- AMINO ALCOHOL DERIVATIVE, PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF
-
The present invention belongs to the field of medicine, and specifically discloses an amino alcohol derivative represented by Formula I, a pharmaceutically acceptable salt, solvate, polymorph or prodrug thereof. In addition, the present invention also discloses a pharmaceutical composition comprising the above substances, and a use of the substance in the preparation of a medicament for the prevention and treatment of an immune inflammatory disease, or a disease or condition associated with immunological competence such as multiple sclerosis, ALS, CIDP, systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, psoriasis, polymyositis, etc.
- -
-
Paragraph 0169; 0170
(2021/11/13)
-
- Novel monocyclic amide-linked phenol derivatives without mitochondrial toxicity have potent uric acid-lowering activity
-
Although benzbromarone (BBR) is a conventional, highly potent uricosuric drug, it is not a standard medicine because it causes rare but fatal fulminant hepatitis. We transformed the bis-aryl ketone structure of BBR to generate novel monocyclic amide-linked phenol derivatives that should possess uric acid excretion activity without adverse properties associated with BBR. The derivatives were synthesized and tested for uric acid uptake inhibition (UUI) in two assays using either urate transporter 1-expressing cells or primary human renal proximal tubule epithelial cells. We also evaluated their inhibitory activity against mitochondrial respiration as a critical mitochondrial toxicity parameter. Some derivatives with UUI activity had no mitochondrial toxicity, including compound 3f, which effectively lowered the plasma uric acid level in Cebus apella. Thus, 3f is a promising candidate for further development as a uricosuric agent.
- Uda, Junichiro,Kobashi, Seiichi,Ashizawa, Naoki,Matsumoto, Koji,Iwanaga, Takashi
-
supporting information
(2021/03/30)
-
- INHIBITORS OF LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE (LMPTP) AND USES THEREOF
-
Protein tyrosine phosphatases (PTPs) are key regulators of metabolism and insulin signaling. As a negative regulator of insulin signaling, the low molecular weight protein tyrosine phosphatase (LMPTP) is a target for insulin resistance and related conditions. Described herein are compounds capable of modulating the level of activity of low molecular weight protein tyrosine phosphatase (LMPTP) and compositions, and methods of using these compounds and compositions.
- -
-
Paragraph 00250
(2018/11/26)
-
- OXADIAZOLE MODULATORS OF S1P METHODS OF MAKING AND USING
-
The invention is directed to Compounds of Formula (I): wherein each variable is defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance for treating graft versus host disease and autoimmune diseases.
- -
-
Paragraph 0157
(2017/01/23)
-
- Preparation method of 3-cyano-4-isopropoxy methyl benzoate
-
The invention discloses a preparation method of 3-cyano-4-isopropoxy methyl benzoate. The preparation method comprises the following steps: step I, preparing 3-aldehyde-4-methyl hydroxybenzoate from methyl p-hydroxybenzoate; step II, preparing 3-cyano-4-m
- -
-
Paragraph 0010; 0018
(2017/08/29)
-
- Method for preparing 3-cyano-4-isopropoxybenzoic acid
-
The invention discloses a method for preparing 3-cyano-4-isopropoxybenzoic acid. A first step, 3-formyl-4-methyl hydroxybenzoate is prepared with methyl parahydroxybenzoate; a second step, 3-cyano-4-methyl hydroxybenzoate is prepared with the 3-formyl-4-methyl hydroxybenzoate; a third step, 3-cyano-4-methyl isopropoxybenzoate is prepared with the 3-cyano-4-methyl hydroxybenzoate; a fourth step, the 3-cyano-4-isopropoxybenzoic acid is prepared with the 3-cyano-4-methyl isopropoxybenzoate. The preparation method of the 3-cyano-4-isopropoxybenzoic acid, which is provided by the invention, has the advantages that 1) the use of the cuprous cyanide of hypertoxic cyanide in a previous process is avoided, and the method is more suitable for industrialization; 2) cyano is prepared by formyl, and the method is high-efficiency and direct, and is suitable for quantity production; 3) all raw materials are cheap and easily obtained, and the cost advantage is obvious.
- -
-
Paragraph 0020
(2017/08/29)
-
- DEUTERIUM-SUBSTITUTED OXADIAZOLES
-
Described are deuterated modulators of S1P1 receptors, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Paragraph 0140
(2016/10/31)
-
- Chromatography-free entry to substituted salicylonitriles: Mitsunobu-triggered domino reactions of salicylaldoximes
-
A mild and efficient one-pot procedure is described to transform salicylaldoximes into salicylonitriles using Mitsunobu chemistry. The reactions proceed through the corresponding 1,2-benzisoxazoles that undergo the Kemp elimination in situ to generate the
- Whiting, Ellis,Lanning, Maryanna E.,Scheenstra, Jacob A.,Fletcher, Steven
-
p. 1229 - 1234
(2015/01/30)
-
- NOVEL PHENOL DERIVATIVE
-
Disclosed are a novel compound and a pharmaceutical product, each having a remarkable uricosuric effect. Specifically disclosed are: a novel phenol derivative represented by general formula (1) that is shown in FIG. 1; a pharmaceutically acceptable salt t
- -
-
Page/Page column 19
(2012/07/28)
-
- COMPOUNDS
-
The present invention relates to novel compounds having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
- -
-
Page/Page column 22
(2011/11/12)
-
- COMPOUNDS AS AGONISTS OF S1P1 RECEPTORS
-
Compounds of formula (I), processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases mediated by S1P1 receptors.
- -
-
Page/Page column 42
(2011/11/12)
-
- OXADIAZOLE SUBSTITUTED INDAZOLE DERIVATIVES FOR USE AS SPHINGOSINE 1-PHOSPHATE 1 (S1P1) RECEPTOR AGONISTS
-
Oxadiazole substituted indazole derivatives of formula (I) or pharmaceutical salts thereof having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their uses in the treatment of various disorders mediated by S1P1 receptor are disclosed.
- -
-
Page/Page column 16; 25-26
(2011/07/07)
-
- Modulators of S1P and Methods of Making And Using
-
The invention is directed to Compounds of Formula I: as well as methods of making and using the compounds.
- -
-
Page/Page column 60
(2010/10/19)
-
- SUBSTITUTED 1,2,3,4- TETRAHYDROCYCLOPENTA[b]INDOL-3-YL) ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
-
The present invention relates to certain substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 receptor-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.
- -
-
Page/Page column 63
(2010/04/03)
-
- 1, 2 DISUBSTITUTED HETEROCYCLIC COMPOUNDS
-
1,2-disubstituted heterocyclic compounds which are inhibitors of phosphodiesterase 10 are described. Also described are processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of mammals, including human(s) for central nervous system (CNS) disorders and other disorders which may affect CNS function. Among the disorders which may be treated are neurological, neurodegenerative and psychiatric disorders including, but not limited to, those associated with cognitive deficits or schizophrenic symptoms.
- -
-
Page/Page column 108-109
(2010/01/30)
-
- COMPOUNDS
-
The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
- -
-
Page/Page column 39
(2009/12/05)
-
- CARBAMOYL-TYPE BENZOFURAN DERIVATIVES
-
The present invention provides a carbamoyl-type benzofuran derivative of the formula [1]: wherein Ring Z is a group of the formula: etc.; A is a single bond, and the like; Y is a cycloalkanediyl group, etc.; R4 and R5 are the same or different and each is an optionally substituted lower alkyl group, etc.; R1 is a halogen atom, etc.; Ring B of the formula: is an optionally substituted benzene ring; and R3 is a hydrogen atom, etc., or a pharmaceutically acceptable salt thereof, which is useful as an FXa inhibitor.
- -
-
Page/Page column 66
(2008/06/13)
-
- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
-
Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of one or more mitotic kinesins are disclosed.
- -
-
Page/Page column 253-254
(2008/06/13)
-
- BENZOFURAN DERIVATIVE
-
The present invention provides a benzofuran derivative of the formula [1]: wherein x is a group of the formula: -N="or" -CH=; Y is an optionally substituted amino group, an optionally substituted cycloalkyl group or an optionally substituted saturated heterocyclic group; A is a single bond, a carbon chain optionally having a double bond within or at the end(s) of the chain, or an oxygen atom; R1 is a hydrogen atom or a halogen atom; Ring B is an optionally substituted benzene ring; and R3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, which is useful as a medicament, especially as an activated blood coagulation factor X inhibitor.
- -
-
-
- Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide
-
Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.
- Madsen, Peter,Ling, Anthony,Plewe, Michael,Sams, Christian K.,Knudsen, Lotte B.,Sidelmann, Ulla G.,Ynddal, Lars,Brand, Christian L.,Andersen, Birgitte,Murphy, Douglas,Teng, Min,Truesdale, Larry,Kiel, Dan,May, John,Kuki, Atsuo,Shi, Shenghua,Johnson, Michael D.,Teston, Kimberly Ann,Feng, Jun,Lakis, James,Anderes, Kenna,Gregor, Vlad,Lau, Jesper
-
p. 5755 - 5775
(2007/10/03)
-
- Human glucagon receptor antagonists based on alkylidene hydrazides.
-
A series of alkylidene hydrazide derivatives containing an alkoxyaryl moiety was optimized. The resulting hydrazide-ethers were competitive antagonists at the human glucagon receptor. Pharmacokinetic experiments showed fast clearance of most of the compou
- Ling, Anthony,Plewe, Michael,Gonzalez, Javier,Madsen, Peter,Sams, Christian K,Lau, Jesper,Gregor, Vlad,Murphy, Doug,Teston, Kimberly,Kuki, Atsuo,Shi, Shenghua,Truesdale, Larry,Kiel, Dan,May, John,Lakis, James,Anderes, Kenna,Iatsimirskaia, Eugenia,Sidelmann, Ulla G,Knudsen, Lotte B,Brand, Christian L,Polinsky, Alex
-
p. 663 - 666
(2007/10/03)
-
- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
-
The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
- -
-
-
- Trisubstituted biphenyls
-
Antihypertensive and antiatherosclerotic trisubstituted biphenyls of the formula STR1 in which R1 represents a carboxyl radical or represents a C1 -C8 -alkoxycarbonyl radical, R2 represents straight-chain or bra
- -
-
-
