摘要:
This invention provides an isolated mutant atpE protein and departing from said mutant atpE protein the identification of an ATPase binding domain. This invention also provides related nucleic acids, vectors, host cells, pharmaceutical compositions and articles of manufacture. This invention further provides methods for determining whether a test compound interacts with an atpE protein, i.e. with the ATPase binding domain of the present invention, as well as pharmaceuticals compositions comprising said test compound, in particular as antimicrobials, more particular as antimycobacterial agent, even more particular for treating tuberculosis in a subject.
摘要:
The present invention relates to the use of a substituted quinoline derivative for the preparation of a medicament for the treatment of an infection with a drug resistant Mycobacterium strain wherein the substituted quinoline derivative is a compound according to Formula (Ia) or Formula (Ib) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof and the N-oxide forms thereof. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the above compounds and one or more other antimycobacterial agents.
摘要:
Use of a compound for the manufacture of a medicament for the treatment of a bacterial infection provided that the bacterial infection is other than a Mycobacterial infection, said compound being a compound of Formula (Ia) or (Ib) a pharmaceutically acceptable acid or base addition salt thereof, a quaternary amine thereof, a stereochemically isomeric form thereof, a tautomeric form thereof or a N-oxide form thereof, wherein R1 is hydrogen, halo, haloalkyl, cyano, hydroxy, Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; p is 1, 2, 3 or 4; R2 is hydrogen, hydroxy, thio, alkyloxy, alkyloxyalkyloxy, alkylthio, mono or di(alkyl)amino or a radical of formula R3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl; R4 is hydrogen, alkyl or benzyl; R5 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; or two vicinal R5 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl; r is 1, 2, 3, 4 or 5; R6 is hydrogen, alkyl, Ar or Het; R7 is hydrogen or alkyl; R5 is oxo; or R7 and R5 together form the radical —CH═CH—N═; Z is CH2 or C(═O).
摘要翻译:使用化合物制造用于治疗细菌感染的药物,只要细菌感染不是分枝杆菌感染,所述化合物是式(Ia)或(Ib)的化合物,其药学上可接受的酸或碱加成 其盐,其季胺,其立体化学异构形式,其互变异构形式或其N-氧化物形式,其中R 1是氢,卤素,卤代烷基,氰基,羟基,Ar,Het 烷基,烷氧基,烷硫基,烷氧基烷基,烷硫基烷基,芳烷基或二(Ar)烷基; p为1,2,3或4; R 2是氢,羟基,硫代,烷氧基,烷氧基烷氧基,烷硫基,一或二(烷基)氨基或式R 3的基团是烷基,Ar,Ar- 烷基,Het或Het-烷基; R 4是氢,烷基或苄基; R 5是氢,卤素,卤代烷基,羟基,Ar,烷基,烷氧基,烷硫基,烷氧基烷基,烷硫基烷基,芳烷基或二(Ar)烷基; 或两个邻位R 5个基团可以与它们所连接的苯环一起形成萘基; r为1,2,3,4或5; R 6是氢,烷基,Ar或Het; R 7是氢或烷基; R 5是氧代; 或R 7和R 5一起形成基团-CH-CH-N-; Z是CH 2或C(-O)。
摘要:
The present invention concerns compounds of formula (I), prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms thereof wherein -a1=a2-a3=a4- represents a radical of formula —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; CH═CH—CH═N—; wherein each hydrogen atom may optionally be substituted; Q is a radical of formulae (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7) and (b-8), wherein Alk is C1-6alkanediyl; Y1 is a bivalent radical of formula —NR2— or —CH(NR2R4); X1 is NR4, S, S(═O), S(═O)2, O, CH2, C(═O), CH(═CH2), CH(OH), CH(CH3), CH(OCH3), CH(SCH3), CH(NR5aR5b), CH2—NR4 or NR4—CH2; X2 is a direct bond, CH2, C(═O), NR4, C1-4alkyl-NR4, NR4—C1-4alkyl, t is 2 to 5; u is 1 to 5; v is 2 or 3; and whereby each hydrogen in Alk and in (b-3), (b-4), (b-5), (b-6), (b-7) and (b-8), may optionally be replaced by R3; provided that when R3 is hydroxy or C1-6alkyloxy, then R3 cannot replace a hydrogen atom in the α position relative to a nitrogen atom; G is a direct bond or optionally substituted C1-10alkanediyl; R1 is an optionally substituted bicyclic heterocycle; R2 is hydrogen, formyl, C1-6alkylcarbonyl, Hetcarbonyl, pyrrolidinyl, piperidinyl, homopiperidinyl, C3-7cycloalkyl or C1-10alkyl substituted with N(R6)2 and optionally with another substituent; R3 is hydrogen, hydroxy, C1-6alkyl, C1-6alkyloxy, arylC1-6alkyl or arylC1-6alkyloxy, R4 is hydrogen, C1-6alkyl or arylC1-6alkyl; R5a, R5b, R5c and R5d are hydrogen or C1-6alkyl; or R5a and R5b, or R5c and R5d taken together from a bivalent radical of formula —(CH2)S— wherein S is 4 or 5; R6 is hydrogen, C1-4alkyl, formyl, hydroxyC1-6alkyl, C1-6alkylcarbonyl or C1-6alkyloxycarbonyl; aryl is optionally substituted phenyl; Het is pyridyl, pyrimidinyl, pyryzinyl, pyridazinyl; as respiratory syncytial virus replication inhibitors; their preparation, compositions containing them and their use as a medicine.
摘要:
This invention concerns the use of compounds of formula (I) wherein -a1=a2-a3=a4- is a radical of for CH═CH—, —N═CH—CH═CH—, —CH═N—CH═CH—, —CH═CH—N═CH—, —CH═CH—CH═N— wherein each hydrogen atom may optionally be substituted; Q is a radical of formulas (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7), (b-8), G is a direct bond or C1-10alkanediyl; R1 is an optionally substituted monocyclic heterocycle; for the manufacture of a medicament for the treatment of viral infections, in particular RSV infections. Certain compounds of formula (I) are new.
摘要:
This invention concerns the use of the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR4 or N; n is 0 to 4; Q is hydrogen or —NR1R2; R1 and R2 are selected from hydrogen, hydroxy, C1-12alkyl, C1-12alkyloxy, C1-12alkylcarbonyl, C1-12alkyloxycarbonyl, aryl, amino, mono- or di(C1-12alkyl)-amino, mono- or di(C1-12alkyl)aminocarbonyl wherein each C1-12alkyl may optionally be substituted; or R1 and R2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C1-12alkyl)aminoC1-4alkylidene; R3 is hydrogen, aryl, C1-6alkylcarbonyl, optionally substituted C1-6alkyl, C16alkyloxy-carbonyl,; and R4 is hydroxy, halo, optionally substituted C1-6alkyl, C1-6alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl, trihalomethyloxy; R5 is hydrogen or C1-4alkyl; L is optionally substituted C1-10alkyl, C3-10alkenyl, C3-10alkynyl, C3-7cycloalkyl; or L is —X1—R6 or —X2-Alk-R7 wherein R6 and R7 are optionally substituted phenyl; X1 and X2 are —NR3—, —NH—NH—, —N═N—, —O—, —S—, —S(═O)— or —S(═O)2—; Alk is C1-4alkanediyl; aryl is potionally substituted phenyl; Het is an optionally substituted aliphatic or aromatic heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection. It further relates to new compounds being a subgroup of the compounds of formula (I), their preparation and compositions comprising them.
摘要:
This invention concerns the use of the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein A is CH, CR4 or N; n is 0 to 4; Q is hydrogen or —NR1R2; R1 and R2 are selected from hydrogen, hydroxy, C1-12alkyl, C1-12alkyloxy, C1-12alkylcarbonyl, C1-12alkyloxycarbonyl, aryl, amino, mono- or di(C1-12alkyl)amino, mono- or di(C1-12alkyl)aminocarbonyl wherein each C1-12alkyl may optionally be substituted; or R1 and R2 taken together may form pyrrolidinyl, piperidinyl, morpholinyl, azido or mono- or di(C1-12alkyl)aminoC1-4alkylidene; R3 is hydrogen, aryl, C1-6alkylcarbonyl, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl,; and R4 is hydroxy, halo, optionally substituted C1-6alkyl, C1-6alkyloxy, cyano, aminocarbonyl, nitro, amino, trihalomethyl, trihalomethyloxy; R5 is hydrogen or C1-4alkyl; L is optionally substituted C1-10alkyl, C3-10alkenyl, C3-10alkynyl, C3-7cycloalkyl; or L is —X1—R6 or —X2—Alk—R7 wherein R6 and R7 are optionally substituted phenyl; X1 and X2 are —NR3—, —NH—NH—, —N═N—, —O—, —S—, —S(═O)— or —S(═O)2—; Alk is C1-4alkanediyl; aryl is potionally substituted phenyl; Het is an optionally substituted aliphatic or aromatic heterocyclic radical: for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection. It further relates to new compounds being a subgroup of the compounds of formula (I), their preparation and compositions comprising them.
摘要:
Method of treating a bacterial infection other than a Mycobacterial infection, using a compound of formula (Ia) or (Ib) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, a tautomeric form thereof or a N-oxide form thereof, wherein the substituents R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined.
摘要:
This invention concerns the use of compounds of formula the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a1=a2-a3=a4- forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R1 is hydrogen, aryl, formyl, C1-6alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, or substituted C1-6alkyloxyC1-6alkylcarbonyl; each R2 independently is hydroxy, halo, optionally substituted C3-6alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkylamino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C1-10alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or L is —X—R3 wherein R3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is —NR1—, —NH—NH—, —N═N—, —O—, —C(═O)—, —CHOH—, —S—, —S(═O)— or —S(═O)2—; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.
摘要:
This invention concerns the use of compounds of formula the N-oxides, pharmaceutically acceptable addition salts, quaternary amines, stereochemically isomeric forms thereof, wherein -a1=a2-a3=a4- forms phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl with the attached vinyl group; n is 0 to 5; R1 is hydrogen, aryl, formyl, C1-6alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, substituted C1-6alkyl, substituted C1-6alkyloxyC1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C3-7cycloalkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6, 5-membered heterocyclic ring; L is optionally substituted C1-10alkyl, C2-10alkenyl, C2-10alkynyl or C3-7cycloalkyl; or —X—R3; Q is hydrogen, C1-6alkyl, halo, polyhalo-C1-6alkyl, optionally substituted amino group; Y represents hydroxy, halo, C3-7cycloalkyl, optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono-or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, 13 NHC(═O)R6,—C(═NH)R6, aryl; for the treatment of subjects suffering from HIV infection.