New aminoalkylaminoalkyl-substituted benzoxazines or benzothiazines, are nitrogen monoxide synthase inhibitors useful for treating neurodegenerative, inflammatory, autoimmune or cardiovascular disease

• Main Authors: HOELSCHER, PETER, SUELZLE, DETLEV, JAROCH, STEFAN, BURTON, GERARDINE ANNE, MCDOUGALL MC DONALD, FIONA, HILLMANN, MARGRIT, REHWINKEL, HARTMUT
• Format: Patent
• Language: English; German
• Published: 23.03.2000
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Aminoalkylaminoalkyl-substituted 3-amino-1,4-benzoxazine or -benzothiazine derivatives (I) are new. Benzoxazine or benzothiazine derivatives of formula (I) and their tautomers, isomers and salts are new. X = O, SOm or Se; R1 = -(CHR9)n-N(R7)-A-N(R9)-B'; R2 = H; or R1 + R2 = group completing an ortho-fused 5-8 membered, mono- or bicyclic, saturated or unsaturated ring (in which 1 or 2 CH2 groups may be replaced by O or CO), which is substituted by -(CHR9)n-N(R7)-A-N(R9)-B' and optionally substituted (os) by T; T = 1-4C alkyl; R3 = H, halo, NO2, CN, CF3, OCF3, SR9, OR9, cycloalkyl, N(R9)C(=NR10)R11, NHC(S)NR12R13, NHC(O)NR12R13, SO2NR12R13, C(O)NR12R13, C(O)NR14, NR15R16, 6-10C aryl (os by halo, CN, T, SR9 or OR9), 5-6 membered heteroaryl (with 1-4 W'), alkyl (os by halo, OR9, SR9, NR12R13, =NR12, =NO-alkyl, =N-NH-aryl, Ph, cycloalkyl or 5- or 6-membered heteroaryl), or alkenyl or alkynyl (both os by halo, CONH2, CN or Ph); R4 = H or acyl; R5, R6 = H; or cycloalkyl, phenyl, alkyl, alkenyl or alkynyl (all os by halo, OH, alkoxy, SH, alkylthio, NR15R16, 5- or 6-membered heteroaryl (with 1-3 W'), Ph or cycloalkyl); R7, R8 = H, alkyl (os by Ph), alkoxycarbonyl or alkylcarbonyl; A = 1-6C alkylene or -(CH2)pQ(CH2)q-; B' = H or -(CH2)pU'; Q = cycloalkyl, indanyl, 5-7 membered heterocycloalkyl (with 1 or 2 W'), 6-10C aryl or 5- or 6-membered heteroaryl (with 1-3 W') optionally fused with benzo (where aryl and heteroaryl residues are os by halo, T, OT, CF3, NO2, NH2, NHT, N(T)2, CN, CONH2, OCH2O, O(CH2)2O, SO2NH2, OH, OPh or COOT); N(R8)B' = 5-7 membered saturated heterocycle (optionally containing W' and os by T, Ph, benzyl or benzoyl) or unsaturated 5-membered heterocycle (containing 1-3 N and os by Ph, T or halo); R7 + (CH2)pQ = group completing a 5-7 membered saturated heterocycle (optionally containing W') or unsaturated 5-membered heterocycle (containing 1-3 N); m = 0-2; n = 1-6; p, q = 0-6; R9, R10 = H or alkyl; R11 = alkyl, NH2, NHMe, NHCN, 6-10C aryl (os by halo, T or CF3) or 5- or 6-membered heteroaryl (containing 1-4 W' and os by halo, CF3 or T); R12, R13 = H, alkyl, phenyl or benzyl (both os by halo or T), or cycloalkyl; R14 = H, OH, alkoxy, Ph, alkyl (os by COOH, alkoxycarbonyl, OH, OT, halo, NR15R16, CONR12R13 or Ph) or alkenyl (os by Ph, CN, CONR12R13 or COOT); R15, R16 = H, alkyl, Ph or benzyl; or NR15R16 = saturated 5-7 membered ring (optionally containing W' and os by T, Ph, benzyl or benzoyl); W' = O, S or N; unless specified otherwise alkyl moieties have 1-6C, cycloalkyl moieties 3-7C and alkenyl or alkynyl moieties 2-6C. An Independent claim is included for the preparation of (I). Es werden Verbindungen der Formel I, deren tautomere und isomere Formen und Salze DOLLAR F1 sowie das Verfahren zu deren Herstellung und deren Verwendung in Arzneimitteln beschrieben.