- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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- ANTIMICROBIAL COMPOUNDS AND METHODS
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The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
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- SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
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The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 562
(2018/01/20)
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- Spirocyclic derivatives
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R5, R6, R9, R10, Q, X, Y, Z, A, L, B, m, n and p are as defined herein.
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- N-(HETERO)ARYL-SUBSTITUTED HETEROYCLIC DERIVATIVES USEFUL FOR THE TREATMENT OF DISEASES OR CONDITIONS RELATED TO THE CENTRAL NERVOUS SYSTEM
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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease, disorder or condition ameliorated by inhibition of a dopamine transporter); and methods of treating patients with such compounds; wherein R1, R2, R3, R4, R9a, R9b, R9c, R9d, R9e, R9f, m, n, A, L and B are as defined herein.
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- 2-[BIS(4-FLUOROPHENYL)METHYL]-2,7-DIAZASPIRO[4.5]DECAN-10-ONE DERIVATIVES AND RELATED COMPOUNDS AS INHIBITORS OF THE HUMAN DOPAMINE-ACTIVE-TRANSPORTER (DAT) PROTEIN FOR THE TREATMENT OF E.G. ATTENTION DEFICIT DISORDER (ADD)
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The present invention provides compounds of formula (I) and in particular 2-[bis(4-fluorophenyl)methyl]-2,7- diazaspiro[4.5]decan-10-one derivatives and related compounds as inhibitors of human dopamine-active-transporter (DAT) protein for the treatment of sexual dysfunction, affective disorders, anxiety, depression, chronic fatigue, Tourette syndrome, Angelman syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), obesity, pain, obsessive-compulsive disorder, movement disorders, CNS disorders, sleep disorders, narcolepsy, conduct disorder, substance abuse (including smoking cessation), eating disorders, and impulse control disorders.
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- ALKYL AND ARYL DERIVATIVES OF 1-OXA-4,9-DIAZASPIRO UNDECANE COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN
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The present invention relates to compounds of general formula (I) having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to diazaspiro undecane compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
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Page/Page column 173; 174
(2015/12/30)
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- Delayed and prolonged histone hyperacetylation with a selective HDAC1/HDAC2 inhibitor
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The identification and in vitro and in vivo characterization of a potent SHI-1:2 are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone hyperacetylation and
- Methot, Joey L.,Hoffman, Dawn Mampreian,Witter, David J.,Stanton, Matthew G.,Harrington, Paul,Hamblett, Christopher,Siliphaivanh, Phieng,Wilson, Kevin,Hubbs, Jed,Heidebrecht, Richard,Kral, Astrid M.,Ozerova, Nicole,Fleming, Judith C.,Wang, Hongmei,Szewczak, Alexander A.,Middleton, Richard E.,Hughes, Bethany,Cruz, Jonathan C.,Haines, Brian B.,Chenard, Melissa,Kenific, Candia M.,Harsch, Andreas,Secrist, J. Paul,Miller, Thomas A.
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p. 340 - 345
(2014/05/06)
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- PIPERIDINE-CONTAINING COMPOUNDS AND USE THEREOF
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A method for preventing and/or treating a metabolic disease, cerebrovascular disease, etc. which comprises administering to a mammal an effective amount of the compound of the formula (I) wherein all symbols have the same meanings as defined in the specification; a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. And a novel compound of the formula (I-1): wherein all symbols have the same meanings as defined in the specification; a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof has an anti-diabetic effect and a neuroprotective effect. Accordingly, the compound of the formula (I) and the compound of the formula (I-1) are useful in a method for preventing and/or treating for a metabolic disease such as diabetes, cerebrovascular disease such as stroke, etc.
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Page/Page column 224
(2010/08/04)
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- N,N'-2,4-DIANILINOPYRIMIDINE DERIVATIVES, PREPARATION THEREOF AS DRUGS, PHARMACEUTICAL COMPOSITIONS ESSENTIALLY AS IKK INHIBITORS
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The disclosure relates to a compound of formula (I): wherein R, R1, R2, R3, R4, R5, R6 and Z are as defined in the specification, to compositions containing them, to processes for preparing them, and to their use in the treatment or prevention of conditio
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Page/Page column 16
(2010/04/30)
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- Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists
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It is thought that selective 5-HT4 receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4-ylmethyl] benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4-ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT4 receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT4 receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N- (piperidin-4-ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT4 receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT4 receptor agonists, and had a similar effect on defecation to compound 2.
- Sonda, Shuji,Kawahara, Toshio,Katayama, Kenichi,Sato, Noriko,Asano, Kiyoshi
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p. 3295 - 3308
(2007/10/03)
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- N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists
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Compounds represented by Formula (I): 1or pharmaceutically acceptable salts thereof, are effective as NMDA NR2B antagonists useful for relieving pain.
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- Inhibitors of prenyl-protein transferase
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The present invention is directed to conformationally constrained compounds which inhibit prenyl-protein transferase and the prenylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.
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- Fused aromatic-spiropiperidine oxazepinones(and thiones)
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Novel aromatic-spiropiperidineoxazepinones and thiones exhibiting antihistamine activity are disclosed having the formula: STR1 wherein A represents an aromatic ring, selected from benzo when Z is carbon or pyrido[3,2-f] when Z is nitrogen either of which rings may be optionally substituted on carbon; B is selected from oxygen or sulfur; R1 is selected from the group consisting of loweralkyl, cycloalkyl, cycloalkyl-loweralkyl or phenyl-loweralkyl of which phenyl may be optionally substituted; R is selected from the group consisting of loweralkyl, cycloalkyl or phenyl-loweralkyl of which phenyl may be optionally substituted and the pharmaceutically acceptable salts thereof and novel chemical intermediates in the preparation thereof.
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