| 1. |
- Aahlin, Kristofer, et al.
(författare)
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Preparation of 1-(4-(5-amino-6-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-yl)benzoyl)piperazine derivatives as glycogen synthase kinase 3 inhibitors.
- 2011
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Patent (populärvet., debatt m.m.)abstract
- Title compds. I [R1 = H or Me], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by cyclization of 3-amino-N-(4-hydroxypyridin-3-yl)pyrazine-2-carboxamide (prepn. given) to get intermediate 3-(oxazolo[4,5-c]pyridin-2-yl)pyrazin-2-amine, which underwent bromination followed by Suzuki reaction with (4-methylpiperazin-1-yl)(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone. Compds. of the invention were tested for their selective inhibitory activity of GSK3β, e.g., II exhibited Ki value of 2.3 nM. The invention compds. are useful for the treatment of cognitive disorders, diabetes, cancer, etc. [on SciFinder(R)]
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| 2. |
- Arvidsson, Per I., et al.
(författare)
-
Preparation of imidazolylpyrimidine derivatives for treatment of glycogen synthase kinase 3 related disorders such as Alzheimer's disease.
- 2010
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Patent (populärvet., debatt m.m.)abstract
- Title compds. I [R1 = H or F; R2 and R3 independently = H or Me], and their pharmaceutically acceptable salts, are prepd. and disclosed as agents for treatment of glycogen synthase kinase 3 (GSK3) related disorders such as Alzheimer's disease. Thus, e.g., II.HCl was prepd. by reductive amination of 4-bromo-3-fluorobenzaldehyde with (S)-3-methylmorpholine followed by amination with 2-amino-5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidine. Select I were evaluated for GSK3β inhibitory activity, and e.g., II·HCl demonstrated a Ki value of 30 nM. [on SciFinder(R)]
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| 3. |
- Arvidsson, Per, et al.
(författare)
-
Preparation of arylimidazopyridine derivatives for use as GSK3 modulators.
- 2008
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Patent (populärvet., debatt m.m.)abstract
- Title compds. I [A = (un)substituted aryl or heteroaryl; Q = halo; R1 = C(O)NR6R7; R2 and R4 independently = H, halo, CN, NO2, alkyl, or haloalkyl; R3 and R5 independently = H, halo, alkyl, or haloalkyl; R6 and R7 = together with the atoms to which they are attached form an (un)substituted heterocyclic ring contg. one or more heteroatoms selected from N, O, or S;], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase-3 (GSK3) modulators. Thus, e.g., II•HCl was prepd. by cyclocondensation of 5-bromopyridine-2,3-diamine with terephthalic monomethyl ester followed by chlorination, iodination, sapon., amidation with N-methylpiperazine, and coupling with 4-methoxyphenyl boronic acid. I were evaluated in GSK3β scintillation proximity assays, e.g., II•HCl demonstrated an Ki value of 97 nM. [on SciFinder(R)]
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| 4. |
- Arvidsson, Per, et al.
(författare)
-
Preparation of imidazopyridinecarboxamide derivatives for use as GSK3 modulators.
- 2008
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Patent (populärvet., debatt m.m.)abstract
- Title compds. I [Q = halo; R1 = CH2NR3R4; each R2 independently = H or alkyl; R3 and R4 = together with the atoms to which they are attached form an (un)substituted heterocyclic ring contg. one or more heteroatoms selected from N, O, or S; R6 = H or alkyl; R7 = H, (un)substituted alkyl, alkylaryl, aryl, or heteroaryl], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase-3 (GSK3) modulators. Thus, e.g., II•HCl was prepd. by cyclocondensation of 5-bromopyridine-2,3-diamine with terephthalic monomethyl ester followed by chlorination, iodination, sapon., amidation with morpholine, redn., and coupling with carbon monoxide and 3-methoxy-1-propanamine. I were evaluated in GSK3β scintillation proximity assays, e.g., II•HCl demonstrated an Ki value of 390 nM. [on SciFinder(R)]
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| 5. |
- Besidski, Yevgeni, et al.
(författare)
-
Preparation of aminotriazole compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The invention relates to aminotriazole compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 is (un)substituted C1-6-alkyl, C3-7-cycloalkyl-C1-3-alkyl, heterocyclyl-C1-3-alkyl, etc.; R3 and R4 are each independently selected from H, C1-6-alkyl, (un)substituted C3-7-cycloalkyl, etc.] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of 3-bromo-N-(cyclopropylmethyl)-1-methyl-1H-1,2,4-triazol-5-amine with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline dihydrochloride under Buchwald-Hartwig conditions in 26% yield. Nine compds. of I were evaluated for inhibition of Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]
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| 6. |
- Besidski, Yevgeni, et al.
(författare)
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Preparation of azetidinotriazole compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.
- 2014
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Patent (populärvet., debatt m.m.)abstract
- The invention relates to azetidinotriazole compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 is (un)substituted C1-6-alkyl, C3-7-cycloalkyl-C1-3-alkyl, heterocyclyl-C1-3-alkyl, etc.; R3, R5, and R7 are each independently selected from H, (un)substituted C1-3-alkyl, C3-7-cycloalkyl, etc.; R4, R6, R8 are each independently selected from H, F, C1-3-alkyl, etc.; or R3 and R4, or R5 and R6, or R7 and R8, together with the carbon to which they are attached, form (un)substituted 3- to 7-membered satd. ring optionally contg. an O or N] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of III with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline under Buchwald-Hartwig conditions in 26% yield. Nine compds. of I were evaluated for activity on Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]
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| 7. |
- Besidski, Yevgeni, et al.
(författare)
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Preparation of pyrimidinylamine compounds as gamma secretase modulators useful for treatment of Aβ-related diseases.
- 2014
-
Patent (populärvet., debatt m.m.)abstract
- The invention relates to pyrimidinylamine compds. of formula I and pharmaceutically acceptable salts and pharmaceutical compns. thereof, as well as processes for making these compds. for use in the treatment and/or prevention of Aβ-related diseases. I [wherein A is (un)substituted 5- or 6-membered heteroaryl ring comprising at least one N; R1 is H, C1-3-alkyl, cyano, etc.; R2 and R3 are each independently selected from C1-3-alkyl and fluoro-C1-3-alkyl; or R2 and R3 together with the carbon to which they are attached form a 3- to 6-membered satd. carbocyclic ring, optionally substituted with one or more fluoro substituents; R4 is C1-3-alkyl, fluoro-C1-3-alkyl, or C3-6-cycloalkyl-C1-3-alkyl; R5 is H, C1-3-alkyl, fluoro, etc.; R6 is, for example, CH3NH-, CNCH2-, or MeO-] or pharmaceutically acceptable salts thereof are claimed and exemplified. Example compd. II was prepd. from the reaction of III with 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)aniline under Buchwald-Hartwig conditions in 77% yield. Fifty-two compds. of I were evaluated for activity on Aβ formation utilizing electrochemiluminescence anal. and HEK cells expressing amyloid precursor protein (data given). [on SciFinder(R)]
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| 8. |
- Burrows, Jeremy, et al.
(författare)
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Preparation of imidazolyl-pyrimidine derivatives as GSK3 inhibitors.
- 2008
-
Patent (populärvet., debatt m.m.)abstract
- Title compds. I [R1 = sulfamoyl, carbamoyl or -R5-R6 and N linked (un)substituted 4- to 7-membered satd. ring which optionally contains an addnl. N, O or S; R5 = O, C(O), C(O)O, C(O)NH, etc., R6 = (un)substituted alkyl, carbocyclyl or heterocyclyl; at least one of X1, X2, X3 and X4 = N, the other three independently = N or C(R9), wherein R9 = H, halo, CN, OH, NH2, alkyl or alkoxy; provided that not more than two of X1, X2, X3 or X4 = N; R2 = halo or CN; R3 = Me, (un)substituted 3-tetrahydropyranyl or 4-tetrahydropyranyl; R4 = H, halo, CN or (un)substituted alkyl], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by amidation of 3,5-dichloro-2-pyridinecarboxylic acid with piperidine followed by coupling reaction with 5-fluoro-4-[2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine, which was prepd. starting from 5-methyl-4-aminoisoxazole and tetrahydro-2H-pyran-4-one in 5 steps. All the exemplar compds. were evaluated for their GSK3 inhibitory activity in GSK3 inhibition assays with typical Ki values ranging from 0.001 to 10,000 nM. For instance, II exhibited a Ki value of 7 nM. As inhibitors of GSK3, I should prove useful in treatment and prevention of GSK3 assocd. diseases including Alzheimer's disease. [on SciFinder(R)]
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| 9. |
- 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
-
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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| 10. |
- 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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