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- Simmen, K. A., et al.
(författare)
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Macrocylic inhibitors of hepatitis C virus
- 2012
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Patent (populärvet., debatt m.m.)abstract
- Inhibitors of HCV replication of formula (I)and the N-oxides, salts, and stereoisomers, whereineach dashed line represents an optional double bond;X is N, CH and where X bears a double bond it is C;R1 is —OR7, —NH—SO2R8;R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl;R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl;R4 is aryl or Het; n is 3, 4, 5, or 6;R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het;R6 is C1-6alkoxy, or dimethylamino;R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het;aryl is phenyl optionally substituted with one, two or three substituents;Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents;pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
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| 4. |
- 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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