- Discovery of clinical candidate (1 R,4 r)-4-((R)-2-((S)-6-Fluoro-5 H-imidazo[5,1-A[isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a potent and selective inhibitor of indoleamine 2,3-dioxygenase 1
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A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.
- Kumar, Sanjeev,Waldo, Jesse P.,Jaipuri, Firoz A.,Marcinowicz, Agnieszka,Van Allen, Clarissa,Adams, James,Kesharwani, Tanay,Zhang, Xiaoxia,Metz, Richard,Oh, Angela J.,Harris, Seth F.,Mautino, Mario R.
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p. 6705 - 6733
(2019/08/20)
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- DERIVATIVES OF PYRROLOIMIDAZOLE OR ANALOGUES THEREOF WHICH ARE USEFUL FOR THE TREATMENT OF INTER ALIA CANCER
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Present invention relates to novel heterocyclic compounds as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) modulators. Compounds of the present invention inhibit tryptophan degradation by modulating IDO and/or TDO. Formula (I) The invention further relates to the process of their preparation, pharmaceutical composition and their use in modulating the activity of indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3- dioxygenase (TDO). The compounds of the invention can be used alone or in combination for the treatment of conditions that benefits from the inhibition of tryptophan degradation.
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Page/Page column 100; 101
(2017/12/28)
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- COMPOUNDS FOR THE INHIBITION OF INDOLEAMINE-2,3-DIOXYGENASE
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The present invention relates to compounds, and pharmaceutically acceptable compositions thereof, useful as antagonists of IDO, and for the treatment of IDO-related disorders.
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Paragraph 0222-0223
(2016/04/09)
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- 4H-IMIDAZO[1,5-A]INDOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS
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This invention relates to novel compounds of formula (I) wherein wherein ?' is a 5 or 6 membered aryl or heteroaryl group, unsubstituted or substituted with 1, 2 or 3 groups as defined in claim 1; X is a bond or -(CRA1R81)n/sub
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Paragraph 00177
(2016/06/28)
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- Use of certain prostaglandin analogues to treat glaucoma and ocular hypertension
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Certain prostaglandin analogues are useful in the treatment of glaucoma and ocular hypertension. Also disclosed are ophthalmic, pharmaceutical compositions comprising such prostaglandin analogues.
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- 2,5,6,7-tetranor-4,8-inter-m-phenylene PGI2 derivatives
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Disclosed herein are novel prostaglandin I2 (PGI2) derivatives exhibiting excellent in vivo duration and activities, said derivatives being represented by the general formula: STR1 wherein R1, X, R2 and R3 are as defined herein.
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- 15-Cycloaliphatic derivatives of 13,14-didehydro-carboprostacyclins and process for their preparation
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13, 14 didehydro-15 cyclic prostacyclins have been prepared.
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- 9-Substituted carbacyclin analogs
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Novel compounds of the following formula: STR1
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- 9-Substituted carbacyclin analogs
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Novel compounds of the following general formula: STR1
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- 9-Substituted carbacyclin analogs
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Novel compounds of the following general formula: STR1
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- 15-Cycloalkyl-prostaglandins
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15-Cycloalkyl-prostaglandins of the formula:- STR1 wherein A represents a grouping of the formula:- STR2 X represents ethylene of cis-vinylene, Y represents ethylene or trans-vinylene, B represents ethylene or trans-vinylene, R represents hydrogen or alkyl of 1 through 4 carbon atoms, R1 represents cycloalkyl of 4 through 7 carbon atoms, and R2 represents hydrogen or alkyl of 1 through 12 carbon atoms, are new compounds possessing the useful pharmacological properties typical of prostaglandins; they are of especial interest in the inhibition of blood platelet aggregation.
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