| 2. |
- Gybaeck, Helena, et al.
(författare)
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Benzoic acid derivatives as glycine receptor inhibitors, their preparation, pharmaceutical compositions, and use in therapy.
- 2006
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Patent (populärvet., debatt m.m.)abstract
- The invention relates to benzoic acid derivs. of formula I, which are inhibitors of glycine receptors (GlyRs). In compds. I, Y is H, OH, halo, (un)substituted C1-6 alkoxy, or (un)substituted C1-6 alkyl; R1 is (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, (un)substituted aryl, (un)substituted alkylaryl, (un)substituted heteroaryl, or (un)substituted C3-6 alkyl; L is selected from a bond, heteroarylene, -C(O)-, -CH2-, -CH(OR4)-, -N(OH)-, -N(R4)-, -S(O)n-, where R4 is H or C1-6 alkyl and n is 0, 1, or 2; R2 is H, halo, cyano, dimethylamino, (un)substituted C1-6 alkyl, (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, (un)substituted aryl, (un)substituted alkylaryl, (un)substituted heterocyclyl or (un)substituted heteroaryl; and R3 is OH or C1-6 alkoxy; with the exclusion of several compds. The invention also relates to the prepn. of I, pharmaceutical compns. comprising a therapeutically effective amt. of a compd. I with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers, as well as to the use of the compns. for the treatment of conditions that respond to glycine receptor inhibition, such as neuropathic or inflammatory pain syndromes. Chlorination of 4-methoxybenzenethiol followed by C-substitution with 3-tert-butyl-2-hydroxy-6-methylbenzoic acid and oxidn. gave (arylsulfonyl)benzoic acid II. Several compds. of the invention expressed IC50 values against human GlyR α1 of about 10 nM to about 30 μM (no specific data). [on SciFinder(R)]
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| 3. |
- Nordvall, Gunnar, et al.
(författare)
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Preparation of piperazinyl quinazolines as 5-HT6 modulators.
- 2007
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Patent (populärvet., debatt m.m.)abstract
- Title compds. represented by the formula I [wherein Q = (hetero)arylalkyl, (hetero)cycloalkylalkyl or alkyl; B = CH or N; R1 = H, OH, halo, alkyl, etc.; R2 = H, (halo)alkyl, aminocarbonylalkyl, etc.; R3 = H, (halo)alkyl or alkylaryl; R4 = CN, halo, alkoxy, etc.; m = 0-2; n = 0-4; and pharmaceutically acceptable salts, solvates or solvated salts thereof] were prepd. as 5-HT6 modulators. For example, reaction of 2,4-dichloroquinazoline with benzenesulfonamide and followed by reaction with N-methylpiperazine, gave N-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]benzenesulfonamide in 6% yield. The radioligand binding assay showed II having Ki of 1.4 nM. Thus, I and their pharmaceutical compns. are useful for the treatment of 5-HT6 mediated disorders, such as Alzheimer's disease, schizophrenia, obesity or Parkinson's disease. [on SciFinder(R)]
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| 5. |
- Wensbo, David, et al.
(författare)
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Preparation of five-membered heterocyclic compounds as mGluR5 receptor antagonists.
- 2004
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Patent (populärvet., debatt m.m.)abstract
- The present invention relates to five-membered heterocyclic compds. (shown as I; variables defined below; e.g. II), a process for their prepn. and new intermediates prepd. therein, pharmaceutical formulations contg. said compds. and to the use of said compds. in therapy, e.g. neurol., psychiatric and chronic and acute pain disorders (no data). Typical IC50 values for mGluR5 receptor antagonist activity are ≤10 μM; no values for individual compds. are given. Methods of prepn. are claimed and example prepns. and/or characterization data are included for ∼800 examples of I and intermediates. For example, [3-[3-[[[4-methyl-5-(thiophen-2-yl)-4H-[1,2,4]triazol-3-yl]sulfanyl]methyl][1,2,4]oxadiazol-5-yl]phenyl]carbamic acid tert-Bu ester was prepd. in 79% yield by condensation of 4-methyl-5-(thiophen-2-yl)-4H-[1,2,4]triazole-3-thiol with [3-(3-chloromethyl-[1,2,4]oxadiazol-5-yl)phenyl]carbamic acid tert-Bu ester in MeCN in the presence of K2CO3. For I: P = H, C3-7alkyl or a 3- to 8-membered ring contg. ≥1 atoms = C, N, O and S, which ring may optionally be fused with a 5- or 6-membered ring contg. ≥1 C, N, O and S; R1 = H, hydroxy, halo, nitro, C1-6-alkylhalo, OC1-6alkylhalo, C1-6alkyl, OC1-6alkyl, C2-6alkenyl, OC2-6alkenyl, C2-6alkynyl, OC2-6alkynyl, C0-6alkylC3-6cycloalkyl, etc. and a 5- or 6-membered ring contg. ≥1 C, N, O and S, wherein said ring may be substituted by ≥1 A. M1 = a bond, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, C0-4alkyl(CO)C0-4alkyl, C0-3alkylOC0-3alkyl, C0-3alkyl(CO)NR5, C0-3alkyl(CO)NR5C0-3alkyl, C0-4-alkylNR5, C0-3alkylSC0-3alkyl, etc.; R2 = H, hydroxy, C0-6alkylcyano, oxo, NR5, NOR5, C1-4alkylhalo, halo, C1-4alkyl, etc. X1, X2 and X3 = CR, CO, N, NR, O and S; R = H, C0-3alkyl, halo, C0-3alkylOR5, C0-3-alkylNR5R6, C0-3alkyl(CO)OR5, C0-3alkylNR5R6 and C0-3alkylaryl; M2 = a bond, C1-3alkyl, C3-7cycloalkyl, C2-3alkenyl, C2-3alkynyl, C0-4alkyl(CO)C0-4alkyl, C0-3alkylOC0-3alkyl, etc.; R3 = H, hydroxy, C0-6alkylcyano, oxo, NR, NOR5, C1-4alkylhalo, halo, C1-4alkyl, etc. X4 = C0-4alkylR5, C0-4alkyl(NR5R6), C0-4-alkyl(NR5R6):N, NR5C0-4alkyl(NR5R6):N, NOC0-4alkyl, C1-4alkylhalo, C, O, SO, SO2 and S; Q is a 5- or 6-membered ring contg. ≥1 C, N, O and S, which group may optionally be fused with a 5- or 6-membered ring contg. ≥1 C, N, O and S and which fused ring may be substituted by ≥1 A. R4 = H, hydroxy, C0-6alkylcyano, oxo, NR5, NOR5, C1-4alkylhalo, halo, C1-4alkyl, OC1-4alkyl, OC0-6alkylaryl, etc. and a 5- or 6-membered ring contg. ≥1 atoms = C, N, O or S, wherein said ring may be substituted by ≥1 A; R5, R6 = H, OH, C1-6alkyl, etc.; A = H, OH, O, halo, nitro, C0-6alkylcyano, etc.; m = 0-4; and n = 0-3; addnl. details are given in the claims. [on SciFinder(R)]
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