTERFERENCE MEDIATED INHIBITION OF CONNECTIVE TISSUE GROWTH FACTOR (CTGF) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
JP2012520685A (ja)	2009-03-19	2012-09-10	メルク・シャープ・エンド・ドーム・コーポレイション	低分子干渉核酸（ｓｉＮＡ）を用いたＧＡＴＡ結合タンパク質３（ＧＡＴＡ３）遺伝子発現のＲＮＡ干渉媒介性阻害
WO2010111468A2 (en)	2009-03-27	2010-09-30	Merck Sharp & Dohme Corp.	RNA INTERFERENCE MEDIATED INHIBITION OF THE NERVE GROWTH FACTOR BETA CHAIN (NGFß) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA)
KR20110138223A (ko)	2009-03-27	2011-12-26	머크 샤프 앤드 돔 코포레이션	짧은 간섭 핵산 (ｓｉＮＡ)을 사용한 세포간 부착 분자 1 (ＩＣＡＭ-1) 유전자 발현의 ＲＮＡ 간섭 매개 억제
US20120022142A1 (en)	2009-03-27	2012-01-26	Merck Sharp & Dohme Corp.	RNA Interference Mediated Inhibition of Signal Transducer and Activator of Transcription 1 (STAT1) Gene Expression Using Short Interfering Nucleic Acid (siNA)
JP2012521760A (ja)	2009-03-27	2012-09-20	メルク・シャープ・エンド・ドーム・コーポレイション	低分子干渉核酸（ｓｉＮＡ）を用いたアポトーシスシグナル調節キナーゼ１（ＡＳＫ１）遺伝子発現のＲＮＡ干渉媒介性阻害
US20120022143A1 (en)	2009-03-27	2012-01-26	Merck Sharp & Dohme Corp	RNA Interference Mediated Inhibition of the Thymic Stromal Lymphopoietin (TSLP) Gene Expression Using Short Interfering Nucliec Acid (siNA)
US20100273744A1 (en)	2009-04-24	2010-10-28	Paul Martin Gore	Compounds
EP2421834A1 (en)	2009-04-24	2012-02-29	Glaxo Group Limited	Pyrazole and triazole carboxamides as crac channel inhibitors
CN102459253B (zh)	2009-04-30	2015-03-25	葛兰素集团有限公司	作为pi3-激酶抑制剂的*唑取代的吲唑化合物
US20120238559A1 (en)	2009-12-03	2012-09-20	Glaxo Group Limited	Novel compounds
WO2011067366A1 (en)	2009-12-03	2011-06-09	Glaxo Group Limited	Indazole derivatives as pi 3 - kinase inhibitors
EP2507223A1 (en)	2009-12-03	2012-10-10	Glaxo Group Limited	Benzpyrazole derivatives as inhibitors of p13 kinases
US20120272951A1 (en)	2009-12-16	2012-11-01	3M Innovative Properties Company	Formulations and methods for controlling mdi particle size delivery
TWI375671B (en) *	2010-03-01	2012-11-01	Univ China Medical	Pharmaceutical compositions containing brazilin for inhibiting expression of cytokines of t helper cell type ii and/or inhibiting expression of chemokines and uses of the same
WO2011110575A1 (en)	2010-03-11	2011-09-15	Glaxo Group Limited	Derivatives of 2-[2-(benzo- or pyrido-) thiazolylamino]-6-aminopyridine, useful in the treatment of respiratoric, allergic or inflammatory diseases
GB201007203D0 (en)	2010-04-29	2010-06-16	Glaxo Group Ltd	Novel compounds
JP5965402B2 (ja)	2010-09-08	2016-08-03	グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅＩｎｔｅｌｌｅｃｔｕａｌＰｒｏｐｅｒｔｙＤｅｖｅｌｏｐｍｅｎｔＬｉｍｉｔｅｄ	Ｎ−［５−［４−（５−｛［（２ｒ，６ｓ）−２，６−ジメチル−４−モルホリニル］メチル｝−１，３−オキサゾール−２−イル）−１ｈ−インダゾール−６−イル］−２−（メチルオキシ）−３−ピリジニル］メタンスルホンアミドの多形体および塩
WO2012032065A1 (en)	2010-09-08	2012-03-15	Glaxo Group Limited	Indazole derivatives for use in the treatment of influenza virus infection
WO2012035055A1 (en)	2010-09-17	2012-03-22	Glaxo Group Limited	Novel compounds
EP2630127A1 (en)	2010-10-21	2013-08-28	Glaxo Group Limited	Pyrazole compounds acting against allergic, inflammatory and immune disorders
EP2630126B1 (en)	2010-10-21	2015-01-07	Glaxo Group Limited	Pyrazole compounds acting against allergic, immune and inflammatory conditions
GB201018124D0 (en)	2010-10-27	2010-12-08	Glaxo Group Ltd	Polymorphs and salts
GB201104153D0 (en)	2011-03-11	2011-04-27	Glaxo Group Ltd	Novel compounds
US20140005188A1 (en)	2011-03-11	2014-01-02	Glaxo Group Limited	Pyrido[3,4-b]pyrazine derivatives as syk inhibitors
KR20160060100A (ko)	2013-09-22	2016-05-27	칼리토르 사이언시즈, 엘엘씨	치환된 아미노피리미딘 화합물 및 이용 방법
WO2015148868A1 (en)	2014-03-28	2015-10-01	Calitor Sciences, Llc	Substituted heteroaryl compounds and methods of use
TW201625247A (zh)	2014-05-12	2016-07-16	葛蘭素史密斯克藍智慧財產權有限公司	用於治療傳染性疾病之醫藥組合物
US9938257B2 (en)	2015-09-11	2018-04-10	Calitor Sciences, Llc	Substituted heteroaryl compounds and methods of use
US10683297B2 (en)	2017-11-19	2020-06-16	Calitor Sciences, Llc	Substituted heteroaryl compounds and methods of use
CA3083040A1 (en)	2018-01-20	2019-07-25	Sunshine Lake Pharma Co., Ltd.	Substituted aminopyrimidine compounds and methods of use
EP4125919A1 (en)	2020-03-26	2023-02-08	GlaxoSmithKline Intellectual Property Development Limited	Cathepsin inhibitors for preventing or treating viral infections

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2049582A (en)	1931-11-04	1936-08-04	Rohm & Haas	Amidines
US4085217A (en)	1964-01-29	1978-04-18	L'oreal	Process and cosmetic compositions for the treatment of skin and scalp
US4085218A (en)	1975-10-30	1978-04-18	Sandoz Ltd.	Elevating mood in geriatric patients
US4512979A (en)	1981-03-23	1985-04-23	Merck & Co., Inc.	Dipeptides containing thialysine and related amino acids as antihypertensives
EP0068173B1 (en)	1981-06-05	1984-09-26	Merck & Co. Inc.	Perhydro-1,4-thiazepin-5-one and perhydro-1,4-thiazocin-5-one derivatives, process for preparing and pharmceutical composition containing the same
US4594341A (en)	1982-04-06	1986-06-10	Merck & Co., Inc.	Perhydro-1,4-thiazepin-5-one and perhydro-1,4-thiazocin-5-one derivatives as antihypertensives
FI832053L (fi)	1982-06-10	1983-12-11	Syntex Inc	Nonapeptid- och dekapeptidanaloger av lhrh anvaendbara som lhrh-antagonister samt deras framstaellningsfoerfarande
DE3514450A1 (de)	1985-04-22	1986-10-23	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung von imidaten sowie neue arylsubstituierte imidate
US5028627A (en)	1989-09-13	1991-07-02	Cornell Research Foundation, Inc.	Method of using arginine derivatives to inhibit systemic hypotension associated with nitric oxide production or endothelial derived relaxing factor
GB8929076D0 (en)	1989-12-22	1990-02-28	Scras	Treatment of shock by blocking agents of edrf effect or formation
AU636713B2 (en)	1990-02-26	1993-05-06	Merrell Dow Pharmaceuticals Inc.	Inhibitors of nitric oxide biosynthesis
GB9127376D0 (en)	1991-12-24	1992-02-19	Wellcome Found	Amidino derivatives
DE4310202A1 (de)	1992-03-30	1993-10-07	Ciba Geigy	µ-Ketoimidoester als Stabilisatoren für chlorhaltige Polymerisate
US5281627A (en)	1992-05-28	1994-01-25	Cornell Research Foundation, Inc.	Substituted arginines and substituted homoarginines and use thereof
US5585402A (en)	1992-12-23	1996-12-17	Glaxo Wellcome Inc.	Nitric oxide synthase inhibitors
US5364881A (en)	1993-11-15	1994-11-15	The Medical College Of Wisconsin Research Foundation, Inc.	S-alkyl-isothioureido-amino acids and use thereof
SI0765308T1 (sl)	1994-06-15	2000-08-31	The Wellcome Foundation Limited	Encimski inhibitorji
FR2727111B1 (fr)	1994-11-21	1997-01-17	Hoechst Lab	Nouveaux analogues soufres d'aminoacides, leur procede de preparation et leurs applications comme medicaments
MY117948A (en) *	1997-01-13	2004-08-30	Glaxo Group Ltd	Nitride oxide synthase inhibitors.

1998
- 1998-05-30 GB GBGB9811599.1A patent/GB9811599D0/en not_active Ceased
1999
- 1999-05-27 BR BR9910849-6A patent/BR9910849A/pt not_active Application Discontinuation
- 1999-05-27 WO PCT/EP1999/003583 patent/WO1999062875A1/en not_active Ceased
- 1999-05-27 NZ NZ508222A patent/NZ508222A/xx unknown
- 1999-05-27 AT AT99926397T patent/ATE245142T1/de not_active IP Right Cessation
- 1999-05-27 IL IL13969799A patent/IL139697A/xx not_active IP Right Cessation
- 1999-05-27 JP JP2000552087A patent/JP3839256B2/ja not_active Expired - Fee Related
- 1999-05-27 RS YUP-746/00A patent/RS49984B/sr unknown
- 1999-05-27 DE DE69909625T patent/DE69909625T2/de not_active Expired - Lifetime
- 1999-05-27 CA CA002333322A patent/CA2333322C/en not_active Expired - Fee Related
- 1999-05-27 KR KR1020007013451A patent/KR20010043920A/ko not_active Ceased
- 1999-05-27 ES ES99926397T patent/ES2203147T3/es not_active Expired - Lifetime
- 1999-05-27 PL PL344368A patent/PL194784B1/pl unknown
- 1999-05-27 CN CNB998068578A patent/CN1218940C/zh not_active Expired - Fee Related
- 1999-05-27 EP EP99926397A patent/EP1084104B1/en not_active Expired - Lifetime
- 1999-05-27 DK DK99926397T patent/DK1084104T3/da active
- 1999-05-27 SK SK1805-2000A patent/SK18052000A3/sk unknown
- 1999-05-27 AP APAP/P/2000/001998A patent/AP1382A/en active
- 1999-05-27 CZ CZ20004450A patent/CZ297473B6/cs not_active IP Right Cessation
- 1999-05-27 EA EA200001122A patent/EA003026B1/ru not_active IP Right Cessation
- 1999-05-27 PT PT99926397T patent/PT1084104E/pt unknown
- 1999-05-27 HU HU0102472A patent/HUP0102472A3/hu unknown
- 1999-05-27 AU AU43671/99A patent/AU757042B2/en not_active Ceased
- 1999-05-27 ID IDW20002495A patent/ID26790A/id unknown
- 1999-05-27 US US09/701,473 patent/US6355689B1/en not_active Expired - Lifetime
- 1999-05-27 TR TR2000/03539T patent/TR200003539T2/xx unknown
- 1999-05-27 EE EEP200000716A patent/EE04149B1/xx not_active IP Right Cessation
2000
- 2000-11-21 IS IS5723A patent/IS2442B/is unknown
- 2000-11-22 ZA ZA200006847A patent/ZA200006847B/en unknown
- 2000-11-29 NO NO20006044A patent/NO20006044L/no not_active Application Discontinuation
2001
- 2001-11-26 US US09/994,969 patent/US6495606B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DK1084104T3 (da)	2003-10-27
GB9811599D0 (en)	1998-07-29
CN1218940C (zh)	2005-09-14
ID26790A (id)	2001-02-08
DE69909625T2 (de)	2004-06-24
JP3839256B2 (ja)	2006-11-01
PL344368A1 (en)	2001-11-05
RS49984B (sr)	2008-09-29
EE04149B1 (et)	2003-10-15
AP1382A (en)	2005-04-01
EA003026B1 (ru)	2002-12-26
IL139697A (en)	2005-12-18
AU757042B2 (en)	2003-01-30
CA2333322C (en)	2008-01-22
EA200001122A1 (ru)	2001-06-25
EP1084104B1 (en)	2003-07-16
JP2002516901A (ja)	2002-06-11
ATE245142T1 (de)	2003-08-15
ES2203147T3 (es)	2004-04-01
CZ297473B6 (cs)	2006-12-13
PT1084104E (pt)	2003-11-28
IS2442B (is)	2008-11-15
CA2333322A1 (en)	1999-12-09
HUP0102472A2 (hu)	2002-03-28
IL139697A0 (en)	2002-02-10
HUP0102472A3 (en)	2002-12-28
KR20010043920A (ko)	2001-05-25
BR9910849A (pt)	2001-02-20
WO1999062875A1 (en)	1999-12-09
YU74600A (sh)	2002-12-10
EP1084104A1 (en)	2001-03-21
NO20006044D0 (no)	2000-11-29
ZA200006847B (en)	2001-11-22
IS5723A (is)	2000-11-21
AP2000001998A0 (en)	2000-12-31
NO20006044L (no)	2001-01-29
CN1303367A (zh)	2001-07-11
AU4367199A (en)	1999-12-20
TR200003539T2 (tr)	2001-06-21
NZ508222A (en)	2003-02-28
CZ20004450A3 (en)	2001-05-16
HK1034241A1 (en)	2001-10-19
US6355689B1 (en)	2002-03-12
US6495606B1 (en)	2002-12-17
PL194784B1 (pl)	2007-07-31
EE200000716A (et)	2002-04-15
DE69909625D1 (en)	2003-08-21

Publication	Publication Date	Title
SK18052000A3 (sk)	2001-06-11	Amidínové deriváty, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie
SK283201B6 (sk)	2003-03-04	Amidínové zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom, ich použitie a medziprodukt
KR100853049B1 (ko)	2008-08-19	산화질소 신타제 억제제 포스페이트염
US6620848B2 (en)	2003-09-16	Nitric oxide synthase inhibitors
US6369272B1 (en)	2002-04-09	Nitric oxide synthase inhibitors
HK1034241B (en)	2003-10-31	Nitric oxide synthase inhibitors
MXPA00011528A (en)	2001-11-21	Nitric oxide synthase inhibitors
MXPA99006172A (en)	2000-02-02	Nitric oxide synthase inhibitors