- COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY
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The present invention relates to chemical entities (for example, a pharmaceutically acceptable compound or salt, and / or a hydrate, and / or a co-crystal, and / or a combination of drug of the compound) which inhibit (for example, antagonize) the stimula
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- N-(2-ARYLETHYL) BENZYLAMINES AS ANTAGONISTS OF THE 5-HT6 RECEPTOR
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The present invention relates to the use compounds of formula I which are antagonists of the 5-HT 6 receptor, for treating a cognitive disorder selected from the group consisting of age-related cognitive decline, mild cognitive impairment and dementia
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- Phenylaminopropanol derivatives and methods of their use
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The present invention is directed to phenylaminopropanol derivatives of formulae I, II, and III: [image] or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromyalgia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, schizophrenia, and combinations thereof.
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Page/Page column 46
(2010/11/26)
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- 3-Benzimidazol-2-yl-1H-indazoles as potent c-ABL inhibitors
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The 3-benzimidazol-2-yl-1H-indazole scaffold was developed as an alternate scaffold for our receptor tyrosine kinase (RTK) inhibitor program. In exploring the SAR of this series, it was discovered that a subset of these compounds potently inhibit the enzy
- McBride, Christopher M.,Renhowe, Paul A.,Gesner, Thomas G.,Jansen, Johanna M.,Lin, Julie,Ma, Sylvia,Zhou, Yasheen,Shafer, Cynthia M.
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p. 3789 - 3792
(2008/12/23)
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- Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications
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Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat, 9) inhibits aldose reductase with an IC50 of 5 nM, while being 5400 times less active against aldehyde reductase, a related enzyme involved in the detoxification of reactive aldehydes. It lowers nerve and lens sorbitol levels with ED50's of 1.9 and 4.5 mg/kg/d po, respectively, in the 5-day STZ-induced diabetic rat model. In a 3-month diabetic intervention model (1 month of diabetes followed by 2 months of drug treatment at 5 mg/kg/d po), it normalizes polyols and reduces the motor nerve conduction velocity deficit by 59% relative to diabetic controls. It has a favorable pharmacokinetic profile (F, 82%; t1/2, 5.6 h; Vd, 0.694 L/kg) with good drug penetration in target tissues (Cmax in sciatic nerve and eye are 2.36 and 1.45 μg equiv/g, respectively, when dosed with [14C] lidorestat at 10 mg/kg po).
- Van Zandt, Michael C.,Jones, Michael L.,Gunn, David E.,Geraci, Leo S.,Jones, J. Howard,Sawicki, Diane R.,Sredy, Janet,Jacot, Jorge L.,DiCioccio, A. Thomas,Petrova, Tatiana,Mitschler, Andre,Podjarny, Alberto D.
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p. 3141 - 3152
(2007/10/03)
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- Methods of reducing serum glucose and triglyceride levels and for inhibiting angiogenesis using substituted indolealkanoic acids
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Disclosed are methods of reducing serum glucose and triglyceride levels and for inhibiting angiogenesis, the methods comprising administration of substituted indolealkanoic acids to patients in need of such treatment. Also disclosed are such compounds use
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- Compositions containing a substituted indolealkanoic acid and an angiotensin converting enzyme inhibitor
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Disclosed are methods of reducing serum glucose and triglyceride levels and for inhibiting angiogenesis, the methods comprising administration of substituted indolealkanoic acids to patients in need of such treatment. Also disclosed are such compounds use
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- Methods for reducing uric acid levels
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Disclosed are methods of reducing serum uric acid levels, the methods comprising administration of substituted indolealkanoic acids to patients in need of such treatment. Also disclosed are such compounds useful in the treatment of gout and related diseas
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- Substituted indolealkanoic acids
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Disclosed are substituted indolealkanoic acids useful in the treatment of chronic complications arising from diabetes mellitus. Also disclosed are pharmaceutical compositions containing the compounds and methods of treatment employing the compounds, as we
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- Tryptamine analogues as 5-ht1-like agonists
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A compound of structure (I), in which A1 is O, S(O)n in which n is 0, 1 or 2, NR, CH2, or CH(OH); A2 is a bond or CH2 ; or A1 A2 is CH=CH; R is hydrogen or C1-4 alkyl;
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- Design, Synthesis, and Study of 9-Substituted Ellipticine and 2-Methylellipticinium Analogues as Potential CNS-Selective Antitumor Agents
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N,N-Dimethylformamide (DMF) dineopentyl acetal-mediated O-alkylations of 9-hydroxyellipticine gave 9-ethoxy-, 9-(1-methylethoxy)-, and 9-(1,1-dimethylethoxy)ellipticine (3a, 4a, and 5a, respectively). Methylation of the O-alkylellipticines gave the corresponding N-methylpyridinium iodides (3b, 4b, and 5b). The iodides were converted to the acetates (3c, 4c, and 5c) by ion-exchange resin. Attempts to prepare 9-(2,2,2-trifluoroethoxy)ellipticine (6a) using the DMF acetal gave 10-(2,2,2-trifluoroethoxy)-9-hydroxyellipticine (8a). 9-(2,2,2-Trifluoroethoxy)- and 9-phenoxyellipticine (6a and 7a, respectively) were prepared by total synthesis. The ellipticines and N-methylellipticinium derivatives were evaluated for in vitro antitumor activity against a panel of human tumors. 2-Methyl-9-(1,1-dimethylethoxy)ellipticinium acetate (5c) was inactive, but all of the other compounds exhibited significant antitumor activity. The ellipticines showed no significant subpanel specificity; however, the N-methylellipticinium compounds tested did exhibit specificity for the CNS tumor subpanel.
- Anderson, Wayne K.,Gopalsamy, Ariamala,Reddy, Peech S.
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p. 1955 - 1963
(2007/10/02)
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- INDOLYLS. SYNTHESIS OF DI(5-INDOLYL) OXIDE
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Bis(2-carbethoxy-5-indolyl) oxide was obtained by cyclization of ethyl pyruvate 4,4'-diphenyloxydihydrazone. 5-Phenoxy-2-carbethoxyindole was also isolated from the reaction products.Saponification of these sters gave the corresponding acids, the thermal
- Samsoniya, Sh. A.,Tabidze, D. M.,Suvorov, N. N.
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