- PCSK9 ANTAGONIST COMPOUNDS
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Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein A, A1, A2, R1, R2 and R3 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.
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Page/Page column 42; 43
(2021/06/26)
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- PCSK9 ANTAGONIST BICYCLO-COMPOUNDS
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Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R4, and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceut
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Page/Page column 72; 74-75
(2020/01/11)
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- CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS
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Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to
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Page/Page column 45
(2017/05/02)
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- THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
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The invention provides compounds having the general Formula (I); and pharmaceutically acceptable salts thereof; wherein the variables RA, RAA, subscript n, subscript q, ring A, X2, L, subscript m, X1, R1, R2, R3, R4, R5, D and E have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
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Page/Page column 171; 172
(2016/01/25)
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- DIFLUOROPYRROLIDINES AS OREXIN RECEPTOR MODULATORS
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The present application relates to certain difluoropyrrolidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.
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Page/Page column 72
(2016/02/29)
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- ANTI-VIRAL COMPOUNDS
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Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
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Paragraph 0504
(2015/11/24)
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- Chemoselective synthesis of N-protected alkoxyprolines under specific solvation conditions
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N-Protected hydroxyprolines (Hyp) were transformed chemoselectively into alkoxyproline derivatives by direct O-alkylation. The starting Hyp was transformed into the corresponding dianion in a mixture of dimethyl sulfoxide and tetrahydrofuran (1:16 v/v) as solvent. Under these conditions, the carboxy-anion showed reduced nucleophilicity because it was specifically solvated, and the more reactive oxy-anion was selectively alkylated. N-Protected trans-4-alkoxy-, cis-4-alkoxy- and trans-3-alkoxyprolines were thus obtained in a single step in very high overall yields and with complete stability of the stereogenic center configuration. Copyright
- Mihali, Voichita,Foschi, Francesca,Penso, Michele,Pozzi, Gianluca
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supporting information
p. 5351 - 5355
(2014/10/15)
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- Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists
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Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure, leading to GLP1 elevation in acutely dosed mice and reduc
- Azimioara, Mihai,Alper, Phil,Cow, Christopher,Mutnick, Daniel,Nikulin, Victor,Lelais, Gerald,Mecom, John,McNeill, Matthew,Michellys, Pierre-Yves,Wang, Zhiliang,Reding, Esther,Paliotti, Michael,Li, Jing,Bao, Dingjiu,Zoll, Jocelyn,Kim, Young,Zimmerman, Matthew,Groessl, Todd,Tuntland, Tove,Joseph, Sean B.,McNamara, Peter,Seidel, H. Martin,Epple, Robert
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supporting information
p. 5478 - 5483
(2015/01/09)
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- Anti-Viral Compounds
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Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
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- N-HYDROXYAMIDE DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
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Described herein are N-hydroxyamlde antibacterial compounds, methods for making the compounds, pharmaceutical compositions containing the compounds and methods of treating bacterial infections utilizing the compounds and pharmaceutical compositions compound of Formula (I): or a salt, solvate ti hydrate thereof, wherein A is (a) eachindicates a point of attachment.
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Page/Page column 16; 33; 36
(2010/02/17)
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- First synthesis of 2,6-diazabicyclo[3.2.0]heptane derivatives
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The first synthesis of 6-phenyl-2,6-diazabicyclo[3.2.0]heptane 1 and its orthogonally protected precursor 2 is herein reported. Our strategy enables to chemically address the two nitrogen atoms of 2,6-diazabicyclo[3.2.0]heptane core individually and selectively, thus allowing rapid access to several subsets of widely substituted fused azetidines.
- Napolitano, Carmela,Borriello, Manuela,Cardullo, Francesca,Donati, Daniele,Paio, Alfredo,Manfredini, Stefano
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scheme or table
p. 7280 - 7282
(2010/03/03)
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- TETRAHYDROCYCLOPENTA[B]INDOLE ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the Formula (I), or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating or preventing physiological disorders, particularly reduced bone mass, osteoporosis, osteopenia, reduced muscle mass or strength, or erectile dysfunction comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
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Page/Page column 32
(2009/12/23)
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- A general route to cyclopeptide alkaloids: total syntheses and biological evaluation of paliurines e and F, ziziphines N and Q, abyssenine A, mucronine E, and analogues
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A full account of the total syntheses of the cyclopeptide alkaloids paliurine E and F, ziziphine N and Q, abyssenine A, and mucronine E is provided. A key feature of the syntheses involves an intramolecular amidation of a vinyl iodide, which allows us sim
- Toumi, Mathieu,Rincheval, Vincent,Young, Ashley,Gergeres, Danielle,Turos, Edward,Couty, Francois,Mignotte, Bernard,Evano, Gwilherm
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experimental part
p. 3368 - 3386
(2011/02/28)
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- AZA-BENZOFURANYL COMPOUNDS AND METHODS OF USE
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The invention relates to azabenzofuranyl compounds of Formula (I) with anti-cancer and/or anti-inflammatory activity and more specifically to azabenzofuranyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 130-131
(2008/06/13)
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- Conformationally restricted dipeptide amides as potent and selective neuronal nitric oxide synthase inhibitors
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Four new conformationally restricted analogues of a potent and selective neuronal nitric oxide synthase inhibitor, L-nitroargininyl-L-2,4- diaminobutyramide (1), have been synthesized. Nα-Methyl and Nα-benzyl derivatives (3 and 4, re
- Ji, Haitao,Gómez-Vidal, José A.,Martásek, Pavel,Roman, Linda J.,Silverman, Richard B.
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p. 6254 - 6263
(2007/10/03)
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- Substituted diazabicycloalkane derivatives
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Compounds of formula (I) [in-line-formulae]Z-Ar1—Ar2??(I) [/in-line-formulae] wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.
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Page/Page column 35-36
(2010/02/11)
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- Stereoelectronic and steric effects in the collagen triple helix: Toward a code for strand association
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Collagen is the most abundant protein in animals. The protein consists of a helix of three strands, each with sequence X-Y-Gly. Natural collagen is most stable when X is (2S)-proline (Pro) and Y is (2S,4R)-4-hydroxyproline (4R-Hyp). We had shown previously that triple helices in which X is (2S,4S)-4- fluoroproline (4S-Flp) or Y is (2S,4R)-4-fluoroproline (4R-Flp) display hyperstability. This hyperstability arises from stereoelectronic effects that preorganize the main-chain dihedral angles in the conformation found in the triple helix. Here, we report the synthesis of strands containing both 4S-Flp in the X-position and 4R-Flp in the Y-position. We find that these strands do not form a stable triple helix, presumably because of an unfavorable steric interaction between fluoro groups on adjacent strands. Density functional theory calculations indicate that (2S,3S)-3-fluoroproline (3S-Flp), like 4S-Flp, should preorganize the main chain properly for triple-helix formation but without a steric conflict. Synthetic strands containing 3S-Flp in the X-position and 4R-Flp in the Y-position do form a triple helix. This helix is, however, less stable than one with Pro in the X-position, presumably because of an unfavorable inductive effect that diminishes the strength of the interstrand 3S-FlpC=O...H-NGly hydrogen bond. Thus, other forces can counter the benefits derived from the proper preorganization. Although (Pro-Pro-Gly) 7 and (4S-Flp-4R-Flp-Gly)7 do not form stable homotrimeric helices, mixtures of these two peptides form stable heterotrimeric helices containing one (Pro-Pro-Gly)7 strand and two (4S-Flp-4R-Flp-Gly) 7 strands. This stoichiometry can be understood by considering the cross sections of the two possible heterotrimeric helices. This unexpected finding portends the development of a "code" for the self-assembly of determinate triple helices from two or three strands.
- Hodges, Jonathan A.,Raines, Ronald T.
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p. 15923 - 15932
(2007/10/03)
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- 3-Mercaptopyrrolidines as farnesyl protein transferase inhibitors
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The present invention relats to inhibitors of ras farnesylation of Formula (I) wherein: R1 is for example H and further values as defined in the specification; R2 is for example H and further values as defined in the specification; R
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Page/Page column 27
(2010/02/14)
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- HIV protease inhibitors
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Combinatorial libraries of HIV and FIV protease inhibitors are characterized by alpha-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.
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Page/Page column 51
(2010/02/11)
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- BIOLOGICALLY ACTIVE COMPOUNDS
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Compounds of general formula (I) wherein: Z = CR3R4, where R3 and R4 are independently chosen from CO-7-alkyl P1 = CR5R6, P2 = O, CR7R8/sup
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Page 504-505
(2008/06/13)
-
- Heterocyclic substituted aminoazacycles useful as central nervous system agents
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Heterocyclic substituted aminoazacyclic compounds of the formula (I):Z-R3, wherein Z is a defined aminoazacycle and R3 is a defined heterocycle moiety, pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.
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-
-
- Bicyclic modulators of androgen receptor function
-
The invention provides compounds of the formula I wherein the substitutents are as described herein. Further provided are methods of using such compounds for the treatment of nuclear hormone receptor-associated conditions, such as age related diseases, for example sarcopenia, and also provided are pharmaceutical compositions containing such compounds.
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-
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- 5-ARALKYSUFONYL-3-(PYRROL-2-YLMETHYLIDENE)-2-INDOLINONE DERIVATIVES AS KINASE INHIBITORS
-
The present invention relates to certain 5-aralkylsulfonyl-3-(pyrrol-2-yl-methylidene)-2-indolinone derivatives that inhibit kinases, in particular met kinase. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.
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-
-
- Diazabicyclic central nervous system active agents
-
Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.
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-
- Synthesis of optically pure N-Boc-protected (2R,3R)- and (2R,3S)-3-fluoroprolines
-
Non-protein amino acids (2R,3R)- and (2R,3S)-3-fluoroprolines were synthesized as novel probes for studying the cis/trans isomerization of the amino acyl-proline peptide bond. The N-Boc-protected target compounds were obtained as optically pure material s
- Demange, Luc,Cluzeau, Jér?me,Ménez, André,Dugave, Christophe
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p. 651 - 653
(2007/10/03)
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- Short, highly efficient syntheses of protected 3-azido- and 4-azidoproline and their precursors
-
matrix presented An improved synthesis of protected cis- and trans-3-azido-L-proline and cis- and frans-4-azido-L- and -D-proline is reported. These compounds have been synthesized from the corresponding hydroxyproline precursors using diphenylphosphoryl azide under Mitsunobu conditions. Short, highly efficient syntheses of these precursors are described, based on a new lactone-opening reaction and p-nitrobenzoate hydrolysis under very mild conditions.
- Gomez-Vidal, Jose A.,Silverman, Richard B.
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p. 2481 - 2484
(2007/10/03)
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- A short synthesis of an important precursor to a new class of bicyclic β-lactamase inhibitors
-
A short synthesis of an important precursor to known bicyclic β-lactamase inhibitors is described. The synthesis uses commercially available trans-3-hydroxy-L-proline 1. Protection of the amino group followed by formation of the hydroxamate and cyclization using Mitsunobu conditions afforded bicyclic β-lactam 4 in three steps in 53% overall yield.
- Bellettini, John R.,Miller, Marvin J.
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p. 167 - 168
(2007/10/03)
-
