- SALT TYPE AND CRYSTAL TYPE OF 4H-PYRAZOLO [1, 5-ALPHA] BENZIMIDAZOLE COMPOUND AND PREPARATION METHOD AND INTERMEDIATE THEREOF
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Disclosed in the present invention are a salt type and crystal type of 4H-pyrazolo[1, 5-alpha]benzimidazole compound and the preparation method and intermediate thereof.
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Paragraph 0149; 0150; 0151
(2018/10/04)
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- ACYL SULFONAMIDE NAV1.7 INHIBITORS
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The present disclosure relates to compounds of formula I which inhibit NaV1.7, and include pharmaceutically acceptable salts, compositions comprising such compounds, and methods using and making such compounds and compositions. (I)
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Page/Page column 60
(2018/05/24)
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- ANALOGUES OF 4H-PYRAZOLO[1,5-a] BENZIMIDAZOLE COMPOUND AS PARP INHIBITORS
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Disclosed is a series of analogues of 4H-pyrazolo[1,5-α]benzimidazole compound as PARP inhibitors. In particular, disclosed in the invention is a compound as shown by formula (I) or a pharmaceutically acceptable salt thereof as a PARP inhibitor.
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Paragraph 0660
(2017/02/28)
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- TRIAZOLOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF
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Compounds of Formula 0, Formula I and Formula II and methods of use as Janus kinase inhibitors are described herein.
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Page/Page column 314
(2015/03/28)
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- PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS
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The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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Page/Page column 82
(2015/10/05)
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- Novel 4,4-disubstituted piperidine-based C-C chemokine receptor-5 inhibitors with high potency against human immunodeficiency virus-1 and an improved human ether-a-go-go related gene (hERG) profile
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We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further finetuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).
- Kazmierski, Wieslaw M.,Anderson, Don L.,Aquino, Christopher,Chauder, Brian A.,Duan, Maosheng,Ferris, Robert,Kenakin, Terrence,Koble, Cecilia S.,Lang, Dan G.,Mcintyre, Maggie S,Peckham, Jennifer,Watson, Christian,Wheelan, Pat,Spaltenstein, Andrew,Wire, Mary B.,Svolto, Angilique,Youngman, Michael
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supporting information; experimental part
p. 3756 - 3767
(2011/07/30)
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- A new synthesis of spiropyrrolidine-tetralones via an unexpected formal ring-contraction of 4-disubstituted piperidine to 3-disubstituted pyrrolidine
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We have developed an efficient synthesis of novel racemic spiropyrrolidine-tetralones via an unexpected ring-contraction reaction of a 4-disubstituted piperidine to 3-disubstituted pyrrolidine. We suggest that intramolecular quaternization of the piperidi
- Bandarage, Upul K.,Davies, Robert J.
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scheme or table
p. 6415 - 6417
(2011/01/03)
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- CARBAMATE AND UREA INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1
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This invention relates to novel compounds of the invention pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.
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Page/Page column 68-69
(2010/12/29)
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- Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist
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We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models.
- He, Shuwen,Ye, Zhixiong,Dobbelaar, Peter H.,Sebhat, Iyassu K.,Guo, Liangqin,Liu, Jian,Jian, Tianying,Lai, Yingjie,Franklin, Christopher L.,Bakshi, Raman K.,Dellureficio, James P.,Hong, Qingmei,Tsou, Nancy N.,Ball, Richard G.,Cashen, Doreen E.,Martin, William J.,Weinberg, David H.,MacNeil, Tanya,Tang, Rui,Tamvakopoulos, Constantin,Peng, Qianping,Miller, Randy R.,Stearns, Ralph A.,Chen, Howard Y.,Chen, Airu S.,Strack, Alison M.,Fong, Tung M.,MacIntyre, D. Euan,Wyvratt Jr., Matthew J.,Nargund, Ravi P.
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scheme or table
p. 2106 - 2110
(2010/08/19)
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- Discovery of bioavailable 4,4-disubstituted piperidines as potent ligands of the chemokine receptor 5 and inhibitors of the human immunodeficiency virus-1
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We describe robust chemical approaches toward putative CCR5 scaffolds designed in our laboratories. Evaluation of analogues in the 125I-[MIP-1β] binding and Ba-L-HOS antiviral assays resulted in the discovery of 64 and 68 in the 4,4-disubstitited piperidine class H, both potent CCR5 ligands (pIC50 = 8.30 and 9.00, respectively) and HIV-1 inhibitors (pIC50 = 7.80 and 7.84, respectively, in Ba-L-HOS assay). In addition, 64 and 68 were bioavailable in rodents, establishing them as lead molecules for further optimization toward CCR5 clinical candidates.
- Kazmierski, Wieslaw M.,Aquino, Christopher,Chauder, Brian A.,Deanda, Felix,Ferris, Robert,Jones-Hertzog, Deborah K.,Kenakin, Terrence,Koble, Cecilia S.,Watson, Christian,Wheelan, Pat,Yang, Hanbiao,Youngman, Michael
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experimental part
p. 6538 - 6546
(2009/11/30)
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- ACYLATED SPIROPIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR MODULATORS
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Certain novel N-acylated spiropiperidine derivatives are ligands of the human melanocortin receptor(s) and, in particular, are selective ligands of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of MC-4R, such as obesity, diabetes, nicotine addiction, alcoholism, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.
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Page/Page column 67
(2010/11/27)
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- Synthesis of 4-substituted piperidines via a mild and scalable two-step Cu2O-mediated decarboxylation of cyanoesters
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A four-step, high-yielding, kilogram-scale protocol to prepare aldehyde 5 is reported. The key reaction is a mild, two-step Cu2O-mediated decarboxylation of cyanoester 3 that proceeds in excellent yield. The general applicability of this method
- Chauder, Brian A.,Boros, Eric E.,Du, Kien S.,Kazmierski, Wieslaw M.,Koble, Cecilia S.,Thompson, James B.,Tabet, Elie A.
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p. 279 - 284
(2007/10/03)
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- NOVEL PIPERIDINE/8-AZABICYCLO [3.2.1] OCTAN DERIVATIVES AS MODUILATORS OF CHEMOKINE RECEPTOR CCR5
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Compounds of formula (I) wherein neither R4 nor R5 is hydrogen; compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating CCR5 receptor activity in a warm blooded animal).
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Page/Page column 71
(2010/02/15)
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- BETA-LACTAMS FOR TREATMENT OF CNS DISORDERS
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The present invention relates to novel compounds of formula (I) wherein ---- represents a single or a double bond; R represents a radical selected from formulae i), ii), iii) and iv) in which R1 is halogen, cyano, C1-4 alkyl, C1
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Page/Page column 52
(2010/02/12)
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- CCR5 ANTAGONISTS AS THERAPEUTIC AGENTS
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The present invention relates to compounds of formula (I) or pharmaceutically acceptable derivatives thereof, useful in the treatment or prophylaxis of CCR5-related diseases and disorders, for example, in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).
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Page 72 - 73
(2010/02/07)
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- CHEMICAL COMPOUNDS
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The present invention relates to cyclic amine derivatives of formula(I) (I)whereinR represents halogen, C1-4 alkyl, cyano, C1-4 alkoxy, trifluoromethyl or trifluoromethoxy;R1 represents hydrogen, halogen, C3-7cycloalkyl, hydroxy, nitro, cyano or C1-4 alkyl optionally substituted by halogen, cyano or C1-4 alkoxy;R2 represents hydrogen or C1-4 alkyl;R3 and R4 independently represent hydrogen, cyano, C1-4 alkyl or R3 together with R4 represents C3-7 cycloalkyl;R5 represents trifluoromethyl, S(O)t C 1-4 alkyl, C1-4 alkyl, C1-4 alkoxy, trifluoromethoxy, halogen or cyano;R6 represents hydrogen or (CH2)rR7;R7 represents hydrogen, C3-7 cycloalkyl, NH(C1-4alkylOC1-4alkoxy), NH(C1-4alkyl), N(C1-4alkyl)2, OC(O)NR9R8, NR8C(O)R9 or C(O)NR9R8;R9 and R8 independently represent hydrogen, C1-4 alkyl or C3-7 cycloalkyl; m represents zero or an integer from 1 to 4;n represents 1 or 2;p is zero or an integer from 1 to 3;q is an integer from 1 to 3;r is an integer from 1 to 4;t is 0, 1 or 2;provided that when m is 0, p is 2, q, r and n represent 1, R1, R2,R3, R4, R5 and R7 are hydrogen and R is chlorine, R5 is not iodine; and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tackykinins and/or by selective inhibition of serotonin reuptake transporter protein.
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- PIPERAZINE UREA DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS
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Certain novel piperazine urea derivatives are agonists of the human melanocortin-4 receptor (MC-4R) and, in particular, are receptor-subtype selective agonists of MC-4R. They are useful for the treatment, control, or prevention of diseases and disorders r
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