- Discovery and Structure-Activity Relationships of Nociceptin Receptor Partial Agonists That Afford Symptom Ablation in Parkinson's Disease Models
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A novel series of C(3)-substituted piperdinylindoles were developed as nociceptin opioid receptor (NOP) partial agonists to explore a pharmacological hypothesis that NOP partial agonists would afford a dual pharmacological action of attenuating Parkinson'
- Kamakolanu, Uma Gayathri,Meyer, Michael E.,Yasuda, Dennis,Polgar, Willma E.,Marti, Matteo,Mercatelli, Daniela,Pisanò, Clarissa Anna,Brugnoli, Alberto,Morari, Michele,Zaveri, Nurulain T.
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p. 2688 - 2704
(2020/03/31)
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- ANTI-INFECTIVE HETEROCYCLIC COMPOUNDS AND USES THEREOF
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The present invention relates to heterocyclic compounds of Formula F-I useful as anti-infective agents. The present invention further relates to a method of treating an infection by administering such compounds, and to pharmaceutical compositions comprising such compounds.
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Page/Page column 18; 21; 22
(2019/05/22)
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- PIPERDINYL NOCICEPTIN RECEPTOR COMPOUNDS
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The present invention provides novel piperidinyl-containing nociceptin receptor ligand compounds and pharmaceutical compositions useful in the treatment of neurological diseases and conditions where such ligands mediate the negative effects of the condition. Such neurological diseases and conditions include acute and chronic pain, substance abuse/dependence, alcohol addiction, anxiety, depression, sleep disorders, gastrointestinal disorders, renal disorders, cardiovascular disorders and Parkinson's disease.
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Paragraph 0147-0149
(2018/06/15)
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- PIPERIDINYL NOCICEPTIN RECEPTOR COMPOUNDS
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The present invention provides novel piperidinyl-containing nociceptin receptor ligand compounds and pharmaceutical compositions useful in the treatment of neurological diseases and conditions where such ligands mediate the negative effects of the condition. Such neurological diseases and conditions include acute and chronic pain, substance abuse/dependence, alcohol addiction, anxiety, depression, sleep disorders, gastrointestinal disorders, renal disorders, cardiovascular disorders and Parkinson' s disease.
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Page/Page column 101; 102
(2017/12/28)
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- MULTIVALENT RAS BINDING COMPOUNDS
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Described herein are compounds that modulate Ras signaling, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with altered Ras signaling. Further described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds and methods of using such compounds in the treatment of cell proliferative disorders, including cancer.
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Paragraph 00905
(2017/07/23)
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- 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: Part 2. Pyridazine-based analogs
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Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.
- Yang, Shyh-Ming,Tang, Yuting,Rano, Thomas,Lu, Huajun,Kuo, Gee-Hong,Gaul, Michael D.,Li, Yaxin,Ho, George,Lang, Wensheng,Conway, James G.,Liang, Yin,Lenhard, James M.,Demarest, Keith T.,Murray, William V.
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supporting information
p. 1437 - 1441
(2014/03/21)
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- 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: Urea-based analogs
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A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.
- Yang, Shyh-Ming,Tang, Yuting,Zhang, Rui,Lu, Huajun,Kuo, Gee-Hong,Gaul, Michael D.,Li, Yaxin,Ho, George,Conway, James G.,Liang, Yin,Lenhard, James M.,Demarest, Keith T.,Murray, William V.
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supporting information
p. 6773 - 6776
(2014/01/06)
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- Discovery of a potent, orally bioavailable and highly selective human neuronal nitric oxide synthase (nNOS) inhibitor, N-(1-(piperidin-4-yl)indolin-5- yl)thiophene-2-carboximidamide as a pre-clinical development candidate for the treatment of migraine
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We recently reported a series of 1,6-disubstituted indoline-based thiophene amidine compounds (5) as selective neuronal nitric oxide synthase (nNOS) inhibitors to mitigate the cardiovascular liabilities associated with hERG K+ channel inhibition (IC50 = 4.7 μM) with previously reported tetrahydroquinoline-based selective nNOS inhibitors (4). The extended structure-activity relationship studies within the indoline core led to the identification of 43 as a selection candidate for further evaluations. The in vivo activity in two different pain (spinal nerve ligation and migraine pain) models, the excellent physicochemical and pharmacokinetic properties, oral bioavailability (Fpo = 91%), and the in vitro safety profile disclosed in this report make 43 an ideal candidate for further evaluation in clinical applications related to migraine pain.
- Annedi, Subhash C.,Maddaford, Shawn P.,Ramnauth, Jailall,Renton, Paul,Rybak, Taras,Silverman, Sarah,Rakhit, Suman,Mladenova, Gabriela,Dove, Peter,Andrews, John S.,Zhang, Dongqin,Porreca, Frank
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p. 94 - 107,14
(2020/07/31)
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- 1-PIPERIDINYL-6-PIPERIDINYLSULFONYLINDOLES AS 5-HT (2B) RECEPTOR ANTAGONISTS
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The present invention relates to novel indole derivatives which bind to the 5-HT2B receptor and are capable of interfering with the effects of 5-hydroxytryptamine (5-HT) at the 5-HT2B receptor; to processes for their preparation; to pharmaceutical compositions containing them; and to the use of such compounds in therapy.
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Page/Page column 14
(2009/03/07)
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- NOVEL COMPOUNDS
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The present invention relates to novel indoline derivatives which bind to the 5-HT2B receptor and are capable of interfering with the effects of 5-hydroxytryptamine (5-HT) at the 5-HT2B receptor; to processes for their preparation; to pharmaceutical compositions containing them; and to the use of such compounds in therapy.
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Page/Page column 13-14
(2009/03/07)
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- QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
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The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.
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Page/Page column 90
(2008/12/08)
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- Strategies for the synthesis of N-(azacycloalkyl)bisindolylmaleimides: Selective inhibitors of PKCβ
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N-(Azacycloalkyl)bisindolylmaleimides 1 have been identified to be selective inhibitors of PKCβ. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for prepa
- Faul, Margaret M.,Grutsch, John L.,Kobierski, Michael E.,Kopach, Michael E.,Krumrich, Christine A.,Staszak, Michael A.,Udodong, Uko,Vicenzi, Jeffrey T.,Sullivan, Kevin A.
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p. 7215 - 7229
(2007/10/03)
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- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
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The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
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