- Anti-influenza virus compound as well as preparation method and application thereof
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The invention provides an anti-influenza virus pharmaceutical compound, and a preparation method and application thereof. The compound provided by the invention is a prodrug, has remarkably improved bioavailability and antiviral activity compared with a parent drug, is suitable for treating/prepaid influenza virus infection related diseases, has improved pharmacokinetic characteristics, and is particularly suitable for being developed into an oral preparation.
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Paragraph 0131; 0134; 0136
(2021/05/01)
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- Halogenated imidazole compound as well as preparation method and application thereof
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The invention discloses alogenated imidazole compounds as well as a preparation method and application thereof. The structure of the halogenated imidazole compounds is disclosed in the invention, wherein, C * in the formula is R-type chiral carbon, and R1 and R2 can be independently selected from H and C1-6 alkyl; R3 is a substituted or unsubstituted C1-18 saturated or unsaturated aliphatic hydrocarbon, the aliphatic hydrocarbon comprises linear, branched or cyclic aliphatic hydrocarbon groups; X is H or a halogen atom; Y is H or a halogen atom; and X and Y cannot be H at the same time. The compounds or pharmaceutically acceptable salts or solvates thereof almost have no corticoid inhibition effect, can generate a rapid reversible anesthetic effect, can be rapidly metabolized into inactivecarboxylic acid metabolites, and have good revival quality after drug withdrawal; the corticoid function of the body can be rapidly recovered after single administration or continuous administration,the occurrence rate of muscular tremor after administration is low, and the body is rapidly awakened after drug withdrawal. The compounds or the salt compounds thereof can be used for preparing central inhibitory drugs which have sedative-hypnotic and/or anesthetic effects on humans or animals.
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Paragraph 0025-0031
(2020/01/25)
-
- Synthesis and characterization of novel analogues of cefpodoxime proxetil
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The present work describes the origin, identification, synthesis, characterization and control of four novel analogues of cefpodoxime proxetil, which are ethyl, methyl, propyl and N-propyl analogues of cefpodoxime proxetil.
- Reddy, Peketi Rajesh,Musunuri, Sivanadh,Reddy, D. Ramasekhara,Chittala, V. Subrahmanyam,Murthy,Krishnamohan
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p. 1751 - 1755
(2020/07/30)
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- Discovery of an Orally Available Diazabicyclooctane Inhibitor (ETX0282) of Class A, C, and D Serine β-Lactamases
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Multidrug resistant Gram-negative bacterial infections are an increasing public health threat due to rapidly rising resistance toward β-lactam antibiotics. The hydrolytic enzymes called β-lactamases are responsible for a large proportion of the resistance phenotype. β-Lactamase inhibitors (BLIs) can be administered in combination with β-lactam antibiotics to negate the action of the β-lactamases, thereby restoring activity of the β-lactam. Newly developed BLIs offer some advantage over older BLIs in terms of enzymatic spectrum but are limited to the intravenous route of administration. Reported here is a novel, orally bioavailable diazabicyclooctane (DBO) β-lactamase inhibitor. This new DBO, ETX1317, contains an endocyclic carbon-carbon double bond and a fluoroacetate activating group and exhibits broad spectrum activity against class A, C, and D serine β-lactamases. The ester prodrug of ETX1317, ETX0282, is orally bioavailable and, in combination with cefpodoxime proxetil, is currently in development as an oral therapy for multidrug resistant and carbapenem-resistant Enterobacterales infections.
- Durand-Réville, Thomas F.,Comita-Prevoir, Janelle,Zhang, Jing,Wu, Xiaoyun,May-Dracka, Tricia L.,Romero, Jan Antoinette C.,Wu, Frank,Chen, April,Shapiro, Adam B.,Carter, Nicole M.,McLeod, Sarah M.,Giacobbe, Robert A.,Verheijen, Jeroen C.,Lahiri, Sushmita D.,Sacco, Michael D.,Chen, Yu,O'Donnell, John P.,Miller, Alita A.,Mueller, John P.,Tommasi, Rubén A.
-
supporting information
p. 12511 - 12525
(2020/12/17)
-
- Benzodiazepine compound as well as preparation method and medical action thereof (by machine translation)
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The invention provides a benzodiazepine compound as well as a preparation method and a medicine effect thereof, and belongs to the field of chemical medicine. The benzodiazepine compound is a compound shown in formula I. Or a salt thereof, or a stereoisomer thereof, or a solvate thereof, or a eutectic thereof, or a composition thereof. The anesthetic effect of the compound of the invention is good, and the anesthetic effect of the compound is equivalent to that of Ramozolam, and even better than that of repirzolam, and particularly shows that the effective dosage is obviously reduced, and the duration and the recovery time are remarkably reduced. At the same time, in the rat tail vein anesthesia model, the compound of the present invention is remarkably improved in comparison with the quality of the Ramozolam wake-up. The compound has the advantages of high effectiveness, short duration, fast resuscitation and good tolerance, can be used for anesthesia induction, anesthesia maintenance and inter-day operation anesthesia, and has a good application prospect. (by machine translation)
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Paragraph 0239-0241
(2021/01/11)
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- SUBSTITUTED CONDENSED THIOPHENES AS MODULATORS OF STING
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A compound of formula (I), wherein: R1 is selected from (i) H, (ii) C3-6cycloalkyl, (iii) C3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A1 is CRA or N; A2 is CRB or N; A3 is CRC or N; A4 is CRD or N; where no more than two of A1, A2, A3, and A4 may be N; one or two of RA, RB, RC, and RD, (if present) are selected from H, F, Cl, Br, Me, CF3, cyclopropyl, cyano, OMe, OEt, CH2OH, CH2OMe and CH2NMe2; the remainder of RA, RB, RC, and RD, (if present) are H; Y is O, NH or CH2; RY is selected from: (RYA) and (RYB).
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Page/Page column 129-130
(2019/12/04)
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- BETA-LACTAMASE INHIBITOR COMPOUNDS
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The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts are useful in combination with beta- lactam antibiotics, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R2, R3, R4, R5 and R6 are described herein.
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Page/Page column 135
(2018/04/13)
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- N-substituted imidazole carboxylate compound, preparation method and use thereof
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A N-substituted imidazole carboxylate compound shown as a formula (I), a preparation method and use thereof are disclosed. In the formula (I), C * is a R type chiral carbon atom, R 1 and R 2 are independently selected from the group consisting of H, methyl, ethyl, cyclopropyl, cyclobutyl or isopropyl or a C2-5 ene-group formed by R1 and R2; and R3 is substituted or unsubstituted C1-18 saturated orunsaturated aliphatic hydrocarbon or aromatic hydrocarbon, wherein the aliphatic hydrocarbon includes a linear, branched or cyclic aliphatic hydrocarbon group. The N-substituted imidazole carboxylatecompound or pharmaceutically acceptable salts thereof can be used to prepare central inhibitory drugs that exert sedative, hypnotic and/or anesthetic effects on humans or animals, can produce rapid and reversible anesthetic effects, and rapidly metabolises into inactive etomidate acid, and after drug withdrawal, recovery quality is good; body's corticosteroid function can be quickly recovered after single administration or continuous administration, the incidence of muscle tremor is low after the administration, and after the drug withdrawal, the recovery is quick.
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Paragraph 0045
(2018/03/26)
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- NEP inhibitor and medicine composition thereof
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The invention relates to an NEP inhibitor and a medicine composition thereof, and in particular, relates to a (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-(3-carboxylpropionylamino)-2-methylpentanoate derivative represented as the formula (I), and a stereoisomer, a hydrate or a solvate thereof, and a medicine composition thereof, wherein the substituent groups in the formula (I) are defined as same as the specification. The series of the compounds in the invention have significant NEP inhibition activity, good solubility and high bioavailability, and can be used for developing medicines used in therapy or prevention of hypertension, pulmonary arterial hypertension, heart failure, kidney diseases and the like, which are related to NEP abnormality, so that it is hopeful to develop a new-generation NEP inhibitor.
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Paragraph 0069; 0070; 0071; 0072
(2017/07/26)
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- Substituted aza indole compounds and salts thereof, composition and use thereof
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The invention provides a substituted azaindole compound having a structure as represented by a formula (I) and a pharmaceutically acceptable salt and a medicinal preparation thereof. The compound is used for adjusting activity of protein kinase and adjusting intercellular or intracellular signal response. The invention further relates to a pharmaceutical composition including the compound and a method of applying the pharmaceutical composition to treatment of highly proliferative diseases of mammals, especially of mankind.
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Paragraph 0620; 0622; 0623
(2018/11/03)
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- 3,3-DISUBSTITUTED-1-HYDROXYTRIAZ-1-ENE 2-OXIDES AND WOUND-HEALING COMPOSITIONS USING THEM
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Esters, carbonates and imides of 3,3-disubstituted-1-hydroxytriaz-1-ene 2-oxides of the formula I are disclosed. The compounds release nitric oxide (NO) under physiologic conditions, and pharmaceutical compositions containing them are useful to aid in wound healing.
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Paragraph 00128
(2015/08/03)
-
- NO-RELEASING NONOATE (NITROGEN-BOUND) SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS
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The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide- linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R1, X, L, R2, R3, R4, and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).
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Paragraph 00161; 00162
(2014/02/15)
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- SUBSTITUTED AZAINDOLE COMPOUNDS, SALTS, PHARMACEUTICAL COMPOSITIONS THEREOF AND METHODS OF USE
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The present invention provides substituted azaindole prodrugs, methods of making said prodrugs, pharmaceutical compositions of said prodrugs and methods of using said prodrugs and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as cancer.
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Paragraph 0459-0460
(2014/03/24)
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- SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES
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There are provided compounds of the formula wherein X, Y, Z, R1, R2, R3 and R4 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.
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Paragraph 0125
(2013/09/26)
-
- NOVEL BETULINIC ACID DERIVATIVES AS HIV INHIBITORS
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(I)The invention relates to novel novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Paragraph 0168
(2013/11/18)
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- SUBSTITUTED METHYLFORMYL REAGENTS AND METHOD OF USING SAME TO MODIFY PHYSICOCHEMICAL AND/OR PHARMACOKINETIC PROPERTIES OF COMPOUNDS
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The present invention relates to the synthesis and application of novel chiral/ achiral substituted methyl formyl reagents to modify pharmaceutical agents and/or biologically active substances to modify the physicochemical, biological and/or pharmacokinetic properties of the resulting compounds from the unmodified original agent.
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Page/Page column 93; 100
(2012/10/18)
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- N-SUBSTITUTED-CYCLIC AMINO DERIVATIVE
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The present invention provides a compound of formula (I): wherein R1a is optionally substituted C1-6 alkyl, etc.; R1m is hydrogen atom, etc.; G1, G2, G3 and G4 are (i), etc. ((i) G1 is -N(R1b)-, G2 is -CO-, G3 is -C(R1c)(R1d)-, and G4 is oxygen, etc.); R1b is optionally substituted C1-6 alkyl, etc.; R1c and R1d are each independently optionally substituted C1-6 alkyl, etc.; R2 is optionally substituted C1-6 alkyl, etc.; R3a, R3b, R3c, and R3d are each independently a group: -A-B (A is a single bond, etc., B is hydrogen atom, etc.), etc.; n is 1, etc.; R5 is C1-4 alkoxycarbonyl, etc., or a pharmaceutically acceptable salt thereof, which is useful as a renin inhibitor.
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Page/Page column 161
(2012/05/20)
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- PRODRUGS OF FUSED HETEROCYCLIC INHIBITORS OF D-AMINO ACID OXIDASE
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The invention relates to prodrugs of fused heterocyclic inhibitors of D-amino oxidase (DAAO) and methods of treating diseases and conditions, wherein modulation of D-amino acid oxidase activity, D-serine levels, D-serine oxidative products and NMDA receptor activity in the nervous system of a mammalian subject is effective.
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Page/Page column 82; 93
(2011/02/26)
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- PRODRUGS OF FUSED HETEROCYCLIC INHIBITORS OF D-AMINO ACID OXIDASE
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The invention relates to prodrugs of fused heterocyclic inhibitors of D-amino oxidase (DAAO) and methods of treating diseases and conditions, wherein modulation of D- amino acid oxidase activity, D-serine levels, D-serine oxidative products and NMDA receptor activity in the nervous system of a mammalian subject is effective.
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Page/Page column 102; 116
(2010/04/03)
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- Imidazole-5-Carboxylic Acid Derivatives, The Preparation Method Therefor and The Uses Thereof
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The invention discloses imidazole-5-carboxylic acid derivatives, and their preparation methods. The derivatives of the invention are Angiotensin II receptor antagonists with angiotensin II antagonistic activity and antihypertensive activity, and thereby can be used as a therapeutical agent to treat hypertension.
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Page/Page column 11-12
(2009/04/24)
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- 2-ARYLMETHYLAZETIDINE-CARBAPENEM-3-CARBOXYLIC ACID ESTER DERIVATIVE OR ITS SALT, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
The present invention provides a 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives or their pharmaceutically acceptable salts show high oral absorption rate, and thus can be orally administered. The active metabolites thereof have a broad spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against methicillin-resistant Staphylococcus aurus (MRSA) and quinolone-resistant strains (QRS). In particular, the acid addition salts of the 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives are obtained in crystalline forms having excellent stability.
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Page/Page column 16-17
(2009/06/27)
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- IMIDAZOL-5-CARBOXYLIC ACID DERIVATIVES, PREPARATION METHODS AND USE THERROF
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The invention discloses imidazole-5-carboxylic acid derivatives, and their preparation methods. The derivatives of the invention are Angiotensin II receptor antagonists with angiotensin II antagonistic activity and antihypertensive activity, and thereby can be used as a therapeutical agent to treat hypertension.
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Page/Page column 13-14
(2008/12/08)
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- PYRIDAZIN-3(2H)-ONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS
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The invention relates to new therapeutically useful pyridazin-3(2H)-one derivatives, to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent and selective inhibitors of phosphodiesterase 4 (PDE4) and are thus useful in the treatment, prevention and suppression of related pathological conditions, diseases and disorders, in particular asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, topic dermatitis, psoriasis or irritable bowel disease.
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Page/Page column 66
(2008/06/13)
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- BETA-LACTAMASE INHIBITOR PRODRUG
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Prodrugs of 6-?-hydroxymethylpenicillanic acid sulfone having the structure wherein R is H or methyl, and solvates thereof, are disclosed. Also disclosed are pharmaceutical compositions comprising a prodrug of the present invention, or a solvate thereof, an optional beta-lactam antibiotic and at least one pharmaceutically acceptable carrier. Further disclosed is a method for increasing the therapeutic effectiveness of a beta-lactam antibiotic in a mammal by administering an effective amount of a betalactam antibiotic and an effectiveness-increasing amount of a prodrug of the present invention, or a solvate thereof. Additionally disclosed is a method for treating a bacterial infection in a mammal by administering a therapeutically effective amount of a pharmaceutical composition of the present invention to a mammal in need thereof.
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- BETA-LACTAMASE INHIBITOR PRODRUG
-
Prodrugs of 6-β-hydroxymethylpenicillanic acid sulfone having the structure wherein R is H or methyl, each X is methylene, and Y is 0, or wherein R is H, each X is 0 and Y is methylene, and solvates thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a prodrug of the present invention, or a solvate thereof, an optional beta-lactam antibiotic and at least one pharmaceutically acceptable carrier. Further disclosed is a method for increasing the therapeutic effectiveness of a beta-lactam antibiotic in 20 a mammal by administering an effective amount of a beta-lactam antibiotic and an effectiveness-increasing amount of a prodrug of the present invention, or a solvate thereof. Additionally disclosed is a method for treating a bacterial infection in a mammal by administering a therapeutically effective amount of a pharmaceutical composition of the present invention to a mammal in need thereof.
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- BENZIMIDAZOLE COMPOUND, PROCESS FOR PRODUCING THE SAME, AND USE THEREOF
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The present invention relates to a compound represented by the following formula wherein each symbol is as defined in the specification, or a salt thereof, which has superior stability to acid and which is a prodrug of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole. This compound (1) shows a superior anti-ulcer activity, a gastric acid secretion-suppressive action, a mucosa-protecting action, an anti-Helicobacter pylori action and the like in living organisms, (2) shows low toxicity, (3) shows superior stability to acid (which obviates the need to formulate an enteric-coated preparation, thereby lowering the cost, and reduces the size of preparation to facilitate swallowing for patients having difficulty in swallowing), (4) shows faster absorption than enteric-coated preparations (rapid expression of gastric acid secretion-suppressive action), and (5) is sustainable.
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- An improved method for preparation of cefpodoxime proxetil
-
Cefpodoxime proxetil, a third-generation cephalosporin for oral administration, was synthesized by a method based on the following sequence of reactions: acylation of 7-aminocephalosporanic acid (7-ACA) with S-benzothiazol-2-yl(2-amino-4-thiazolyl)(methoxyimino)thioacetate (MAEM), chloroacetylation of the cefotaxime formed with chloroacetyl chloride, esterification of the acid function with 1-iodoethyl isopropyl carbonate and final cleavage of chloroacetamide protective group by treatment with thiourea in N,N-dimethylacetamide. The developed procedure allows us to obtain better yields of cefpodoxime proxetil and to eliminate the final purification step by column chromatography, necessary during the synthesis of this antibiotic by the previously reported methods.
- Rodriguez, Juan C.,Hernandez, Ricardo,Gonzalez, Maritza,Rodriguez, Zalua,Tolon, Blanca,Velez, Herman,Valdes, Barbara,Lopez, Miguel A.,Fini, Adamo
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p. 363 - 369
(2007/10/03)
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- Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor
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Certain enol ether derivatives of oxicams (1,1-dioxides of N-heteroaryl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamides and N-heteroaryl-4-hydroxy-2-methyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamides) are useful as prodrugs of these antiinflammatory compounds.
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- Antifibrinolytically active derivatives of tranexamic acid
-
Novel antifibrinolytically active compounds of the formula STR1 and therapeutically acceptable salt thereof, wherein R1 is selected from the group consisting of (a) alkyl groups containing 1-4 carbon atoms, (b) alkoxy groups containing 1-4 carbon atoms, STR2 R2 is selected from the group consisting of (a) H, (b) alkyl groups containing 1-4 carbon atoms, (c) --COOR3, wherein R3 is an alkyl group containing 1-4 carbon atoms, (d) --CONR4 R5, wherein R4 and R5 are the same or different alkyl groups containing 1-3 carbon atoms; or wherein R1 and R2 represent together the radical STR3
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