摘要:
Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8; J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C1-3alkylene, C2-4alkenylene, and substituted C2-4alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.
摘要:
Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I) an enantiomer, diastereomer, tautomer, solvate (e.g. a hydrate), or a pharmaceutically-acceptable salt, thereof, wherein: M is selected from alkyl, substituted alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl, provided that if M is alkyl then R6 and R7 taken together with the carbon atom to which they are both attached are selected from a group other than cycloalkyl; Q is selected from (i) hydrogen, C1-C4 alkyl, and substituted C1-C4 alkyl; or (ii) Q and R6 are combined with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and MaM are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO2, and N which ring may be optionally substituted with 0-2 R5 groups or carbonyl; Z is selected from cycloalkyl, heterocyclo, aryl, or heteroaryl; and Ma, Za, R1, R2, R3, R4, R6, R7, and R22 are as defined herein. Also provided are pharmaceutical compositions and methods of treating metabolic and inflammatory- or immune-associated diseases or disorders using said compounds.
摘要:
Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is —N—, —NR1—, —O—, —S—, —SO2— or —CR2—; F is —N—, —NR1a—, —O—, —S—, —SO2— or —CR2a—; G is N, —NR1b—, —O—, —S—, —SO2— or —CR2b—, provided that the E-F-G containing heterocyclic ring formed does not contain a S—S or S—O bond, and at least one of E, F and G is a heteroatom; J, Ja, M, Ma, Q, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, and R3 to R21, Z, Za, Zb, and Zc are as defined above.
摘要翻译:提供了新的非甾体化合物,其可用于治疗与调节糖皮质激素受体,AP-1和/或NF-κB活性相关的疾病,包括具有式(I)结构的炎性和免疫疾病,肥胖症和糖尿病 ),其对映异构体,非对映异构体或其药学上可接受的盐或水合物,其中X为(Ia); 或X为(Ib); 或X为(Ic); (Id)是杂环或杂芳基; E是-N-,-NR1 - , - O - , - S - , - SO2-或-CR2-; F是-N-,-NR1 - , - O - , - S - , - SO2-或-CR2a-; G是N,-NR1b - , - O - , - S - , - SO2-或-CR2b-,条件是所形成的含有EFG的杂环不含S-S或S-O键, E,F和G是杂原子; J,Ja,M,Ma,Q,Rx,Ry,R1,R1a,R1b,R2,R2a,R2b和R3至R21,Z,Za,Zb和Zc如上所定义。
摘要:
The present invention is directed to compounds having the formula (I): useful in treating inflammatory and immune diseases, in which K and L are independently, O or S; Q is —C(═O)— or optionally substituted C1-6alkylene; Ar is optionally-substituted aryl or heteroaryl; J1, J2, J3 and Y are selected so that ring A is a five-to-six membered optionally-substituted cycloalkenyl or heterocyclo ring having 0 to 2 nitrogen heteroatoms; R1 is N or C(R9); and R2, and R3, are as defined in the specification.
摘要:
Urazole compounds having the formula (I), or pharmaceutically-acceptable salts thereof, are effective as anti-inflammatory or immunosuppressive agents, wherein L and K are O or S; Q is a linker such as —O—, —S—, C(═O), and so forth, R1 is an aryl or heteroaryl group, and R3, R4a, R4c, Z, r, s and t are as defined in the specification.
摘要:
Compounds having the formula (I), are effective as inhibitors of IMPDH enzyme and/or serine protease Factor VIIa, wherein B is a monocyclic or bicyclic carbocyclic or heterocyclic ring, D is a monocyclic or bicyclic carbocyclic or heterocyclic ring except when A is a heterocyclic ring, then D is a heterocyclic ring system, R is hydrogen or C1-4alkyl, and A, R1, R2 and R4 are as defined in the specification.
摘要:
The present invention discloses the identification of the novel inhibitors of IMPDH (inosine-5′-monophosphate dehydrogenase). The compounds and pharmaceutical compositions disclosed herein are useful in treating or preventing IMPDH-associated disorders, such as transplant rejection and autoimmune diseases.
摘要:
A compound of Formula I and enantiomers, diastereomers and pharmaceutically-acceptable salts thereof. Also disclosed are pharmaceutical compositions containing compounds of Formula I, and methods of treating conditions associated with the activity of p38 kinase.
摘要:
Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is —N—, —NR1—, —O—, —S—, —SO2— or —CR2—; F is —N—, —NR1a—, —O—, —S—, —SO2— or —CR2a—; G is N, —NR1b—, —O—, —S—, —SO2— or —CR2b—, provided that the E-F-G containing heterocyclic ring formed does not contain a S—S or S—O bond, and at least one of E, F and G is a heteroatom; J, Ja, M, Ma, Q, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, and R3 to R21, Z, Za, Zb, and Zc are as defined above.
摘要翻译:提供了新的非甾体化合物,其可用于治疗与调节糖皮质激素受体,AP-1和/或NF-κB活性相关的疾病,包括具有式(I)结构的炎性和免疫疾病,肥胖症和糖尿病 ),其对映异构体,非对映异构体或其药学上可接受的盐或水合物,其中X为(Ia); 或X为(Ib); 或X为(Ic); (Id)是杂环或杂芳基; E是-N-,-NR1 - , - O - , - S - , - SO2-或-CR2-; F是-N-,-NR1 - , - O - , - S - , - SO2-或-CR2a-; G是N,-NR1b - , - O - , - S - , - SO2-或-CR2b-,条件是所形成的含有EFG的杂环不含S-S或S-O键, E,F和G是杂原子; J,Ja,M,Ma,Q,Rx,Ry,R1,R1a,R1b,R2,R2a,R2b和R3至R21,Z,Za,Zb和Zc如上所定义。
摘要:
A compound of Formula I and enantiomers, diastereomers and pharmaceutically-acceptable salts thereof. Also disclosed are pharmaceutical compositions containing compounds of Formula I, and methods of treating conditions associated with the activity of p38 kinase.