- A Simple Synthesis of 1-Aminocyclopropane-1-carboxylic Acid
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Conversion of N-carbobenzyloxy-L-glutamic acid α-methylester (Z-L-glu(OH)OCH3, 1) into the bromo derivative 2 and subsequent γ-elimination by the use of sodium hydride leads to the fully protected synthon 3 in good yields.Deprotection by sodium hydroxide and hydrogenolysis yields almost quantitively the key substance 5.
- Strazewski, Peter,Tamm, Christoph
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Read Online
- HERBICIDAL COMPOSITIONS
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The present invention relates herbicidal combinations and their use in controlling plants or inhibiting plant growth. In particular, herbicidal combinations of the invention comprise at least one pyridazine derivative of Formula (I) as defined herein, in combination with at least one further herbicide that is a pyrrolidinone derivatives of the Formula (II) as defined herein.
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Page/Page column 56-57
(2020/08/28)
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- HERBICIDAL COMPOSITIONS
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The present invention relates novel herbicidal combinations and their use in controlling plants or inhibiting plant growth. In particular, herbicidal combinations of the invention comprise at least one pyridazine derivative as defined herein, in combination with at least one futher herbicide that is an acetoclactase synthase (ALS) inhibitor.
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Page/Page column 52-53
(2020/08/28)
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- HERBICIDAL COMPOSITIONS
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The present invention relates to novel herbicidal combinations and their use in controlling plants or inhibiting plant growth. In particular, herbicidal combinations of the invention comprise at least one pyridazine derivative of Formula (I), in combination with at least one futher herbicide that is a non-selective herbicide, a herbicide that acts through the inhibition of protoporphoryinogen oxidase, or a herbicide that inhibits photosystem II in photosynthesis.
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Page/Page column 60; 61
(2020/08/28)
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- HERBICIDAL COMPOSITIONS
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The present invention relates to herbicidal combinations and their use in controlling plants or inhibiting plant growth. In particular, herbicidal combinations comprising at least one pyridazine derivative of Formula (I) as defined herein, in combination with at least one further herbicide that is a compound of Formula (II) as defined herein.
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Page/Page column 50
(2020/08/28)
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- PRE-HARVEST DESICCATION METHOD
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A method for the pre-harvest desiccation of crop plants which comprises applying to the crop plants an effective amount of a compound of formula (I) or an agronomically acceptable salt or zwitterionic species thereof, wherein the substituents are as defined in claim 1.
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Page/Page column 83
(2020/08/28)
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- HERBICIDAL COMPOSITIONS
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The present invention relates novel herbicidal combinations and their use in controlling plants or inhibiting plant growth. In particular, herbicidal combinations of the invention comprise at least one pyridazine derivative of Formula (I), in combination with at least one futher herbicide that is a HPPD-inhibitor herbicide, a synthetic AUXIN herbicide, a herbicide that acts through the inhibition of ACCase, or a herbicide that inhibits cell division through interference with VLCFA biosynthesis.
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Page/Page column 60
(2020/08/28)
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- HERBICIDAL COMPOUNDS
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Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.
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Page/Page column 89; 90
(2019/03/05)
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- 4-((R)-2-{[6-((S)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y12 Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel
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Recent post hoc analyses of several clinical trials with P2Y12 antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y12 antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.
- Caroff, Eva,Hubler, Francis,Meyer, Emmanuel,Renneberg, Dorte,Gnerre, Carmela,Treiber, Alexander,Rey, Markus,Hess, Patrick,Steiner, Beat,Hilpert, Kurt,Riederer, Markus A.
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p. 9133 - 9153
(2015/12/23)
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- SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES
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The present invention relates to compounds of formula I wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
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Page/Page column 32
(2011/04/14)
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- PREPARATION OF ALKENES BY MILD THERMOLYSIS OF SULFOXIDES
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Embodiments of this disclosure, among others, encompass methods for generating alkenes under mild thermolytic conditions that can provide almost total conversion of a precursor compound to an alkene without isomerization or the need to chromatographically purify the final product By selectively blocking the amino and carboxy groups of the depvatized amino acid, the methods of the disclosure provide for the synthesis of a peptide having the vinylglycine moiety at either the carboxy or the amino terminus of the peptide The mild conditions for the thermolytic removal of an o-NO2-phenyl substituted aryl group ensure that there is minimal if any damage to thermally sensitive conjugates such as a peptide bearing the vinylglycine The methods of the present disclosure have practical applications for the preparation of unsaturated compounds under mild, thermolytic conditions.
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Page/Page column 22
(2010/07/02)
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- Preparation of vinylglycines by thermolysis of homocysteine sulfoxides
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The synthesis and efficacy of preparing Cbz-VG-OMe (1) by thermolysis of alkyl and aryl homocysteine sulfoxides were surveyed. This investigation determined that aryl sulfoxide analogs were more effective for the reaction and that the 2-nitrophenyl analog 10f possessed a unique ability to syn eliminate at temperatures as low as 100 °C. The thermolysis of sulfoxide 10f was additionally discovered to occur under toluene reflux and when sodium acetate was added, Cbz-VG-OMe (1) could be obtained in high purity by simple filtration of the precipitated sulfenic acid byproduct 12. This mild protocol which was also applied in the synthesis of VG dipeptide 13 would have utility in the general synthesis of olefins and alkenes from 2-nitrophenylsulfoxides.
- Patel, Sravan Kumar,Long, Timothy E.
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supporting information; experimental part
p. 5067 - 5070
(2009/12/01)
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- SUBSTITUTED 2-PHENYL-PYRIDINE DERIVATIVES
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The present invention relates to compounds of formula (I) wherein R1, R2, R4, R5, Ra, Rb, n, W and Z are as defined in the application, their preparation and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
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Page/Page column 79-80
(2009/11/29)
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- PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
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The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).
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Page/Page column 68
(2009/07/03)
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- A stereoselective synthesis of phosphinic acid phosphapeptides corresponding to glutamyl-γ-glutamate and incorporation into potent inhibitors of folylpoly-γ-glutamyl synthetase
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Radical addition of H3PO2 to N-/C-protected vinyl glycine led to the corresponding H-phosphinic acid in excellent yield. The non-nucleophilic H-phosphinic acid was converted to a nucleophilic P III species, RP(OTMS)2, which was used in two approaches to the target phosphinic acid containing pseudopeptide. New methodology was developed that led to excellent yields in the reaction of RP(OTMS)2 with unactivated electrophiles, including an acyclic homoallylic bromide. However, en route to the target pseudopeptide, Arbuzov reaction of RP(OTMS) 2 with a cyclic homoallylic bromide, (R)-3-(bromomethyl)-cyclopent-1- ene, led to a rearranged allylic phosphinic acid rather than the desired homoallylic derivative, a putative glutarate surrogate. Conjugate addition of RP(OTMS)2 to α-methylene glutarate containing a chiral auxiliary resulted in only modest diastereoselectivity. Purification by flash chromatography provided protected derivatives of both diastereomers of the pseudopeptide. Following global deprotection, coupling of (S)-H-Glu-γ- [Ψ(P(O)(OH)(CH2))]-(S)-Glu-OH and (S)-H-Glu-γ-[Ψ(P(O) (OH)(CH2))]-(R)-Glu-OH to (4-amino-4-deoxy-10-methyl)pteroyl azide led to the target compounds for biochemical study as inhibitors of the ATP-dependent ligase, folylpoly-γ-glutamate synthetase.
- Hartley, David M.,Coward, James K.
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p. 6757 - 6774
(2007/10/03)
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- Utility of tetrathiomolybdate and tetraselenotungstate: Efficient synthesis of cystine, selenocystine, and their higher homologues
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Efficient synthesis of cystine, selenocystine, and their higher homologues like homo and bishomo amino acid derivatives from natural amino acid derivatives using tetrathiomolybdate and tetraselenotungstate reagents under mild and neutral conditions is reported. The generality of the reaction has been studied by capping various groups to amino and carboxyl components of canonical amino acids.
- Bhat, Ramakrishna G.,Porhiel, Emmanuel,Saravanan, Vadivelu,Chandrasekaran, Srinivasan
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p. 5251 - 5253
(2007/10/03)
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- The chemistry of phosphapeptides: Investigations on the synthesis of phosphonamidate, phosphonate, and phosphinate analogues of glutamyl-γ-glutamate
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The synthesis of the phosphonamidate, 1d, and phosphonate, 1e, analogues of a γ-glutamyl peptide are reported. Michaelis-Albuzov reaction with the alkyl halide, 7b, derived from L-glutamic acid, yielded dimethyl phosphonate, 8b. Selective aminolysis of th
- Malachowski,Coward
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p. 7625 - 7634
(2007/10/02)
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- MANIPULATION OF THE CARBOXYL GROUPS OF α-AMINO-ACIDS AND PEPTIDES USING RADICAL CHEMISTRY BASED ON ESTERS OF N-HYDROXY-2-THIOPYRIDONE
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Photolysis of α-amino-acid or peptide esters derived from N-hydroxy-2-thiopyridone in the presence of t-butylthiol affords the expected decarboxylation products in good yield.The reaction can be applied to the α-carboxyl or to the side chain carboxyl of g
- Barton, Derek H. R.,Herve, Yolande,Potier, Pierre,Thierry, Josiane
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p. 5479 - 5486
(2007/10/02)
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- THE FREE RADICAL CHEMISTRY OF CARBOXYLIC ESTERS OF 2-SELENOPYRIDINE-N-OXIDE: A CONVENIENT SYNTHESIS OF (L)-VINYLGLYCINE
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Optically pure (L)-vinylglycine has been synthesised by two different methods.The first of these involves protected (L)-glutamate esters of N-hydroxy-2-seleno-pyridine.Such esters are shown to undergo the same decarboxylative rearrangement as their thio-a
- Barton, Derek H. R.,Crich, David,Herve, Yolande,Potier, Pierre,Thierry, Josiane
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p. 4347 - 4358
(2007/10/02)
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