Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1992-09-23
1994-11-22
O'Sullivan, Peter O.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
5142382, 514255, 514315, 514426, 514601, 514929, 544164, 544382, 546244, 548557, 564 81, 564113, A61K 3113, A61K 31535, A61K 31445, C07C24304
Patent
active
053669975
ABSTRACT:
There are disclosed cardiovascularly active compounds possessing antihypertensive properties, and pharmaceutical compositions containing these agents and a method of treating cardiovascular disorders with the compounds. The active components of the pharmaceutical compositions are compounds of formula I ##STR1## wherein R.sub.1 and R.sub.2 are independently chosen from straight chain and branched chain alkyl and olefinic groups, which may be unsubstituted or substituted; or R.sub.1 and R.sub.2 together with the nitrogen atom they are bonded to form a heterocyclic group; and R.sub.3 is a pharmaceutically acceptable organic group selected from alkyl and olefinic groups which may be unsubstituted or substituted, acyl, a sulfonyl, sulfinyl, sulfenyl, carbonate, or carbamate derivative; or R.sub.3 is a group of the formula--(CH.sub.2).sub.n ONN(O)NR.sub.1 R.sub.2, wherein n is 2-8, and R.sub.1 and R.sub.2 are as described above. Novel compounds are disclosed wherein at least one of R.sub.1, R.sub.2 and R.sub.3 is an olefinic group or heteroatom-substituted straight or branched chain alkyl or olefinic group. Novel methods of synthesizing the compounds are also disclosed.
REFERENCES:
patent: 3153094 (1964-10-01), Reilly
patent: 4265714 (1981-05-01), Nolan et al.
patent: 4482533 (1984-11-01), Keith
patent: 4638079 (1987-01-01), Inskip et al.
patent: 4708854 (1987-11-01), Grinstead
patent: 4921683 (1990-05-01), Bedell
patent: 4952289 (1990-08-01), Ciccone et al.
patent: 4954526 (1990-09-01), Keefer
patent: 4985471 (1991-01-01), Ohta et al.
patent: 5039705 (1992-08-01), Keefer et al.
patent: 5087631 (1992-02-01), Shaffer et al.
patent: 5087671 (1992-02-01), Loeppky et al.
patent: 5094815 (1992-03-01), Conboy et al.
1991 Article by Maragos, et al., Complexes of NO with Nucleophiles as Agents for the Controlled Biological Release of Nitric Oxide. Vasorelaxant Effects, J. Med. Chem., 34, 3242-3247.
1990 Article by Myers, et al., Vasorelaxant Properties of the Endothelium-Derived Relaxing Factor more closely Resemble S-Nitrosocystein Than Nitric Oxide, Nature, vol. 345.
1989 Article by Ignarro, Endothelium-Derived Nitric Oxide: Actions and Properties, The FASEB Journal, vol. 3, Jan.
1988 Article by DeFeudis, Endothelium-Dependent Vasorelaxation--A New Basis for Developing Cardiovascular Drugs, Drugs of Today, vol. 24, No. 2, pp. 103-115.
1987 Article by Palmer, et al., Nitric Oxide Release Accounts for the Biological Activity of Endothelium-Derived Relaxing Factor, Nature, vol. 327 11, Jun.
1987 Article by Kruszyna, et al., Red Blood Cells Generate Nitric Oxide from Directly Acting, Nitrogenous Vasodilators, Toxicol. Appl. Pharmacol., 91, 429-438.
1986 Article by Trissel, Intravenous Infusion Solutions, Handbook on Injectable Drugs, Fourth Addition.
1984 Article by Furchgott, The Role of Endothelium in the Responses of Vascular Smooth Muscle to Drugs, Ann. Rev. Pharmacol, Toxicol, 24:175-97.
1982 Article by DeLuca, et al., Parenteral Drug-Delivery Systems, Pharmaceutics and Pharmacy Practice.
1982 Article by Hansen, et al., N-Nitrosation of Secondary Amines by Nitric Oxide Via the `Drago Complex`, IARC Sci., Publ. No. 41 pp. 21-29.
1981 Article by Ignarro, et al., Mechanism of Vascular Smooth Muscle Relaxation by Organic Nitrates, Nitrites, Nitroprusside and Nitric Oxide: Evidence for the Involvement of S-Nitrosothiols as Active Intermediates, J. Pharmacol. Exp. Ther., 218, 739-749.
Article by Lutz, et al., Isolation of Trioxodinitrato (II) Complexes of Some First Row Transition Metal Ions, J. C. S. Chem. Comm.
1977 Article by Nakanishi, et al., Participation of Hydrocarbons in the Photodimerization of 3, 4-Dichlorocinnamic Acid, J. C. S. Chem. Comm.
1963 Article by Longhi, et al., Metal-Containing Compounds of the Anion (C.sub.2 H.sub.5).sub.2 NN.sub.2 O.sub.2 -, Insrg. Chem., vol. 2 Feb.
1962 Article by Drago, Reactions of Nitrogen (II) Oxide, Advances In Chemistry Series, No. 36.
1961 Article by Drago, et al., The Reaction of Nitrogen (II) Oxide with Various Primary and Secondary Amines, Journal of Amer. Chem. Soc., vol. 83, Apr. 20.
1990 Article by Garg, et al., Nitric Oxide-Generating Vasodilators Inhibit Mitogenesis and Proliferation of Balb/C3T3 Fibroblasts By A Cyclic GMP-Independent Mechanism, Biochem. and Biophys. Res. Comm., 171, 474-479.
1988 Article by Hibbs, Jr., et al., Nitric Oxide: A Cytotoxic Activated Macrophage Effector Molecule, Biochem. and Biophys. Res. Comm., 157, 87-94.
1981 Article by Holford, et al., Understanding the Dose-Effect Relationship: Clinical Application of Pharmacokinetic-Pharmacodynamic Models, Clinical Pharmacokinetics, 6, 429-453.
1990 Article by Ignarro, Nitric Oxide. A Novel Signal Transduction Mechanism for Transcellular Communication, Hypertension (Dallas), 16, 477-483.
1990 Article by Ignarro, Biosynthesis and Metabolism of Endothelium-Derived Nitric Oxide, Annu. Rev. Pharmacol. Toxicol., 30, 535-560.
1985 Article by Ignarro, et al., The Pharmacological and Physiological Role of Cyclic GMP in Vascular Smooth Muscle Relaxation, Annu. Rev. Pharmacol. Toxicol., 25, 171-191.
1989 Article by Kuhn, et al., Endothelium-Dependent Vasodilation in Human Epicardial Coronary Arteries: Effect of Prolonged Exposure to Glycerol Trinitrate or SIN-1, J. Cardiovasc. Pharmacol., 14 (Suppl. 11), S47-S54.
1990 Marletta, et al., Unraveling the Biological Significance of Nitric Oxide, BioFactors, 2, 219-225.
1991 Smith, et al., Nitroprusside: A Potpourri of Biologically Reactive Intermediates, Biological Reactive Intermediates IV. Molecular and Cellular Effects and Thier Impact on Human Health (Witmer, et al., eds.), Advances in Experimental Medicine and Biology, vol. 283 (Plenum Press, pp. 365-369).
1989 Stuehr, et al., Nitric Oxide: A Macrophage Product Responsible for Cytostasis and Respiratory Inhibition in Tumor Target Cells, J. Exp. Med., 169, 1543-1555.
1977 WHO Task Group on Environmental Health Criteria for Oxides of Nitrogen, Oxides of Nitrogen, Environmental Health Criteria 4 (World Health Organization: Geneva).
1990 Article by Wilcox, et al., Effect of Cyanide on the Reaction of Nitroprusside with Hemoglobin: Relevance to Cyanide Interference With the Biological Activity of Nitroprusside, Chem. Res. Toxicol., 3, 71-76.
1992 Article by Stamler, et al., S-Nitrosylation of Proteins With Nitric Oxide: Synthesis and Characterization of Biologically Active Compounds, Proc. Natl. Acad, Sci., USA, vol. 89, pp. 444-448, Jan.
1992 Article by Smith, et al., Complex Contractile Patterns in Canine Colon Produced by Spontaneous Release of Nitric Oxide, Gastroenterology, vol. 102, No. 4 Part 2, Apr.
1991 Article by Jones, Metastable Polymers of the Nitrogen Oxides. 1. Open Chain Nitric Oxide Analogues of Polythlazyl: A MNDO/AM1 Study, J. Phys. Chem., 95, 2588-2595.
1981 Article by Middleton, et al., Further Studies on the Interaction of Nitric Oxide With Transition-Metal Alkyls, J. C. S. Dalton, pp. 1898-1905, Feb. 6.
1989 Article by Bonakdar, et al., Continuous-Flow Performance of Carbon Electrodes Modified With Immobilized Fe(II)/Fe(III) Centers, Calanta, vol., 36, No. 1/2, pp. 219-225.
1992 Article by Park, et al., Controlled Protein Release from Polyethyleneimine-Coated Poly (L-lactic Acid)/Pluronic Blend Matrices, Pharmaceutical Research, vol. 9, No. 1.
1932 Uber Reaktionen und Eigenschaften des Stickoxyds und seiner Verbindungen, II. Mitteil: Zur Kenntnis der Salze Der stickoxyd-schwefligen Saure, Heinz Gehlen, Aus D. Chem. Institut D. Universitat Konigsberg I. PR., Eingegaugen am 1. Juni.
1932 Der Raman-Effekt als Grundlage einer organischen Spektralanalyse (I. Mitteil.), Birchkenbach, et al., Aus D. Chem. Institut D. Betgakademie Clausthal, Eingegaugen am 9, Juni.
1987 Synthesis of 1-Alkoxy-3,3-Dialkyltriazene 2-Oxides from Alkoxyamines and Nitrosoamines, Artsybasheva, et al., A. A. Zhdanov Leningrad State University, Translated from Zhurnal Organicheskoi Khimii, vol. 28, No. 6, pp. 1168-1173, Jun., Original article submitted May 28, 1986.
Kuznetsov et al., "Photoelectron spectra and electronic structures of 2-alkoxy-1-tert-alkydiazen-1-oxides and 1-alkoxy-3,3-di
Dunams Tambra M.
Keefer Larry K.
Saavedra Joseph E.
O'Sullivan Peter O.
The United States of America as represented by the Secretary of
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