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 present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
Novel inhibitors of cathepsin S, K, B, and L, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
The present invention relates to novel cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
The present invention relates to novel cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
摘要:
This invention is directed to physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; R1 represents hydrogen or a straight- or branched-chain alkyl group of 1 to about 4 carbon atoms, optionally substituted by hydroxy or one or more halogen atoms, or when Z1 represents a direct bond R1 may also represent a lower alkenyl or lower alkynyl group, or a formyl group; R2 represents hydrogen, alkenyl, alkoxy, alkyl, alkylsulphinyl, alkylsulphonyl, alkylthio, aryl, arylalkyloxy, arylalkylsulphinyl, arylalkylsulphonyl, arylalkylthio, aryloxy, arylsulphinyl, arylsulphonyl, arylthio, cyano, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy, hydroxy, —SO2NR4R5, —NR4SO2R5, —NR4R5, —C(═O)R5, —C(═O)C(═O)R5, —C(═O)NR4R5, —C(═O)OR5, —O(C═O)NR4R5, or —NR4C(═O)R5; R3 represents —C(=Z)—N(R7)R6, —C(=Z)—CHR12R6, —C(=Z)—R6, —CR8═C(R9)(CH2)p—R6, —C(R10)═C(R11)R12, —C(R13)(R10)C(R11)(R14)R12, —C(R8)(R15)CH(R9)(CH2)p—R6, —R6, —N(R16)C(=Z)R6, —C(R17)═N—OC(=0)R18, —C(═O)—N(R19)OR20, —C≡C—R6, —CH2—C(=Z)—R6, —C(=Z)—C(=Z)R6, —CH2—NHR6, —CH2-ZR6, —CH2—SOR6, —CH2—SO2R6, —CF2—OR6, —NH—CH2R6, -Z-CH2R6, —SO—CH2R6, —SO2—CH2R6, —O—CF2R6, —O—C(=Z)R6, —N═N—R6, —NH—SO2R6, —SO2—NR21R22, —CZ-CZ-NHR6, —NH—CO—OR6, —O—CO—NHR6, —NH—CO—NHR6, —R23, —CX1═CX2R6, —C(═NOR24), —(CH2)qR6, —CH2—CO—NH(CH2)qR6, —CH2—NH—CO(CH2)qR6, —CH2—CO—CH2R6, —C(═NR25)—NH(CH2)qR6, —C(X3)═N—(CH2)qR6 or —CH(X4)—CH2R6; A1 represents a direct bond, or a straight or branched C1-6 alkylene chain optionally substituted by hydroxyl, alkoxy, oxo, cycloalkyl, aryl or heteroaryl, or A1 represents a straight or branched C2-6alkenylene or C2-6alkynylene chain; Z1 represents a direct bond, an oxygen or sulphur atom or NH; n and m each represent zero or 1, provided that n is 1 when m is zero and n is zero when m is 1; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.
摘要翻译:本发明涉及式(I)的生理活性化合物,其中代表双环体系,约10至约13个环成员,其中该环是氮杂环,并且该环代表氮杂杂芳基环,或任选地被卤素取代 苯环; R 1表示氢或1至约4个碳原子的直链或支链烷基,任选被羟基或一个或多个卤素原子取代,或当Z 1表示直接键R 1时 也代表低级烯基或低级炔基或甲酰基; R 2表示氢,烯基,烷氧基,烷基,烷基亚磺酰基,烷基磺酰基,烷硫基,芳基,芳基烷氧基,芳基烷基亚磺酰基,芳基烷基磺酰基,芳基烷硫基,芳氧基,芳基亚磺酰基,芳基磺酰基,芳硫基,氰基,环烯基,环烯氧基,环烷基,环烷氧基,杂芳基, ,杂芳氧基,羟基,-SO 2 NR 4 R 5,-NR 4 SO 2 R 5,-NR 4 R 5,-C(= O)R 5,-C(= O)C(= O)R 5,-C(= O)NR 4 R 5,-C(= O)OR 5,-O(C = O)NR 4 R 5或-NR 4 C(= O)R 5; R 3表示-C(= Z)-N(R 7)R 6,-C(= Z)-CHR 12 R 6,-C(= Z)-R 6 ,-CR 8 = C(R 9)(CH 2)p R 6,-C(R 10)= C(R 11)R 12,-C(R 13) (R 10)C(R 11)(R 14)R 12,-C(R 8)(R 15)CH(R 9)(CH 2) pR 6,-R 6,-N(R 16)C(= Z)R 6,-C(R 17)= N-OC(= O)R 18, -C(= O)-N(R <19)
摘要:
Manganese vanadium tantalum oxide that can be represented by the formula MnxVyTazOw, where 1≦x≦3, 0.001≦y≦3, 0.001≦z≦2, and w=7, and alternately, x=1.25≦x≦2.45, 0.1≦y≦2.39, 0.2≦z≦1.9, and w=7, methods of producing MnxVyTazOw, a pigment coated with MnxVyTazOw and a chalcogenide glass layer, and a method of producing the coated pigment are described. The disclosed manganese vanadium tantalum oxide has superior near-infrared reflective properties. The disclosed methods of producing the manganese vanadium tantalum oxide provide products with superior phase purity, appearance and performance and take health and safety into consideration. The construction of the disclosed coated pigment combines the reflective properties of the substrate with the near-infrared reflective properties of MnxVyTazOw, while the chalcogenide glass layer provides aesthetic appeal. The disclosed method of producing the coated pigment involves physical vapor deposition of MnxVyTazOw and the chalcogenide glass layer.
摘要翻译:锰钒氧化钽,其可以由式Mn x V y TazOw表示,其中1&nlE; x&nlE; 3,0.001&nlE; y&nlE; 3,0.001&nlE; z&nlE; 2和w = 7,或者,x = 1.25&nlE; x& ,0.1&nlE; y&nlE; 2.39,0.2&nlE; z&nlE; 1.9和w = 7,描述了生产MnxVyTazOw的方法,涂覆有Mn x V y TazOw和硫族化物玻璃层的颜料以及制备涂层颜料的方法。 所公开的锰钒氧化钽具有优异的近红外反射性能。 所公开的锰钒钽氧化物的制造方法提供具有优异的相纯度,外观和性能的产品,并考虑健康和安全性。 所公开的涂层颜料的结构将基材的反射性能与Mn x V y TazOw的近红外反射性质结合,而硫族化物玻璃层提供了美学吸引力。 所公开的生产涂层颜料的方法包括物理气相沉积Mn x V y TazOw和硫族化物玻璃层。