Serving 500+ biopharmaceutical companies globally:
Generated: June 26, 2017
|Title:||Substituted benzimidazole-, benztriazole-, and benzimidazolone-O-glucosides|
|Abstract:||This invention relates to substituted benzimidazole-O-glucosides, benztriazole-O-glucosides, and benzimidazolone-O-glucosides, compositions containing them, and methods of using them, for example, for the treatment or prophylaxis of diabetes and Syndrome X.|
|Inventor(s):||Urbanski; Maud (Flemington, NJ)|
|Assignee:||Janssen Pharmaceutica NV (BE)|
|Filing Date:||Sep 11, 2009|
|Claims:||1. A method for treating diabetes or Syndrome X, or associated symptoms or complications thereof in a subject, comprising (a) administering to said subject a jointly effective amount of a glucose reabsorption inhibitor of formula (III) ##STR00019## wherein: X is CH, N, or C.dbd.O; R.sub.1 is H or absent; R.sub.2 is H, F, Cl, OCH.sub.3, OCH.sub.2CH.sub.3, or C.sub.1-4 alkyl, CF.sub.3, SCH.sub.3, substituted or unsubstituted phenyl or NR.sub.3R.sub.4; R.sub.3 and R.sub.4 are H, C.sub.1-C.sub.6 alkyl, or taken together with the nitrogen atom to which they are both attached form a 5-6 membered heterocyclyl with optionally 1-2 additional heteroatoms independently selected from O, S, and N; Q is --(CH.sub.2).sub.n-- where n is 1 or 2; P is H, C.sub.1-7 acyl, or (C.sub.1-6 alkoxy)carbonyl; and Z is substituted or unsubstituted, and is selected from C.sub.3-7 cycloalkyl, phenyl, 5- or 6-membered heteroaryl having 1 or 2 heteroatoms independently selected from N, O, and S, a biaryl, and a 9- or 10-membered fused bicyclyl or fused heterobicyclyl, wherein said fused heterobicyclyl has between 1 and 4 heteroatoms independently selected from N, O, and S; or a pharmaceutically acceptable salt thereof; (b) administering to said subject a jointly effective amount of a second antidiabetic agent, and (c) administering to said subject a jointly effective amount of a third antidiabetic agent; said co-administration being in any order and the combined jointly effective amounts providing the desired therapeutic effect. |
2. The method of claim 1, wherein the third antidiabetic agent is selected from (aa) insulins, (bb) insulin analogues; (cc) insulin secretion modulators, and (dd) insulin secretagogues.
3. The method of claim 1, wherein the second antidiabetic agent is an RXR agonist.
4. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is selected from IDDM, NIDDM, IGT, IFG, obesity, nephropathy, neuropathy, retinopathy, atherosclerosis, polycystic ovarian syndrome, hypertension, ischemia, stroke, heart disease, irritable bowel disorder, inflammation, and cataracts.
5. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complication thereof is IDDM.
6. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is NIDDM.
7. The method of claim 1, wherein the diabetes or Syndrome X, or associated symptoms or complications thereof is IGT or IFG.
8. The method of claim 1, wherein R.sup.1 is H or absent.
9. The method of claim 1, wherein R.sup.2 is H, methyl, or ethyl.
10. The method of claim 1, wherein Q is --(CH.sub.2).sub.n-- and n is 1.
11. The method of claim 1, wherein Z is independently substituted with between 1 and 3 substituents independently selected from C.sub.1-4 alkoxy, phenoxy, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, halo, hydroxy, cyano, amino, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkylsulfinyl, C.sub.1-4 aminoalkyl, mono- and di(C.sub.1-4 alkyl)amino, phenyl, C.sub.1-4 alkylaminosulfonyl (SO.sub.2NHR), amino-(alkylsulfonyl) (--NHSO.sub.2R--), C.sub.1-4 dialkylaminosulfinyl (SONHRR), C.sub.1-4 alkylamido (NHCOR), C.sub.1-4 alkylcarbamido (CONHR), 5-6 membered heterocyclyl containing between 1 and 3 heteroatoms independently selected from N, S, and O; and wherein the substituent(s) on Z can be further independently substituted with between 1 and 3 substituents independently selected from C.sub.1-4 alkoxy, C.sub.1-4 alkyl, halo, hydroxy, cyano, amino, mono or di C.sub.1-4 alkyl amino and C.sub.1-4 alkylthio.
12. The method of claim 1, wherein Z is 4-substituted phenyl, 3,4-disubstituted phenyl, benzhydryl, substituted or unsubstituted thiophene, biaryl, benzofuranyl, dihydrobenzofuranyl, 4-substituted pyridyl, benzo[b]thienyl, chromanyl, benzothiophenyl, indenyl, indanyl, naphthyl, or 2,3-dihydro-benzo[1,4]dioxanyl.
13. The method of claim 1, wherein Z is unsubstituted or substituted with between 1 and 2 substituents independently selected from methoxy, ethoxy, fluoro, chloro, methyl, ethyl, propyl, butyl and isopropyl.
14. The method of claim 1, wherein Z is biphenyl, 4-(3-pyridyl)phenyl, 4-(2-thienyl)phenyl, 4-(1H-imidazole-1-yl)-phenyl, 4-(1H-pyrazol-1-yl)-phenyl, (4-ethyl)phenyl, (4-propyl)phenyl, (4-methoxyphenyl), dihydrobenzofuran-5-yl, or dihydrobenzofuran-6-yl.
15. The method of claim 1, wherein R.sub.1 is absent; X is CH and R.sub.2 is H, methyl, ethyl, or methoxy.
Serving 500+ biopharmaceutical companies globally:
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.