- Optimization of 2-(1H-imidazo-2-yl)piperazines series of Trypanosoma brucei growth inhibitors as potential treatment for the second stage of HAT
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A previous publication from our laboratory reported the identification of a new class of 2-(1H-imidazo-2-yl)piperazines as potent T. brucei growth inhibitors as potential treatment for Human African Trypanosomiasis (HAT). This work describes the structure–activity relationship (SAR) around the hit compound 1, which led to the identification of the optimized compound 18, a single digit nanomolar inhibitor (EC50 7 nM), not cytotoxic and with optimal in vivo profile that made it a suitable candidate for efficacy studies in a mouse model mimicking the second stage of disease.
- Basta, Andreina,Biancofiore, Ilaria,Ciammaichella, Alina,D'Amico, Melania,Ferrigno, Federica,Fini, Ivan,Gennari, Nadia,Graziani, Rita,Harper, Steven,Nardi, Valentina,Ontoria, Jesus M.,Paonessa, Giacomo,Ponzi, Simona,Summa, Vincenzo,Vittoria Orsale, Maria
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- (R)-4-(1-(6-(4-(TRIFLUOROMETHYL)BENZYL)-6-AZASPIRO[2.5]OCTANE-5-CARBOXAMIDO)-CYCLOPROPYL) BENZOIC ACID OR ITS SALT ALSO IN POLYMORPHIC FORM A FOR USE IN THE PREVENTION OF HETEROTOPIC OSSIFICATION
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There is described a compound of formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)- cyclopropyl)benzoic acid or a pharmaceutically acceptable salt thereof or the form A of its sodium salt for use in the prevention of heterotopic ossification. Preferably such a compound is effective in a specific dose range.
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Paragraph 0044-0046
(2021/06/03)
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- PHARMACEUTICAL COMBINATION OF AN EP4 ANTAGONIST AND IMMUNE CHECKPOINT INHIBITORS FOR THE TREATMENT OF TUMOURS
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The present invention provides a pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5- carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor, preferably the sodium salt of (R)-4-(1- (6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl) benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ ±0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9 is also described. The combination and the polymorphic form A are described for use in the treatment of tumours.
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Page/Page column 11; 12
(2020/10/21)
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- SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
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The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
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Paragraph 0339
(2019/10/15)
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- COMPOUNDS FOR USE IN THE TREATMENT OF KINETOPLASTID INFECTION
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The present invention relates to a class of novel heterocyclic compounds, to pharmaceutical compositions comprising the compounds and their use in the treatment of kinetoplastid infections.
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Page/Page column 65
(2018/07/29)
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- NOVEL DISUBSTITUTED 1, 2, 4-TRIAZINE COMPOUND
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This invention provides a novel disubstituted 1,2,4-triazine compound or a pharmaceutically acceptable salt thereof, which has an aldosterone synthetase inhibitory activity and is useful for preventing and/or treating various diseases or conditions associated with aldosterone; a method for preparing it; use of it; as well as a pharmaceutical composition comprising it as an active ingredient. A compound of the general formula [I]: wherein RA is, for example, a group of the following formula (A-1): wherein ring A1 is, for example, a cycloalkyl group which may be substituted, and RB is, for example, a monocyclic cycloalkyl group, or a pharmaceutically acceptable salt thereof.
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Paragraph 0360
(2017/03/23)
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- Heterocyclic acylamide derivative and preparation method and pharmaceutical application thereof
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The invention relates to a heterocyclic acylamide derivative and a preparation method and pharmaceutical application thereof, in particular to a heterocyclic acylamide derivative shown as a general formula (I) or a stereoisomer and a pharmaceutically-acce
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Paragraph 0585; 0586; 0587; 0588; 0589; 0590; 059
(2017/07/19)
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- Substituted piperidine amide derivative, preparation method thereof, and application of derivative to pharmacy
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The invention relates to a substituted piperidine amide derivative as shown in a general formula (I) or a stereisomer and pharmaceutically acceptable salt thereof, a preparation method of the derivative, medicinal combination as well as application of the derivative to the aspects of local anaesthesia or analgesia. The definition of each group of the general formula (I) is consistent with that of the description. (The general formula (I) is as shown in the description).
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Paragraph 0232; 0233; 0234; 0235; 0236; 0237
(2017/08/30)
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- PDD AND BPD COMPOUNDS
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The invention relates to pyrridinobenzodiazepines (PDDs) comprising three fused 6-7- 6–membered rings and to benzopyrridodiazecines (BPDs) comprising three fused 6-8- 6–membered rings and, in particular, to PDD or BPD dimers linked together or PDD and BPD monomers linked to aromatic groups, and pharmaceutically acceptable salts thereof, which are useful as medicaments, such as anti-proliferative agents. PDDs and BPDs may be represented by formula (I): and salts or solvates thereof, wherein R2, R4-R6 and R8 are independently selected substituent groups; and either: (i) R9 and R10 together form a double bond; (ii) R9 is H and R10 is OH; or (iii) R9 is H and R10 is ORA and RA is C1-6 alkyl; wherein each of m, n, u and w may be 0 or 1; where (a) the compound is a dimer with each monomer being the same or different and being of formula (I) where one of R1, R2, R3 and R7 of the first monomer and one of R'1, R'2, R3 and R'7 of the second monomer form together a bridge having the formula –X-L-X'- linking the monomers and m + n + u + w = 1; or (b) a dimer and one of R1, R2 and R3 of the first monomer and one of R'1, R'2 and R3 of the second monomer form together a bridge having the formula –X-L-X'- linking the monomers and m = n = u = w = o; or (c) one of R1, R2, R3 and R7 has the formula: –X- L-X'-D or -(CH2)f-O-R14 and m + n + u + w = o or 1; or (d) R7 has the formula: –X-L-X'- D or -(CH2)g-O -15 and m + n + u + w = 1; and X-L-X'- is a linker group and D has the formula (II) or (III):
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Page/Page column 92
(2016/12/26)
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- PHENOXYETHYL CYCLIC AMINE DERIVATIVES AND THEIR ACTIVITY AS EP4 RECEPTOR MODULATORS
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The present invention provides a compound of the Formula (I): wherein X, R, R1,R2,R3, R4,R5,R6, R7, R8, and R9 are as defined herein, or a pharmaceutically acceptable salt thereof.
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Page/Page column 12
(2015/07/07)
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- HETEROCYCLIC COMPOUNDS AND METHODS FOR THEIR USE
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The present invention relates to heterocyclic compounds useful for antagonising angiotensin II Type 2 (AT2) receptor. More particularly the invention relates to piperidine compounds, compositions containing them and their use in methods of treating or preventing disorders or diseases associated with AT2 receptor function including neuropathic pain, inflammatory pain, conditions associated with neuronal hypersensitivity, impaired nerve conduction velocity, cell proliferation disorders, disorders associated with an imbalance between bone resorption and bone formation and disorders associated with aberrant nerve regeneration.
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Page/Page column 70-71
(2013/08/15)
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- Novel lincomycin derivatives possessing antimicrobial activity
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Novel lincomycin derivatives are disclosed. These lincomycin derivatives exhibit antibacterial activity. The compounds of the subject invention may exhibit potent activities against bacteria, including gram positive organisms, and may be useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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- Novel lincomycin derivatives possessing antibacterial activity
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Novel lincomycin derivatives are disclosed. These lincomycin derivatives exhibit antibacterial activity. The compounds of the subject invention may exhibit potent activities against bacteria, including Gram positive organisms, and may be useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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- NEW COMPOUNDS
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The present invention relates to new compounds of formula I, wherein P Q X1 X2 X3 X4 X5 R R1 R2 R3 R4R5 G M1 M2 M3 m and n are defined as in formula I, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.
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- AMINO ACID DERIVATIVES
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There is provided amino acid derivatives of formula I, wherein p, q, R 1, R 2, R 3, R 4, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
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Page column 43-44
(2010/01/30)
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- Hydroxy pipecolate hydroxamic acid derivatives
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A compound of the formula wherein R1, R2R3, R4R5, R6, R7, R8, R9and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, and other diseases characterized by matrix metalloproteinase or mammalian reprolysin activity. In addition, the compounds of the present invention may be used in combination therapy with standard non-steroidal anti-inflammatory drugs (NSAID'S), COX-2 inhibitors and analgesics, and in combination with cytotoxic drugs such as adriamycin, daunomycin, cis-platinum, etoposide, taxol, taxotere and other alkaloids, such as vincristine, in the treatment of cancer.
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- A new synthesis of (2S)-4-oxopipecolic acid by thermal rearrangement of enantiopure spirocyclopropaneisoxazolidine
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A novel synthesis of (2S)-4-oxo-pipecolic acid is reported. The synthetic route employs as a key step the diastereoselective cycloaddition of the N- glycosylnitrone 7 to methylenecyclopropane followed by thermal rearrangement of the spirocyclopropaneisoxazolidine 8a. Stereoselective reduction of the N- BOC methyl ester of 4-oxopipecolic acid by L-selectride gives the protected cis-4-hydroxy-pipecolic acid 14.
- Machetti, Fabrizio,Cordero, Franca M.,De Sarlo, Francesco,Guarna, Antonio,Brandi, Alberto
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p. 4205 - 4208
(2007/10/03)
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- PREPARATION OF DI- AND TRIACYLIMINES AND THEIR USE IN THE SYNTHESIS OF NITROGEN HETEROCYCLES
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Reaction of aza-Wittig reagents with glyoxylates and keto malonates produces di- and triacylimines which are moderately reactive dienophiles for Diels-Alder cycloaddition.
- Jung, Michael E.,Shishido, Kozo,Light, Lynn,Davis, Leonard
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p. 4607 - 4610
(2007/10/02)
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