CA2352154A1 - Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus - Google Patents

Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus Download PDF

Info

Publication number: CA2352154A1
Authority: CA; Canada
Prior art keywords: atoms; het; methyl; formula; insulin
Prior art date: 1998-11-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002352154A

Other languages

English (en)

French (fr)

Inventor

Rolf Gericke

Manfred Baumgarth

Klaus Minck

Didier Mesangeau

Liliane Doare

Micheline Kergoat

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck Patent GmbH

Original Assignee

Individual

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.)

1998-11-26

Filing date

1999-11-16

Publication date

2000-06-02

1999-11-16 Application filed by Individual filed Critical Individual

2000-06-02 Publication of CA2352154A1 publication Critical patent/CA2352154A1/en

Status Abandoned legal-status Critical Current

Links

208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 17
AJDQRQQNNLZLPM-UHFFFAOYSA-N n-(diaminomethylidene)benzamide Chemical class NC(N)=NC(=O)C1=CC=CC=C1 AJDQRQQNNLZLPM-UHFFFAOYSA-N 0.000 title claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 25
150000003839 salts Chemical class 0.000 claims abstract description 19
239000003814 drug Substances 0.000 claims abstract description 14
238000004519 manufacturing process Methods 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 12
239000012453 solvate Substances 0.000 claims abstract description 10
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
XYEIQWWYUKARGX-UHFFFAOYSA-N n-(diaminomethylidene)-2-methyl-5-methylsulfonyl-4-(trifluoromethyl)benzamide Chemical compound CC1=CC(C(F)(F)F)=C(S(C)(=O)=O)C=C1C(=O)N=C(N)N XYEIQWWYUKARGX-UHFFFAOYSA-N 0.000 claims description 2
UADMBZFZZOBWBB-UHFFFAOYSA-N n-(diaminomethylidene)-2-methyl-5-methylsulfonyl-4-pyrrol-1-ylbenzamide Chemical compound C1=C(C(=O)N=C(N)N)C(C)=CC(N2C=CC=C2)=C1S(C)(=O)=O UADMBZFZZOBWBB-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
HNFKKQSEFIJHEP-UHFFFAOYSA-N n-(diaminomethylidene)-2-methyl-5-methylsulfonyl-4-propan-2-ylbenzamide Chemical compound CC(C)C1=CC(C)=C(C(=O)N=C(N)N)C=C1S(C)(=O)=O HNFKKQSEFIJHEP-UHFFFAOYSA-N 0.000 claims 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 4
-1 alkyl radical Chemical class 0.000 description 70
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 9
239000002253 acid Substances 0.000 description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
239000000243 solution Substances 0.000 description 7
239000003826 tablet Substances 0.000 description 7
206010012601 diabetes mellitus Diseases 0.000 description 6
125000004076 pyridyl group Chemical group 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
230000037396 body weight Effects 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
125000005479 oxodihydropyridyl group Chemical group 0.000 description 4
239000000126 substance Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012154 double-distilled water Substances 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000000829 suppository Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
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 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
102000052126 Sodium-Hydrogen Exchangers Human genes 0.000 description 2
108091006672 Sodium–hydrogen antiporter Proteins 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
230000003178 anti-diabetic effect Effects 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
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 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000000203 mixture Substances 0.000 description 2
239000002674 ointment Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
235000019271 petrolatum Nutrition 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
235000011007 phosphoric acid Nutrition 0.000 description 2
WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 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
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
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241000416162 Astragalus gummifer Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
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208000035475 disorder Diseases 0.000 description 1
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229940079593 drug Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
235000021588 free fatty acids Nutrition 0.000 description 1
235000011389 fruit/vegetable juice Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
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239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
235000013773 glyceryl triacetate Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
239000007943 implant Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
238000000034 method Methods 0.000 description 1
125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 description 1
125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
WNBSDCKJFDZMHT-UHFFFAOYSA-N n-(diaminomethylidene)pyrazine-2-carboxamide Chemical class NC(N)=NC(=O)C1=CN=CC=N1 WNBSDCKJFDZMHT-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
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 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
229960001052 streptozocin Drugs 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
229960002622 triacetin Drugs 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/402—1-aryl substituted, e.g. piretanide
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones

Landscapes

Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Diabetes (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Hematology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyrrole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA002352154A 1998-11-26 1999-11-16 Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus Abandoned CA2352154A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP98122419.9		1998-11-26
EP98122419		1998-11-26
PCT/EP1999/008795 WO2000030624A2 (en)	1998-11-26	1999-11-16	Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus

Publications (1)

Publication Number	Publication Date
CA2352154A1 true CA2352154A1 (en)	2000-06-02

Family

ID=8233036

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002352154A Abandoned CA2352154A1 (en)	1998-11-26	1999-11-16	Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus

Country Status (14)

Country	Link
EP (1)	EP1131064A2 (id)
JP (1)	JP2002530325A (id)
KR (1)	KR20010080597A (id)
CN (1)	CN1328452A (id)
AR (1)	AR023064A1 (id)
AU (1)	AU1553500A (id)
BR (1)	BR9915667A (id)
CA (1)	CA2352154A1 (id)
CZ (1)	CZ20011785A3 (id)
HU (1)	HUP0104418A2 (id)
ID (1)	ID29523A (id)
NO (1)	NO20012563L (id)
PL (1)	PL348152A1 (id)
WO (1)	WO2000030624A2 (id)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN101103977A (zh) *	2002-06-05	2008-01-16	株式会社医药分子设计研究所	糖尿病治疗药
US7381841B2 (en)	2003-08-22	2008-06-03	Sanofi-Aventis Deutschland Gmbh	Pentafluorosulfanylphenyl-substituted benzoylguanidines, processes for their preparation, their use as medicament or diagnostic aid, and medicament comprising them
DE102004054847A1 (de) *	2004-11-13	2006-05-24	Sanofi-Aventis Deutschland Gmbh	Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4430916A1 (de) *	1994-08-31	1996-03-07	Merck Patent Gmbh	Alkyl-benzoylguanidin-Derivate
DE4430861A1 (de) *	1994-08-31	1996-03-07	Merck Patent Gmbh	Heterocyclyl-benzoylguanidine
DE4437874A1 (de) *	1994-10-22	1996-04-25	Merck Patent Gmbh	Alkyl-5-methylsulfonyl-benzoylguanidin-Derivate
DE19502644A1 (de) *	1995-01-28	1996-08-01	Merck Patent Gmbh	4-Amino-benzoylguanidin-Derivate
DE19502895A1 (de) *	1995-01-31	1996-08-01	Merck Patent Gmbh	4-Mercapto-benzoylguanidin-Derivate
DE19517848A1 (de) *	1995-05-16	1996-11-21	Merck Patent Gmbh	Fluorhaltige Benzoylguanidine
DE19531138A1 (de) *	1995-08-24	1997-02-27	Merck Patent Gmbh	Alkenyl-benzoylguanidin-Derivate

1999
- 1999-11-16 BR BR9915667-9A patent/BR9915667A/pt not_active Application Discontinuation
- 1999-11-16 KR KR1020017006615A patent/KR20010080597A/ko not_active Withdrawn
- 1999-11-16 CZ CZ20011785A patent/CZ20011785A3/cs unknown
- 1999-11-16 WO PCT/EP1999/008795 patent/WO2000030624A2/en not_active Ceased
- 1999-11-16 HU HU0104418A patent/HUP0104418A2/hu unknown
- 1999-11-16 EP EP99958047A patent/EP1131064A2/en not_active Ceased
- 1999-11-16 JP JP2000583507A patent/JP2002530325A/ja active Pending
- 1999-11-16 ID IDW00200101318A patent/ID29523A/id unknown
- 1999-11-16 CA CA002352154A patent/CA2352154A1/en not_active Abandoned
- 1999-11-16 AU AU15535/00A patent/AU1553500A/en not_active Abandoned
- 1999-11-16 CN CN99813826A patent/CN1328452A/zh active Pending
- 1999-11-16 PL PL99348152A patent/PL348152A1/xx unknown
- 1999-11-26 AR ARP990106043A patent/AR023064A1/es unknown
2001
- 2001-05-25 NO NO20012563A patent/NO20012563L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO20012563D0 (no)	2001-05-25
CN1328452A (zh)	2001-12-26
CZ20011785A3 (cs)	2001-10-17
ID29523A (id)	2001-09-06
PL348152A1 (en)	2002-05-06
HUP0104418A2 (hu)	2002-04-29
EP1131064A2 (en)	2001-09-12
JP2002530325A (ja)	2002-09-17
AU1553500A (en)	2000-06-13
BR9915667A (pt)	2001-08-14
KR20010080597A (ko)	2001-08-22
WO2000030624A3 (en)	2000-10-05
NO20012563L (no)	2001-05-25
AR023064A1 (es)	2002-09-04
WO2000030624A2 (en)	2000-06-02

Legal Events

Date	Code	Title	Description
2002-11-18	FZDE	Discontinued

Publication	Publication Date	Title
US6174925B1 (en)	2001-01-16	Use of sibutramine analogues to prevent the development of diabetes
US12201602B2 (en)	2025-01-21	Medicament comprising combination of sepetaprost and Rho-associated coiled-coil containing protein kinase inhibitor
AU2004271740A1 (en)	2005-03-24	Benzothiazole derivatives for the treatment of diabetes
US5837723A (en)	1998-11-17	Pharmaceutical composition useful for treating ophthalmological diseases
US6399658B1 (en)	2002-06-04	Composition containing ascorbic acid
JP2009001591A (ja)	2009-01-08	緑内障治療用のデプレニル化合物
CA2352154A1 (en)	2000-06-02	Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus
KR20040025882A (ko)	2004-03-26	신경성 통증 치료 및 예방약
EP3231428B1 (en)	2020-03-04	Pharmacotherapy for preventing or treating glaucoma
EP1297849B1 (en)	2009-04-15	Remedial agent for optic nerve diseases
WO1998016224A1 (de)	1998-04-23	Pyrazolinone zur behandlung von potenzstörungen
US20040171663A1 (en)	2004-09-02	Method for prophylaxis and treatment of diabetic complications with 4[alpha-hydroxy-2-methyl-5-(1-imidazolyl)benzyl]-3,5-dimethylbenzoic acid and derivatives
ES2865118T3 (es)	2021-10-15	Composición farmacéutica que comprende (S)-(3-(1-(1H-imidazol-4-il)etil)-2-metilfenil)metanol para el tratamiento de neuropatía óptica
MXPA01005295A (en)	2002-06-05	Use of benzoylguanidines for the treatment of non-insulin-dependent diabetes mellitus
HK40102807A (en)	2024-06-14	Combination of sepetaprost and netarsudil for use in the prophylaxis or treatment of glaucoma or ocular hypertension
HK40102807B (en)	2025-10-10	Combination of sepetaprost and netarsudil for use in the prophylaxis or treatment of glaucoma or ocular hypertension
DE10129508A1 (de)	2003-01-09	Verwendung von Inhibitoren des Na+/H+-Antiporters zur Krebsbekämpfung
EP3730143A1 (en)	2020-10-28	Omidenepag combination
AU2003244430A1 (en)	2003-09-02	Combination preparation of the sodium-hydrogen exchange inhibitor cariporide with ace inhibitors for preventing heart failure and other age-related dysfunctions of organs, age- related diseases and for prolonging lifespan
HK40029829B (en)	2024-05-03	Combination of sepetaprost and ripasudil for use in the prophylaxis or treatment of glaucoma or ocular hypertension
HK40029828A (en)	2021-02-19	Omidenepag combination
HK40029829A (en)	2021-02-19	Combination of sepetaprost and ripasudil for use in the prophylaxis or treatment of glaucoma or ocular hypertension
WO1993012794A1 (en)	1993-07-08	Use of an animazoline derivative for the treatment of glaucoma