通过立体保守方法合成了新的(R)-4-benzamido-5-oxopentanoic酸衍生物,并在体外评估了其抑制[125I](BH)-CCK-8与任一大鼠外周血(CCK-A)结合的能力)或中枢(CCK-B)CCK受体,或[3H] pentagastrin与兔胃腺的结合,以及在体内抑制五肽胃泌素在灌注的大鼠胃中输注所诱导的酸分泌。该系列的母体化合物(洛格米特)是CCK-A受体的第一种非肽类,有效和选择性拮抗剂。化学处理洛格鲁胺的结构导致发现CCK-B /胃泌素受体的选择性拮抗剂。讨论了构效关系。其中一些新衍生物与兔胃腺细胞和大鼠皮质膜表现出不同的亲和力,提示胃胃泌素受体(任意称为CCK-B1受体)与先前假设的与CCK中枢受体(称为CCK-B2)的关系不那么紧密。该系列中最有效的化合物,即(R)-4-(3,5-dichlorobenzamido)-5-(8-azaspiro [4.5] d
TGR5 agonists of structural formula VIII(Q), wherein X, R1, R2, and R5 are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
TGR5 agonists of structural formula VIII(Q), wherein X, R
1
, R
2
, and R
5
are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases.
The present invention relates to an aqueous polyurethane-urea dispersion and a preparation process thereof, an adhesive containing the same, and an adhesion article obtained by adhering with said adhesive. The aqueous polyurethane-urea dispersion comprises a polyurethane-urea dispersed therein, said polyurethane-urea is obtained from a reaction of a system comprising the following components: a polyisocyanate mixture; a polyester polyol having a melting temperature of greater than 32 °C, wherein the melting temperature is measured by using a DSC-7 from Perkin-Elmer at 20-100 °C according to DIN 6 5467, and taken from the first temperature-rising curve; an emulsifier; an optional monohydroxy polyether and an optional diamine; the polyisocyanate mixture contains hexamethylene diisocyanate and dicyclohexylmethane diisocyanate, the amount of hexamethylene diisocyanate is 0.01 wt% - 25 wt%, the amount of dicyclohexylmethane diisocyanate is 0.01 wt% -6 wt%, based on the amount of the system as 100 wt%. The adhesive containing the aqueous polyurethane-urea dispersion of the present invention has a low activation temperature and a good mechanical property.