- Preparation method of 2-methylpyridine-4-formic acid
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The invention provides a preparation method of 2-methylpyridine-4-formic acid. The preparation method comprises the following steps: carrying out a substitution reaction on 4,4-dialkoxy butyronitrileor 4,4-dialkoxy butyrate (II) with chloroacetone, or carrying out a ring-opening addition reaction and oxidation reaction on 4,4-dialkoxy butyronitrile or 4,4-dialkoxybutyrate with propylene oxide toprepare 6,6-dialkoxy-4-cyano-n-hexyl-2-one or 6,6-dialkoxy-4-alkoxycarbonyl-n-hexyl-2-one (III); then carrying out a cyclization reaction with ammonia and ammonium salt; and finally carrying out an oxidation reaction and hydrolysis, and carrying out acidification by hydrochloric acid to prepare the 2-methylpyridine-4-formic acid (I). The method provided by the invention has mild conditions, concise process flow, and safe and simple operation; the generation amount of waste acid and waste water is small, greenness and environment friendliness are achieved; reaction selectivity is good; productcost is low; the yield and purity of the product are high; and green industrial production of 2-methylpyridine-4-formic acid and popularization of downstream products of 2-methylpyridine-4-formic acidare facilitated.
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Paragraph 0062-0076
(2019/11/28)
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- HUMAN PLASMA KALLIKREIN INHIBITORS
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Disclosed are compounds of formula I, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.
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Page/Page column 150
(2017/05/10)
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- PIPERIDINYLPYRAZOLOPYRIMIDINONES AND THEIR USE
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The present application relates to novel substituted piperidinylpyrazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired hemostatic disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of heavy menstrual bleeding, postpartum hemorrhage, hemorrhagic shock, hemorrhagic cystitis, gastrointestinal hemorrhage, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.
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Page/Page column 154
(2016/06/01)
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- (Aza)pyridopyrazolopyrimidinones and indazolopyrimidinones and their use
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The present application relates to novel substituted (aza)pyridopyrazolopyrimidinones and indazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired bleeding disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of menorrhagia, postpartum hemorrhage, hemorrhagic shock, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.
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Paragraph 0340 - 0342
(2015/05/13)
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- (AZA)PYRIDOPYRAZOLOPYRIMIDINONES AND INDAZOLOPYRIMIDINONES AS INHIBITORS OF FIBRINOLYSIS
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The present application relates to novel substituted (aza)pyridopyrazolopyrimidinones and indazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired bleeding disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of menorrhagia, postpartum hemorrhage, hemorrhagic shock, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.
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Page/Page column 61
(2015/05/26)
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- HUMAN PLASMA KALLIKREIN INHIBITORS
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Disclosed are compounds of formula (I), as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.
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Page/Page column 840
(2015/11/02)
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- INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF
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The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]
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Page/Page column 186; 187
(2013/02/27)
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- New 2-aminothiadiazole derivatives
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The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or N-oxide thereof: wherein: ? L represents a direct bond or a -S(O)2- group, ? n is an integer having a value from 0 to 2, ? R1 represents a pyridyl group or an imidazo[1,2-a]pyridinyl group, wherein the pyridyl group is substituted with one or more substituents selected from halogen atoms, a hydroxy group, a C1-4 alkyl group and a C1-4 alkoxy group, or ? R1 represents a group of formula: wherein: o Ra and Rb independently represent a hydrogen atom, halogen atom or a linear or branched C1-4 alkyl group, o Rc represents a hydroxy group, a linear or branched C1-4 alkyl group or C1-4 alkoxy group wherein the alkyl and the alkoxy groups independently are optionally substituted with one or more substituents selected from hydroxy group, cyano group and-NR'R" groups and wherein ■ R' represents a hydrogen atom or a linear or branched C1-4 alkyl group, ■ R" represents a hydrogen atom or a linear or branched C1-4 alkyl group optionally substituted with a hydroxycarbonyl group; or ■ R' and R" together with the nitrogen atom to which they are attached form a 4 to 6 membered, saturated heterocyclic ring optionally substituted with a hydroxycarbonyl group. ? R2 represents a pyridyl group, a C3-6 cycloalkyl group or a phenyl group which is optionally substituted with one or more substituents selected from halogen atoms, cyano group, and C1-4 alkoxy group; and ? R3 represents a C3-6 cycloalkyl group, a C3-6 cycloalkyl-C1-2 alkyl group or a linear or branched C2-4 alkyl group optionally substituted with one or more substituents selected from halogen atoms and C1-2 alkoxy group.
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Page/Page column 18
(2011/08/03)
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- NON-PEPTIDYL, POTENT, AND SELECTIVE MU OPIOID RECEPTOR ANTAGONISTS
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Selective, non-peptide antagonists of the ma opioid receptor { MOR) and methods of their use are provided. The antagonists may be used, for example, to identify MOR agonists in competitive binding assays, and to treat conditions related to addiction in which MOR is involved, e.g. heroin, prescription drug and alcohol addiction.
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Page/Page column 62
(2010/08/08)
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- BETA-LACTAMASE INHIBITORY COMPOUNDS
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Inhibitors of the enzyme beta-lactamase are provided. The compounds are adapted to inhibit beta-lactamase as produced by beta-lactam resistant bacterial strains. Methods of treatment of beta-lactam resistant bacterial infections in patients are provided.
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Page/Page column 46; 47
(2010/02/17)
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- Design, synthesis, and crystal structures of 6-alkylidene-2′- substituted penicillanic acid sulfones as potent inhibitors of acinetobacter baumannii OXA-24 carbapenemase
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Class D β-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial β-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel β-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2′-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important β-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 β-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC50 values against OXA-24 and two OXA-24 β-lactamase variants ranged from 10 ± 1 (4 vs WT) to 338 ± 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest Ki (500 ± 80 nM vs WT), and 1 possessed the highest inactivation efficiency (kinact/ Ki = 0.21 ± 0.02 μM-1 s-1). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 A) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2′-substituted penicillin sulfones are effective mechanism-based inactivators of class D β-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D β-lactamases is proposed.
- Bou, German,Santillana, Elena,Sheri, Anjaneyulu,Beceiro, Alejandro,Sampson, Jared M.,Kalp, Matthew,Bethel, Christopher R.,Distler, Anne M.,Drawz, Sarah M.,Pagadala, Sundar Ram Reddy,Van Den Akker, Focco,Bonomo, Robert A.,Romero, Antonio,Buynak, John D.
-
supporting information; scheme or table
p. 13320 - 13331
(2010/12/18)
-
- 2′ Biaryl amides as novel and subtype selective M1 agonists. Part I: Identification, synthesis, and initial SAR
-
Biaryl amides were discovered as novel and subtype selective M1 muscarinic acetylcholine receptor agonists. The identification, synthesis, and initial structure-activity relationships that led to compounds 3j and 4c, possessing good M1 agonist potency and intrinsic activity, and subtype selectivity for M1 over M2-5, are described.
- Budzik, Brian,Garzya, Vincenzo,Shi, Dongchuan,Foley, James J.,Rivero, Ralph A.,Langmead, Christopher J.,Watson, Jeannette,Wu, Zining,Forbes, Ian T.,Jin, Jian
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scheme or table
p. 3540 - 3544
(2010/08/22)
-
- FUSED THIAZOLE DERIVATIVES HAVING AFFINITY FOR THE HISTAMINE H3 RECEPTOR
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The present invention relates to novel fused thiazole derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.
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Page/Page column 30
(2008/06/13)
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- Process for the preparation of isonicotinic acid derivatives
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The present invention relates to a process for the manufacture of compounds of formula Ia or Ib and pharmaceutically acceptable additional salts thereof, wherein R is lower alkyl. The compounds of formula Ia or Ib are valuable intermediate products for the manufacture of compounds that are pharmaceutically active as adenosine A2a receptor antagonist or metabotropic Glutamate receptor 2 antagonist. Such compounds are important in the regulation of many aspects of cellular metabolism and in the modulation of different central nervous system activities.
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Page/Page column 3
(2010/11/08)
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- Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
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The present invention relates to new compounds of formula I, to pharmaceutical formulations containing the compounds, and to the use of the compounds in the prevention and/or treatment of mGluR5 receptor-mediated disorders.
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Page/Page column 57
(2008/06/13)
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- NEW COMPOUNDS
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The present invention relates to new compounds of formula I, (I) a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
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-
- Protease inhibitors
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The present invention provides compounds of formula (I) which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia or malignancy; and metabolic bone disease therewith.
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- Imidazole derivatives and their use as cytokine inhibitors
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As cytokine inhibitors 2,4,5-triarylimidazole compounds and compositions for use as cytokine inhibitors.
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-
- TRANSFORMATION OF 3-FORMYLCHROMONES INTO PYRIDINES AND PYRROLES
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Interaction of 3-formylchromones with ethyl aminoethanoate provides a novel route to pyridines and pyrroles.
- Fitton, Alan O.,Kosmirak, Mario,Suschitzky, Hans,Suschitzky, John L.
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p. 3953 - 3956
(2007/10/02)
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