- Novel μ opioid antagonists derived from the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2)
-
Hybrid analogues of the μ opioid agonists endomorphin and [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2, Dmt?=?2′,6′-dimethyltyrosine) containing cis-4-amino-Pro, trans-4-amino-Pro, cis-4-aminoethyl-Pro or cis-4-guanidinylethyl-Pro in the 2 p
- Shi, Saijian,Xu, Jian,Feng, LingLing,Fan, Xin,Chen, Zhen,Qin, Yajuan,Chung, Nga N.,Li, Tingyou,Schiller, Peter W.
-
p. 1305 - 1314
(2020/08/05)
-
- BENZIMIDAZOLE-LINKED INDOLE COMPOUND ACTING AS NOVEL DIVALENT IAP ANTAGONIST
-
The present invention discloses a benzimidazole-linked indole compound acting as novel divalent IAP antagonist, specifically disclosing the compound shown in fomulas (I) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0280; 0281
(2019/03/14)
-
- Compound as apoptosis protein inhibitor, and application thereof
-
The present invention belongs to the field of medical chemistry, relates to a class of compounds of apoptosis protein inhibitors, and applications thereof, and particularly provides a compound represented by a formula I, or an isomer thereof, a pharmaceut
- -
-
-
- Oxyfunctionalization of the Remote C?H Bonds of Aliphatic Amines by Decatungstate Photocatalysis
-
Aliphatic amines, oxygenated at remote positions within the molecule, represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported herein is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H2O2 or O2 as the terminal oxidant. By using these reaction conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value-added ketone products. Lastly, NMR spectroscopy using in situ LED-irradiated samples was utilized to monitor the kinetics of the reaction, thus enabling direct translation of the reaction into flow.
- Schultz, Danielle M.,Lévesque, Fran?ois,DiRocco, Daniel A.,Reibarkh, Mikhail,Ji, Yining,Joyce, Leo A.,Dropinski, James F.,Sheng, Huaming,Sherry, Benjamin D.,Davies, Ian W.
-
supporting information
p. 15274 - 15278
(2017/11/01)
-
- As hepatitis c inhibitor spiro compound and its use in medicine
-
The invention provides a spiro compound serving as a hepatitis c inhibitor and application thereof in a medicine. The compound is a compound as shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, an aquo-complex, a solvate, a metabolite, pharmaceutically acceptable salt or prodrug of the compound as shown in the formula (I). The invention also provides a pharmaceutical composition containing the compound, application of the compound and the pharmaceutical composition in inhibition of HCV (Hepatitis C Virus) copy and HCV virus protein, as well as the application of the compound and the pharmaceutical composition in prevention, handling, treatment or relieving of HCV infection or hepatitis c disease for a patient. The formula I is as shown in the specification.
- -
-
Paragraph 1263; 1270; 1271
(2017/12/28)
-
- Structure-activity relationships of 4-hydroxy-4-biaryl-proline acylsulfonamide tripeptides: A series of potent NS3 protease inhibitors for the treatment of hepatitis C virus
-
The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relatin
- Wang, Alan Xiangdong,Chen, Jie,Zhao, Qian,Sun, Li-Qiang,Friborg, Jacques,Yu, Fei,Hernandez, Dennis,Good, Andrew C.,Klei, Herbert E.,Rajamani, Ramkumar,Mosure, Kathy,Knipe, Jay O.,Li, Danshi,Zhu, Jialong,Levesque, Paul C.,McPhee, Fiona,Meanwell, Nicholas A.,Scola, Paul M.
-
p. 590 - 596
(2017/01/17)
-
- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
-
Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
- -
-
Paragraph 0706-0716
(2015/11/09)
-
- FUSED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided are fused tricyclic compounds effective to inhibit the function of the NS5A protein of formula (I), wherein X, X', Y, Y', A, A',Q1, Q2, R1-R4, X4, R5a, f and W are defined as in the description. Also provided herein are pharmaceutical compositions thereof, and uses in the manufacture of a medicament for treating HCV infection or a HCV disorder thereof.
- -
-
Paragraph 00510; 00513
(2014/06/23)
-
- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
- -
-
Page/Page column 176
(2014/09/16)
-
- Synthesis and biological evaluation of 4-hydroxy-4-(4-methoxyphenyl)- substituted proline and pyrrolidin-2-ylacetic acid derivatives as GABA uptake inhibitors
-
A series of enantiomerically pure 4-hydroxy-4-(4-methoxyphenyl)-substituted proline and pyrrolidin-2-ylacetic acid derivatives have been synthesized starting from the respective N-protected 4-hydroxy derivatives via oxidation to the corresponding 4-oxo co
- Zhao, Xueqing,Pabel, Joerg,Hoefner, Georg C.,Wanner, Klaus T.
-
p. 470 - 484
(2013/03/13)
-
- CHEMICAL COMPOUNDS
-
Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.
- -
-
Page/Page column 25-26
(2011/04/14)
-
- N-HYDROXYAMIDE DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
-
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.
- -
-
Page/Page column 34-35; 41
(2010/02/17)
-
- Hepatitis C Virus Inhibitors
-
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
- -
-
Page/Page column 10
(2010/06/22)
-
- Hepatitis C Virus Inhibitors
-
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
- -
-
Page/Page column 12; 14
(2009/12/23)
-
- HEPATITIS C VIRUS INHIBITORS
-
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
- -
-
-
- MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
-
Macrocyclic peptides having the general formula (I): are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
- -
-
Page/Page column 96
(2008/12/05)
-
- Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration
-
A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species.
- Kondo, Takashi,Nekado, Takahiro,Sugimoto, Isamu,Ochi, Kenya,Takai, Shigeyuki,Kinoshita, Atsushi,Tajima, Yohei,Yamamoto, Susumu,Kawabata, Kazuhito,Nakai, Hisao,Toda, Masaaki
-
p. 2631 - 2650
(2008/02/05)
-
- Discovery and synthesis of HIV integrase inhibitors: Development of potent and orally bioavailable N-methyl pyrimidones
-
The human immunodeficiency virus type-1 (HIV-1) encodes three enzymes essential for viral replication: a reverse transcriptase, a protease, and an integrase. The latter is responsible for the integration of the viral genome into the human genome and, therefore, represents an attractive target for chemotherapeutic intervention against AIDS. A drug based on this mechanism has not yet been approved. Benzyl-dihydroxypyrimidine-carboxamides were discovered in our laboratories as a novel and metabolically stable class of agents that exhibits potent inhibition of the HIV integrase strand transfer step. Further efforts led to very potent compounds based on the structurally related N-Me pyrimidone scaffold. One of the more interesting compounds in this series is the 2-N-Me-morpholino derivative 27a, which shows a CIC95 of 65 nM in the cell in the presence of serum. The compound has favorable pharmacokinetic properties in three preclinical species and shows no liabilities in several counterscreening assays.
- Gardelli, Cristina,Nizi, Emanuela,Muraglia, Ester,Crescenzi, Benedetta,Ferrara, Marco,Orvieto, Federica,Pace, Paola,Pescatore, Giovanna,Poma, Marco,Ferreira, Maria Del Rosario Rico,Scarpelli, Rita,Homnick, Carl F.,Ikemoto, Norihiro,Alfieri, Anna,Verdirame, Maria,Bonelli, Fabio,Paz, Odalys Gonzalez,Taliani, Marina,Monteagudo, Edith,Pesci, Silvia,Laufer, Ralph,Felock, Peter,Stillmock, Kara A.,Hazuda, Daria,Rowley, Michael,Summa, Vincenzo
-
p. 4953 - 4975
(2008/03/14)
-
- Inhibitors of tripeptidyl peptidase II. 3. Derivation of butabindide by successive structure optimizations leading to a potential general approach to designing exopeptidase inhibitors
-
The cholecystokinin-8 (CCK-8)-inactivating peptidase is a serine peptidase that has been shown to be a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10). It cleaves the neurotransmitter CCK-8 sulfate at the Met-Gly bond to give Asp-Tyr(SO
- Ganellin, C. Robin,Bishop, Paul B.,Bambal, Ramesh B.,Chan, Suzanne M. T.,Leblond, Bertrand,Moore, Andrew N. J.,Zhao, Lihua,Bourgeat, Pierre,Rose, Christiane,Vargas, Froylan,Schwartz, Jean-Charles
-
p. 7333 - 7342
(2007/10/03)
-
- Method for the preparation of N-substituted 4-ketoproline derivatives
-
Method for the preparation of N-protected 4-ketoproline derivatives of formula I STR1 by oxidation of the corresponding N-protected 4-hydroxyproline derivatives of STR2 using the system TEMPO (2,2,6,6-tetramethylpiperidinyl oxy free radical)/NaOCl.
- -
-
-
- (Phosphinyloxy)acid amino acid inhibitors of angiotensin converting enzyme. 2. Terminal amino acid analogues of (S)-1-[6-Amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]- L-proline
-
Analogues of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]- L-proline (1, SQ 29,852) in which the terminal proline residue has been replaced by a variety of substituted and heteroatom-substituted prolines, N-arylglycines, N-cycloalkylglycines, and bicyclic amino acids have been synthesized and evaluated as inhibitors of angiotensin converting enzyme in vitro an in vivo. In general, the addition of lipophilic substituents to the 4-position of proline of the parent phosphate 1 resulted in substantial increases in vitro activity. The largest improvements were observed in the case of cis-benzyl (36-fold) and dithioketal (24-fold) analogues 2r and 2x, respectively. These enhancements of in vitro activity were accompanied by modest increases (2-3.5-fold) in in vivo (iv) activity. Among the various terminal amino acid replacements examined in this study, the indoline-based analogue 2i was by far the most potent compound on iv administration in the normotensive rat.
- Karanewsky,Badia,Cushman,DeForrest,Dejneka,Lee,Loots,Petrillo
-
p. 1459 - 1469
(2007/10/02)
-
- Boron trifluoride promoted cleavage of benzyl carbamates
-
A new efficient method for the cleavage of benzyl carbamates (CBZ protective groups) is described that involves a hard acid (BF3·OEt2) - soft nucleophile (EtSH) system. Unlike other available methods, this combination avoids the reduction of olefins, acetylenes, imines, halides and nitro groups, or the possibility of carboxylic ester hydrolysis.
- Subhas Bose,Thurston, David E.
-
p. 6903 - 6906
(2007/10/02)
-
- Synthesis and Pharmacological Activity of Angiotensin Converting Enzyme Inhibitors: N-(Mercaptoacyl)-4-substituted-(S)-prolines
-
The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described.These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition.The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril.The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.
- Smith, Elisabeth M.,Swiss, Gerald F.,Neustadt, Bernard R.,Gold, Elijah H.,Sommer, Jane A.,et al.
-
p. 875 - 885
(2007/10/02)
-