- 2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS
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Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.
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Paragraph 0798; 0998-1001
(2021/04/17)
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- Design, Synthesis, and Pharmacological Characterization of Heterobivalent Ligands for the Putative 5-HT2A/mGlu2Receptor Complex
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We report the synthesis of the first series of heterobivalent ligands targeting the putative heteromeric 5-HT2A/mGlu2 receptor complex, based on the 5-HT2A antagonist MDL-100,907 and the mGlu2 ago-PAM JNJ-42491293. The functional properties of monovalent and heterobivalent ligands were characterized in 5-HT2A-, mGlu2/Gqo5-, 5-HT2A/mGlu2-, and 5-HT2A/mGlu2/Gqo5-expressing HEK293 cells using a Ca2+ imaging assay and a [3H]ketanserin binding assay. Pronounced functional crosstalk was observed between the two receptors in 5-HT2A/mGlu2 and 5-HT2A/mGlu2/Gqo5 cells. While the synthesized monovalent ligands retained the 5-HT2A antagonist and mGlu2 ago-PAM functionalities, the seven bivalent ligands inhibited 5-HT-induced responses in 5-HT2A/mGlu2 cells and both 5-HT- and Glu-induced responses in 5-HT2A/mGlu2/Gqo5 cells. However, no definitive correlation between the functional potency and spacer length of the ligands was observed, an observation substantiated by the binding affinities exhibited by the compounds in 5-HT2A, 5-HT2A/mGlu2, and 5-HT2A/mGlu2/Gqo5 cells. In conclusion, while functional crosstalk between 5-HT2A and mGlu2 was demonstrated, it remains unclear how these heterobivalent ligands interact with the putative receptor complex.
- Poulie, Christian B. M.,Liu, Na,Jensen, Anders A.,Bunch, Lennart
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p. 9928 - 9949
(2020/09/12)
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- SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
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Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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Paragraph 00693
(2016/04/26)
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- Potent P2Y1 urea antagonists bearing various cyclic amine scaffolds
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A number of new amine scaffolds with good inhibitory activity in the ADP-induced platelet aggregation assay have been found to be potent antagonists of the P2Y1 receptor. SAR optimization led to the identification of isoindoline 3c and piperidine 4a which showed good in vitro binding and functional activities, as well as improved aqueous solubility. Among them, the piperidine 4a showed the best overall profile with favorable PK parameters.
- Ruel, Réjean,L'Heureux, Alexandre,Thibeault, Carl,Lapointe, Philippe,Martel, Alain,Qiao, Jennifer X.,Hua, Ji,Price, Laura A.,Wu, Qimin,Chang, Ming,Zheng, Joanna,Huang, Christine S.,Wexler, Ruth R.,Rehfuss, Robert,Lam, Patrick Y.S.
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p. 6825 - 6828
(2014/01/06)
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- Heteroaryl compounds as P2Y1 receptor inhibitors
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The present invention provides novel heteroaryl compounds and analogues thereof, which are selective inhibitors of the human P2Y1 receptor. The invention also provides for various pharmaceutical compositions of the same and methods for treating diseases responsive to modulation of P2Y1 receptor activity.
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Page/Page column 138
(2008/06/13)
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- INHIBITORS OF TRYPTASE
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The present invention related to certain inhibitors of tryptase that are inhibitors of tryptase, pharmaceutical composition comprising these compounds and method of treating asthma, allergic rhinitis, and/or Chronic Obstructive Pulmonary Disease utilizing these compounds.
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Page/Page column 179
(2008/06/13)
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- 2,2-DIPHENYLBUTANAMIDE DERIVATIVES AND MEDICINES CONTAINING THE SAME
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2,2-Diphenylbutanamide derivatives represented by the following formula (1): [wherein A represents -(CH2)n- (n is 1 or 2) or a methine (CH) group; when A is -CH2-, B represents a methine group or a nitrogen atom, with A and B forming a single bond; when A is -(CH2)2-, B represents a nitrogen atom, with A and B forming a single bond; when A is a methine group, B represents a quaternary carbon atom, with A and B forming a double bond; each of R1 and R2, which are identical to or different from each other, represents a hydrogen atom, a lower alkyl group, or a cycloalkyl group, or R1 and R2 may form a heterocyclic ring together with the adjacent nitrogen atom; and Ar represents an optionally substituted phenyl group, bicyclic aromatic ring, monocyclic heterocyclic ring, bicyclic heterocyclic ring, or fluorene group]; or salts of the derivatives. The derivatives or salts thereof exhibit excellent μ-opioid agonist activity and analgesic activity against neuropathic pain, and are useful as medicines such as peripheral analgesic drugs and neuropathic pain relieving drugs.
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- N-SUBSTITUTED NAPHTHALENE CARBOXAMIDES AS NEUROKININ-RECEPTOR ANTAGONISTS
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A compound of formula I wherein: R is alkyl; R1 is optionally substituted phenyl 2-oxo-tetrahydro-1(2H)-pyrimidinyl, or 2-oxo-1-piperidinyl; R2 is hydrogen, alkoxy, alkanoyloxy, alkoxycarbonyl, alkanoylamino, acyl, alkyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl where the alkyl groups are the same or different, hydroxy, thioacyl, thiocarbamoyl, N-alkylthiocarbamoyl, or N,N-dialkylthiocarbamoyl where the alkyl groups are the same or different. X1 and X2 are independently hydrogen or halo, provided that at least one of X1 or X2 is halo; and R3, R4, R5 and R6 are independently hydrogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, or alkylsulfonyl are antagonists of at least one tachykinin receptor and are useful in the treatment of depression, anxiety, asthma, pain, inflammation, urinary incontinence and other disease conditions. Process for their preparation are described, as are compositions containing them and their use.
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- New μ-opioid receptor agonists with phenoxyacetic acid moiety
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New μ-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, [2-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl] phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of δ- and κ-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.
- Sato, Susumu,Komoto, Teruo,Kanamaru, Yoshihiko,Kawamoto, Noriyuki,Okada, Tomomi,Kaiho, Terumitsu,Mogi, Kinichi,Morimoto, Shinichi,Umehara, Norimitsu,Koda, Tadayuki,Miyashita, Akira,Sakamoto, Takao,Niino, Yasuhiro,Oka, Tetsuo
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p. 292 - 297
(2007/10/03)
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- New strong fibrates with piperidine moiety
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New fibrates containing piperidine, 4-hydroxypiperidine, piperidin-3-ene, and piperazine moieties in the structures were synthesized and evaluated. Among the synthesized compounds, 2-[3-[1-(4-fluorobenzoyl)-piperidin-4yl]phenoxy]-2-methylpropanoic acid (9
- Komoto, Teruo,Hirota, Hiroyuki,Otsuka, Mari,Kotake, Jiro,Hasegawa, Susumu,Koya, Hidehiko,Sato, Susumu,Sakamoto, Takao
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p. 1978 - 1985
(2007/10/03)
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- Aryl substituted heterocycles
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The present invention concerns the novel use of aryl substituted heterocycles of formula I, set out below, which antagonize the pharmacological actions of one of ent endogenous neuropeptide tachykinins an the neurokinin 2 (NK2) receptor making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the aryl substituted heterocycles for use in such treatment. Certain novel aryl substituted heterocycles of formula I and novel intermediates for their manufacture are also provided. STR1
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- Cyclic amide derivatives for treating asthma
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Compounds of formula I STR1 wherein Q1, Q2, Q3, and Q4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
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