Abstract:
Compound represented by structural formula (I) or a pharmaceutically acceptable salt thereof, wherein Ar and Ar are optionally substituted heteroaryl or optionally substituted phenyl; X is -O-, -S-, -SO-, -SO2-, -NR -, -NCOR - or -NR SO2R ; (a) is selected from the group consisting of (b), (c), (d) and (e); X is -O-, -S- or -NR -; Y is =O, =S or =NR ; Y is H, C1-C6 alkyl, -NR R , -SCH3, R -aryl(CH2)n6-, R -heteroaryl-(CH2)n6-, -(CH2)n6-heterocycloalkyl, -(C1-C3)alkyl-NH-C(O)O(C1-C6)alkyl or -NHC(O)R ; R is H or -(CH2)n1-G, wherein n1 is 0-5 G is H, -CF3, -CHF2, -CH2F, -OH, -O-(C1-C6 alkyl), -SO2R , -O-(C3-C8 cycloalkyl), -NR R , -SO2NR R , -NR SO2R , -NR COR , -NR (CONR R ), -CONR R , -COOR , C3-C8 cycloalkyl, R -aryl, R -heteroaryl, and provided when n1=0, G is not H; R , R , R and R are H, alkyl, cycloalkyl, -CHF2, -CH2F or -CF3; or R and R , together with the carbon to which they are attached, form an alkylene ring; or R and R together are =O; R is R or -OH; and the remaining variables are as defined in the specifiation, methods of treating diseases susceptible to treatment with neurokinin antagonists with said compounds, and pharmaceutical compositions comprising said compounds are disclosed. Also disclosed are pharmaceutical compositions comprising an effective amount of a compound of claim 1, at least one pharmaceutically acceptable carrier, and in combination with an effective amount of a selective serotonin reuptake inhibitor.
Abstract translation:由结构式(I)表示的化合物或其药学上可接受的盐,其中Ar 1和Ar 2是任选取代的杂芳基或任选取代的苯基; X 1是-O - , - S - , - SO - , - SO 2 - , - NR 12 - , - NR C 12 - 或-NR 12 SO 2 R 15。 (a)选自(b),(c),(d)和(e); X 2是-O - , - S-或-NR 5 - ; Y = O,= S或= NR 11; Y 1是H,C 1 -C 6烷基,-NR 17 R 13,-SCH 3,R 19 - 芳基(CH 2)n6-,R 19 - 杂芳基 - (CH 2)n6-, - (CH 2)n 6-杂环烷基, - (C 1 -C 3)烷基-NH-C(O)O(C 1 -C 6)烷基或-NHC(O)R 15; R 5是H或 - (CH 2)n1-G,其中n1是0-5G是H,-CF3,-CHF2,-CH2F,-OH,-O-(C1-C6烷基),-SO2R 13 C,-O-(C 3 -C 8环烷基),-NR 13 R 14,-SO 2 NR 13 R 14,-NR 13 SO 2 R 15,-NR 13 COR R 12,-NR 12(CONR 13 R 14),-CONR 13 R 14,-COOR 12,C 3 -C 8环烷基,R 19 - 芳基,R 19 当n1 = 0时,G不为H; R 1,R 2,R 3和R 7是H,烷基,环烷基,-CHF 2,-CH 2 F或-CF 3; 或R 1和R 2与它们所连接的碳一起形成亚烷基环; 或R 1和R 2一起为= O; R 6是R 7或-OH; 并且剩余的变量如规定中所定义,治疗易受神经激肽拮抗剂治疗的疾病的方法,以及包含所述化合物的药物组合物。 还公开了包含有效量的权利要求1的化合物,至少一种药学上可接受的载体和与有效量的选择性5-羟色胺再摄取抑制剂组合的药物组合物。
Abstract:
This present invention generally relates to muscarinic receptor antagonists, which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors.
Abstract:
The invention provides a complexant compound of formula (I): R S(CR 2)nN(R )i(CR 2)nX(CR 2)nN(R )i(CR 2)nSR , (wherein each n, which may be the same or different, is an integer 2, 3 or 4 (preferably 2); each i, which may be the same or different, represents 0 or 1; each R , which may be the same or different, is H or a thiol protecting group, preferably a protecting group; X is O, S, N, NR or a substituted phosphorus (e.g. oxo substituted phosphorus), preferably S or N; each R , which may be the same or different, is hydrogen or an optionally substituted organic group; each R , which may be the same or different, is hydrogen or an optionally substituted organic group; each R , which may be the same or different, is hydrogen or an optionally substituted organic group, or a moiety CR 2 may represent a carbonyl group or two, three or four R S on two different carbons together with those carbons and any intervening atoms may represent an optionally substituted saturated or unsaturated homocyclic or heterocyclic ring; and preferably, at least one CR 2 moiety is other than CH2 or CH(CH3)) or a salt or complex thereof, wherein optionally at least one of the R , R , R and R moieties is coupled directly or indirectly to a vector moiety.
Abstract:
Compounds of formula (I) are provided, in which R and R each independently represents a C8-C24 saturated or unsaturated hydrocarbon chain, which is optionally interrupted by form 1 to 3 heteroatom moieties, such as -O-, -S-, -NH- and -NR-. The symbol X represents -CH2-, -O-, -S-, -NH- or -NR-. The R group for each of the -NR- moieties represents an alkyl group having form 1 to 4 carbon atoms. Finally, the subscript n represents the integer 1 or 2, and A- represents an anion, preferably chloride or citrate.
Abstract:
The present invention generally relates to improved processes for the preparation of amphiphilic imidazolinium compounds such as 1-[2-(9(Z)-octadecenoyloxy)ethy1]-2-(8(Z)-heptadecenyl)-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM). In particular, the invention relates to processes for the synthesis of such compounds that avoid the need for toxic reagents, are more economical, and result in less waste than conventional methods. DOTIM and similar compounds can be formulated as cationic liposomes, which are useful as chemical vectors for nucleic acid delivery in gene therapy.
Abstract:
The invention relates to compositions comprising substituted imidazoline compounds including prodrugs, and salts thereof. In some embodiments, the invention relates to the use of these compositions as therapeutic agents, preferably for the treatment of arthritis or cancer. In further embodiments, The invention relates to the pharmaceutical compositions with effective amounts of substituted imidazoline compounds disclosed herein that function as agonist or antagonists of the genetic expression or interactions with transcription factor NF-κB.
Abstract:
The invention provides N,N'-disubstituted monothiourea or bisthiourea-Pd(0) complexes that are useful as catalysts for palladium-catalyzed Heck reaction of aryl iodides and bromides with olefins, and as catalysts for palladium catalyzed Suzuki reactions of organoboric compounds and aryl halides (Formula A).
Abstract:
The present invention relates to novel alkanoic acid derivatives thereof, their synthesis, and their use as alpha v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors alpha v beta 3 and/or alpha beta 5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth.