- GPR52 MODULATOR COMPOUNDS
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The disclosures herein relate to novel compounds of Formula (1): (1) and salts thereof, wherein R1, Q, X, Y and Z are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of disorders associated with GPR52 receptors.
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Page/Page column 54; 87; 91
(2021/05/15)
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- RET inhibitor, pharmaceutical composition and application thereof
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The invention belongs to the field of medicines, and relates to an RET inhibitor, a pharmaceutical composition and application thereof, specifically to a compound as shown in a formula (I), or a stereoisomer, a geometrical isomer, a tautomer, nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug of the compound as shown in the formula (I). The invention also relates to a pharmaceutical composition comprising the compound, and use of the compound and the pharmaceutical composition thereof in manufacture of medicine, wherein the medicine is particularly used for treatment and prevention of diseases and disorders associated with available RET, including cancers, irritable bowel syndrome and/or pain associated with irritable bowel syndrome.
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Paragraph 0423; 0424
(2021/03/31)
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- RET Inhibitor. Pharmaceutical composition and use thereof
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The invention belongs to the field of medicines, and relates to a novel RET inhibitor, a pharmaceutical composition and application thereof. , The present invention relates to a compound represented by formula (I), a stereoisomer, a geometric isomer, a tautomer, an oxynitride, a solvate, a metabolite, a pharmaceutically acceptable salt or prodrug thereof, I, and a pharmaceutical composition thereof in the manufacture of a medicament, in particular for the treatment and prevention and RET of diseases and disorders associated with irritable bowel syndrome.
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Paragraph 0324-0325
(2021/11/26)
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- Development of inhibitors against mycobacterium abscessus tRNA (m1G37) Methyltransferase (TrmD) Using Fragment-Based Approaches
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Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in accelerated lung function decline and premature death. There is therefore an urgent need to develop novel antibiotics with improved efficacy. tRNA (m1G37) methyltransferase (TrmD) is a promising target for novel antibiotics. It is essential in Mab and other mycobacteria, improving reading frame maintenance on the ribosome to prevent frameshift errors. In this work, a fragment-based approach was employed with the merging of two fragments bound to the active site, followed by structure-guided elaboration to design potent nanomolar inhibitors against Mab TrmD. Several of these compounds exhibit promising activity against mycobacterial species, including Mycobacterium tuberculosis and Mycobacterium leprae in addition to Mab, supporting the use of TrmD as a target for the development of antimycobacterial compounds.
- Whitehouse, Andrew J.,Thomas, Sherine E.,Brown, Karen P.,Fanourakis, Alexander,Chan, Daniel S.-H.,Libardo, M. Daben J.,Mendes, Vitor,Boshoff, Helena I. M.,Floto, R. Andres,Abell, Chris,Blundell, Tom L.,Coyne, Anthony G.
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supporting information
p. 7210 - 7232
(2019/08/20)
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- MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of compound formula (I).
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Page/Page column 40-41
(2018/03/25)
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- Modular Route to Azaindanes
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A convergent radical based route to azaindanes is described, relying on the degenerative addition transfer of various substituted S-(pyridylmethyl)-O-ethyl dithiocarbonates (xanthates) to functional alkenes followed by radical cyclization onto the pyridine ring activated by protonation with trifluoroacetic acid. In one case, a richly decorated cyclohepta[b]pyridine could be assembled swiftly by allowing the first adduct to N-phenylmaleimide to undergo addition to N-allylphthalimide prior to cyclization.
- Huang, Qi,Zard, Samir Z.
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supporting information
p. 3895 - 3898
(2017/07/26)
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- HETEROARYL SUBSTITUTED HETEROCYCLYL SULFONES
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The invention relates to aryl substituted heterocyclyl sulfones as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
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Page/Page column 132
(2015/11/09)
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- Synthesis and reduction reactions of pyridones and 5-acyl-2-methoxypyridines
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The synthesis of a series of pyridones, from their 2-hydroxypyridine or 2-methoxypyridine precursors, is described, along with studies into their reductions to saturated heterocycles. A number of 5-acylpyridones were prepared and were evaluated as substrates for asymmetric transfer hydrogenation prior to conversion to saturated heterocycles. The enantioselective reduction of 5-acetyl-1-benzylpyrimidine-2,4(1H,3H)-dione is also described.
- Bisset, Alexander A.,Dishington, Allan,Jones, Teyrnon,Clarkson, Guy J.,Wills, Martin
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p. 7207 - 7220
(2017/09/12)
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- HETEROARYL INHIBITORS OF PDE4
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The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of disease.
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Paragraph 0808
(2014/05/24)
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- Palladium-catalyzed arylation of aldehydes with bromo-substituted 1,3-diaryl-imidazoline carbene ligand
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The combination of 0 valent palladium precursor and bromo-substituted 1,3-diaryl-imidazoline carbene ligand precursor such as 1-(2-bromophenyl)-3-(2,6-diisopropylphenyl)-imidazolinium chloride 1a exhibited high catalytic activity for the 1,2-addition of arylboronic acids to aldehydes including aqueous formaldehyde.
- Yamamoto, Tetsuya,Furusawa, Takuma,Zhumagazin, Azamat,Yamakawa, Tetsu,Oe, Yohei,Ohta, Tetsuo
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- Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity
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(-)-6-(7-Methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4, 5-dihydro-3-(2H)-pyridazinone (KCA-1490) is a dual PDE3/4 inhibitor that exhibits potent combined bronchodilatory and anti-inflammatory activity. A survey of potential bicyclic heteroaromatic replacement subunits for the pyrazolo[1,5-a]pyridine core of KCA-1490 has identified the 4-methoxy-2- (trifluoromethyl)benzo[d]thiazol-7-yl and 8-methoxy-2-(trifluoromethyl)quinolin- 5-yl analogues as dual PDE3/4-inhibitory compounds that potently suppress histamine-induced bronchoconstriction and exhibit anti-inflammatory activity in vivo.
- Ochiai, Koji,Takita, Satoshi,Eiraku, Tomohiko,Kojima, Akihiko,Iwase, Kazuhiko,Kishi, Tetsuya,Fukuchi, Kazunori,Yasue, Tokutaro,Adams, David R.,Allcock, Robert W.,Jiang, Zhong,Kohno, Yasushi
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supporting information; experimental part
p. 1644 - 1658
(2012/04/23)
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- N-LINKED HYDROXAMIC ACID DERIVATIVES USEFUL AS ANTIBACTERIAL AGENTS
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The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors, and more specifically their use to treat bacterial infections. Formula (I).
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Page/Page column 123
(2011/07/07)
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- Inhibitors of protein kinases
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Compounds of general Formula (I): wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.
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Page/Page column 23
(2011/10/04)
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- Synthesis of bridgehead-substituted azabicyclo[2.2.1]heptane and -[3.3.1]nonane derivatives for the elaboration of α7 nicotinic ligands
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Azabicyclo[2.2.1]heptane and -[3.3.1]nonane scaffolds (X = Cl, Br) containing a pyridinyl substituent at the bridgehead position were prepared via two complementary chemical pathways, either by the transformation of a methoxy group into a synthetically valuable chlorine atom at the C-6 position of the pyridine moiety or by means of a regioselective C-6 deprotonation/halogenation process of the pyridine moiety exemplified by chlorination or bromination. These newly generated scaffolds were then engaged in Suzuki-Miyaura coupling reactions to provide α7 nicotinic ligands. Both chemical series were evaluated in vitro for their affinity at α7 nicotinic receptors, revealing nanomolar potency with significant selectivity over the α4Β2 nicotinic subtype. These approaches offer a general access to these α7 nicotinic scaffolds and ligands.
- Slowinski, Franck,Ben Ayad, Omar,Vache, Julien,Saady, Mourad,Leclerc, Odile,Lochead, Alistair
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experimental part
p. 8336 - 8346
(2011/12/22)
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- TETRAHYDROQUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to tetrahydroquinoline amide compounds of formula (I) (Formula should be inserted here) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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Page/Page column 31-32
(2012/01/06)
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- HETEROCYCLIC FUSED PHENANTHROLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to heterocyclic fused phenanthrolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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Page/Page column 27-28
(2012/01/06)
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- QUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
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The present invention is directed to quinoline amide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
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Page/Page column 54-55
(2011/08/03)
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- Inhibition of 1-deoxy-d-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies
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1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including antituberculosis) and antimalaria drugs. Forty-one lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a K i of 420 nM. Structure-activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been performed well, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198-208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors.
- Deng, Lisheng,Diao, Jiasheng,Chen, Pinhong,Pujari, Venugopal,Yao, Yuan,Cheng, Gang,Crick, Dean C.,Prasad, B. V. Venkataram,Song, Yongcheng
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experimental part
p. 4721 - 4734
(2011/09/19)
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- SALT OF 5-[2-AMINO-4-(2-FURYL)PYRIMIDIN-5-YL]-1-METHYLPYRIDIN-2(1H)-ONE AND CRYSTAL THEREOF
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The present invention provides a salt of 5-[2-amino-4-(2-furyl)pyrimidin-5-yl]-1-methylpyridin-2(1H)-one and a crystal thereof.
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Page/Page column 3-4
(2010/08/03)
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- Synthesis of new bridgehead substituted azabicyclo-[2.2.1]heptane and -[3.3.1]nonane derivatives as potent and selective α7 nicotinic ligands
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New azabicyclo[2.2.1]heptane and -[3.3.1]nonane derivatives containing a pyridinyl substituent at the bridgehead position have been synthesized via an efficient ten chemical steps pathway. Both chemical series were then evaluated in vitro for their affinity at α7 nicotinic receptors revealing nanomolar potency with notably excellent selectivity over the α4β2 nicotinic subtype.
- Slowinski, Franck,Ayad, Omar Ben,Vache, Julien,Saady, Mourad,Leclerc, Odile,Lochead, Alistair
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supporting information; experimental part
p. 5004 - 5007
(2010/12/25)
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- PYRAZOLOPYRIDINE DERIVATIVE AND PHOSPHODIESTERASE (PDE) INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
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A novel pyrazolopyridine derivative is provided which is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine derivative is represented by the following general formula (1): [wherein R1 is a hydroge
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Page/Page column 36-37
(2009/06/27)
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- PYRAZOLOPYRIDINE CARBOXAMIDE DERIVATIVE AND PHOSPHODIESTERASE (PDE) INHIBITOR COMPRISING THE DERIVATIVE
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A novel pyrazolopyridine carboxamide derivative is provided that is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine carboxamide derivative is represented by the following general formula (1): (Example: 2-
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Page/Page column 50
(2009/06/27)
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- Substituted 2-oxo-azepane derivatives are potent, orally active γ-secretase inhibitors
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A hydroxamic acid screening hit 1 was elaborated to 5,5-dimethyl-2-oxoazepane derivatives exhibiting low nanomolar inhibition of γ-secretase, a key proteolytic enzyme involved in Alzheimer's disease. Early ADME data showed a high metabolic clearance for t
- Kitas, Eric A.,Galley, Guido,Jakob-Roetne, Roland,Flohr, Alexander,Wostl, Wolfgang,Mauser, Harald,Alker, Andre M.,Czech, Christian,Ozmen, Laurence,David-Pierson, Pascale,Reinhardt, Dieter,Jacobsen, Helmut
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p. 304 - 308
(2008/04/07)
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- Pyrazolones as inhibitors of 11B-hydroxysteroid dehydrogenase
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, type II diabetes mellitus and metabolic syndrome.
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Page/Page column 38
(2008/06/13)
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- Fluoro substituted 2-oxo-azepan derivatives
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The invention relates to compounds of general formula wherein R1, R2, R3/R3′, R4/R4′ and R5/R5′ are as defined in the specification and to pharmaceutically acceptable
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Page/Page column 10
(2008/06/13)
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- Crystals of 5-[2-amino-4-(2-furyl) pyrimidin-5-yl]-1-methylpyridin-2(1H)-one and processes for preparing the same
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Crystals of 5-[2-amino-4-(2-furyl)pyrimidin-5-yl]-1-methylpyridin-2(1H)-one having a diffraction peak at a diffraction angle (2θ±0.2°) of 12.8°, 18.1° and/or 23.5° in a powder X-ray diffraction are excellent in stability against light, therefore are suitable for an active ingredient of a preventing and therapeutic agent for diseases such as constipation.
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Page/Page column 3
(2008/06/13)
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- Sulfonamides
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The invention relates to compounds of the general formula in which R1, R2, R3, R4, R2′, R3′, R4′, R5, and X is —CHR— are as defined in the specification. The invention also provides pharmac
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Page/Page column 39
(2010/02/15)
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- FIVE-MEMBERED HETEROCYCLIC DERIVATIVE
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The present invention relates to a compound represented by formula (I): a salt of the compound, or a solvate of the compound or the salt; a drug containing any of the compounds, the salts, and the solvates; a preventive and/or therapeutic agent for an ischemic disease containing any of the compounds, the salts, and the solvates; and a platelet coagulation inhibitor containing any of the compounds, the salts, and the solvates. The compound of the present invention is useful as a strong platelet coagulation inhibitor without inhibiting COX-1 or COX-2.
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Page/Page column 35
(2010/11/08)
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- NOVEL PYRIDINONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
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The present invention relates to novel compounds, in particular novel pyridinone derivat ives according to Formula (I) X R1 N Y (I) R2 R3 wherein all radicals are defined in the application. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subt ype 2 ("mGluR2") which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved. "
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Page/Page column 104-105
(2010/10/20)
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- New amino acids from the poisonous mushroom Clitocybe acromelalga
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New amino acids, L-3-(2-carboxy-4-pyrrolyl)-alanine (1) and L-3-(2-oxo-5-pyridyl)-alanine (2), were isolated from Clitocybe acromelalga and their structures were deduced by spectral data and biogenesis and confirmed by syntheses. Stizolobic acid (5) was also found in this fungus.
- Yamano, Kimiaki,Shirahama, Haruhisa
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p. 1457 - 1464
(2007/10/02)
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- Process for the preparation of 2-chloro-5-chloromethylpyridine
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A process for the preparation of 2-chloro-5-chloromethylpyridine of the formula (I) STR1 which is used as an intermediate for the preparation of insecticides, the process comprising (a) reacting in a first step nicotinic acid of the formula (II) STR2 with phosphorus pentachloride, if appropriate in the presence of thionyl chloride and if appropriate in the presence of a diluent, (b) reacting in a second step the resulting 3-trichloromethylpyridine from the first step, of the formula III, STR3 with an alkali metal alkoxide of the formual (IV) in which R represents alkyl and M represents an alkali metal cation, if appropriate in the presence of a diluent, (c) reacting in a third step the resulting pyridine ether acetal from the second step, of the formula (V), STR4 in which R has the abovementioned meaning with water, if appropriate in the presence of a catalyst acid, (d) hydrogenating in a fourth step the resulting pyridine aldehyde from the third step, of the formula (VI), STR5 in which R has the abovementioned meaning with molecular hydrogen in the presence of a hydrogenation catalyst and, if appropriate, in the presence of a diluent, and, finally, (e) reacting in a fifth step the resulting pyridylmethanol from the fourth step of the formula (VII), STR6 in which R has the abovementioned meaning.
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