- Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors
-
A series of macrocyclic analogues were designed and synthesized based on the cocrystal structure of small molecule plasma kallikrein (pKal) inhibitor, 2, with the pKal protease domain. This led to the discovery of a potent macrocyclic pKal inhibitor 29, w
- Li, Zhe,Partridge, James,Silva-Garcia, Abel,Rademacher, Peter,Betz, Andreas,Xu, Qing,Sham, Hing,Hu, Yunjin,Shan, Yuqing,Liu, Bin,Zhang, Ying,Shi, Haijuan,Xu, Qiong,Ma, Xubo,Zhang, Li
-
-
Read Online
- As neuroprotective agents of pharmaceutical compounds
-
The invention discloses a medicinal compound as a neuroprotective agent. The medicinal compound is a neuronal nitric oxide synthase-postsynaptic density protein 95 (nNOS-PSD95) decoupling agent. The medicinal compound is a benzene ring derivative shown in the general formula (I) or its pharmaceutically acceptable salt. The invention further discloses a preparation method of the medicinal compound and a use of the medicinal compound in prevention and treatment on neuronal damage influence-caused diseases.
- -
-
-
- A pharmaceutical composition containing 2-hydroxy-7-methyl octahydrophenanthrene derivative as an estrogen receptor ligand or a pharmaceutically acceptable salt thereof as an effective component
-
Provided are a compound represented by chemical formulas I and II, or a pharmaceutically acceptable ester, amide, or carbamate salt thereof; and a solvent compound comprising a solvent compound of the ester, amide, or carbamate salt thereof. In addition, provided are use of the compound in treating or preventing diseases or disorders related to activation of an estrogen receptor, and a pharmaceutical composition comprising the compound. In chemical formulas I and II, definitions of R_1, R_2, R_3, and R_4 are the same as those in the specification.COPYRIGHT KIPO 2016
- -
-
-
- PHARMACEUTICAL COMPOUNDS
-
This invention relates to compounds that inhibit or modulate the activity of Chk-1 kinase. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds.
- -
-
-
- Mild Benzylic Monobromination of Methyl Toluates in Aqueous CTAB
-
A strategy has been developed for the regioselective monobromination of methyl toluates by using tert-butylhydrogen peroxide and potassium bromide (TBHP/KBr) in a cetyltrimethylammonium bromide (CTAB) micellar medium. Ultrasonic and microwave-assisted protocols recorded increased rates and product yields under mild reaction conditions, coupled with a straightforward isolation procedure.
- Reddy, Kancharla Rajendar,Rajanna, Kamatala C.,Venkateswarlu, Marri,Saiprakash
-
p. 2485 - 2487
(2015/07/27)
-
- COMPOUNDS HAVING MUSCARINIC RECEPTOR ANTAGONIST AND BETA2 ADRENERGIC RECEPTOR AGONIST ACTIVITY
-
Compounds of formula (I) defined herein act both as muscarinic receptor antagonists and beta2 adrenergic receptor agonists and are useful for the prevention and/or treatment of broncho-obstructive or inflammatory diseases.
- -
-
Paragraph 0313-0314
(2014/06/24)
-
- TRIAZOLONE COMPOUNDS AS mPGES-1 INHIBITORS
-
The present disclosure is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthma, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases.
- -
-
Page/Page column 107; 108
(2014/01/08)
-
- Design, synthesis and biological evaluation of nuclear receptor-degradation inducers
-
Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation in
- Itoh, Yukihiro,Kitaguchi, Risa,Ishikawa, Minoru,Naito, Mikihiko,Hashimoto, Yuichi
-
p. 6768 - 6778
(2012/01/13)
-
- NOVEL FIVE-MEMBERED RING COMPOUND
-
Disclosed is a five-membered ring compound represented by formula (1) or a pharmaceutically acceptable salt thereof. The compound inhibits infiltration of leukocytes including eosinophils and lymphocytes, and is effective as a drug for treating various inflammations. The compound is highly safe and can be administered for a long period. A pharmaceutical product containing the five-membered ring compound or a pharmaceutically acceptable salt thereof is also disclosed. (In the formula, R1 represents a halogen atom or a phenyl group which may be substituted by a C1-C3 alkyl group or a C1-C3 alkoxy group; R2 represents a C1-C3 alkylene group which may be substituted by a C1-C3 alkyl group or a carbonyl group; R3 represents a C1-C3 alkyl group; R4 and R5 independently represent a hydrogen atom or a C1-C3 alkyl group, or -N(R4)R5 may represent a morpholino group which may be substituted by a C1-C3 alkyl group; Y2 represents a C2-C4 alkylene group; and R6 represents a hydrogen atom, a halogen atom, a C1-C3 alkyl group or a C1-C3 alkoxy group.)
- -
-
Page/Page column 19-20
(2011/02/17)
-
- IMIDAZOLE CARBOXAMIDES
-
The present invention provides certain imidazole carboxamide derivatives, pharmaceutical compositions thereof, methods of using the same and processes for preparing the same.
- -
-
Page/Page column 13
(2010/02/17)
-
- PIPERIDINE DERIVATIVES AS HUMAN PAPILLOMA VIRUS INHIBITORS
-
HPV inhibitors with formula (I) where G1 represents a hydrocarbonated bond or chain possibly substituted by one or two alkyl groups, G2 represents a group (see formula Ia+Ib) or R represents a hydrogen, an alkyl, halogenoalkyl, or a prodrug radical such as carbamate, acetyl or dialkylaminomethyl, G represents a bond or a hydrocarbonated chain possibly substituted by one or two alkyls, W represents an oxygen or sulphur, R1 and R2 each represent a group chosen from among hydrogen, halogen, hydroxyl, thio, alkoxy, halogenoalkoxy, alkylthio, halogenoalkylthio, amino, monoalkylamino, dialkylamino, cycloalkyl, alkyl or halogenoalkyl, R3 represents an acid or a prodrug radical of the acid function or a bioisostere of the acid function, A represents an aryl, cycloalkyl, cycloalkenyl or a heterocycle, each possibly substituted, and B represents an aryl or a heterocycle with 6 chains, each possibly substituted, and pharmaceutically acceptable salts.
- -
-
Page/Page column 13
(2009/09/05)
-
- NOVEL ADENINE COMPOUND
-
A novel adenine compound represented by the formula (1): wherein A represents an (un)substituted aromatic carbocycle or (un)substituted aromatic heterocycle; L1 and L2 each independently represents straighted or branched alkylene, et
- -
-
Page/Page column 54-55
(2009/12/27)
-
- NOVEL BENSOPHENONE DERIVATIVES OR SALTS THEREOF
-
A benzophenone derivative represented by the following formula: whereinR1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R2 represents, for example, a carboxyl group optionally protected with alkyl;R3 represents, for example, an optionally protected hydroxyl group; R4 represents, for example, an optionally substituted cycloalkyloxy group; and R5 represents, for example, a hydrogen atom, ???or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.
- -
-
Page 119-120
(2010/02/07)
-
- ANTITHROMBOTIC ETHERS
-
This application relates to a compound of formula I (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa and/or thrombin, as well as a process for its preparation and intermediates therefor (I).
- -
-
-
- FUSED PYRIMIDINONE MATRIX METALLOPROTEINASE INHIBITORS
-
Selective MMP-13 inhibitors are fused pyrimidinones of the formula or a pharmaceutically acceptable salt thereof, wherein: W, together with the carbon atoms to which it is attached, form a 5-membered ring diradical X is O, S, SO, SO2, NR5, or CH 2; B is O or NR5; or A and B are taken together to form--C≡C--; R1, R4, and R 5 are hydrogen, alkyl, alkenyl, alkynyl, (CH2)n aryl, (CH2)n cycloalkyl, C1-C6 alkanoyl, or (CH2)n heteroaryl; R2 and R3 are hydrogen, alkyl, alkenyl, alkynyl CN, NO2, NR 4R5, (CH2)n cycloalkyl, (CH2) n aryl, or (CH2)n heteroaryl; R2 may further be halo; n is an integer of from 0 to 5; and R4 and R5 when taken together with a nitrogen to which they are both attached complete a 3-to 8-membered ring containing carbon atoms and optionally containing O, S, or N, and substituted or unsubstituted; with the proviso that R1 and R3 are not both selected from hydrogen and C1-C6 alkyl.
- -
-
-
- Antithrombotic agents
-
This application relates to novel compounds of formula I (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula I, and the
- -
-
-
- Superoxide dismutase mimetics: synthesis and structure-activity relationship study of MnTBAP analogues.
-
Carboxylic ester and amide-substituted analogues of [5,10,15,20-tetrakis(4-carboxyphenyl)-porphyrinato]manganese(III) chloride (MnTBAP) were synthesized and assayed as potential superoxide dismutase (SOD) mimetics. The tetraester analogues 4a and 4b were
- Gauuan, Polivina Jolicia F,Trova, Michael P,Gregor-Boros, Livia,Bocckino, Stephen B,Crapo, James D,Day, Brian J
-
p. 3013 - 3021
(2007/10/03)
-
- Sulfonamide derivatives, their production and use
-
The present invention provides compounds which specifically inhibit FXa, which are effective when orally administered and which are useful as a safe medicine for the prevention or treatment of diseases caused by thrombus or infarction. Compounds of this invention are piperazinones of the formula: wherein R1is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group of the formula: and the group of the formula: Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group; X is a direct bond or an optionally substituted alkylene chain; Z is (1) an amino group substituted with an optionally substituted hydrocarbon group, (2) an optionally substituted imino group or (3) an optionally substituted nitrogen-containing heterocyclic group; provided that when X is a direct bond and Z is an optionally substituted 6-membered nitrogen-containing aromatic heterocyclic group, Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group; or a salt thereof.
- -
-
Referential example 28
(2010/11/29)
-
- Antithrombotic agents
-
This application relates to novel compounds of formula I (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula I, and the
- -
-
-
- Amide derivatives having ACAT inhibitory activity, their preparation and their therapeutic and prohylactic use
-
Compounds of formula (I): STR1 wherein: R1 is alkyl; R2a, R2b, R2c and R2d are the same or different and each is hydrogen, optionally substituted alkyl, --(C=O)--B1 (wherein B1 i
- -
-
-
- 5-SUBSTITUTED IMIDAZO[4,5-C]PYRIDINES
-
The present invention relates to a class of compounds represented by the formula STR1 or a pharmaceutically acceptable salt thereof useful in the treatment of diseases or disorders mediated by platelet activating factor (PAF).
- -
-
-
- Secondary amines, their preparation and use in pharmaceutical compositions
-
The compounds of the formula (II): STR1 and their pharmaceutically acceptable salts wherein R1 is a hydrogen, fluorine or chlorine atom or a hydroxyl, hydroxymethyl, methyl, methoxyl, amino, formamido, acetamido, methylsulphonylamido, nitro, benzyloxy, methylsulphonylmethyl, ureido, trifluoromethyl or p-methoxybenzylamino group; R2 is a hydrogen, fluorine or chlorine atom or a hydroxyl group; R3 is a hydrogen or chlorine atom or a hydroxyl group; R4 is a carboxylic acid group or a salt, ester or amide thereof; R5 is a hydrogen, chlorine or fluorine atom or a methyl, methoxyl or hydroxyl group or a carboxylic acid group or a salt, ester or amide thereof; R6 is a hydrogen atom or a methyl, or propyl group; X is an oxygen atom or a bond; and Y is an alkylene group of up to 6 carbon atoms or a bond have been found to possess anti-obesity and/or antihyperglycaemic activity.
- -
-
-
