Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-19
2000-05-16
Seaman, D. Margaret
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514310, 546114, 546143, A61K 3147, A61K 31435, C07D47102, C07D21700
Patent
active
060637897
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel compounds which are aminopyridine derivatives. The invention also concerns related aspects including processes for the preparation of the compounds, compositions containing them and their use as pharmaceuticals. There are also provided chemical intermediates useful for the production of the compounds.
U.S. Pat. No. 4,127,720 discloses 1-amino-3,4-dihydroisoquinolines of the following formula: ##STR2## wherein R represents hydrogen, alkyl C1 to 6, or phenyl; R.sup.1 represents hydrogen, alkyl C1to 6, alkoxy C1 to 6 or halogen; and R.sup.2 represents hydrogen, alkyl C1 to 6 or unsubstituted phenyl.
U.S. Pat. No. 4,127,720 discloses the use of these compounds as starting materials for the synthesis of other compounds. There is no disclosure of pharmaceutical use. Specifically mentioned compounds are: 1-amino-3,4-dihydro-7-methoxyisoquinoline, 1-amino-3,4-dihydro-6-methoxyisoquinoline and (.+-.)-1-amino-4-ethyl-3,4-dihydroisoquinoline.
"Synthesis and antihypertensive activity of 1-amino-3,4-dihydroisoquinolines", G D Diana et al, J Med. Chem., vol 20, No 3, March 1977, pp 449 to 452 discloses that the hydroiodide salt of 1-amino-3,4-dihydroisoquinoline has antihypertensive activity.
WO 95/11231 discloses a decahydroisoquinoline as a nitric oxide synthase (NOS) inhibitor.
"Synthesis of heterocyclic combinations using nitrile salts. XIII. 1-amino-3,4-dihydroisoquinoline derivatives", V Gomez-Parra et al, An. Quim., vol 70, No 12, 1974, pp 980 to 985 discloses 1-amino-3,4-dihydroisoquinoline derivatives in which the amino group is substituted.
"Bischler-Napieralski reaction of N(3,4-dimethoxyphenylethyl)urea", T Yamazaki et al, Yakugaku Zasshi, vol 82, 1962, pp 352 to 355 discloses 1-amino-6,7-dimethoxy-3,4-dihydroisoquinoline.
According to the invention, there is provided a compound of formula I ##STR3## wherein: R represents containing 1 to 3 nitrogen atoms, which phenyl, benzo ring of the benzothiazolyl or heterocyclic aromatic ring is optionally substituted by alkyl C1 to 6, alkoxy C1 to 6, halogen, hydroxy, thioalkyl C1 to 6, benzyloxy, or a group --Q(CH.sub.2).sub.p NR.sup.4 R.sup.5 ; or phenylalkyl C7 to 14, which alkyl, cycloalkyl, alkynyl, or piperidyl is optionally substituted by a group --(CH.sub.2).sub.p NR.sup.4 R.sup.5, the phenylalkyl being optionally substituted by a group --(CH.sub.2).sub.p NR.sup.4 R.sup.5, alkyl C1 to 6, alkoxy C1 to 6, halogen or nitro; or selected from O, N or S, optionally substituted by alkyl C1 to 6, phenylalkyl C7 to 14 or halogen; or or halogen; by alkyl C1 to 6, alkoxy C1 to 6, halogen or hydroxy; to 6, or --NR.sup.4 R.sup.5 together represents piperidyl, pyrrolidinyl or morpholinyl; represent 1; or a pharmaceutically acceptable salt, enantiomer or tautomer thereof; which R represents hydrogen, alkyl C1 to 6 or phenyl, R.sup.1 represents hydrogen, alkyl C1 to 6, alkoxy C1 to 6 or halogen, R.sup.2 represents hydrogen, alkyl C1 to 6 or unsubstituted phenyl and R represents hydrogen are excluded.
The invention further provides a process for the preparation of these compounds or pharmaceutically acceptable salts, enantiomers or tautomers thereof.
According to the invention, there is also provided a compound of formula I, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, for use as a pharmaceutical, provided that the hydroiodide salt of the compound of formula I in which A represents a benzo ring and each of R, R.sup.1, R.sup.2 and R.sup.3 represents hydrogen, for use as a pharmaceutical is excluded.
Another aspect of the invention provides the use of a compound of formula I or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, in the manufacture of a medicament, for the treatment or prophylaxis of inflammatory disease.
According to the invention, there is also provided a method of treating, or reducing the risk of, inflammatory disease in a patient suffering from, or at risk of, said disease, wherein the method comprises administering to the patient a compound of formula I or a pharmaceutically acc
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Hamley Peter R
MacDonald James E
Matz James R
Tinker Alan C
Astra Pharmaceuticals Ltd.
Seaman D. Margaret
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