摘要:
The present invention concerns compounds of general formula (I): in which: R1 represents hydrogen, R4, —C(═Y)—NHR4, —SO2NHR4, —C(=Z1)—R4, —SO2—R4 or —C(=Z1)—OR4; R2 represents hydrogen, cyano, halogen or —C≡C—R5; R3 represents hydrogen, acyl, alkoxycarbonyl, alkyl, aroyl, aryl, aryloxycarbonyl, carboxy, cycloalkenyl, cycloalkyl, heteroaroyl, heteroaryl, heterocycloalkyl or —C(═O)—NY1Y2; R4 represents optionally substituted alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl or heteroaryl R5 represents hydrogen or alkyl; R6 represents alkyl, acyl, alkoxycarbonyl, alkylsulfonyl, aryl, arylsulfonyl, aroyl, cycloalkyl, cycloalkenyl, heteroaryl, heteroarylsulfonyl, heteroaroyl and heterocycloalkyl; R7 represents optionally substituted alkyl, cycloalkyl or cycloalkylalkyl, R8 represents hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; R9 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; R10 represents hydrogen or lower alkyl; R11 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; or alkyl optionally substituted by —NY1Y2; R12 represents aryl or heteroaryl; or alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl or heterocycloalkylalkyl each optionally substituted Y represents O, S or NCN; Y1 and Y2 (Y3 and Y4) are independently in particular hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocycloalkyl; or the group —NY1Y2 may form 5-7 membered ring or the group —NY3Y4 (—NY5Y6) may form a cyclic amine; Z (Z1) represents O or S; Z2 represents O or S(O)p; n is zero or an integer 1 or 2; m is 1 or 2; p is 1 or 2; and their corresponding N-oxides, their prodrugs; their pharmaceutically acceptable salts and solvates (e.g. hydrates), also together with one or more pharmaceutically acceptable carriers or excipients, such novel indolizines derivatives with inhibitory effects towards kinase proteins and especially for use for preventing or treating diseases that may be modulated by the inhibition of such kinase proteins and particularly solid tumours.
摘要:
The invention is directed to physiologically active compounds of general formula (I):— and compositions containing such compounds; and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (I). Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit kinases.
摘要:
The invention is directed to physiologically active compounds of the general formula (Ix) and compositions containing such compounds, and their prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their prodrugs, as well as to novel compounds within the scope of formula (Ix), and to processes for their preparation. Such compounds and compositions have valuable pharmaceutical properties, in particular the ability to inhibit kinases.
摘要:
Compounds of the formula I are suitable for producing pharmaceuticals for the prophylaxis and therapy of diseases whose course involves an increased activity of NIK.
摘要:
This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.
摘要:
This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H;R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted;R.sup.3 is halogen;R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl;R.sup.5 is carboxy or an acid isostere;X is oxygen or sulphur; andn is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.
摘要翻译:本发明涉及式Ⅰ化合物,其中R1是CN,CH2CN,CH = CHCN,CHO或CH = CHCO2H; R 2是芳基低级烷氧基,杂芳基低级烷氧基,芳基低级烷硫基或杂芳基低级烷硫基,其中芳基和杂芳基部分中的每一个任选被取代; R3是卤素; R 4是任选取代的芳基或任选取代的杂芳基; R5是羧基或酸等isostere; X是氧或硫; n为0或1; 或其N-氧化物,其前体药物溶剂化物或其药学上可接受的盐,该化合物具有内皮素拮抗剂活性。 本发明还涉及制备式I化合物及其药物用途的方法。
摘要:
This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H;R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted;R.sup.3 is halogen;R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl;R.sup.5 is carboxy or an acid isostere;X is oxygen or sulphur; andn is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.
摘要翻译:本发明涉及式Ⅰ化合物,其中R1是CN,CH2CN,CH = CHCN,CHO或CH = CHCO2H; R 2是芳基低级烷氧基,杂芳基低级烷氧基,芳基低级烷硫基或杂芳基低级烷硫基,其中芳基和杂芳基部分中的每一个任选被取代; R3是卤素; R 4是任选取代的芳基或任选取代的杂芳基; R5是羧基或酸等isostere; X是氧或硫; n为0或1; 或其N-氧化物,其前体药物溶剂化物或其药学上可接受的盐,该化合物具有内皮素拮抗剂活性。 本发明还涉及制备式I化合物及其药物用途的方法。