The present invention relates to novel tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidine compounds that are antagonists of alpha V (.alpha.v) integrins, for example .alpha..sub.v.beta..sub.3 and .alpha..sub.v.beta..sub.5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment and/or prevention of pathological conditions mediated by .alpha..sub.v.beta..sub.3 and .alpha..sub.v.beta..sub.5 integrins such as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, rheumatoid arthritis, sickle cell anemia, and in treatment and/or prevention of central nervous system (CNS) related disorders such as neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, surgery, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, adverse consequences of overstimulation of one or more excitatory amino acids, anxiety, convulsions, chronic pain, psychosis, schizophrenia, anesthesia, and opiate tolerance. The compounds have the general formula: ##STR1##where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, m and n are defined herein.

3-Dimensional Pharmaceuticals, Inc.

Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists

Disclosed are compounds of the formula: ##STR1## or pharmaceutically acceptable salts thereof; wherein n is zero or 1; R.sup.4, R.sup.5, R.sup.6 are independently hydrogen, nitro, amino, halo, haloalkyl, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, azido, acylamino, alkylsulfonyl, aryl, substituted aryl, heteroaryl, alkoxy, trialkylsilyl-substituted alkoxy, aryloxy, substituted aryloxy, heteroaryloxy, a heterocyclic group, a heterocyclicoxy group, aralkoxy, or haloalkoxy; and R.sup.c and R.sup.d are defined in the specification. These compounds have high binding to the glycine site of the NMDA receptor. Also disclosed are methods of treating pathophysiologic conditions associated with neuronal degeneration, convulsions, anxiety, chronic pain, pyschosis, opiate tolerance, and inducing anesthesia.

State of Oregon, Acting by and Through the Oregon State Board of Higher-Education, Acting for and on Behalf of the Oregon Health

The Regents of the University of California

Cocensys, Inc.

8-aza, 6-aza and 6,8-diaza-1,4-dihydroquinoxaline-2,3-diones and the use thereof as antagonists for the glycine/NMDA receptor

A comprehensive system for inducing cellular regeneration and/or degeneration processes and methods of treatment based on such processes through generating and applying a sequentially programmed magnetic field (SPMF) to the area to be treated. In the case of regeneration and degeneration of cells, the pulsing frequencies are in the range of about 0.1 to about 2000 Hz based on the indication of the disease type which was determined by either the patient's MRI, CT, Ultrasound or other diagnostic information. Methods for treating diseases or conditions that will benefit from regeneration and/or degeneration of cells. For example, methods for treating cancer, arthritis, neuro degeneration conditions, such as the age-related progressive loss of nerve cells, Alzheimer's, Parkinson's, ALS, and Huntington's disease, retinal degeneration, and other damage to sensory systems (e.g., visual, auditory, somatosensory), in stroke, head and spinal trauma, epilepsy, in drug and alcohol abuse, in infectious diseases, in exposure to industrial and environmental toxicants, and, perhaps, in mental disorders and chronic pain. Methods for treating non-healing fractures and other bone disorders are also disclosed.

Vasishta; Vishwanath Gopalakrishna

SBF Healthcare Pvt. Ltd.

Sequentially programmed magnetic field therapeutic system (SPMF)

Apparatus for supplying electric energy to biological tissue with a view to supporting different physiological processes, including different phases of healing, growth, modification og pathological states, for example deterioration in blood flow, chronic pain, fluid accumulation in tissue etc., and similarly with a view to influencing viability conditions of, for instance, tumor tissue, the apparatus essentially comprising at least two electrodes connected to a voltage source. One electrode is adapted to be disposed in or on the biological tissue which is to be supported in its physiological or pathophysiological cycle, and the other electrode is adapted to be disposed in spaced-apart relationship from the biological tissue in such a position that electrically conducting circuits exist between the electrodes, the voltage source being arrnaged, via said electrodes, to supply current through the biological tissue.For simulating the physiological healing process, a controller is connected to the voltage source to supply a current whose amplitude values alternate with time, and each maximum amplitude value is lower in absolute terms than the immediately preceding amplitude value. The alternation of the current is caused to take place several times.

chronic pain/atrophy

Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists

8-aza, 6-aza and 6,8-diaza-1,4-dihydroquinoxaline-2,3-diones and the use thereof as antagonists for the glycine/NMDA receptor

Sequentially programmed magnetic field therapeutic system (SPMF)

Method and apparatus for supplying electric energy to biological tissue for simulating the physiological healing process

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