- KRAS G12C INHIBITORS
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The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0324
(2020/07/25)
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- ROCK KINASE INHIBITORS
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The present invention relates to compounds that inhibit ROCK activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention.
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Paragraph 0201-0203; 0273-0277
(2020/05/29)
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- Co-administration of dopamine-receptor binding compounds
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Methods for treating a patient having neurological, psychotic, and psychiatric disorders are described comprising the steps of administering to the patient an effective amount of a partial and/or full dopamine D1 receptor agonist, and administering to the patient an effective amount of a dopamine D2 receptor antagonist. Pharmaceutical compositions comprising a dopamine D1 receptor agonist and a dopamine D2 receptor antagonist are also described. The D1 dopamine receptor agonist and the D2 dopamine receptor antagonist can be administered to the patient in the same or in a different composition or compositions.
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Page/Page column 20
(2010/11/27)
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- Indazolecarboxamide derivatives, preparation and use thereof as CDK1, CDK2 and CDK4 inhibitors
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Compound corresponding to general formula (I): [image] in which, R1 represents a hydrogen or halogen atom, an NH2, NHR2, NHCOR2, NO2, CN, CH2NH2 and CH2NHR2; or alternatively R1 represents an optionally substituted phenyl or an optionally substituted heteroaromatic group; Ar represents an optionally substituted phenyl group or an optionally substituted heteroaromatic group; n represents 0, 1, 2 or 3; in the form of a base, of an addition salt with an acid, of a hydrate or of a solvate. Application in therapy.
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Page/Page column 20; 22
(2008/06/13)
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- METHOD OF ADMINISTRATION OF DOPAMINE RECEPTOR AGONISTS
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Methods for treating a patient having pulmonary edema are described. The methods include administering to the lung endobronchial space of the airways of the patient an effective amount of a dopamine D1 receptor agonist. Dopamine D1 receptor agonists, including hexahydrobenzophenanthridine, hexahydrothienophenanthridine, phenylbenzodiazepine, chromenoisoquinoline, naphthoisoquinoline dopamine receptor agonists, and their pharmaceutically acceptable salts, formulated as aerosols and dry powders are also described.
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Page/Page column 43
(2008/06/13)
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- NITROGENEOUS TRICYCLIC COMPOUND
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A novel compound represented by the following formula (1) [wherein R1, R5, R6, R7, and R8 each represents hydrogen, halogeno, hydroxy, alkyl, alkenyl, etc.; X1···X2 represents -C
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Page/Page column 194
(2010/11/08)
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- Nitrogen-containing tricyclic compounds
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A novel compound represented by the following formula (1) or a salt thereof [wherein R1, R5, R6, R7, and R8 represent hydrogen atom, a halogen atom, hydroxyl group, an alkyl group, an alkenyl group an
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Page/Page column 73-74
(2010/11/24)
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- 5-Substituted isoquinoline derivatives
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A compound represented by the following formula (1) or a salt thereof: wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents —O—X—C(A1)(A11)—C(A2)(A2l)—N(A3l)(A3)(X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.
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- Tricyclic compound
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A novel compound represented by the formula (1): [R1 represents hydrogen atom, chlorine atom, or hydroxyl group; X1 . . . X2 represents —CH(R2)—CH(R3)—, —CH(R2)—CH(R3)—CH(R4)—, etc.; R2to R4represent hydrogen atom, or an alkyl group; A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents —CH(A3)-, —CH(A3)-C(A4)(A41)-, —CH(A3)-C(A4)(A41)-C(A5)(A51)-, or a single bond; A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group; Z represents hydroxyl group, or —N(A6)(A61); A6 represents hydrogen atom, or an alkyl group, A61 represents hydrogen atom, an alkyl group, an aralkyl group, etc.; and groups in each of one or more combinations selected from the group consisting of combinations of A6 and A3, A6 and A4, A6 and A1, A6 and A2, A2 and A3, A2 and A4, A6 and A5, A3 and A1, and A5 and A1 may bind to each other to form a 5- or 6-membered ring], or a salt thereof, which potently inhibits the phosphorylation of myosin regulatory light chain.
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Page/Page column 58
(2010/02/11)
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- 8,9-Dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (dinoxyline), a high affinity and potent agonist at all dopamine receptor isoforms
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The synthesis and preliminary pharmacological evaluation of 8,9-dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (5, now named dinoxyline) is described. This molecule was designed as a potential bioisostere that would conserve the essential elements of our β-phenyldopamine D 1 pharmacophore (i.e., position and orientation of the nitrogen, hydroxyls, and phenyl rings). Previously, we have rigidified these elements using alkyl bridges, as exemplified in the dopamine D1 full agonist molecules dihydrexidine (1) and dinapsoline (2). This approach has been modified and we now show that it is possible to tether these elements using an ether linkage. Preliminary pharmacology has revealed that 5 is a potent full D1 agonist (K0.5 50=30 nM), but also has high affinity for brain D2-like and cloned D2 and D3 receptors. Interestingly, whereas 1 and 2 and their analogues have only moderate affinity for the human D4 receptor, 5 also has high affinity for this isoform. Moreover, although N-alkylation of 1 and 2 increases D2 affinity, the N-allyl (15) and N-n-propyl (17) derivatives of 5 had decreased D2 affinity. Therefore, 5 may be engaging different amino acid residues than do 1 and 2 when they bind to the D2 receptor. This is the first example of a ligand with high affinity at all dopamine receptors, yet with functional characteristics similar to dopamine. These rigid ligands also will be useful tools to determine specific residues of the receptor transmembrane domains that are critical for agonist ligand selectivity for the D4 receptor.
- Grubbs, Russell A.,Lewis, Mechelle M.,Owens-Vance, Connie,Gay, Elaine A.,Jassen, Amy K.,Mailman, Richard B.,Nichols, David E.
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p. 1403 - 1412
(2007/10/03)
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- Method of treatment of dopamine-related dysfunction
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The present invention relates to the treatment of dopamine-related dysfunction using full D1 dopamine receptor agonists in an intermittent dosing protocol with a short, but essential, “off-period.” The D1 agonist concentration is red
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- Chromeno[4,3,2-DE]isoquinolines as potent dopamine receptor ligands
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Novel dopamine receptor ligands of the formula: pharmaceutical formulations of such compounds, and a method using such compounds for treating a patient suffering from dopamine-related dysfunction of the central or peripheral nervous system, are described.
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- 3-Chloro-5-acetamidaisoquinoline as a herbicide
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Biologically active compositions of matter comprising substituted isoquinolines and salts thereof. Certain of the compounds and their salts are novel. Acaricidal, fungicidal, herbicidal and insecticidal activity is demonstrated. In particular 3-chloro-5-acetamido-isoquinoline shows good activity as a selective pre-emergence herbicide, and 4-bromo-5-nitro-isoquinoline shows good fungicidal activity against Erysiphe graminis (wheat powdery mildew).
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