Arginine analogues having nitric oxide synthase inhibitor activi

Details Arginine analogues having nitric oxide synthase inhibitor activi Arginine analogues having nitric oxide synthase inhibitor activi

1997-09-10

1999-10-26

Bernhardt, Emily

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

514315, 514399, 514634, 544162, 544399, 546246, 5483341, 5483361, 5483001, 5483751, 5483561, 548561, A61K 31535, C07D23361, C07D29515, C07C27914

Patent

active

059729406

DESCRIPTION:

BRIEF SUMMARY
The invention concerns derivatives of L-arginine, a procedure for their preparation and pharmaceutical compositions containing them.
The compounds of the invention have a biological activity as inhibitors of the NO synthase. Taking into account the potential role of NO synthase in physiopathology (S. Moncada, R. M. J. Palmer et al, Nitric Oxide: Physiology, Pathophysiology, and Pharmacology. Pharmaceutical Reviews, vol. 43, number 2, pp. 109-142), such compounds may thus be interesting as hypotension, antibacterial, immunosuppressant, antiarterosclerotic, vasotropic, analgesic, antimigraine, ophthalmological, or antidiabetic agents. Thus one may consider using these compounds as the active principle of a medication for the treatment of pathologies of the central and peripheral nervous system such as: cerebral infarctus, migraine and headaches, epilepsy, cerebral or spinal trauma, neurodegenerative and/or autoimmune diseases such as Alzheimer's disease, Parkinson's disease, Saint Vitus' dance, amyotrophic lateral sclerosis, infectious cerebral neuropathies (AIDS), acute and chronic pain, tolerance to and dependence upon morphine derivatives, psychotropic drugs and alcohol, occular neuropathy, and depression. One may likewise consider using them for other pathologies such as those related to dysfunctions of the gastrointestinal and urinary system of the inflammatory type or not like ulcerous colitis, gastritis, Chronn's disease, urination troubles, esophagus gastro reflux, diarrhea, but also for pathologies connected to the cardiovascular or bronchopulminary system such as hypertension, atherosclerosis, pulmonary fibrosis, sclerodermia, asthma, pulmonary hypertension, cirrhosis, diabetes, for inflammatory or infectious diseases such as arthrosis, polyarthritis, septic shock, vasculitis, or even for troubles of erection, priapism, or contraception.
The invention concerns the derivatives of L-argkdfle of the general formula I: ##STR1## in which: A represents a hydrogen atom, a lower alkyl group, or the nitro radical; lower alkyl chain, or R.sub.1 and R.sub.2 form with the nitrogen atom to which they are attached, a ring of 5 or 6 groups, saturated or unsaturated, of the formula: ##STR2## in which X represents an atom of oxygen, of sulfur, or of nitrogen, the imino, alkylimino, or methylene radical, with the exception of general formula I compounds in which n is equal to zero. E represents a covalent bond and either A represents the hydrogen atom and R.sub.1 and R.sub.2 represent independently a lower alkyl radical or form together the piperidine, morpholine, or imidazole ring, or A represents the nitro radical and R.sub.1 and R.sub.2 form the piperidine ring.
By lower alkyl is meant the alkyl radicals containing from 1 to 6 carbon atoms. This preferably concerns alkyl radicals, linear or branched, containing from 1 to 4 carbon atoms chosen from among the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or ter-butyl groups.
R.sub.1 and R.sub.2 may form together with the nitrogen atom to which they are attached, a ring with 5 or 6 groups, saturated or unsaturated. The rings thus formed may be chosen from among pyrrole, piperidine, pyrrolodine, imidazole, imidazolidine, pyrazole, pyrazolidine, pyridine, piperazone, pyrazine, pyrimidine, pyridazine, isothiazole, or morpholine.
The invention concerns more particularly the compounds of general formula I in which n is an integer from 1 to 12, and preferably when E represents the oxygen atom, A represents the nitro radical or the hydrogen atom, and R.sub.1 and R.sub.2 form the morpholine, piperidine, or imidazole ring. The invention concerns more particularly likewise the compound of general formula I in which n is equal to zero, E represents a covalent bond, A the nitro radical, and R.sub.1 and R.sub.2 form the morpholine ring.
The invention likewise concerns pharmaceutically acceptable salts of the derivatives according to the invention. The salts are formed from organic or inorganic acids such as hydrochloric acid, hydrobromic acid, acetic, fumaric, sulfonic,

REFERENCES:
patent: 3978045 (1976-08-01), Okamoto et al.
patent: 4133880 (1979-01-01), Okamoto et al.
Etemad--Moghadam et al., Eur. J. Med. Chem. 23 pp. 577-585, 1988.
Stock, Z. NaturforschTeil C, 28, pp. 319-321, 1973.
Weitzel et al in Hope-Seyler's Z. Physiol. Chem., 353, pp. 1661-1670, 1972.
Ferrario et al, Synthetic Communications, 21, pp. 99-105, 1991.
Kinjo et al, Origins of Life, 14, pp. 351-357, 1984.
Kikumoto et al. Biochemistry 23, pp. 85-90, 1984.
Weitzel et al, Chemical Abstracts, vol. 77, No. 29320, 1972.
Whittle, European Journalof Gastroenterology & Hepatology, vol. 9 pp. 1026-1032, 1997.

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