- HEPATITIS B VIRUS SURFACE ANTIGEN INHIBITOR
-
Disclosed in the present invention is a new 11-oxo-7,11-dihydro-6h-benzo-[f]pyrido[1,2-d][1,4]azepine oxepin-10-carboxylic acid derivative serving as a hepatitis B virus surface antigen inhibitor. Specifically disclosed are a compound represented by formula (V) or a pharmaceutically acceptable salt thereof, and applications of the compound represented by formula (V) or the pharmaceutically acceptable salt thereof and a pharmaceutical composition thereof in the treatment of viral hepatitis B.
- -
-
Paragraph 0151; 0158; 0159
(2020/04/21)
-
- Aliskiren intermediate preparation method
-
The present invention relates to the technical field of pharmaceutical preparation method, the preparation method of the existing long reaction time, the problem of low yield, provides a aliskiren preparation method, comprises the following steps: S1, 1st intermediate preparation: the raw material is dissolved in a solvent, adding sodium hypochlorite and sodium bisulfite reaction, shall be 1st intermediate; S2, intermediate in the preparation of 2nd: to the 1st intermediate dropping 4 - bromo - 1 - methoxy - 2 - (3 - methoxy third oxygen radical) benzene, tetrahydrofuran solution, adding low [...] catalyst, to obtain the 2nd intermediate; S3, aliskiren intermediate preparation: will be soluble in ethyl acetate in the 2nd intermediate, then adding water, nitrogen replacement 3 times, the hydrogen replaced 3 times after adding the hydrogen hydrogenation reaction, to obtain the product. By adding low deuterium water as a catalyst, help to accelerate the step S2 of the reaction rate, the reaction time is shortened, while at the same time help to improve the step S2 in the reaction yield, and then make the total reaction yield can be improved.
- -
-
Paragraph 0091; 0093; 0094
(2019/03/25)
-
- DIHYDROQUINOLIZINONES AS ANTIVIRALS
-
Compounds, specifically hepatitis B virus and/or hepatitis D virus inhibitors, more specifically compounds that inhibit HBe antigen and HBs antigen in a subject, for the treatment of viral infections, and methods of preparing and using such compounds. Formula (I):
- -
-
Paragraph 00483; 00485; 00486; 00659; 00661; 00662; 001602
(2018/09/19)
-
- Formal total synthesis of aliskiren
-
The efficient and selective formal total synthesis of aliskiren is described. Aliskiren, a renin inhibitor drug, has received considerable attention, primarily because it is the first of the renin inhibitor drugs to be approved by the FDA. Herein, the formal synthesis of aliskiren by iridium-catalyzed asymmetric hydrogenation of two allylic alcohol fragments is reported. Screening a number of N,P-ligated iridium catalysts yielded two catalysts that gave the highest enantioselectivity in the hydrogenation, which gave the saturated alcohols in 97 and 93 % ee. In only four steps after hydrogenation, the fragments were combined by using the Julia-Kocienski reaction to produce late-stage intermediate in an overall yield of 18 %.
- Peters, Byron K.,Liu, Jianguo,Margarita, Cristiana,Andersson, Pher G.
-
supporting information
p. 7292 - 7296
(2015/05/05)
-
- An improved and economical process for the manufacture of the key intermediate of aliskiren, a new potent renin inhibitor
-
An improved, practical, economical and efficient process for the production of (2S,4S)-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoic acid, a key intermediate of the new potent renin inhibitor of aliskiren, in a total yield over 30% is described. This process avoids expensive reagents and chromatographic purifications, and is easily scaled up in industry.
- Wang, Fan,Xu, Xiao-Ying,Wang, Fei-Ying,Peng, Lin,Zhang, Yong,Tian, Fang,Wang, Li-Xin
-
p. 1458 - 1462
(2013/12/04)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF ALISKIREN
-
The present invention relates to an improved process for the preparation of renin inhibitor Aliskiren intermediates of Formula-II and further conversion into Aliskiren and its pharmaceutically acceptable salts.
- -
-
Page/Page column 3; 4; 5; 9; 13
(2013/12/03)
-
- PROCESS FOR THE PREPARATION OF (2S,4S,5S,7S)-N-(2-CARBAMYL-2- METHYLPROPYL)-5-AMINO-4-HYDROXY-2,7-DIISOPROPYL-8-[4-METHOXY-3-(3- METHOXYPROPOXY)PHENYL]-OCTANAMIDE HEMIFUMARATE AND ITS INTERMEDIATES THEREOF
-
The present invention relates to a process for the preparation of (2S,4S,5S,7S)-N-(2- Carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxy propoxy )phenyl]-octanamide compound of formula- 1 and its pharmaceutically acceptable salts thereof. Further, relates to the processes for the preparation of (R)-4-(2-(halomethyl)-3- methylbutyl)-l-methoxy-2-(3-methoxypropoxy) benzene and (R)-2-(4-methoxy-3-(3-methoxy propoxy) benzyl)-3-methyIbutan-l-ol useful intermediates in the synthesis of compound of formula- 1.
- -
-
Page/Page column 58
(2011/12/14)
-
- AMIDE INHIBITORS OF RENIN
-
The present invention relates to new amide inhibitors of renin, pharmaceutical compositions thereof, and methods of use thereof
- -
-
-
- Aryl- and Heteroaryl-Ethyl-Acylguanidine Derivatives, Their Preparation and Their Application in Therapeutics
-
Disclosed are compounds according to formula (I): wherein A, Q, X, Y, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as defined herein. The disclosure also relates to pharmaceutical compositions containing a compound of formula (I), to processes for preparing the compounds of formula (I), and to methods of using the compounds of formula (I).
- -
-
Page/Page column 20
(2009/08/18)
-
- 1-HETEROCYCLYLAMINO-2-HYDROXY-3-AMINO-ω-ARYLALKANES
-
1-Heterocyclylamino-2-hydroxy-3-amino-?-arylalkanes of formula (I) and the salts thereof have renin-inhibiting properties and can be used as antihypertensive, medicinally active ingredients.
- -
-
-
- 1-ACYLAMINO-2-HYDROXY-3-AMINO-W-ARYLALKANES AS RENIN INHIBITORS
-
1-Acylamino-2-hydroxy-3-amino-ω-arylalkanes of formula I. and the salts thereof, have renin-inhibiting properties and can be used as antihypertensive, medicinally active ingredients.
- -
-
Page/Page column 73
(2008/06/13)
-
- Practical synthesis of an orally active renin inhibitor aliskiren
-
A convergent synthesis of aliskiren was accomplished via the use of Segment AB as the key intermediate, which was prepared via the coupling of the Grignard reagent derived from Segment B with Segment A, followed by subsequent oxidative lactonization.
- Dong, Hua,Zhang, Zhi-Liu,Huang, Jia-Hui,Ma, Rujian,Chen, Shu-Hui,Li, Ge
-
p. 6337 - 6340
(2007/10/03)
-
- 4-PHENYLPIPERIDINE DERIVATIVES AS RENIN INHIBITORS
-
Compounds of the present invention having the formula (I) exhibit inhibitory activity on the natural enzyme renin. Thus, compounds of formula (I) may be employed for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy postinfarction, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes, such as nephropathy, vasculopathy and neuropathy, diseases of the coronary vessels, restenosis following angioplasty, raised intra-ocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, alzheimers, dementia, anxiety states and cognitive disorders.
- -
-
Page/Page column 65
(2008/06/13)
-
- The nonchiral bislactim diethoxy ether as a highly stereo-inducing synthon for sterically hindered, γ-branched α-amino acids: A practical, large-scale route to an intermediate of the novel renin inhibitor aliskiren
-
The diastereoselective synthesis of the sterically hindered, γ-branched α-amino acid derivative (2S,4S)-24a and its N-[(tert-butoxy)carbonyl](Boc)-protected alcohol (2S,4S)-19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)-17 was obtained by alkylation of the chiral Schoellkopf dihydropyrazine (R)-12a with the dialkoxy-substituted alkyl bromide (R)-11a, which proceeded with explicitly high diastereofacial selectivity (ds > 98%) to give (2S,SR,2′S)-13a (Scheme 4), followed by mild acid hydrolysis and N-Boc protection (Scheme 5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)-11a with the enantiomeric (S)-12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeO-C(6) and the bulky residues of (R)-11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)-11a was found to provide a 95:5 mixture of diastereoisomers (2S,2′S)-22a and (2R,2′S)-23a in high yield (Scheme 6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)-24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)-28a and (R)-28b with both (R)-12a and (S)-12b as well as with the achiral 21 was investigated (Schemes 7-9). The precursor bromides (R)-11a, (S)-11b, (R)-28a, and (S)-28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)-7a and (S)-7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes 3 and 7). A practical and economical protocol of the preparation of (2S,4S)-24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N-protected γ-branched α-amino acid with (2S) absolute configuration.
- Goeschke, Richard,Stutz, Stefan,Heinzelmann, Walter,Maibaum, Juergen
-
p. 2848 - 2870
(2007/10/03)
-