- PIPERIDINYL-METHYL-PURINEAMINES AS NSD2 INHIBITORS AND ANTI-CANCER AGENTS
-
The present invention provides a compound of Formula (I): (I) or an enantiomer, an enantiomeric mixture, or a pharmaceutically acceptable salt thereof; wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds; and methods of using such compounds for treating a disease or condition mediated by nuclear SET domain-containing protein 2 (NSD2).
- -
-
Page/Page column 95
(2021/02/19)
-
- PDE9 inhibitor and uses thereof
-
The invention belongs to the technical field of medicines, particularly relates to a PDE9 inhibitor compound shown as a formula (I) or pharmaceutically acceptable salt, isomer, a deuterated compound,metabolite and prodrug thereof, and further relates to pharmaceutical preparations, pharmaceutical compositions and application of the compounds. X1, X2, X3, X4, R1, R2, ring A, L and m are defined inthe specification. The compounds can be used for preparing medicines for treating or preventing related diseases mediated by PDE9.
- -
-
Paragraph 0359; 0360; 0361; 0362
(2020/08/12)
-
- Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii
-
Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.
- Khalifa, Muhammad M.,Martorelli Di Genova, Bruno,McAlpine, Sarah G.,Gallego-Lopez, Gina M.,Stevenson, David M.,Rozema, Soren D.,Monaghan, Neil P.,Morris, James C.,Knoll, Laura J.,Golden, Jennifer E.
-
supporting information
p. 2382 - 2388
(2020/11/05)
-
- FUSED QUADRACYCLIC COMPOUNDS, COMPOSITIONS AND USES THEREOF
-
Provided herein are substituted fused quadracyclic compounds useful as inhibitors of MK2. The invention further provides pharmaceutical compositions of the compounds of the invention. The invention also provides medical uses of substituted fused quadracyclic compounds.
- -
-
Paragraph 0260
(2017/08/01)
-
- HETEROCYCLIC COMPOUND
-
The present invention provides a heterocyclic compound having an RORγt inhibitory action. The present invention relates to a compound represented by the formula (I): wherein Ar is a the partial structure (1) to the partial structure (5), Q is a bivalent group selected from the group consisting of (Ia)-(If), and B is a ring optinally having substituent(s), or a salt thereof.
- -
-
Paragraph 1070
(2016/03/18)
-
- Azaindole synthesis through dual activation catalysis with N-heterocyclic carbenes
-
A convergent, transition-metal-free synthesis of 2-aryl-azaindoles has been developed. The interception of a reactive aza-ortho-azaquinone methide intermediate by an acyl anion equivalent generated through carbene catalysis provides high yields, a wide substrate scope, and the synthesis of previously inaccessible azaindoles.
- Sharma, Hayden A.,Todd Hovey,Scheidt, Karl A.
-
supporting information
p. 9283 - 9286
(2016/07/25)
-
- SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
-
Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
- -
-
Paragraph 1163-1164
(2015/02/25)
-
- Iminooxazolidine Derivatives and Their Use
-
The present application relates to novel iminooxazolidine derivatives, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular thromboembolic disorders.
- -
-
Page/Page column 16
(2010/02/16)
-
- FUSED HETEROARYL PYRIDYL AND PHENYL BENZENESUFLONAMIDES AS CCR2 MODULATORS FOR THE TREAMENT OF INFLAMMATION
-
Compounds are provided that act as potent antagonists of the CCR2 receptor. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2- mediated diseases and as controls in assays for the identification of CCR2 antagonists. A compound of the formula (I) or a salt thereof: where: R1 and R2 are each independently hydrogen, halogen, C1-8alkyl, -CN. or C1-8 haloalkyl, provided that at least one of R11or R2 is other than hydrogen; each R3 is independently hydrogen; R4 is hydrogen; R5 is halogen or C1-8 alkyl; R6 is hydrogen; X1 is CR7, N or NO; X2 and X4 are N or NO; X3 is CR7; X6 and X7 are each independently selected from CR7, N, and NO; each R7 is independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C2-8 alkyl, substituted or unsubstituted C2-8 alkeπyl, substituted or unsubstituted C2-8 alkynyl, -CN. =O, -NO2, -OR6, -OC(O)R8, -CO2R8, -C(O)R8, -C(O)NR0R8, -OC(O)NR9R8, -NR10C(O)R8, -NR10C(O)NR9R8, -NR9R8, -NR10CO2R8, -SR8, -S(O)R8, -S(O)2R8, -S(O)2NR9R8, -NR10S(O)2R8, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl and substituted or unsubstituted 3- to 10-membered heterocyclyl;
- -
-
Page/Page column 58
(2009/03/07)
-
- HERBICIDAL COMPOUNDS
-
The present invention relates to a method of controlling plants or inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I): wherein A1, A2, A3, A4, R3, R4 and R5 are as defined in claim 1; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes for preparing compounds of formula (I), to intermediates used in the preparation of compounds of formula (I), to herbicidal compositions comprising compounds of formula (I) and to certain novel pyridopyridines, pyridodiazines and pyridotriazines.
- -
-
Page/Page column 45
(2009/08/16)
-
- Synthesis and antiviral activity of 7-benzyl-4-hydroxy-1,5-naphthyridin- 2(1H)-one HIV integrase inhibitors
-
The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naph
- Boros, Eric E.,Edwards, Cynthia E.,Foster, Scott A.,Fuji, Masahiro,Fujiwara, Tamio,Garvey, Edward P.,Golden, Pamela L.,Hazen, Richard J.,Jeffrey, Jerry L.,Johns, Brian A.,Kawasuji, Takashi,Kiyama, Ryuichi,Koble, Cecilia S.,Kurose, Noriyuki,Miller, Wayne H.,Mote, Angela L.,Murai, Hitoshi,Sato, Akihiko,Thompson, James B.,Woodward, Mark C.,Yoshinaga, Tomokazu
-
scheme or table
p. 2754 - 2761
(2010/01/16)
-
- BICYCLIC PYRIMIDIN-4-(3H)-ONES AND ANALOGUES AND DERIVATIVES THEREOF WHICH MODULATE THE FUNCTION OF THE VANILLOID-1 RECEPTOR (VR1)
-
Compounds of formula (I); which are useful as therapeutic compounds, particularly in the treatment of pain and other conditions ameliorated by the modulation of the function of the vanilloid-1 receptor (VR1).
- -
-
Page/Page column 39
(2010/02/12)
-
- COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA
-
The present invention discloses compounds of formula I wherein A, n, m, j, q, K, W, X, K, Z, R1, R2, R3, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and its sequelae.
- -
-
Page/Page column 53-54
(2008/06/13)
-
- Synthesis and SAR of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one as NMDA/glycine site antagonists
-
A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [3H]5,7-dicholorokynurenic acid ([3H]DCKA) in rat brain cortical membranes. Selected compounds were also tested for functional antagonism using electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor (NR) 1A/2C subunits. Among the 5-, 6-, 7-, and 8-aza-3-aryl-4-hydroxyquinoline-2(1H)-ones investigated, 5-aza-7-chloro-4-hydroxy-3-(3-phenoxyphenyl)quinolin-2-(1H)-one (13i) is the most potent antagonist, having an IC50 value of 110 nM in [3H]DCKA binding and a Kb of 11 nM in the electrophysiology assay. Compound 13i is also an active anticonvulsant when administered systemically in the mouse maximum electroshock-induced seizure test (ED50 = 2.3 mg/kg, IP).
- Zhou, Zhang-Lin,Navratil, James M.,Cai, Sui Xiong,Whittemore, Edward R.,Espitia, Stephen A.,Hawkinson, Jon E.,Tran, Minhtam,Woodward, Richard M.,Weber, Eckard,Keana, John F.W.
-
p. 2061 - 2071
(2007/10/03)
-
