- UREA PEPTOID BORIC ACID COMPOUND, PHARMACEUTICAL COMPOSITION THEREOF, PREPARATION METHOD THEREFOR, AND USES THEREOF
-
The present invention provides a urea peptidomimetic boronic compound and pharmaceutical compositions thereof, their preparative methods and uses. The compounds are represented by the following formula (I).
- -
-
Paragraph 0153
(2018/09/08)
-
- FXR RECEPTOR MODULATOR, PREPARATION METHOD THEREFOR, AND USES THEREOF
-
The present disclosure disclosed a modulator of FXR receptor and preparation and use thereof, which relates to the technical filed of medicinal chemistry. The present disclosure provides a modulator of FXR receptor having a structural formula I or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, which can combine with FXR receptor (that is NR1H4) and be acted as a FXR agonist or a partial agonist for preventing and treating the disease mediated by FXR, such as chronic intrahepatic or extrahepatic cholestasis, hepatic fibrosis caused by chronic cholestasis or acute intrahepatic cholestasis, chronic hepatitis B, gallstone, hepatic carcinoma, colon cancer or intestinal inflammatory disease, etc. Specifically, for some chemical compounds, their EC50 for FXR agonist activity reach below 100nM, which show an excellent FXR agonist activity and an excellent prospect to provide a new pharmaceutical selection in clinical treatment for the disease mediated by FXR.
- -
-
Paragraph 0148; 0149
(2018/11/27)
-
- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
-
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
- -
-
Paragraph 0668
(2015/09/22)
-
- A structure-activity analysis of biased agonism at the dopamine D2 receptor
-
Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4-dihydroisoquinolin- 2(1H)-yl)ethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.
- Shonberg, Jeremy,Herenbrink, Carmen Klein,López, Laura,Christopoulos, Arthur,Scammells, Peter J.,Capuano, Ben,Lane, J. Robert
-
p. 9199 - 9221
(2014/01/06)
-
- NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
-
The present invention relates to novel carboxamide compounds, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating or controlling medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders
- -
-
-
- In vitro efficacy of 7-benzylamino-1-isoquinolinamines against Plasmodium falciparum related to the efficacy of chalcones
-
A series of 1,7-diaminoisoquinolinamines, that are expected to mediate antimalarial activity by the same mechanism employed by the chalcones, were produced. Six 7-benzylamino-1-isoquinolinamines were found to be submicromolar inhibitors in vitro of drug-r
- Gutteridge, Clare E.,Hoffman, Marshall M.,Bhattacharjee, Apurba K.,Milhous, Wilbur K.,Gerena, Lucia
-
scheme or table
p. 786 - 789
(2011/03/17)
-
- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
-
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
- -
-
-
- Substituted Spiroamide Compounds
-
Substituted spiroamide compounds corresponding to formula (I): wherein A, B, Q1, Q2, Q3, Q4, R1, R8, R9a, R9b, R12, R13, R200 and R210 have defined meanings, processes for their preparation, pharmaceutical compositions containing such compounds, and the use of such compounds for treating or inhibiting pain or other conditions mediated at least in part by the bradykinin 1 receptor (B1R).
- -
-
Page/Page column 21
(2010/09/18)
-
- BICYCLOANILINE DERIVATIVE
-
The invention relates to a compound of a general formula (I): wherein A1 and A2 each mean a nitrogen atom or an optionally-substituted methine group; Ring B means a 5-membered to 7-membered aliphatic ring, or a spiro or bicyclo ring formed from the aliphatic ring and any other 3-membered to 7-membered aliphatic ring; R1 means a hydrogen atom, or an optionally-substituted C1-C6 alkyl group, or an optionally-substituted aryl, aralkyl or heteroaryl group; R2 means an optionally-substituted aryl, aralkyl or heteroaryl group; and X means a group of =NH or =O, etc. Based on its excellent Wee1 kinase-inhibitory effect, the compound of the invention has cell growth-inhibitory effect and has an additive/synergistic effect with any other anticancer agent, and is therefore useful in the field of medicine.
- -
-
Page/Page column 56
(2010/04/25)
-
- PYRIDONE-SUBSTITUTED-DIHYDROPYRAZOLOPYRIMIDINONE DERIVATIVE
-
The invention relates to a compound of general formula (I-0): wherein R1 means a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, or a C3-C6 cycloalkyl group; R2, R3, R4 and R5 mean a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, or a halo-C1-C6 alkoxy group; R6 means a hydrogen atom, or a C1-C6 alkyl group; R7a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group, a hydroxy-C1-C6 alkyl group, -Q2-N(R1c)R1d or a nitrogen-containing heterocyclic group; R8a means a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a C1-C6 alkoxy group or a hydroxy-C1-C6 alkyl group; or R7a and R8a form, as taken together, a C2-C6 alkylene group, or R7a and R8a and the ring atoms to which they bond may form a spiro ring or a bicyclo ring; and X and Y mean a methine group or a nitrogen atom. The compound of the invention has, based on its excellent Wee1 kinase-inhibitory effect, a cell growth-inhibitory effect and an additive/synergistic effect with any other anticancer agent, and is therefore useful in the field of medicine.
- -
-
Page/Page column 53
(2010/08/09)
-
- Luminescent bimetallic lanthanide bioprobes for cellular imaging with excitation in the visible-light range
-
A series of homoditopic ligands H2LCX (X=4-6) has been designed to self-assemble with lanthanide ions (LnIII), resulting in neutral bimetallic helicates of overall composition [Ln 2(LCX)3] with the aim of testing the influence of substituents on the photophysical properties, particularly the excitation wavelength. The complex species are thermodynamically stable in water (logβ23 in the range 26-28 at pH 7.4) and display a metal-ion environment with pseudo-D3 symmetry and devoid of coordinated water molecules. The emission of EuIII, TbIII and Yb III is sensitised to various extents, depending on the properties of the ligand donor levels. The best helicate is [Eu2(L C5)3] with excitation maxima at 350 and 365 nm and a quantum yield of 9%. The viability of cervix cancer HeLa cells is unaffected when incubated with up to 500 μm of the chelate during 24 h. The helicate permeates into the cells by endocytosis and locates into lysosomes, which co-localise with the endoplasmatic reticulum, as demonstrated by counterstaining experiments. The relatively long excitation wavelength allows easy recording of bright luminescent images on a confocal microscope (μcxc = 405 nm). The new lanthanide bioprobe remains undissociated in the cell medium, and is amenable to facile derivatisation. Examination of data for seven Eu III and TbIII bimetallic helicates point to shortcomings in the phenomenological rules of thumb between the energy gap ΔE( 3ππ*-5DJ) and the sensitisation efficiency of the ligands.
- Deiters, Emmanuel,Song, Bo,Chauvin, Anne-Sophie,Vandevyver, Caroline D. B.,Gumy, Frederic,Buenzli, Jean-Claude G.
-
experimental part
p. 885 - 900
(2009/07/01)
-
- 6-SUBSTITUTED PHENOXYCHROMAN CARBOXYLIC ACID DERIVATIVES
-
Compounds of Formula (I): in which A1, A2, W, L, G, R7a, R7b, R8, R9 and R10 have the meanings given in the specification, are DP2 receptor modulators useful in the treatment of immunologic diseases.
- -
-
Page/Page column 107-108
(2010/01/30)
-
- PHARMACEUTICAL COMPOUNDS
-
The invention provides compounds which are pyrimidines of formula (I): wherein R2 is bonded at ring position 2 and -YR1 is bonded at ring position 5 or 6, or YR1 is bonded at ring position 2 and R2 is bonded at ring position 6; R is an indol-4-yl group which is substituted at the 5- or 6-position; either: (a) Y is selected from -O-(CH2)n-, -NH-(CH2)n-,. -NHC(O)-(CH2)n and -C(O)NH-(CH2)n- wherein n is 0 or an integer of 1 to 3, and R1 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic group which is unsubstituted or substituted and a group -NR3R4 wherein R3 and R4, which are the same or different, are each independently selected from H, C1-C6 alkyl which is unsubstituted or substituted, C3 - C10 cycloalkyl which is unsubstituted or substituted, -C(O)R, -C(O)N(R)2 and -S(O)mR, or R3 and R4 together form, with the nitrogen atom to which they are attached, a saturated 5-, 6- or 7- membered N-containing heterocyclic group which is unsubstituted or substituted; (b) Y is a direct bond and R1 is selected from an unsaturated 5- to 12-membered carbocyclic or heterocyclic group which is unsubstituted or substituted, and a group -NR3R4 wherein R3 and R4, which are the same or different, are each independently selected from H, C1-C6 alkyl which is unsubstituted or substituted, C3-C10 cycloalkyl which is unsubstituted or substituted, -C(O)R, -C(O)N(R)2 and -S(O)mR; R is selected from H, C1-C6 alkyl, C3-C10 cycloalkyl and a 5- to 12-membered aryl or heteroaryl group, which group is unsubstituted or substituted; and m is 1 or 2; or a pharmaceutically acceptable salt thereof. These compounds are inhibitors of PO K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PB kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
- -
-
Page/Page column 41
(2008/12/08)
-
- 5-HT7 receptor antagonists
-
The invention relates to compounds having pharmacological activity towards the 5-HT7 receptor, and more particularly to some tetrahydroisoquinoline substituted sulfonamide compounds, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which 5-HT is involved, such as CNS disorders.
- -
-
Page/Page column 9
(2008/06/13)
-
- COMPOUNDS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
-
The present invention relates to a class of small molecule hydroxamic acid compounds capable of inhibiting histone deacetylases (HDACs). The present invention also relates to methods of preparation of hydroxamic acid HDAC inhibitor compounds of the invent
- -
-
Page/Page column 13; 27-28
(2010/02/14)
-
- Amide derivatives and nociceptin antagonists
-
The present invention relates to a compound of the formula [1′] wherein R2is lower alkyl optionally substituted by hydroxy, amino and the like, ring B is phenyl, thienyl and the like, E is a single bond, —O—, —S— and the like, ring G is aryl, heterocyclic group and the like, R5is halogen atom, hydroxy, lower alkyl optionally substituted by halogen atom etc., and the like, t is 0 or an integer of 1 to 5, when t is an integer of 2 to 5, each R5may be the same or different, m is 0 or an integer of 1 to 8, and n is 0 or an integer of 1 to 4, and a nociceptin antagonist containing compound [1′] as an active ingredient. The compound [1′] shows, due to nociceptin antagonistic action, analgesic effect against sharp pain such as postoperative pain and the like. The present invention also relates to the use of certain amide derivative inclusive of compound [1′] as a nociceptin antagonist or analgesic.
- -
-
-
- Pharmaceutically active compounds
-
The invention relates to a class of tetrahydroisoquinolinylalkanoic acids containing an aryl sulphonamide group which have activity as thromboxane A2 antagonists.
- -
-
-
