Use of imidazole and indole compounds as inhibitors of nitric ox

Details Use of imidazole and indole compounds as inhibitors of nitric ox Use of imidazole and indole compounds as inhibitors of nitric ox

1999-07-16

2000-07-11

Henley, III, Raymond

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

A61K 31495

Patent

active

060873639

ABSTRACT:
Imidazole and indole compounds were found to inhibit neural nitric oxide synthase (bNOS) activity. Nortopsentin-C inhibited bNOS as well as calcineurin activities suggesting that its actions are directed against calmodulin, a co-factor common to these two enzymes. Two indole compounds, as well as dragmacidin-D, inhibited bNOS, but not calcineurin, activity. Murine macrophage viability and induced NOS (iNOS) activity in cultured cells was also unaffected by these compounds.

REFERENCES:
patent: 4866084 (1989-09-01), Gunasekera et al.
patent: 4895844 (1990-01-01), Komoto et al.
patent: 4970226 (1990-11-01), Sun et al.
patent: 5290777 (1994-03-01), McConnell et al.
patent: 5464835 (1995-11-01), McConnell et al.
Armin, Ashok, R., Mukundan Attur, Steven B. Abramson (1999) "Nitric oxide synthase and cyclooxygenases: distribution, regulation, and intervention in arthritis" Current Opinion in Rheumatology 11(3):202-209.
Baraldi, Eugenio, Cinzia Dario, Riccardo Ongaro, Massimo Scollo et al. (1999) "Exhaled Nitric Oxide Concentrations During Treatment of Wheezing Exacerbation in Infants and Young Children" Am. J. Respir. Crit. Care Med. 159(4 Pt. 1):1284-1288.
Bredt, David S., Solomon H. Snyder (1990) "Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme" Proc. Natl. Ac. Sci. USA 87:682-685.
Faulkner, D. (1995) J. Nat. Prod. Rep. 12-223-269.
Faulkner, D. (1994) J. Nat. Prod. Rep. 11:355-394.
Faulkner, D. (1993) J. Nat. Prod. Rep. 10:497-539.
Faulkner, D. (1992) J. Nat. Prod. Rep. 9:323-364.
Faulkner, D. (1991) J. Nat. Prod. Rep. 8:97-147.
Faulkner, D. (1990) J. Nat. Prod. Rep. 7:269-309.
Faulkner, D. (1988) J. Nat. Prod. Rep. 5:613-663.
Faulkner, D. (1987) J. Nat. Prod. Rep. 4:539-576.
Faulkner, D. (1986) J. Nat. Prod. Rep. 3:1-33.
Faulkner, D. (1984) J. Nat. Prod. Rep. 1:551-598.
Fukuto, J.M. and G. Chaudhuri (1995) "Inhibition Of Constitutive And Inducible Nitric Oxide Synthase: Potential Selective Inhibition" Annu. Rev. Pharmacol. Toxicol. 35:165-194.
Gahtan, Ethan, J. Bruce Overmier (1999) "Inflammatory pathogenesis in Alzheimer's disease: biological mechanisms and cognitive sequeli" Neurosciences and Biobehavioral Reviews 23:615-633.
Greenberg, Stan S., Jianming Xie, John J. Spitzer et al. (1995) "Nitro Containing L-Arginine Analogs Interfere With Assays For Nitrate And Nitrite" Life Sciences 57(21):1949-1961.
Gunasekera, Sarath P., Peter J. McCarthy, Michelle Kelly-Borges (1994 Hamacanthins A and B, New Antifungal Bis Indole Alkaloids From The Deep-Water Marine Sponge, Hamacantha Sp. 57(10):1437-1441.
Handy, Rachael L.C., H.L. Harb, P. Wallace, Z. Gaffen, K.J. Whitehead, P.K. Moore (1996) "Inhibition of nitric oxide synthase by 1-(2-trifluoromethylphenyl) imidazole (TRIM) in vitro: antinociceptive and Cardiovascular effects" British J. of Pharmacology119:423-431.
Hays, Sheryl J. (1998) "Therapeutic Approaches to the Treatment of Neuroinflammatory Diseases" Current Pharmaceutical Design 4:335-348.
Klee, Claude B., Hao Ren, Xutong Wang (1998) "Regulation of the Calmodulin-stimulated Protein Phosphatase, Calcineurin" J. Biological Chemistry 273(22):13367-13370.
Kohmoto, Shigeo, Yoel Kashman, Oliver J. McConnel, Kenneth L. Rinehart, Jr., Amy Wright, Frank Koehn (1988) "Dragmacidin, a New Cytotoxic Bis(indole) Alkaloid from a Deep Water Marine Sponge, Dragmacidon sp." J. Organic Chemistry 53:3116-3118.
McCann, S.M. (1997) "The Nitric Oxide Hypothesis Of Brain Agin" Experimental Gerontology 32(4/5):431-440.
McCann, S.M., J. Licinio, M.L. Wong et al. (1998) "The Nitric Oxide Hypothesis Of Aging" Experimental Gerontology 33(7/8):813-826.
Molina et al. (1998) "The Role of Nitric Oxide in Neurodgeneration" Drugs & Aging 12(4):251-259.
Mosmann, Tim (1983) "Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays" J. Immunol. Methods 65:55-63.
Moquin, Carole, Michele Guyot (1984) Tetrahedron Letters 25(44):5047-5048.
Norton, Raymond S., Robert J. Wells (1982) "A Series of Chiral Polybrominated Biindoles from the Marine Blue-Green Alga Rivularia firma. Application . . . Elucidation" J. Am. Chem. Soc. 104:3628-3635.
Ohshima, H., S. Oguchi, H. Adachi, S. Iida, H. susuki, T. Sugimura, H. Esumi (1992) "Purification of Nitric Oxide Synthase from Bovine Brain: Immunological Characterization and Tissue Distribution" Biochemical and Biophysical Research Communications 183(1):238-244.
Sakemi, Shinichi, Hao H. Sun (1991) "Nortopsentins A, B, and C. Cytotoxic and Antifungal Imidazolediylbis[indoles] from the Sponge Spongosorites ruetzleri" J. Organic Chemistry 56(13):4304-4307.
Sanders, Scherer P. (1999) "Asthma, Viruses, and Nitric Oxide (44354)" Proc. Soc. Exp. Biol. Med. 220(3):123-132.
Scheuer, P.J., ed. (1978-1983) Marine Natural Products, chemical and Biological Perspectives, Academic Press, New York. (see entire book) copy not enclosed.
Sterling, R.G., S.A. Kharitonov, D. Campbell, D.S. Robinson, S.R. Durham, K.F. Chung, P.J. Barnes (1998) "Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids" Thorax 53(12):1030-1034.
Thorns, Veronika, Lawrence Hansen, Eliezer Masliah (1998) "nNOS Expressing Neurons in the Entorhinal Cortex and Hippocampus Are Affected in Patients with Alzheimer's Disease" Experimental Neurology 150:14-20.
Tsujii, Shinji, and L. Rinehart (1988) "Topsentin, Bromotopsentin, and Dihydrodexybromotopsentin: Antiviral and Antitumor Bis(indolyl)imidazoles from Caribbean Deep-Sea Sponges of the Family Halichondriidae. Structural and Synthetic Studies." J. Org. Chem. 53(23):5446-5453.
Uemura, Daisuke, Kanji Takahashi, Toshihiro Yamamoto et al. (1985) "Norhalichondrin A: An Antitumor Polyether Macrelide from a Marine Sponge" J. Am. Chem. Soc. 107:4796-4798.
Wright, Amy E., Shirley A. Pomponi, Sue S. Cross, Peter McCarthy (1992) "A New Bis(indole) Alkaloid from a Deep-Water Marine Spone of the Genus Spongosorites" J. Org. Chem. 57(17):4772-4775.
Yun, Hye-Young, Valina L. Dawson, Ted M. Dawson (1996) "Neurobiology of Nitric Oxide" Critical Reviews in Neurobiology 10(3/4):291-316.

Affiliated with

Also associated with

Rating

Use of imidazole and indole compounds as inhibitors of nitric ox does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Use of imidazole and indole compounds as inhibitors of nitric ox, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of imidazole and indole compounds as inhibitors of nitric ox will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-542674