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Substituted heterocyclic compoundsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered Consisting Of Two Nitrogens And Four Carbon Atoms (e.g., Pyridazines, Etc.), 1,4-diazine As One Of The Cyclos, Piperazines (i.e., Fully Hydrogenated 1,4-diazines), Additional Hetero Ring Attached Directly Or Indirectly To The Piperazine Ring By Nonionic Bonding, ,Substituted heterocyclic compounds description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070191390, Substituted heterocyclic compounds. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. patent application Ser. No. 10/862,798, filed Jun. 7, 2004, which issued ______, as U.S. Pat. No. ______, which claims priority to U.S. Provisional Patent Application Ser. No. 60/480,924, filed Jun. 23, 2003, and U.S. Provisional Patent Application Ser. No. 60/524,504, filed Nov. 24, 2003, the complete disclosure of which are hereby incorporated by reference. FIELD OF THE INVENTION [0002] The present invention relates to novel heterocyclic compounds, in particular piperidine and piperazine derivatives, and to their use in the treatment of various disease states, including cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, ischemia, reperfusion injury and myocardial infarction, diabetes, such as Type II diabetes, and disease states related to diabetes. The invention also relates to methods for their preparation, and to pharmaceutical compositions containing such compounds. SUMMARY OF THE INVENTION [0003] Certain classes of piperazine compounds are known to be useful for the treatment of cardiovascular diseases, including arrhythmias, angina, myocardial infarction, and related diseases such as intermittent claudication. For example, U.S Pat. No. 4,567,264 discloses a class of substituted piperazine compounds that includes a compound known as ranolazine, (.+-.)-N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)-propy1]-1- -piperazineacetamide, and its pharmaceutically acceptable salts, and their use in the above disease states. [0004] Despite the desirable properties demonstrated by ranolazine, which is a very effective cardiac therapeutic agent, believed to function as a fatty acid oxidation inhibitor, there remains a need for compounds that have similar therapeutic properties to ranolazine, but are more potent and have a longer half-life. SUMMARY OF THE INVENTION [0005] It is an object of this invention to provide novel substituted piperazine and piperidine derivatives that function as fatty acid oxidation inhibitors. Accordingly, in a first aspect, the invention relates to compounds of Formula I: wherein: [0006] R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are hydrogen, lower alkyl, or --C(O)R; in which R is --OR.sup.9 or --NR.sup.12R.sup.13, where R.sup.12 and R.sup.13 are hydrogen or lower alkyl; or [0007] R.sup.1 and R.sup.2, R.sup.3 and R.sup.4, R.sup.5 and R.sup.6, R.sup.7 and R.sup.8, when taken together with the carbon to which they are attached, represent carbonyl; or [0008] R.sup.1 and R.sup.5, or R.sup.1 and R.sup.7, or R.sup.3 and R.sup.5, or R.sup.3 and R.sup.7, when taken together form a bridging group --(CR.sup.14R.sup.15).sub.n--, in which n is 1, 2 or 3, and R.sup.14 and R.sup.15 are independently hydrogen or lower alkyl; [0009] with the proviso that [0010] (i) the maximum number of carbonyl groups is 2; and [0011] (ii) the maximum number of bridging groups is 1; [0012] R.sup.9 and R.sup.11 are independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; [0013] R.sup.10 is hydrogen or lower alkyl; [0014] T is oxygen, sulfur, or .dbd.NR.sup.16, in which R.sup.16 is hydrogen, lower alkyl, cyano, lower alkoxy, or C(O)OR.sup.17, in which R.sup.17 is lower alkyl; [0015] X is --N< or --NH--CH<; [0016] Y is optionally substituted alkylene of 1-3 carbon atoms; and [0017] Z is --O--, --S--, --N(R.sup.18)-- where R.sup.18 is hydrogen or lower alkyl, or a covalent bond. [0018] A second aspect of this invention relates to pharmaceutical formulations, comprising a therapeutically effective amount of a compound of Formula I and at least one pharmaceutically acceptable excipient. [0019] A third aspect of this invention relates to a method of using the compounds of Formula I in the treatment of a disease or condition in a mammal that is amenable to treatment by a fatty acid oxidation inhibitor. Such diseases include, but are not limited to, protection of skeletal muscles against damage resulting from trauma, intermittent claudication, shock, and cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, exercise induced angina, congestive heart disease, diabetes, such as Type II diabetes, and myocardial infarction. The compounds of Formula I are also useful for lowering plasma level of HbAlc, lowering glucose plasma levels, lowering total cholesterol plasma levels, lowering triglyceride plasma levels, raising HDL cholesterol levels, and/or delaying onset of diabetic retinopathy. They can also be used to preserve donor tissue and organs used in transplants. [0020] A fourth aspect of this invention relates to methods of preparing the compounds of Formula I. [0021] The preferred compounds presently include, but are not limited to: [0022] N-(2,6-dimethylphenyl)({1-[2-hydroxy-3-(2-methoxyphenoxy)propyl](4-- piperidyl)}amino)carboxamide; Continue reading about Substituted heterocyclic compounds... 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