Imidazole-type abscisic acid receptor antagonists and their use

Abstract

The present invention relates to a novel type of compounds which modulate the activity of Abscisic Acid (ABA) receptors in plants. More particularly, such novel compounds are acting as ABA antagonists, which specifically and potently block activation of clade III ABA receptors including but not only PYL1, while another subfamily of compounds has agonistic mode of action promoting activation of the receptor and the ABA signaling pathway. These compounds are, therefore, applicable in different fields of modulating target plant seed germination, modulating target plant growth, modulating tolerance to drought and abiotic stress, modulating fruit ripening, or modulating immunity of a target plant. More particularly, said compounds can be used to stimulate the germination of plant seeds, either under conditions favorable for the growth of crop plants, or unfavorable for the survival of weeds. The compounds can also be used to enhance plant growth under growing conditions where water is not a limiting factor on plant growth. The selectivity of the compounds for clade III ABA receptors will prevent unwanted effects from blocking other ABA receptor subtypes (for example in clade II and clade I groups) present in the plants of interest. The present invention also provides corresponding agrochemical compositions comprising such novel compounds.

Description

[0001]EMBL 2020-011IMIDAZOLE-TYPE ABSCISIC ACID RECEPTOR MODULATORS AND THEIR USEFIELD OF THE INVENTION The present invention relates to a novel type of compounds which modulate theactivity of Abscisic Acid (ABA) receptors in plants. More particularly, such novelcompounds are acting as ABA antagonists, which specifically and potently blockactivation of clade III ABA receptors including but not only PYL1, while another subfamilyof compounds has agonistic mode of action promoting activation of the receptor and theABA signaling pathway. These compounds are, therefore, applicable in different fields of modulating target plant seed germination, modulating target plant growth, modulatingtolerance to drought and abiotic stress, modulating fruit ripening, or modulating immunityof a target plant. More particularly, said compounds can be used to stimulate thegermination of plant seeds, either under conditions favorable for the growth of cropplants, or unfavorable for the survival of weeds. The compounds can also be used toenhance plant growth under growing conditions where water is not a limiting factor onplant growth. The selectivity of the compounds for clade III ABA receptors will preventunwanted effects from blocking other ABA receptor subtypes (for example in clade II andclade I groups) present in the plants of interest. The present invention also providescorresponding agrochemical compositions comprising such novel compounds. BACKGROUND OF THE INVENTION ABA is a phytohormone involved in regulating plant growth, plant response to bioticand abiotic stress and seed germination or dormancy along with other key physiologicalprocesses (REFS https: / / doi.org / 10.1111 / jipb.12899; DOI: 10.1002 / advs.202001265). Itacts on a family of ABA receptors whose individual function in plant homeostasis is still not fully elucidated. Compounds which activate some of these receptors are known (DOI: 10.1002 / advs.202001265 ; https: / / doi.org / 10.1016 / bs.mie.2022.03.062), and their effects on plant stress responses have been studied. However, there are very few inhibitors of ABA signaling reported and these have numerous limitations including phytotoxicity athigh concentrations, complicated synthetic routes, low potency in vitro and in vivo andno selectivity between the ABA receptor subtypes (DOI: 10.1073 / pnas.2108281118 ;https: / / doi.org / 10.1016 / bs.mie.2022.03.062). The physiological response to ABA is controlled by the ABA signaling pathway, which is present in all terrestrial plants. The core components of this pathway include the 1 M / 64069-PCTEMBL 2020-011so called PYR / PYL / RCAR ABA intracellular receptors, a series of protein phosphatases of the Type 2C family (PP2Cs) and the SNIF1-related protein kinases (SnRKs). The molecular mechanism of ABA pathway activation has been elucidated (Cutler, Sean R., Pedro L. Rodriguez, Ruth R. Finkelstein, and Suzanne R. Abrams.2010. “Abscisic Acid:Emergence of a Core Signaling Network.” Annual Review of Plant Biology 61 (1): 651–79. https: / / doi.org / 10.1146 / annurev-arplant-042809-112122. Dupeux, Florine, Regina Antoni, Katja Betz, Julia Santiago, Miguel Gonzalez-Guzman, Lesia Rodriguez, Silvia Rubio, et al. 2011. “Modulation of Abscisic Acid Signaling in Vivo by an EngineeredReceptor-Insensitive Protein Phosphatase Type 2C Allele.” Plant Physiology 156 (1):106–16. https: / / doi.org / 10.1104 / pp.110.170894. Dupeux, Florine, Julia Santiago, Katja Betz, Jamie Twycross, Sang-Youl Park, Lesia Rodriguez, Miguel Gonzalez-Guzman, et al. 2011. “A Thermodynamic Switch Modulates Abscisic Acid Receptor Sensitivity: AThermodynamic Switch in the ABA Pathway.” The EMBO Journal 30 (20): 4171–84.https: / / doi.org / 10.1038 / emboj.2011.294. Santiago, Julia, Florine Dupeux, Katja Betz, Regina Antoni, Miguel Gonzalez-Guzman, Lesia Rodriguez, José Antonio Márquez, and Pedro L. Rodriguez.2012. “Structural Insights into PYR / PYL / RCAR ABA Receptors andPP2Cs.” Plant Science 182 (January): 3–11.https: / / doi.org / 10.1016 / j.plantsci.2010.11.014. Santiago, Julia, Florine Dupeux, AdamRound, Regina Antoni, Sang-Youl Park, Marc Jamin, Sean R. Cutler, Pedro Luis Rodriguez, and José Antonio Márquez. 2009. “The Abscisic Acid Receptor PYR1 inComplex with Abscisic Acid.” Nature 462 (7273): 665–68.https: / / doi.org / 10.1038 / nature08591. Santiago, Julia, Americo Rodrigues, Angela Saez, Silvia Rubio, Regina Antoni, Florine Dupeux, Sang-Youl Park, José Antonio Márquez, Sean R. Cutler, and Pedro L. Rodriguez.2009. “Modulation of Drought Resistance by the Abscisic Acid Receptor PYL5 through Inhibition of Clade A PP2Cs: Regulation ofHAB1 by ABA-Binding Proteins.” The Plant Journal 60 (4): 575–88.https: / / doi.org / 10.1111 / j.1365-313X.2009.03981.x.Weiner, Joshua J, Francis C Peterson, Brian F Volkman, and Sean R Cutler.2010. “Structural and Functional Insightsinto Core ABA Signaling.” Current Opinion in Plant Biology 13 (5): 495–502.https: / / doi.org / 10.1016 / j.pbi.2010.09.007). Under optimal growth conditions PP2Cs and SnrKs form stable complexes leading to the down-regulation of the kinase activity of SnrKs. Under water shortage, ABA biosynthesis is activated and hormone levels rise in all plant tissues. ABA binds into a deep cavity of the ABA intracellular receptors (PYR / PYL / RCAR proteins). This cavity is 2 M / 64069-PCTEMBL 2020-011lined by two flexible loops that close over the hormone upon binding, locking it into the cavity. This conformational change induces the formation of a high affinity complexbetween the receptor and the PP2C phosphatases, releasing the SnRKs and leading tothe activation of the protein kinase activity. SnrKs in turn, phosphorylate a number of cellular factors like Abscisic Acid Responsive Element transcription factors (ABREs), which activate the stress-specific transcriptional program and membrane channels regulating stomata. Most plant species have about a dozen genes coding for differentABA receptor isoforms distributed in three subgroups or clades (clade I, clade II andclade III). Each of these isoforms show different properties.For example, Clade III receptors are known to form homodimers while Clade I and Clade II receptors are mostly monomeric (Dupeux, Santiago, et al.2011). The different receptor isoforms also differ in expression profiles and are thought to have either redundant or relatively specializedfunctions (Dupeux, Santiago, et al. 2011). However, the function of some of thesereceptors is still unknow. ABA also acts as a negative regulator of plant growth and counteracts the effects of growth-stimulating hormones such as gibberellins. Further it inhibits seed germinationand induces maintenance of seed dormancy. These inhibitory effects of ABA ongermination and growth further help plants to withstand stressful conditions and germinate only when the conditions are favorable for growth. ABA also controls a number of important physiological process in plants like seed development andmaturation, bud dormancy, fruit maturation and ripening or the defense response againstcertain pathogens( Gupta, Kapil, Shabir H. Wani, Ali Razzaq, Milan Skalicky, KajalSamantara, Shubhra Gupta, Deepu Pandita, et al. 2022. “Abscisic Acid: Role in FruitDevelopment and Ripening.” Frontiers in Plant Science 13 (May): 817500.https: / / doi.org / 10.3389 / fpls.2022.817500. Huai, Baoyu, Qian Yang, Yingrui Qian, Wenhao Qian, Zhensheng Kang, and Jie Liu. 2019. “ABA-Induced Sugar TransporterTaSTP6 Promotes Wheat Susceptibility to Stripe Rust.” Plant Physiology 181 (3): 1328–43. https: / / doi.org / 10.1104 / pp.19.00632. Kavi Kishor, Polavarapu B., Rhowell N. Tiozon, Alisdair R. Fernie, and Nese Sreenivasulu. 2022. “Abscisic Acid and Its Role in the Modulation of Plant Growth, Development, and Yield Stability.” Trends in Plant Science 27 (12): 1283–95. https: / / doi.org / 10.1016 / j.tplants.2022.08.013. Sun, Liang, Yufei Sun, Mei Zhang, Ling Wang, Jie Ren, Mengmeng Cui, Yanping Wang, et al. 2012.“Suppression of 9 - Cis - Epoxycarotenoid Dioxygenase, Which Encodes a Key Enzymein Abscisic Acid Biosynthesis, Alters Fruit Texture in Transgenic Tomato.” Plant 3 M / 64069-PCTEMBL 2020-011Physiology 158 (1): 283–98. https: / / doi.org / 10.1104 / pp.111.186866. Yoshida, Takuya,Alexander Christmann, Kazuko Yamaguchi-Shinozaki, Erwin Grill, and Alisdair R.Fernie. 2019. “Revisiting the Basal Role of ABA – Roles Outside of Stress.” Trends inPlant Science 24 (7): 625–35. https: / / doi.org / 10.1016 / j.tplants.2019.04.008).ABA antagonists offer the potential to release seed dormancy and promote germination of crops as required, or to promote inappropriate seed germination of weeds at times which are either environmentally unfavorable for weed growth or to allowphysical destruction of weed seedlings, and thus act as non-cytotoxic herbicides. Theycould also be used to decrease susceptibility to infection by certain pathogens (Huai,Baoyu, Qian Yang, Yingrui Qian, Wenhao Qian, Zhensheng Kang, and Jie Liu. 2019. “ABA-Induced Sugar Transporter TaSTP6 Promotes Wheat Susceptibility to StripeRust.” Plant Physiology 181). Moreover, the exact role of some ABA receptor families isstill unknown, therefore such molecules could also modulate other important physiological process in crops and ornamental plants. Modulation of ABA signaling is possible by generating genetic mutants of plants lacking or overexpressing particular ABA receptors. However these changes are permanent for the particular mutant. In order to control and isolate the physiological effects of ABA receptor modulationit is desirable to produce a chemical modulator that can be applied externally to the plants and only when required. US 11,641,857 B2 suggests ABA antagonists derived from the known ABA agonistOpabactin (OP) by attaching in C4 position an azide residue which can be diversified viaCu(I) catalyzed click chemistry to corresponding OP-4-triazoles, like for example compounds of the general formula These ABA antagonists suffer from the drawback of limited receptor selectivity 4 M / 64069-PCTEMBL 2020-011acting on all receptor types rather than on specific receptor isoforms, They show arelatively elevated molecular weight and complex chemical formula. On the other handa number of ABA agonists have been described (Hewage, Kamalani Achala H., Jing-Fang Yang, Di Wang, Ge-Fei Hao, Guang-Fu Yang, and Jian-Kang Zhu. 2020. “Chemical Manipulation of Abscisic Acid Signaling: A New Approach to Abiotic and BioticStress Management in Agriculture.” Advanced Science 7 (18): 2001265.https: / / doi.org / 10.1002 / advs.202001265 but they show limited activity.There is, therefore, a need for providing improved ABA modulators. SUMMARY OF THE INVENTION The above-mentioned problem could, surprisingly, be solved by the provision ofnovel ABA modulators, more particularly ABA antagonists and agonists as furtherdefined herein below. The compounds of the present invention can be tailored to obtain specificselectivity towards certain ABA receptor subtypes, like for example Clade III or dimericreceptors to prevent unwanted effects from blocking other ABA receptor subtypes ,or to have broad activity over different receptor types. For example, based on the FRET assay results described below one example ofbroad specificity would be compound 3r while a selective Clade III compound would becompound 3ac. `DESCRIPTION OF FIGURESFigure 1 shows the results of seed germination assays in wt A. thaliana plants.Figure 2 shows the results of seed germination assays in pyr1 / pyl1 / pyl2 / pyl4 mutant A.thaliana plants.Figure 3 shows the results of seedling establishment assays in wt A. thaliana plants.Figure 4 shows the results of seedling establishment assays in pyr1 / pyl1 / pyl2 / pyl4mutant A. thaliana plants.Figure 5 shows the results of gene expression assays measuring expression level of5 M / 64069-PCTEMBL 2020-011ABA-inducible gene atRD29B in wt A. thaliana plants. (A) shows the antagonistic effectsas observed for Compounds 7i and 7j of the invention. (B) shows the antagonistic effectsas observed for Compound 7k of the invention. (C) shows the antagonistic effects asobserved for Compounds 3ab, 3ag, 7b and 7e of the invention.Figure 6 shows results of seed germination assays in eggplant (var. Tijuana) withcompound 7k. Figure 7 shows results of seedling establishment assays in eggplant (var. Tijuana) with compound 7k.Figure 8 shows the crystallographic structure of the complexe between the tomatoSlPYL1 ABA receptor and the precursor of molecule 3a (2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide). The precursor molecule is depicted beneath the aminoacids in the receptor gate and latch loops of the receptor. Receptor gate loop aminoacids Ser 122, Gly 123 and Pro 125 ar highlighted. Receptor latch amino acids Leu 154,Arg 153 and His 152 are also highlighted. Selected receptor aminonacids and theirinteractions with the molecule are also indicated. As can be observed, the molecule occupies the ABA binding pocket. The imidazole moiety is stabilized by either direct orwater-mediated interactions with Lys 96, Asn204 and Glu 178 at the bottom of the cavity.Additional interactions between the quinoline moiety and amino acids in the gate andlatch loops stabilize the open conformation of the receptor preventing closure of the loops needed for activation of the ABA signalling pathway, thereby confirming the antagonistic mode of action of this molecule.Figure 9 illustrates an example of design rule 1. The X-ray structure of the complexbetween the tomato SlPYL1 ABA receptor and Compound (3a) is shown. As can beappreciated, addition of a hydroxy group at position A of Formula (I) or also present inthe corresponding position in Formula (Ia) further stabilizes the molecule through polarinteractions and hydrogen bonding increasing antagonistic activity. For clarity, here only selected additional direct and water-mediated interactions established between the hydroxy group of the molecule and receptor residues Glu131 and Arg116 are shown.Figure 10 shows an example of design rule 2. The X-ray structure of the complex6 M / 64069-PCTEMBL 2020-011between the tomato SlPYL1 ABA receptor and Compound (7b) is shown. As can beappreciated, addition of, hydrophobic groups (in this case an ethyl group, indicated byan arrow in Figure 10) at position E4 of Formula (I) or a methyl at residue X in Formula(Ia) create further stabilising interactions with a pocket near Leu 154, Ala 197, Val 182, Val 200 and Tyr 157 increasing antagonistic activity.Figure 11 shows an example of design rule 3. The X-ray structure of the complexbetween the tomato SlPYL1 ABA receptor and Compound (3ab) is shown. In this casethe second receptor subunit within the receptor dimer is also depicted on the right half ofthe figure. As can be appreciated, addition of groups at position Q2 of Formula (I) or atthe corresponding position R2 in Formula (Ia) (in this case a phenoxy group) contributeto establish favourable interactions at the interface between the two subunits in a receptor dimer further obstructing gate and latch loops closure and stabilising the receptor dimer, which leads to increased antagonistic activity of the molecules. ABBREVIATIONS ABA: Abscisic Acid ABREs: Abscisic Acid Responsive Element transcription factors Ac: Acetyl AKT1 ATK2: K+membrane transporter isoforms type 1 and 2 Boc: tert-butyl carbamate BOP: benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate tBu: tert-butyl DIPEA: N,N-Diisopropylethylamine DMF: Dimethylformamide Fm: 9-Fluorenylmethyl Fmoc: 9-Fluorenylmethyl carbamate HBTU: hexafluorophosphate benzotriazole tetramethyl Uronium HATU: hexafluorophosphate azabenzotriazole tetramethyl uronium MOM: Methoxymethyl ether PG: protecting groupPyBOP: benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphatePYR / PYL / RCAR: pyrabactin resistance 1 / pyrabactin resistance 1-like / regulatory 7 M / 64069-PCTEMBL 2020-011components of aba receptors PP2C: protein phosphatases of the Type 2C family SnRK: sucrose nonfermenting 1-related protein kinasesSLAC1: S-type channelsTEA: trimethylamineTFA: trifluoroacetic acidFRET: Förster´s Resonance Energy TransferTR-FRET: Time-Resolved FRET Tr: Trityl Ts: Tosyl Z: Benzyl carbamate DETAILED DESCRIPTIN OF THE INVENTIONa) General DefinitionsUnless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The terms "purified", "substantially purified," and "isolated" as used herein refer to the state of being free of other, dissimilar compounds with which a compound of the invention is normally associated in its natural state, so that the "purified", "substantially purified," and "isolated" subject comprises at least 0.5%, 1%, 5%, 10%, or 20%, or at least 50% or 75% of the mass, by weight, of a given sample. In one embodiment, these terms refer to the compound of the invention comprising at least 95, 96, 97, 98, 99 or 100%, of the mass, by weight, of a given sample. As used herein, the terms "purified", "substantially purified," and "isolated" when referring to a nucleic acid or protein, also refers to a state of purification or concentration different than that which occurs naturally, for example in a prokaryotic or eukaryotic environment, like, for example in a bacterial or fungal cell, or in the mammalian organism, especially human body. Any degree of purification or concentration greater than that which occurs naturally, including (1) the 8 M / 64069-PCTEMBL 2020-011purification from other associated structures or compounds or (2) the association with structures or compounds to which it is not normally associated in said prokaryotic or eukaryotic environment, are within the meaning of "isolated”. The nucleic acid or protein or classes of nucleic acids or proteins, described herein, may be isolated, or otherwise associated with structures or compounds to which they are not normally associated in nature, according to a variety of methods and processes known to those of skill in the art. In the context of the descriptions provided herein and of the appended claims, the use of “or” means “and / or” unless stated otherwise. Similarly, “comprise,” “comprises,” “comprising”, “include,” “includes,” and “including” are interchangeable and not intended to be limiting. It is to be further understood that where descriptions of various embodiments usethe term "comprising," those skilled in the art would understand that in some specificinstances, an embodiment can be alternatively described using language "consisting essentially of" or "consisting of.” The term “one or more” or the similar term “at least one” refers to e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more. When the lower and upper limits of a numerical range are disclosed, any numerical value and any inclusive range falling within that range is specifically disclosed, including its upper and lower end value. In particular, every range of values disclosed herein should be understood to mean every value and narrower range that falls within the broader range. The term “about” indicates a potential variation of ± 25% of the stated value, in particular ± 15%, ±10 %, more particularly ± 5%, ± 2% or ± 1%. The term "substantially" describes a range of values of from about 80 to 100%, such as, for example, 85-99.9%, in particular 90 to 99.9%, more particularly 95 to 99.9%, or 98 to 99.9% and especially 99 to 99.9%. “Predominantly” refers to a proportion in the range of above 50%, as for example in the range of 51 to 100%, particularly in the range of 75 to 99,9%; more particularly 85 to 98,5%, like 95 to 99%. If the present disclosure refers to features, parameters and ranges thereof of different degree of preference (including general, not explicitly preferred features, parameters and ranges thereof) then, unless otherwise stated, any combination of two or more of such features, parameters and ranges thereof, irrespective of their respective 9 M / 64069-PCTEMBL 2020-011degree of preference, is encompassed by the disclosure of the present description.b) Chemical and Biochemical DefinitionsThe term "alkyl" as used herein and in the alkyl moieties of “alkoxy” and the likerefers to saturated straight-chain or branched hydrocarbon radicals having 1 to 2 ("C1-C2-alkyl"), 1 to 3 ("C1-C3-alkyl"), 1 to 4 ("C1-C4-alkyl") or 1 to 6 ("C1-C6-alkyl"). C1-C2-Alkyl is methyl or ethyl. C1-C3-Alkyl is additionally propyl and isopropyl. C1-C4-Alkyl is additionally butyl, 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl) or 1,1- dimethylethyl (tert-butyl). C1-C6-Alkyl is additionally also, for example, pentyl, 1- methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1,1- dimethylpropyl, 1,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3- methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2- trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl. The term "haloalkyl" as used herein, which may also be expressed as "alkyl whichis partially or fully halogenated", refers to straight-chain or branched alkyl groups having1 to 2 ("C1-C2-haloalkyl"), 1 to 3 ("C1-C3-haloalkyl"), 1 to 4 ("C1-C4-haloalkyl") or 1 to 6 ("C1-C6-haloalkyl") carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these groups are replaced by fluorine atoms. Examples for C1-C2- haloalkyl (indeed for fluorinated C1-C2-alkyl) are fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, or pentafluoroethyl. Examples for C1-C3-haloalkyl (indeed for fluorinated C1-C3-alkyl) are, in addition to those mentioned for C1-C2-haloalkyl, 1-fluoropropyl, 2-fluoropropyl, (R)-2- fluoropropyl, (S)-2-fluoropropyl, 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl,1,2-difluoropropyl, 2,3-difluoropropyl, 3,3-difluoropropyl, 2,2,3-trifluoropropyl, 3,3,3-trifluoropropyl, 2,2,3,3-tetrafluoropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl,1,1,1-trifluoroprop-2-yl, 2-fluoro-1-methylethyl, (R)-2-fluoro-1-methylethyl, (S)-2-fluoro-1-methylethyl, 2,2-difluoro-1-methylethyl, (R)-2,2-difluoro-1-methylethyl, (S)-2,2-difluoro- 1-methylethyl, 2,2,2-trifluoro-1-methylethyl, (R)-2,2,2-trifluoro-1-methylethyl, (S)-2,2,2- trifluoro-1-methylethyl, 2-fluoro-1-(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2- difluoroethyl, 1-(trifluoromethyl)-2,2,2-trifluoroethyl, 1-(trifluoromethyl)-1,2,2,2- tetrafluoroethyl and the like. Examples for C1-C4-haloalkyl are, in addition to those mentioned for C1-C3-haloalkyl, 2-fluorobutyl, (R)-2-fluorobutyl, (S)-2-fluorobutyl, 3- 10 M / 64069-PCTEMBL 2020-011fluorobutyl, (R)-3-fluorobutyl, (S)-3-fluorobutyl, 4-fluorobutyl, 2,2-difluorobutyl, 3,3-difluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, 3,3,4,4-tetrafluorobutyl, 3,4,4,4- tetrafluorobutyl, 2,2,4,4,4-pentafluorobutyl, 3,3,4,4,4-pentafluorobutyl, 2,2,3,4,4,4- hexafluorobutyl, 1-methyl-2,2-3,3-tetrafluoropropyl and the like. "Alkylene" is a linear or branched divalent alkanediyl radical. C1-C3-Alkylene is alinear or branched divalent alkyl radical having 1, 2 or 3 carbon atoms. C1-C4-Alkylene isa linear or branched divalent alkyl radical having 1, 2, 3 or 4 carbon atoms. C1-C6- Alkylene is a linear or branched divalent alkyl radical having 1, 2, 3, 4, 5 or 6 carbon atoms. Examples are -CH2-, -CH2CH2-, -CH(CH3)-, -CH2CH2CH2-, -CH(CH3)CH2-, - CH2CH(CH3)-, -C(CH3)2-, -CH2CH2CH2CH2-, -CH(CH3)CH2CH2-, -CH2CH2CH(CH3)-, -C(CH3) 2CH2-, -CH2C(CH3)2-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9-, -(CH2)10- andpositional isomers thereof. “Alkenylene” refers to the mono-unsaturated analogues of the above mentionedalkylenes, having 2, 3 or 4 carbon atoms (C2-C4-alkenylenes) or having 2, 3, 4, 5 or 6carbon atoms (C2-C6-alkenylenes). "Carboxyl" refers to a group of the formula -C(=O)OH.The term “hydroxylalkyl” refers to the hydroxyl-substitued analogues of the above-identified alkyl residues. They carry 1 or more , in particular 1, 2 or 3, more particularlyone hydroxyl residue. Non-limiting examples for C1-C2-hydroxyalkyl are hydroxymethyl,1-hydroxyethyl, and 2-hydroxyethyl. Examples for C1-C3-hydroxyalkyl are, in addition tothose mentioned for C1-C2-hydroxyalkyl, 1-hydroxypropyl, 2-hydroxypropyl, (R)-2- hydroxypropyl, (S)-2-hydroxypropyl, 3-hydroxypropyl, 2-hydroxy-1-methylethyl, (R)-2-hydroxy-1-methylethyl, (S)-2-hydroxy-1-methylethyl, Examples for C1-C4-hydroxyalkylare, in addition to those mentioned for C1-C3-hydroxyalkyl, 2-hydroxybutyl, (R)-2- hydroxybutyl, (S)-2-hydroxybutyl, 3-hydroxybutyl, (R)-3-hydroxybutyl, (S)-3- hydroxybutyl, 4-hydroxybutyl, and the like. The term “cyanoalkyl” refers to the cyano-substitued analogues of the above-identified alkyl residues. They carry 1 or more , in particular 1, 2 or 3, more particularly one cyano residue. Non-limiting examples for C1-C2-cyanoalkyl are cyanomethyl, 1- cyanoethyl, and 2-cyanoethyl. Examples for C1-C3-cyanoalkyl are, in addition to those mentioned for C1-C2-cyanoalkyl, 1-cyanopropyl, 2-cyanopropyl, (R)-2-cyanopropyl, (S)- 2-cyanopropyl, 3-cyanopropyl, 2-cyano-1-methylethyl, (R)-2-cyano-1-methylethyl, (S)-2-cyano-1-methylethyl, Examples for C1-C4-cyanoalkyl are, in addition to those mentionedfor C1-C3-cyanoalkyl, 2-cyanobutyl, (R)-2-cyanobutyl, (S)-2-cyanobutyl, 3-cyanobutyl, 11 M / 64069-PCTEMBL 2020-011(R)-3-cyanobutyl, (S)-3-cyanobutyl, 4-cyanobutyl, and the like. The term “alkoxy” as used herein refers to residues of the general formula -O-alkyl,as for example –O-C1-C3-alkyl or -O-C1-C4-alkyl, wherein its “-alkyl” moiety is as definedabove. The term “carbocyclic” refers to a moiety comprising 3 to 14, like, for example, 5 or6, ring carbon atoms. Said carbocyclic ring may be a mono- or polycyclic, like di- or tri-cyclic, carbocyclic ring, and may be a saturated or mono- or polyunsaturated,nonaromatic or aromatic ring system. The term “heterocyclic” refers to a monocyclic or polycyclic, like di- or tri-cyclicsaturated, or mono- or polyunsaturated non-aromatic or aromatic ring moiety, containing5 to 14, in particular 5 to 10, like 5 or 6 ring atoms. including 1 to 5, in particular 1, 2 or 3identical or different ring heteroatom, selected from N, O and S.The term "cycloalkyl" as used herein refers to monocyclic saturated carbocyclicradicals having 3 to 8 carbon ring members ("C3-C8-cycloalkyl"). Examples arecyclopropyl, cyclobutyl, cyclopentyl ,cyclohexyl, cycloheptyl and cyclooctyl.The term “aryl” denotes an aromatic, mono- or polycyclic, like di- or tri-cyclic,carbocyclic ring containing 6 to 14, in particular 6 to 10 carbon atoms. Examples are phenyl, naphthyl, phenanthrenyl and anthracenyl. The term “heteroaryl” refers to an aromatic, monocyclic or polycyclic, like di- or tri-cyclic aromatic ring moiety, containing 5 to 14, in particular 5 to 10 ring atoms, including1 to 5, in particular 1, 2 or 3 identical or different ring heteroatom selected from N, O andS. Examples for 5- or 6-membered monocyclic heteroaromatic rings or bicyclicheteroaromatic rings containing 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S as ring members are, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 1- pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1,3,4-triazol-1-yl, 1,3,4-triazol-2-yl, 1,3,4-triazol-3-yl, 1,2,3- triazol-1-yl, 1,2,3-triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,5-oxadiazol-3-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,5-thiadiazol-3-yl, 1,2,3-thiadiazol-4-yl,1,2,3-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 5-pyridinyl,3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5- triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,3,4-tetrazin-1-yl, 1,2,3,4-tetrazin-2-yl, 1,2,3,4-tetrazin-5-yl, quinolin-3-yl, 1H-pyrrolo[2,3-b]pyridine-5-yl, 1,8-naphthyridin-3-yl, 12 M / 64069-PCTEMBL 2020-0111H-benzo[d]imidazol-2-yl and the like.The term “aryloxy” or “heteroaryloxy” as used herein refers to residues of thegeneral formula -O-aryl or –O-heteroaryl, wherein “aryl” or “heteroaryl” are as definedherein above.The term “arylamino” refers to residues of formula “ -NH-aryl” or “-NH-heteroaryl”,i.e. “aryl” or “heteroaryl” rings as defined above which are attached to a nitrogen atomthrough a single bond.The term “substituted carbocyclic ring” refers to mono- or poly-substitutedanalogues of the above-mentioned aromatic or non-aromatic carbocyclic rings asdefined above. In particular, they may be substituted by 1 or more, in particular 1, 2, 3,4 or 5 identical or different substituents as defined herein below. The term “substituted heteroaryl ring” refers to mono- or poly-substitutedanalogues of the above-mentioned heteroaryl rings. In particular, they may besubstituted by 1 or more, in particular 1, 2, 3, 4 or 5 identical or different substituents as defined herein below. Unless indicated otherwise, the term "substituted" or “substituent” means that aradical is substituted with residues selected from the group of halogen, like F, Cl and Br,–C(halogen)3, wherein halogen residues thereof are identical or different and areselectedfrom F, Cl and Br; -C1-C3-alkyl, -C1-C3-hydroxyalkyl, -C1-C3-cyanoalkyl, -C1-C3-alkylene-C(O)O-C1-C4-alkyl, -C3-C8-cycloalkyl, -OH, -CN, -C(O)OH,- C(O)O(-C1-C4-alkyl), -O-C1-C3-alkyl or -C(O)NRaRb, wherein Raand Rbare independently selected from H or -C1-C4- alkyl. The term "halogen" denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine. Halogen as a substituent on an aromatic or heteroaromatic group is particularly selected from F, Cl or Br. The term “protecting group” or “protective group” as used herein refers to anunreactive moiety hosted in a molecule and obtainable by reversible modification of agiven functional group. The protecting group serves as reversible protection to prevent undesired reaction of the protected functional group during the course of a reaction. If more than one functional group are present in a molecule, chemoselectivity can be achieved by orthogonally protecting the reactive functionalities by means of protectinggroups which can be removed under substantially different conditions thereby enablingselective deprotection of one protecting group while not affecting other protecting groups present in the same molecule. The specific nature of protecting groups depends on 13 M / 64069-PCTEMBL 2020-011multiple factors such as the nature of the chemical functionality to be protected and overall synthetic strategy employed. Non-limiting examples of protecting groups are: ^Amino or nitrogen protecting groups: Fmoc, Fm, Boc, tBu, Z, Ac, Tr, Ts;^ Caboxyl protecting groups: methyl-, benzyl- and tert-butyl esters;^ Hydroxyl protecting groups: MOM, tBu ether, allyl ether, benzyl ether, aceticacid ester, benzoic acid ester. The term “orthogonal protection” refers to a strategy allowing the specificdeprotection of one protective group in a multiply-protected structure. Compounds as herein described may contain one or more asymmetric elements such as stereogenic centers, stereogenic axes and the like, e.g. asymmetric carbon atoms, so that the compounds can exist in different stereoisomeric forms. These compounds can be, for example, racemates or optically active forms. All stereoisomers,diastereomers, Z- and E-forms, in purified and mixture forms are included. Accordingly,when a compound is recited by specific name or a class of compounds is recited, all these forms are intended to be included. Compounds as herein described may also exist in more than one form ofstructural isomers also designated as constitutional isomers or regioisomers. These aremolecules that differ only in the different sequence of their atoms or atomic groups while having the same gross formula. Therefore, unless otherwise stated, for each of the compounds as describedherein, any such potential stereo- or regiosomeric form or mixture of more than onestereo- and / or regiosomeric form is within the scope of the present invention.The PYR / PYL / RCAR receptor complex and receptor subtypes which compounds of the present interact with are well known. Clade I, II and III receptor subtypes are forexample described by Helander et al., Bioorganic & Medicinal Chemistry Volume 24,Issue 3, 2016, Pages 493-500, https: / / doi.org / 10.1016 / j.bmc.2015.11.010.c) Particular aspects and embodiments of the inventionA first aspect of the present invention relates to the use of a compound of the generalformula I 14 M / 64069-PCTEMBL 2020-011 wherein Q1is H Q2is -C(O)-NH-( alkylene)-aryl, in particular -C(O)-NH-(C1-C4-alkylene)- aryl, or Q1and Q2, together with the carbon atoms to which they are attached, form an unsubstituted or substituted, in particular unsubstituted or 1-, 2- or3-fold substituted, in particular 1-fold substituted, 5-6 memberedcarbocyclic or heterocyclic ring, in particular 6 membered carbocyclicring being unsubstituted or substituted, as for example 1-, 2- or 3-foldsubstituted, in particular 1-fold substituted or unsubstituted 6- membered carobocyclic ring; wherein said optional substituents of each 5-6 membered carbocyclic or heterocyclic ring are independently selected from residues ofgroup a): halogen, alkyl, -O- alkyl, -C(O)O- alkyl, cycloalkyl, haloalkyl, or areindependently selected from optionally substituted residues ofgroup b): unsubstituted or substituted aryl,unsubstituted or substituted -O-aryl, unsubstituted or substituted -NH-aryl, unsubstituted or substituted –S(O)n- aryl with n = 0, 1 or 2,unsubstituted or substituted -O-alkylene-aryl, unsubstituted or substituted -O-alkenylene-aryl, and unsubstituted or substituted heteroaryl;15 M / 64069-PCTEMBL 2020-011more particularly, said optional substituents of each 5-6 membered carbocyclic or heterocyclic ring being selected from residues of subgroup a1): halogen, -C1-C3-alkyl, -O-C1-C3-alkyl, -C(O)O-C1-C3- alkyl, -C3-C8-cycloalkyl, -C1-C3-haloalkyl, or are independently selected from optionally substituted residues of subgroup b1): unsubstituted or substituted -C6-C10-aryl, unsubstituted or substituted -O-C6-C10-aryl, unsubstituted or substituted -NH-C6-C10-aryl, unsubstituted or substituted –S(O)n-C6-C10-aryl with n = 0, 1 or 2, unsubstituted or substituted -O-C1-C4-alkylene-C6-C10- aryl, unsubstituted or substituted -O-C2-C4-alkenylene-C6-C10- aryl, and unsubstituted or substituted -C3-C8-heteroaryl, wherein said optional substituents of optionally substituted residues of group b) and subgroup b1) are aryl or heteroaryl ring substituents, independently selected from residues of group c):halogen, -CN, –C(halogen)3, -alkyl, and -O-alkyl; in particular selected from halogen, -CN, –C(halogen)3, -C1-C3-alkyl, and -O-C1-C3-alkyl; A is selected from -OH, -NH2, -NH-alkyl, -N(alkyl)2, -NH-CO-alkyl, -in particular -OH, -NH2, -NH-(C1-C3 alkyl), -N(C1-C3-alkyl)2, -NH-CO-(C1- C3-alkyl), more particularly –OH; Z3is nitrogen or CH; E1, E2, E3and E4are independently from each other selected from unsubstituted carbon (i.e. C-H) ring atoms, substituted carbon orunsubstituited nitrogenring atom; with the proviso that E1, E2, E3and E4are not simultaneously N; 16 M / 64069-PCTEMBL 2020-011or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof, as abscisic acid (ABA) plant hormone receptor modulator.These compounds offormula (I) may act as ABA plant hormone receptor antagonistor agonist, in particular as ABA plant hormone receptor antagonist. Particularly, said compounds modulate the action of the ABA plant hormone viainteraction with the PYR / PYL / RCAR receptor complex of a plant. In particular, they interact with at least one of the following PYL receptor subtypeswithin Clade III including PYL1, PYR1, PYL2 and PYL3; Clade II including PLY4, PYL5,PYL6, PYL11 and PYL12; and Clade I including PYL7, PYL8, PYL9 and PYL10More particularly, they interact with at least one Clade III receptor sutype, selectedfrom PYL1, PYR1, PYL2 and PYL3, and oprionally also with at least one of the Clade I receptor subtypes selected from PYL7, PYL8, PYL9 and PYL10; and / or at least one ofthe Clade II receptor subtypes selected from PLY4, PYL5, PYL6, PYL11 and PYL12.An interaction with PYL1 and optionally also with at least one of its structurally mostrelated Clade III receptor subtypes PYR1, PYL2 and / or PYL3 showing similar ligandbindng propensities (Helander et al., Bioorganic & Medicinal Chemistry Volume 24, Issue3, 2016, Pages 493-500, https: / / doi.org / 10.1016 / j.bmc.2015.11.010 is very particular.Most particularly the interaction comprises an interaction with PYL1 and optionallyan interaction also with PYL2 and / or PYR1 subtype.According to another most particular embodiment said compounds act as ABAplant hormone antagonist via an interaction comprising the interaction with the PYL1receptor subtype. Non-limiting examples of receptor substyples, like in particular PYL1 receptorsubtypes, are those isolated from Solanum or Arabidopsis plants, in particulatr from S.lycopersicum (SL) and A. thaliana (AT).In a particular embodiment compounds of formula I are used, whereinQ1and Q2, together with the carbon atoms to which they are attached, form anunsubstituted or substituted, more particularly mono-, di- or tri-substituted, 5-6membered carbocyclic or heterocyclic ring, wherein said substituents are independently selected from residues of group aa):17 M / 64069-PCTEMBL 2020-011F, Cl, Br, -CH3, -O-CH3, -C(O)O-CH3, -cyclopropyl, -CF3, or are independently selected from residues of group bb): unsubstituted or substituted -phenyl, unsubstituted or substituted -O-phenyl, unsubstituted or substituted -NH-phenyl, unsubstituted or substituted –S(O)n-phenyl with n = 0, 1 or 2, unsubstituted or substituted -O-ethylene-phenyl, unsubstituted or substituted -O-ethenylene-phenyl, unsubstituted or substituted pyrrazole, unsubstituted or substituted thiophene or unsubstituted or substituted pyridine, wherein said optional substituents of residues of group bb) are aryl or heteroaryl ring substituents, independently selected from residues of group cc): halogen, -CN, –C(halogen)3, -C1-C3-alkyl, and -O-C1-C3-alkyl. In a particular embodiment compounds of formula I are used, wherein residue E1represents CH. In a particular embodiment compounds of formula I are used, wherein residue E2represents an unsubstituted nitrogen ring atom (-N=).In still another particular embodiment compounds of formula I are used, wherein E1and E2are unsubstituted nitrogen ring atoms (-N=). In still another particular embodiment compounds of formula I are used, whereinE3and E4are independently from each other optionally substituted carbon ring atoms, wherein said optional substituents are selected from halogen, –C(halogen)3, -C1-C3-alkyl, -C1-C3-hydroxyalkyl, -C1-C3-cyanoalkyl, -C1-C3-alkylene-C(O)O-C1-C3 alkyl, and -C3-C8- cycloalkyl. In still another particular embodiment compounds of formula I are used, whereinE2 is an unsubstituted nitrogen ring atom (-N=).In still another particular embodiment compounds of formula I are used, whereinE1, E3and E4are independently from each other optionally substituted carbon ring atoms, wherein said optional substituents are selected from halogen, –C(halogen)3, -C1-C3-alkyl, 18 M / 64069-PCTEMBL 2020-011-C1-C3-hydroxyalkyl, -C1-C3-cyanoalkyl, -C1-C3-alkylene-C(O)O-C1-C3alkyl, and -C3-C8- cycloalkyl. An “unsubstituted ring carbon atom” carries in place of such substituent a hydrogen atom, and may also be described as C-H group). In still another particular embodiment compounds of formula I are used, whereinA is OHZ3is N E1is CH E2is N E3is CH E4is CH, or a substituted carbon atom, where said substituent is selected from halogen, -C1-C3-alkyl or -C3-C8-cycloalkyl. Q1is H and Q2is -C(O)-NH-(C1-C4-alkylene)-phenyl, or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof isused. In a particular alternative the compounds used are compounds of formula Ia wherein, Xis H, alkyl, in particular -C1-C4-alkyl, more particularly methyl, ethyl,isopropyl or isopropyl, cycloalkyl, in particular -C3-C6-cycloalkyl, moreparticularly cyclopropyl, -CF3, -CF2H, -CFH2, -C1-C2-alkyl optionallysubstituted by -OH, -CN, -C(O)OH,- C(O)OR or -C(O)NRaRb; ,wherein R is alkyl, in particular -C1-C4-alkyl, and Raand Rbare independently selected from H or alkyl, in particular -C1-C4-alkyl 19 M / 64069-PCTEMBL 2020-011Z1is nitrogen or >CH, or >C-alkyl, in particular >C-C1-C4-alkyl Z2 is nitrogen, >CH or >C-alkyl, in particular >C-C1-C4-alkyl,Z3is nitrogen or >CH, R1, R2, R3 and R4, independently of each other are selected from residues ofgroup d): H, halogen, alkyl, -O- alkyl, -C(O)O-alkyl, cycloalkyl, haloalkyl; orare independently selected from optionally substituted residues of group e): unsubstituted or 1-, 2- or 3-fold substituted aryl,unsubstituted or 1-, 2- or 3-fold substituted -O-aryl,unsubstituted or 1-, 2- or 3-fold substituted -NH- aryl,unsubstituted or 1-, 2- or 3-fold substituted –S(O)n-aryl with n = 0, 1 or2, unsubstituted or -, 2- or 3-fold substituted -O-alkylene-aryl,unsubstituted or 1-, 2- or 3-fold substituted -O- alkenylene-aryl, andunsubstituted or 1-, 2- or 3-fold substituted heteroaryl;more particularly, R1, R2, R3 and R4, independently of eachother are selected from residues of group dd):selected from the group consisting of H, halogen, -C1-C3-alkyl, -O-C1-C3-alkyl, -C(O)O-C1-C3- alkyl, -C3-C8-cycloalkyl, -C1-C3-haloalkyl, or are independently selected from optionally substituted residues of group ee): unsubstituted or 1-, 2- or 3-fold substituted -C6-C10-aryl, unsubstituted or 1-, 2- or 3-fold substituted -O-C6-C10-aryl, unsubstituted or 1-, 2- or 3-fold substituted -NH-C6-C10-aryl, unsubstituted or 1-, 2- or 3-fold substituted –S(O)n-C6-C10-aryl with n = 0, 1 or 2, unsubstituted or 1-, 2- or 3-fold substituted -O-C1-C4-alkylene-C6-C10-aryl, 20 M / 64069-PCTEMBL 2020-011unsubstituted or 1-, 2- or 3-fold substituted -O-C2-C4-alkenylene-C6-C10-aryl, and unsubstituted or 1-, 2- or 3-fold substituted -C3-C8-heteroaryl, wherein said optional substituents of groups e) or ee) are aryl or heteroaryl ring substituents, independently selected from residues of group f): halogen, -CN, –C(halogen)3, -alkyl, and -O-alkyl; in particular selected from halogen, -CN, –C(halogen)3, -C1-C3-alkyl, and - O-C1-C3-alkyl; or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. This preferred group of compounds of formula Ia may act as ABA plant hormone receptor antagonist or agonist, in particular as ABA plant hormone receptor antagonist. These preferred compounds of formula Ia may act as ABA plant hormoneantagonist or agonist, in particular as potent ABA plant hormone antagonist. Particularly, said compounds modulate the action of the ABA plant hormone via interaction with the PYR / PYL / RCAR receptor complex of a plant. In particular, they interact with at least one of the following PYL receptor subtypesof the Clade III including PYL1, PYR1, PYL2 and PYL3, or of the Clade II including PLY4,PYL5, PYL6, PYL11 and PYL12 or of the clade I including PYL7, PYL8, PYL9, PYL10, , More particularly, they interact with at least one Clade III receptor subtype. SaidClade III receptor subtype is preferably selected from PYL1, PYR1, PYL2 and PYL3.Oprionally they also interact with at least one of the Clade I receptor subtypes selectedfrom PYL7, PYL8, PYL9 and PYL10; or at least one of the Clade II receptor subtypesselected from PLY4, PYL5, PYL6, PYL11 and PYL12. An interaction with PYL1 and optionally also with at least one of its structurally mostrelated subtypes PYR1, PYL2 and / or PYL3 subtype (Helander et al., Bioorganic &Medicinal Chemistry Volume 24, Issue 3, 2016, Pages 493-500,https: / / doi.org / 10.1016 / j.bmc.2015.11.010) ) is very particular.Most particularly the interaction comprises an interaction with PYL1 and optionallyan interaction also with PYL2 and / or PYR1 subtype.21 M / 64069-PCTEMBL 2020-011According to another most particular embodiment said compounds act as ABAplant hormone antagonist via an interaction comprising the interaction with the PYL1receptor subtype. Non-limiting examples of PYL1 receptor subtypes are those isolated from Solanumor Arabidopsis plants, in particulatr fro S. lycopersicum (SL) and A. thaliana (AT).According to a particular embodiment compounds of formula Ia are used, wherein X is H, C1-C4-alkyl, like methyl, ethyl, isopropyl or cyclopropyl, C1-C2-alkyl optionally substituted by -OH, -CN, -C(O)OH, -C(O)OR or -C(O)NRaRbwherein R, Raand Rbare independently selected from H or C1-C4-alkyl. According to another particular embodiment compounds of formula Ia are used, wherein Xis H, methyl, ethyl, isopropyl, cyclopropyl, cyanomethyl , or -CH2-C(O)O-C1-C4-alkyl Z1is nitrogen or CH Z2is nitrogen, CH or C--C1-C4-alkyl Z3is nitrogen or CH R1is H, -O-C1-C4-alkyl, or halogen R2is halogen, phenyl, phenoxy, -CF3, -C1-C4-alkyl, -C1-C4-alkoxy, -C(O)O- C1-C4-alkyl, -C1-C4-alkylene-phenyl, -C2-C4-alkenylene-phenyl, 5- or 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from N and S; R3is H or –O-C1-C4-alkyl, and R4is H, Hal, -O-C1-C4-alkylor an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof.According to still another particular embodiment compounds of formula Ia areused, whereinX H, methyl, ethyl, isopropyl, cyanomethyl or cyclopropyl, or -CH2-C(O)O-methyl Z1is nitrogen or CH Z2is CH or C-CH322 M / 64069-PCTEMBL 2020-011Z3is nitrogen or CH R1 is H, -O-methyl, or BrR2is F, Cl, Br, phenyl, phenoxy, -CF3, methyl, methoxy, -C(O)O-methyl, --n- butylene-phenyl, -2-butenylene-pheny, pyrazolyl, thiophenyl or pyridinyl or H;R3is H or Br and R4is H, Br, -O-methyl. or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. According to another particular embodiment compounds of formula Ia are used, wherein Z1is CH. According to another particular embodiment compounds of formula Ia are used, wherein Z2is CH. According to another particular embodiment compounds of formula Ia are used,wherein Z3is nitrogen or CH. According to another particular embodiment compounds of formula Ia are used, wherein Z3is nitrogen. According to another particular embodiment compounds of formula Ia are used,wherein X is H, methyl, ethyl, isopropyl, or cyclopropyl.According to another particular embodiment compounds of formula Ia are used, wherein R1is H. According to another particular embodiment compounds of formula Ia are used, wherein R2is Br or Cl or –O-methyl. According to another particular embodiment compounds of formula Ia are used, wherein R3is H. According to another particular embodiment compounds of formula Ia are used, wherein R4is H. According to another particular embodiment compounds of formula Ia are used,wherein R1, R3 and R4 are H.According to another particular embodiment compounds of formula Ia are used,wherein R1, R2 and R4 are H.According to another particular embodiment compounds offormula Ia are used, wherein R1, R2 and R3 are H.23 M / 64069-PCTEMBL 2020-011According to another particular embodiment compounds of formula Ia are used,wherein R2, R3 and R4 are H.According to another particular embodiment compounds of formula Ia are used,wherein R1, R3 and R4 are H and R2 is is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl.According to another particular embodiment compounds of formula Ia are used,wherein R1, R2 and R4 are H and R3 is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl.According to another particular embodiment compounds of formula Ia are used,wherein R1, R2 and R3 are H and R4 is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl.According to another particular embodiment compounds of formula Ia are used,wherein R2, R3 and R4 are H and R1 is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl.According to still another particular embodiment compounds of formula Ia areused, whereinX H, methyl, ethyl, isopropyl, or cyclopropyl,Z1is CH Z2is CH Z3is nitrogen R1is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl, R2is H; R3is H and R4is H; or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. According to still another particular embodiment compounds of formula Ia areused, whereinX H, methyl, ethyl, isopropyl, or cyclopropyl,Z1is CH Z2is CH Z3is nitrogen R1is H, R2is H; R3 is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl, and24 M / 64069-PCTEMBL 2020-011R4is H; or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. According to still another particular embodiment compounds of formula Ia areused, whereinX H, methyl, ethyl, isopropyl, or cyclopropyl,Z1is CH Z2is CH Z3is nitrogen R1is H, R2is H; R3is H; and R4 is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl;or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. According to still another even more particular embodiment compounds of formulaIa are used, whereinX H, methyl, ethyl, isopropyl, or cyclopropyl,Z1is CH Z2is CH Z3is nitrogen R1is H, R2is H, F, Cl, Br, phenyl, phenoxy, or thiophenyl; R3is H and R4is H; or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof. According to another aspect the present invention relates to the use of at least onecompound of general formulae I or Ia as abscisic acid (ABA) plant hormone antagonist. Particularly, said at least one ABA antagonist is applied for the control of target plant seed dormancy, wherein said target plant seed is selected from crop and non-crop plant seeds. More particularly, said target plant seeds are subjected to seed priming or anysimilar treatments, either by applying a solution containing at least one ABA antagonist 25 M / 64069-PCTEMBL 2020-011as defined herein above; or by dry-coating or soaking said target plant seeds with at least one ABA antagonist as defined herein above. “Seed priming” is understood as a process of controlled hydration of seeds to alevel that permits pre-germinative metabolic activity to proceed, but prevents actualemergence of the radicle. As a consequence, it enhances the germination percentage,it enhances the speed and uniformity of germination, it increases the shelf life of seed and it enhances yield. “Seed priming” is highly suitable for small seeds. Consequently the present invention in a particular embodiment relates to the useof at least one antagonist compound of general formulae I or Ia in order to enhance thegermination percentage, and / or in order to enhance the speed and / or the uniformity ofgermination and / or in order to decrease the time between sowing and germination.The present invention in another particular embodiment relates to the use of atleast one antagonist compound of general formulae I or Ia, in order to improve the targetplant seed resistance towards temperature stress, and / or in order to increase the shelflife of target plant seed; and / or in order to enhance the target plant yield.In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia in order to promote robust seedling establishment. More particularly, said target plant seeds are dry-coated with at least one ABA antagonist as defined herein above in order to promote, synchronize or accelerate plant seed germination, by localized release of the antagonist. The present invention in another particular embodiment relates to the use of atleast one antagonist compound of general formulae I or Ia in order to improve the heat stress tolerance of plant seeds. The present invention in another particular embodiment relates to the use of atleast one antagonist compound of general formulae I or Ia for modulating plant resistance against pathogens. Sowing of the said plant seeds may particularly followed by spraying of at least oneABA antagonist as defined herein above on the planted field.In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia in order to promote primary rootgrowth of said plant. 26 M / 64069-PCTEMBL 2020-011In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia wherein said plant seeds are selected from weed seeds, and weed seed germination is induced by soil treatment with at least one ABA antagonist as defined herein above, and in particular followed by removal, mechanical, chemical or thermal destruction of the weed seedlings before crop planting More particularly, said soil treatment is preceded by shallow tillage. More particularly, said removal, mechanical, chemical or thermal destruction of the weed seedlings is followed by crop sowing, either of crop seeds dry-coated with at least one ABA antagonist as defined herein above, or of uncoated crop seeds followed byspraying of at least one ABA antagonist as defined herein above on the planted field orwith seeds pre-treated with at least one ABA antagonist as defined herein above. In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia, wherein said least one ABAantagonist is applied for the control of plant growth and development. This may be achieved in that ABA induced plant growth inhibition is antagonized by treatment with at least one ABA antagonist as defined herein above. This may also be achieved in that ABA induced bud dormancy of a plant is antagonized by treating said plant with at least one ABA antagonist as defined hereinabove or by spraying the plants with at least one ABA antagonist or by delivering it withthe watering or nutrient solutions. In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia, wherein said least one ABA antagonist is applied for the control of plant seed development, in particular in order to modulate plant seed storability and / or to modulate commercial traits of the plant seed. In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia, wherein said least one ABA antagonist is applied for the control of plant fruit maturation, in particular for increasing plant fruit yield and / or plant fruit quality. In another particular embodiment the present invention relates to the use of at leastone antagonist compound of general formulae I or Ia, wherein said least one ABA antagonist is applied for modulating plant resistance against pathogens. In still another particular embodiment the present invention relates to the use of atleast one antagonist compound of general formulae I or Ia, wherein said least one ABA27 M / 64069-PCTEMBL 2020-011antagonist is applied to a legume plant or seed in order to enhance nitrogen fixation by an enhancement of nodulation. According to another aspect the present invention relates to the use of at least onecompound of general formulae I or Ia as abscisic acid (ABA) plant hormone agonist. In a particular embodiment thereof, said at least one ABA agonist is applied for promoting drought tolerance of the plant, in particular by improving the photosynthetic capacity and / or the water-use efficiency of the plant. In another particular embodiment thereof, said at least one ABA agonist is applied to the plant or pant seed for promoting the abiotic stress tolerance of the plant. In another particular embodiment thereof, said at least one ABA agonist is acting as herbicide, as seed preservative, or to improve long-term storage stability of germplasm resources. In another particular embodiment thereof, said at least one ABA agonist is applied for promoting fruit ripening of climacteric or non-climacteric fruits. In another particular embodiment thereof, said at least one ABA agonist is applied to enhance stomata immunity of a plant. In another aspect of the invention agrochemical compositions are provided, comprising an agrochemically acceptable solid, semisolid or liquid carrier and at least one ABA antagonist or agonist as defined herein above, optionally in combination with at least one further agrochemically active co-ingredient, like for example, but not limited to osmolites, like sucrose, sorbitol and manitol, solubilizers, like DMSO or wetting agents, like Silwet-77. In another aspect of the invention a method to control plant growth, plant development, plant seed dormancy, plant seed development, to improve the plant seed resistance towards water and temperature stress, to increase the shelf life of target plant seed, to enhance the plant yield, to promote robust seedling establishment, to promote primary root growth of said plant, to modulate plant seed storability, to modulate commercial traits of the plant seed, to control plant fruit maturation, to increasing plant fruit yield and / or plant fruit quality; to modulate plant resistance against pathogens and / or to enhance nitrogen fixation of the plant by an enhancement of nodulation is provided, which method comprises treating said plant, said plant seed or the soil with an effectiveamount of at least one ABA antagonist compound of formula I or Ia as herein above, oran N-oxide, a tautomer, a stereoisomer or an agriculturally acceptable salt thereof, orwith an effective amount of a composition as defined above comprising at least one28 M / 64069-PCTEMBL 2020-011compound of formula I or Ia as defined herein above or an N-oxide, a tautomer, a stereoisomer or an agriculturally acceptable salt thereof. In another aspect of the invention a method of promote drought tolerance of theplant, in particular by improving the photosynthetic capacity and / or the water-use efficiency of the plant, to promote the abiotic stress tolerance of the plant, to inhibit plant seed germination, to improve long-term storage stability of germplasm resources, to promote fruit ripening of climacteric or non-climacteric fruits, to enhance stromataimmunity of a plant; of applying a seed preservative; or of applying a herbicide, whichmethod comprises treating said plant, said plant seed or the soil with an effective amountof at least one ABA agonist compound of formula I or Ia as defined above or an N-oxide,a tautomer, a stereoisomer or an agriculturally acceptable salt thereof, or with aneffective amount of a composition as defined above comprising at least one compoundof formula I or Ia as defined herein above or an N-oxide, a tautomer, a stereoisomer oran agriculturally acceptable salt thereof Another aspect of the invention relates to compound of the general formula I or Ia as defined above. In particular, such compounds are selected from: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide hydrochloride (3a) (S)-2-(4,5-Dimethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (3b) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyridin-3-yl)propanamide (3c) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)propanamide hydrochloride (3d) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1,8-naphthyridin-3-yl)propanamide (3e) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyrimidin-5-yl)propanamide (3f) Methyl (S)-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinate hydrochloride (3g) (S)-N-(1H-Benzo[d]imidazol-2-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide hydrochloride (3h) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(naphthalen-2-yl)propanamide (3i) (S)-N-(6,7-Dimethoxyquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3j) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(7-methoxyquinolin-3-yl)propanamide (3k) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(5-methoxyquinolin-3-yl)propanamide (3l) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(8-methoxyquinolin-3-yl)propanamide (3m) (S)-N-(7-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3n) 29 M / 64069-PCTEMBL 2020-011(S)-N-(5-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3o) (S)-N-(8-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3p) Methyl (S)-3-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)quinoline-6-carboxylate (3q) (S)-N-(6-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3r) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methoxyquinolin-3-yl)propanamide (3s) (S)-N-(6-Chloroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3t) (S)-N-(7-Bromoquinoxalin-2-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3u) (S)-N-(6-Cyclopropylquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3w) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(pyridin-3-yl)quinolin-3-yl)propanamide (3x) (S)-N-(6-Fluoroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3y) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methylquinolin-3-yl)propanamide (3z) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(trifluoromethyl)quinolin-3-yl)propanamide (3aa) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3-yl)propanamide (3ab) (S,E)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-styrylquinolin-3-yl)propanamide (3ac) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenethylquinolin-3-yl)propanamide (3ad) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(1-methyl-1H-pyrazol-4-yl)quinolin-3- yl)propanamide (3ae) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(thiophen-3-yl)quinolin-3-yl)propanamide (3af) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenylquinolin-3-yl)propanamide (3ag) 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7a) 2-(5-Ethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7b) 3-Hydroxy-2-(5-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7c) 3-Hydroxy-2-(4-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7d) 2-(5-Cyclopropyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7e) 2-(5-(Cyanomethyl)-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7f) Methyl2-(1-(3-hydroxy-1-oxo-1-(quinolin-3-ylamino)propan-2-yl)-1H-imidazol-5- yl)acetate (7g) 3-Hydroxy-2-(5-(2-hydroxyethyl)-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7h) N-(6-Chloroquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3-hydroxypropanamide (7i) N-(6-Bromoquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3-hydroxypropanamide (7j)3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3-yl)propanamide (7k)N-Benzyl-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinamide (9a) 5-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N-phenethylpicolinamide (9b) 5-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N-(3-phenylpropyl)picolinamide (9c) 30 M / 64069-PCTEMBL 2020-0115-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N-(4-phenylbutyl)picolinamide (9d) (S)-3-Hydroxy-2-(2-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (12) (S)-3-Hydroxy-2-(5-methyl-1H-1,2,3-triazol-1-yl)-N-(quinolin-3-yl)propanamide (14) or any N-oxide, tautomer, stereoisomer or a salt thereof. A particular group of compounds comprises compounds 3a, 3r, 3ab, 3ag, 3af, 7a, 7b, 7e, 7i, 7j, and 7k, in particular 7i, 7j, and most particularly 7k. According to a further aspect, the invention relates to a process for the preparationof a compound according to the preceding aspects and embodiments, comprising thesteps of: a) providing compound of formula X: b) optionally converting compound X into compound of formula I as definedabove, wherein PG is a hydroxyl protecting group, particularly selected from C1-C4 linear orbranched alkyl groups, more particularly tBu or methyl ;and Q1,Q2, Z3and E1to E4are as defined above. According to particular embodiments, step a) comprises the sub-steps of: aa) reacting compound of formula XI in presence of arylamine XII: 31 M / 64069-PCTEMBL 2020-011(XI) (XII) wherein PG is a hydroxyl protecting group, particularly selected from C1-C4 linear orbranched alkyl groups, more particularly tBu or methyl; Q1, Q2 and Z3 are as defined above.Y is selected from halogen, particularly Br or I, and -NH-PG2wherein PG2 is an amine-protecting group, particularly the Fmoc protectinggroup. thereby obtaining compound of formula XIII: ab) converting compound XIII into a compound of formula X wherein Q1, Q2, Z3., PG and E1 to E4 are as defined above.PG represents a temporary protecting group installed on the side chain ofcompound of formula XI to prevent undesired side reactions during amide formationreaction between compound of formula XI and XII. Generally, any suitable protecting group may be employed as long as it is stable during the latter reaction and it can be 32 M / 64069-PCTEMBL 2020-011removed upon step b) above, under conditions not substantially affecting the structuralstability of the final product. To that end, typical side chain protecting groups are selectedfrom acid-labile protecting groups such as the tBu, t-butyldimethylsilyl, trimethylsilyl, trityl,pivalyl, and tetrahydropyranyl groups, tBu being preferred.PG2represents an amine protecting group installed on the amine functionality ofcompound of formula XI. Any suitable protecting group can be used as long as it is stableduring the amide bond formation reaction between compound of formula XI an XII andits removal can be performed under conditions not resulting in premature removal ofprotecting group PG. Typical amine protecting group can be selected from the group consisting of formyl, Ac, trifluoroacetyl, benzyloxycarbonyl, allyloxycarbonyl, Fmoc,nitroveratryloxycarbonyl, p-methoxybenzyl, and Ts, the Fmoc protecting group beingpreferred. According to particular embodiments, the process is characterized in that: Y is Br; and step ab) comprises reacting compound of formula XIII in presence of compound of formula XIV: and subsequently removing PG3wherein PG3is: absent if E2is carbon; an amino protecting group, such as PG2, if E2 is N; ora thiol protecting group if E2 is S.PG3is a typical protecting group employed for temporary protection of the E2incompound of formula XIV. The specific identity of PG3 depend on the chemical nature ofE2. For E2=N PG3 represents any suitable nitrogen protecting group PG2 as definedabove. For E2=S, PG3 represents a suitable thiol protecting group. A free thiolfunctionality can be protected as a thioether or a thioester, or oxidized to a symmetrical33 M / 64069-PCTEMBL 2020-011disulfide, from which it is regenerated by reduction. Typical protecting groups can be selected from trityl, diphenylmethyl, 4,4′-dimethoxydiphenylmethyl and acetamidomethyl groups. The choice of PG3is not critical. For all the matter concerning ease of removal and orthogonality, the trityl protecting group is particularly preferred. According to particular embodiments, the process is characterized in that:Y is -NH-PG2; step aa) comprises selectively removing PG2thereby obtaining compound of formula XV; step ab) comprises reacting compound of formula XV in the presence of glyoxal, acetaldehyde and ammonia. According to an alternative particular embodiments, step a) comprises the sub- steps of: ac) reacting compound of formula XVI wherein 34 M / 64069-PCTEMBL 2020-011PG is as defined above in presence in presence of glyoxal, acetaldehyde and ammonia; thereby obtaining compound of formula XVII: wherein PG, E1, E2, E3 and E4 are as defined above.ad) reacting compound XVII with arylamine XII as defined above;wherein E2is N; and PG, E1, E3, E4 are as defined above.In anther particular embodiment, Q1is –C(O)-OMe and the process further comprises the sub-steps of: ae) converting Q 1 to –COOH thereby obtaining compound of formula XVIII andreacting the latter with an arylamine of formula XIX: thereby obtaining a compound of formula XX: 35 M / 64069-PCTEMBL 2020-011 wherein n is an integer between 1 and 10, particularly 1 and 4; and Z3, Q2, PG and E1to E4are as defined above; and optionally af) removing PG.d) Further aspects and embodiments of the inventionAbscisic Acid (ABA) is a key plant hormone that controls many aspects of plant physiology and development. It is involved in the adaptation to biotic and abiotic stress but it also controls plant growth and development (Chen et al.2020). The best studied role of ABA is its involvement in adaptation to drought and other types of environmental stress (Santiago, Dupeux, et al.2009; Santiago, Rodrigues, et al.2009; Dupeux, Antoni, et al.2011; Dupeux, Santiago, et al.2011). However, ABA participates in the control of other key processes in the plant under both normal and stress conditions including regulation of plant growth, seed development and maturation, germination, post- germination processes like root growth, dormancy of buds and seeds, many aspects of fruit ripening among and defense against pathogens, among others (Chen et al.2020; Gupta et al.2022; Kavi Kishor et al.2022). Plant ABA responses are controlled through the ABA signaling pathway, which is sensitive to intracellular ABA concentrations. Basal ABA concentrations under non-stress conditions are essential to promote growth while under abiotic stress, a rise in ABA is observed, eliciting specific responses through transcriptional, translational and post-translational mechanism. ABA levels also vary naturally at different developmental stages, for example, during embryo development, flowering or fruit maturation(Yoshida et al. 2019; Chen et al. 2020). Synthetic, small molecules able to modulate the activity of certain components of the ABA signaling pathway can be used to control many important plant processes of commercial relevance, either in agriculture, ornamental plants or industrial processing. Here we 36 M / 64069-PCTEMBL 2020-011describe a strategy to generate small molecules able to antagonize the effects of ABA with potential commercial applications and include as example a collection of molecules designed according to these principles that show the desired activity in plants. The ABA signaling pathway is present in all terrestrial plants and its molecular components are highly conserved across species. The core components of this pathway include the so called PYR / PYL / RCAR ABA intracellular receptors, a series of protein phosphatases of the Type 2C family (PP2Cs) and the SNIF1-related protein kinases (SnRKs). The molecular mechanism of ABA pathway activation has been recently elucidated by the Marquez Team and other groups worldwide(Santiago, Dupeux, et al. 2009; Santiago, Rodrigues, et al.2009; Dupeux, Santiago, et al.2011; Santiago et al. 2012; Weiner et al.2010; Cutler et al.2010). Under optimal growth conditions PP2Cs and SnrKs form stable complexes leading to the inactivation of the kinase activity of SnrKs. Under water shortage, ABA biosynthesis is activated and hormone levels rise in all plant tissues. ABA binds into a deep cavity of the ABA intracellular receptors (PYR / PYL / RCAR proteins). This cavity is lined by two flexible loops that close over the hormone upon binding, locking it into the cavity. This conformational change induces the formation of a high affinity complex between the receptor and the PP2C phosphatases, releasing the SnRKs and leading to the activation of the protein kinase activity. SnrKs in turn, phosphorylate a number of cellular factors like ABscisic Acid Responsive Element transcription factors (ABREs), which activate the stress-specific transcriptional program and other cellular factors. The adaptive response to draught in plants is complex and include a variety of different responses at the cellular level. However, a key factor is the closure of the stomata, small apertures on the surface of leaves that regulate gas exchanges. The closure of the stomata is controlled by the SLAC1, AKT1 and AKT2 membrane ion transporters, which are directly phosphorylated by SnRKs upon activation of the ABA pathway, leading to the rapid closure of stomata, thereby limiting evapotranspiration and water loss by the plant. The ABA content in plants rises significantly; stimulating stress-tolerance effects that help plants adapt and survive under these adverse conditions. It has been demonstrated that mutant plants engineered with enhanced ABA sensitivity adapt to drought conditions better than their wild-type counterparts and that ABA treatments improve performance of cultures under water limiting conditions. However, ABA is not viable as agrochemical due to its chemical instability and uneconomic synthesis. A number of small molecule effectors including both inhibitors and activators have been developed with the capacity to bind to 37 M / 64069-PCTEMBL 2020-011PYL / RCAR receptors and modify the ability of plants to tolerate hydric stress (Vaidya et al.2022; Hewage et al.2020). ABA also acts as a regulator of plant growth, and controls other important physiological and developmental processes in plants. Basal levels of ABA are required to promote optimal growth while higher levels of ABA can have an inhibitory effect on plant growth. ABA is also involved in embryo and seed development and can influence the accumulation of storage products in the seed, like the amount of proteins, lipids etc. The activity of ABA in the induction and maintenance of seed dormancy is attributed to its potent effects on the inhibition of seed germination. ABA also influences the growth and development of whole plants or plant parts and counteracts the effects of growth- stimulating hormones such as gibberellins. High ABA levels also induce dormancy of buds and can influence flowering as well appearance of new leaves. ABA levels are known to increase during fruit maturation in certain species influence processes like fruit development ripening, fruit softening among others. Pathogen infections can also influence ABA levels in host plants. For example, in wheat, certain pathogens can induce increases in ABA which producing in turn higher cellular levels of sugars which promote expansion of the pathogen(Huai et al. 2019). Also an interplay between ABA and Jasmonic Acid levels, involved in pathogen response have been reported. Most plant species have about dozen genes coding different for different ABA receptors isoforms distributed in three major subgroups or clades (clade I, clade II and clade III). Each of these isoforms show different properties and expression profiles and are thought to have either redundant or relatively specialized functions (Dupeux, Santiago, et al. 2011). However, the function of some of these receptors is still unknow. Till recently, the focus has been in the development of wide spectrum ABA agonists capable of activating the ABA pathway, but fewer compounds with highly specific inhibitory activities have been reported to data. Through a combination of Structural biology and medicinal chemistry approaches we have developed two novel strategies to develop small molecules able to bind to PYL / RCAR type ABA receptors either inhibit (antagonists) or promote the activation (agonists) and signaling through the ABA signaling pathway. Such ABA antagonists and agonists can have a number of commercial applications. 38 M / 64069-PCTEMBL 2020-011d1) Potential applications of Abscisic Acid (ABA) PYL1 receptor antagonistsControl of seed dormancy During the late stages of seed development ABA levels increase in the embryo. This inhibits germination before the seeds are released from the plant and favors seed dissemination. High ABA levels in seeds activating the ABA signaling pathway areresponsible for the induction of seed dormancy. Therefor the inventions described herecan be used to counteract the effects of ABA and promote seed germination. This can be applied in a number of different applications, some of which are described here as examples: -Non-herbicidal weed controlThere are many biotic obstacles to agricultural production in both developing and developed countries, including plant pathogens such as fungi or bacteria, and animal pests such as insects or rodents. However the most serious potential crop yield loss is caused by weeds. Weeds compete with crops for sunlight, water, nutrients, and space and thus reduce crop yields. Weed control is often time and labor-intensive, requires soil disturbance and often requires the use of toxic herbicides. The aim of long-term weed control in crops is to reduce the weed seed bank of a piece of land over multiple years. Fundamentally this means that weed suppression in one year reduces weed seed production and thus the size of the weed seed bank in the following years. There are several general approaches to achieving this, but the most relevant to this particular project are: Stimulation of seed germination and destruction of the weed seedlings before crop planting. Rapid establishment of crop cover to suppress weed seed germination and weed growth. It is envisioned that ABA receptor antagonists, and specific PYL1 antagonists can make a major contribution in both these areas without any major changes to existing farming practices, with a reduction or elimination of the use of herbicides and less soil disturbance. 39 M / 64069-PCTEMBL 2020-011- Stimulation of seed germination and destruction of the weed seedlings beforecrop planting As applications in which stimulation of germination is beneficial there may be mentioned : Herbice control Stimulation of crop germinationSynchronization or timely control of germination (benefit from favorable wether spells, synchronization of crop growthAny industrial process where germination plays an important role. For examplebeer production may be mentioned (in some malting operations, gibberellic acid issprayed onto the barley to speed up germination, and bromates are used to suppressrootlet growth and malting loss) The “Stale Seed Bed” method is an underused but nonetheless commontechnique for weed control in both conventional and organic farming (Cerruti RR Hookset al, 2021). Shallow soil disturbance, for example shallow tillage of the field encourages weed seed germination. The seedlings can then be destroyed either physically by mechanical removal or by re-tillage of the field, flame weeding, or by chemical herbicides before crop planting for example. A major problem with the stale seed bed method is that not all dormant or quiescent weed seeds germinate in the first round and the method may need to be repeated to cause appreciable reduction in weed load. This repeated soil disturbance may not be beneficial to soil health. Seed dormancy is an adaptation of plants which prevents seed germination underconditions not conducive to the short- or long-term survival of the seedlings. There are anumber of mechanisms which control or delay germination of seeds, however for both weed and crop seeds a major mechanism is seed quiescence controlled by the ABAsignaling pathway. ABA is produced in seeds under unfavorable environmentalconditions and this inhibits seed germination. Exposure to favorable conditions leads to washout or degradation of the ABA, allowing the quiescent seeds to germinate. Under stale seed bed conditions weed seeds at shallow depth are exposed to light and moisture from precipitation or irrigation. These are conducive to ABA degradation and thus seed 40 M / 64069-PCTEMBL 2020-011germination. Seeds at greater depth will not experience the same level of ABA degradation and will thus remain quiescent until tilling associated with crop planting exposes them. Soil treatment with an ABA receptor antagonist during the stale seed bed procedure will mimic the signals for “ideal growing conditions” and stimulate seed germination of all quiescent weed seeds simultaneously. This can even be achieved without any soil disturbance as this stimulated weed seed germination will not depend on any of the normal stimuli required for germination. The major ABA receptor subtype associated with seed quiescence is PYL1. Ourcompounds are highly selective for this receptor subtype and should therefore not have any undesired or phytotoxic effects due to generalized inhibition of the complete ABA system. Unintentional exposure of surrounding fields or runoff would tend to stimulate plant growth and seed germination rather than have any toxic effects. We believe that our compounds will dramatically improve the efficiency of the stale seed bed method of weed control. The potential to apply the method without soil disturbance would be a major improvement in terms of time, money and soil health. -Rapid establishment of crop cover to suppress weed seed germination andweed growth In combination with the improved stale seed bed method described above, weed suppression can be further improved by the rapid establishment of crop cover resulting in suppression of dormant weed seed germination and growth. This can be achieved by increasing the rate of crop seed germination as well as improving the synchronicity of seed germination. In addition, rapid initial stimulation of seedling growth would allow the rapid establishment of crop cover. Similarly to stimulation of weed seed germination in the stale seed bed method, germination of quiescent crop seeds can be stimulated and synchronized by application of ABA receptor antagonists. In addition, initial seedling growth is under the control of the ABA system. Seedling growth, as well as subsequent plant growth can be stimulated by inhibition of ABA receptors. However simultaneous inhibition of all ABA receptor subtypes may have deleterious or toxic effects. The key ABA receptor subtype involved in plant growth, in particular vegetative growth is PYL1. Our compounds are specific PYL1 antagonists and are envisioned to stimulate initial vegetative growth in crop 41 M / 64069-PCTEMBL 2020-011seedlings, and later in growing plants. This will allow rapid establishment of crop cover and inhibit late germinating weed growth. Approaches to applying PYL1 antagonists to crops seeds may involve the dry- coating of seeds for localized release of the compound on irrigation following planting, or spraying on planted fields which have previously been subjected to the improved stale seed bed method described above. We believe that our compounds can dramatically improve weed control by stimulating both crop seed germination and initial seedling growth. This requires no additional soil disturbance and would be a major improvement in terms of time, money and soil health. -Improved seed germination in plantsMany seeds from in either crops or ornamental plants will not germinate immediately after sowing. They require a certain time until internal ABA levels in the seed decrease sufficiently to enable germination. Sometimes seeds are subjected toprocesses called stratification or seed priming, among others to promote the decreaseof internal ABA levels. This processes may involve seed storage a 4 degree or roomtemperature during long periods (weeks to month) or imbibition of seeds in differentsolutions, for example. In general controlling the rate and timing of seed germination isof key important in agriculture. The inventions described here can be used to treat seeds at a desired time point to release the inhibition of germination, thereby promoting a higher rate of germination, more synchronous germination, improve or avoid treatments likeStratification, priming or others or accelerate germination, reducing the time betweensowing and germination providing more control over the sowing and germination processor extending the commercial life of the seeds. The later for example can help profit fromshort spells of favorable weather for sowing. -Control of germination in industrial processes.Some industrial processes, like for example beer production, require controlled germination of plants species. As described above the use of our invention can provide faster germination at a higher rate and with a higher level of synchronicity. Control of plant growth and development 42 M / 64069-PCTEMBL 2020-011- Plant growth stimulation and improved biomass crop yieldsBasal levels of ABA are required for growth. However, higher ABA levels are correlated with stress conditions and can induce growth inhibition. For example high ABA levels are known to inhibit the growth the root and other plant parts. The use of inhibitors of the ABA signaling pathway like those described here can be used to accelerateseedling establishment (“seedling establishment” is the developmental process followingseed germination through which the root develops and penetrates the soil to start capturing nutrients and water, the shoot elongates and photosynthesis is initiated in thefirst leaves) following germination, stimulate plant growth leading to increased crop yieldor biomass or to influence plant development. -Control of bud dormancy, flowering and leaf developmentHigh ABA levels are known to induce bud dormancy. Upon release of dormancy buds will produce either flowers or new leaves. The Inventions described here can be used to inhibit ABA signaling in buds and other parts of the plant and promote flowering and seed development. The rate and timing of flowering is a critical aspect in agriculture. The inventions described here could be used to control the flowering process, for example increasing the flowering rate to increase total output or its timing to benefit from favorable weather windows or influence the timing of harvest. They can also be appliedto improve biomass production of any other aspects through the promotion of leafformation . -Control of seed developmentAbscisic acid plays a central role in embryo development. It participates both in early and late stages of embryo development and controls the accumulation of seedstorage products including lipids, proteins and carbohydrates (Chen et al. 2020). Thecurrent invention can be applied for the control of seed development and to modulate commercial traits, like seed storability or oil content. -Control of fruit maturationFruit growth, ripening and senescence are under the control of ABA both in climacteric and non-climateric species (Gupta et al.2022) . As an example, it has been shown that in transgenic plants with reduce levels of endogenous ABA in Fruits a 43 M / 64069-PCTEMBL 2020-011reduction genes coding for cell-wall modifying enzymes are downregulated leading to a significant increase on the self-life of the fruit and its firmness at mature stage, both ow which are attributes of key commercial interest(Sun et al.2012). Therefore addition of the ABA receptor inhibitors described here during key stages of fruit maturation couldhave a similar, helping improving fruit properties. In general, the invention described herecould be used to increase fruit yield and / or quality. -Control of pathogens.Pathogen infections can influence ABA levels in host plants. The wheat rust fungi induce increases in ABA upon infection, which produces in turn higher cellular levels of sugars promoting expansion of the pathogen (Huai et al. 2019). Also an interplay between ABA and Jasmonic Acid levels, involved in pathogen response have been reported. Inhibitors of ABA could be applied to modulate resistance of plants against certain pathogens and to biotic stress in general. -Exploration the function of ABA receptors in different plant speciesMost plant species have about a dozen different genes coding for PYL / RCAR type ABA receptors. While some of them may have redundant functions, others seem to have more specialized expression patterns and are likely to have specialized functions. The function of these receptors is still not completely understood and as research progresses they are shown to influence a growing number of developmental and physiological process in plants. The inventions described here can be used to explore the function of ABA receptors in different plant species therefore leading to the discovery of new commercial applications for the inventions described hered2) Potential applications of ABA PYL1 receptor agonistsAbscisic acid (ABA) agonists are chemicals that mimic the action of abscisic acid (ABA). ABA plays a pivotal role in minimizing leaf transpiration and mediating enhanced water productivity but also in controlling responses to other types of abiotic and biotic challenges. In addition to promoting drought tolerance, ABA can influence waterefficiency. High water productivity means efficient biomass accumulation at reducedtranspiration. ABA agonists have the potential to improve crop water productivity (i.e. high water efficiency combined with high crop productivity). It has been shown that 44 M / 64069-PCTEMBL 2020-011overexpression of TaPYL1-1B in wheat leads to higher photosynthetic capacity andwater-use efficiency. Water stress in plants is a condition that occurs when the watersupply is insufficient to meet the plant’s needs. This can happen due to a lack of rainfall, high soil salinity, or the inability to storeenough water to get through dry months 1. Water stress can adversely impact manyaspects of plant physiology, especially photosynthetic capacity. If the stress isprolonged, plant growth and productivity are severely diminished 2.ABA agonists couldhave application in combating water stress, especially as the climate continues to change and become more erratic. Furthermore, ABA agonists have also been studied for their potential applications in stress tolerance. The environment that plants depend on for survival is constantly changing, and some adverse conditions, such as extreme temperature, drought, salinization, and other abiotic stresses, can seriously affect the growth and development of plants. Therefore, it is important to improve the adaptability of plants to these abiotic stresses, especially drought. ABA) synthesis is one of the fastest responses to stresses in plants and it has been reported to control the expression of many stress-responsive genes and involve many kinds of stress responses in plants, including both biotic and abiotic stress. ABA agonists could act as germination inhibitors and hence potentially find use as herbicides. Furthermore, they could have potential applications as preservatives for seed preservation following harvest or for the storage of long-term germplasm resources. ABA also plays an important role during maturation and ripening. ABA levels generally increase during the ripening process in most fruits, and applying ABA externally can enhance fruit flavor, hasten softening, and promote color development throughcomplex signal regulation. ABA is a dominant regulator of ripening in non-climatericfruits, such as: grapefruit, lemon, raspberries, strawberry, cherry, grapes, pineapple,melon, watermelon and pomegranate. Non-climateric fruits can only ripen fully if they areallowed to remain attached to the parent plant. ABA and ethylene are relevant for the ripening processes e.g. climateric fruits, such as tomato, apples, avocados, bananas, plums, peaches, pears, blackberries, apricots, kiwis. Climateric fruits can ripen after being picked and these fruits produce more ethylene than the non-climateric ones. ABA promotes the synthesis of ethylene: that accelerates cell wall softening, pigment synthesis and accumulation of aromatic substances. Therefore, ABA antagonists could have useful applications for regulating various fruit characteristics, making them more 45 M / 64069-PCTEMBL 2020-011suitable for consumption or storage, as well as extending their shelf-life. ABA plays a positive role in stomata immunity. Stomata are tiny openings on leaves that enable plants to exchange gases, regulating carbon dioxide intake andoxygen and water vapor release . Plants can close stomata to prevent the pathogen fromentering the plant . ABA agonists could therefore contribute to the initial defensemechanisms of plants.d3) Additional potential uses of ABA antagonistsNitrogen is an essential mineral nutrient for plant growth, but its availability is often limited in soil. Legumes have evolved the ability to develop root nodules to accommodate rhizobia, which fix nitrogen to promote plant growth and in return receive carbohydrates from the host plants in this specialized organ. This mutualistic interaction is known to be highly influenced by environmental conditions. Water-related stresses such as drought, salinity and osmotic stresses are major environmental factors that negatively affect formation and function of nodules. ABA acts as a negative regulator of nodule formation and nitrogen fixation. Plants that are deficient in ABA show hyperrnodulation and higher N fixation and, as a result, ABA antagonists could be used to enhance nodulation in legumes and therefore higher nitrogen fixation. Furthermore, it has been shown that genetic or chemical disruption of ABAbiosynthesis or signaling enhances pathogen resistance in Arabidopsis thaliana, tomato,barley and rice. Therefore, ABA antagonists could potentially find useful application in enhancing and promoting the defense mechanisms of plants, thus potentially limiting the need for conventional crop protection products. d4) Plants to be treated and formulations The types of “plant” that can be treated with the ABA modulators describedherein include both monocotyledonous (i.e., monocot) and dicotyledonous (i.e., dicot) plant species including cereals such as barley, rye, sorghum, tritcale, oats, rice, wheat, soybean and corn; beets (for example sugar beet and fodder beet); cucurbits including cucumber, muskmelon, cantaloupe, squash and watermelon; cole crops including broccoli, cabbage, cauliflower, bok choi, and other leafy greens, other vegetables including tomato, pepper, lettuce, beans, pea, onion, garlic and peanut; oil crops including canola, peanut, sunflower, rape, and soybean; solanaceous plants including tobacco; tuber and root crops including potato, yam, radish, beets, carrots and sweet 46 M / 64069-PCTEMBL 2020-011potatoes; fruits including strawberry; fiber crops including cotton and hemp; other plants including coffee, bedding plants, perennials, woody ornamentals, turf and cut flowers including carnation and roses; sugar cane; containerized tree crops; evergreen trees including fir and pine; deciduous trees including maple and oak; and fruit and nut trees including cherry, apple, pear, almond, peach, walnut and citrus. The ABA modulators compounds or formulations can be applied to plants usinga variety of known methods, e.g., by spraying, atomizing, dipping, pouring, irrigating, dusting or scattering the formulations over the propagation material, or brushing orpouring or otherwise contacting the formulations over the plant or, in the event of seed,by coating, encapsulating, spraying, dipping, immersing the seed in a liquid formulation, or otherwise treating the seed. In an alternative to directly treating a plant or seed before planting, the formulations of the invention can also be introduced into the soil or other media into which the seed is to be planted. For example, the formulations can be introduced into the soil by spraying, scattering, pouring, irrigating or otherwise treating the soil. In some embodiments, a carrier is also used in this embodiment. The carrier can be solid or liquid, as noted above. In some embodiments peat is suspended in water as a carrier of the ABA modulators and this mixture is sprayed into the soil or planting media or over the seed as it is planted. The present invention provides agricultural chemical formulations formulated forcontacting to plants or weeds, wherein the formulation comprises an ABA modulator ofthe present invention. In some aspects, the plants that are contacted with the modulatorcomprise or express an endogenous PYR / PYL polypeptide. In some aspects, the plantsthat are contacted with the modulator do comprise or express a heterologous PYR / PYLpolypeptide. The formulations can be suitable for treating plants or plant propagation material,weeds or weed propagation material, such as seeds, in accordance with the presentinvention. The formulations contain, besides the ABA-modulator or the active ingredient composition comprising the ABA modulator, at least one organic or inorganic carrier material. The formulations may also contain, if desired, one or more surfactants and, ifdesired, one or more further auxiliaries / additives customary for plant protection or weedtreatment compositions. Suitable additives include buffering agents, wetting agents, coating agents, polysaccharides, and abrading agents. 47 M / 64069-PCTEMBL 2020-011In some aspects, the present invention provides an agricultural formulationcomprising the modulator compound as disclosed herein and an agriculturallyacceptable adjuvant. In some embodiments, the agricultural chemical formulation comprises at least one of a surfactant, an herbicide, a pesticide, such as but not limited to a fungicide, a bactericide, an insecticide, a molluscicide, an acaricide, and a nematicide, a plant activator, a synergist, an herbicide safener, a plant growth regulator, an insect repellant, or a fertilizer. The formulation may be in the form of a single package formulation containing atleast one ABA modulator of the invention together with liquid and / or solid carriermaterials, and, if desired, one or more surfactants and, if desired, one or more furtherauxiliaries customary for plant protection or weed treatment compositions. Theformulation may be in the form of a two or multi (e.g. three, four or five) packageformulation, wherein one package a formulation of the at least one ABA modulator whilethe other package contains a formulation of the at least one further active co-ingedient as defined herein below, wherein all formulations contain at least one carrier material, if desired, one or more surfactants and, if desired, one or more further auxiliariescustomary for plant protection or weed treatment compositions. In the case of two ormulti package formulations, the formulations containing the ABA modulator and theformulation containing the other active co-ingredient or co-ingredients are mixed prior toapplication. Preferably, the mixing is performed as a tank mix, i.e. the formulations are mixed immediately prior or upon dilution with water. In the formulations the active ingredients and optional further actives are present in suspended, emulsified or dissolved form. The formulation can be in the form of aqueous solutions, powders, suspensions, also highly-concentrated aqueous, oily or other suspensions or dispersions, aqueous emulsions, aqueous microemulsions, aqueous suspo-emulsions, oil dispersions, pastes, dusts, materials for spreading or granules. Depending on the formulation type, they comprise one or more liquid or solid carriers, if appropriate surfactants (such as dispersants, protective colloids, emulsifiers, wetting agents and tackifiers), and if appropriate further auxiliaries which are customaryfor formulating plant protection or weed treatment products. The person skilled in the artis sufficiently familiar with the recipes for such formulations. Further auxiliaries include e.g. organic and inorganic thickeners, bactericides, antifreeze agents, antifoams, 48 M / 64069-PCTEMBL 2020-011colorants and, for seed formulations, adhesives. Suitable carriers include liquid and solid carriers. Liquid carriers include e.g. non- aqueous solvents such as cyclic and aromatic hydrocarbons, e.g. paraffins, tetrahydronaphthalene, alkylated naphthalenes and their derivatives, alkylated benzenes and their derivatives, alcohols such as methanol, ethanol, propanol, butanol and cyclohexanol, ketones such as cyclohexanone, strongly polar solvents, e.g. amines such as N-methylpyrrolidone, and water as well as mixtures thereof. Solid carriers include e.g. mineral earths such as silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, many forms of calcium carbonate, magnesium sulfate, magnesium oxide, ground synthetic materials, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, and products of vegetable origin such as cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders, or other solid carriers, like, peat, wheat, bran, vermiculite, clay, pasteurized soil, various grades of gypsum, bentonite and other clay minerals, rock phosphates and other phosphorous compounds, titanium dioxide, humus, talc, alginate and activated charcoal. Any agriculturally suitable carrier known to one skilled in the art would be acceptable and is contemplated for use in the present invention. Optionally, the formulations can also include at least one surfactant, herbicide, fungicide, pesticide, or fertilizer. Suitable surfactants (adjuvants, wetting agents, tackifiers, dispersants and also emulsifiers) are the alkali metal salts, alkaline earth metal salts and ammonium salts of aromatic sulfonic acids, for example lignosulfonic acids (e.g. Borrespers-types, Borregaard), phenolsulfonic acids, naphthalenesulfonic acids (Morwet types, Akzo Nobel) and dibutylnaphthalenesulfonic acid (Nekal types, BASF), and of fatty acids, alkyl- and alkylarylsulfonates, alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates, andsalts of sulfated hexa-, hepta- and octadecanols, and also of fatty alcohol glycol ethers,condensates of sulfonated naphthalene and its derivatives with formaldehyde, condensates of naphthalene or of the naphthalenesulfonic acids with phenol andformaldehyde, polyoxyethylene octylphenol ether, ethoxylated isooctyl-, octyl- ornonylphenol, alkylphenyl or tributylphenyl polyglycol ether, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol / ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignosulfite waste liquors and proteins, denaturated 49 M / 64069-PCTEMBL 2020-011proteins, polysaccharides (e.g. methylcellulose), hydrophobically modified starches, polyvinyl alcohol (Mowiol types Clariant), polycarboxylates (BASF, Sokalan types), polyalkoxylates, polyvinylamine (BASF AG, Lupamine types), polyethyleneimine (BASF, Lupasol types), polyvinylpyrrolidone and copolymers thereof. Examples of thickeners (i.e. compounds which impart to the formulation modified flow properties, i.e. high viscosity in the state of rest and low viscosity in motion) are polysaccharides, such as xanthan gum (Kelzan® from Kelco), Rhodopol® 23 (Rhone Poulenc) or Veegum® (from R.T. Vanderbilt), and also organic and inorganic sheet minerals, such as Attaclay® (from Engelhardt). Examples of antifoams are silicone emulsions (such as, for example, Silikon©SRE, Wacker or Rhodorsil® from Rhodia), long-chain alcohols, fatty acids, salts of fatty acids, organofluorine compounds and mixtures thereof. Bactericides can be added for stabilizing the aqueous herbicidal formulations. Examples of bactericides are bactericides based on diclorophen and benzyl alcohol hemiformal (Proxel® from ICI or Acticide® RS from Thor Chemie and Kathon® MK fromRohm & Haas), and also isothiazolinone derivates, such as alkylisothiazolinones andbenzisothiazolinones (Acticide MBS from Thor Chemie). Examples of antifreeze agents are ethylene glycol, propylene glycol, urea or glycerol. Examples of colorants are both sparingly water-soluble pigments and water- soluble dyes. Examples which may be mentioned are the dyes known under the names Rhodamin B, C.I. Pigment Red 112 and C.I. Solvent Red 1, and also pigment blue 15:4,pigment blue 15:3, pigment blue 15:2, pigment blue 15:1, pigment blue 80, pigmentyellow 1, pigment yellow 13, pigment red 112, pigment red 48:2, pigment red 48:1, pigment red 57:1, pigment red 53:1, pigment orange 43, pigment orange 34, pigmentorange 5, pigment green 36, pigment green 7, pigment white 6, pigment brown 25, basicviolet 10, basic violet 49, acid red 51, acid red 52, acid red 14, acid blue 9, acid yellow 23, basic red 10, basic red 108. Examples of adhesives are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose. To prepare emulsions, pastes or oil dispersions, the active components, as such or dissolved in an oil or solvent, can be homogenized in water by means of wetting agent, tackifier, dispersant or emulsifier. Alternatively, it is possible to prepare concentrates consisting of active substance, wetting agent, tackifier, dispersant or emulsifier and, if 50 M / 64069-PCTEMBL 2020-011desired, solvent or oil, and these concentrates are suitable for dilution with water. Powders, materials for spreading and dusts can be prepared by mixing or concomitant grinding of the active the herbicides A and B with a solid carrier. Granules, e.g. coated granules, impregnated granules and homogeneous granules, can be prepared by binding the active ingredients to solid carriers. The formulations of the invention comprise an effective amount of at least one ABA plant hormone modulator of the invention. The concentrations of the activeingredient(s) in the formulations can be varied within wide ranges. In general, theformulations comprise from 1 to 98% by weight, preferably 10 to 60 % by weight, of activeingredient(s) (sum of ABA modulator and optionally further actives). The activeingredients are employed in a purity of from 90% to 100%, preferably 95% to 100% (according to NMR spectrum). The ABA plant hormone modulators, i.e. active compound or composition, can,for example, be formulated as follows: Products for dilution with water are:- Water-soluble concentrates:10 parts by weight of active compound (or composition) are dissolved in 90 parts by weight of water or a water-soluble solvent. As an alternative, wetters or other adjuvants are added. The active compound dissolves upon dilution with water. This gives a formulation with an active compound content of 10% by weight. -Dispersible concentrates20 parts by weight of active compound (or composition) are dissolved in 70 parts by weight of cyclohexanone with addition of 10 parts by weight of a dispersant, for example polyvinylpyrrolidone. Dilution with water gives a dispersion. The active compound content is 20% by weight. -Emulsifiable concentrates15 parts by weight of active compound (or composition) are dissolved in 75 parts by weight of an organic solvent (e.g. alkylaromatics) with addition of calcium dodecylbenzenesulfonate and castor oil ethoxylate (in each case 5 parts by weight). Dilution with water gives an emulsion. The formulation has an active compound content 51 M / 64069-PCTEMBL 2020-011of 15% by weight. -Emulsions25 parts by weight of active compound (or composition) are dissolved in 35 parts by weight of an organic solvent (e.g. alkylaromatics) with addition of calcium dodecylbenzenesulfonate and castor oil ethoxylate (in each case 5 parts by weight). This mixture is introduced into 30 parts by weight of water by means of an emulsifier (Ultraturrax) and made into a homogeneous emulsion. Dilution with water gives an emulsion. The formulation has an active compound content of 25% by weight. -SuspensionsIn an agitated ball mill, 20 parts by weight of active compound (or composition) arecomminuted with addition of 10 parts by weight of dispersants and wetters and 70 partsby weight of water or an organic solvent to give a fine active compound suspension. Dilution with water gives a stable suspension of the active compound. The active compound content in the formulation is 20% by weight. -Water-dispersible granules and water-soluble granules50 parts by weight of active compound (or composition) are ground finely with addition of 50 parts by weight of dispersants and wetters and made into water-dispersible or water-soluble granules by means of technical appliances (for example extrusion, spray tower, fluidized bed). Dilution with water gives a stable dispersion or solution of the active compound. The formulation has an active compound content of 50% by weight. -Water-dispersible powders and water-soluble powders75 parts by weight of active compound (or composition) are ground in a rotor-stator mill with addition of 25 parts by weight of dispersants, wetters and silica gel. Dilution with water gives a stable dispersion or solution of the active compound. The active compound content of the formulation is 75% by weight. -Gel formulationsIn a ball mill, 20 parts by weight of active compound (or composition), 10 parts by weight of dispersant, 1 part by weight of gelling agent and 70 parts by weight of water or of an organic solvent are mixed to give a fine suspension. Dilution with water gives a stable 52 M / 64069-PCTEMBL 2020-011suspension with active compound content of 20% by weight. Aqueous use forms can be prepared from emulsion concentrates, suspensions,pastes, wettable powders or water-dispersible granules by adding water.It may furthermore be beneficial to apply the ABA plant hormone modulator alone or in combination with other herbicides, or else in the form of a mixture with other plant protection agents, for example together with agents for controlling pests or phytopathogenic fungi or bacteria. Other additives such as non-phytotoxic oils and oil concentrates may also be added. The aqueous formulation of the invention may contain one or more further co- solvent.Suitable co-solvents are water-miscible up to at least a ratio of the co-solvent to water of 1:1, preferably at least 2:1, more preferably at least 4:1. Suitable co-solvents are alcohols, e.g. ethanol, propanol, butanol, benzyl alcohol, cyclo-hexanol; glycols; DMSO; ketones, e.g. heptanone, cyclohexanone; esters, e.g. carbonates, fatty acid esters, fatty acids; phosphonates; amines; amides, e.g. fatty acid dimethylamides; and mixtures thereof. The concentration of the co-solvent in the formulation will generally not exceed 5 wt%, in particular 2 wt% or 1 wt%. In particular, the formulations of the invention do not contain a further co-solvent or less than 1 wt% of co-solvent. The formulations of the present invention can be prepared by analogy to known methods, such as described by Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or Knowles, New developments in crop protection product formulation, Agrow Reports DS243, T&F Informa, London, 2005. Usually, formulations of the present invention are produced by mixing active ingredient with water and at leastone co-solvent and optionally any further component contained in the formulation. Themixing of the components may be carried out in any order. Mixing is typically achieved by stirring, shaking, homogenizing and the like. The aqueous formulation of the invention may be co-formulated with a further pesticide. Therefore, the present invention also relates to co-formulations, wherein a further pesticide is included in a formulation of the present invention. The term pesticide refers to at least one active substance selected from the group of fungicides, insecticides, nematicides, herbicides, safeners, biopesticides and / or growth regulators. In one embodiment, the pesticide is an insecticide. In another embodiment, the pesticide is a fungicide. In yet another embodiment the pesticide is a 53 M / 64069-PCTEMBL 2020-011herbicide. The skilled worker is familiar with such pesticides, which can be found, for example, in the Pesticide Manual, 16th Ed. (2013), The British Crop Protection Council, London. Suitable insecticides are insecticides from the class of the carbamates, organophosphates, organochlorine insecticides, phenylpyrazoles, pyrethroids, neonicotinoids, spinosins, avermectins, milbemycins, juvenile hormone analogs, alkyl halides, organotin compounds nereistoxin analogs, benzoylureas, diacylhydrazines, METI acarizides, and insecticides such as chloropicrin, pymetrozin, flonicamid, clofentezin, hexythiazox, etoxazole, diafenthiuron, propargite, tetradifon, chlorofenapyr, DNOC, buprofezine, cyromazine, amitraz, hydramethylnon, acequinocyl, fluacrypyrim, rotenone, or their derivatives. Suitable fungicides are fungicides from the classes of dinitroanilines, allylamines, anilinopyrimidines, antibiotics, aromatic hydrocarbons, benzenesulfonamides, benzimidazoles, benzisothiazoles, benzophenones, benzothiadiazoles, benzotriazines, benzyl carbamates, carbamates, carboxamides, carboxylic acid diamides, chloronitriles cyanoacetamide oximes, cyanoimidazoles, cyclopropanecarboxamides, dicarboximides, dihydrodioxazines, dinitrophenyl crotonates, dithiocarbamates, dithiolanes, ethylphosphonates, ethylaminothiazolecarboxamides, guanidines, hydroxy-(2-amino)pyrimidines, hydroxyanilides, imidazoles, imidazolinones, inorganic substances, isobenzofuranones, methoxyacrylates, methoxycarbamates, morpholines, N phenylcarbamates, oxazolidinediones, oximinoacetates, oximinoacetamides, peptidylpyrimidine nucleosides, phenylacetamides, phenylamides, phenylpyrroles, phenylureas, phosphonates, phosphorothiolates, phthalamic acids, phthalimides, piperazines, piperidines, propionamides, pyridazinones, pyridines, pyridinylmethylbenzamides, pyrimidinamines, pyrimidines, pyrimidinonehydrazones, pyrroloquinolinones, quinazolinones, quinolines, quinones, sulfamides, sulfamoyltriazoles, thiazolecarboxamides, thiocarbamates, thiophanates, thiophenecarboxamides, toluamides, triphenyltin compounds, triazines, triazoles. Suitable herbicides are herbicides from the classes of the acetamides, amides, aryloxyphenoxypropionates, benzamides, benzofuran, benzoic acids, benzothiadiazinones, bipyridylium, carbamates, chloroacetamides, chlorocarboxylic acids, cyclohexanediones, dinitroanilines, dinitrophenol, diphenyl ether, glycines, imidazolinones, isoxazoles, isoxazolidinones, nitriles, N-phenylphthalimides, oxadiazoles, oxazolidinediones, oxyacetamides, phenoxycarboxylic acids, phenylcarbamates, phenylpyrazoles, phenylpyrazolines, phenylpyridazines, phosphinic acids, phosphoroamidates, 54 M / 64069-PCTEMBL 2020-011phosphorodithioates, phthalamates, pyrazoles, pyridazinones, pyridines, pyridinecarboxylic acids, pyridinecarboxamides, pyrimidinediones, pyrimidinyl(thio)benzoates, quinolinecarboxylic acids, semicarbazones, sulfonylaminocarbonyltriazolinones, sulfonylureas, tetrazolinones, thiadiazoles, thiocarbamates, triazines, triazinones, triazoles, triazolinones, triazolocarboxamides, triazolopyrimidines, triketones, uracils, ureas. Examples of herbicides are glyphosate, glufosinate, paraquat, diquat, imazamox, 2,4-dichlorophenoxyacetic acid, aminopyralid, clopyralid, fluroxypyr, imazapyr, imazapic, triclopyr, and pyroxasulfone. The user applies the formulations according to the invention usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigationsystem. For this, the formulation of the invention is made up with water, optionally buffer,and / or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the ready-to-use spray liquor are applied per hectare of agricultural useful area. d5) Particular Co-ingredients As non-limiting examples of suitable co-ingredients, the following classes of compounds and representative, non-limiting examples of particular co- ingredients are may be mentioned: ^Auxins, as for example Indole-3-acetic acid (IAA), Indole-3-propionic acid (IPrA),Phenyl acetic acid, Indole-3-butyric acid, 2,4- Dichlorophenoxyaceti c acid, α-Naphthalene acetic acid and 2-Methoxy-3,6- dichlorobenzoic acid (Dicamba).^ Gibberellins, as for example GA1, GA2, GA3, GA4, GA4, GA5, GA6, GA7.^ Cytokinins, as for example Zeatin and Kinetic.^ Brassinosteroids, as for example Brassinolide, Castasterone and Typhasterol.^ Jasmonates, as for example Jasmonic acid, Methyl jasmonate and Jasmonoyl-isoleucine (JA-Ile). ^Other PGRs, as for example Triacontanol (TRIA), Chlormequat-chloride,Prohexadione, mepiquat chloride, Paclobutrazol, Cyclanilide (1-(2,4- dichlorophenyl aminocarbonyl)-cyclopropane carboxylic acid), Alpha napthyl acetic acid, Ethepon and Trinexapac-ethyl. ^Biological agents that enhance plant defense mechanisms, as for example55 M / 64069-PCTEMBL 2020-011Trichoderma, Bacillus subtilis, Pseudomonas fluorescens, Azospirillum, Rhizobium and Mycorrhizae^ Non-selective herbicides, as for example Glyphosate, Diquat, Glufosinate,Imazapyr, Triclopyr, Diuron, Bromacil and Pelargonic acid. ^Seed treatment fungicides, as for example Metalaxyl, Thiram, Zineb, Maneb,Captan, Azoxystrobin, Pyraclostrobin, Thiabendazole, Mefenoxam, Difenoconazole, Fluxapyroxad, Pentachloronitrobenzene, Ipconazole, Tebuconazole, Triticonazole, Thiophanate-methyl, Sedaxane, Oxathiapiproline, Trifluxistrobin, Inpyrfluxam and Fludioxonil. ^Seed treatment insecticides as for example Thiamethoxam, Sufloxaflor,Imidachloprid, Clothianidin, Chlorpyriphos, Endosulfan, Acetamiprid, Dimethoate, Carbosulfan, Cyantraniliprole and Chlorantraniliprole.d6) Further methods of preparation of compounds according to the inventionThe compounds according to the invention can be prepared by analogy to methods commonly know by the person skilled in the art and as described in the examples of the present application. In particular, the compounds of the present invention can be prepared according to the following schemes, wherein the variables, if not stated otherwise, are as defined above. Routine experimentations, including appropriate manipulation of the reaction conditions, reagents and sequence of the synthetic route, protection of any chemical functionality that may not be compatible with the reaction conditions, and deprotection at a suitable point in the reaction sequence of the preparation methods are within routine techniques. Starting materials, if not commercially available, may be prepared by procedures selected from standard organic chemical techniques, techniques that are analogous to the synthesis of known, structurally similar compounds, or techniques that are analogous to the above described schemes or the procedures described in the synthetic examples section. The reaction mixtures are worked up in a conventional way, e.g. by mixing with water, separating the phases and, where appropriate, purifying the crude products by chromatography. If the intermediates and final products are obtained as solids, the purification can also take place by recrystallization. The concrete chemical nature of all variables such as its polarity and bulkiness 56 M / 64069-PCTEMBL 2020-011may require appropriate adjustment of the of the peculiar reaction conditions such as reaction time, temperature and solvent. Scheme 1: According to particular embodiments, compounds of the present invention may be prepared starting from precursors 1 and A1 as depicted in Scheme 1: Scheme 1 depicts the coupling reaction between compound 1 and A1. In scheme1 the Fmoc protecting group can be replaced by any other suitable amine protecting group. Analogously, the tert-butyl protecting group on the side chain of serine can bereplaced by any other suitable alcohol protecting group. Any kind of orthogonal protection well known in the art may be used as long asremoval of the protecting group on the amine functionality does not result in undesiredpremature deprotection of serine side chain alcohol functionality. For the coupling reaction to take place, compound 1 may be activated viaformation of the corresponding activated precursor. Active esters, which may be formed via reaction of compound 1 with derivatives of nitrophenols, pentafluorophenol, N-hydroxysuccinimide, or hydroxybenzotriazole, in presence of appropriate activating agents are examples of valuable activated precursors. In that context, any active agent commonly known in the art such as carbodiimides, triphosgene or carbonyldiimidazole can be employed. Other widely employed reagents are phosphonium or aminiumsalts, such as BOP (benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate), PyBOP (benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate) andHBTU (hexafluorophosphate benzotriazole tetramethyl Uronium), HATU (hexafluorophosphate azabenzotriazole tetramethyl uronium) which can generate active esters in situ. 57 M / 64069-PCTEMBL 2020-011The reaction typically occurs at room temperature, in a polar aprotic solvent, such as DMF, and in presence of a tertiary base, such as TEA (trimethylamine) or DIPEA (N,N-Diisopropylethylamine). The protecting group may be removed before proceeding to the following steps. When Fmoc is used, said deprotection may be performed by treatment with a secondary amine, such as piperidine. Following deprotection, compound 2 may undergo imidazole ring formation asdepicted in Scheme 1. The reaction can be effected by Debus–Radziszewski imidazolesynthesis in which compound 2 is reacted with an appropriate 1,2-dicarbonyl (D) inpresence of ammonia and an aldehyde, particularly formaldehyde. The person skilled inthe art will readily understand that the choice of the specific reaction conditions to beemployed is strictly related to the identity of the substituents characterizing the reactants.It will be also understood that D and the aldehyde can be added as such or in the corresponding acetal or hemiacetal form which readily hydrolyze under the reaction conditions. The reaction may be done in aqueous, organic or mixed aqueous-organic media and can be conducted at a temperature in the range of from 20 °C to 100 °C, particularly 50 °C to 90 °C, more particularly 70 °C to 85 °C, such as at about 50°C or 80 °C and can run for about 1h to 20h, more particularly for about 5h. Finally, the side chain protecting group is removed. In case tert-butyl protectionis chosen, the corresponding deprotection can be effected by treatment with an organicacid. Any organic acid can be used, TFA being particularly suitable. Optionally, so called“scavengers” such as sulphides can be used to trap alkyl cations delivered during thecourse of the deprotection thereby avoiding unwanted alkylation with formation of by- products. Scheme 2: Triazole ring formation Compound 2 may be reacted with an azide reagent, like 4-azidonitrobenzene as58 M / 64069-PCTEMBL 2020-011shown above (or another suitable azide reagent like 4-azidobenzoic acid, tosylazide andmethansulfonyl azide; not shown here) and acetone to afford triazole 5. It is understoodthat depending on the specific substituent on the triazole ring, ketones, other than acetone may be employed. The multicomponent reaction may follow a mechanism proceeding via initial Schiff base formation, tautomerisation to the enamine, followed by 3+2 cycloaddition reaction with 4-azidonitrobenzene, and finally aromatization with the loss of 4- nitroaniline. The reaction may be performed under acid catalysis using a Lewis acid, such scandium triflate. Alternatively, other organic acids, such as acetic acid can be used. The reaction may be conducted in organic solvent, such as DMF or toluene, and can be conducted at a temperature in the range of from 10 °C to 100 °C, particularly 20 °C to 80 °C, more particularly 30 °C to 60 °C, such as at about 40° and can run for about 5h to 30h, more particularly for about 24h. Finally, the side chain protecting group is removed as described under Scheme1, thereby affording compound 6.Scheme 3: Substituted imidazole formation In Scheme 3, compound 1.1 is reacted with arylamine Ar1NH2thereby affording intermediate 7. The reaction can be mediated using anhydrides, such as propylphosphonic anhydride, as activating agent. Alternatively the coupling reaction may be conducted using any suitable activation methods, such as those already described for the coupling reaction between compound 1 and amine A1 (see Scheme 1 above). It is understood that, the methyl protecting group on the side chain of serine canbe replaced by any other suitable alcohol protecting group. Subsequently, intermediate 7 is subjected to reaction with compound A2 thereby obtaining intermediate 8. Conveniently, the nitrogen imidazole on compound A2 may be 59 M / 64069-PCTEMBL 2020-011protected during the reaction such to avoid by products formation. Any kind of orthogonal protection well known in the art may be used as long asits removal does not result in undesired premature deprotection of serine side chainalcohol functionality. Preferably, the trityl protecting group is employed. The reaction foresees a first step of formation of a tritylated imidazolinium salt.This first step may follow a nucleophilic substitution mechanism in which imidazole A2displaces the halogen atom of compound 7. Advantageously, an external nucleophilesuch as KI can be employed as catalyst, resulting in a higher reaction rate due to in-situgeneration of highly reactive alkyl iodide species. The reaction may be done in anhydrous organic media such as acetonitrile or methanol, preferably in inert atmosphere. Advantageously, microwave irradiation can be used and the reaction can be conducted at a temperature in the range of from 60 °C to 150 °C, particularly 70 °C to 130 °C, more particularly 75 °C to 125 °C, such as at about 80 °C or 120°C and can be run for about 1h to 10h, more particularly for about 1h to 2h. The tritylated imidazolinium salt is then subjected to trityl group removal thereby affording compound 8. Finally, the protecting group on the serine side chain is removed by methods well known in the art. In case the methyl ester protection is used, the deprotection can be effected by treatment with boron tribromide.Scheme 4: Synthesis of unsubstituted imidazoles Scheme 4 depicts an alternative route for the synthesis of the compoundsaccording to the present invention. In the first step, compound 1.2 can be directly reactedwith an appropriate 1,2-dicarbonyl compound, such as glyoxal, in presence of ammoniaand an aldehyde, thereby obtaining intermediate 10. Preferably, the reaction is conducted in an alkaline medium, particularly, using a solution of NaOH, either alone or as mixture with a liquid ammonia solution. Alternatively, following completion of the reaction an acidic workup followed by60 M / 64069-PCTEMBL 2020-011isolation of the carboxylic acid form of compound 10 can be performed. Intermediate 10 can be then subjected to amidation by reaction with arylamine Ar1NH2, following any of the coupling protocol described for the formation of compound 7 above. Finally, the side chain protecting group is removed as described under Scheme 1.Scheme 5: Synthesis of imidazole compound derivatives The compounds of the present invention can be subjected to further derivatization as depicted in scheme 5. The methyl ester group of imidazole compound 13 can be hydrolyzed, for example, by alkaline hydrolysis using an inorganic base, such as LiOH and the resulting acid group subjected to amidation by reaction with amine R-NH2as depicted in scheme 5, thereby obtaining compound 14. The amidation reaction can be performed by methods well known in the art. To that end, carbodiimides or benzotriazole derivatives coupled with active esters activation as described for the coupling reaction between compound 1 and amine A1 (see scheme 1 above) can be used. Preferably, the reaction can be mediated using anhydrides, such as propylphosphonic anhydride, as activating agent. Finally, the side chain protecting group is removed as described under Scheme 1. d7) Rational design of ABA antagonist imidazole compounds. Structure-activity relationships. X-ray based screening experimentsusing the CrystalDirect technology (Actacrystallographica. Section D, Structural biology, 2016, doi:10.1107 / s2059798316000954; Journal of visualized experiments: JoVE, 2021 doi:10.3791 / 62491; and Methods in molecular biology (Clifton, N.J.), 2014, 61 M / 64069-PCTEMBL 2020-011doi:10.1007 / 978-1-62703-691-7_14) allow identifying small molecule modulators ofplant abscisic acid receptors.The Solanum lycopersicum PYL1 ABA receptor (SlPYL1,see sequence in the experimental section) was used as a representative and wellcharacterized ABA receptor in general and particularly of the Clade III receptor subtype.As a result, a high-resolution atomic model of the tomato SlPYL1 receptor incomplex with the precursor of molecule 3a (2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide) was obtained. Said precursor shows the following chemical formula: This molecule showed antagonistic activity with an EC50 of 386 µM. Compoundsof the present invention were synthesized by considering the following design rules in order to obtain compounds with improved EC50 values. The structural analysis revealed that this molecule binds in the ABA binding cavityof the receptor and has an antagonistic mode of action. As can be observed in Figure 8,the imidazole moiety of this molecule inserts deep into the ABA binding cavity of thereceptor an is stabilized by polar interactions with Lys 96 and a series of water-mediated interactions with side chains of Glu 178 and Asn 204. This corresponds to the position typically occupied by the carboxylic group of ABA. The quinoline moiety of the molecule on the other hand is located at the upper part of the cavity and stabilized by polar and hydrophobic interactions. These interactions and the size of the quinoline moiety at the upper part of the cavity are incompatible with the closed conformation of the receptorlatch (highlighted in the figure by amino acids 151 to 154) and gate (highlighted in thefigure by amino acids 122 to 125) loops, necessary for receptor activation. The fact thatthis molecule binds to the ABA receptor in the same site as ABA does, and contrary to ABA its binding would prevent closure of the gate and latch loops demonstrates its antagonistic mode of action. The inventors predicted and discovered that additional molecules based on thisprecursor compound could also have strong potential as ABA antagonists. Throughcareful structural analysis they predicted three key characteristics that such moleculeswould need to have either independently or in combination, including the followingdesign rules: 62 M / 64069-PCTEMBL 2020-011(1) Additional hydrophilic groups at position A of formula I like a hydroxymethylresidue in formula Ia able to stabilize polar interactions or either direct or water-mediated hydrogen bonds with the receptor in the area near amnioacids 92 to 93, 96, 99, 129 to 131,and 116 to 120, like for example Glu 131and Lys 96. (2) Additional groups that are either hydrophobic or a combination ofhydrophobic and polar groups at position E4 of formula I or position X in formula Ia that could establish stabilizing interactions with one or multipleamino acids in a receptor sub-pocket near amino acid residues 154 to 157,147, 180 to 182, 196 to 197, 200 to 201, like for example Leu 154, Ala 197,Val 182, Val 200 and Tyr 157. (3) Additional groups at position Q2 of formula I or position R2 of formula Ía ableto establish further stabilizing interactions with receptor amino acids at the upper part of the receptor cavity further obstructing the closure of the gate and latch loops or stabilizing the receptor dimer through interactions at theinterface between two receptor subunits within a receptor dimer. Thisincludes amino acids in the lach and gate loops (151 to 154 and 122 to 126respectively) as well as amino acids 98, 196 to 200, 153 in either of the twosubunits within a receptor dimer, like for example Arg 153, Phe 98, Phe 196,.It was predicted that such molecules would also act as antagonist with other ABAreceptors, due to the high level of sequence conservation across receptor subtypes and plant species. The structures indicated in Table 5 demonstrate that molecules designed following these principles do indeed show additional stabilizing interactions between themolecules and the receptor, while the in vitro activity assays presented in Table 3 andTable 4 confirm that these compounds have increased affinity for receptor molecules demonstrating a clear relationship between the structure and the activity of thecompounds confirming each of our predictions concerning compound design. Moreover,assays presented in Figures 1, 2, 3, 4, 5, 6 and 7, show selected molecules designedaccording to these principles demonstrating antagonist activity in vivo with strongimprovements on seed germination and acceleration of seedling establishment. As an illustration of design rule 1, molecules 3a and 3i have an hydroxyl group atposition A for formula I corresponding to the hydroxmethyl group at the corresponding63 M / 64069-PCTEMBL 2020-011position in formula Ia leading to additional, stabilising polar interactions and both directand water-mediated hydrogen bonds with amino acids Glu 131, Lys 96 and Arg116 (see Figure 9), which in turn leads to an increase in antagonistic activity. Other molecules containing this group show the same characteristics. (see Tables 3 and 4). As an illustration of design rule 2, molecules 7b (Figure 10), 7c 7e, 7f and 7gpresent different groups at position E4 of formula I, corresponding to position X in formulaIa, and show additional stabilizing interactions with residues Leu 154, ala 197, Val 182 and Val 200 or Tyr 157 and other residues in this area (Table 5 structures) and show increased agonistic activity against various receptors as compared to molecule 3a (see Tables 3 and 4). As an illustration of design rule 3, molecules 3ab (Figure 11), 3ag, 3af, 3aa, 3x,3t, with different chemical groups fulfilling rule 3 at position Q2 of formula I corresponding to positron R2of formula Ia show additional stabilizing interactions with amino acids inthe upper area of the ABA binding cavity including amino acids in the lach and gate loops(151 to 154 and 122 to 126 respectively) in either of the two subunits within a receptordimer, further interfering with the closure of the receptor gate and latch loops andstabilizing the receptor dimer through further interactions at the interface between tworeceptor subunits including amino acids 98, 196 to 200, 153 in either of the two subunitswithin a receptor dimer, , like for example Phe 98 and Phe 196 (Figure 11). This againleads to increased antagonistic activity as compared to molecule 3a (see Tables 3 and 4). As shown above, one of the afore-mentioned design rules is sufficient to producemolecules with improved antagonistic activity, as compared to the precursor molecule.At the same time, the combination of two or three of the design rules in a single molecule leads to synergistic effects and even stronger antagonistic activity. As an illustration ofthis, molecules 7a, 7b and 7e conform to design rules 1 and 2 and show increasedantagonistic activities as compared to molecules that fulfill only either rule 1 or rule 2 (see Tables 3 and 4). As another illustration, molecules 3r, 3t, 3w, 3x , 3ab fulfill design rules 1 and 3 and show increased antagonistic activities as compared to molecules thatfulfill only either rule 1 or rule 3 (see Tables 3 and 4). As another illustration, molecules7k, 7i and 7j, fulfill the three design principles at once and have stronger agonistic activityas compared to molecules fulfilling only one or two of the design principles at once (see Tables 3 and 4). 64 M / 64069-PCTEMBL 2020-011The data demonstrate that the three design rules described above applied eitherindividually or in combination lead to novel molecules with improved ABA receptorantagonistic activity. By applying the priciples of the above design rules 1, 2 and / or 3 a skilled reader will be enabled to generate, in addition to the exemplified compounds, without unreasonable effort further suitable, particularly improved ABA antagonists of the invention. d8) Rational design of ABA agonist imidazole compounds. Structure-activity relationships. Further to this, the inventors predicted and discovered that additional moleculesbased on molecules of formula (I) could be designed to have agonistic activity, i.e promotion of the formation of a ternary (receptor-molecule-PP2C) complexe leading to the activation of the ABA pathway, by introducing substituents at positions Q1, Q2 andZ3 of molecules of formula (I) thata) are sufficiently small in size to fit in the closed conformation of the receptors(with gate and latch loops in the so called closed confrmation) and b) promote the receptor-phosphatase intraction leading to the formation of astable ternary complex. These agonistic molecules can also fullfil either one of both of the above mentioneddesing rule 1 and design rule 2 providing increased stabilization of the agonisticmolecule through stabilizing interations with amino acids in the bottom part of the ABAbinding cavity (as already described in design rule 1 and design rule 2). An example of such molecule is molecule 3c, which leads to the formation of a ternary receptor-molecule-PP2C complex as demonstated by X-ray crystallography (see table 5).References:Guihua Chen, and Cerruti RR Hooks https: / / extension.umd.edu / resource / stale-seedbed-technique-relatively-underused-alternative-weed-management-tactic-vegetable- production 65 M / 64069-PCTEMBL 2020-011Chen, Kong, Guo-Jun Li, Ray A. Bressan, Chun-Peng Song, Jian-Kang Zhu, and Yang Zhao. 2020. “Abscisic Acid Dynamics, Signaling, and Functions in Plants.” Journal of Integrative Plant Biology 62 (1): 25–54. https: / / doi.org / 10.1111 / jipb.12899. Cutler, Sean R., Pedro L. Rodriguez, Ruth R. Finkelstein, and Suzanne R. Abrams.2010. “Abscisic Acid: Emergence of a Core Signaling Network.” Annual Review of Plant Biology 61 (1): 651–79. https: / / doi.org / 10.1146 / annurev-arplant-042809-112122. Dupeux, Florine, Regina Antoni, Katja Betz, Julia Santiago, Miguel Gonzalez-Guzman, Lesia Rodriguez, Silvia Rubio, et al.2011. “Modulation of Abscisic Acid Signaling in Vivo by an Engineered Receptor-Insensitive Protein Phosphatase Type 2C Allele.” Plant Physiology 156 (1): 106–16. https: / / doi.org / 10.1104 / pp.110.170894. Dupeux, Florine, Julia Santiago, Katja Betz, Jamie Twycross, Sang-Youl Park, Lesia Rodriguez, Miguel Gonzalez-Guzman, et al.2011. “A Thermodynamic Switch Modulates Abscisic Acid Receptor Sensitivity: A Thermodynamic Switch in the ABA Pathway.” The EMBO Journal 30 (20): 4171–84. https: / / doi.org / 10.1038 / emboj.2011.294. Gupta, Kapil, Shabir H. Wani, Ali Razzaq, Milan Skalicky, Kajal Samantara, Shubhra Gupta, Deepu Pandita, et al. 2022. “Abscisic Acid: Role in Fruit Development and Ripening.” Frontiers in Plant Science 13 (May): 817500. https: / / doi.org / 10.3389 / fpls.2022.817500. Hewage, Kamalani Achala H., Jing-Fang Yang, Di Wang, Ge-Fei Hao, Guang-Fu Yang, and Jian-Kang Zhu. 2020. “Chemical Manipulation of Abscisic Acid Signaling: A New Approach to Abiotic and Biotic Stress Management in Agriculture.” Advanced Science 7 (18): 2001265. https: / / doi.org / 10.1002 / advs.202001265.Huai, Baoyu, Qian Yang, Yingrui Qian, Wenhao Qian, Zhensheng Kang, and Jie Liu.2019. “ABA-Induced Sugar Transporter TaSTP6 Promotes Wheat Susceptibility to Stripe Rust.” Plant Physiology 181 (3): 1328–43. https: / / doi.org / 10.1104 / pp.19.00632. Kavi Kishor, Polavarapu B., Rhowell N. Tiozon, Alisdair R. Fernie, and Nese Sreenivasulu. 2022. “Abscisic Acid and Its Role in the Modulation of Plant Growth, Development, and Yield Stability.” Trends in Plant Science 27 (12): 1283–95. https: / / doi.org / 10.1016 / j.tplants.2022.08.013. 66 M / 64069-PCTEMBL 2020-011Santiago, Julia, Florine Dupeux, Katja Betz, Regina Antoni, Miguel Gonzalez-Guzman, Lesia Rodriguez, José Antonio Márquez, and Pedro L. Rodriguez. 2012. “Structural Insights into PYR / PYL / RCAR ABA Receptors and PP2Cs.” Plant Science 182 (January): 3–11. https: / / doi.org / 10.1016 / j.plantsci.2010.11.014. Santiago, Julia, Florine Dupeux, Adam Round, Regina Antoni, Sang-Youl Park, Marc Jamin, Sean R. Cutler, Pedro Luis Rodriguez, and José Antonio Márquez.2009. “The Abscisic Acid Receptor PYR1 in Complex with Abscisic Acid.” Nature 462 (7273): 665– 68. https: / / doi.org / 10.1038 / nature08591. Santiago, Julia, Americo Rodrigues, Angela Saez, Silvia Rubio, Regina Antoni, Florine Dupeux, Sang-Youl Park, José Antonio Márquez, Sean R. Cutler, and Pedro L.Rodriguez. 2009. “Modulation of Drought Resistance by the Abscisic Acid ReceptorPYL5 through Inhibition of Clade A PP2Cs: Regulation of HAB1 by ABA-Binding Proteins.” The Plant Journal 60 (4): 575–88. https: / / doi.org / 10.1111 / j.1365- 313X.2009.03981.x.Sun, Liang, Yufei Sun, Mei Zhang, Ling Wang, Jie Ren, Mengmeng Cui, Yanping Wang,et al. 2012. “Suppression of 9 - Cis - Epoxycarotenoid Dioxygenase, Which Encodes aKey Enzyme in Abscisic Acid Biosynthesis, Alters Fruit Texture in Transgenic Tomato.” Plant Physiology 158 (1): 283–98. https: / / doi.org / 10.1104 / pp.111.186866. Vaidya, Aditya S., Sang-Youl Park, Zenan Xing, and Sean R. Cutler.2022. “Synthesis and Characterization of Abscisic Acid Receptor Modulators.” In Methods in Enzymology, 671:435–70. Elsevier. https: / / doi.org / 10.1016 / bs.mie.2022.03.062. Weiner, Joshua J, Francis C Peterson, Brian F Volkman, and Sean R Cutler. 2010. “Structural and Functional Insights into Core ABA Signaling.” Current Opinion in Plant Biology 13 (5): 495–502. https: / / doi.org / 10.1016 / j.pbi.2010.09.007. Yoshida, Takuya, Alexander Christmann, Kazuko Yamaguchi-Shinozaki, Erwin Grill, andAlisdair R. Fernie. 2019. “Revisiting the Basal Role of ABA – Roles Outside of Stress.”Trends in Plant Science 24 (7): 625–35. https: / / doi.org / 10.1016 / j.tplants.2019.04.008. EXPERIMENTAL PART 67 M / 64069-PCTEMBL 2020-011A. Reagents and buffersReagents were purchased from Sigma Aldrich (Germany), TCI Chemicals, (Japan), Enamine (Ukraine), and abcr (Germany) and used without further purification. All solvents, including anhydrous solvents, were used as obtained from the commercial sources. Air and water-sensitive reagents and reactions were generally handled under argon atmosphere. The reaction progress was monitored by TLC on Merck silica gel plates 60 F254. Detection was executed with a UV-Kabinett HP-UVIS (biostep) at 254 nm or with potassium permanganate staining. Flash chromatographic purification was performed on a Biotage Isolera.B. Analytical methodsOne purification system using Biotage® Sfär Silica D or Biotage® Sfär C18 D flash cartridges. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Avance (400 MHz) NMR System at 298 K. Chemical shifts (δ) are given in parts permillion (ppm), coupling constants (J) given in Hertz (Hz) and multiplicity is reported usingstandard abbreviations. Only signals for the main conformers are reported. UHPLC-MS analyses were performed on Agilent 1290 series equipment consisting of an Agilent 1290 quaternary pump, a 1290 sampler, a 1290 thermostated column compartment and a 1290 Diode array detector VL+ equipped with a quadrupole LC / MS 6120 and an Infinity 1260 ELSD. The analytical column used was a Supelco Titan C18 (1.9 µm; 2.1 x 30 mm) operated at 40 °C with a flow rate of 1.5 ml / min using linear gradient programs. Solvent A consisted of water and solvent B consisted of acetonitrile, both containing 0.1% trifluoroacetic acid. Compound purity was determined by ELSD monitoring.C. Biochemical characterizationC.1 Protein production, purification and structural characterization:Protein used in this study were expressed and purified as described in DOI: 10.1038 / emboj.2011.294 (Florine Dupeux, Julia Santiago, Katja Betz, Jamie Twycross, Sang-Youl Park, Lesia Rodriguez, Miguel Gonzalez-Guzman, Malene Ringkjøbing Jensen, Natalio Krasnogor, Martin Blackledge, Michael Holdsworth, Sean R Cutler, 68 M / 64069-PCTEMBL 2020-011Pedro L Rodriguez, José Antonio Márquez, A thermodynamic switch modulates abscisic acid receptor sensitivity. EMBO J. 2011 Aug 16;30(20):4171-84) andhttps: / / doi.org / 10.1016 / j.molp.2017.07.004 (Moreno- Alvero et. al. Structure of Ligand-Bound Intermediates of Crop ABA Receptors Highlights PP2C as Necessary ABA Co- receptor. Molecular Plant 10, 1250–1253). To summarize: protein expression andpurification of His tagged ABA receptors SlPYL1 from tomato (Solanum Licopersicum),and his-tagged ABA receptors AtPYL1, AtPYR1, AtPYL2, AtPYL5 and AtPYL9 and DN-HAB1 phosphatase (amino acids 179-511) from Arabidopsis thaliana was carried out.The complete amino acid sequences are listed in Table 1. Protein expression Escherichia coli BL21 (DE3) cells were transformed with the correspondingpETM11 (NovoPro, Cat No V012847) constructs and grown at 37 oC to an optical densityat 600 nm of 0.7 in 750 ml of 2-TY medium (16 g / L bacto-tryptone, 10 g / L yeast extract and 5 g / L de NaCl) supplemented with 50 μg / ml kanamycin. Then, 0.3 mM isopropyl-β- D-thiogalactoside (IPTG) was added to the medium, and the cells were harvested after overnight incubation at 16oC Protein purification Cell pellets were resuspended in lysis buffers (see below) including 4 mg / ml DNase I and 18 mg / ml PMSF protease inhibitor, and lysed by sonication in a Bransonsonifier. Clear lysates were obtained after centrifugation at 20,000 g for 40 min at 4 oC,and the His-tagged proteins were firstly purified using a 5 ml nickel-nitrilotriacetic acidagarose column (Amersham Biosciences Limited, UK), followed by different stepsdepending on their use, as described below. Purification of ABA receptors for activity assays Lysis buffer was 50 mM Tris-HCl pH 8, 250 mM KCl, 0.1% Tween-20, 10% glycerol, 10 mM imidazole, 10 mM DTT, and binding buffer was 50 mM Tris-HCl pH 8, 100 mM KCl, 0.1% Tween-20, 10% glycerol, 20 mM imidazole, 10 mM DTT. The latter was used for a washing step including 40 mM imidazole, and proteins were then eluted with 50 mM Tris-HCl pH 8, 250 mM KCl, 0.1% Tween-20, 20% glycerol, 250 mM imidazole, 10 mM DTT buffer. Fractions showing concentration above 0.5 mg / ml werepooled and frozen at -80 oC until use.69 M / 64069-PCTEMBL 2020-011Purification of ΔN-HAB1 for activity assays Lysis and binding buffer were 30 mM Tris pH 7.5, 500 mM NaCl, 15 mM imidazole, 1 mM MnCl2, 5% glycerol, 1 mM 2-mercaptoethanol (ßME). A washing step was performed including 300 mM NaCl, and the protein was eluted under a gradient up to 250 mM imidazole. Protein fractions were pooled and cleaved by TEV protease while on dialysis with 20 mM Tris pH 7.5, 300 mM NaCl, 1 mM MnCl2, 5% glycerol, 1 mM ^MEfor 1.5 h at 4 oC. The protein was then run through the nickel column again to removethe TEV protease, and dialyzed overnight with 20 mM Tris pH 7.5, 150 mM NaCl, 1 mMMnCl2, 5% glycerol, 1 mM ^ME at 4 oC. Protein was concentrated to a maximum of 1mg / ml and stored at -80 oC until use.Purification of SlPYL1 for crystallization assays Lysis buffer and nickel column binding buffer were 30 mM Tris pH 7.5, 150 mM NaCl, 1 mM DTT. A washing step was performed using 30 mM Tris pH 7.5, 150 mM NaCl, 20 mM imidazole, 1 mM DTT, and the His tags were cleaved by tobacco etch virus (TEV) protease. The protein was eluted using 30 mM Tris pH 7.5, 150 mM NaCl, 40 mM imidazole, 1 mM DTT buffer, and then loaded on a HiLoad Superdex 20016 / 60 column (GE Healthcare) previously equilibrated with 30 mM Tris pH 7.5, 1 mM DTT buffer. Fractions corresponding to dimeric proteins were pooled, concentrated to 10 mg / ml andfrozen at -80 oC until use.Purification of CsPYL1 for crystallization assays Lysis buffer and nickel column binding buffer were 25 mM Tris-HCl pH 8, 200 mM NaCl, 15 mM imidazole, 5 mM beta-mercaptoethanol (ßME). A washing step was performed adding 40 mM imidazole to this buffer, and protein was eluted using 500 mM imidazole. The His tags were cleaved by tobacco etch virus (TEV) protease over night while dialyzing the protein to 25 mM Tris-HCl pH 8, 5 mM ßME buffer. Then, it was loaded on a HiLoad Superdex 20016 / 600 column (Cytiva) previously equilibrated with 25 mM Tris-HCl pH 8, 5 mM ßME buffer. Fractions corresponding to dimeric protein were pooled, concentrated to 3 mg / ml and frozen at -80oC until use. Purification of ΔN-HAB1 for crystallization assays Lysis and binding buffer were 30 mM Tris pH 7.5, 500 mM NaCl, 15 mM 70 M / 64069-PCTEMBL 2020-011imidazole, 1 mM MnCl2, 5% glycerol, 1 mM 2-mercaptoethanol (ßME). A washing step was performed including 300 mM NaCl, and the protein was eluted under a gradient up to 250 mM imidazole. Protein fractions were pooled and cleaved by TEV protease while on dialysis with 20 mM Tris pH 7.5, 300 mM NaCl, 1 mM MnCl2, 5% glycerol, 1 mM ßMEfor 1.5 h at 4 oC. The protein was then run through the nickel column again to removethe TEV protease, and dialyzed overnight with 20 mM Tris pH 7.5, 150 mM NaCl, 1 mMMnCl2, 5% glycerol, 1 mM ßME at 4 oC. Protein was concentrated to a maximum of 1mg / ml and stored at -80 oC until use.Table 1. Amino acid sequences of purified proteins and corresponding genesequences In the amino acid sequences depicted below sequence motifs applied to introduce a terminal His-tag are underlined. In the gene sequences depicted below the sequence portion encoding the respective protein (without His-tag) is stated in bold letters. SlPYL1 (Crystallization assays)Protein sequence (SEQ ID NO: 1)QGMDNKPETSLDNPVHQRSEPGSETGSSLSTITTHHLTVPPGLTPEEFQELSSSIAEFHSYRINPGQCSS LLAQRIHAPVETVWTVVRRFDKPQTYKHFIKSCSVGEDFRMTVGSTRDVTVISGLPAATSTERLDILDDD RHVTGFSIIGGEHRLRNYRSVTTVHGFERDGEIWTVVLESYVVDVPEGNTEEDTRLFADTVVKLNLQKLA SVTETLAREAGNGSVNSRDASHRSGene sequence (SEQ ID NO: 2)ATAAAATCTCTCGCTTTCTCCATCTCCATTTCTTCAATCTCCTTTCTCTCTCTATTTCTTCAATGGATAA TAAACCGGAAACGTCATTAGATAACCCGGTTCATCAACGATCTGAACCGGGTTCCGAAACCGGTTCCTCT CTATCAACAATTACAACTCACCACTTAACGGTTCCACCCGGTTTAACTCCGGAAGAATTCCAAGAGCTAA GCTCATCTATCGCTGAGTTTCACTCCTACAGAATCAACCCGGGCCAATGCTCTTCCCTACTCGCGCAGCG AATCCACGCGCCTGTCGAAACCGTCTGGACCGTCGTCCGCCGGTTCGACAAGCCACAAACGTACAAGCAC TTCATTAAAAGCTGTTCGGTAGGTGAAGACTTCCGTATGACCGTCGGATCCACCCGTGACGTCACCGTCA TCTCCGGCTTGCCGGCCGCTACCAGTACCGAACGGTTAGATATATTGGACGATGACCGGCACGTCACCGG ATTTAGTATCATTGGCGGAGAACACCGGTTGAGGAATTACCGTTCAGTTACGACGGTGCATGGATTCGAA CGCGACGGAGAGATCTGGACGGTTGTTTTGGAATCGTATGTTGTAGATGTACCGGAAGGGAATACGGAGG AAGATACACGCCTTTTCGCTGATACAGTTGTGAAATTGAACCTTCAGAAATTAGCTTCTGTTACTGAAAC TTTGGCGCGTGAAGCCGGTAATGGTAGTGTTAATAGTCGTGATGCGAGTCACAGGTGATACATGTGATTT ATTCAAACTATAAAAAGAAAATTGTCCTCTTTTCTTTTTATTTTTTATTTTTACTTCTTACTCGTTCTTT CTATTGTTTTGGGGTTTATGTGTTTGACAATGGATTAATAGAAAAAAGATAAATTAAATTTTCACCGTTA 71 M / 64069-PCTEMBL 2020-011AATTTTTTTTTAGCATTATACTATGAGTTATGAAATTGTTGATAGTCAATTGAGTAGAGTACGTTTTTAT GTGGCATATATGTTAAGTTTGTGCTTTTGATTGGATCA SlPYL1 (Activity assays)Protein sequence (SEQ ID NO: 3)MKHHHHHHPMSDYDIPTTENLYFQGMDNKPETSLDNPVHQRSEPGSETGSSLSTITTHHLTVPPGLTPEE FQELSSSIAEFHSYRINPGQCSSLLAQRIHAPVETVWTVVRRFDKPQTYKHFIKSCSVGEDFRMTVGSTR DVTVISGLPAATSTERLDILDDDRHVTGFSIIGGEHRLRNYRSVTTVHGFERDGEIWTVVLESYVVDVPE GNTEEDTRLFADTVVKLNLQKLASVTETLAREAGNGSVNSRDASHRSGene sequence (SEQ ID NO: 2)ATAAAATCTCTCGCTTTCTCCATCTCCATTTCTTCAATCTCCTTTCTCTCTCTATTTCTTCAATGGATAA TAAACCGGAAACGTCATTAGATAACCCGGTTCATCAACGATCTGAACCGGGTTCCGAAACCGGTTCCTCT CTATCAACAATTACAACTCACCACTTAACGGTTCCACCCGGTTTAACTCCGGAAGAATTCCAAGAGCTAA GCTCATCTATCGCTGAGTTTCACTCCTACAGAATCAACCCGGGCCAATGCTCTTCCCTACTCGCGCAGCG AATCCACGCGCCTGTCGAAACCGTCTGGACCGTCGTCCGCCGGTTCGACAAGCCACAAACGTACAAGCAC TTCATTAAAAGCTGTTCGGTAGGTGAAGACTTCCGTATGACCGTCGGATCCACCCGTGACGTCACCGTCA TCTCCGGCTTGCCGGCCGCTACCAGTACCGAACGGTTAGATATATTGGACGATGACCGGCACGTCACCGG ATTTAGTATCATTGGCGGAGAACACCGGTTGAGGAATTACCGTTCAGTTACGACGGTGCATGGATTCGAA CGCGACGGAGAGATCTGGACGGTTGTTTTGGAATCGTATGTTGTAGATGTACCGGAAGGGAATACGGAGG AAGATACACGCCTTTTCGCTGATACAGTTGTGAAATTGAACCTTCAGAAATTAGCTTCTGTTACTGAAAC TTTGGCGCGTGAAGCCGGTAATGGTAGTGTTAATAGTCGTGATGCGAGTCACAGGTGATACATGTGATTT ATTCAAACTATAAAAAGAAAATTGTCCTCTTTTCTTTTTATTTTTTATTTTTACTTCTTACTCGTTCTTT CTATTGTTTTGGGGTTTATGTGTTTGACAATGGATTAATAGAAAAAAGATAAATTAAATTTTCACCGTTA AATTTTTTTTTAGCATTATACTATGAGTTATGAAATTGTTGATAGTCAATTGAGTAGAGTACGTTTTTAT GTGGCATATATGTTAAGTTTGTGCTTTTGATTGGATCA AtPYR1Protein sequence (SEQ ID NO: 4)MGSSHHHHHHSSGLVPRGSHMPSELTPEERSELKNSIAEFHTYQLDPGSCSSLHAQRIHAPPELVWSIVR RFDKPQTYKHFIKSCSVEQNFEMRVGCTRDVIVISGLPANTSTERLDILDDERRVTGFSIIGGEHRLTNY KSVTTVHRFEKENRIWTVVLESYVVDMPEGNSEDDTRMFADTVVKLNLQKLATVAEAMARNSGDGSGSQV TGene sequence (SEQ ID NO: 5)TTTACCCTTACTATTTAATATAATTCCATGTTTACCCTTCATCTTCCCTCTAAAATCCAACACAGAGAGA TTTCAACGCTAAATAAAGAGAGAGAGAGTCTAAAAGCTCGTCGTCGTCTTCAATGGTGAATCTCAAACCA ATTGGATAAATAAAACAAAACAAAAAAAACTTCACAAAAAAAAAAAAAAGATCCAAATTACAACCATGCC TTCGGAGTTAACACCAGAAGAACGATCGGAACTAAAAAACTCAATCGCCGAGTTCCACACATACCAACTC GATCCAGGAAGCTGTTCATCACTCCACGCGCAACGAATCCACGCGCCTCCGGAACTCGTCTGGTCAATCG TACGACGATTCGACAAACCACAAACATACAAACACTTCATCAAATCCTGCTCCGTCGAACAAAACTTCGA GATGCGCGTCGGATGCACGCGCGACGTGATCGTCATCAGTGGATTACCGGCGAACACATCAACGGAAAGA CTCGATATACTCGACGACGAACGGAGAGTTACCGGATTCAGTATCATCGGAGGCGAACATAGGCTGACGA ATTACAAATCCGTTACGACGGTGCATCGGTTCGAGAAAGAGAATCGGATCTGGACGGTGGTTTTGGAATC TTACGTCGTTGATATGCCGGAAGGTAACTCGGAGGATGATACTCGTATGTTTGCTGATACGGTTGTGAAG CTTAATTTGCAGAAACTCGCGACGGTTGCTGAAGCTATGGCTCGTAACTCCGGTGACGGAAGTGGTTCTC AGGTGACGTGAAAATGAAGAAAAAAATATGATTTAATTTCTTTTATTAAAAACAAAATCCAGAAATGTTA TTTATGTTGCTTCGTATAAGATTCTCTTCTTCTTTTGTCTGTTTTTGCTTTTTTAACCTCATATAGTCAT ATTTTTACCATTTTCTTATGATGAGAATGACGTGCAAGGTTATTTTGGGCATTTTATGTTTGTGGATAAC TATGAATCTTTCCATTTTCGTTAGGTATATTCCGGCGAGTAAGTCAAAATTTTCGGCTATGCAACAAACT CTCATAAAAAGTTACAAAAAAACTTACTATAAAGTTACCAAAGGTTTATTTGACACAAAAAAAAAAAAAG TAAATAACCATTCGTGTAAGGTTTTACTTTTCTTTGAATGTAAAAAAAAAGAAAGGTTTTCCTTTTCTTT TCCTTTTGTTAAAAAAACATGGGGATAAGATTTTTTTCACGTGTTTTTTGCTGTTATTGCTTTAAGTATG GTAGATTTAGTGTGTGATTCGTATGAAAT 72 M / 64069-PCTEMBL 2020-011AtPYL1Protein sequence (SEQ ID NO: 6)MKHHHHHHPMSDYDIPTTENLYFQGMANSESSSSPVNEEENSQRISTLHHQTMPSDLTQDEFTQLSQSIA EFHTYQLGNGRCSSLLAQRIHAPPETVWSVVRRFDRPQIYKHFIKSCNVSEDFEMRVGCTRDVNVISGLP ANTSRERLDLLDDDRRVTGFSITGGEHRLRNYKSVTTVHRFEKEEEEERIWTVVLESYVVDVPEGNSEED TRLFADTVIRLNLQKLASITEAMNRNNNNNNSSQVRGene sequence (SEQ ID NO: 7)TTACTAATTTTGATGTACGTGTCTACAAATATAGTAATTATCAACTAAAAGTAGAAAGATTCAGTGCCTA ATGACATTTATGTGATAGCCATTAAAAAAAACTCAAGTCTATTAAATTCCAAATATACCCTTCTTCTCTT TCTTCTTCCTTCAAATTTTCAACTTCTCTCTTTCAAGTTTCAACAAACAATATCAATGGCGAATTCAGAG TCCTCCTCCTCACCAGTAAACGAAGAAGAGAACAGCCAGAGAATCTCAACACTCCATCACCAAACCATGC CTTCCGATTTAACTCAAGACGAATTCACCCAACTCTCCCAATCAATCGCCGAGTTCCACACGTACCAACT CGGTAACGGCCGTTGCTCATCTCTCCTAGCTCAGCGAATCCACGCGCCGCCGGAAACAGTATGGTCCGTG GTGAGACGTTTCGATAGGCCACAGATTTACAAACACTTCATCAAAAGCTGTAACGTGAGTGAAGATTTCG AGATGCGAGTGGGATGCACGCGCGACGTGAACGTGATAAGTGGATTACCGGCGAATACGTCTCGAGAGAG ATTAGATCTGTTGGACGATGATCGGAGAGTGACTGGGTTTAGTATAACCGGTGGTGAACATAGGCTGAGG AATTATAAATCGGTTACGACGGTTCATAGATTTGAGAAAGAAGAAGAAGAAGAAAGGATCTGGACCGTTG TTTTGGAATCTTATGTTGTTGATGTACCGGAAGGTAATTCGGAGGAAGATACGAGATTGTTTGCTGATAC GGTTATTAGATTGAATCTTCAGAAACTTGCTTCGATCACTGAAGCTATGAACCGGAACAACAACAACAAC AACTCTTCTCAGGTTAGGTAATGATGAAATTTGGGGGAAAGAAAAATGTTTCTAAATTGGGGGAGTTTTA ATTTTTATTTTGATTTGTAAAACGTTTTTTTTCTTCTCTTGAATTGTAATTTCCTTGTTTGATTTTATGG TTATGTTTTATTTTTTAAAAAAAATCAGTCTCCTGGATAATTGGAATGGTCGAGATAGGTTAAATTTAAT AACATACTTGTTATATCATAGAATTAGGAATGATAACATACTAATTATAGTAGTTAGTTTTCTTTAACTG TT AtPYL2Protein sequence (SEQ ID NO: 8)MKHHHHHHPMSDYDIPTTENLYFQGMSSSPAVKGLTDEEQKTLEPVIKTYHQFEPDPTTCTSLITQRIHA PASVVWPLIRRFDNPERYKHFVKRCRLISGDGDVGSVREVTVISGLPASTSTERLEFVDDDHRVLSFRVV GGEHRLKNYKSVTSVNEFLNQDSGKVYTVVLESYTVDIPEGNTEEDTKMFVDTVVKLNLQKLGVAATSAP MHDDEGene sequence (SEQ ID NO: 9)TAGTAATATATAAAAAAACACTCATAGCTCCCAAAAAAAGAACTGTCTTTTATTCTCATCTCTTTCACAA ACCCCCCAACCTCCAACAAGAAGACCTCTCTTTCATAAAACCCTCACACGTGTGACTGATTCATCACCAT GAGCTCATCCCCGGCCGTGAAAGGCCTAACCGATGAAGAGCAGAAAACCCTCGAACCGGTTATCAAAACG TACCACCAGTTCGAACCAGACCCAACCACGTGCACTTCTCTCATAACCCAACGCATCCACGCTCCGGCCT CCGTGGTTTGGCCTCTTATCCGCCGCTTCGACAACCCCGAACGCTACAAACACTTTGTAAAAAGGTGCCG TCTCATCTCCGGTGATGGTGACGTCGGAAGCGTCAGAGAAGTGACCGTAATCTCCGGCCTCCCAGCCTCA ACCAGTACCGAGCGGCTTGAGTTCGTCGATGACGACCACCGTGTTCTAAGCTTCAGGGTCGTCGGCGGAG AGCACCGACTCAAGAACTACAAATCAGTGACGTCGGTCAATGAGTTCTTGAATCAAGATTCCGGCAAGGT TTACACGGTGGTTCTTGAATCTTACACCGTTGATATTCCCGAGGGAAACACAGAGGAAGACACTAAAATG TTTGTGGACACTGTCGTCAAACTCAACCTTCAGAAACTCGGAGTTGCCGCCACATCTGCACCTATGCATG ATGATGAATAATTTCAAGTTTATTTCTTATATTTTCTCTCGGTAAGTTTTTTCCTTTCTTCTGATGATTA TTGATTATTTACTTAATTTGTGAGATTTACTATTGGAAGCAAATGTTTAATTCGATTCCGTTAACGAAAC TATTGTTGCATAACGCATATTAGTTCTCTGTTTATTTTTTTCCAATAAACGGCAAATCACGAATTCTGTC ATTTGATTTTGCTTTTTCACCATCTATTTTTGAATAAATTTGGACTATTTTTGAATAAACTTTGGACTAT TTTTGATGATGTCAAAAATTGGTATTACACTCTTAATTAATATTGGTTATAGTTGGTCTATAGTATTTGC GCTACAAAGAGTCAAGAAATCTTGCCGGTTATCAAAAAGCAAAAAGGAACTTAGAAATCACTTCTTGTCG CAATGTTGAATTAGATTTTTATTTACCTTACCAAAATCATTCTTCTTCTTCTTCTTATTAGGTTAACGTT TTTTAGGGCACCTTTGAAAAAAGTTTATACATATATATTCCGATGGTTTGTGTCTCCACAAAACTTGTCC AATACATTTTTTTTCATTAATTATA 73 M / 64069-PCTEMBL 2020-011AtPYL5:Protein sequence (SEQ ID NO: 10)MKHHHHHHPMSDYDIPTTENLYFQGMRSPVQLQHGSDATNGFHTLQPHDQTDGPIKRVCLTRGMHVPEHV AMHHTHDVGPDQCCSSVVQMIHAPPESVWALVRRFDNPKVYKNFIRQCRIVQGDGLHVGDLREVMVVSGL PAVSSTERLEILDEERHVISFSVVGGDHRLKNYRSVTTLHASDDEGTVVVESYIVDVPPGNTEEETLSFV DTIVRCNLQSLARSTNRQGene sequence (SEQ ID NO: 11)AGGAAAGAAATCATGGGGGCATAAGATGGTACAATGTATCATACATGGTCACACACATCTATATGATACA AATGCGTCTATATACACAACTGTTTCTATATACATACAAACACAAAGCCTTCACATCCCCAGCTATCTCT ATCCATCTATCTTCAAATATATATTTTTAAAAACACACAATGTTCATATCTTATTGTTATTGTTATAAAA TAAAAGATGATCATACTTTTTAAATTTCTCAAACAAAACCAACTTGACAACCGACAGCGAACAAGATCAA AAAGCTAGCTCTCTTCTTTTCTCATCAAACTTATTTCTCTCTCGATCGCAATATATACGATTCCATAAAT TCTCCCAAAAACAAATTAAGAGATAGAGGAGAGATCATGAGGTCACCGGTGCAACTCCAACACGGCTCAG ACGCCACTAACGGTTTCCACACGCTGCAGCCTCACGATCAGACCGATGGTCCGATCAAGAGAGTGTGTCT CACGCGCGGTATGCATGTCCCTGAACACGTTGCGATGCACCACACACACGACGTTGGTCCGGACCAGTGT TGCTCCTCGGTGGTGCAGATGATCCACGCGCCGCCTGAGTCCGTGTGGGCTCTTGTGCGGCGTTTCGATA ATCCGAAGGTTTACAAGAACTTCATCAGACAGTGCCGTATCGTCCAAGGCGATGGACTACACGTCGGCGA TCTCCGGGAGGTCATGGTGGTCTCTGGACTCCCGGCGGTCTCGAGCACCGAGAGGCTCGAGATCTTGGAC GAGGAGCGTCACGTGATAAGCTTTAGTGTCGTTGGTGGGGACCACAGGCTCAAGAACTACCGATCGGTGA CGACACTACACGCGTCGGACGACGAAGGTACCGTGGTGGTGGAGTCTTACATCGTTGATGTGCCGCCGGG AAACACGGAGGAGGAAACTCTAAGCTTCGTTGATACTATCGTCCGGTGCAACCTTCAGTCTCTGGCTCGA AGTACCAACCGGCAATAATCTCATCTTTCTTATATAAATTGCAATTATGTATCTAATTTTTTTTGTTGTT CTATTTCTTTTAGATGTTCGATCTTCTTTACAAGGAAGAAAATTTCGAGTACCTTTTCTTTCTTTTTAAA TAGATATATCGGCTTAGAAAGAATTGTAATTTAATGGGGATTTCTTTGGGAGATTTATGTTGGAAATTTC GAAGTACTGTTGGGGGATTCACAAAACTTTGGATTTGGAGGGTGTTAGTACTGGTACATAAAACATTTTA AGGTGAATCTGTTAAATGAATTAATCCATTTGTTGTTTTGTACATGGTATCATTCTTTGTGACATTGTTT AATTTCTTGTACTCTTTTAAATGTTACTCTTAACCGTTTTTTTCTTTTGTGGTTTGTAAATGAATATTTG ATGCATCGGTATTGTTAATGATAGACTTATTAATTTATTTCTTCATAGTATGTAACATTACTATAAGTTT GTTTTTTGTTGGTTGATCCTTGTGTCCAAATGTTCTAAATAGAAAATATAATACAAAGCCGATATTCTGA AtPYL9Protein sequence (SEQ ID NO: 12)MKHHHHHHPMSDYDIPTTENLYFQGMMDGVEGGTAMYGGLETVQYVRTHHQHLCRENQCTSALVKHIKAP LHLVWSLVRRFDQPQKYKPFVSRCTVIGDPEIGSLREVNVKSGLPATTSTERLELLDDEEHILGIKIIGG DHRLKNYSSILTVHPEIIEGRAGTMVIESFVVDVPQGNTKDETCYFVEALIRCNLKSLADVSERLASQDI TQGene sequence (SEQ ID NO: 13)TTAGTATCTTGTTGTGTTTTTGTTTGGTTTGAAAAGCTGAAAATGTGTGAAGGAGAAGAAGGAAGCTATA AAAAAGAGTTTAGGTACAAAAGTAAAAAGTTATTATGTCGGTGGGTTCATTAAAAGAAACCAAAAAACAT AAACAAGTAATTTTGTTTTGGCATAACGAAGCATCTTCTTCTTCTTCCTTGTATTTATTATCCATTTCCA GAGATTCTCCCTTGTGAGATAACAACGAAGAACGAAAGAGAGAGAGAGAGAGAGAGATATGATGGACGGC GTTGAAGGCGGCACGGCGATGTACGGTGGTCTCGAGACGGTGCAATACGTACGGACGCATCATCAACATC TGTGCAGAGAAAACCAGTGTACCTCTGCTCTTGTCAAACACATCAAAGCTCCTCTTCATCTCGTTTGGTC ACTTGTACGGAGATTTGATCAGCCGCAGAAATACAAACCGTTTGTGAGCAGATGTACAGTAATCGGTGAT CCTGAAATCGGCAGTCTTAGAGAAGTCAATGTTAAATCTGGTCTTCCTGCAACAACATCTACTGAGAGAT TAGAACTTCTTGATGATGAAGAACACATCCTCGGTATCAAAATCATCGGTGGTGATCACAGACTTAAGAA TTACTCGTCGATTTTGACGGTTCATCCGGAGATAATCGAGGGAAGAGCAGGAACGATGGTGATTGAATCG TTTGTAGTTGATGTTCCTCAAGGTAACACAAAGGATGAGACTTGCTACTTTGTTGAAGCACTTATCAGAT GTAATCTCAAGTCACTAGCAGATGTTTCTGAAAGATTGGCTTCTCAGGACATTACTCAGTGAACTACATA ATCAATGAACAAGGGCATTGAAGTGAAGTATCAATTCCAGTTTGTGATATAATCAATATTCTTCAGGATT 74 M / 64069-PCTEMBL 2020-011TTTTTGGTTTGGCCTAGATATATATATAGATATCTATCCTCGGTAATGACCAGTCTAAAAAGATGTACAT ATTGTCCCAATGGTGAAGTTTTGATGTAAGATATCTCCTGGTGGTTTGTTATTTGTAGATATTTTTGTAA ACAATGTAAATGTGAATGGTTTATGATGTATAATATATAGTTCACAAAAGATGTTTCTGTAGACTTCAGA TTCCACTTCTCTATTGAACAGAACCTATGATTGGATGCTGAGAACTTGTAAAGAATCTG ^N-HAB1 (Activity and Crystallization assays)Protein sequence (SEQ ID NO: 14)SVYELDCIPLWGTVSIQGNRSEMEDAFAVSPHFLKLPIKMLMGDHEGMSPSLTHLTGHFFGVYDGHGGHK VADYCRDRLHFALAEEIERIKDELCKRNTGEGRQVQWDKVFTSCFLTVDGEIEGKIGRAVVGSSDKVLEA VASETVGSTAVVALVCSSHIVVSNCGDSRAVLFRGKEAMPLSVDHKPDREDEYARIENAGGKIVQWQGAR VFGVLAMSRSIGDRYLKPYVIPEPEVTFMPRSREDECLILASDGLWDVMNNQEVCEIARRRILMWHKKNG APPLAERGKGIDPACQAAADYLSMLALQKGSKDNISIIVIDLKAQRKFKTRTGene sequence (SEQ ID NO: 15)CAGAGAGAAAAAGCAAACCACACAATATTCTCTTCTCTCTCTCTTTGTTTCGCTGATAGAGAGAGCCTCT CTCTAAGCAATTTAGCTCGAGCGAGAAATAATCCTGAGGGAAGAAAATAAAAAGAAGAAGAAGAAGAAGA ACATCTTTACTTTTGTTCTCTCTCTCTCTTCTGTTCGATTTTAATTTTTTTGCAGATGCGAATATCTTCT AAAGATTCATCAACTGGGTTGAAATCAAGATAAGGATTTGAGAAAAGATCGACGAAGTTGTTGCGATTTT GGGATCAAGAGAGTGATATAATCGAGTGAGGAGAATTCGTCGTATAGATTCGTCAGATCTGGTTATCTCC GGTACTTAATTCTCCTTGATTCGTCGTTTTAACTATGCTAAGTTAGTGTATGAATAAAGCGGCATTTGGG TCGCTGACAAAAACTTATTTGGAGCAAGGATTCTTCAACATCATGAAACCATTGCTTAGAGTATTCGAAG AAGAAGATGAAAACAATTGATTTCTCCTAAGTCCATCTTTGAAATTTAAAGCTTTGTTGTGGTGTGGTGT GGAAATCTCTGATTTTGGAGAGCTCATGGAGGAGATGACTCCCGCAGTTGCAATGACTCTTAGCTTAGCA GCCAACACCATGTGTGAATCATCACCTGTCGAGATCACTCAGCTAAAGAACGTTACTGATGCAGCTGACT TGTTATCTGATTCTGAAAATCAAAGCTTTTGCAACGGAGGGACTGAATGCACTATGGAAGATGTTTCTGA ACTGGAAGAGGTAGGTGAACAGGATTTGTTGAAAACTTTATCCGATACGAGAAGCGGGTCTTCCAATGTT TTTGATGAAGACGATGTATTGTCTGTTGTGGAGGATAATAGTGCTGTCATAAGTGAGGGCTTGTTAGTTG TTGATGCAGGCTCTGAATTAAGCTTGTCTAATACAGCTATGGAAATAGATAACGGGCGAGTTCTTGCAAC CGCGATTATCGTAGGCGAATCAAGCATTGAGCAGGTTCCCACCGCGGAAGTTCTTATCGCGGGTGTAAAT CAGGATACCAATACTTCGGAGGTTGTCATTAGATTGCCAGATGAAAATAGTAATCATCTGGTGAAAGGGA GAAGTGTTTATGAACTAGATTGTATACCGCTTTGGGGCACGGTTTCCATTCAAGGGAATAGATCTGAGAT GGAGGATGCTTTTGCCGTGTCACCTCATTTTCTGAAACTACCCATCAAAATGCTTATGGGGGACCATGAG GGTATGAGTCCAAGCCTCACACACCTCACCGGTCATTTTTTCGGTGTTTATGATGGTCATGGAGGCCATA AGGTTGCTGACTATTGCCGAGATAGACTCCATTTTGCTTTGGCTGAAGAAATAGAACGTATAAAAGACGA ATTATGCAAGAGGAATACAGGAGAGGGTAGGCAGGTGCAGTGGGATAAAGTCTTCACGAGTTGTTTTCTA ACTGTCGATGGTGAGATTGAAGGAAAAATTGGTAGAGCCGTTGTTGGTTCTTCTGATAAGGTTCTTGAGG CTGTTGCGTCTGAGACCGTAGGATCAACTGCTGTTGTTGCCTTGGTTTGCTCATCACATATAGTAGTTTC TAACTGCGGTGATTCGAGGGCGGTTTTATTCCGTGGCAAAGAAGCCATGCCCTTGTCAGTTGATCACAAA CCAGATAGAGAGGATGAATATGCAAGAATAGAAAATGCTGGAGGCAAAGTTATACAATGGCAAGGCGCAC GTGTTTTTGGTGTTCTCGCCATGTCTAGGTCCATCGGTGACAGATATCTGAAGCCATATGTGATCCCAGA ACCGGAAGTGACATTCATGCCTCGGTCAAGAGAAGACGAGTGTCTCATACTAGCCAGTGACGGTCTTTGG GATGTAATGAACAACCAAGAAGTCTGCGAAATAGCAAGGAGACGGATATTGATGTGGCACAAGAAGAACG GTGCACCGCCTCTAGCAGAGAGAGGCAAAGGAATAGATCCAGCTTGCCAAGCCGCAGCTGACTACCTCTC AATGCTTGCTCTACAAAAAGGAAGTAAAGACAACATCTCCATCATTGTGATTGACTTGAAAGCTCAAAGA AAGTTCAAGACCAGAACCTGAAGCTTAATTACAAGCAGTACGCTTACTTACTTTTTTTTTTACTGGGGGT AAAAAAAATAAAGAAAAAAAATGGAAATGCGGGTTGGGGAGGAGAAGTAAAGACTAAAGACTGAAGATTA AGAAGATGATGCATAGCTAATTATAAGTACATTCCTTTTTTTCTCATGGTACTTGAATTCGTATGTATAA GAAGAAATAGGCAGAGAAATGCTTTTTTTTTTTGGGGTATTGAAATAGTTGAATATGTTGTAATAGTTTG AGAGATGTGGCAAATGAAATTGTAATTGAAACTATGTCACATTAACCTTCTTGCATTTGTCTTTTCATGT TGTGTTCTTCGCT CsPYL1 (Crystallization assays) 75 M / 64069-PCTEMBL 2020-011Protein sequence (SEQ ID NO: 16)QGMDNNKAEADTSSSMADPETRPTYTTHHLAIPSGVTQDEFDELKQSVVEFHTYQLSQNQCSSLLAQRIR APNDVVWSIVRRFDQPQTYKHFIKSCSVSDNFTMAVGSTRDVNVISGLPAATSTERLDILDDDRQVTGFS IIGGEHRLRNYRSVTSVHGFNRDGAICTVVLESYVVDVPEGNTEEDTRLFADTVVKLNLQKLVSVAESQV IGene sequence (SEQ ID NO: 17)CTCTCTCTTCTCTAATTTTTATCGTCAATGAACAACAACAAAGCAGAAGCAGACACATCTTCTTCAATGG CCGACCCGGAAACCCGACCCACTTACACAACCCACCACTTAGCGATTCCATCCGGGGTAACTCAGGACGA GTTTGACGAGTTAAAACAGTCCGTCGTCGAGTTTCACACGTACCAACTCAGCCAAAACCAATGCTCTTCT TTACTGGCACAGCGAATCCGAGCCCCAAACGACGTCGTCTGGTCCATAGTCCGCCGTTTCGACCAGCCCC AGACCTACAAACACTTCATCAAGAGCTGTTCCGTCTCCGATAACTTCACAATGGCTGTGGGATCTACCAG GGACGTTAACGTCATCTCCGGGCTACCGGCTGCTACCAGTACTGAGAGACTTGACATTCTGGACGATGAC CGGCAAGTCACCGGTTTCAGTATCATTGGAGGGGAACATAGGTTGAGGAATTACCGGTCGGTCACCTCGG TGCATGGATTCAATCGTGACGGCGCGATCTGTACCGTTGTTTTGGAATCTTACGTTGTTGATGTGCCCGA AGGGAATACCGAAGAGGACACGCGTCTTTTTGCGGATACGGTCGTCAAGTTAAATCTGCAGAAGCTGGTC TCTGTCGCTGAATCACAGGTGATATGATATCATAATATGATATGAATAAACACGAAGTTAAAACAAAATA AATAATTTTTTCCTATTTTTCTTTTTATGTTCTAAGAGTATTTTTTTTTTTCTTCCTCTTTTGGGTTCCT TTGAATCGGGTAATGTTCGAGGTTTGAGTGGCATTTAAATCGAAGCATTTGTACAAAAATGTTTGAACAT TTCAAGATC.2 Phosphatase assayThe activity of HAB1 phosphatase was measured as kinetic fluorescence intensity assay using 6,8-Difluoro-4-Methylumbelliferyl Phosphate (DiFMUP) as substrate in black 384-well ProxiPlates (PerkinElmer) at room temperature in 10 µl / well final assay volume. The assay was started with the addition of 40 µM DIFMUP to 50 nM HAB1 phosphatase in 25 mM Tris pH 8, 10 mM NaCl, 2 mM DTT, 0.05% Tween 20, 1 mM MnCl2 as assay buffer. Fluorescence intensity (FI) of the fluorophore increases when phosphate is released and was measured at 460nm after excitation at 340nm in an Envision 2104 plate reader (PerkinElmer). Assay plates with serially diluted compounds were prepared as described for the TR-FRET assay. Compounds were tested for their activity as ABA-agonists in the presence of 100 nM His-tagged ABA-receptors and for their activity as ABA-antagonists in the presence of 100 nM ABA-receptors and 3 µM ABA. The effect of compounds on the assay read out or on the phosphatase activity was determined with 50 nM HAB1 phosphatase alone.C.3 TR-FRET assayA Europium labelled anti-His6 tag antibody is coupled to His-tagged ABA receptor protein. When the ABA-receptor is bound by the dye-labelled tracer molecule Cy5-Ant, excitation with 340 nm light produces FRET between Europium (620 nM emission) and the dye (665 nM emission). In the presence of an ABA-receptor binder, which is capable 76 M / 64069-PCTEMBL 2020-011of competing with the tracer ligand, FRET is disrupted and a change in the signal is observed. The concentrations of reagents in 10 µl final assay volume were 5 nM His-tagged receptor, 0.5 nM Europium-labeled anti-6X His antibody, 30 nM Cy5-ANT. Eu-W1024 Anti-6xHis for capturing His-tagged proteins in TR-FRET assays were purchased from PerkinElmer, the ANT-Cy5-Tracer was synthesized in-house as described. An eleven-fold 1:3-serial dilution of test compounds starting at 50 or 1 mM wasprepared in 384well pp-plates (Greiner) from 50 mM stocks in pure DMSO and 5 µltransferred to another 384well pp-plate.45 µl of water was added with a Multidrop bulk- dispenser resulting in a serial dilution starting at 10 and 0.2 mM.1 µl of this serial dilution in 20% DMSO was transferred to several copies of assay plates. The assay was started by the addition of 5 µl of Eu-donor + / - His-tagged receptorto the assay plate followed by an incubation for 15 min. Then 4 µl of ANT-Cy5 tracer were added to all wells and after 45 min incubation, TR-FRET was measured in an EnVision™ plate reader equipped with a TR-FRET Laser module. Sample wells were exited with the TRF-Europium Laser, emission measured at 620 nm and 665 nm to get the 665nm / 620nm ratio. Percent inhibition was calculated for each well from negative control wells containing 2% DMSO and positive control wells containing only Eu-donor and no His- receptor. The resulting dose-response curves were fitted in ActivityBase (IDBS) using a four-parameter logistic model and IC50-values calculated.C.4. Synthesis of ANT-Cy5 Tracer77 M / 64069-PCTEMBL 2020-011 Step 1: Synthesis of 1-(2-(3,5-Dicyclopropyl-4-(4-((7-ethynylquinoline-2- carboxamido)methyl)-1H-1,2,3-triazol-1-yl)phenyl)acetamido)cyclohexane-1- carboxylic acid (ANT-alkyne) The title compound was synthesized according to literature known procedurehttps: / / doi.org / 10.1073 / pnas.2108281118 (Vaidya et. al., PNAS, 2021, 118, 1-7).LC-MS (ESI): m / z = 617 [M + H]+.1H NMR (400 MHz, DMSO-d6) δ 12.22 (bs, 1H), 9.43 (t, J = 6.0 Hz, 1H), 8.57 (d, J = 8.5Hz, 1H), 8.31 – 8.26 (m, 2H), 8.20 (d, J = 8.5 Hz, 1H), 8.14 – 8.07 (m, 2H), 7.87 (dd, J =8.7, 1.9 Hz, 1H), 6.79 (s, 2H), 4.74 (d, J = 6.0 Hz, 2H), 4.47 (s, 1H), 3.45 (s, 2H), 1.97(d, J = 13.2 Hz, 2H), 1.70 – 1.54 (m, 2H), 1.56 – 1.32 (m, 5H), 1.30 – 1.08 (m, 3H), 0.81– 0.64 (m, 4H), 0.64 – 0.52 (m, 4H).Step 2: Synthesis of ANT-Cy5 Tracer78 M / 64069-PCTEMBL 2020-011 Cyanin-5-azide (12 mg, 20 µmol), ANT-alkyne (12 mg, 20 µmol) and 3,3',3''- ((nitrilotris(methylene))tris(1H-1,2,3-triazole-4,1-diyl))tris(propan-1-ol) (THPTA, 7.0 mg, 16 µmol) were dissolved in DMSO (400 µl). To this mixture was added a solution of sodium ascorbate (3.2 mg, 26 µmol) in water (50 µl) followed by a solution of copper (II) sulfate (1.3 mg, 8.0 µmol) in water (50 µl). The reaction mixture was stirred at room temperature overnight and then directly loaded on a Biotage® Sfär C18 D column. The crude product was purified using a linear gradient of water and Methanol to obtain 13 mg (11 µmol / 53%) of the analytically pure title compound and used in TR-FRET binding assays.LC-MS (ESI): m / z = 1182 [M - Cl]+.1H NMR (400 MHz, Methanol-d4) δ 8.57 (s, 1H), 8.42 (d, J = 8.6 Hz, 1H), 8.38 (s, 1H),8.29 – 8.11 (m, 6H), 7.43 (dd, J = 7.3, 4.5 Hz, 2H), 7.36 (q, J = 7.2 Hz, 2H), 7.22 (td, J =7.4, 6.9, 4.4 Hz, 4H), 6.90 (s, 2H), 6.53 (t, J = 12.4 Hz, 1H), 6.23 (d, J = 13.6 Hz, 1H),6.14 (d, J = 13.7 Hz, 1H), 4.86 (d, J = 8.6 Hz, 2H), 4.51 (t, J = 6.6 Hz, 2H), 4.05 (t, J =7.4 Hz, 2H), 3.54 – 3.51 (m, 5H), 3.25 (t, J = 6.5 Hz, 2H), 2.24 – 2.06 (m, 6H), 1.83 –1.70 (m, 4H), 1.67 (s, 6H), 1.65 (s, 6H), 1.61 – 1.47 (m, 4H), 1.47 – 1.18 (m, 10H), 0.76– 0.56 (m, 8H).D. Synthesis of Exemplary ImidazolesReaction Scheme for Imidazoles 3a-b 79 M / 64069-PCTEMBL 2020-011 Example 1: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide hydrochloride (3a) Step (i): 2-Amino-3-(tert-butoxy)-N-(quinolin-3-yl)propanamide (1). Fmoc-Ser(tBu)OH (1.00 g, 2.61 mmol) and HATU (826 mg, 2.17 mmol) were dissolved in DMF (40 mL). The mixture was stirred overnight after the addition of 3- aminoquinoline (313 mg, 2.17 mmol) and DIPEA (0.76 mL, 4.35 mmol). All volatiles were removed under vacuum and the product was purified by column chromatography using a linear gradient of ethyl acetate in cyclohexane (5 to 70%) to obtain the Fmoc protected intermediate (1.09 g, 2.14 mmol). For Fmoc removal, the protected intermediate (1.09 g, 2.14 mmol) was dissolved in 10% piperidine in DMF (20 mL). The mixture was stirred for 1 h. All volatiles were removed under vacuum. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to obtainintermediate 1 (505 mg, 1.76 mmol).Step (ii): (S)-3-(tert-Butoxy)-2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propan-amide (2a). To a mixture of intermediate 1 (505 mg, 1.76 mmol) in isopropanol (14 mL)and 25 wt% ammonia solution (126 mg, 1.85 mmol) were added a mixture of 40 wt% glyoxal solution (255 mg, 1.76 mmol), 37 wt% formaldehyde solution (143 mg, 1.76 mmol), and isopropanol (3 mL) dropwise. It was stirred at 80 °C. After 5h of stirring, it was cooled to room temperature and all volatiles were evaporated under vacuum. The residue was purified by column chromatography using a linear gradient of methanol indichloromethane (0 to 20%, v / v) to obtain intermediate 2a (178 mg, 0.53 mmol).Step (iii): (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide hydrochloride (3a). Intermediate 2a (134 mg, 0.40 mmol) was dissolved in dichloromethane (1.5 mL). At room temperature, trifluoroacetic acid (1.5 mL) was added 80 M / 64069-PCTEMBL 2020-011slowly and the mixture was stirred for 5 h. All volatiles were evaporated. The residue was purified by reverse phase column chromatography using a linear gradient of water and acetonitrile with 0.1% trifluoroacetic acid. The compound containing fractions were treated with 1 M HCl and lyophilized to obtain compound 3a (71 mg, 0.22 mmol) as a hydrochloride salt.LC-MS (ESI): m / z (free base) = 283.1 [M + H]+.1H NMR (400 MHz, D2O) δ 8.17 (d, J = 8.5 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 8.03 ()ddd,J = 8.6, 7.0, 1.3 Hz, 1H), 7.88 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H), 5.65 (dd, J = 5.9, 4.0 Hz,1H), 4.40 (dd, J = 12.6, 6.0 Hz, 1H), 4.31 (dd, J = 12.6, 3.9 Hz, 1H).[α]D25= +29.8 ° (c 0.3, MeOH) Example 2: (S)-2-(4,5-Dimethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3- yl)propanamide (3b) (S)-2-(4,5-Dimethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (3b) was synthesized similar to compound 3a. The title compound (9 mg, 0.03 mmol) was isolated as hydrochloride salt.LC-MS (ESI): m / z (free base) = 311.2 [M + H]+.1H NMR (400 MHz, DMSO-d6) δ 14.65 (s, 1H), 12.18 (s, 1H), 9.28 (s, 1H), 9.22 (s, 1H),8.94 (s, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 7.1 Hz, 1H), 7.82 (dd, J = 8.6, 6.8 Hz,1H), 7.72 (dd, J = 8.2, 6.8 Hz, 1H), 5.54 (dd, J = 6.7, 4.5 Hz, 1H), 4.25 (dd, J = 11.9, 7.0Hz, 1H), 4.19 (dd, J = 11.9, 4.4 Hz, 1H), 2.26 (s, 3H), 2.25 (s, 3H).13C NMR (101 MHz, DMSO-d6) δ 165.5, 142.2, 132.5, 130.1, 128.3, 128.2, 128.0, 126.6,126.1, 125.6, 124.2, 61.5, 61.2, 8.8, 7.9. General Procedure 1 (GP-1) for the Synthesis of Imidazoles 3 81 M / 64069-PCTEMBL 2020-011 Step (i): Formaldehyde solution (37 wt% in H2O, 0.73 g, 9 mmol) and glyoxalsolution (40 wt% in H2O, 1.3 g, 9 mmol) were mixed and heated to 50 °C. At this temperature, a mixture of L-Ser(tBu)OH (1.5 g, 9 mmol), concentrated ammonia solution (0.61 g, 9 mmol) and 1M of NaOH solution (9 mL, 9 mmol) was added slowly. The final mixture was then stirred 4 h at 50 °C. All volatiles were evaporated under vacuum. The residue was dissolved in methanol-dichloromethane mixture (1:1, 20 mL) and diluted with diethyl ether (200 mL). Intermediate S1 (1.89 g, 90% yield) was precipitated and collected by filtration. Step (ii): To a solution of intermediate S1 (1.0 equiv), the correspondingarylamine (1.2 equiv), and pyridine (10 equiv) were added propylphosphonic anhydride (T3P) solution (50 wt% in ethyl acetate, 2.0 equiv) dropwise. The reaction mixture was stirred overnight at room temperature. The reaction was quenched with saturated NaHCO3solution and the product was extracted with ethyl acetate three times. Combined organic extracts were dried over Na2SO4or MgSO4, filtered and concentrated under vacuum. Further purification was performed by column chromatography to obtain intermediate S2. Step (iii): Intermediate S2 was dissolved in dichloromethane (4 mL). At roomtemperature, trifluoroacetic acid (2 mL) was added slowly and the mixture was stirred overnight. All volatiles were evaporated. The residue was dissolved in dichloromethane or 10 % methanol in dichloromethane. It was washed with saturated sodium bicarbonate solution. Organic phase was dried over sodium sulfate, filtered and concentrated under vacuum. In most cases, the crude product was purified by reverse phase columnchromatography using a linear gradient of water and methanol to obtain compound 3 asa free base. In some cases, the crude product was treated with excess amount oftriethylamine before column chromatography. In some cases, a linear gradient of water and acetonitrile (both containing 0.1% trifluoroacetic acid) was used. The compound containing fractions were treated with 1 M HCl and lyophilized to obtain compound 3 as a hydrochloride salt. 82 M / 64069-PCTEMBL 2020-011Example 3: 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyridin-3-yl)propanamide (3c) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyridin-3-yl)propanamide (3c) was synthesized according to GP-1 as described above. The crude product was treated with triethylamine and purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (34mg, 0.14 mmol) as a racemic mixture.LC-MS (ESI): m / z = 233.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.75 (dd, J = 2.6, 0.7 Hz, 1H), 8.29 (dd, J = 4.9, 1.5Hz, 1H), 8.14 (ddd, J = 8.4, 2.6, 1.5 Hz, 1H), 7.87 (bs, 1H), 7.42 (ddd, J = 8.4, 4.8, 0.8Hz, 1H), 7.33 (bs, J = 1.3 Hz, 1H), 7.02 (bs, 1H), 5.08 (dd, J = 6.8, 5.7 Hz, 1H), 4.16 (dd,J = 11.4, 5.8 Hz, 1H), 4.08 (dd, J = 11.4, 6.9 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.5, 145.8, 142.1, 138.1, 136.9, 129.3, 128.6,125.4, 120.4z, 63.9, 63.6. Example 4: (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1H-pyrrolo[2,3-b]pyridin-5- yl)propanamide hydrochloride (3d) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)propanamide hydrochloride (3d) was synthesized according to GP-1 as described above. The crude product was analytically pure and no column chromatography was performed. It was treated with 1M HCl and lyophilized to obtain the title compound (39mg, 0.13 mmol) as a racemic mixture. 83 M / 64069-PCTEMBL 2020-011LC-MS (ESI): m / z (free base) = 272.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 9.24 – 9.19 (m, 1H), 8.89 – 8.82 (m, 1H), 8.78 – 8.68(m, 1H), 7.85 (q, J = 1.8 Hz, 1H), 7.71 (t, J = 3.6 Hz, 1H), 7.63 (t, J = 1.7 Hz, 1H), 6.88 –6.81 (m, 1H), 5.62 – 5.52 (m, 1H), 4.37 (dd, J = 12.3, 6.0 Hz, 1H), 4.25 (dd, J = 12.1, 3.9Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 166.5, 139.7, 131.5, 129.7, 129.6, 128.8, 126.7, 123.9, 120.2, 103.8, 63.4. Example 5: (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1,8-naphthyridin-3- yl)propanamide (3e) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1,8-naphthyridin-3-yl)propanamide (3e) was synthesized according to GP-1 as described above. The crude product was treated with triethylamine and purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (9 mg, 0.03 mmol) as a racemic mixture.LC-MS (ESI): m / z = 284.2 [M + H]+.1H NMR (400 MHz, DMSO-d6) δ 11.11 (s, 1H), 9.09 (d, J = 2.8 Hz, 1H), 8.98 (dd, J =4.2, 1.9 Hz, 1H), 8.83 (d, J = 2.8 Hz, 1H), 8.45 (dd, J = 8.2, 2.0 Hz, 1H), 7.94 (s, 1H),7.61 (dd, J = 8.1, 4.2 Hz, 1H), 7.38 (s, 1H), 7.01 (s, 1H), 5.48 (bs, 1H), 5.20 (dd, J = 6.8,5.5 Hz, 1H), 4.09 (dd, J = 11.2, 5.5 Hz, 1H), 4.03 (dd, J = 11.2, 6.9 Hz, 1H).13C NMR (101 MHz, DMSO-d6) δ 167.3, 152.4, 152.0, 147.2, 137.4, 137.0, 132.8, 126.9,123.8, 122.9, 122.5, 119.5, 62.3, 61.7. Example 6: (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyrimidin-5-yl)propanamide (3f) 84 M / 64069-PCTEMBL 2020-011 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyrimidin-5-yl)propanamide (3f) was synthesized according to GP-1 as described above. The crude product was treated with triethylamine and purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (9 mg, 0.03 mmol) as a racemic mixture.LC-MS (ESI): m / z = 234.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 9.06 (s, 1H), 8.90 (s, 1H), 7.86 (s, 1H), 7.33 (s, 1H),7.02 (s, 1H), 5.11 (t, J = 6.1 Hz, 1H), 4.17 (dd, J = 11.4, 5.7 Hz, 1H), 4.10 (dd, J = 11.5,6.6 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 154.6, 149.2, 135.6, 128.7, 120.4, 63.8, 63.6. Example 7: Methyl (S)-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinate hydrochloride (3g) Methyl (S)-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinate hydrochloride (3g) was synthesized according to GP-1 as described above. The title compound (67 mg, 0.21 mmol) was isolated as hydrochloride salt.LC-MS (ESI): m / z (free base) = 233.2 [M + H]+.1H NMR (400 MHz, DMSO-d6) δ 14.68 (bs, 1H), 11.61 (s, 1H), 9.28 (t, J = 1.5 Hz, 1H),8.96 (d, J = 2.5 Hz, 1H), 8.27 (dd, J = 8.6, 2.5 Hz, 1H), 8.08 (d, J = 8.6 Hz, 1H), 7.88 (t,J = 1.7 Hz, 1H), 7.72 (t, J = 1.7 Hz, 1H), 5.57 (dd, J = 6.8, 3.7 Hz, 1H), 4.29 (dd, J = 12.0,6.8 Hz, 1H), 4.13 (dd, J = 12.0, 3.8 Hz, 1H), 3.85 (s, 3H).85 M / 64069-PCTEMBL 2020-01113C NMR (101 MHz, DMSO-d6) δ 165.9, 165.1, 142.6, 141.1, 138.6, 126.9, 126.1, 123.1,64.8, 61.6, 52.7. [α]D25= +31.7 ° (c 1, MeOH) Example 8: (S)-N-(1H-Benzo[d]imidazol-2-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide hydrochloride (3h) (S)-N-(1H-Benzo[d]imidazol-2-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamidehydrochloride (3h) was synthesized according to GP-1 as described above. The crudeproduct was treated with triethylamine and purified by reverse phase column chromatography using a linear gradient of water and acetonitrile with 0.1% trifluoroacetic acid. Fractions were collected, treated with 1M HCl and lyophilized to give the title compound (13 mg, 0.04 mmol) as a hydrochloride salt.LC-MS (ESI): m / z (free base)= 272.2 [M + H]+.1H NMR (400 MHz, DMSO-d6) δ 9.28 (t, J = 1.6 Hz, 1H), 7.89 (t, J = 1.7 Hz, 1H), 7.74 (t,J = 1.7 Hz, 1H), 7.56 (dd, J = 6.0, 3.3 Hz, 1H), 7.31 (dd, J = 6.0, 3.2 Hz, 1H), 5.65 – 5.61(m, 1H), 4.38 (dd, J = 12.1, 6.5 Hz, 1H), 4.16 (dd, J = 12.1, 3.4 Hz, 1H).13C NMR (101 MHz, DMSO-d6) δ 171.7, 143.8, 136.3, 123.8, 122.8, 118.8, 113.0, 65.2,61.3. [α]D25= +7.4 ° (c 0.5, MeOH) Example 9: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(naphthalen-2-yl)propanamide (3i) 86 M / 64069-PCTEMBL 2020-011(S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(naphthalen-2-yl)propanamide (3i) wassynthesized according to GP-1 as described above. The crude product was purified bycolumn chromatography using a linear gradient of methanol in dichloromethane (0 to 20%, v / v) to give the title compound (92 mg, 0.33 mmol).LC-MS (ESI): m / z = 282.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.24 (d, J = 2.1 Hz, 1H), 7.87 (t, J = 1.2 Hz, 1H),7.85 – 7.76 (m, 3H), 7.57 (dd, J = 8.8, 2.2 Hz, 1H), 7.46 (ddd, J = 8.2, 6.9, 1.5 Hz, 1H),7.41 (ddd, J = 8.1, 6.8, 1.5 Hz, 1H), 7.35 (t, J = 1.4 Hz, 1H), 7.03 (t, J = 1.3 Hz, 1H), 5.10(dd, J = 7.1, 5.8 Hz, 1H), 4.20 (dd, J = 11.4, 5.9 Hz, 1H), 4.10 (dd, J = 11.4, 7.1 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.1, 138.4, 136.7, 135.1, 132.3, 129.7, 128.8, 128.6, 128.6, 127.6, 126.3, 121.1, 120.3, 118.3, 64.1, 63.6. [α]25D= - 65.0 ° (c 1, MeOH)Example 10: (S)-N-(6,7-Dimethoxyquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3j) (S)-N-(6,7-Dimethoxyquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3j) was synthesized according to GP-1 as described above. The crude product was dissolved in methanol and treated with an acid scavenger. It was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (31 mg, 0.91 mmol).LC-MS (ESI): m / z = 343.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.64 (d, J = 2.4 Hz, 1H), 8.46 (d, J = 2.3 Hz, 1H),8.01 (s, 1H), 7.41 (s, 1H), 7.20 (s, 1H), 7.09 (s, 1H), 7.08 (s, 1H), 5.16 (t, J = 6.2 Hz, 1H),4.22 (dd, J = 11.5, 5.7 Hz, 1H), 4.15 (dd, J = 11.5, 6.8 Hz, 1H), 3.93 (s, 3H), 3.92 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.2, 153.7, 152.0, 142.7, 142.2, 138.4, 132.0, 127.8, 125.6, 125.3, 120.8, 107.3, 106.4, 64.2, 63.6, 56.5, 56.4.[α] 25D = - 3.0 ° (c 1, MeOH)87 M / 64069-PCTEMBL 2020-011Example 11: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(7-methoxyquinolin-3- yl)propanamide (3k) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(7-methoxyquinolin-3-yl)propanamide (3k) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (51mg, 0.16 mmol).LC-MS (ESI): m / z = 313.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.82 (d, J = 2.6 Hz, 1H), 8.59 (s, 1H), 7.89 (s, 1H),7.74 (d, J = 9.0 Hz, 1H), 7.36 (s, 1H), 7.30 (s, 1H), 7.23 (dd, J = 9.0, 2.6 Hz, 1H), 7.04(s, 1H), 5.12 (t, J = 6.3 Hz, 1H), 4.21 (dd, J = 11.5, 5.7 Hz, 1H), 4.12 (dd, J = 11.4, 6.9Hz, 1H), 3.93 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 162.1, 147.6, 145.3, 138.5, 131.7, 130.0, 128.8, 126.9, 124.6, 121.7, 120.4, 107.0, 64.0, 63.7, 56.0. Example 12: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(5-methoxyquinolin-3- yl)propanamide (3l) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(5-methoxyquinolin-3-yl)propanamide (3l) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (29 mg, 0.09 mmol).LC-MS (ESI): m / z = 313.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.88 (s, 2H), 7.91 (s, 1H), 7.53 (dd, J = 8.5, 7.3 Hz,88 M / 64069-PCTEMBL 2020-0111H), 7.49 (d, J = 8.5 Hz, 1H), 7.38 (s, 1H), 7.05 (s, 1H), 6.93 (d, J = 7.3 Hz, 1H), 5.14 (t,J = 6.6 Hz, 1H), 4.21 (dd, J = 11.2, 6.1 Hz, 1H), 4.14 (dd, J = 11.3, 6.9 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.5, 156.4, 146.5, 145.2, 138.5, 132.7, 130.1, 128.8, 121.7, 121.2, 120.8, 120.4, 106.3, 64.0, 63.7, 56.4. [α]25D= - 47.7 ° (c 1, MeOH)Example 13: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(8-methoxyquinolin-3- yl)propanamide (3m) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(8-methoxyquinolin-3-yl)propanamide(3m) was synthesized according to GP-1 as described above. The crude product wasdissolved in DMF and treated with an acid scavenger. It was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (59 mg, 0.19 mmol).LC-MS (ESI): m / z = 313.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.84 (d, J = 2.4 Hz, 1H), 8.69 (d, J = 2.3 Hz, 1H),7.93 (s, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.38 (s, 1H), 7.11 (d, J =7.6 Hz, 1H), 7.05 (s, 1H), 5.15 (t, J = 6.2 Hz, 1H), 4.21 (dd, J = 11.4, 5.7 Hz, 1H), 4.13(dd, J = 11.4, 6.8 Hz, 1H), 4.03 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 156.2, 143.6, 138.5, 137.5, 134.0, 130.8, 129.2, 128.5, 125.9, 120.5, 120.5, 108.4, 64.1, 63.6, 56.3.[α] 25D = - 31.8 ° (c 1, MeOH)Example 14: (S)-N-(7-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3n) 89 M / 64069-PCTEMBL 2020-011 (S)-N-(7-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3n) was synthesized according to GP-1 as described above. The crude product was dissolved in DMF and treated with an acid scavenger. It was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (71 mg, 0.20 mmol).LC-MS (ESI): m / z = 361.0, 363.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.90 (d, J = 2.4 Hz, 1H), 8.74 (d, J = 2.3 Hz, 1H),8.13 (d, J = 1.5 Hz, 1H), 7.93 (s, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.68 (dd, J = 8.7, 2.0 Hz,1H), 7.38 (s, 1H), 7.05 (s, 1H), 5.15 (t, J = 6.2 Hz, 1H), 4.21 (dd, J = 11.4, 5.7 Hz, 1H),4.13 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 146.5, 146.3, 138.5, 133.9, 132.0, 131.3, 130.6, 128.5, 128.3, 125.8, 123.5, 120.5, 64.1, 63.6.[α] 25D = - 35.9 ° (c 1, MeOH)Example 15: (S)-N-(5-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3o) (S)-N-(5-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3o)was synthesized according to GP-1 as described above. The crude product wasdissolved in DMF and treated with an acid scavenger. It was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (37 mg, 0.10 mmol).LC-MS (ESI): m / z = 361.0, 363.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.98 (d, J = 1.9 Hz, 1H), 8.94 (d, J = 2.4 Hz, 1H),90 M / 64069-PCTEMBL 2020-0117.95 – 7.88 (m, 2H), 7.83 (d, J = 6.9 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.39 (s, 1H), 7.05(s, 1H), 5.16 (t, J = 6.3 Hz, 1H), 4.23 (dd, J = 11.4, 5.8 Hz, 1H), 4.15 (dd, J = 11.4, 6.8Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 146.3, 145.9, 138.5, 134.8, 132.4, 130.0, 129.2, 128.8, 128.8, 124.5, 122.3, 120.4, 64.0, 63.6. [α]25D= - 38.3 ° (c 1, MeOH)Example 16: (S)-N-(8-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3p) (S)-N-(8-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3p)was synthesized according to GP-1 as described above. The crude product was purifiedby reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (15 mg, 0.04 mmol).LC-MS (ESI): m / z = 361.0, 363.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.5 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H),7.96 (dd, J = 7.5, 1.1 Hz, 1H), 7.91 (s, 1H), 7.82 (dd, J = 8.2, 0.9 Hz, 1H), 7.41 (t, J = 7.8Hz, 1H), 7.37 (s, 1H), 7.04 (s, 1H), 5.16 (t, J = 6.3 Hz, 1H), 4.22 (dd, J = 11.4, 5.8 Hz,1H), 4.14 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 146.1, 142.8, 138.5, 134.2, 133.4, 131.0, 129.1, 128.7, 125.8, 124.7, 120.5, 64.0, 63.6.[α] 25D = - 36.4 ° (c 0.5, MeOH)Example 17: Methyl (S)-3-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)quinoline- 6-carboxylate (3q) 91 M / 64069-PCTEMBL 2020-011 Methyl-(S)-3-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)quinoline-6-carboxylate (3q) was synthesized according to GP-1 as described above. The crudeproduct was purified by reverse phase column chromatography using a linear gradientof water and methanol to give the title compound (28 mg, 0.08 mmol).LC-MS (ESI): m / z = 341.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.5 Hz, 1H), 8.71 (d, J = 2.3 Hz, 1H),8.41 (d, J = 1.7 Hz, 1H), 8.09 (dd, J = 8.8, 1.8 Hz, 1H), 7.94 (s, 1H), 7.92 (d, J = 8.8 Hz,1H), 7.39 (s, 1H), 7.05 (s, 1H), 5.16 (t, J = 6.2 Hz, 1H), 4.23 (dd, J = 11.5, 5.7 Hz, 1H),4.16 (dd, J = 11.5, 6.8 Hz, 1H), 3.94 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 167.7, 147.5, 147.3, 138.6, 134.1, 131.8, 130.0, 129.4, 128.9, 128.7, 128.7, 126.6, 120.5, 64.0, 63.7, 53.0.[α] 25D = - 52.3 ° (c 1, MeOH)Example 18: (S)-N-(6-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3r) (S)-N-(6-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3r) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (30 mg, 0.08 mmol).LC-MS (ESI): m / z = 361.0, 363.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.5 Hz, 1H), 8.71 (d, J = 2.4 Hz, 1H),8.10 (d, J = 2.1 Hz, 1H), 7.89 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.77 (dd, J = 9.0, 2.2 Hz,1H), 7.36 (s, 1H), 7.03 (s, 1H), 5.14 (t, J = 6.3 Hz, 1H), 4.21 (dd, J = 11.4, 5.8 Hz, 1H),92 M / 64069-PCTEMBL 2020-0114.12 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 145.9, 144.4, 138.5, 134.3, 133.2, 131.0, 131.0, 130.9, 128.8, 124.7, 122.4, 120.4, 64.0, 63.6. [α]25D = - 61.4 ° (c 1, MeOH)Example 19: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methoxyquinolin-3- yl)propanamide (3s) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methoxyquinolin-3-yl)propanamide (3s) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (68 mg, 0.22 mmol).LC-MS (ESI): m / z = 313.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.73 (d, J = 2.4 Hz, 1H), 8.66 (d, J = 2.2 Hz, 1H),7.92 (t, J = 1.0 Hz, 1H), 7.84 (d, J = 9.2 Hz, 1H), 7.37 (t, J = 1.3 Hz, 1H), 7.31 (dd, J =9.2, 2.8 Hz, 1H), 7.23 (d, J = 2.7 Hz, 1H), 7.05 (t, zJ = 1.0 Hz, 1H), 5.14 (dd, J = 6.5, 6.1Hz, 1H), 4.21 (dd, J = 11.4, 5.8 Hz, 1H), 4.13 (dd, J = 11.4, 6.9 Hz, 1H), 3.93 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 160.2, 142.5, 141.9, 138.5, 133.8, 131.1, 130.2, 128.6, 125.2, 122.9, 120.5, 106.3, 64.1, 63.6, 56.1.[α] 25D = - 32.7 ° (c 1, MeOH)Example 20: (S)-N-(6-Chloroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3t) 93 M / 64069-PCTEMBL 2020-011(S)-N-(6-Chloroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3t) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (81 mg, 0.26 mmol).LC-MS (ESI): m / z = 317.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.89 (d, J = 2.5 Hz, 1H), 8.70 (d, J = 2.3 Hz, 1H),7.94 (d, J = 9.0 Hz, 1H), 7.93 (s, 1H), 7.90 (d, J = 2.3 Hz, 1H), 7.63 (dd, J = 9.0, 2.3 Hz,1H), 7.38 (s, 1H), 7.05 (s, 1H), 5.15 (t, J = 6.2 Hz, 1H), 4.21 (dd, J = 11.4, 5.7 Hz, 1H),4.13 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 145.8, 144.2, 138.5, 134.3, 134.3, 130.9, 130.5, 130.4, 128.6, 127.6, 124.8, 120.5, 64.1, 63.6. [α]25D= - 30.4 ° (c 1, MeOH)Example 21: (S)-N-(7-Bromoquinoxalin-2-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3u) (S)-N-(7-Bromoquinoxalin-2-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3u) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (16 mg, 0.04 mmol).LC-MS (ESI): m / z = 362.0, 364.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 9.63 (s, 1H), 8.02 (d, J = 2.1 Hz, 1H), 7.90 (s, 1H),7.88 (d, J = 8.9 Hz, 1H), 7.77 (dd, J = 8.9, 2.2 Hz, 1H), 7.37 (t, J = 1.3 Hz, 1H), 7.03 (s,1H), 5.26 (t, J = 5.8 Hz, 1H), 4.22 (dd, J = 11.5, 5.6 Hz, 1H), 4.16 (dd, J = 11.5, 6.5 Hz,1H).13C NMR (101 MHz, Methanol-d4) δ 169.2, 148.8, 142.9, 141.1, 139.9, 138.7, 133.0, 131.2, 131.2, 128.8, 125.5, 120.5, 63.7, 63.6. Example 22: (S)-N-(6-Cyclopropylquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- 94 M / 64069-PCTEMBL 2020-011yl)propanamide (3w) (S)-N-(6-Cyclopropylquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide(3w) was synthesized according to GP-1 as described above. The crude product waspurified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (80 mg, 0.25 mmol).LC-MS (ESI): m / z = 323.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.78 (d, J = 2.5 Hz, 1H), 8.59 (d, J = 2.3 Hz, 1H),7.89 (s, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 1.8 Hz, 1H), 7.38 (dd, J = 8.6, 2.0 Hz,1H), 7.36 (s, 1H), 7.04 (s, 1H), 5.13 (t, J = 6.3 Hz, 1H), 4.21 (dd, J = 11.4, 5.8 Hz, 1H),4.12 (dd, J = 11.4, 6.8 Hz, 1H), 2.12 – 2.01 (m, 1H), 1.11 – 1.02 (m, 2H), 0.86 – 0.76 (m,2H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 145.3, 144.5, 144.1, 138.5, 133.5, 129.7, 128.8, 128.7, 128.6, 125.6, 124.4, 120.4, 64.0, 63.6, 16.3, 10.2. [α]25D = - 71.8 ° (c 1, MeOH)Example 23: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(pyridin-3-yl)quinolin-3- yl)propanamide (3x) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(pyridin-3-yl)quinolin-3-yl)propanamide(3x) was synthesized according to GP-1 as described above. The crude product waspurified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (9 mg, 0.03 mmol).LC-MS (ESI): m / z = 360.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.94 (d, J = 2.0 Hz, 1H), 8.91 (d, J = 2.5 Hz, 1H),95 M / 64069-PCTEMBL 2020-0118.83 (d, J = 2.3 Hz, 1H), 8.57 (dd, J = 4.8, 1.3 Hz, 1H), 8.23 (ddd, J = 8.0, 1.9, 1.9 Hz,1H), 8.16 (d, J = 1.9 Hz, 1H), 8.08 (d, J = 8.8 Hz, 1H), 8.02 (s, 1H), 7.99 (dd, J = 8.8, 2.0Hz, 1H), 7.57 (dd, J = 7.9, 4.9 Hz, 1H), 7.42 (s, 1H), 7.09 (s, 1H), 5.19 (t, J = 6.2 Hz, 1H),4.23 (dd, J = 11.4, 5.7 Hz, 1H), 4.16 (dd, J = 11.5, 6.7 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 149.3, 148.7, 145.9, 145.5, 138.5, 137.7, 137.6, 136.9, 134.0, 130.0, 129.9, 129.0, 128.1, 127.2, 126.2, 125.6, 120.8, 64.2, 63.6.[α] 25D = - 64.2 ° (c 0.4, MeOH)Example 24: (S)-N-(6-Fluoroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1- yl)propanamide (3y) (S)-N-(6-Fluoroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3y) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (106 mg, 0.35 mmol).LC-MS (ESI): m / z = 301.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.87 (d, J = 2.4 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H),8.01 (dd, J = 9.2, 5.3 Hz, 1H), 7.89 (s, 1H), 7.57 (dd, J = 9.3, 2.8 Hz, 1H), 7.50 (ddd, J =9.1, 8.8, 2.8 Hz, 1H), 7.36 (t, J = 1.2 Hz, 1H), 7.04 (s, 1H), 5.14 (t, J = 6.3 Hz, 1H), 4.21(dd, J = 11.4, 5.8 Hz, 1H), 4.12 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 162.5 (d, J = 247.7 Hz), 144.8, 142.9, 138.5,134.2, 131.8 (d, J = 9.7 Hz), 130.7 (d, J = 10.7 Hz), 128.8, 125.2 (d, J = 5.2 Hz), 119.8(d, J = 26.3 Hz), 111.9 (d, J = 22.6 Hz), 64.0, 63.6.19F NMR (376 MHz, Methanol-d4) δ -114.3.[α] 25D = - 62.9 ° (c 1, MeOH)Example 25: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methylquinolin-3- yl)propanamide (3z) 96 M / 64069-PCTEMBL 2020-011 (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methylquinolin-3-yl)propanamide (3z) was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (111 mg, 0.38 mmol).LC-MS (ESI): m / z = 297.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.81 (d, J = 2.5 Hz, 1H), 8.63 (d, J = 2.3 Hz, 1H),7.89 (s, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.63 (s, 1H), 7.53 (dd, J = 8.6, 1.8 Hz, 1H), 7.36(s, 1H), 7.04 (s, 1H), 5.13 (t, J = 6.3 Hz, 1H), 4.21 (dd, J = 11.4, 5.8 Hz, 1H), 4.12 (dd, J= 11.4, 6.9 Hz, 1H), 2.52 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 144.4, 144.4, 139.1, 138.5, 133.4, 132.3, 129.7, 128.8, 128.6, 127.7, 125.7, 120.4, 64.0, 63.6, 21.6. [α]25D= - 78.9 ° (c 1, MeOH)Example 26: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(trifluoromethyl)quinolin-3- yl)propanamide (3aa) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(trifluoromethyl)quinolin-3-yl)propanamide (3aa) was synthesized according to GP-1 as described above. Thecrude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (44 mg, 0.13 mmol).LC-MS (ESI): m / z = 351.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 9.06 (d, J = 2.5 Hz, 1H), 8.91 (d, J = 2.3 Hz, 1H),8.33 (s, 1H), 8.29 (s, 1H), 8.15 (d, J = 8.8 Hz, 1H), 7.88 (dd, J = 8.8, 1.9 Hz, 1H), 7.53(s, 1H), 7.23 (s, 1H), 5.28 (t, J = 5.8 Hz, 1H), 4.25 – 4.19 (m, 2H).97 M / 64069-PCTEMBL 2020-01113C NMR (101 MHz, Methanol-d4) δ 168.1, 147.8, 146.8, 138.2, 134.6, 130.7, 130.3 (q,J = 32.6 Hz), 128.9, 127.1 (q, J = 4.6 Hz), 126.3, 126.0, 125.5 (q, J = 271.8 Hz), 125.2(q, J = 2.9 Hz), 121.6, 64.7, 63.5.19F NMR (376 MHz, Methanol-d4) δ -64.0.[α]25D= - 36.4 ° (c 0.5, MeOH)Example 27: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3- yl)propanamide (3ab) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3-yl)propanamide(3ab) was synthesized according to GP-1 as described above. The crude product waspurified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (21 mg, 0.06 mmol).LC-MS (ESI): m / z = 375.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.83 (d, J = 2.4 Hz, 1H), 8.51 (d, J = 2.3 Hz, 1H),8.32 (s, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.51 (s, 1H), 7.45 – 7.36 (m, 3H), 7.24 – 7.14 (m,3H), 7.12 – 7.04 (m, 2H), 5.26 (t, J = 5.9 Hz, 1H), 4.24 – 4.15 (m, 2H).13C NMR (101 MHz, Methanol-d4) δ 167.9, 158.1, 157.6, 143.8, 142.5, 138.2, 133.9, 131.2, 131.0, 130.7, 125.9, 125.5, 125.1, 123.3, 121.6, 120.8, 113.4, 64.7, 63.5.[α] 25D = - 37.7 ° (c 0.9, MeOH)Example 28: (S,E)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-styrylquinolin-3- yl)propanamide (3ac) (S,E)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-styrylquinolin-3-yl)propanamide (3ac) 98 M / 64069-PCTEMBL 2020-011was synthesized according to GP-1 as described above. The crude product was purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (51 mg, 0.13 mmol).LC-MS (ESI): m / z = 385.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.81 (d, J = 2.4 Hz, 1H), 8.71 (d, J = 2.2 Hz, 1H),7.98 (dd, J = 8.9, 1.8 Hz, 1H), 7.95 – 7.84 (m, 3H), 7.60 (d, J = 7.5 Hz, 2H), 7.40 – 7.32(m, 4H), 7.33 (s, 1H), 7.27 (t, J = 7.3 Hz, 1H), 7.05 (s, 1H), 5.14 (t, J = 6.3 Hz, 1H), 4.22(dd, J = 11.4, 5.8 Hz, 1H), 4.14 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 145.5, 144.8, 138.5, 138.5, 138.2, 133.8, 131.8, 130.0, 129.8, 129.2, 129.1, 128.8, 128.5, 127.8, 127.8, 127.0, 126.0, 120.4, 64.0, 63.7. [α]25D= - 61.6 ° (c 1, MeOH)Example 29: (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenethylquinolin-3- yl)propanamide (3ad) To a solution of (S,E)-3-hydroxy-2-(1H-imidazol-1-yl)-N-(6-styrylquinolin-3- yl)propanamide (132 mg, 0.30 mmol) in methanol (5 mL) was added 10 wt% palladium on carbon (31 mg, 10 mol%). The solution was purged with argon and three times with hydrogen. The mixture was stirred overnight under hydrogen. It was purged with argon and filtered through a pad of celite. All volatiles were evaporated to give the title compound (116 mg, 0.26 mmol).LC-MS (ESI): m / z = 387.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ δ 8.82 (s, 1H), 8.61 (s, 1H), 7.89 (s, 1H), 7.86 (d, J= 8.6 Hz, 1H), 7.59 – 7.50 (m, 2H), 7.36 (s, 1H), 7.26 – 7.19 (m, 2H), 7.19 – 7.10 (m,3H), 7.04 (s, 1H), 5.13 (t, J = 6.3 Hz, 1H), 4.21 (dd, J = 11.4, 5.8 Hz, 1H), 4.12 (dd, J =11.4, 6.9 Hz, 1H), 3.09 (t, J = 7.2 Hz, 2H), 2.99 (t, J = 7.3 Hz, 2H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 144.7, 144.5, 142.8, 142.6, 138.5, 133.4, 131.7, 129.6, 129.6, 129.3, 128.8, 128.7, 127.6, 127.0, 125.9, 120.4, 64.0, 63.6, 38.9, 99 M / 64069-PCTEMBL 2020-01138.6. Example 30: 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(1-methyl-1H-pyrazol-4- yl)quinolin-3-yl)propanamide (3ae) Step (i): (S)-N-(6-bromoquinolin-3-yl)-3-(tert-butoxy)-2-(1H-imidazol-1-yl)propanamide (200 mg, 0.48 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrazole (150 mg, 0.72 mmol), cesium carbonate (235 mg, 0.72 mmol) was combined under argon atmosphere. Anhydrous dioxane (2 mL) was added and the solution was purged with argon. Pd(dppf)Cl2(17 mg, 10%) was added and the mixture stirred overnight at 85 °C. It was cooled to room temperature and diluted with dichloromethane and water. Phases were separated and aqueous phase was extracted with dichloromethane twice. Combined organic extracts were dried over Na2SO4, filtered,and concentrated under vacuum. The product was purified by column chromatographyusing a linear gradient of methanol in dichloromethane (0 to 20%, v / v) to obtain 3-(tert- butoxy)-2-(1H-imidazol-1-yl)-N-(6-(1-methyl-1H-pyrazol-3-yl)quinolin-3-yl)propanamide (117 mg, 80 wt% purity, 0.22 mmol). Step (ii): To a solution of 3-(tert-butoxy)-2-(1H-imidazol-1-yl)-N-(6-(1-methyl-1H-pyrazol-3-yl)quinolin-3-yl)propanamide (117 mg, 80wt% purity, 0.22 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (2 mL). The mixture was stirred overnight at room temperature. All volatiles were evaporated and quenched with saturated sodium bicarbonate solution. The product was extracted with dichloromethane and purified by reverse phase column chromatography using a linear gradient of waterand methanol to give the title compound (33 mg, 0.09 mmol) as a racemic mixture.LC-MS (ESI): m / z = 363.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.79 (t, J = 2.6 Hz, 1H), 8.72 – 8.66 (m, 1H), 8.10 (d,J = 4.3 Hz, 1H), 7.97 (t, J = 3.4 Hz, 2H), 7.92 (s, 1H), 7.94 – 7.84 (m, 2H), 7.38 (s, 1H),7.05 (s, 1H), 5.15 (t, J = 6.2 Hz, 1H), 4.22 (dd, J = 11.8, 5.4 Hz, 1H), 4.14 (dd, J = 11.4,6.8 Hz, 1H), 3.95 (s, 3H). 100 M / 64069-PCTEMBL 2020-01113C NMR (101 MHz, Methanol-d4) δ 168.7, 144.7, 144.5, 138.5, 137.9, 133.7, 133.3, 130.1, 129.9, 129.4, 128.7, 128.4, 125.8, 123.7, 123.5, 120.5, 64.1, 63.7, 39.1. Example 31: 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(thiophen-3-yl)quinolin-3- yl)propanamide (3af) Step (i): (S)-N-(6-bromoquinolin-3-yl)-3-(tert-butoxy)-2-(1H-imidazol-1- yl)propanamide (120 mg, 0.29 mmol), thiophen-3-ylboronic acid (55 mg, 0.43 mmol), cesium carbonate (141 mg, 0.43 mmol) was combined under argon atmosphere. Anhydrous dioxane (2 mL) was added and the solution was purged with argon. Pd(dppf)Cl2(11 mg, 5%) was added and the mixture stirred overnight at 100 °C. It was cooled to room temperature and diluted with dichloromethane and water. Phases were separated and aqueous phase was extracted with dichloromethane twice. Combined organic extracts were dried over Na2SO4, filtered, and concentrated under vacuum. The product was purified by column chromatography using a linear gradient of methanol in dichloromethane (0 to 20%, v / v) to obtain 3-(tert-butoxy)-2-(1H-imidazol-1-yl)-N-(6- (thiophen-3-yl)quinolin-3-yl)propanamide (101 mg, 0.24 mmol). Step (ii): To a solution of 3-(tert-butoxy)-2-(1H-imidazol-1-yl)-N-(6-(thiophen-3-yl)quinolin-3-yl)propanamide (101 mg, 0.24 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL). The mixture was stirred overnight at room temperature. All volatiles were evaporated and quenched with saturated sodium bicarbonate solution. The product was extracted with dichloromethane-methanol mixture (9:1, v / v) and purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (35 mg, 0.10 mmol) as a racemic mixture.LC-MS (ESI): m / z = 365.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.83 (d, J = 2.4 Hz, 1H), 8.75 (d, J = 2.3 Hz, 1H),8.10 (d, J = 1.7 Hz, 1H), 8.02 (dd, J = 8.8, 1.9 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.91 (s,1H), 7.83 (dd, J = 2.9, 1.3 Hz, 1H), 7.61 (dd, J = 5.0, 1.3 Hz, 1H), 7.54 (dd, J = 5.0, 2.9Hz, 1H), 7.38 (s, 1H), 7.05 (s, 1H), 5.15 (t, J = 6.3 Hz, 1H), 4.22 (dd, J = 11.4, 5.8 Hz,101 M / 64069-PCTEMBL 2020-0111H), 4.14 (dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 145.0, 144.9, 142.3, 138.5, 136.3, 133.8, 130.0, 129.4, 129.1, 128.8, 127.8, 127.2, 126.2, 125.2, 122.9, 120.4, 64.0, 63.7. Example 32: 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenylquinolin-3- yl)propanamide (3ag) Step (i): (S)-N-(6-bromoquinolin-3-yl)-3-(tert-butoxy)-2-(1H-imidazol-1- yl)propanamide (120 mg, 0.29 mmol), phenylboronic acid (53 mg, 0.43 mmol), cesium carbonate (141 mg, 0.43 mmol) was combined under argon atmosphere. Anhydrous dioxane (2 mL) was added and the solution was purged with argon. Pd(dppf)Cl2(11 mg, 5%) was added and the mixture stirred overnight at 100 °C. It was cooled to room temperature and diluted with dichloromethane and water. Phases were separated and aqueous phase was extracted with dichloromethane twice. Combined organic extracts were dried over Na2SO4, filtered, and concentrated under vacuum. The product was purified by column chromatography using a linear gradient of methanol in dichloromethane (0 to 20%, v / v) to obtain 3-(tert-butoxy)-2-(1H-imidazol-1-yl)-N-(6- phenylquinolin-3-yl)propanamide (87 mg, 0.21 mmol). Step (ii): To a solution of 3-(tert-butoxy)-2-(1H-imidazol-1-yl)-N-(6-phenylquinolin-3-yl)propanamide (87 mg, 0.21 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL). The mixture was stirred overnight at room temperature. All volatiles were evaporated and quenched with saturated sodium bicarbonate solution. The product was extracted with dichloromethane-methanol mixture (9:1, v / v) and purified by reverse phase column chromatography using a linear gradient of water and methanol to give the title compound (58 mg, 0.16 mmol) as a racemic mixture.LC-MS (ESI): m / z = 359.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.89 (d, J = 2.4 Hz, 1H), 8.80 (d, J = 2.3 Hz, 1H),8.09 (d, J = 1.7 Hz, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.98 (dd, J = 8.8, 1.9 Hz, 1H), 7.91 (s,1H), 7.76 (d, J = 7.3 Hz, 2H), 7.50 (t, J = 7.6 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H), 7.38 (s,102 M / 64069-PCTEMBL 2020-0111H), 7.05 (s, 1H), 5.15 (t, J = 6.3 Hz, 1H), 4.22 (dd, J = 11.4, 5.8 Hz, 1H), 4.14 (dd, J =11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.7, 145.3, 145.2, 141.7, 141.2, 138.5, 133.8, 130.1, 129.9, 129.6, 129.5, 129.0, 128.8, 128.4, 126.4, 126.3, 120.4, 64.0, 63.7. Reaction Scheme for the Substituted Imidazoles 7 Example 33: 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(quinolin-3- yl)propanamide (7a) Step (i): 2-Bromo-3-methoxy-N-(quinolin-3-yl)propanamide (4a). To a solution of 3-aminoquinoline (827 mg, 5.74 mmol), 2-bromo-3-methoxypropanoic acid (700 mg, 3.83 mmol), and triethylamine (1.6 mL, 11.5 mmol) in DMF (25 mL) were added 50 wt% propylphosphonic anhydride solution (4.87 g, 7.65 mmol). The mixture was stirred overnight at room temperature. All volatiles were removed under vacuum and the residue was dissolved in ethyl acetate again. The solution was washed with saturated sodium bicarbonate solution. Organic phase was dried over sodium sulfate, filtered, and concentrated under vacuum. The product was purified by column chromatography usinga linear gradient of ethyl acetate and cyclohexane to give compound 4a (1.02 g, 3.31mmol). Step (ii): 3-Methoxy-2-(5-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (6a). A microwave vessel was charged with compound 4a (500 mg, 1.62 mmol), 4-methyl-1-trityl-1H-imidazole (787 mg, 2.43 mmol), and potassium iodide (402 mg, 2.43 mmol). Anhydrous acetonitrile (10 mL) was added under argon atmosphere 103 M / 64069-PCTEMBL 2020-011and vial was sealed. The reaction mixture was heated for 1h at 120 °C with microwave irradiation. The vial was opened and methanol (5 mL) was added and it was resealed again. The mixture further stirred for 1 h at 80 °C with microwave irradiation. The vial opened and the mixture transferred into a flask. All volatiles were evaporated under vacuum. The crude product was purified by column chromatography using a linear gradient of methanol in dichloromethane (0 to 20%, v / v). Two regioisomers were not separated. Therefore, a reverse phase column chromatography was performed using alinear gradient of water and methanol to obtain product 6a (46 mg, 0.148 mmol).Step (iii): 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7a).To a solution of compound 6a (46 mg, 0.148 mmol) were added 1M boron tribromide indichloromethane (1.48 mL, 1.48 mmol) in anhydrous dichloromethane (10 mL) at -78 °C. After stirring for 2 h at this temperature, the cooling bath was removed and the mixture was warmed up to room temperature. It was further stirred for 1h and cooled to 0 °C before quenching with a saturated sodium bicarbonate. The crude product was extracted three times with 10 % methanol in dichloromethane. Combined organic extracts were dried over sodium sulfate, filtered and concentrated under vacuum. The residue waspurified by reverse phase column chromatography using a linear gradient of water andmethanol to obtain the title compound (28 mg, 0.095 mmol).LC-MS (ESI): m / z = 297.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.4 Hz, 1H), 8.77 (d, J = 2.4 Hz, 1H),7.99 (dd, J = 8.7, 0.9 Hz, 1H), 7.94 (d, J = 1.2 Hz, 1H), 7.90 (dd, J = 8.1, 1.7 Hz, 1H),7.70 (ddd, J = 8.6, 6.9, 1.5 Hz, 1H), 7.61 (ddd, J = 8.2, 6.9, 1.3 Hz, 1H), 6.75 (s, 1H),5.04 (t, J = 6.3 Hz, 1H), 4.24 (dd, J = 11.5, 5.9 Hz, 1H), 4.14 (dd, J = 11.5, 6.7 Hz, 1H),2.30 (d, J = 1.1 Hz, 3H).13C NMR (101 MHz, Methanol-d4) δ 169.0, 145.9, 145.4, 133.4, 130.0, 129.7, 129.0,128.9, 128.7, 126.2, 126.1, 63.6, 61.7, 9.4. Example 34: 2-(5-Ethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7b) 104 M / 64069-PCTEMBL 2020-011 The title compound (13 mg, 0.042 mmol) was synthesized similar to compound 7a.4-Ethyl-1-trityl-1H-imidazole was used instead of 4-methyl-1-trityl-1H-imidazole and potassium iodide was replaced by sodium iodide in step (ii).LC-MS (ESI): m / z = 311.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.5 Hz, 1H), 8.74 (d, J = 2.3 Hz, 1H),7.98 (dd, J = 8.4, 1.2 Hz, 1H), 7.98 (d, J = 1.0 Hz, 1H), 7.88 (dd, J = 8.2, 1.4 Hz, 1H),7.69 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.59 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 6.77 (q, J = 1.1Hz, 1H), 5.04 (t, J = 6.2 Hz, 1H), 4.25 (dd, J = 11.4, 5.9 Hz, 1H), 4.15 (dd, J = 11.4, 6.6Hz, 1H), 2.71 – 2.62 (m, 2H), 1.30 (t, J = 7.5 Hz, 3H).13C NMR (101 MHz, Methanol-d4) δ 169.0, 145.8, 145.4, 137.6, 135.3, 133.4, 130.0, 129.6, 129.0, 128.9, 128.7, 126.2, 124.6, 63.7, 61.6, 18.3, 13.0. Example 35: 3-Hydroxy-2-(5-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3- yl)propanamide (7c) The title compound (4 mg, 0.013 mmol) was synthesized similar to compound 7a. 4-Isopropyl-1-trityl-1H-imidazole was used instead of 4-methyl-1-trityl-1H-imidazole, potassium iodide was replaced by sodium iodide, and the reaction time was increased to 5 h at 120 °C in step (ii).LC-MS (ESI): m / z = 325.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.4 Hz, 1H), 8.75 (d, J = 2.2 Hz, 1H),8.08 (s, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.70 (ddd, J = 8.0, 7.2,105 M / 64069-PCTEMBL 2020-0111.2 Hz, 1H), 7.60 (dd, J = 7.3, 7.3 Hz, 1H), 6.83 (s, 1H), 5.14 (t, J = 6.1 Hz, 1H), 4.25(dd, J = 11.4, 5.8 Hz, 1H), 4.18 (dd, J = 11.4, 6.6 Hz, 1H), 3.02 (p, J = 6.8 Hz, 1H), 1.34(d, J = 6.8 Hz, 3H), 1.28 (d, J = 6.8 Hz, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.9, 145.9, 145.3, 140.1, 137.8, 133.4, 130.1, 129.7, 129.0, 129.0, 128.8, 126.2, 122.7, 64.0, 61.6, 25.2, 23.2, 22.9. Example 36: 3-Hydroxy-2-(4-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3- yl)propanamide (7d) The title compound (5 mg, 0.015 mmol) was obtained during the synthesis of 7c.LC-MS (ESI): m / z = 325.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.3 Hz, 1H), 8.75 (d, J = 2.0 Hz, 1H),7.98 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.82 (s, 1H), 7.69 (ddd, J = 8.3, 7.2,1.0 Hz, 1H), 7.60 (dd, J = 7.4, 7.4 Hz, 1H), 7.06 (s, 1H), 5.05 (t, J = 6.3 Hz, 1H), 4.20(dd, J = 11.3, 5.9 Hz, 1H), 4.10 (dd, J = 11.3, 6.8 Hz, 1H), 2.87 (p, J = 6.8 Hz, 1H), 1.25(d, J = 6.9 Hz, 6H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 149.3, 145.9, 145.4, 137.7, 133.4, 130.0, 129.7, 129.0, 128.9, 128.7, 126.2, 114.7, 64.0, 63.6, 28.8, 22.8, 22.7. Example 37: 2-(5-Cyclopropyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3- yl)propanamide (7e) 106 M / 64069-PCTEMBL 2020-011The title compound (25 mg, 0.078 mmol) was synthesized similar to compound 7a. 4-Cyclopropyl-1-trityl-1H-imidazole was used instead of 4-methyl-1-trityl-1H- imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 4 h at 125 °C instead of 1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 323.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.4 Hz, 1H), 8.74 (d, J = 2.2 Hz, 1H),7.98 (d, J = 8.0 Hz, 1H), 7.96 (s, 1H), 7.86 (d, J = 8.2 Hz, 1H), 7.69 (ddd, J = 8.1, 6.7,0.9 Hz, 1H), 7.58 (dd, J = 7.5, 7.5 Hz, 1H), 6.68 (s, 1H), 5.35 (t, J = 6.2 Hz, 1H), 4.28(dd, J = 11.5, 5.8 Hz, 1H), 4.23 (dd, J = 11.5, 6.5 Hz, 1H), 1.78 – 1.68 (m, 1H), 1.01 –0.86 (m, 2H), 0.72 – 0.63 (m, 1H), 0.62 – 0.54 (m, 1H).13C NMR (101 MHz, Methanol-d4) δ 169.2, 145.8, 145.4, 137.9, 136.0, 133.5, 130.0, 129.6, 129.0, 128.9, 128.7, 126.2, 125.0, 63.5, 62.0, 6.3, 6.2, 5.2. Example 38: 2-(5-(Cyanomethyl)-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3- yl)propanamide (7f) The title compound (1.4 mg, 0.004 mmol) was synthesized similar to compound 7a. 2-(1-Trityl-1H-imidazol-4-yl)acetonitrile was used instead of 4-methyl-1-trityl-1H- imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 2 h instead of 1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 322.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.92 (d, J = 2.4 Hz, 1H), 8.75 (d, J = 2.1 Hz, 1H),8.11 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.70 (ddd, J = 8.3, 6.9,1.3 Hz, 1H), 7.60 (ddd, J = 8.1, 7.0, 0.9 Hz, 1H), 7.03 (s, 1H), 5.13 (t, J = 5.9 Hz, 1H),4.27 – 4.23 (m, 2H), 4.12 – 4.04 (m, 2H).13C NMR (101 MHz, Methanol-d4) δ 168.1, 145.9, 145.5, 140.0, 133.4, 130.1, 129.7, 129.0, 128.9, 128.7, 128.0, 126.4, 63.7, 62.1, 17.3. 107 M / 64069-PCTEMBL 2020-011Example 39: Methyl 2-(1-(3-hydroxy-1-oxo-1-(quinolin-3-ylamino)propan-2-yl)-1H- imidazol-5-yl)acetate (7g) The title compound (21 mg, 0.059 mmol) was synthesized similar to compound 7a. Methyl 2-(1-trityl-1H-imidazol-4-yl)acetate was used instead of 4-methyl-1-trityl-1H- imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 4 h at 125 °C instead of 1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 355.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.5 Hz, 1H), 8.75 (d, J = 2.3 Hz, 1H),8.10 (d, J = 0.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.70 (ddd, J =8.4, 6.9, 1.4 Hz, 1H), 7.60 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 6.94 (s, 1H), 5.12 (t, J = 6.0Hz, 1H), 4.25 (dd, J = 11.4, 5.7 Hz, 1H), 4.20 (dd, J = 11.4, 6.3 Hz, 1H), 3.88 (d, J = 2.5Hz, 2H), 3.68 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 170.8, 167.4, 144.4, 143.9, 137.6, 132.1, 128.6, 128.2, 127.6, 127.5, 127.3, 126.5, 125.1, 124.6, 62.5, 60.5, 51.5, 28.8. Example 40: 3-Hydroxy-2-(5-(2-hydroxyethyl)-1H-imidazol-1-yl)-N-(quinolin-3- yl)propanamide (7h) The title compound (21 mg, 0.059 mmol) was synthesized similar to compound 7a.1-Trityl-4-(2-(trityloxy)ethyl)-1H-imidazole was used instead of 4-methyl-1-trityl-1H- 108 M / 64069-PCTEMBL 2020-011imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 4 h at 125 °C instead of 1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 327.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.5 Hz, 1H), 8.75 (d, J = 2.4 Hz, 1H),7.99 (d, J = 7.9 Hz, 1H), 7.98 (s, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.70 (ddd, J = 8.4, 6.9,1.4 Hz, 1H), 7.60 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H), 6.85 (s, 1H), 5.18 (t, J = 6.2 Hz, 1H),4.24 (dd, J = 11.4, 5.8 Hz, 1H), 4.16 (dd, J = 11.4, 6.7 Hz, 1H), 3.90 – 3.73 (m, 2H), 2.90(t, J = 6.4 Hz, 2H).13C NMR (101 MHz, Methanol-d4) δ 169.1, 145.8, 145.4, 137.7, 133.5, 131.5, 130.0, 129.7, 129.0, 128.9, 128.7, 126.2, 126.1, 63.8, 62.4, 61.6, 28.0. Example 41: N-(6-Chloroquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3- hydroxypropanamide (7i) The title compound (27 mg, 0.078 mmol) was synthesized similar to compound 7a.6-Chloroquinolin-3-amine was used instead of quinolin-3-amine in step Step (i):.4- ethyl-1-trityl-1H-imidazole was used instead of 4-methyl-1-trityl-1H-imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 4 h at 125 °C instead of 1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 345.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.88 (d, J = 2.5 Hz, 1H), 8.68 (d, J = 2.2 Hz, 1H),7.99 (s, 1H), 7.91 (d, J = 9.0 Hz, 1H), 7.86 (d, J = 2.1 Hz, 1H), 7.61 (dd, J = 9.0, 2.3 Hz,1H), 6.77 (d, J = 1.0 Hz, 1H), 5.04 (t, J = 6.2 Hz, 1H), 4.24 (dd, J = 11.4, 5.9 Hz, 1H),4.15 (dd, J = 11.4, 6.6 Hz, 1H), 2.71 – 2.61 (m, 3H), 1.30 (t, J = 7.5 Hz, 3H).13C NMR (101 MHz, Methanol-d4) δ 169.1, 145.8, 144.2, 137.7, 135.3, 134.4, 134.3, 130.9, 130.5, 130.4, 127.6, 124.8, 124.5, 63.7, 61.6, 18.3, 12.9. Example 42: N-(6-Bromoquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3- 109 M / 64069-PCTEMBL 2020-011hydroxypropanamide (7j) The title compound (13 mg, 0.033 mmol) was synthesized similar to compound 7a.6-Bromoquinolin-3-amine was used instead of quinolin-3-amine in step (i).4-ethyl-1- trityl-1H-imidazole was used instead of 4-methyl-1-trityl-1H-imidazole, potassium iodide was replaced by sodium iodide, and the reaction was stirred for 4 h at 125 °C instead of1 h at 120 °C in step (ii).LC-MS (ESI): m / z = 389.0, 391.0 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.90 (d, J = 2.5 Hz, 1H), 8.68 (d, J = 2.3 Hz, 1H),8.05 (d, J = 2.1 Hz, 1H), 8.00 (s, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.74 (dd, J = 9.0, 2.1 Hz,1H), 6.77 (s, 1H), 5.05 (t, J = 6.2 Hz, 1H), 4.24 (dd, J = 11.4, 5.9 Hz, 1H), 4.15 (dd, J =11.4, 6.6 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 169.0, 145.9, 144.4, 137.7, 135.3, 134.2, 133.1,131.0, 130.9, 130.9, 124.7, 124.5, 122.4, 63.7, 61.6, 18.3, 12.9.Example 43: 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3- yl)propanamide (7k) The title compound (23 mg, 0.057 mmol) was synthesized similar to compound 7a. 6-Phenoxyquinolin-3-amine instead of quinolin-3-amine and pyridine instead of triethylamine were used in step (i).4-ethyl-1-trityl-1H-imidazole was used instead of 4- methyl-1-trityl-1H-imidazole, potassium iodide was replaced by sodium iodide, and thereaction was stirred for 4 h at 125 °C instead of 1 h at 120 °C in step (ii).110 M / 64069-PCTEMBL 2020-011LC-MS (ESI): m / z = 403.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.81 (d, J = 2.4 Hz, 1H), 8.54 (d, J = 2.3 Hz, 1H),8.09 (s, 1H), 7.94 (d, J = 9.2 Hz, 1H), 7.45 – 7.36 (m, 3H), 7.24 – 7.15 (m, 2H), 7.11 –7.05 (m, 2H), 6.84 – 6.78 (m, 1H), 5.06 (t, J = 6.1 Hz, 1H), 4.27 – 4.09 (m, 2H), 2.74 –2.58 (m, 2H), 1.29 (t, J = 7.5 Hz, 3H).13C NMR (101 MHz, Methanol-d4) δ 167.3, 156.7, 156.2, 142.4, 141.1, 136.2, 134.2, 132.5, 129.8, 129.6, 129.3, 124.1, 123.7, 122.3, 121.9, 119.4, 112.1, 62.3, 60.3, 16.9, 11.4. Reaction Scheme for the Imidazoles 9 Example 44: N-Benzyl-5-(3-hydroxy-2-(1H-imidazol-1- yl)propanamido)picolinamide (9a) Step (i): N-Benzyl-5-(3-(tert-butoxy)-2-(1H-imidazol-1- yl)propanamido)picolinamide (8a). To a solution of methyl (S)-5-(3-(tert-butoxy)-2-(1H- imidazol-1-yl)propanamido)picolinate (256 mg, 0.74 mmol, synthesized for compound 3g) in tetrahydrofuran (20 mL) was added lithium hydroxide powder (18 mg, 0.74 mmol).The mixture was stirred overnight at room temperature. All volatiles were evaporated.The residue was dissolved in ethyl acetate (5 mL) then benzylamine (95 mg, 0.89 mmol) and pyridine (0.60 mL, 7.4 mmol) were added to the solution. The reaction was stirred overnight at room temperature after the addition of propylphosphonic anhydride (T3P) solution in ethyl acetate (0.941 g, 1.48 mmol). It was quenched with 0.5M HCl and the 111 M / 64069-PCTEMBL 2020-011solution was neutralized with a saturated sodium bicarbonate solution. The crude product was extracted three times with dichloromethane. Combined organic extracts were dried over sodium sulfate, filtered, and concentrated under vacuum. The product was purified by column chromatography using a linear gradient of methanol in dichloromethane (0 to20%, v / v) to obtain intermediate 8a (174 mg, 0.41 mmol).Step (ii): N-Benzyl-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinamide(9a). To a solution of intermediate 8a (174 mg, 0.41 mmol) in dichloromethane (6 mL)was added trifluoroacetic acid (2 mL). The mixture was stirred overnight at room temperature. All volatiles were evaporated under vacuum and excess acid was quenched with saturated sodium bicarbonate solution. The product was extracted three times with 10% methanol solution in dichloromethane. Combined organic extracts were dried over sodium sulfate, filtered, and concentrated under vacuum. The product was purified by reverse phase column chromatography using a linear gradient of water in methanol to obtain the title compound (114 mg, 0.31 mmol).LC-MS (ESI): m / z = 366.3 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.83 (s, 1H), 8.20 (ddd, J = 8.4, 2.4, 2.4 Hz, 1H),8.06 (dd, J = 8.5, 1.2 Hz, 1H), 7.85 (s, 1H), 7.35 – 7.26 (m, 5H), 7.25 – 7.19 (m, 1H),7.01 (s, 1H), 5.09 (t, J = 6.3 Hz, 1H), 4.58 (s, 2H), 4.17 (dd, J = 11.4, 5.8 Hz, 1H), 4.08(dd, J = 11.4, 6.8 Hz, 1H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 166.3, 146.5, 141.3, 140.0, 138.9, 138.5, 129.5, 128.8, 128.6, 128.5, 128.2, 123.6, 120.4, 63.9, 63.6, 44.0. Example 45: 5-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N- phenethylpicolinamide (9b) The title compound (134 mg, 0.35 mmol) was synthesized similar to compound 9a. Phenethylamine was used instead of benzylamine in step (i).LC-MS (ESI): m / z = 380.2 [M + H]+.112 M / 64069-PCTEMBL 2020-0111H NMR (400 MHz, Methanol-d4) δ 8.82 (d, J = 2.1 Hz, 1H), 8.20 (dd, J = 8.6, 2.5 Hz,1H), 8.04 (d, J = 8.6 Hz, 1H), 7.85 (s, 1H), 7.32 (t, J = 1.1 Hz, 1H), 7.30 – 7.23 (m, 4H),7.22 – 7.16 (m, 1H), 7.02 (s, 1H), 4.17 (dd, J = 11.4, 5.8 Hz, 1H), 4.08 (dd, J = 11.4, 6.8Hz, 1H), 3.63 (t, J = 7.5 Hz, 2H), 2.91 (t, J = 7.4 Hz, 2H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 166.2, 146.5, 141.3, 140.4, 138.9, 138.5, 129.8, 129.5, 128.8, 128.6, 127.4, 123.4, 120.4, 64.0, 63.6, 42.1, 36.7. Example 46: 5-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N-(3- phenylpropyl)picolinamide (9c) The title compound (125 mg, 0.32 mmol) was synthesized similar to compound9a.3-Phenylpropan-1-amine was used instead of benzylamine in step (i).LC-MS (ESI): m / z = 394.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.84 (d, J = 2.1 Hz, 1H), 8.20 (dd, J = 8.6, 2.5 Hz,1H), 8.04 (d, J = 8.5 Hz, 1H), 7.85 (s, 1H), 7.32 (s, 1H), 7.27 – 7.17 (m, 4H), 7.17 – 7.10(m, 1H), 7.02 (s, 1H), 5.09 (t, J = 6.3 Hz, 1H), 4.17 (dd, J = 11.4, 5.8 Hz, 1H), 4.08 (dd,J = 11.4, 6.8 Hz, 1H), 3.42 (t, J = 7.1 Hz, 2H), 2.68 (t, J = 7.2 Hz, 2H), 1.92 (dt, J = 7.5,7.5 Hz, 2H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 166.3, 146.6, 143.0, 141.3, 138.8, 138.5, 129.4, 128.8, 128.6, 126.9, 123.4, 120.4, 63.9, 63.6, 40.2, 34.3, 32.5. Example 47: 5-(3-Hydroxy-2-(1H-imidazol-1-yl)propanamido)-N-(4- phenylbutyl)picolinamide (9d) 113 M / 64069-PCTEMBL 2020-011 The title compound (112 mg, 0.28 mmol) was synthesized similar to compound 9a.3-Phenylpropan-1-amine was used instead of benzylamine in step (i).LC-MS (ESI): m / z = 408.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.84 (d, J = 2.4 Hz, 1H), 8.20 (dd, J = 8.6, 2.5 Hz,1H), 8.03 (d, J = 8.6 Hz, 1H), 7.85 (s, 1H), 7.32 (t, J = 1.2 Hz, 1H), 7.26 – 7.19 (m, 2H),7.19 – 7.09 (m, 3H), 7.02 (s, 1H), 5.09 (t, J = 6.3 Hz, 1H), 4.17 (dd, J = 11.4, 5.8 Hz, 1H),4.08 (dd, J = 11.4, 6.8 Hz, 1H), 3.42 (t, J = 6.6 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 1.73 –1.58 (m, 4H).13C NMR (101 MHz, Methanol-d4) δ 168.6, 166.3, 146.6, 143.5, 141.3, 138.8, 138.5, 129.4, 129.3, 128.8, 128.6, 126.7, 123.4, 120.4, 63.9, 63.6, 40.2, 36.5, 30.2, 30.0. Reaction scheme for imidazole 12 Example 48: (S)-3-Hydroxy-2-(2-methyl-1H-imidazol-1-yl)-N-(quinolin-3- yl)propanamide (12) Step (i): (S)-3-(tert-Butoxy)-2-(2-methyl-1H-imidazol-1-yl)propanoic acid (10). Toa solution of acetaldehyde (164 mg, 3.72 mmol) in methanol (0.3 mL) were added a mixture of a solution of (L)-Ser(tBu)OH (500 mg, 3.1 mmol) in methanol (0.5 mL) and 10 wt% NaOH solution (1.24 g, 3.1 mmol) at 0 °C. In a separate vial, 40 wt% glyoxal solution 114 M / 64069-PCTEMBL 2020-011in water (540 mg, 3.72 mmol) was mixed with ammonium bicarbonate (245 mg, 3.1 mmol) and methanol (0.5 mL). It was then added to the reaction mixture at 0 °C. The final mixture was stirred for 8 h at room temperature. It was filtered with a syringe filterand 1M HCl solution was added to the filtrate until pH reaches to 6. All volatiles wereevaporated under vacuum. The product was purified by reverse phase column chromatography using a linear gradient of water in methanol to obtain intermediate 10 (134 mg, 90 wt% purity, 0.53 mmol). Step (ii): (S)-3-(tert-butoxy)-2-(2-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (11). Intermediate 10 (130 mg, 90 wt% purity, 0.52 mmol), 3-aminoquinoline (100 mg, 0.69 mmol), and pyridine (454 mg, 5.75 mmol) were dissolved in ethyl acetate (10 mL). The solution was cooled to 0 °C and propylphosphonic anhydride (T3P) solution in ethyl acetate (1.46 g, 2.30 mmol) was added dropwise. The reaction was stirred overnight at room temperature. It was quenched with 0.5M HCl and the solution was neutralized with a saturated sodium bicarbonate solution. The crude product was extracted three times with dichloromethane. Combined organic extracts were dried over sodium sulfate, filtered, and concentrated under vacuum. The product was purified by column chromatography using a linear gradient of methanol indichloromethane (0 to 20%, v / v) to obtain intermediate 11 (92 mg, 0.26 mmol).Step (iii): (S)-3-Hydroxy-2-(2-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (12). To a solution of intermediate 11 (92 mg, 0.26 mmol) indichloromethane (2 mL) was added trifluoroacetic acid (2 mL). The mixture was stirred for 3 h at room temperature. All volatiles were evaporated under vacuum and excess acid was quenched with saturated sodium bicarbonate solution. The product wasextracted three times with 10% methanol solution in dichloromethane. Combined organicextracts were dried over sodium sulfate, filtered, and concentrated under vacuum. The product was purified by reverse phase column chromatography using a linear gradient of water in methanol to obtain the title compound (41 mg, 0.14 mmol).LC-MS (ESI): m / z = 297.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.4 Hz, 1H), 8.74 (d, J = 2.6 Hz, 1H),7.97 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.2 Hz, 1H), 7.69 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H),7.59 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.36 (s, 1H), 6.89 (s, 1H), 5.09 (dd, J = 7.2, 5.9 Hz,1H), 4.22 (dd, J = 11.4, 5.9 Hz, 1H), 4.06 (dd, J = 11.4, 7.2 Hz, 1H), 2.48 (s, 3H).13C NMR (101 MHz, Methanol-d4) δ 168.8, 145.9, 145.5, 133.4, 130.0, 129.6, 129.0, 128.9, 128.7, 127.0, 126.3, 119.3, 63.6, 62.4, 49.9, 49.6, 49.4, 49.2, 49.0, 48.8, 48.6, 115 M / 64069-PCTEMBL 2020-01148.4, 12.9.[α] = - 91.6 ° (c 1, MeOH)Reaction scheme for Triazole 14 Example 49: (S)-3-Hydroxy-2-(5-methyl-1H-1,2,3-triazol-1-yl)-N-(quinolin-3- yl)propanamide (14) Step (i): 3-(tert-Butoxy)-N-(quinolin-3-yl)-2-(1H-1,2,3-triazol-1-yl)propanamide (13). To a solution of intermediate 1 (as described in step (i) for imidazole 3a) (100 mg, 0.35 mmol), 4-azidonitrobenzene (80 mg, 0.49 mmol), and acetone (26µL, 0.35 mmol) in DMF (0.5 mL) were added scandium triflate (171 mg, 0.35 mmol). The mixture wasstirred for 24 h at 40 °C. It was quenched with a saturated sodium bicarbonate solutionand the product was extracted three times with dichloromethane. Combined organic extracts were dried over sodium sulfate, filtered, and concentrated under vacuum.Further purification was done by column chromatography using a linear gradient ofmethanol in dichloromethane (0 to 20%) and did not work efficiently. It was then purified by reverse phase column chromatography using a linear gradient of water in methanol to obtain the intermediate 13 (3 mg, 0.008 mmol). Step (ii): 3-Hydroxy-2-(5-methyl-1H-1,2,3-triazol-1-yl)-N-(quinolin-3-yl)propanamide (14). Intermediate 13 (3.0 mg, 8.0 µmol) was treated with a mixture oftrifluoroacetic acid in DCM (2:1, 3.0 ml) at room temperature overnight. After completion of the reaction (monitored by UPLC) all volatiles were removed under reduced pressure. 116 M / 64069-PCTEMBL 2020-011The crude product was purified by revers phase column chromatography using a linear gradient of water and methanol to obtain 0.8 mg (3.0 µmol, 32%) of the analytically pure title compound.LC-MS (ESI): m / z = 298.2 [M + H]+.1H NMR (400 MHz, Methanol-d4) δ 8.91 (d, J = 2.5 Hz, 1H), 8.73 (d, J = 2.5 Hz, 1H),7.99 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.71 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H),7.61 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H), 7.58 (s, 1H), 5.45 (dd, J = 7.6, 6.0 Hz, 1H), 4.49 (dd,J = 11.5, 5.9 Hz, 1H), 4.39 (dd, J = 11.6, 7.6 Hz, 1H), 2.45 (s, 3H).E. Structural analysis of mode of action and protein-compound interactions. Structural analysis of binary ABA receptor-compound and ternary ABA receptor- compound-phosphatase complexes was carried by X-ray crystallography to determine the mode of action and the details of the protein-ligand interactions according to protocols described in doi:10.3791 / 62491 (Cornaciu et. al. The Automated Crystallography Pipelines at the EMBL HTX Facility in Grenoble. J Vis Exp. 2021 Jun 5;(172) PMID: 34152315,), 10.1038 / emboj.2011.294. (Florine Dupeux , Julia Santiago, Katja Betz, Jamie Twycross, Sang-Youl Park, Lesia Rodriguez, Miguel Gonzalez- Guzman, Malene Ringkjøbing Jensen, Natalio Krasnogor, Martin Blackledge, Michael Holdsworth, Sean R Cutler, Pedro L Rodriguez, José Antonio Márquez, Athermodynamic switch modulates abscisic acid receptor sensitivity. EMBO J. 2011 Aug16;30(20):4171-84), https: / / doi.org / 10.1016 / j.molp.2017.07.004 (Moreno- Alvero et. al.Structure of Ligand-Bound Intermediates of Crop ABA Receptors Highlights PP2C as Necessary ABA Co-receptor. Molecular Plant 10, 1250–1253) and DOI:10.1126 / sciadv.ade9948 (Jorge Lozano-Juste et al., Sci Adv. 2023 Mar 10;9(10).Structural analysis of binary complexes was carried out with tomato SIPYL1 receptor and selected compounds (binary complexes) using the crystal soaking approach as indicated described in doi:10.3791 / 62491. Briefly, crystallization experiments were carried out at the High Throughput Crystallization Laboratory (HTX Lab) at EMBL Grenoble using automated protocols (Cornaciu et al., 2021; Dimasi et al., 2007; Dupeux et al., 2011; Mariaule et al., 2014). The crystallization experiments were carried out using the sitting-drop vapor-diffusion method with a crystallization robot (Mosquito, SPTLabtech). A total of 0.2 µL of protein solution and 0.2 µL of reservoir were mixed to equilibrate against 45 µL reservoir solution at 20 °C in 96-well CrystalDirect 117 M / 64069-PCTEMBL 2020-011plates (MiTeGen) and automatically imaged in RockImager robot (Formulatrix). Optimalcrystals grew in crystallization drops with precipitant condition composed of 1.8 M ammonium sulfate, 0.1 M TRIS pH 7.0 and 5% (v / v) glycerol. Crystals acquired maximal size after 1-2 weeks. At this point compounds were delivered to the crystals through the soaking method using the same protocol for all the compounds.50 nanolitres of stock compound solution in DMSO at 100 mM concentration were added to the crystallization drops containing crystals using a Mosquito robot (SPTLabtech) and incubated for 2 hours at room temperature. After this, automated high-throughput crystal cryo-cooling and harvesting was performed with CrystalDirect Technology (Cipriani et al., 2012; Márquez and Cipriani, 2014; Zander et al., 2016). Structural analysis of ternary complexes was carried out with Citrus sinensisPYL1 (CsPYL1) receptor, A. thaliana ΔN HAB1 phosphatase and the correspondingcompounds using the co-crystallization approach. Protein purification and crystallization and structural analysis were carried out as indicated above. The crystallization protocol for CsPYL1:HAB1 in complex with any ligand was identical. Crystals were obtained using the microbatch under-oil method, with protein concentrations of 3 mg / ml for CsPYL1 and5 mg / ml for ΔN-HAB1. Both proteins were mixed in a 1:1 volume ratio, and thecorresponding ligand was added to the mixture at a final concentration of 0.5-1 mM. The precipitant conditions consisted on a 16-solution screening with 0.5 M CaCl2 combined with varying pH (0.1 M Bis-Tris pH 6.0-7.5) and PEG 3350 (25% to 40%). These solutions were mixed with the CsPYL1:HAB1:ligand mixture in a protein:precipitant ratio of 1:1 and 1:2. Crystals of the ternary complex grew 2-3 days after the experiment set up. Crystals were cryoprotected in the crystallization solution using 10-20% PEG 400, mounted on a fiber loop and flash-frozen in liquid nitrogen. The collected diffraction images dataset was processed with XDS (Kabsch, 2010) and merged with AIMLESS from the CCP4 package (Collaborative Computational Project, Number 4, 1994) (Winn et al., 2011). The crystal structure of the ternary complex CsPYL1:HAB1:ABA (PDB code 5MN0) (Moreno-Alvero et al., 2017) (https: / / doi.org / 10.1016 / j.molp.2017.07.004) was used to solve the structure using difference Fourier synthesis techniques. Multiple cycles of restrained refinement with PHENIX (Adams et al., 2010) and iterative model building with COOT (Emsley and Cowtan, 2004) were performed to obtain the final models. The stereochemistry of the models was verified with MolProbity. X-ray diffraction data for either binary or ternary complexes was collected at the crystallography beam lines of the European Synchrotron Radiation Facility (ESRF, 118 M / 64069-PCTEMBL 2020-011Grenoble, France) and the ALBA synchrotron (Barcelona, Spain) in numerous sessions starting in April 162018. Data for these experiments was automatically tracked and logged in the automated data management systems of the HTX facility at EMBL Grenoble and the respective synchrotron facilities. Data processing and structure refinement was carried out using standard crystallography software, as described in the publications mentioned above.F Bioactivity assaysSelected compounds were assayed for their ability to modulate ABA perception to shape plant growth and germination. Three different experimental approaches usingthe model plant Arabidopsis thaliana were followed (wild type or wt). In order todetermine whether the effect of the compounds is mediated by the ABA pathway, control experiments were carried out in the Arabidopsis thaliana quadruple mutant lacking ABA receptor genes pyr1 / pyl1 / pyl2 / pyl4 (doi:10.1126 / science.1173041 ; Sang-Youl Park1, Abscisic acid inhibits PP2Cs via the PYR / PYL family of ABA binding START proteins. Science.2009 May 22; 324(5930): 1068–1071.) Experiment 1: Seed Germination assays. Radicle emergence was established in wild type (wt, Figure 1) andpyr1 / pyl1 / pyl2 / pyl4 mutant (Figure 2) Arabidopsis thaliana seeds 24 hrs after sowing inthe presence of 1 µM ABA, which inhibits seed germination with and without selectedcompounds -, 7i, and 7j. For this, ca. 34 Arabidopsis thaliana seeds were sowed in apetri dish with medium containing 1 / 2MS (Murashige & Skoog medium half strength, Duchefa, M0255) + 0,7% agar + 0,5% sucrose, pH5.7 KOH supplemented with final concentrations of 1 µM ABA and 25 µM of each of the selected compounds and stratified at 4 °C for 48 hours. After this time, the petri dishes were transferred to an incubator with long day conditions (16h light / 8h dark) . After 24 hrs germination and appearance of the radicle was evaluated. Experiments were done in replicates in independent plates. At least two biological replicates were carried out. Compounds and ABA were delivered from 100 mM stock solutions in 100% DMSO. Experiments with DMSO only were carried out as control. Effects of compound 7k in the germination of Eggplant seeds of the variety Tijuana (Figure 6) were measured based on International Seed Testing Association(ISTA) protocols. Compound 7k was delivered from 100 mM stock solutions in 100%119 M / 64069-PCTEMBL 2020-011DMSO. At least 15 seeds were deposited in a layer of whatmant paper (WhatmanTM cat.no. 1001-070) inside a petri plate. Two ml of water either containing compound 7k at afinal cocentration of 100 microM delivered from the stock solution mentioned above orno compound but the equivalent amount of DMSO was added to the petri plate and theplates were incubated with a temperature and photoperiod of 16 hrs of darkness at 20ºC and 8 hrs of light at 30 ºC. The seeds were allowed to germinate under theseconditions and the number of seeds showing radicle emergence were counted after 2,3, 6,7,1011 and 12 days. Each of the experiments was carried out in triplicate (three petri dishes per condition) and repeated at least two times independently.Experiment 2: Seedling establishment assays..In these experiments the appearance of green cotyledons is evaluated at differenttime points in wild type (wt, Figure 3) and pyr1 / pyl1 / pyl2 / pyl4 mutant (Figure 4)Arabidopsis thaliana seeds 24 hrs after sowing in the presence of 1 µM ABA, whichinhibits seed germination with and without selected compounds 7i and 7j. For this, ca.34 Arabidopsis thaliana seeds were sowed in a petri dish with medium containing 1 / 2MS+ 0,7% agar + 0,5% sucrose, pH5.7 KOH supplemented with final concentrations of 1 µM ABA and 25 µM of each of the selected compounds and stratified at 4 °C for 48 hours. After this time, the petri dishes were transferred to an incubator with long day conditions (16h light / 8h dark). and 22°C temperature The number of plants displaying green cotyledons is counted after 2, 3, 4, 7 and 8 days. At least two biological replicates were carried out. Compounds and ABA were delivered from 100 mM stock solutions in 100% DMSO. Experiments with DMSO only were carried out as control. Effects of compound 7k in seedling establishment in Eggplants of the varietyTijuana (Figure 7) were measured by following the appearance of green cotyledons atdifferent time points after sowing in the presence or absence or compound 7k.Compound 7k was delivered from 100 mM stock solutions in 100% DMSO. At least 15seeds were deposited in a layer of whatmant paper (WhatmanTMcat. no. 1001-070) inside a petri plate. Two ml of water either containing compound 7k at a final cocentration of 100 microM delivered from the stock solution mentioned above or no compound but 120 M / 64069-PCTEMBL 2020-011the equivalent amount of DMSO were added to the petri plate and the plates wereincubated with a temperature and photoperiod of 16 hrs of darkness at 20 ºC and 8 hrsof light at 30 ºC. The seeds were allowed to germinate under these conditions and thenumber of plants (seedlings) displaying green cotyledons after 7, 10, 11,12, and 13 dayswere counted. Each of the experiments was carried out in triplicate (three petri dishes per condition) and repeated at least two times independently. Experiment 3: Expression levels of the specific ABA molecular marker: AtRD29B. In this experiment, the effect of selected compounds 3ab, 3ae, 7b, 7e, 7i, 7j and7k on ABA-induced gene expression were evaluated. For this, the levels of expressionof the ABA specific marker gene AtRD29B were measured by qRT-PCR in seedlingsgrown in the presence of either ABA or Mannitol (inducer of intrinsic ABA levels in theplant) or ABA / Mannitol + selected compounds 7i and 7j (see Figure 5A). Compounds3ab, 3ae, 7b, 7e and 7k were tested in the presence of ABA and compared to ABA alone(see Figures 5B and 5C). wt Arabidopsis thaliana seeds were sowed in a petri dish containing 1 / 2MSmedium + 0,7% agar + 0,5% sucrose, pH5.7 KOH and stratified at 4 °C for 48 hours. After this, the plates were transferred to an incubator with long day conditions (16h light / 8h dark) at 22°C in a vertical position and grown during 8 days. Then, the 8 days- old-seedlings were transferred to in 1ml 1 / 2MS media pH5.7, 0.25% sucrose in sterile 6- well-plates and acclimated in long day overnight. The media was removed and 1ml of 1 / 2MS pH5.7, 0.25% sucrose supplemented with either 400mM mannitol or 25 µM ABA and 100 µM compounds. The plates were incubated under long day conditions and the seedlings were collected 6 hours after treatment, RNA was extracted and subject to qRT- PCR analysis to evaluate the levels of expression of the AtRD29B gene using AtSAND as reference gene (DNA coding sequences for both genes are listed in Table 2, below). Compounds and ABA were delivered from 100 mM stock solutions in 100% DMSO at the final concentrations indicated above. Experiments with 1 / 2MS media and DMSOwere carried out as controls.qRT-PCR analysis was carried as follows: RNA extraction was carried out with the relia Prep RNA Tissue Mini Prep System (Promega) following the manufacturer’s instructions. cDNA synthesis was conducted using 1 µg of total RNA for reverse- transcription using GoScript Reverse Transcriptase (Promega) in a final volume of 20 121 M / 64069-PCTEMBL 2020-011μL. cDNA was then diluted eightfold with water for subsequent quantitative real-timePCR (qPCR) analysis. qPCR analysis was performed with gene specific primersfor AtRD29B (At5g52300; FW: 5′-TGGTGGGGAAAGTTAAAGGA -3′ (SEQ ID NO: 18),RV: 5′-GGAATCCGAAAACCCCATAGTCC -3′ (SEQ ID NO: 19)) in a final volume of 20μL containing 2 μL of diluted cDNA, 0.2 μM of each primer, 0.03 μM of reference dye (ROX), and 10 µL of Brilliant III Ultra Fast SYBR Green QPCR Master Mix (Agilent) on a QuantStudio three real-time PCR machine (Applied Biosystems; Thermo Scientific) with the following program: 95°C for 3 min, then 40 cycles of 10 s at 95°C and 20 s at 60°C.mRNA levels were normalized to the house keeping gene AtSAND (At2g28390; FW: 5′-AACTCTATGCAGCATTTGATCCACT-3′ (SEQ ID NO: 20), RV: 5′- TGATTGCATATCTTTATCGCCATC-3′ (SEQ ID NO: 21)).Table 2. DNA sequences of AtRD29B and AtSAND genes used in qRT-PCRAtRD29B gene - coding sequence: (SEQ ID NO: 22)ATGGAGTCACAGTTGACACGTCCTTATGGTCATGAGCAAGCAGAAGAACCAATCAGAATTCACCATCCAG AAGAAGAAGAGCATCATGAGAAGGGAGCATCCAAAGTGTTGAAGAAAGTAAAAGAAAAGGCTAAGAAAAT CAAGAACAGTCTCACTAAACATGGAAATGGTCATGATCACGATGTGGAAGATGATGATGATGAGTATGAC GAGCAAGACCCAGAAGTTCACGGCGCACCAGTGTATGAATCCTCTGCCGTGAGAGGTGGTGTAACGGGTA AACCTAAGTCTCTTAGTCATGCCGGAGAAACTAATGTTCCGGCATCGGAGGAGATTGTTCCTCCAGGGAC AAAAGTTTTTCCTGTCGTGTCTTCTGACCACACCAAACCCATTGAGCCTGTATCATTACAAGATACCTCT TACGGACATGAGGCACTGGCTGATCCTGTAAGAACGACGGAAACATCGGACTGGGAAGCGAAAAGAGAGG CACCGACTCATTATCCTCTCGGAGTGTCAGAATTTTCAGACAGAGGAGAGAGCAGAGAGGCTCATCAAGA GCCATTGAACACTCCTGTGTCTCTGCTTTCAGCAACAGAGGACGTGACTAGGACGTTTGCTCCTGGTGGT GAAGATGACTATCTCGGTGGTCAACGGAAAGTCAACGTCGAGACGCCAAAACGTTTGGAGGAAGATCCGG CTGCTCCAGGAGGAGGATCGGATTATCTCAGTGGTGTATCTAATTATCAGTCCAAAGTTACTGATCCCAC GCATAAAGGTGGAGAAGCTGGAGTACCAGAGATTGCTGAGTCTCTTGGTAGAATGAAAGTGACTGATGAG TCTCCTGATCAGAAATCAAGACAAGGACGCGAAGAAGACTTTCCGACGAGAAGCCATGAGTTTGATCTGA AGAAGGAATCTGATATCAACAAGAATTCTCCGGCAAGATTTGGAGGGGAATCAAAAGCTGGGATGGAGGA AGATTTTCCGACAAGAGGTGATGTGAAAGTAGAGAGTGGATTGGGAAGAGACTTACCGACGGGAACTCAT GATCAGTTCTCACCAGAACTATCTCGTCCCAAAGAGAGAGATGATTCTGAGGAAACCAAAGATGAGTCGA CACATGAGACAAAACCAAGCACCTACACAGAGCAGTTAGCTTCAGCTACATCAGCCATAACTAACAAAGC TATAGCCGCAAAGAACGTCGTTGCCTCAAAGCTAGGTTACACCGGAGAGAATGGCGGCGGGCAAAGCGAG AGCCCTGTAAAAGATGAAACTCCGAGATCTGTTACTGCTTACGGGCAGAAAGTGGCGGGAACTGTTGCTG AGAAGTTGACTCCGGTTTACGAAAAAGTCAAAGAAACAGGATCAACGGTGATGACAAAGCTACCTCTCTC CGGAGGTGGAAGTGGAGTGAAGGAGACGCAACAAGGGGAAGAGAAAGGTGTGACGGCTAAAAATTATATA TCAGAGAAGCTGAAACCTGGAGAAGAGGACAAAGCTTTATCGGAAATGATAGCTGAGAAACTTCATTTTG GAGGAGGAGGAGAGAAGAAGACAACGGCTACAAAGGAGGTGGAAGTGACGGTTGAGAAGATACCTTCCGA CCAGATAGCGGAGGGGAAAGGACATGGTGAGGCGGTTGCAGAGGAAGGAAAAGGTGGAGAAGGAATGGTG GGGAAAGTTAAAGGAGCGGTCACTTCTTGGCTCGGTGGTAAACCGAAGTCGCCACGGTCCGTTGAAGAGT CTCCACAATCACTTGGCACCACCGTTGGGACTATGGGGTTTTCGGATTCCGGTGGAAGTGAGTTGGGAGG CAGTGGCGGAGGTAAGGGAGTTCAAGATTCTGGGAACTGAAtSAND gene - coding sequence: (SEQ ID NO: 23)ATGGCGACTTCAGATTCGAGGTCTTCTCCTTCATCATCCGACACCGAATTCGCCGATCCAAATCCTAGCT CCGATCCAGAGACGAATTCGGAGCGTGTTCAAAGTCAATTAGAGTCAATGAATTTATCTCAACCTAGCGA AGTCTCTGATGGTAGCCACACCGAATTTAGCGGTGGCGGCGATGATAATGATGATGAGGTTGCATCGGCT AACGGGAACGAAGGCGGAGTTAGCAATGGAGGTTTATTGCGTGAAGGTGTGGCGGGAACTAGCGGAGGAG 122 M / 64069-PCTEMBL 2020-011AGGTTTTGTTAAGGGCGGAAAATCCGGTGGAAATGGAAGCAGGTGAAGAACCACCGAGTCCGACTAGTAG CGGTTACGATGGAGAGAGAGGAAGTAGCGGCGGAGCTACTTCTACTTATAAAGCTGATGATGGAAGCGAG GATGAGATTAGGGAAGCTAATGTGGATGGTGACACTGCCTCGCAGCATGAAGCTGCGTGGTTGCCTGGAA AACGCCATGTTGATGAGGATGATGCTTCTACGTCATGGAGAAAGAGGAAGAAGCATTTCTTCATACTGAG TAACTCAGGCAAACCGATATATTCCAGATATGGAGATGAACATAAGCTTGCTGGATTTTCAGCTACTCTT CAAGCTATTATTTCTTTTGTGGAGAATGGTGGTGACCGTGTCAACTTAGTCAAGGCAGGAAATCACCAGG TTGTCTTTCTCGTTAAGGGGCCAATATATCTGGTCTGCATCAGCTGTACAGATGAAACATATGAGTATTT AAGGGGGCAGTTGGATCTTCTATATGGTCAGATGATACTAATTTTAACAAAATCAATAGACAGATGTTTT GAAAAGAATGCAAAGTTCGATATGACACCCTTGCTTGGAGGGACAGATGCTGTCTTCTCATCTCTTGTCC ATTCATTTAGCTGGAACCCAGCTACATTTCTTCATGCCTATACTTGTCTTCCCCTTCCATATGCGTTAAG GCAAGCTACAGGAACCATATTGCAAGAAGTTTGCGCGTCTGGTGTCTTATTCTCACTACTAATGTGCAGA CACAAGGTTGTCAGTCTTGCTGGTGCACAGAAAGCGTCTCTCCATCCCGATGACTTGCTTCTACTCTCAA ATTTTGTCATGTCATCAGAATCATTCAGGACATCAGAATCTTTCTCACCAATCTGCCTACCAAGATACAA CGCTCAGGCCTTTTTGCATGCCTATGTCCACTTCTTTGATGATGATACATATGTAATATTGCTTACCACA CGTTCAGATGCGTTCCATCATCTCAAAGATTGCAGGGTACGCCTTGAGGCTGTTCTTCTCAAGTCAAATA TTCTAAGTGTGGTTCAAAGATCAATCGCGGAAGGTGGAATGCGTGTTGAAGATGTACCAATAGACCGCAG GCGTCGATCATCTACTACTAATCAAGAACAAGACTCACCTGGTCCCGACATATCTGTGGGAACCGGAGGT CCCTTTGGACTTTGGCATTTCATGTACCGTAGTATATACTTAGATCAATACATTTCCTCGGAATTCTCAC CCCCAGTAACTAGTCACAGACAACAGAAAAGTCTATATCGAGCATACCAGAAACTTTATGCTTCAATGCA TGTAAAAGGATTGGGACCCCACAAGACTCAATATAGAAGAGATGAAAACTACACTCTTCTATGTTGGGTC ACACCAGATTTTGAACTCTATGCAGCATTTGATCCACTTGCAGACAAGGCGATGGCGATAAAGATATGCA ATCAGGTGTGCCAAAGGGTAAAAGATGTGGAGAATGAAGTGTTCTTGCAAGGAGCTAGTCCTTTCTCTTG GTGAE. ResultsE.1 Biochemical Assay Results Table 3. Phosphatase Assay Results 123 M / 64069-PCTEMBL 2020-011 In addition to the observed antagonistic or agonistic activity, the data of Table 3 also show, whether a test compound also shows side activity with phosphatase. 124 M / 64069-PCTEMBL 2020-011Table 4. Results of the TR-FRET Binding assays to ABA receptors withindifferent receptor subfamilies 125 M / 64069-PCTEMBL 2020-0113333a3a3a3a3a3a3a77777777777999911 126 M / 64069-PCTEMBL 2020-011SL = Solanum lycopersicum;At = Arabidopsis thalianaE.2 Structural analysis of mode of action and protein-compound interactionsThe compounds indicated in Table 5 have been structurally characterized by X- ray crystallography either in complex with the ABA receptor alone (Binary) or in complex with the ABA receptor and the HAB1 phosphatase (see methods) revealing the protein- compound interactions and mode of action.Table 5: Summary on results of the mode of action of different compounds(Agonist / Antagonist) based on X-ray crystallography analysis of binary and ternary complexes. 127 M / 64069-PCTEMBL 2020-011 E.3 Bioactivity assays resultsFigure 1 illustrates for compound 7i and 7j the results of seed germination assays in wt plants.Figure 2 illustrates for compound 7i and 7j the results of seed germination assays inpyr1 / pyl1 / pyl2 / pyl4 mutant plants. (Control experiment)Figure 3 illustrates for compound 7i and 7j the results of seedling establishment assaysin wt plants.Figure 4 illustrates for compound 7i and 7j the results of seedling establishment assaysin pyr1 / pyl1 / pyl2 / pyl4 mutant. (Control experiment)Figures 5A, B and C illustrate the results of gene expression assays measuringexpression level of ABA-inducible gene AtRD29B in wt A. thaliana plants.Figure 6 illustrates for compound 7k the results of seed germination assays in eggplantTijuana.Figure 7 illustrates compound 7k the results of seedling establishment assays in eggplantTijuana. 128 M / 64069-PCTEMBL 2020-011Table 6: Amino acid and nucleotide sequences referred to herein The content of any reference as cited herein above is incorporated by reference. 129 M / 64069-PCT

Claims

1. CLAIMS1. The use of a compound of formula Ia wherein, X is H, -C1-C4-alkyl, in particular methyl, ethyl, isopropyl or isopropyl, - C3-C6-cycloalkyl, in particular cyclopropyl, -CF3, -CF2H, -CFH2 , -C1- C2-alkyl optionally substituted by -OH, -CN, -C(O)OH,- C(O)OR or -C(O)NRaRb;, wherein R is -C1-C4-alkyl, and Raand Rbare independently selected from H or -C1-C4-alkyl Z1 is nitrogen or CH, or C-C1-C4-alkylZ2is nitrogen, CH or C-C1-C4-alkyl, Z3is nitrogen or CH, R1, R2, R3and R4, independently of each other are selected from residues of group d): H, halogen, -C1-C3-alkyl, -O-C1-C3-alkyl, -C(O)O-C1-C3-alkyl, -C3- C8-cycloalkyl, -C1-C3-haloalkyl, or are independently selected from optionally substituted residuesof group e): unsubstituted or 1-, 2- or 3-fold substituted -C6-C10-aryl,unsubstituted or 1-, 2- or 3-fold substituted -O-C6-C10-aryl,unsubstituted or 1-, 2- or 3-fold substituted -NH-C6-C10-aryl,unsubstituted or 1-, 2- or 3-fold substituted –S(O)n-C6-C10-arylwith n = 0, 1 or 2,unsubstituted or 1-, 2- or 3-fold substituted -O-C1-C4-alkylene-C6-C10-aryl, unsubstituted or 1-, 2- or 3-fold substituted -O-C2-C4-alkenylene-C6-C10-aryl, and unsubstituted or 1-, 2- or 3-fold substituted -C3-C8-heteroaryl,wherein said optional substituents of group e) are aryl or heteroaryl ring substituents, independently selected from halogen, -CN,–C(halogen)3, -C1-C3-alkyl, and -O-C1-C3-alkyl or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof,as abscisic acid (ABA) plant hormone receptor antagonist.

2. The use of claim 1, whereinX is H, C1-C4-alkyl, like methyl, ethyl, isopropyl or cyclopropyl, C1-C2-alkyl optionally substituted by -OH, -CN, -C(O)OH, -C(O)OR or -C(O)NRaRbwherein R, Raand Rbare independently selected from H or C1-C4-alkyl.

3. The use of claim 1 or 2, whereinX is H, methyl, ethyl, isopropyl, cyclopropyl, cyanomethyl , or -CH2-C(O)O-C1-C4-alkyl Z1is nitrogen or CH Z2is nitrogen, CH or C--C1-C4-alkyl Z3is nitrogen or CH R1is H, -O-C1-C4-alkyl, or halogen R2is H, halogen, phenyl, phenoxy, -CF3, -C1-C4-alkyl, -C1-C4-alkoxy, - C(O)O-C1-C4-alkyl, -C1-C4-alkylene-phenyl, -C2-C4-alkenylene-phenyl, 5- or 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from N and S; R3is H or –O-C1-C4-alkyl, and R4is H, Hal, -O-C1-C4-alkyl or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof.

4. The use of anyone of the claims 1 to 3 , whereinX H, methyl, ethyl, isopropyl, cyanomethyl or cyclopropyl, or -CH2-C(O)O-methyl Z1is nitrogen or CH Z2is CH or C-CH3Z3is nitrogen or CH R1is H, -O-methyl, or Br R2 is H, F, Cl, Br, phenyl, phenoxy, -CF3, methyl, methoxy, -C(O)O-methyl, --n-butylene-phenyl, -2-butenylene-pheny, pyrazolyl, thiophenyl and pyridinyl; R3is H or Br and R4is H, Br, -O-methyl. or an N-oxide, tautomer, stereoisomer or agriculturally acceptable salt thereof.

5. The use of anyone of the claims 1 to 4, wherein Z3 is nitrogen.

6. The use of anyone of the claims 1 to 5, wherein R2 is H, Br or Cl, phenyl,phenoxy, thiophenyl or –O-methyl.

7. The use of anyone of the claims 1 to 6, wherein R3 is H.

8. The use of anyone of the claims1 to 7, wherein R4 is H.

9. The use of anyone of the preceding claims, wherein at least one compound ofgeneral formula Ia is applied as abscisic acid (ABA) plant hormone antagonist, comprising an interaction with at least one of the receptor subtypes selected fromthe dimeric Clade III receptors PYL1, PYR1, PYL2, and PYL3; the monomericClade II receptors PLY4, PYL5, PYL6, PYL11 and PYL12; or the monomericClade I receptors PYL7, PYL8, PYL9, and PYL10, , particularly comprising an interaction with at least one of said dimeric Clade III receptors, more particularly comprising an interaction with receptor subtype PYL1 and optionally also with atleast one receptor subtype selected from PYR1, PYL2, PYL5 and PYL9.

10. The use of claim 9, wherein at least one compound of general formula Ia isapplied as ABA plant hormone antagonist comprising an interaction with PYL 1.

11. The use of anyone of the preceding claims, wherein at least one compound ofgeneral formula Ia is applied for enhancing seed germination and / or seedlingestablishment of a target plant, wherein said target plant seed or seedling isselected from crop and non-crop plant seeds or seedlings..

12. The use of anyone of the preceding claims, wherein said at least one ABAantagonist is applied for the control of target plant seed dormancy, wherein said target plant seed is selected from crop and non-crop plant seeds.

13. The use of claim 12, where the said target plant seeds are subjected to seedpriming or any similar treatments, either by applying a solution containing at leastone ABA antagonist as defined herein above; or by dry-coating or soaking saidtarget plant seeds with at least one ABA antagonist as defined herein above.

14. The use of anyone of the claims 9 to 13, wherein said least one ABA antagonistis applied in order to enhance the germination percentage, and / or in order toenhance the speed and / or the uniformity of germination and / or in order todecrease the time between sowing and germination.

15. The use of anyone of the claim 1 to 9, wherein said at least one ABA antagonistis applied in order to improve the heat stress tolerance of plant seeds.

16. The use of anyone of the claim 1 to 9, wherein said least one ABA antagonist isapplied for modulating plant resistance against pathogens.

17. Agrochemical composition, comprising an agrochemically acceptable solid,semisolid or liquid carrier and at least one ABA antagonist or agonist as definedin anyone of the claims 1 to 10 optionally in combination with at least one furtheragrochemically active co-ingredient, like for example, but not limited to osmolites,like sucrose, sorbitol and manitol, solubilizers, like DMSO or wetting agents, likeSilwet-77.

18. A method to control plant seed dormancy, plant seed development or to promoteseed germination and / or seedling establishment,which method comprises treating said plant, said plant seed or the soil with an effective amount of at least one ABA antagonist compound of formula Ia asdefined in any of claims 1 to 10 or an N-oxide, a tautomer, a stereoisomer or an agriculturally acceptable salt thereof, or with an effective amount of a composition of claim 17 comprising at least one compound of formula Ia as defined in any ofclaims 1 to 10 or an N-oxide, a tautomer, a stereoisomer or an agriculturallyacceptable salt thereof.

19. A compound of the general formula Ia as defined in anyone of the claims 1 to 10.

20. The compound of claim 19, selected from(S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide hydrochloride(3a) (S)-2-(4,5-Dimethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (3b) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyridin-3-yl)propanamide (3c) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1H-pyrrolo[2,3-b]pyridin-5-yl)propanamide hydrochloride (3d) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(1,8-naphthyridin-3-yl)propanamide (3e) (±)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(pyrimidin-5-yl)propanamide (3f) Methyl-(S)-5-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)picolinate hydrochloride (3g) (S)-N-(6,7-Dimethoxyquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3j) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(7-methoxyquinolin-3-yl)propanamide (3k) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(5-methoxyquinolin-3-yl)propanamide (3l) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(8-methoxyquinolin-3-yl)propanamide (3m) (S)-N-(7-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3n) (S)-N-(5-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3o) (S)-N-(8-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3p) Methyl (S)-3-(3-hydroxy-2-(1H-imidazol-1-yl)propanamido)quinoline-6-carboxylate (3q) (S)-N-(6-Bromoquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3r) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methoxyquinolin-3-yl)propanamide (3s) (S)-N-(6-Chloroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3t)(S)-N-(6-Cyclopropylquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3w) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(pyridin-3-yl)quinolin-3-yl)propanamide (3x) (S)-N-(6-Fluoroquinolin-3-yl)-3-hydroxy-2-(1H-imidazol-1-yl)propanamide (3y) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-methylquinolin-3-yl)propanamide (3z) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(trifluoromethyl)quinolin-3- yl)propanamide (3aa) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3-yl)propanamide (3ab) (S,E)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-styrylquinolin-3-yl)propanamide (3ac) (S)-3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenethylquinolin-3-yl)propanamide (3ad) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(1-methyl-1H-pyrazol-4-yl)quinolin-3- yl)propanamide (3ae) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-(thiophen-3-yl)quinolin-3-yl)propanamide (3af) 3-Hydroxy-2-(1H-imidazol-1-yl)-N-(6-phenylquinolin-3-yl)propanamide (3ag) 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7a) 2-(5-Ethyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7b) 3-Hydroxy-2-(5-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7c) 3-Hydroxy-2-(4-isopropyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7d) 2-(5-Cyclopropyl-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7e) 2-(5-(Cyanomethyl)-1H-imidazol-1-yl)-3-hydroxy-N-(quinolin-3-yl)propanamide (7f) Methyl2-(1-(3-hydroxy-1-oxo-1-(quinolin-3-ylamino)propan-2-yl)-1H-imidazol-5- yl)acetate (7g) 3-Hydroxy-2-(5-(2-hydroxyethyl)-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (7h) N-(6-Chloroquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3-hydroxypropanamide (7i) N-(6-Bromoquinolin-3-yl)-2-(5-ethyl-1H-imidazol-1-yl)-3-hydroxypropanamide (7j) 3-Hydroxy-2-(5-methyl-1H-imidazol-1-yl)-N-(6-phenoxyquinolin-3-yl)propanamide (7k) (S)-3-Hydroxy-2-(2-methyl-1H-imidazol-1-yl)-N-(quinolin-3-yl)propanamide (12) (S)-3-Hydroxy-2-(5-methyl-1H-1,2,3-triazol-1-yl)-N-(quinolin-3-yl)propanamide (14) or any N-oxide, tautomer, stereoisomer or a salt thereof.

Images