2-amino-n-(oxo-aryl-lambda6-sulfanylidene)acetamide compounds and their therapeutic use

Abstract

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 2-amino-N-(oxo-aryl-A6- sulfanylidene)acetamide compounds (referred to herein as ANOSA compounds) that, inter alia, inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase; to treat disorders that are ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase; to treat bacterial infections; etc.

Description

[0001] 2-AMINO-N-(OXO-ARYL-LAMBDA6-SULFANYLIDENE)ACETAMIDE COMPOUNDS AND THEIR THERAPEUTIC USE

[0002] RELATED APPLICATION

[0003] This application is related to United Kingdom (GB) patent application number 2317786.8 filed 21 November 2023, the contents of which are incorporated herein by reference in their entirety.

[0004] TECHNICAL FIELD

[0005] The present invention pertains generally to the field of therapeutic compounds.

[0006] More specifically the present invention pertains to 2-amino- / V-(oxo-aryl-A6- sulfanylidene)acetamide compounds (referred to herein as ANOSA compounds) that, inter alia, inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit (e.g., selectively inhibit) bacterial aminoacyl-tRNA synthetase; to treat disorders that are ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase; to treat bacterial infections; etc.

[0007] BACKGROUND

[0008] A number of publications are cited herein in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Each of these references is incorporated herein by reference in its entirety into the present disclosure, to the same extent as if each individual reference was specifically and individually indicated to be incorporated by reference.

[0009] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise,” and variations such as “comprises” and “comprising,” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0010] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a pharmaceutical carrier” includes mixtures of two or more such carriers, and the like. Ranges are often expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment.

[0011] This disclosure includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0012] Bacterial Aminoacyl-tRNA

[0013] Widespread resistance to currently used antibacterial drugs has encouraged the search for novel chemotherapeutics with slow or completely blocked resistance development. This could be achieved by targeting functional bacterial proteins, the mutation of which leads to reduction of bacterial fitness.

[0014] Bacterial enzymes called aminoacyl-tRNA synthetases (aaRS) have been recognized as such molecular targets for drug development. See, e.g., Gadakh et al., 2012; Vondenhoff et al., 2011 ; and Pham et al., 2014.

[0015] The aminoacyl-tRNA synthetase (aaRS) family of enzymes catalyse the addition of proteinogenic amino acids to their cognate tRNA. The product aminoacyl-tRNA participates in the translation of messenger RNA into protein at the ribosome. The aaRS mechanism proceeds as follows: it binds ATP and the corresponding amino acid and forms an aminoacyl-adenylate intermediate, releasing inorganic pyrophosphate (PPi). The adenylate-aaRS complex binds the appropriate tRNA molecule, and the amino acid is transferred from the aminoacyl-AMP to either the 2’- or the 3’-OH of the last tRNA nucleotide at the 3’-end.

[0016] The mechanism can be summarized in the following reaction series: amino acid + ATP aminoacyl-AMP + PPi aminoacyl-AMP + tRNA aminoacyl-tRNA + AMP

[0017] Two classes of aminoacyl-tRNA synthetases (aaRS) are known: “Class I” (with two highly conserved sequence motifs, and which aminoacylates at the 2’-OH of a terminal adenosine nucleotide on tRNA) and “Class II” (with three highly conserved sequence motifs, and which aminoacylates at the 3’-OH of a terminal adenosine on tRNA).

[0018] Included among the known aminoacyl-tRNA synthetases are: Alanyl-tRNA synthetase; Arginyl-tRNA synthetase; Aspartyl-tRNA synthetase; Glutamyl-tRNA synthetase; Glycyl- tRNA synthetase; Histidyl-RNA synthetase; Isoleucyl-tRNA synthetase; Leucyl-tRNA synthetase; Lysyl-tRNA synthetase; Methionyl-tRNA synthetase; Phenylalanyl-tRNA synthetase; Seryl-tRNA synthetase; Threonyl-tRNA synthetase; Tryptophanyl-tRNA synthetase; Tyrosyl-tRNA synthetase; and Valyl-tRNA synthetase.

[0019] Bacterial aminoacyl-tRNA synthetases (aaRS) possess several features that render them promising broad-spectrum antibacterial drug targets; they are essential for viability, found in all bacterial pathogens, and are in many cases sufficiently structurally distinct from their eukaryotic counterparts to allow selective targeting (see, e.g., Hurdle et al., 2005;

[0020] Ochsner et al., 2007). Furthermore, there exists both chemical and clinical validation for these enzymes as useful targets for antibacterial chemotherapy.

[0021] However, despite the potential promise of this family of targets, only one aaRS inhibitor with a relatively limited indication has to date been approved for the management of bacterial infection. Specifically, mupirocin (also known as Bactroban and Centany; shown below) is an inhibitor of isoleucyl-tRNA synthetase that has been approved for use as a topical agent for nasal decolonization of Staphylococcus aureus and for the treatment of superficial skin infection (see, e.g., Laupland et al., 2003).

[0022] Several inhibitors for other bacterial tRNA synthetases have been developed; however, so far none have been approved for use in medicine.

[0023] The inventors have identified a novel class of small molecule inhibitors of bacterial aminoacyl-tRNA synthetase (specifically, bacterial leucyl-tRNA synthetase) which are useful in the treatment of a range of conditions, including bacterial infections.

[0024] Known

[0025] Jirgensons et al., 2016, describe certain N-acyl-arylsulfonamide derivatives of the following formula as aminoacyl-tRNA synthetase inhibitors which are useful, inter alia, in the treatment of bacterial infections.

[0026] Finn et al., 2018, describe certain 2-amino-N-(arylsulfinyl)-acetamide compounds of the following formula as inhibitors of bacterial aminoacyl-tRNA synthetase inhibitors which are useful, inter alia, in the treatment of bacterial infections.

[0027] Edmund et al., 2021, describe certain 2-amino-N-(amino-oxo-aryl-lambda6- sulfanylidene)acetamide compounds of the following formula as inhibitors of bacterial aminoacyl-tRNA synthetase inhibitors which are useful, inter alia, in the treatment of bacterial infections.

[0028] In contrast to these known compounds, the aminoacyl-tRNA synthetase inhibitors described herein have the following formula:

[0029] That is, unlike the compounds described in Edmund et al., 2021 , the compounds described herein additionally comprise a substituted acyl group, -NRNC(=O)Y. SUMMARY OF THE INVENTION

[0030] One aspect of the invention pertains to certain 2-amino- / V-(oxo-aryl-A6- sulfanylidene)acetamide compounds (referred to herein as ANOSA compounds), as described herein.

[0031] Another aspect of the invention pertains to a composition (e.g., a pharmaceutical composition) comprising an ANOSA compound, as described herein, and a pharmaceutically acceptable carrier or diluent.

[0032] Another aspect of the invention pertains to a method of preparing a composition (e.g., a pharmaceutical composition) comprising the step of mixing an ANOSA compound, as described herein, and a pharmaceutically acceptable carrier or diluent.

[0033] Another aspect of the present invention pertains to a method of inhibiting (e.g., selectively inhibiting) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS, etc.), in vitro or in vivo, comprising contacting the synthetase with an effective amount of an ANOSA compound, as described herein.

[0034] Another aspect of the present invention pertains to a method of inhibiting (e.g., selectively inhibiting) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS, etc.) function in a cell (e.g., a bacterial cell), in vitro or in vivo, comprising contacting the cell with an effective amount of an ANOSA compound, as described herein.

[0035] Another aspect of the present invention pertains to an ANOSA compound as described herein for use in a method of treatment of the human or animal body by therapy, for example, for use in a method of treatment of a disorder (e.g., a disease) as described herein.

[0036] Another aspect of the present invention pertains to use of an ANOSA compound, as described herein, in the manufacture of a medicament, for example, for use in a method of treatment, for example, for use in a method of treatment of a disorder (e.g., a disease) as described herein.

[0037] Another aspect of the present invention pertains to a method of treatment, for example, a method of treatment of a disorder (e.g., a disease) as described herein, comprising administering to a subject in need of treatment a therapeutically-effective amount of an ANOSA compound, as described herein, preferably in the form of a pharmaceutical composition. In one embodiment, the treatment is treatment of a disorder of the human or animal body that is ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS).

[0038] In one embodiment, the treatment is treatment of a bacterial infection.

[0039] Another aspect of the present invention pertains to a kit comprising (a) an ANOSA compound, as described herein, preferably provided as a pharmaceutical composition and in a suitable container and / or with suitable packaging; and (b) instructions for use, for example, written instructions on how to administer the compound.

[0040] Another aspect of the present invention pertains to an ANOSA compound obtainable by a method of synthesis as described herein, or a method comprising a method of synthesis as described herein.

[0041] Another aspect of the present invention pertains to an ANOSA compound obtained by a method of synthesis as described herein, or a method comprising a method of synthesis as described herein.

[0042] Another aspect of the present invention pertains to novel intermediates, as described herein, which are suitable for use in the methods of synthesis described herein.

[0043] Another aspect of the present invention pertains to the use of such novel intermediates, as described herein, in the methods of synthesis described herein.

[0044] As will be appreciated by one of skill in the art, features and preferred embodiments of one aspect of the invention will also pertain to other aspects of the invention.

[0045] DETAILED DESCRIPTION OF THE INVENTION

[0046] Compounds

[0047] One aspect of the present invention relates to certain compounds that may conveniently be described as 2-amino- / V-(oxo-aryl-A6-sulfanylidene)acetamide compounds. One simple example of such compounds is 2-amino- / V-(acetamido-oxo-phenyl-A6- sulfanylidene)-acetamide, shown below.

[0048] Another simple example of such compounds is 2-amino- / V-(oxo-phenyl-ureido-A6- sulfanylidene)acetamide, shown below.

[0049] Thus, one aspect of the present invention pertains to compounds of the following formula, and pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein -A, -RN, -Y, -R1, and -R2are as defined herein (for convenience, collectively referred to herein as “2-amino-N-(oxo-aryl-A6-sulfanylidene)acetamide compounds” or “ANOSA compounds”): The left-hand group, A-S(=O)(NRNC(=O)Y)=NH-, may be conveniently considered to be an arylsulfonimidamide moiety. The right-hand group, -C(=O)-CR1R2-NH2, may be conveniently considered to be an alpha-amino acid residue. arylsulfonimidamide alpha-amino acidSome embodiments of the invention include the following: (1) A compound selected from compounds of the following formula, and pharmaceutically acceptable salts, hydrates, and solvates thereof: wherein: -Y is independently -NRUARUBor -RP; -RUAis independently -H or -RUUA; -RUUAis independently: -RU1, -RU2, -RU3, -RU4, -RU5, -LU-RU2, -LU-RU3, -LU-RU4, -C(=O)-RU4, -LU-RU5, or -C(=O)-RU5; -RU1is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups -RUU2; each -RU2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU3is non-aromatic C3-8heterocyclyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU5is C5-10heteroaryl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -LU- is linear or branched saturated C1-4alkylene, and is optionally substituted with one group selected from -OH, -ORUL, -NH2, -NHRUL, and -NRUL2; each -RULis independently linear or branched saturated Ci-4alkyl; each -RUU1is independently selected from:

[0050] -Ruu,

[0051] -LUU-OH, -LUU-ORUU,

[0052] -LUU-NH2, -LUU-NHRUU, -LUU-N(RUU)2, and -LUU-RUM; each -RUU2is independently selected from:

[0053] -F, -Cl, -Br, -I,

[0054] -OH, -ORUU,

[0055] -CF3, -CHF2, -OCF3, -OCHF2,

[0056] -NH2, -NHRUU, -N(RUU)2, -RUM,

[0057] -C(=O)OH, -C(=O)ORUU, -OC(=O)RUU,

[0058] -C(=O)NH2, -C(=O)NHRUU, -C(=O)N(RUU)2, -C(=O)RUM,

[0059] -NHC(=O)RUU, -NRUNC(=O)RUU,

[0060] -NHC(=O)NH2, -NHC(=O)NHRUU, -NHC(=O)N(RUU)2, -NHC(=O)RUM, -NRUNC(=O)NH2, -NRUNC(=O)NHRUU, -NRUNC(=O)N(RUU)2, -NRUNC(=O)RUM,

[0061] -NHC(=O)ORUU, -NRUNC(=O)ORUU,

[0062] -OC(=O)NH2, -OC(=O)NHRUU, -OC(=O)N(RUU)2, -OC(=O)RUM,

[0063] -NHC(=NH)NH2,

[0064] -C(=O)RUU,

[0065] -S(=O)NH2, -S(=O)NHRUU, -S(=O)N(RUU)2, -S(=O)RUM,

[0066] -S(=O)2NH2, -S(=O)2NHRUU, -S(=O)2N(RUU)2, -S(=O)2RUM,

[0067] -NHS(=O)RUU, -NRUNS(=O)RUU,

[0068] -NHS(=O)2RUU, -NRUNS(=O)2RUU,

[0069] -S(=O)RUU, -S(=O)2RUU,

[0070] -SH, -SRUU, -CN, and -NO2; wherein: each -Luu- is linear or branched saturated Ci-4alkylene; each -Ruuis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RUNis linear or branched saturated Ci-4alkyl; each -RUMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:

[0071] -RUMM, -C(=O)RUMM, -C(=O)ORUMM, and -S(=O)2RUMM; wherein each -RUMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;

[0072] -RUBis independently -H or -RUUB;

[0073] -RUUBis independently linear or branched saturated Ci-4alkyl;

[0074] -Rpis independently:

[0075] -RP1, -RP2, -RP3, -RP4, -RP5, -LP-RP2, -LP-RP3, -LP-RP4, or -Lp-RP5;

[0076] -RP1is linear or branched saturated Ci-ealkyl, and is optionally substituted with one or more groups -RPP2; each -RP2is saturated Cs-ecycloalkyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP3is non-aromatic Cs-sheterocyclyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP5is Cs-wheteroaryl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -Lp- is linear or branched saturated Ci-4alkylene, and is optionally substituted with one group selected from -OH, -ORPL, -NH2, -NHRPL, and -NRPL2; each -RPLis independently linear or branched saturated Ci-4alkyl; each -RPP1is independently selected from:

[0077] -Rpp,

[0078] -LPP-OH, -LPP-ORPP,

[0079] -LPP-NH2, -LPP-NHRPP, -LPP-N(RPP)2, and -LPP-RPM; each -RPP2is independently selected from:

[0080] -F, -Cl, -Br, -I,

[0081] -OH, -ORPP,

[0082] -CF3, -CHF2, -OCF3, -OCHF2,

[0083] -NH2, -NHRPP, -N(RPP)2, -RPM,

[0084] -C(=O)OH, -C(=O)ORPP, -OC(=O)RPP,

[0085] -C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2, -C(=O)RPM,

[0086] -NHC(=O)RPP, -NRPNC(=O)RPP,

[0087] -NHC(=O)NH2, -NHC(=O)NHRPP, -NHC(=O)N(RPP)2, -NHC(=O)RPM, -NRPNC(=O)NH2, -NRPNC(=O)NHRPP, -NRPNC(=O)N(RPP)2, -NRPNC(=O)RPM, -NHC(=O)ORPP, -NRPNC(=O)ORPP,

[0088] -OC(=O)NH2, -OC(=O)NHRPP, -OC(=O)N(RPP)2, -OC(=O)RPM,

[0089] -NHC(=NH)NH2,

[0090] -C(=O)RPP,

[0091] -S(=O)NH2, -S(=O)NHRPP, -S(=O)N(RPP)2, -S(=O)RPM,

[0092] -S(=O)2NH2, -S(=O)2NHRPP, -S(=O)2N(RPP)2, -S(=O)2RPM,

[0093] -NHS(=O)RPP, -NRPNS(=O)RPP,

[0094] -NHS(=O)2RPP, -NRPNS(=O)2RPP,

[0095] -S(=O)RPP, -S(=O)2RPP,

[0096] -SH, -SRPP, -CN, and -NO2; wherein: each -Lpp- is linear or branched saturated Ci-4alkylene; each -Rppis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RPNis linear or branched saturated Ci-4alkyl; each -RPMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:

[0097] -RPMM, -C(=O)RPMM, -C(=O)ORPMM, and -S(=O)2RPMM; wherein each -RPMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;

[0098] -RNis independently -H or -RNN;

[0099] -RNNis independently linear or branched saturated Ci-4alkyl; and wherein:

[0100] -A is independently -Acor -AH;

[0101] -Acis independently phenyl or naphthyl, and is optionally substituted with one or more substituents -Rx;

[0102] -AHis independently C5-i2heteroaryl, and is optionally substituted with one or more substituents -Rx; wherein: each -Rxis independently selected from:

[0103] _RXX _RXXU _RXXV

[0104] -F, -Cl, -Br, -I,

[0105] -OH, -OR™,

[0106] -L™-OH, -L™-OR™,

[0107] -CF3, -CHF2, -OCF3, -OCHF2,

[0108] -NH2, -NHR™, -NR™2, -RXM,

[0109] -L™-NH2I-L™-NHR™, -L™-NR™2, -L™-RXM,

[0110] -C(=O)OH, -C(=O)OR™, -OC(=O)RXX,

[0111] -C(=O)NH2, -C(=O)NHRXX, -C(=O)NRXX2, -C(=O)RXM,

[0112] -NHC(=O)R™, -NRXNC(=O)RXX,

[0113] -NHC(=O)NH2, -NHC(=O)NHRXX, -NHC(=O)NRXX2, -NHC(=O)RXM,

[0114] -NRXNC(=O)NH2, -NRXNC(=O)NHRXX, -NRXNC(=O)NRXX2, -NRXNC(=O)RXM,

[0115] -NHC(=O)ORXX, -NRXNC(=O)ORXX,

[0116] -OC(=O)NH2, -OC(=O)NHRXX, -OC(=O)NRXX2, -OC(=O)RXM,

[0117] -NHC(=NH)NH2,

[0118] -C(=O)R™,

[0119] -S(=O)NH2, -S(=O)NHRXX, -S(=O)NRXX2, -S(=O)RXM,

[0120] -S(=O)2NH2, -S(=O)2NHRXX, -S(=O)2NRXX2, -S(=O)2RXM,

[0121] -NHS(=O)RXX, -NRXNS(=O)RXX,

[0122] -NHS(=O)2RXX, -NRXNS(=O)2RXX,

[0123] -S(=O)RXX, -S(=O)2RXX,

[0124] -SH, -SRXX, -ON, and -NO2; and additionally, two adjacent groups -Rx, if present, may together form: -O-CH2-O-, -O-CH2CH2-O-, -CH2-CH2-O-, -CH2-CH2CH2-O-, -CH2-O-CH2-, or -CH2-CH2-O-CH2-; wherein: each -Lxx- is linear or branched saturated Ci-4alkylene; each -R™ is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -R™uis independently linear or branched C2-4alkenyl; each -Rxxvis independently linear or branched C2-4alkynyl; each -RXNis linear or branched saturated Ci-4alkyl; each -RXMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from: -RXMM, -C(=O)RXMM, -C(=O)ORXMM, and -S(=O)2RXMM; wherein each -RXMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; -R1is independently -H or -R11; -R11is independently -R11Aor -R11B; -R11Ais independently: -RA1, -RA2, -RA3, -RA4, -RA5, -LA-RA2, -LA-RA3, -LA-RA4, or -LA-RA5; -RA1is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups -RAA2; each -RA2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2; each -RA3is non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2; each -RA4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2; each -RA5is C5-10heteroaryl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2; each -LA- is linear or branched saturated C1-4alkylene; each -RAA1is independently selected from: -RAA, -LAA-OH, -LAA-ORAA, -LAA-NH2, -LAA-NHRAA, -LAA-N(RAA)2, and -LAA-RAM; each -RAA2is independently selected from: -F, -Cl, -Br, -I, -OH, -ORAA, -CF3, -CHF2, -OCF3, -OCHF2, -NH2, -NHRAA, -N(RAA)2, -RAM, -C(=O)OH, -C(=O)ORAA, -OC(=O)RAA, -C(=O)NH2, -C(=O)NHRAA, -C(=O)N(RAA)2, -C(=O)RAM, -NHC(=O)RAA, -NRANC(=O)RAA, -NHC(=O)NH2, -NHC(=O)NHRAA, -NHC(=O)N(RAA)2, -NHC(=O)RAM, -NRANC(=O)NH2, -NRANC(=O)NHRAA, -NRANC(=O)N(RAA)2, -NRANC(=O)RAM, -NHC(=O)ORAA, -NRANC(=O)ORAA,

[0125] -OC(=O)NH2, -OC(=O)NHRAA, -OC(=O)N(RAA)2, -OC(=O)RAM,

[0126] -NHC(=NH)NH2,

[0127] -C(=O)RAA,

[0128] -S(=O)NH2, -S(=O)NHRAA, -S(=O)N(RAA)2, -S(=O)RAM,

[0129] -S(=O)2NH2, -S(=O)2NHRAA, -S(=O)2N(RAA)2, -S(=O)2RAM,

[0130] -NHS(=O)RAA, -NRANS(=O)RAA,

[0131] -NHS(=O)2RAA, -NRANS(=O)2RAA,

[0132] -S(=O)RAA, -S(=O)2RAA,

[0133] -SH, -SRAA, -CN, and -NO2; wherein: each -LAA- is linear or branched saturated Ci-4alkylene; each -RMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RANis linear or branched saturated Ci-4alkyl; each -RAMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:

[0134] -RAMM, -C(=O)RAMM, -C(=O)ORAMM, and -S(=O)2RAMM; wherein each -RAMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;

[0135] -R11Bis independently selected from:

[0136] -F, -Cl, -Br, -I,

[0137] -OH, -ORBB,

[0138] -CF3, -CHF2, -OCF3, -OCHF2,

[0139] -NH2, -NHRBB, -NRBB2, -RBM,

[0140] -C(=O)OH, -C(=O)ORBB, -OC(=O)RBB,

[0141] -C(=O)NH2, -C(=O)NHRBB, -C(=O)NRBB2, -C(=O)RBM,

[0142] -NHC(=O)RBB, -NRBNC(=O)RBB,

[0143] -NHC(=O)NH2, -NHC(=O)NHRBB, -NHC(=O)NRBB2, -NHC(=O)RBM,

[0144] -NRBNC(=O)NH2, -NRBNC(=O)NHRBB, -NRBNC(=O)NRBB2, -NRBNC(=O)RBM, -NHC(=O)ORBB, -NRBNC(=O)ORBB,

[0145] -OC(=O)NH2, -OC(=O)NHRBB, -OC(=O)NRBB2, -OC(=O)RBM,

[0146] -NHC(=NH)NH2,

[0147] -C(=O)RBB,

[0148] -S(=O)NH2, -S(=O)NHRBB, -S(=O)NRBB2, -S(=O)RBM, -S(=O)2NH2, -S(=O)2NHRBB, -S(=O)2NRBB2, -S(=O)2RBM,

[0149] -NHS(=O)RBB, -NRBNS(=O)RBB,

[0150] -NHS(=O)2RBB, -NRBNS(=O)2RBB,

[0151] -S(=O)RBB, -S(=O)2RBB,

[0152] -SH, -SRBB, -CN, and -NO2; wherein: each -RBBis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RBNis linear or branched saturated Ci-4alkyl; each -RBMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:

[0153] -RBMM, -C(=O)RBMM, -C(=O)ORBMM, and -S(=O)2RBMM; wherein each -RBMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;

[0154] -R2is independently -H or -R22;

[0155] -R22is independently -R22Cor -R22D;

[0156] -R22Cis independently:

[0157] -RC1, -RC2, -RC3, -RC4, -RC5, -LC-RC2, -LC-RC3, -LC-RC4, or -Lc-RC5;

[0158] -RC1is linear or branched saturated Ci-ealkyl, and is optionally substituted with one or more groups -RCC2; each -RC2is saturated Cs-ecycloalkyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC3is non-aromatic Cs-yheterocyclyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC5is Cs-wheteroaryl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -Lc- is linear or branched saturated Ci-4alkylene; each -RCC1is independently selected from:

[0159] -Rcc,

[0160] -LCC-OH, -LCC-ORCC,

[0161] -LCC-NH2, -LCC-NHRCC, -LCC-N(RCC)2, and -LCC-RCM; each -RCC2is independently selected from:

[0162] -F, -Cl, -Br, -I,

[0163] -OH, -ORCC,

[0164] -CF3, -CHF2, -OCF3, -OCHF2,

[0165] -NH2, -NHRCC, -N(RCC)2, -RCM,

[0166] -C(=O)OH, -C(=O)ORCC, -OC(=O)RCC,

[0167] -C(=O)NH2, -C(=O)NHRCC, -C(=O)N(RCC)2, -C(=O)RCM,

[0168] -NHC(=O)Rcc, -NRCNC(=O)RCC,

[0169] -NHC(=O)NH2, -NHC(=O)NHRCC, -NHC(=O)N(RCC)2, -NHC(=O)RCM, -NRCNC(=O)NH2, -NRCNC(=O)NHRCC, -NRCNC(=O)N(RCC)2, -NRCNC(=O)RCM,

[0170] -NHC(=O)ORCC, -NRCNC(=O)ORCC,

[0171] -OC(=O)NH2, -OC(=O)NHRCC, -OC(=O)N(RCC)2, -OC(=O)RCM,

[0172] -NHC(=NH)NH2,

[0173] -C(=O)RCC,

[0174] -S(=O)NH2, -S(=O)NHRCC, -S(=O)N(RCC)2, -S(=O)RCM,

[0175] -S(=O)2NH2, -S(=O)2NHRCC, -S(=O)2N(RCC)2, -S(=O)2RCM,

[0176] -NHS(=O)RCC, -NRCNS(=O)RCC,

[0177] -NHS(=O)2RCC, -NRCNS(=O)2RCC,

[0178] -S(=O)RCC, -S(=O)2RCC,

[0179] -SH, -SRCC, -CN, and -NO2; wherein: each -Lcc- is linear or branched saturated Ci-4alkylene; each -Rccis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RCNis linear or branched saturated Ci-4alkyl; each -RCMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:

[0180] -RCMM, -C(=O)RCMM, -C(=O)ORCMM, and -S(=O)2RCMM; wherein each -RCMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; -R22Dis independently selected from: -F, -Cl, -Br, -I, -OH, -ORDD, -CF3, -CHF2, -OCF3, -OCHF2, -NH2, -NHRDD, -NRDD2, -RDM, -C(=O)OH, -C(=O)ORDD, -OC(=O)RDD, -C(=O)NH2, -C(=O)NHRDD, -C(=O)NRDD2, -C(=O)RDM, -NHC(=O)RDD, -NRDNC(=O)RDD, -NHC(=O)NH2, -NHC(=O)NHRDD, -NHC(=O)NRDD2, -NHC(=O)RDM, -NRDNC(=O)NH2, -NRDNC(=O)NHRDD, -NRDNC(=O)NRDD2, -NRDNC(=O)RDM, -NHC(=O)ORDD, -NRDNC(=O)ORDD, -OC(=O)NH2, -OC(=O)NHRDD, -OC(=O)NRDD2, -OC(=O)RDM, -NHC(=NH)NH2, -C(=O)RDD, -S(=O)NH2, -S(=O)NHRDD, -S(=O)NRDD2, -S(=O)RDM, -S(=O)2NH2, -S(=O)2NHRDD, -S(=O)2NRDD2, -S(=O)2RDM, -NHS(=O)RDD, -NRDNS(=O)RDD, -NHS(=O)2RDD, -NRDNS(=O)2RDD, -S(=O)RDD, -S(=O)2RDD, -SH, -SRDD, -CN, and -NO2; wherein: each -RDDis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RDNis linear or branched saturated C1-4alkyl; each -RDMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from: -RDMM, -C(=O)RDMM, -C(=O)ORDMM, and -S(=O)2RDMM; wherein each -RDMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; or -R1and -R2, together with the carbon atom to which they are attached, form a saturated C3-6cycloalkyl or a non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RCC2. For convenience, the following table sets out the various groups mentioned above.

[0181] For the avoidance of doubt, it is intended that the -NH2 group which is attached to a carbon atom in the -S(=O)(NRN(C(=O)Y))=NH-C(=O)-C(NH2)< linkage is unmodified (e.g., is unsubstituted; is unprotected; etc.). However, it may be protonated, i.e. , to form -NH3+.

[0182] Furthermore, for the avoidance of doubt, it is not intended that any part of the -S(=O)(NRN(C(=O)Y))=NH-C(=O)-C(NH2)< linkage forms part of ring.

[0183] Furthermore, for the avoidance of doubt, it is not intended that -A and -R1, taken together, or -A and -R2, taken together, form part of a ring. For example, it is not intended that -A and -R1are additionally linked, other than via the -S(=O)(NRN(C(=O)Y))=NH-C(=O)- C(NH2)(R2)- linkage. Similarly, it is not intended that -A and -R2are additionally linked, other than via the -S(=O)(NRN(C(=O)Y))=NH-C(=O)-C(NH2)(R1)-linkage. However, in certain embodiments, as described herein, -R1and -R2, together with the carbon atom to which they are attached, may form a ring.

[0184] Similarly, for the avoidance of doubt, it is not intended that -A and -RN, taken together, or -A and -Y, taken together, form part of a ring. Similarly, for the avoidance of doubt, it is not intended that -R1and -RN, taken together, or -R1and -Y, taken together, form part of a ring. Similarly, for the avoidance of doubt, it is not intended that -R2and -RN, taken together, or -R2and -Y, taken together, form part of a ring.

[0185] Furthermore, for the avoidance of doubt, it is intended that when a given substituent group is described as “optionally substituted with one of more groups XXX and one or more groups YYY” (for example, wherein XXX and YYY are, respectively: -RUU1 and -RUU2; -RPP1and -RPP2; -RM1and -RM2; or -RCC1and -RCC2), said substituent group may be: (i) unsubstituted, (ii) substituted with one or more of the groups XXX,

[0186] (iii) substituted with one or more of the groups YYY, or (iv) substituted with one or more of each of the groups XXX and YYY.

[0187] Note that the compounds have at least one chiral centre, specifically, the sulfur atom which forms part of the sulfonimidamido group, marked with an asterisk (*) in the following formula. Unless otherwise stated, the sulfur atom at this position may be in either (R) or (S) configuration.

[0188] Also note that, depending upon the identity of the groups -R1and -R2, the compounds may have a second chiral centre, specifically, the carbon atom to which -R1and -R2are attached, marked with a hash (#) in the following formula. Unless otherwise stated, the carbon atom at this position may be in either (R) or (S) configuration.

[0189] For the avoidance of doubt, and unless otherwise stated, a reference to a compound or compounds without specifying the configuration of one or both chiral centres is intended to encompass all possible configurations. For example, the following formula (which is silent with respect to stereochemistry): is intended to encompass all four diastereomers:

[0190] Similarly, the following formula (which is silent with respect to the stereochemistry at the sulfur atom): is intended to encompass both diastereomers: and Note that, depending upon the identity of -RN, tautomerism of the sulfonimidamide linkage is possible, as shown below. Primarily, the compounds are depicted herein in one tautomeric form. However, unless otherwise stated, a reference to a compound or compounds with one tautomeric form is intended to encompass both tautomeric forms.

[0191] Note that, in principle, stereoisomerism (e.g., cis, trans, E, Z) about the S=N double bond is possible, for example, as shown below. Primarily, the compounds are depicted herein in one configuration. However, unless otherwise stated, a reference to a compound or compounds with one configuration is intended to encompass both configurations.

[0192] Furthermore, for the avoidance of doubt:

[0193] The index “Cx-y” in terms such as “Cg-ioheteroaryl”, “Ca-yheterocyclyl”, and the like, refers to the number of ring atoms, which may be carbon atoms or heteroatoms (e.g., N, O, S, as the case may be). For example, pyridyl is an example of a Ceheteroaryl group, and piperidino is an example of a Ceheterocyclyl group.

[0194] The compounds named herein are named as drawn using the chemical drawing software Chemaxon Marvin Sketch version 19.24 or Perkin Elmer ChemDraw Professional version 19.1.

[0195] The Group -Y

[0196] (2) A compound according to (1), wherein -Y is -NRUARUB.

[0197] (3) A compound according to (1), wherein -Y is -Rp. The Group -RUA

[0198] (4) A compound according to any one of (1) to (3), wherein -RUA, if present, is -H.

[0199] (5) A compound according to any one of (1) to (3), wherein -RUA, if present, is -RUUA.

[0200] The Group -RUUA

[0201] (6) A compound according to any one of (1) to (5), wherein -RUUA, if present, is independently:

[0202] -RU1, -RU2, -RU4, -RU5, -LU-RU2, -LU-RU4, -C(=O)-RU4, or -Lu-RU5.

[0203] (7) A compound according to any one of (1) to (5), wherein -RUUA, if present, is independently:

[0204] -RU1, -RU2, -RU4, -LU-RU4, or -C(=O)-RU4.

[0205] (8) A compound according to any one of (1) to (5), wherein -RUUA, if present, is independently:

[0206] -RU1, -RU4, or -Lu-RU4.

[0207] (9) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -RU1.

[0208] (10) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -RU2.

[0209] (11) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -RU3.

[0210] (12) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -RU4.

[0211] (13) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -RU5.

[0212] (14) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -LU-RU2.

[0213] (15) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -LU-RU3.

[0214] (16) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -LU-RU4.

[0215] (17) A compound according to any one of (1) to (5), wherein -RUUA, if present, is - C(=O)-RU4.

[0216] (18) A compound according to any one of (1) to (5), wherein -RUUA, if present, is -LU-RU5. (19) A compound according to any one of (1) to (5), wherein -RUUA, if present, is - C(=O)-RU5.

[0217] The Group -RU1

[0218] (20) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, -tBu, -n-pentyl, -s-pentyl, or - / -pentyl; and is optionally substituted with one or more groups -RUU2.

[0219] (21) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, -nPr, -nBu, or -n-pentyl; and is optionally substituted with one or more groups -RUU2.

[0220] (22) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, or -nPr; and is optionally substituted with one or more groups -RUU2.

[0221] (23) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, -nPr, -nBu, or -n-pentyl; and is substituted with one group -RUU2.

[0222] (24) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, or -nPr; and is substituted with one group -RUU2.

[0223] (25) A compound according to any one of (1) to (19), wherein -RU1, if present, is -Et; and is optionally substituted with one or more groups -RUU2.

[0224] (26) A compound according to any one of (1) to (19), wherein -RU1, if present, is -nPr; and is optionally substituted with one or more groups -RUU2.

[0225] (27) A compound according to any one of (1) to (19), wherein -RU1, if present, is -Me; and is optionally substituted with one or more groups -RUU2.

[0226] (28) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu.

[0227] (29) A compound according to any one of (1) to (19), wherein -RU1, if present, is independently -Me, -Et, or -nPr. (30) A compound according to any one of (1) to (19), wherein -RU1, if present, is -Me.

[0228] (31) A compound according to any one of (1) to (19), wherein -RU1, if present, is -Et.

[0229] (32) A compound according to any one of (1) to (19), wherein -RU1, if present, is -nPr.

[0230] The Group -RU2

[0231] (33) A compound according to any one of (1) to (32), wherein each -RU2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0232] (34) A compound according to any one of (1) to (32), wherein each -RU2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0233] (35) A compound according to any one of (1) to (32), wherein each -RU2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and is substituted with one group -RUU2.

[0234] (36) A compound according to any one of (1) to (32), wherein each -RU2, if present, is independently cyclohexyl.

[0235] The Group -RU3

[0236] (37) A compound according to any one of (1) to (36), wherein each -RU3, if present, is independently oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, or diazepanyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; or -RU3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0237] (38) A compound according to any one of (1) to (36), wherein each -RU3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; or -RU3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7- thieno[3,4-c(]imidazolyl.

[0238] (39) A compound according to any one of (1) to (36), wherein each -RU3, if present, is independently piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; or -RU3, if present, is (3aS,6aR)- 2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl. (40) A compound according to any one of (1) to (36), wherein each -RU3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl; or -RU3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0239] (41) A compound according to any one of (1) to (36), wherein each -RU3, if present, is pyrrolidinyl.

[0240] (42) A compound according to any one of (1) to (36), wherein each -RU3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0241] The group (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl is a radical of a compound having the following structure:

[0242] For the avoidance of doubt, this group is intended to be covered by the definition of “non-aromatic Ca-sheterocyclyl”, for example, as recited for the group -RU3.

[0243] The Group -RU4

[0244] (43) A compound according to any one of (1) to (42), wherein each -RU4, if present, is phenyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0245] (44) A compound according to any one of (1) to (42), wherein each -RU4, if present, is phenyl, and is substituted with one or more groups -RUU2.

[0246] (45) A compound according to any one of (1) to (42), wherein each -RU4, if present, is phenyl, and is substituted with one group -RUU2.

[0247] (46) A compound according to any one of (1) to (42), wherein each -RU4, if present, is phenyl, and is substituted with two groups -RUU2.

[0248] (47) A compound according to any one of (1) to (42), wherein each -RU4, if present, is phenyl. The Group -RU5

[0249] (48) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzoimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, quinazolinyl, or phthalazinyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0250] (49) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0251] (50) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, or tetrazolyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0252] (51) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2.

[0253] (52) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0254] (53) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl.

[0255] (54) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently thienyl, thiazolyl, tetrazolyl, pyridyl, or pyrimidinyl.

[0256] (55) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0257] (56) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently pyridyl or pyrimidinyl. (57) A compound according to any one of (1) to (47), wherein each -RU5, if present, is independently thienyl, thiazolyl, or tetrazolyl.

[0258] The Group -Lu-

[0259] (58) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-, and is optionally substituted with one group selected from -OH, -ORUL, -NH2, -NHRUL, and -NRUL2.

[0260] (59) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2or -CH2-, and is optionally substituted with one group selected from -OH, -ORUL, -NH2, -NHRUL, and -NRUL2.

[0261] (60) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2or -CH2-, and is optionally substituted with one group selected from -NH2, -NHRUL, and -NRUL2.

[0262] (61) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-, and is substituted with -NH2.

[0263] (62) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2or -CH2-, and is substituted with -NH2.

[0264] (63) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0265] (64) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is independently -CH2CH2or -CH2-.

[0266] (65) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is -CH2CH2-.

[0267] (66) A compound according to any one of (1) to (57), wherein each -Lu-, if present, is -CH2-. The Group -RUU1

[0268] (67) A compound according to any one of (1) to (66), wherein each -RUU1, if present, is independently -Ruu, -LUU-OH, or -Luu-ORuu

[0269] (68) A compound according to any one of (1) to (66), wherein each -RUU1, if present, is -Ruu

[0270] The Group -RUU2

[0271] (69) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0272] -F, -Cl, -Br, -I,

[0273] -OH, -ORUU,

[0274] -CF3, -CHF2, -OCF3, -OCHF2,

[0275] -NH2, -NHRUU, -N(RUU)2, -RUM,

[0276] -C(=O)OH, -C(=O)ORUU, -OC(=O)RUU,

[0277] -C(=O)NH2, -C(=O)NHRUU, -C(=O)N(RUU)2, -C(=O)RUM,

[0278] -NHC(=O)RUU, -NRUNC(=O)RUU,

[0279] -NHC(=O)NH2, -NHC(=O)NHRUU, -NHC(=O)N(RUU)2, -NHC(=O)RUM,

[0280] -NRUNC(=O)NH2, -NRUNC(=O)NHRUU, -NRUNC(=O)N(RUU)2,

[0281] -NRUNC(=O)RUM,

[0282] -NHC(=O)ORUU, -NRUNC(=O)ORUU,

[0283] -OC(=O)NH2, -OC(=O)NHRUU, -OC(=O)N(RUU)2, -OC(=O)RUM,

[0284] -C(=O)RUU,

[0285] -SH, -SRUU, -CN, and -NO2.

[0286] (70) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0287] -F, -Cl,

[0288] -OH, -ORUU,

[0289] -CF3, -CHF2,

[0290] -NH2, -NHRUU, -N(RUU)2, -RUM,

[0291] -C(=O)OH, -C(=O)ORUU, -OC(=O)RUU,

[0292] -C(=O)NH2, -C(=O)NHRUU, -C(=O)N(RUU)2, -C(=O)RUM,

[0293] -NHC(=O)RUU, -NRUNC(=O)RUU,

[0294] -C(=O)RUU, and

[0295] -CN. (71) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0296] -OH, -ORUU,

[0297] -NH2, -NHRUU, -N(RUU)2,

[0298] -C(=O)OH, -C(=O)ORUU,

[0299] -C(=O)NH2, -C(=O)NHRUU, -C(=O)N(RUU)2,

[0300] -NHC(=O)RUU, -NRUNC(=O)Ruu,and

[0301] -CN.

[0302] (72) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0303] -OH, -NH2, -NHRUU, -N(RUU)2, -C(=O)OH, -NHC(=O)RUU, and -CN.

[0304] (73) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0305] -OH, -ORUU, -NH2, -NHRUU, -N(RUU)2, and -C(=O)OH.

[0306] (74) A compound according to any one of (1) to (68), wherein each -RUU2, if present, is independently selected from:

[0307] -ORUU, -NH2, and -C(=O)OH.

[0308] The Group -RUL

[0309] (75) A compound according to any one of (1) to (74), wherein each -RUL, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0310] (76) A compound according to any one of (1) to (74), wherein each -RUL, if present, is independently -Me, -Et, -nPr, or -iPr.

[0311] (77) A compound according to any one of (1) to (74), wherein each -RUL, if present, is independently -Me or -Et.

[0312] (78) A compound according to any one of (1) to (74), wherein each -RUL, if present, is -Me.

[0313] The Group -Ruu

[0314] (79) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl. (80) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is independently linear or branched saturated Ci-4alkyl.

[0315] (81) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0316] (82) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is independently -Me, -Et, -nPr, or -iPr.

[0317] (83) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is independently -Me or -Et.

[0318] (84) A compound according to any one of (1) to (78), wherein each -Ruu, if present, is -Me.

[0319] The Group -RUN

[0320] (85) A compound according to any one of (1) to (84), wherein each -RUN, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0321] (86) A compound according to any one of (1) to (84), wherein each -RUN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0322] (87) A compound according to any one of (1) to (84), wherein each -RUN, if present, is independently -Me or -Et.

[0323] (88) A compound according to any one of (1) to (84), wherein each -RUN, if present, is -Me.

[0324] The Group -RUM

[0325] (89) A compound according to any one of (1) to (88), wherein each -RUM, if present, is independently azetidino, pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from: -RUMM, -C(=O)RUMM, -C(=O)ORUMM, and -S(=O)2RUMM

[0326] (90) A compound according to any one of (1) to (88), wherein each -RUM, if present, is independently azetidino, pyrrolidino, piperidino, piperazino, or morpholino. (91) A compound according to any one of (1) to (88), wherein each -RUM, if present, is independently pyrrolidino or piperidino.

[0327] The Group -Luu-

[0328] (92) A compound according to any one of (1) to (91), wherein each -Luu-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0329] (93) A compound according to any one of (1) to (91), wherein each -Luu-, if present, is independently -CH2CH2or -CH2-.

[0330] (94) A compound according to any one of (1) to (91), wherein each -Luu-, if present, is -CH2CH2-.

[0331] (95) A compound according to any one of (1) to (91), wherein each -Luu-, if present, is -CH2-.

[0332] The Group -RUMM

[0333] (96) A compound according to any one of (1) to (95), wherein each -RUMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0334] (97) A compound according to any one of (1) to (95), wherein each -RUMM, if present, is independently linear or branched saturated Ci-4alkyl.

[0335] (98) A compound according to any one of (1) to (95), wherein each -RUMM, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0336] (99) A compound according to any one of (1) to (95), wherein each -RUMM, if present, is independently -Me, -Et, -nPr, or -iPr.

[0337] (100) A compound according to any one of (1) to (95), wherein each -RUMM, if present, is independently -Me or -Et.

[0338] (101) A compound according to any one of (1) to (95), wherein each -RUMM, jf present, is -Me. The Group -RUB

[0339] (102) A compound according to any one of (1) to (101), wherein -RUB, if present, is -H.

[0340] (103) A compound according to any one of (1) to (101), wherein -RUB, if present, is -RUUB.

[0341] The Group -RUUB

[0342] (104) A compound according to any one of (1) to (103), wherein each -RUUB, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0343] (105) A compound according to any one of (1) to (103), wherein each -RUUB, if present, is independently -Me, -Et, -nPr, or -iPr.

[0344] (106) A compound according to any one of (1) to (103), wherein each -RUUB, if present, is independently -Me or -Et.

[0345] (107) A compound according to any one of (1) to (103), wherein each -RUUB, if present, is -Me.

[0346] The Group -Rp

[0347] (108) A compound according to any one of (1) to (107), wherein -Rp, if present, is independently:

[0348] -RP1, -RP2, -RP3, -RP4, -LP-RP3, -LP-RP4, or -Lp-RP5.

[0349] (109) A compound according to any one of (1) to (107), wherein -Rp, if present, is independently:

[0350] -RP1, -RP2, -LP-RP3, -LP-RP4, or -Lp-RP5.

[0351] (110) A compound according to any one of (1) to (107), wherein -Rp, if present, is independently:

[0352] -RP1, -LP-RP4, or -Lp-RP5.

[0353] (111) A compound according to any one of (1) to (107), wherein -Rp, if present, is -RP1.

[0354] (112) A compound according to any one of (1) to (107), wherein -Rp, if present, is -RP2.

[0355] (113) A compound according to any one of (1) to (107), wherein -Rp, if present, is -RP3. (114) A compound according to any one of (1) to (107), wherein -Rp, if present, is -RP4.

[0356] (115) A compound according to any one of (1) to (107), wherein -Rp, if present, is -RP5.

[0357] (116) A compound according to any one of (1) to (107), wherein -Rp, if present, is -LP-RP2.

[0358] (117) A compound according to any one of (1) to (107), wherein -Rp, if present, is -LP-RP3.

[0359] (118) A compound according to any one of (1) to (107), wherein -Rp, if present, is -LP-RP4.

[0360] (119) A compound according to any one of (1) to (107), wherein -Rp, if present, is -LP-RP5.

[0361] The Group -RP1

[0362] (120) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, -tBu, -n-pentyl, -s-pentyl, or - / -pentyl; and is optionally substituted with one or more groups -RPP2.

[0363] (121) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, -nPr, -nBu, or -n-pentyl; and is optionally substituted with one or more groups -RPP2.

[0364] (122) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, or -nPr; and is optionally substituted with one or more groups -RPP2.

[0365] (123) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, -nPr, -nBu, or -n-pentyl; and is substituted with one or two groups -RPP2.

[0366] (124) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, or -nPr; and is substituted with one or two groups -RPP2.

[0367] (125) A compound according to any one of (1) to (119), wherein -RP1, if present, is -Et; and is optionally substituted with one or more groups -RPP2.

[0368] (126) A compound according to any one of (1) to (119), wherein -RP1, if present, is -nPr; and is optionally substituted with one or more groups -RPP2. (127) A compound according to any one of (1) to (119), wherein -RP1, if present, is -Me; and is optionally substituted with one or more groups -RPP2.

[0369] (128) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu.

[0370] (129) A compound according to any one of (1) to (119), wherein -RP1, if present, is independently -Me, -Et, or -nPr.

[0371] (130) A compound according to any one of (1) to (119), wherein -RP1, if present, is -Et.

[0372] (131) A compound according to any one of (1) to (119), wherein -RP1, if present, is -nPr.

[0373] (132) A compound according to any one of (1) to (119), wherein -RP1, if present, is -Me.

[0374] (133) A compound according to any one of (1) to (119), wherein -RP1, if present, is selected from groups of the following structural formula: wherein RP1Ris -H or CM alkyl which is optionally substituted with one group RPP2.

[0375] (134) A compound according to any one of (1) to (119), wherein -RP1, if present, is selected from groups of the following structural formula: wherein RP1Ris -Me or -Et and is substituted with one group RPP2.

[0376] The Group -RP2

[0377] (135) A compound according to any one of (1) to (134), wherein each -RP2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0378] (136) A compound according to any one of (1) to (134), wherein each -RP2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0379] (137) A compound according to any one of (1) to (134), wherein each -RP2, if present, is independently cyclopropyl, and is substituted with one group RPP2. (138) A compound according to any one of (1) to (134), wherein each -RP2, if present, is independently cyclopropyl.

[0380] The Group -RP3

[0381] (139) A compound according to any one of (1) to (138), wherein each -RP3, if present, is independently oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, or diazepanyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; or -RP3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0382] (140) A compound according to any one of (1) to (138), wherein each -RP3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; or -RP3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7- thieno[3,4-c(]imidazolyl.

[0383] (141) A compound according to any one of (1) to (138), wherein each -RP3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; or -RP3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0384] (142) A compound according to any one of (1) to (138), wherein each -RP3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl; or -RP3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0385] (143) A compound according to any one of (1) to (138), wherein each -RP3, if present, is pyrrolidinyl.

[0386] (144) A compound according to any one of (1) to (138), wherein each -RP3, if present, is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl.

[0387] The group (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-c(]imidazolyl is a radical of a compound having the following structure:

[0388] For the avoidance of doubt, this group is intended to be covered by the definition of “non-aromatic Ca-sheterocyclyl”, for example, as recited for the group -RP3. The -RP4

[0389] (145) A compound according to any one of (1) to (144), wherein each -RP4, if present, is phenyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0390] (146) A compound according to any one of (1) to (144), wherein each -RP4, if present, is phenyl, and is substituted with one or more groups -RPP2.

[0391] (147) A compound according to any one of (1) to (144), wherein each -RP4, if present, is phenyl, and is substituted with one group -RPP2.

[0392] (148) A compound according to any one of (1) to (144), wherein each -RP4, if present, is phenyl, and is substituted with two groups -RPP2.

[0393] (149) A compound according to any one of (1) to (144), wherein each -RP4, if present, is phenyl.

[0394] The Group -RP5

[0395] (150) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzoimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzothiazolyl, benzisoxazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, quinazolinyl, or phthalazinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0396] (151) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0397] (152) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently:

[0398] (a) pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; or

[0399] (b) thienyl, thiazolyl, or tetrazolyl. (153) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, or tetrazolyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0400] (154) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2.

[0401] (155) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently thienyl, thiazolyl, tetrazolyl, pyridyl, or pyrimidinyl.

[0402] (156) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0403] (157) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently thienyl, thiazolyl, or tetrazolyl.

[0404] (158) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently thiazolyl optionally substituted with one or more groups RPP1and one or more groups RPP2.

[0405] (159) A compound according to any one of (1) to (149), wherein each -RP5, if present, is independently pyridyl optionally substituted with one or more groups RPP1and one or more groups RPP2.

[0406] The Group -Lp-

[0407] (160) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-, and is optionally substituted with one group selected from -OH, -ORPL, -NH2, -NHRPL, and -NRPL2.

[0408] (161) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2or -CH2-, and is optionally substituted with one group selected from -OH, -ORPL, -NH2, -NHRPL, and -NRPL2.

[0409] (162) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2or -CH2-, and is optionally substituted with one group selected from -NH2, -NHRPL, and -NRPL2. (163) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-, and is substituted with -NH2.

[0410] (164) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2or -CH2-, and is substituted with -NH2.

[0411] (165) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0412] (166) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is independently -CH2CH2- or -CH2-.

[0413] (167) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is -CH2CH2-.

[0414] (168) A compound according to any one of (1) to (159), wherein each -Lp-, if present, is -CH2-.

[0415] The Group -RPP1

[0416] (169) A compound according to any one of (1) to (168), wherein each -RPP1, if present, is independently -Rpp, -LPP-OH, or -Lpp-ORpp.

[0417] (170) A compound according to any one of (1) to (168), wherein each -RPP1, if present, is -Rpp.

[0418] The Group -RPP2

[0419] (171) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0420] -F, -Cl, -Br, -I,

[0421] -OH, -ORPP,

[0422] -CF3, -CHF2, -OCF3, -OCHF2,

[0423] -NH2, -NHRPP, -N(RPP)2, -RPM,

[0424] -C(=O)OH, -C(=O)ORPP, -OC(=O)RPP,

[0425] -C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2, -C(=O)RPM,

[0426] -NHC(=O)RPP, -NRPNC(=O)RPP,

[0427] -NHC(=O)NH2, -NHC(=O)NHRPP, -NHC(=O)N(RPP)2, -NHC(=O)RPM, -NRPNC(=O)NH2, -NRPNC(=O)NHRPP, -NRPNC(=O)N(RPP)2, -NRPNC(=O)RPM, -NHC(=O)ORPP, -NRPNC(=O)ORPP,

[0428] -OC(=O)NH2, -OC(=O)NHRPP, -OC(=O)N(RPP)2, -OC(=O)RPM,

[0429] -C(=O)RPP,

[0430] -SH, -SRPP, -CN, and -NO2.

[0431] (172) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0432] -F, -Cl,

[0433] -OH, -ORPP,

[0434] -CF3, -CHF2,

[0435] -NH2, -NHRPP, -N(RPP)2, -RPM,

[0436] -C(=O)OH, -C(=O)ORPP, -OC(=O)RPP,

[0437] -C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2, -C(=O)RPM,

[0438] -NHC(=O)RPP, -NRPNC(=O)RPP,

[0439] -C(=O)RPP, and

[0440] -CN.

[0441] (173) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0442] -OH, -ORPP,

[0443] -NH2, -NHRPP, -N(RPP)2,

[0444] -C(=O)OH, -C(=O)ORPP,

[0445] -C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2,

[0446] -NHC(=O)RPP, -NRPNC(=O)Rpp,and -CN.

[0447] (174) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0448] -OH, -NH2, -NHRPP, -N(RPP)2, and -C(=O)OH.

[0449] (175) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0450] -OH, -NH2, and -C(=O)OH.

[0451] (176) A compound according to any one of (1) to (170), wherein each -RPP2, if present, is independently selected from:

[0452] -OH and -NH2. The Group -RPL

[0453] (177) A compound according to any one of (1) to (176), wherein each -RPL, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0454] (178) A compound according to any one of (1) to (176), wherein each -RPL, if present, is independently -Me, -Et, -nPr, or -iPr.

[0455] (179) A compound according to any one of (1) to (176), wherein each -RPL, if present, is independently -Me or -Et.

[0456] (180) A compound according to any one of (1) to (176), wherein each -RPL, if present, is -Me.

[0457] The Group -Rpp

[0458] (181) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0459] (182) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is independently linear or branched saturated Ci-4alkyl.

[0460] (183) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu.

[0461] (184) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is independently -Me, -Et, -nPr, or -iPr.

[0462] (185) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is independently -Me or -Et.

[0463] (186) A compound according to any one of (1) to (180), wherein each -Rpp, if present, is -Me.

[0464] The Group -RPN

[0465] (187) A compound according to any one of (1) to (186), wherein each -RPN, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu. (188) A compound according to any one of (1) to (186), wherein each -RPN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0466] (189) A compound according to any one of (1) to (186), wherein each -RPN, if present, is independently -Me or -Et.

[0467] (190) A compound according to any one of (1) to (186), wherein each -RPN, if present, is -Me.

[0468] The Group -RPM

[0469] (191) A compound according to any one of (1) to (190), wherein each -RPM, if present, is independently azetidino, pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[0470] -RPMM, -C(=O)RPMM, -C(=O)ORPMM, and -S(=O)2RPMM

[0471] (192) A compound according to any one of (1) to (190), wherein each -RPM, if present, is independently azetidino, pyrrolidino, piperidino, piperazino, or morpholino.

[0472] (193) A compound according to any one of (1) to (190), wherein each -RPM, if present, is independently pyrrolidino or piperidino.

[0473] The Group -Lpp-

[0474] (194) A compound according to any one of (1) to (193), wherein each -Lpp-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0475] (195) A compound according to any one of (1) to (193), wherein each -Lpp-, if present, is independently -CH2CH2or -CH2-.

[0476] (196) A compound according to any one of (1) to (193), wherein each -Lpp-, if present, is -CH2CH2-.

[0477] (197) A compound according to any one of (1) to (193), wherein each -Lpp-, if present, is -CH2-.

[0478] The Group -RPMM

[0479] (198) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl. (199) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is independently linear or branched saturated Ci-4alkyl.

[0480] (200) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is independently -Me, - Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0481] (201) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is independently -Me, -Et, -nPr, or -iPr.

[0482] (202) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is independently -Me or -Et

[0483] (203) A compound according to any one of (1) to (197), wherein each -RPMM, if present, is -Me.

[0484] The Group -RN

[0485] (204) A compound according to any one of (1) to (203), wherein -RNis -H.

[0486] (205) A compound according to any one of (1) to (203), wherein -RNis -RNN.

[0487] The Group -RNN

[0488] (206) A compound according to any one of (1) to (205), wherein each -RNN, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, or -tBu.

[0489] (207) A compound according to any one of (1) to (205), wherein each -RNN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0490] (208) A compound according to any one of (1) to (205), wherein each -RNN, if present, is independently -Me or -Et.

[0491] (209) A compound according to any one of (1) to (205), wherein each -RNN, if present, is -Me.

[0492] The Group -A

[0493] (210) A compound according to any one of (1) to (209), wherein -A is -Ac.

[0494] (211) A compound according to any one of (1) to (209), wherein -A is -AH. The Group -Ac

[0495] (212) A compound according to any one of (1) to (211), wherein -Ac, if present, is phenyl or naphthyl, and is optionally substituted with 1 , 2, or 3 substituents -Rx.

[0496] (213) A compound according to any one of (1) to (211), wherein -Ac, if present, is phenyl, and is optionally substituted with one or more substituents -Rx.

[0497] (214) A compound according to any one of (1) to (211), wherein -Ac, if present, is phenyl, and is optionally substituted with 1 , 2, or 3 substituents -Rx.

[0498] (215) A compound according to any one of (1) to (211), wherein -Ac, if present, is independently selected from: wherein each -RX1, -RX2, -RX3, -RX4, and -RX5, is independently as defined for -Rx. (216) A compound according to any one of (1) to (211), wherein -Ac, if present, is independently selected from: wherein each -RX1, -RX2, -RX3, -RX4, and -RX5is independently as defined for -Rx.

[0499] (217) A compound according to any one of (1) to (211), wherein -Ac, if present, is independently selected from: wherein each -RX1, -RX2, and -RX3is independently as defined for -Rx.

[0500] (218) A compound according to any one of (1) to (211), wherein -Ac, if present, is independently selected from: wherein each -RX1, -RX2, and -RX3is independently as defined for -Rx. (219) A compound according to any one of (1) to (211), wherein -Ac, if present, is: wherein -RX1is independently as defined for -Rx.

[0501] (220) A compound according to any one of (1) to (211), wherein -Ac, if present, is: wherein -RX2is independently as defined for -Rx.

[0502] (221) A compound according to any one of (1) to (211), wherein -Ac, if present, is: wherein -RX3is independently as defined for -Rx.

[0503] (222) A compound according to any one of (1) to (211), wherein -Ac, if present, is phenyl.

[0504] (223) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphthyl, and is optionally substituted with one or more substituents -Rx.

[0505] (224) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphthyl, and is optionally substituted with 1 , 2, or 3 substituents -Rx.

[0506] (225) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphthyl.

[0507] (226) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphth-1-yl, and is optionally substituted with one or more substituents -Rx.

[0508] (227) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphth-2-yl, and is optionally substituted with one or more substituents -Rx. naphth-1-yl naphth-2-yl

[0509] (228) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphth-1-yl.

[0510] (229) A compound according to any one of (1) to (211), wherein -Ac, if present, is naphth-2-yl.

[0511] The Group -AH

[0512] (230) A compound according to any one of (1) to (229), wherein -AH, if present, is Cs-wheteroaryl, and is optionally substituted with one or more substituents -Rx.

[0513] (231) A compound according to any one of (1) to (229), wherein -AH, if present, is Cs-wheteroaryl, and is optionally substituted with 1 , 2, or 3 substituents -Rx.

[0514] (232) A compound according to any one of (1) to (229), wherein -AH, if present, is Cs-sheteroaryl or Cg-wheteroaryl, and is optionally substituted with one or more substituents -Rx.

[0515] (233) A compound according to any one of (1) to (229), wherein -AH, if present, is furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, thienylpyridinyl, thienylthiophenyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, or benzopyranyl, and is optionally substituted with one or more substituents -Rx.

[0516] (234) A compound according to any one of (1) to (229), wherein -AH, if present, is furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, or benzopyranyl, and is optionally substituted with one or more substituents -Rx. (235) A compound according to any one of (1) to (229), wherein -AH, if present, is thienyl, thiazolyl, or thienothiophenyl, and is optionally substituted with one or more substituents -Rx.

[0517] Monocyclic groups:

[0518] (236) A compound according to any one of (1) to (229), wherein -AH, if present, is furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more substituents -Rx.

[0519] (237) A compound according to any one of (1) to (229), wherein -AH, if present, is pyridyl, thienyl, or thiazolyl, and is optionally substituted with one or more substituents -Rx.

[0520] (238) A compound according to any one of (1) to (229), wherein -AH, if present, is thienyl, and is optionally substituted with one or more substituents -Rx.

[0521] (239) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX2, -RX3, -RX4, and -RX5is independently as defined for -Rx. (240) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX3, -RX4, and -RX5is independently as defined for -Rx.

[0522] (241) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX2, -RX3, -RX4, and -RX5is independently as defined for -Rx.

[0523] (242) A compound according to any one of (1) to (229), wherein -AH, if present, is thien-2-yl, and is optionally substituted with one or more substituents -Rx.

[0524] (243) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX3, -RX4, and -RX5is independently as defined for -Rx.

[0525] (244) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX3and -RX4is independently as defined for -Rx. (245) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX3and -RX4is independently as defined for -Rx.

[0526] (246) A compound according to any one of (1) to (229), wherein -AH, if present, is: wherein -RX4is independently as defined for -Rx.

[0527] (247) A compound according to any one of (1) to (229), wherein -AH, if present, is thien-3-yl, and is optionally substituted with one or more substituents -Rx.

[0528] (248) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX2, -RX4, and -RX5is independently as defined for -Rx.

[0529] (249) A compound according to any one of (1) to (229), wherein -AH, if present, is: wherein -RX5is as defined for -Rx.

[0530] (250) A compound according to any one of (1) to (229), wherein -AH, if present, is thiazolyl, and is optionally substituted with one or more substituents -Rx. (251) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from:

[0531] (252) A compound according to any one of (1) to (229), wherein -AH, if present, is thiazol-2-yl, and is optionally substituted with one or more substituents -Rx.

[0532] (253) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX4and -RX5are independently as defined for -Rx.

[0533] (254) A compound according to any one of (1) to (229), wherein -AH, if present, is thiazol-4-yl, and is optionally substituted with one or more substituents -Rx.

[0534] (255) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: wherein each -RX2and -RX5are independently as defined for -Rx.

[0535] (256) A compound according to any one of (1) to (229), wherein -AH, if present, is thiazol-5-yl, and is optionally substituted with one or more substituents -Rx. (257) A compound according to any one of (1) to (229), wherein -AH, if present, is independently selected from: , wherein each -RX2and -RX4are independently as defined for -Rx.

[0536] (258) A compound according to any one of (1) to (229), wherein -AH, if present, is independently pyrazolyl or imidazolyl, and is optionally substituted with one or more substituents -Rx.

[0537] (259) A compound according to any one of (1) to (229), wherein -AH, if present, is pyrazolyl, and is optionally substituted with one or more substituents -Rx.

[0538] (260) A compound according to any one of (1) to (229), wherein -AH, if present, is independently 1 H-pyrazol-3-yl, 1 H-pyrazol-4-yl, 1 H-pyrazol-5-yl, or pyrazol-1-yl, and is optionally substituted with one or more substituents -Rx.

[0539] (261) A compound according to any one of (1) to (229), wherein -AH, if present, is 1 H-pyrazol-3-yl, and is optionally substituted with one or more substituents -Rx.

[0540] 1 H-pyrazol-3-yl 1 H-pyrazol-4-yl

[0541] 1 H-pyrazol-5-yl pyrazol-1-yl

[0542] (262) A compound according to any one of (1) to (229), wherein -AH, if present, is imidazolyl, and is optionally substituted with one or more substituents -Rx.

[0543] (263) A compound according to any one of (1) to (229), wherein -AH, if present, is independently 1 H-imidazol-2-yl, 1 H-imidazol-5-yl, 1 H-imidazol-4-yl, or imidazol-1-yl, and is optionally substituted with one or more substituents -Rx.

[0544] 1 H-imidazol-2-yl 1 H-imidazol-5-yl

[0545] 1 H-imidazol-4-yl imidazol-1-yl

[0546] (264) A compound according to any one of (1) to (229), wherein -AH, if present, is pyridyl, and is optionally substituted with one or more substituents -Rx.

[0547] (265) A compound according to any one of (1) to (229), wherein -AH, if present, is pyrid-2-yl, and is optionally substituted with one or more substituents -Rx.

[0548] (266) A compound according to any one of (1) to (229), wherein -AH, if present, is pyrid-3-yl, and is optionally substituted with one or more substituents -Rx.

[0549] (267) A compound according to any one of (1) to (229), wherein -AH, if present, is pyrid-4-yl, and is optionally substituted with one or more substituents -Rx. pyrid-2-yl pyrid-3-yl pyrid-4-yl

[0550] Fused Bicyclic Groups:

[0551] (268) A compound according to any one of (1) to (229), wherein -AH, if present, is indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, thienylpyridinyl, thienylthiophenyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, or benzopyranyl, and is optionally substituted with one or more substituents -Rx.

[0552] (269) A compound according to any one of (1) to (229), wherein -AH, if present, is indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzisoxazolyl, benzothiazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, or benzopyranyl, and is optionally substituted with one or more substituents -Rx. (270) A compound according to any one of (1) to (229), wherein -AH, if present, is indolyl, benzimidazolyl, indazolyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, quinazolinyl, or quinoxalinyl, and is optionally substituted with one or more substituents -Rx.

[0553] (271) A compound according to any one of (1) to (229), wherein -AH, if present, is benzofuranyl, benzothienyl, quinolinyl, or isoquinolinyl, and is optionally substituted with one or more substituents -Rx.

[0554] (272) A compound according to any one of (1) to (229), wherein -AH, if present, is benzofuranyl or benzothienyl, and is optionally substituted with one or more substituents -Rx.

[0555] (273) A compound according to any one of (1) to (229), wherein -AH, if present, is benzothienyl, and is optionally substituted with one or more substituents -Rx.

[0556] (274) A compound according to any one of (1) to (229), wherein -AH, if present, is benzothien-2-yl, and is optionally substituted with one or more substituents -Rx.

[0557] (275) A compound according to any one of (1) to (229), wherein -AH, if present, is benzothien-3-yl, and is optionally substituted with one or more substituents -Rx. benzothien-2-yl benzothien-3-yl

[0558] (276) A compound according to any one of (1) to (229), wherein -AH, if present, is benzothiazolyl, and is optionally substituted with one or more substituents -Rx.

[0559] (277) A compound according to any one of (1) to (229), wherein -AH, if present, is

[0560] 1.2-benzothiazol-3-yl, and is optionally substituted with one or more substituents -Rx.

[0561] (278) A compound according to any one of (1) to (229), wherein -AH, if present, is

[0562] 1.3-benzothiazol-2-yl, and is optionally substituted with one or more substituents -Rx.

[0563] 1 ,2-benzothiazol-3-yl 1 ,3-benzothiazol-2-yl

[0564] (279) A compound according to any one of (1) to (229), wherein -AH, if present, is thienopyridinyl, and is optionally substituted with one or more substituents -Rx.

[0565] (280) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]pyridi nyl, and is optionally substituted with one or more substituents -Rx.

[0566] (281) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]pyridin-2-yl, and is optionally substituted with one or more substituents -Rx.

[0567] (282) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]pyridin-3-yl, and is optionally substituted with one or more substituents -Rx. thieno[3,2-b]pyridin-2-yl thieno[3,2-b]pyridin-3-yl

[0568] (283) A compound according to any one of (1) to (229), wherein -AH, if present, is thienothiophenyl, and is optionally substituted with one or more substituents -Rx.

[0569] (284) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]thiophenyl, and is optionally substituted with one or more substituents -Rx.

[0570] (285) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]thiophen-5-yl, and is optionally substituted with one or more substituents -Rx.

[0571] (286) A compound according to any one of (1) to (229), wherein -AH, if present, is thieno[3,2-b]thiophen-6-yl, and is optionally substituted with one or more substituents -Rx. thieno[3,2-b]thiophen-5-yl thieno[3,2-b]thiophen-6-yl (287) A compound according to any one of (1) to (229), wherein -AH, if present, is quinolinyl, and is optionally substituted with one or more substituents -Rx.

[0572] (288) A compound according to any one of (1) to (229), wherein -AH, if present, is quinolin-7-yl, and is optionally substituted with one or more substituents -Rx.

[0573] The Group(s) -Rx

[0574] (289) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0575] -Rxx,

[0576] -F, -Cl, -Br, -I,

[0577] -OH, -OR™,

[0578] -L™-OH, -L™-OR™,

[0579] -CF3, -CHF2, -OCF3, -OCHF2,

[0580] -NH2, -NHR™, -NR™2, -RXM,

[0581] -L™-NH2I-L™-NHR™, -L™-NR™2, -L™-RXM,

[0582] -C(=O)OH, -C(=O)OR™, -OC(=O)RXX,

[0583] -C(=O)NH2, -C(=O)NHRXX, -C(=O)NRXX2, -C(=O)RXM,

[0584] -NHC(=O)R™, -NRXNC(=O)RXX,

[0585] -NHC(=O)NH2, -NHC(=O)NHRXX, -NHC(=O)NRXX2, -NHC(=O)RXM,

[0586] -NRXNC(=O)NH2, -NRXNC(=O)NHRXX, -NRXNC(=O)NRXX2, -NRXNC(=O)RXM,

[0587] -NHC(=O)ORXX, -NRXNC(=O)OR™,

[0588] -OC(=O)NH2, -OC(=O)NHRXX, -OC(=O)NRXX2, -OC(=O)RXM,

[0589] -NHC(=NH)NH2,

[0590] -C(=O)R™,

[0591] -S(=O)NH2, -S(=O)NHRXX, -S(=O)NRXX2, -S(=O)RXM,

[0592] -S(=O)2NH2, -S(=O)2NHRXX, -S(=O)2NRXX2, -S(=O)2RXM,

[0593] -NHS(=O)RXX, -NRXNS(=O)RXX,

[0594] -NHS(=O)2RXX, -NRXNS(=O)2RXX,

[0595] -S(=O)RXX, -S(=O)2RXX,

[0596] -SH, -SRXX, -ON, and -NO2; and additionally, two adjacent groups -Rx, if present, may together form: -O-CH2-O-, -O-CH2CH2-O-, -CH2-CH2-O-, -CH2-CH2CH2-O-, -CH2-O-CH2-, or -CH2-CH2-O-CH2-. (290) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0597] _RXX _RXXU _RXXV

[0598] -F, -Cl, -Br, -I,

[0599] -OH, -OR™,

[0600] -CF3, -CHF2, -OCF3, -OCHF2,

[0601] -NH2, -NHR™, -NRXX2, -RXM,

[0602] -C(=O)OH, -C(=O)OR™, -OC(=O)RXX,

[0603] -C(=O)NH2, -C(=O)NHRXX, -C(=O)NRXX2, -C(=O)RXM,

[0604] -NHC(=O)R™, -NRXNC(=O)RXX,

[0605] -C(=O)R™,

[0606] -S(=O)NH2, -S(=O)NHRXX, -S(=O)NRXX2, -S(=O)RXM,

[0607] -S(=O)2NH2, -S(=O)2NHRXX, -S(=O)2NRXX2, -S(=O)2RXM,

[0608] -NHS(=O)RXX, -NRXNS(=O)RXX,

[0609] -NHS(=O)2RXX, -NRXNS(=O)2RXX,

[0610] -S(=O)RXX, -S(=O)2RXX,

[0611] -SR™, -ON, and -NO2.

[0612] (291) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0613] _RXX _RXXU _RXXV

[0614] -F, -Cl, -Br, -I,

[0615] -OH, -OR™,

[0616] -CF3, -CHF2, -OCF3, -OCHF2,

[0617] -NH2, -NHR™, -NR™2, -RXM,

[0618] -C(=O)OH, -C(=O)OR™, -OC(=O)R™,

[0619] -SR™, -CN, and -NO2.

[0620] (292) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0621] _RXX _RXXU

[0622] -F, -Cl, -Br,

[0623] -OH, -OR™,

[0624] -CF3, -CHF2, -OCF3, -OCHF2,

[0625] -C(=O)NH2, -C(=O)NHR™, -C(=O)NR™2, -C(=O)RXM,

[0626] -C(=O)R™, and

[0627] -CN; and additionally, two adjacent groups -Rx, if present, may together form: -O-CH2-O- or -CH2-CH2-O-. (293) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0628] -Rxx,

[0629] -F, -Cl, -Br, -I,

[0630] -OH, -OR™,

[0631] -CF3, -CHF2, -OCF3, -OCHF2,

[0632] -NH2, -NHR™, -NRXX2, -RXM, and

[0633] -CN.

[0634] (294) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0635] -Rxx,

[0636] -F, -Cl, -Br, -I,

[0637] -OH, -OR™,

[0638] -CF3, -CHF2, -OCF3, and -OCHF2.

[0639] (295) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0640] -Rxx,

[0641] -F, -Cl, -Br, and -I.

[0642] (296) A compound according to any one of (1) to (288), wherein each -Rx, if present, is independently selected from:

[0643] -F, and -Cl.

[0644] (297) A compound according to any one of (1) to (288), wherein each -Rx, if present, is -Cl.

[0645] Some Preferred Combinations of -A and -Rx

[0646] (298) A compound according to any one of (1) to (288), wherein -AH, if present, is: wherein -RX4is -Cl. (299) A compound according to any one of (1) to (288), wherein -Ac, if present, is: wherein -RX2is -Cl.

[0647] The Group -

[0648] (300) A compound according to any one of (1) to (299), wherein each -L^-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0649] (301) A compound according to any one of (1) to (299), wherein each -L^-, if present, is independently -CH2CH2- or -CH2-.

[0650] (302) A compound according to any one of (1) to (299), wherein each -L^-, if present, is -CH2-.

[0651] The Group -Rxx

[0652] (303) A compound according to any one of (1) to (302), wherein each -Rxx, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0653] (304) A compound according to any one of (1) to (302), wherein each -Rxx, if present, is linear or branched saturated Ci-4alkyl.

[0654] (305) A compound according to any one of (1) to (302), wherein each -Rxx, if present, is -Me.

[0655] The Group -R^

[0656] (306) A compound according to any one of (1) to (305), wherein each -R^, if present, is independently -CH=CH2or -CH2-CH=CH2.

[0657] (307) A compound according to any one of (1) to (305), wherein each -R50^, if present, is -CH=CH2.

[0658] The Group -Rxxy

[0659] (308) A compound according to any one of (1) to (307), wherein each -Rxxv, if present, is independently -CHECH or -CH2-C=CH. (309) A compound according to any one of (1) to (307), wherein each -Rxxv, if present, is -CHECH.

[0660] The Group -RXN

[0661] (310) A compound according to any one of (1) to (309), wherein each -RXN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0662] (311) A compound according to any one of (1) to (309), wherein each -RXN, if present, is -Me.

[0663] The Group -RXM

[0664] (312) A compound according to any one of (1) to (311), wherein each -RXM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[0665] -RXMM, -C(=O)RXMM, -C(=O)ORXMM, and -S(=O)2RXMM

[0666] (313) A compound according to any one of (1) to (311), wherein each -RXM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino.

[0667] The Group -RXMM

[0668] (314) A compound according to any one of (1) to (313), wherein each -RXMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0669] (315) A compound according to any one of (1) to (313), wherein each -RXMM, if present, is linear or branched saturated Ci-4alkyl.

[0670] (316) A compound according to any one of (1) to (313), wherein each -RXMM, if present, is -Me.

[0671] The Group -R1

[0672] (317) A compound according to any one of (1) to (316), wherein -R1is -R11.

[0673] (318) A compound according to any one of (1) to (316), wherein -R1is -H. The Group -R11

[0674] (319) A compound according to any one of (1) to (318), wherein -R11, if present, is -R11A.

[0675] (320) A compound according to any one of (1) to (318), wherein -R11, if present, is -R11B.

[0676] The Group -R11A

[0677] (321) A compound according to any one of (1) to (320), wherein -R11A, if present, is independently -RA1, -RA4, -LA-RA2, -LA-RA4, or -LA-RA5.

[0678] (322) A compound according to any one of (1) to (320), wherein -R11A, if present, is independently -RA1, -LA-RA2, -LA-RA4, or -LA-RA5.

[0679] (323) A compound according to any one of (1) to (320), wherein -R11A, if present, is independently -RA1or -LA-RA2.

[0680] (324) A compound according to any one of (1) to (320), wherein -R11A, if present, is -RA1.

[0681] (325) A compound according to any one of (1) to (320), wherein -R11A, if present, is -LA-RA2.

[0682] (326) A compound according to any one of (1) to (320), wherein -R11A, if present, is -LA-RA4.

[0683] (327) A compound according to any one of (1) to (320), wherein -R11A, if present, is -LA-RA5.

[0684] The Group -RA1

[0685] (328) A compound according to any one of (1) to (327), wherein -RA1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu; and is optionally substituted with one or more groups -RAA2.

[0686] (329) A compound according to any one of (1) to (327), wherein -RA1, if present, is -iBu; and is optionally substituted with one or more groups -RM2.

[0687] (330) A compound according to any one of (1) to (327), wherein -RA1, if present, is -sBu; and is optionally substituted with one or more groups -RM2. (331) A compound according to any one of (1) to (327), wherein -RA1, if present, is -iPr; and is optionally substituted with one or more groups -RM2.

[0688] (332) A compound according to any one of (1) to (327), wherein -RA1, if present, is -Me; and is optionally substituted with one or more groups -RM2.

[0689] (333) A compound according to any one of (1) to (327), wherein -RA1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu.

[0690] (334) A compound according to any one of (1) to (327), wherein -RA1, if present, is independently -iPr, -iBu, or -sBu.

[0691] (335) A compound according to any one of (1) to (327), wherein -RA1, if present, is -iBu.

[0692] (336) A compound according to any one of (1) to (327), wherein -RA1, if present, is -sBu.

[0693] (337) A compound according to any one of (1) to (327), wherein -RA1, if present, is -iPr.

[0694] (338) A compound according to any one of (1) to (327), wherein -RA1, if present, is -Me.

[0695] The Group -RA2

[0696] (339) A compound according to any one of (1) to (338), wherein each -RA2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and is optionally substituted with one or more groups -RM1and one or more groups -RAA2.

[0697] (340) A compound according to any one of (1) to (338), wherein each -RA2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0698] (341) A compound according to any one of (1) to (338), wherein each -RA2, if present, is independently cyclopropyl.

[0699] The Group -RA3

[0700] (342) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, or diazepanyl, and is optionally substituted with one or more groups -RM1and one or more groups -RAA2.

[0701] (343) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RM1and one or more groups -RAA2.

[0702] (344) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, or dioxanyl, and is optionally substituted with one or more groups -RM1and one or more groups -RAA2.

[0703] (345) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2.

[0704] (346) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl.

[0705] (347) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, or dioxanyl.

[0706] (348) A compound according to any one of (1) to (341), wherein each -RA3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl.

[0707] The Group -RA4

[0708] (349) A compound according to any one of (1) to (348), wherein each -RA4, if present, is phenyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2.

[0709] (350) A compound according to any one of (1) to (348), wherein each -RA4, if present, is phenyl.

[0710] The Group -RA5

[0711] (351) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzoimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzothiazolyl, benzisoxazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, quinazolinyl, or phthalazinyl, and is optionally substituted with one or more groups -RAA1and one or more groups -RAA2. (352) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2.

[0712] (353) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, or isothiazolyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2.

[0713] (354) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2.

[0714] (355) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently imidazolyl or indolyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2.

[0715] (356) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0716] (357) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, or isothiazolyl.

[0717] (358) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0718] (359) A compound according to any one of (1) to (350), wherein each -RA5, if present, is independently imidazolyl or indolyl.

[0719] The Group -LA-

[0720] (360) A compound according to any one of (1) to (359), wherein each -LA-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0721] (361) A compound according to any one of (1) to (359), wherein each -LA-, if present, is independently -CH2CH2or -CH2-. (362) A compound according to any one of (1) to (359), wherein each -LA-, if present, is -CH2-.

[0722] The Group -RM1

[0723] (363) A compound according to any one of (1) to (362), wherein each -RAA1, if present, is -RAA.

[0724] The Group -RM2

[0725] (364) A compound according to any one of (1) to (363), wherein each -RAA2, if present, is independently selected from:

[0726] -F, -Cl, -Br, -I,

[0727] -OH, -OR™,

[0728] -OCF3,

[0729] -NH2, -NHR™, -N(R™)2, -RAM,

[0730] -C(=O)OH, -C(=O)OR™, -OC(=O)RAA,

[0731] -C(=O)NH2, -C(=O)NHRAA, -C(=O)N(RAA)2, -C(=O)RAM,

[0732] -NHC(=O)R™, -NRANC(=O)RAA,

[0733] -C(=O)R™,

[0734] -S(=O)NH2, -S(=O)NHRAA, -S(=O)N(RAA)2, -S(=O)RAM,

[0735] -S(=O)2NH2, -S(=O)2NHRAA, -S(=O)2N(RAA)2, -S(=O)2RAM,

[0736] -NHS(=O)RAA, -NRANS(=O)RAA,

[0737] -NHS(=O)2RAA, -NRANS(=O)2RAA,

[0738] -S(=O)RAA, -S(=O)2RAA,

[0739] -SH, -SRAA, -ON, and -NO2.

[0740] (365) A compound according to any one of (1) to (363), wherein each -R™2, if present, is independently selected from:

[0741] -F, -Cl, -Br, -I,

[0742] -OH, -OR™,

[0743] -OCF3,

[0744] -NH2, -NHR™, -N(R™)2, -RAM, and

[0745] -CN. (366) A compound according to any one of (1) to (363), wherein each -RAA2, if present, is independently selected from:

[0746] -F, -Cl, -Br, -I,

[0747] -OH, -OR™, and

[0748] -OCF3.

[0749] (367) A compound according to any one of (1) to (363), wherein each -R™2, if present, is independently selected from:

[0750] -OH, -OR™,

[0751] -NH2, -NHR™, -N(R™)2, -RAM,

[0752] -C(=O)OH, -C(=O)OR™,

[0753] -C(=O)NH2, -C(=O)NHR™, -C(=O)N(R™)2, -C(=O)RAM,

[0754] -NHC(=NH)NH2,

[0755] -SH, and -SR™.

[0756] (368) A compound according to any one of (1) to (363), wherein each -R™2, if present, is independently selected from:

[0757] -OH,

[0758] -NH2,

[0759] -C(=O)OH,

[0760] -C(=O)NH2,

[0761] -NHC(=NH)NH2, -SH, and -SMe.

[0762] The Group -L™-

[0763] (369) A compound according to any one of (1) to (368), wherein each -L™-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0764] (370) A compound according to any one of (1) to (368), wherein each -L™-, if present, is independently -CH2CH2or -CH2-.

[0765] The Group -RAA

[0766] (371) A compound according to any one of (1) to (370), wherein each -RAA, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl. (372) A compound according to any one of (1) to (370), wherein each -RAA, if present, is linear or branched saturated Ci-4alkyl.

[0767] (373) A compound according to any one of (1) to (370), wherein each -RAA, if present, is -Me.

[0768] The Group -RAN

[0769] (374) A compound according to any one of (1) to (373), wherein each -RAN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0770] (375) A compound according to any one of (1) to (373), wherein each -RAN, if present, is -Me.

[0771] The Group -RAM

[0772] (376) A compound according to any one of (1) to (375), wherein each -RAM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[0773] -RAMM, -C(=O)RAMM, -C(=O)ORAMM, and -S(=O)2RAMM

[0774] (377) A compound according to any one of (1) to (375), wherein each -RAM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino.

[0775] The Group -RAMM

[0776] (378) A compound according to any one of (1) to (377), wherein each -RAMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0777] (379) A compound according to any one of (1) to (377), wherein each -RAMM, if present, is linear or branched saturated Ci-4alkyl.

[0778] (380) A compound according to any one of (1) to (377), wherein each -RAMM, if present, is -Me.

[0779] The -R11A: Some

[0780] (381) A compound according to any one of (1) to (320), wherein -R11A, if present, is independently selected from:

[0781] -CH3 (e.g., as in alanine),

[0782] -CH2CH(CH3)2 (e.g., as in leucine), -CH(CH3)CH2CH3 (e.g., as in isoleucine),

[0783] -CH2CH2-S-CH3 (e.g., as in methionine),

[0784] -CH2-(phenyl) (e.g., as in phenylalanine),

[0785] -CH2-(1 H-indol-3-yl) (e.g., as in tryptophan),

[0786] -CH(CH3)2(e.g., as in valine),

[0787] -CH2-C(=O)NH2 (e.g., as in asparagine),

[0788] -CH2-SH (e.g., as in cysteine),

[0789] -CH2CH2-C(=O)NH2 (e.g., as in glutamine),

[0790] -CH2-OH (e.g., as in serine),

[0791] -CH(OH)CH3 (e.g., as in threonine),

[0792] -CH2-(4-hydroxy-phenyl) (e.g., as in tyrosine),

[0793] -CH2CH2CH2-NH-C(=NH)-NH2 (e.g., as in arginine),

[0794] -CH2-(1 H-imidazol-4-yl) (e.g., as in histidine),

[0795] -CH2CH2CH2CH2-NH2 (e.g., as in lysine),

[0796] -CH2-C(=O)OH (e.g., as in aspartic acid), and

[0797] -CH2CH2-C(=O)OH (e.g., as in glutamic acid).

[0798] (382) A compound according to any one of (1) to (320), wherein -R11A, if present, is independently selected from:

[0799] -CH2CH(CH3)2 (e.g., as in leucine),

[0800] -CH(CH3)CH2CH3 (e.g., as in isoleucine),

[0801] -CH(CH3)2(e.g., as in valine).

[0802] (383) A compound according to any one of (1) to (320), wherein -R11A, if present, is -CH2CH(CH3)2 (e.g., as in leucine).

[0803] (384) A compound according to any one of (1) to (320), wherein -R11A, if present, is -CH(CH3)CH2CH3 (e.g., as in isoleucine).

[0804] (385) A compound according to any one of (1) to (320), wherein -R11A, if present, is -CH(CH3)2(e.g., as in valine).

[0805] The Group -R11B

[0806] (386) A compound according to any one of (1) to (385), wherein -R11B, if present, is independently selected from:

[0807] -F, -Cl, -Br, -I,

[0808] -OH, -ORBB,

[0809] -OCF3,

[0810] -NH2, -NHRBB, -NRBB2, -RBM, -C(=O)OH, -C(=O)ORBB, -OC(=O)RBB,

[0811] -C(=O)NH2, -C(=O)NHRBB, -C(=O)NRBB2, -C(=O)RBM,

[0812] -NHC(=O)RBB, -NRBNC(=O)RBB,

[0813] -C(=O)RBB,

[0814] -S(=O)NH2, -S(=O)NHRBB, -S(=O)NRBB2, -S(=O)RBM,

[0815] -S(=O)2NH2, -S(=O)2NHRBB, -S(=O)2NRBB2, -S(=O)2RBM,

[0816] -NHS(=O)RBB, -NRBNS(=O)RBB,

[0817] -NHS(=O)2RBB, -NRBNS(=O)2RBB,

[0818] -S(=O)RBB, -S(=O)2RBB,

[0819] -SRBB, -CN, and -NO2.

[0820] (387) A compound according to any one of (1) to (385), wherein each -R11B, if present, is independently selected from:

[0821] -F, -Cl, -Br, -I,

[0822] -OH, -ORBB,

[0823] -OCF3,

[0824] -NH2, -NHRBB, -NRBB2, -RBM,

[0825] -SRBB, and -CN.

[0826] (388) A compound according to any one of (1) to (385), wherein each -R11B, if present, is independently selected from:

[0827] -F, -Cl, -Br, -I,

[0828] -OH, -ORBB,

[0829] -OCF3, and

[0830] -SRBB.

[0831] (389) A compound according to any one of (1) to (385), wherein each -R11B, if present, is independently selected from:

[0832] -F, -Cl, -Br, -I, -OH, -ORBB, and -OCF3.

[0833] The Group -RBB

[0834] (390) A compound according to any one of (1) to (389), wherein each -RBB, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl. (391) A compound according to any one of (1) to (389), wherein each -RBB, if present, is linear or branched saturated Ci-4alkyl.

[0835] (392) A compound according to any one of (1) to (389), wherein each -RBB, if present, is -Me.

[0836] The Group -RBN

[0837] (393) A compound according to any one of (1) to (392), wherein each -RBN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0838] (394) A compound according to any one of (1) to (392), wherein each -RBN, if present, is -Me.

[0839] The Group -RBM

[0840] (395) A compound according to any one of (1) to (394), wherein each -RBM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[0841] -RBMM, -C(=O)RBMM, -C(=O)ORBMM, and -S(=O)2RBMM

[0842] (396) A compound according to any one of (1) to (394), wherein each -RBM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino.

[0843] The Group -RBMM

[0844] (397) A compound according to any one of (1) to (396), wherein each -RBMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0845] (398) A compound according to any one of (1) to (396), wherein each -RBMM, if present, is linear or branched saturated Ci-4alkyl.

[0846] (399) A compound according to any one of (1) to (396), wherein each -RBMM, if present, is -Me.

[0847] The Group -R2

[0848] (400) A compound according to any one of (1) to (399), wherein -R2is -H.

[0849] (401) A compound according to any one of (1) to (399), wherein -R2is -R22. The Group -R22

[0850] (402) A compound according to any one of (1) to (401), wherein -R22, if present, is -R22C.

[0851] (403) A compound according to any one of (1) to (401), wherein -R22, if present, is -R22D.

[0852] The Group -R22C

[0853] (404) A compound according to any one of (1) to (403), wherein -R22C, if present, is independently -RC1, -RC4, -LC-RC4, or -Lc-RC5.

[0854] (405) A compound according to any one of (1) to (403), wherein -R22C, if present, is independently -RC1, -LC-RC4, or -Lc-RC5.

[0855] (406) A compound according to any one of (1) to (403), wherein -R22C, if present, is independently -RC1or -Lc-RC4.

[0856] (407) A compound according to any one of (1) to (403), wherein -R22C, if present, is -RC1.

[0857] (408) A compound according to any one of (1) to (403), wherein -R22C, if present, is -LC-RC4.

[0858] (409) A compound according to any one of (1) to (403), wherein -R22C, if present, is -LC-RC5.

[0859] The Group -RC1

[0860] (410) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu; and is optionally substituted with one or more groups -RCC2.

[0861] (411) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -Me; and is optionally substituted with one or more groups -RCC2.

[0862] (412) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -iPr; and is optionally substituted with one or more groups -RCC2.

[0863] (413) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -iBu; and is optionally substituted with one or more groups -RCC2. (414) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -Me, - Et, -nPr, -iPr, -nBu, -iBu, -sBu, or -tBu.

[0864] (415) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -Me.

[0865] (416) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -iPr.

[0866] (417) A compound according to any one of (1) to (409), wherein -RC1, if present, is independently -iBu.

[0867] The Group -RC2

[0868] (418) A compound according to any one of (1) to (417), wherein each -RC2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0869] (419) A compound according to any one of (1) to (417), wherein each -RC2, if present, is independently cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0870] The Group -RC3

[0871] (420) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, azepanyl, or diazepanyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0872] (421) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0873] (422) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, or dioxanyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0874] (423) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2. (424) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl.

[0875] (425) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently tetrahydrofuranyl, tetrahydropyranyl, or dioxanyl.

[0876] (426) A compound according to any one of (1) to (419), wherein each -RC3, if present, is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl.

[0877] The Group -RC4

[0878] (427) A compound according to any one of (1) to (426), wherein each -RC4, if present, is phenyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0879] (428) A compound according to any one of (1) to (426), wherein each -RC4, if present, is phenyl.

[0880] The Group -RC5

[0881] (429) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, benzoimidazolyl, indazolyl, benzofuranyl, benzothienyl, benzooxazolyl, benzothiazolyl, benzisoxazolyl, benzoisothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, quinazolinyl, or phthalazinyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0882] (430) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0883] (431) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, or isothiazolyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2. (432) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0884] (433) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently imidazolyl or indolyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2.

[0885] (434) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0886] (435) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, or isothiazolyl.

[0887] (436) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl.

[0888] (437) A compound according to any one of (1) to (428), wherein each -RC5, if present, is independently imidazolyl or indolyl.

[0889] The Group -Lc-

[0890] (438) A compound according to any one of (1) to (437), wherein each -Lc-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0891] (439) A compound according to any one of (1) to (437), wherein each -Lc-, if present, is independently -CH2CH2or -CH2-.

[0892] (440) A compound according to any one of (1) to (437), wherein each -Lc-, if present, is -CH2-.

[0893] The Group -RCC1

[0894] (441) A compound according to any one of (1) to (440), wherein each -RCC1, if present, is -Rcc. The Group -RCC2

[0895] (442) A compound according to any one of (1) to (441), wherein each -RCC2, if present, is independently selected from:

[0896] -F, -Cl, -Br, -I,

[0897] -OH, -ORCC,

[0898] -OCF3,

[0899] -NH2, -NHRCC, -N(RCC)2, -RCM,

[0900] -C(=O)OH, -C(=O)ORCC, -OC(=O)RCC,

[0901] -C(=O)NH2, -C(=O)NHRCC, -C(=O)N(RCC)2, -C(=O)RCM,

[0902] -NHC(=O)Rcc, -NRCNC(=O)RCC,

[0903] -C(=O)RCC,

[0904] -S(=O)NH2, -S(=O)NHRCC, -S(=O)N(RCC)2, -S(=O)RCM,

[0905] -S(=O)2NH2, -S(=O)2NHRCC, -S(=O)2N(RCC)2, -S(=O)2RCM,

[0906] -NHS(=O)RCC, -NRCNS(=O)RCC,

[0907] -NHS(=O)2RCC, -NRCNS(=O)2RCC,

[0908] -S(=O)RCC, -S(=O)2RCC,

[0909] -SH, -SRCC, -CN, and -NO2.

[0910] (443) A compound according to any one of (1) to (441), wherein each -RCC2, if present, is independently selected from:

[0911] -F, -Cl, -Br, -I,

[0912] -OH, -ORCC,

[0913] -OCF3,

[0914] -NH2, -NHRCC, -N(RCC)2, -RCM, and

[0915] -CN.

[0916] (444) A compound according to any one of (1) to (441), wherein each -RCC2, if present, is independently selected from:

[0917] -F, -Cl, -Br, -I, -OH, -ORCC, and -OCF3. (445) A compound according to any one of (1) to (441), wherein each -RCC2, if present, is independently selected from:

[0918] -OH, -ORCC,

[0919] -NH2, -NHRCC, -N(RCC)2, -RCM,

[0920] -C(=O)OH, -C(=O)ORCC,

[0921] -C(=O)NH2, -C(=O)NHRCC, -C(=O)N(RCC)2, -C(=O)RCM,

[0922] -NHC(=NH)NH2,

[0923] -SH, and -SRCC

[0924] (446) A compound according to any one of (1) to (441), wherein each -RCC2, if present, is independently selected from:

[0925] -OH,

[0926] -NH2,

[0927] -C(=O)OH,

[0928] -C(=O)NH2,

[0929] -NHC(=NH)NH2,

[0930] -SH, and -SMe.

[0931] The Group -Lcc-

[0932] (447) A compound according to any one of (1) to (446), wherein each -Lcc-, if present, is independently -CH2CH2CH2-, -CH2CH2-, -CH(CH3)CH2-, -CH(CH3)-, or -CH2-.

[0933] (448) A compound according to any one of (1) to (446), wherein each -Lcc-, if present, is independently -CH2CH2or -CH2-.

[0934] (449) A compound according to any one of (1) to (446), wherein each -Lcc-, if present, is -CH2-.

[0935] The Group -Rcc

[0936] (450) A compound according to any one of (1) to (449), wherein each -Rcc, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0937] (451) A compound according to any one of (1) to (449), wherein each -Rcc, if present, is linear or branched saturated Ci-4alkyl.

[0938] (452) A compound according to any one of (1) to (449), wherein each -Rcc, if present, is -Me. The pCN

[0939] (453) A compound according to any one of (1) to (452), wherein each -RCN, if present, is independently -Me, -Et, -nPr, or -iPr.

[0940] (454) A compound according to any one of (1) to (452), wherein each -RCN, if present, is -Me.

[0941] The Group -RCM

[0942] (455) A compound according to any one of (1) to (454), wherein each -RCM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[0943] -RCMM, -C(=O)RCMM, -C(=O)ORCMM, and -S(=O)2RCMM

[0944] (456) A compound according to any one of (1) to (454), wherein each -RCM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino.

[0945] The Group -RCMM

[0946] (457) A compound according to any one of (1) to (456), wherein each -RCMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[0947] (458) A compound according to any one of (1) to (456), wherein each -RCMM, if present, is linear or branched saturated Ci-4alkyl.

[0948] (459) A compound according to any one of (1) to (456), wherein each -RCMM, if present, is -Me.

[0949] The -R22C: Some

[0950] (460) A compound according to any one of (1) to (403), wherein -R22C, if present, is independently selected from:

[0951] -CH3 (e.g., as in alanine),

[0952] -CH2CH(CH3)2 (e.g., as in leucine),

[0953] -CH(CH3)CH2CH3 (e.g., as in isoleucine),

[0954] -CH2CH2-S-CH3 (e.g., as in methionine),

[0955] -CH2-(phenyl) (e.g., as in phenylalanine),

[0956] -CH2-(1 H-indol-3-yl) (e.g., as in tryptophan),

[0957] -CH(CH3)2(e.g., as in valine), -CH2-C(=O)NH2 (e.g., as in asparagine),

[0958] -CH2-SH (e.g., as in cysteine),

[0959] -CH2CH2-C(=O)NH2 (e.g., as in glutamine),

[0960] -CH2-OH (e.g., as in serine),

[0961] -CH(OH)CH3 (e.g., as in threonine),

[0962] -CH2-(4-hydroxy-phenyl) (e.g., as in tyrosine),

[0963] -CH2CH2CH2-NH-C(=NH)-NH2 (e.g., as in arginine),

[0964] -CH2-(1 H-imidazol-4-yl) (e.g., as in histidine),

[0965] -CH2CH2CH2CH2-NH2 (e.g., as in lysine),

[0966] -CH2-C(=O)OH (e.g., as in aspartic acid), and

[0967] -CH2CH2-C(=O)OH (e.g., as in glutamic acid).

[0968] The Group -R22D

[0969] (461) A compound according to any one of (1) to (460), wherein -R22D, if present, is independently selected from:

[0970] -F, -Cl, -Br, -I,

[0971] -OH, -ORDD,

[0972] -OCF3,

[0973] -NH2, -NHRDD, -NRDD2, -RDM,

[0974] -C(=O)OH, -C(=O)ORDD, -OC(=O)RDD,

[0975] -C(=O)NH2, -C(=O)NHRDD, -C(=O)NRDD2, -C(=O)RDM,

[0976] -NHC(=O)RDD, -NRDNC(=O)RDD,

[0977] -C(=O)RDD,

[0978] -S(=O)NH2, -S(=O)NHRDD, -S(=O)NRDD2, -S(=O)RDM,

[0979] -S(=O)2NH2, -S(=O)2NHRDD, -S(=O)2NRDD2, -S(=O)2RDM,

[0980] -NHS(=O)RDD, -NRDNS(=O)RDD,

[0981] -NHS(=O)2RDD, -NRDNS(=O)2RDD,

[0982] -S(=O)RDD, -S(=O)2RDD,

[0983] -SRDD, -CN, and -NO2.

[0984] (462) A compound according to any one of (1) to (460), wherein each -R22D, if present, is independently selected from:

[0985] -F, -Cl, -Br, -I,

[0986] -OH, -ORDD,

[0987] -OCF3,

[0988] -NH2, -NHRDD, -NRDD2, -RDM,

[0989] -SRDD, and -CN. (463) A compound according to any one of (1) to (460), wherein each -R22D, if present, is independently selected from:

[0990] -F, -Cl, -Br, -I,

[0991] -OH, -ORDD,

[0992] -OCF3, and

[0993] -SRDD

[0994] (464) A compound according to any one of (1) to (460), wherein each -R22D, if present, is independently selected from:

[0995] -F, -Cl, -Br, -I,

[0996] -OH, -ORDD, and

[0997] -OCF3.

[0998] The Group -RDD

[0999] (465) A compound according to any one of (1) to (464), wherein each -RDD, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[1000] (466) A compound according to any one of (1) to (464), wherein each -RDD, if present, is linear or branched saturated Ci-4alkyl.

[1001] (467) A compound according to any one of (1) to (464), wherein each -RDD, if present, is -Me.

[1002] The Group -RDN

[1003] (468) A compound according to any one of (1) to (467), wherein each -RDN, if present, is independently -Me, -Et, -nPr, or -iPr.

[1004] (469) A compound according to any one of (1) to (467), wherein each -RDN, if present, is -Me.

[1005] The Group -RDM

[1006] (470) A compound according to any one of (1) to (469), wherein each -RDM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from:

[1007] -RDMM, -C(=O)RDMM, -C(=O)ORDMM, and -S(=O)2RDMM (471) A compound according to any one of (1) to (469), wherein each -RDM, if present, is independently pyrrolidino, piperidino, piperazino, or morpholino.

[1008] The Group -RDMM

[1009] (472) A compound according to any one of (1) to (471), wherein each -RDMM, if present, is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl.

[1010] (473) A compound according to any one of (1) to (471), wherein each -RDMM, if present, is linear or branched saturated Ci-4alkyl.

[1011] (474) A compound according to any one of (1) to (471), wherein each -RDMM, if present, is -Me.

[1012] The Groups R1and R2Taken Together

[1013] (475) A compound according to any one of (1) to (474), wherein -R1and -R2, together with the carbon atom to which they are attached, form a saturated C3-6cycloalkyl or a non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RCC2.

[1014] (476) A compound according to any one of (1) to (474), wherein -R1and -R2, together with the carbon atom to which they are attached, form a saturated C3-6cycloalkyl, and is optionally substituted with or one or more groups -RCC2.

[1015] (477) A compound according to any one of (1) to (474), wherein -R1and -R2, together with the carbon atom to which they are attached, form a saturated Cscycloalkyl, and is optionally substituted with or one or more groups -RCC2.

[1016] The optional substituents -RCC2may be, for example, as defined above.

[1017] Some Preferred Combinations of R1and R2

[1018] (478) A compound according to any one of (1) to (477), wherein:

[1019] -R1is independently -CH(CH3)CH2CH3, -CH2CH(CH3)2, or -CH(CH3)2; and -R2is -H.

[1020] (479) A compound according to any one of (1) to (477), wherein:

[1021] -R1is independently -CH(CH3)CH2CH3or -CH2CH(CH3)2; and -R2is -H. (480) A compound according to any one of (1) to (477), wherein:

[1022] -R1is -CH2CH(CH3)2; and

[1023] -R2is -H.

[1024] Chiral Centres

[1025] (481) A compound according to any one of (1) to (480), wherein the sulfur atom which forms part of the sulfonimidamido group is in the configuration shown in the following structural formula:

[1026] (482) A compound according to any one of (1) to (480), wherein the sulfur atom which forms part of the sulfonimidamido group is in the configuration shown in the following structural formula:

[1027] (483) A compound according to any one of (1) to (482), wherein the carbon atom to which -R1and -R2are attached (i.e., marked with a hash (#) in the following formula) is in the (S) configuration.

[1028] (484) A compound according to any one of (1) to (482), wherein the carbon atom to which -R1and -R2are attached (i.e. , marked with a hash (#) in the previous formula) is in the (R) configuration. (485) A compound according to any one of (1) to (482), wherein R2is -H, and which is a compound selected from compounds of the following formula, and pharmaceutically acceptable salts, hydrates, and solvates thereof:

[1029] (486) A compound according to any one of (1) to (480), wherein: the sulfur atom which forms part of the sulfonimidamido group (i.e., marked with an asterisk (*) in the following formula) is in the configuration shown in (481); and the carbon atom to which -R1and -R2are attached (i.e., marked with a hash (#) in the following formula) is in the (S) configuration.

[1030] (487) A compound according to any one of (1) to (480), wherein: the sulfur atom which forms part of the sulfonimidamido group (i.e., marked with an asterisk (*) in the above formula) is in the configuration shown in (481); and the carbon atom to which -R1and -R2are attached (i.e., marked with a hash (#) in the above formula) is in the (R) configuration.

[1031] (488) A compound according to any one of (1) to (480), wherein: the sulfur atom which forms part of the sulfonimidamido group (i.e., marked with an asterisk (*) in the above formula) is in the configuration shown in (482); and the carbon atom to which -R1and -R2are attached (i.e., marked with a hash (#) in the above formula) is in the (S) configuration. (489) A compound according to any one of (1) to (480), wherein: the sulfur atom which forms part of the sulfonimidamido group (i.e. , marked with an asterisk (*) in the above formula) is in the configuration shown in (482); and the carbon atom to which -R1and -R2are attached (i.e., marked with a hash (#) in the above formula) is in the (R) configuration.

[1032] Some Preferred Combinations

[1033] (490) A compound according to any one of (1) to (316), wherein:

[1034] -R1is independently -CH(CH3)CH2CH3, -CH2CH(CH3)2, or -CH(CH3)2;

[1035] -R2is -H; and the carbon atom to which -R1and -R2are attached is in the (S) configuration.

[1036] (491) A compound according to any one of (1) to (316), wherein:

[1037] -R1is independently -CH(CH3)CH2CH3or -CH2CH(CH3)2;

[1038] -R2is -H; and the carbon atom to which -R1and -R2are attached is in the (S) configuration.

[1039] (492) A compound according to any one of (1) to (316), wherein:

[1040] -R1is -CH2CH(CH3)2;

[1041] -R2is -H; and the carbon atom to which -R1and -R2are attached is in the (S) configuration.

[1042] Some Specific Compounds

[1043] (493) A compound according to (1), which is selected from compounds of the following formulae, and pharmaceutically acceptable salts, hydrates, and solvates thereof: (494) A compound according to (493), which is selected from ANOSA-001 to ANOSA-068, and pharmaceutically acceptable salts, hydrates, and solvates thereof.

[1044] Combinations

[1045] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination. All combinations of the embodiments pertaining to the chemical groups represented by the variables (e.g., -A, -RN, -R1, -R2, etc.) are specifically embraced by the present invention and are disclosed herein just as if each and every combination was individually and explicitly disclosed, to the extent that such combinations embrace compounds that are stable compounds (i.e. , compounds that can be isolated, characterised, and tested for biological activity). In addition, all sub-combinations of the chemical groups listed in the embodiments describing such variables are also specifically embraced by the present invention and are disclosed herein just as if each and every such sub-combination of chemical groups was individually and explicitly disclosed herein.

[1046] Substantially Purified Forms

[1047] One aspect of the present invention pertains to ANOSA compounds, in purified form.

[1048] In one embodiment, the compound is in substantially purified form and / or in a form substantially free from contaminants.

[1049] In one embodiment, the compound is in a substantially purified form with a purity of least 50% by weight, e.g., at least 60% by weight, e.g., at least 70% by weight, e.g., at least

[1050] 80% by weight, e.g., at least 90% by weight, e.g., at least 95% by weight, e.g., at least

[1051] 97% by weight, e.g., at least 98% by weight, e.g., at least 99% by weight.

[1052] Unless specified, the substantially purified form refers to the compound in any stereoisomeric or enantiomeric form. For example, in one embodiment, the substantially purified form refers to a mixture of stereoisomers, i.e., purified with respect to other compounds. In one embodiment, the substantially purified form refers to one stereoisomer, e.g., optically pure stereoisomer. In one embodiment, the substantially purified form refers to a mixture of enantiomers. In one embodiment, the substantially purified form refers to an equimolar mixture of enantiomers (i.e., a racemic mixture, a racemate). In one embodiment, the substantially purified form refers to one enantiomer, e.g., optically pure enantiomer. In one embodiment, the compound is in a form substantially free from contaminants wherein the contaminants represent no more than 50% by weight, e.g., no more than 40% by weight, e.g., no more than 30% by weight, e.g., no more than 20% by weight, e.g., no more than 10% by weight, e.g., no more than 5% by weight, e.g., no more than 3% by weight, e.g., no more than 2% by weight, e.g., no more than 1 % by weight.

[1053] Unless specified, the contaminants refer to other compounds, that is, other than stereoisomers or enantiomers. In one embodiment, the contaminants refer to other compounds and other stereoisomers. In one embodiment, the contaminants refer to other compounds and the other enantiomer.

[1054] In one embodiment, the compound is in a substantially purified form with an optical purity of at least 60% (i.e. , 60% of the compound, on a molar basis, is the desired stereoisomer or enantiomer, and 40% is undesired stereoisomer(s) or enantiomer), e.g., at least 70%, e.g., at least 80%, e.g., at least 90%, e.g., at least 95%, e.g., at least 97%, e.g., at least 98%, e.g., at least 99%.

[1055] Isomers

[1056] Certain compounds may exist in one or more particular geometric, optical, enantiomeric, diasteriomeric, epimeric, atropic, stereoisomeric, tautomeric, conformational, or anomeric forms, including but not limited to, cis- and trans-forms; E- and Z-forms; c-, t-, and r- forms; endo- and exo-forms; R-, S-, and meso-forms; D- and L-forms; d- and l-forms; (+) and (-) forms; keto-, enol-, and enolate-forms; syn- and anti-forms; synclinal- and anticlinal-forms; a- and p-forms; axial and equatorial forms; boat-, chair-, twist-, envelope-, and halfchair-forms; and combinations thereof, hereinafter collectively referred to as “isomers” (or “isomeric forms”).

[1057] Note that, except as discussed below for tautomeric forms, specifically excluded from the term “isomers,” as used herein, are structural (or constitutional) isomers (i.e., isomers which differ in the connections between atoms rather than merely by the position of atoms in space). For example, a reference to a methoxy group, -OCH3, is not to be construed as a reference to its structural isomer, a hydroxymethyl group, -CH2OH. Similarly, a reference to ortho-chlorophenyl is not to be construed as a reference to its structural isomer, meta-chlorophenyl. However, a reference to a class of structures may well include structurally isomeric forms falling within that class (e.g., Ci-3alkyl includes n-propyl and iso-propyl; butyl includes n-, iso-, sec-, and tert-butyl; methoxyphenyl includes ortho-, meta-, and para-methoxyphenyl).

[1058] The above exclusion does not pertain to tautomeric forms, for example, keto-, enol-, and enolate-forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, N-nitroso / hydroxyazo, and nitro / aci-nitro. keto enol enolate

[1059] For example, 1 H-pyridin-2-one-3-yl and 2-hydroxyl-pyridin-3-yl (shown below) are tautomers of one another. A reference herein to one is intended to encompass both.

[1060] 2-oxo-1 H-pyridin-3-yl 2-hydroxy-3-pyridyl

[1061] Note that specifically included in the term “isomer” are compounds with one or more isotopic substitutions. For example, H may be in any isotopic form, including1H,2H (D), and3H (T); C may be in any isotopic form, including12C,13C, and14C; O may be in any isotopic form, including16O and18O; S may be in any isotopic form, including32S,33S,34S,35S, and36S; and the like.

[1062] For example, a reference herein to a non-deuterated compound, is intended also to encompass corresponding deuterated compounds. In one particular example, the H atoms of the substituents at the R1and R2positions in the compound ANOSA-003 may be replaced with D atoms.

[1063] Unless otherwise specified, a reference to a particular compound includes all such isomeric forms, including mixtures (e.g., racemic mixtures) thereof. Methods for the preparation (e.g., asymmetric synthesis) and separation (e.g., fractional crystallisation and chromatographic means) of such isomeric forms are either known in the art or are readily obtained by adapting the methods taught herein, or known methods, in a known manner.

[1064] Salts

[1065] It may be convenient or desirable to prepare, purify, and / or handle a corresponding salt of the compound, for example, a pharmaceutically-acceptable salt. Examples of pharmaceutically acceptable salts are discussed in Berge et al., 1977, “Pharmaceutically Acceptable Salts,” J. Pharm. Sci., Vol. 66, pp. 1-19.

[1066] For example, if the compound is anionic, or has a functional group which may be anionic (e.g., -COOH may be -COO'), then a salt may be formed with a suitable cation.

[1067] Examples of suitable inorganic cations include, but are not limited to, alkali metal ions such as Na+and K+, alkaline earth cations such as Ca2+and Mg2+, and other cations such as Al3+. Examples of suitable organic cations include, but are not limited to, ammonium ion (i.e., NFV) and substituted ammonium ions (e.g., NH3R+, NH2R2+, NHR3+, NR4+). Examples of some suitable substituted ammonium ions are those derived from: ethylamine, diethylamine, dicyclohexylamine, triethylamine, butylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, benzylamine, phenylbenzylamine, choline, meglumine, and tromethamine, as well as amino acids, such as lysine and arginine. An example of a common quaternary ammonium ion is N(CH3)4+.

[1068] If the compound is cationic, or has a functional group which may be cationic (e.g., -NH2 may be -NH3+), then a salt may be formed with a suitable anion. Examples of suitable inorganic anions include, but are not limited to, those derived from the following inorganic acids: hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfurous, nitric, nitrous, phosphoric, and phosphorous.

[1069] Examples of suitable organic anions include, but are not limited to, those derived from the following organic acids: 2-acetyoxybenzoic, acetic, ascorbic, aspartic, benzoic, camphorsulfonic, cinnamic, citric, edetic, ethanedisulfonic, ethanesulfonic, formic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, hydroxymaleic, hydroxynaphthalene carboxylic, isethionic, lactic, lactobionic, lauric, maleic, malic, methanesulfonic, mucic, oleic, oxalic, palmitic, pamoic, pantothenic, phenylacetic, phenylsulfonic, propionic, pyruvic, salicylic, stearic, succinic, sulfanilic, tartaric, toluenesulfonic, and valeric. Examples of suitable polymeric organic anions include, but are not limited to, those derived from the following polymeric acids: tannic acid, carboxymethyl cellulose.

[1070] Unless otherwise specified, a reference to a particular compound also includes salt forms thereof. Hydrates and Solvates

[1071] It may be convenient or desirable to prepare, purify, and / or handle a corresponding solvate of the compound. The term “solvate” is used herein in the conventional sense to refer to a complex of solute (e.g., compound, salt of compound) and solvent. If the solvent is water, the solvate may be conveniently referred to as a hydrate, for example, a hemi-hydrate, a mono-hydrate, a sesqui-hydrate, a di-hydrate, a tri-hydrate, etc.

[1072] Unless otherwise specified, a reference to a particular compound also includes solvate and hydrate forms thereof.

[1073] Chemically Protected Forms

[1074] It may be convenient or desirable to prepare, purify, and / or handle the compound in a chemically protected form. The term “chemically protected form” is used herein in the conventional chemical sense and pertains to a compound in which one or more reactive functional groups are protected from undesirable chemical reactions under specified conditions (e.g., pH, temperature, radiation, solvent, and the like). In practice, well known chemical methods are employed to reversibly render unreactive a functional group, which otherwise would be reactive, under specified conditions. In a chemically protected form, one or more reactive functional groups are in the form of a protected or protecting group (also known as a masked or masking group or a blocked or blocking group). By protecting a reactive functional group, reactions involving other unprotected reactive functional groups can be performed, without affecting the protected group; the protecting group may be removed, usually in a subsequent step, without substantially affecting the remainder of the molecule. See, for example, Protective Groups in Organic Synthesis (T. Greene and P. Wuts; 4th Edition; John Wiley and Sons, 2006).

[1075] A wide variety of such “protecting,” “blocking,” or “masking” methods are widely used and well known in organic synthesis. For example, a compound which has two nonequivalent reactive functional groups, both of which would be reactive under specified conditions, may be derivatized to render one of the functional groups “protected,” and therefore unreactive, under the specified conditions; so protected, the compound may be used as a reactant which has effectively only one reactive functional group. After the desired reaction (involving the other functional group) is complete, the protected group may be “deprotected” to return it to its original functionality.

[1076] For example, a hydroxy group may be protected as an ether (-OR) or an ester (-OC(=O)R), for example, as: a t-butyl ether; a benzyl, benzhydryl (diphenylmethyl), or trityl (triphenylmethyl) ether; a trimethylsilyl or t-butyldimethylsi lyl ether; or an acetyl ester (-OC(=O)CH3, -OAC). For example, an amine group may be protected, for example, as an amide (-NRCO-R) or a urethane (-NRCO-OR), for example, as: a methyl amide (-NHCO-CH3); a benzyloxy amide (-NHCO-OCH2C6H5, -NH-Cbz); as a t-butoxy amide (-NHCO-OC(CH3)3, -NH-Boc); a 2-biphenyl-2-propoxy amide (-NHCO-OC(CH3)2C6H4C6Hs, -NH-Bpoc), as a 9-fluorenylmethoxy amide (-NH-Fmoc), as a 6-nitroveratryloxy amide (-NH-Nvoc), as a 2-trimethylsilylethyloxy amide (-NH-Teoc), as a 2,2,2-trichloroethyloxy amide (-NH-Troc), as an allyloxy amide (-NH-Alloc), as a 2(-phenylsulfonyl)ethyloxy amide (-NH-Psec); or, in suitable cases (e.g., cyclic amines), as a nitroxide radical (>N-O»).

[1077] Prodrugs

[1078] It may be convenient or desirable to prepare, purify, and / or handle the compound in the form of a prodrug. The term “prodrug,” as used herein, pertains to a compound which, when metabolised (e.g., in vivo), yields the desired active compound. Typically, the prodrug is inactive, or less active than the desired active compound, but may provide advantageous handling, administration, or metabolic properties.

[1079] For example, some prodrugs are esters of the active compound (e.g., a physiologically acceptable metabolically labile ester). During metabolism, the ester group (-C(=O)OR) is cleaved to yield the active drug. Such esters may be formed by esterification, for example, of any of the carboxylic acid groups (-C(=O)OH) in the parent compound, with, where appropriate, prior protection of any other reactive groups present in the parent compound, followed by deprotection if required.

[1080] Also, some prodrugs are activated enzymatically to yield the active compound, or a compound which, upon further chemical reaction, yields the active compound (for example, as in ADEPT, GDEPT, LI DEPT, etc.). For example, the prodrug may be a sugar derivative or other glycoside conjugate, or may be an amino acid ester derivative.

[1081] Chemical Synthesis

[1082] Methods for the chemical synthesis of the ANOSA compounds are described herein. These and / or other well-known methods may be modified and / or adapted in known ways in order to provide alternative or improved methods of synthesis of the ANOSA compounds. Compositions

[1083] One aspect of the present invention pertains to a composition (e.g., a pharmaceutical composition) comprising an ANOSA compound, as described herein, and a pharmaceutically acceptable carrier, diluent, or excipient.

[1084] Another aspect of the present invention pertains to a method of preparing a composition (e.g., a pharmaceutical composition) comprising mixing an ANOSA compound, as described herein, and a pharmaceutically acceptable carrier, diluent, or excipient.

[1085] Uses

[1086] The ANOSA compounds, as described herein, are useful, for example, in the treatment of disorders (e.g., diseases) that are ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS; etc.), as described herein.

[1087] Selectivity

[1088] In one embodiment, the inhibition of bacterial aminoacyl-tRNA synthetase (aaRS) is selective inhibition, e.g., with respect to mammalian aminoacyl-tRNA synthetase (aaRS), e.g., the corresponding mammalian aminoacyl-tRNA synthetase.

[1089] In one embodiment, the inhibition of bacterial aminoacyl-tRNA synthetase (aaRS) is selective inhibition, e.g., with respect to human aminoacyl-tRNA synthetase (aaRS), e.g., the corresponding human aminoacyl-tRNA synthetase.

[1090] For example, in one embodiment, the ANOSA compound selectively inhibits bacterial leucyl-tRNA synthetase (LeuRS), as compared to human leucyl-tRNA synthetase (LeuRS).

[1091] Use in Methods of Inhibiting Bacterial Aminoacyl-tRNA Synthetase

[1092] One aspect of the present invention pertains to a method of inhibiting (e.g., selectively inhibiting) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS, etc.), in vitro or in vivo, comprising contacting the synthetase with an effective amount of an ANOSA compound, as described herein.

[1093] One aspect of the present invention pertains to a method of inhibiting (e.g., selectively inhibiting) bacterial aminoacyl-tRNA synthetase (aaRS) (e.g., bacterial leucyl-tRNA synthetase, LeuRS, etc.) function in a cell (e.g., a bacterial cell), in vitro or in vivo, comprising contacting the cell with an effective amount of an ANOSA compound, as described herein.

[1094] One of ordinary skill in the art is readily able to determine whether or not a candidate compound inhibits bacterial aminoacyl-tRNA synthetase (e.g., bacterial leucyl-tRNA synthetase, etc.). For example, suitable assays are described herein or are known in the art.

[1095] In one embodiment, the method is performed in vitro.

[1096] In one embodiment, the method is performed in vivo.

[1097] In one embodiment, the ANOSA compound is provided in the form of a pharmaceutically acceptable composition.

[1098] One aspect of the present invention pertains to a method of inhibiting bacterial aminoacyl- tRNA synthetase (e.g., bacterial leucyl-tRNA synthetase, etc.), in a cell (e.g., a bacterial cell), in vitro or in vivo, comprising contacting the cell with an effective amount of an ANOSA compound, as described herein.

[1099] For example, a sample of cells may be grown in vitro and a compound brought into contact with said cells, and the effect of the compound on those cells observed. As an example of “effect,” the morphological status of the cells (e.g., alive or dead, etc.) may be determined. Where the compound is found to exert an influence on the cells, this may be used as a prognostic or diagnostic marker of the efficacy of the compound in methods of treating a patient carrying cells of the same cellular type.

[1100] Use in Methods of Therapy

[1101] Another aspect of the present invention pertains to an ANOSA compound, as described herein, for use in a method of treatment of the human or animal body by therapy, for example, for use in a method of treatment of a disorder (e.g., a disease) as described herein.

[1102] Use in the Manufacture of Medicaments

[1103] Another aspect of the present invention pertains to use of an ANOSA compound, as described herein, in the manufacture of a medicament, for example, for use in a method of treatment, for example, for use a method of treatment of a disorder (e.g., a disease) as described herein.

[1104] In one embodiment, the medicament comprises the ANOSA compound. Methods of Treatment

[1105] Another aspect of the present invention pertains to a method of treatment, for example, a method of treatment of a disorder (e.g., a disease) as described herein, comprising administering to a subject in need of treatment a therapeutically-effective amount of an ANOSA compound, as described herein, preferably in the form of a pharmaceutical composition.

[1106] Disorders Treated - Disorders Ameliorated by the Inhibition of Bacterial Aminoacyl-tRNA Synthetase

[1107] In one embodiment (e.g., of use in methods of therapy, of use in the manufacture of medicaments, of methods of treatment), the treatment is treatment of a disorder (e.g., a disease) that is ameliorated by the inhibition (e.g., selective inhibition) of bacterial aminoacyl-tRNA synthetase (e.g., bacterial leucyl-tRNA synthetase, etc.).

[1108] Disorders Treated - Bacterial Infections

[1109] In one embodiment (e.g., of use in methods of therapy, of use in the manufacture of medicaments, of methods of treatment), the treatment is treatment of: a bacterial infection.

[1110] In one embodiment, the bacteria are Gram-positive bacteria (i.e., the bacterial infection is an infection with Gram-positive bacteria; the bacterial infection is a Gram-positive bacterial infection; etc.).

[1111] In one embodiment, the bacteria are Gram-negative bacteria.

[1112] In one embodiment, the bacteria are aerobic bacteria.

[1113] In one embodiment, the bacteria are anaerobic bacteria.

[1114] In one embodiment, the bacteria are intracellular bacteria.

[1115] In one embodiment, the bacteria are:

[1116] Staphylococci, for example S. aureus;

[1117] Enterococci, for example E. faecalis;

[1118] Streptococci, for example S. pneumoniae;

[1119] Haemophilus, for example H. influenza;

[1120] Moraxella, for example M. catarrhalis', Klebsiella, for example K. pneumoniae’, Acinetobacter, for example A. baumanii;

[1121] Pseudomonas, for example P. aeruginosa’,

[1122] Proteus, for example P. mirabilis;

[1123] Neisseria, for example Neisseria gonorrhoeae;

[1124] Clostridioides, for example Clostridioides difficile;

[1125] Campylobacter, for example C. jejuni;

[1126] Salmonella, for example S. typhi;

[1127] Shigella, for example S. flexneri;

[1128] Enterobacter, for example E. cloacae;

[1129] Citrobacter, for example C. freundii;

[1130] Francisella, for example F. tularensis;

[1131] Yersinia, for example Y. pestis;

[1132] Burkholderia, for example B. pseudomallei;

[1133] Morganella, for example M. morganii;

[1134] Stenotrophomonas, for example S. maltophilia;

[1135] Serratia, for example Serratia marcescens; or Escherichia, for example E. coli.

[1136] In one embodiment, the bacteria are: Mycobacteria, for example M. tuberculosis.

[1137] In one embodiment, the bacteria are:

[1138] Chlamydia, for example, C. trachomatis;

[1139] Rickettsiae, for example, R. prowazekii; or

[1140] Mycoplasma, for example, M. pneumoniae.

[1141] Type / Location of Infection

[1142] The infection may be associated with a particular location, organ, etc.

[1143] In one embodiment, the infection is: a central nervous system infection; an external ear infection; an infection of the middle ear, including acute otitis media; an infection of the cranial sinuses; an eye infection; an infection of the oral cavity, including an infection of the teeth, gums, or mucosa; an upper respiratory tract infection; a lower respiratory tract infection; a genitourinary infection; a urinary tract infection; an intra-abdominal infection; a gastrointestinal infection; a gynecological infection; septicaemia; a bone or joint infection; a skin or skin structure infection; bacterial endocarditis; a wound infection; or a burn infection.

[1144] The treatment may be treatment as prophylaxis, for example: antibacterial prophylaxis in surgery; and antibacterial prophylaxis in immunosuppressed patients, including patients receiving cancer chemotherapy, or organ transplant patients.

[1145] T reatment

[1146] The term “treatment,” as used herein in the context of treating a disorder, pertains generally to treatment of a human or an animal (e.g., in veterinary applications), in which some desired therapeutic effect is achieved, for example, the inhibition of the progress of the disorder, and includes a reduction in the rate of progress, a halt in the rate of progress, alleviation of symptoms of the disorder, amelioration of the disorder, and cure of the disorder. Treatment as a prophylactic measure (i.e. , prophylaxis) is also included. For example, use with patients who have not yet developed the disorder, but who are at risk of developing the disorder, is encompassed by the term “treatment.”

[1147] For example, treatment of bacterial infection includes the prophylaxis of bacterial infection, reducing the incidence of bacterial infection, alleviating the symptoms of bacterial infection, etc.

[1148] The term “therapeutically-effective amount,” as used herein, pertains to that amount of a compound, or a material, composition or dosage form comprising a compound, which is effective for producing some desired therapeutic effect, commensurate with a reasonable benefit / risk ratio, when administered in accordance with a desired treatment regimen.

[1149] Combination Therapies

[1150] The term “treatment” includes combination treatments and therapies, in which two or more treatments or therapies are combined, for example, sequentially or simultaneously. For example, the compounds described herein may also be used in combination therapies, e.g., in conjunction with other agents.

[1151] One aspect of the present invention pertains to a compound as described herein, in combination with one or more (e.g., 1 , 2, 3, 4, etc.) additional therapeutic agents, for example, other anti-bacterial agents.

[1152] The particular combination would be at the discretion of the physician who would select dosages using their common general knowledge and dosing regimens known to a skilled practitioner.

[1153] The agents (i.e. , the ANOSA compound described herein, plus one or more other agents) may be administered simultaneously or sequentially, and may be administered in individually varying dose schedules and via different routes. For example, when administered sequentially, the agents can be administered at closely spaced intervals (e.g., over a period of 5-10 minutes) or at longer intervals (e.g., 1 , 2, 3, 4 or more hours apart, or even longer periods apart where required), the precise dosage regimen being commensurate with the properties of the therapeutic agent(s).

[1154] The agents (i.e., the compound described here, plus one or more other agents) may be formulated together in a single dosage form, or alternatively, the individual agents may be formulated separately and presented together in the form of a kit, optionally with instructions for their use.

[1155] Other Uses

[1156] The ANOSA compounds described herein may also be used as cell culture additives to inhibit bacterial aminoacyl-tRNA synthetase (e.g., bacterial leucyl-tRNA synthetase, etc.).

[1157] The ANOSA compounds described herein may also be used as part of an in vitro assay, for example, in order to determine whether a candidate host is likely to benefit from treatment with the compound in question.

[1158] The ANOSA compounds described herein may also be used as a standard, for example, in an assay, in order to identify other active compounds, other bacterial aminoacyl-tRNA synthetase inhibitors, etc.

[1159] Kits

[1160] One aspect of the invention pertains to a kit comprising (a) an ANOSA compound as described herein, or a composition comprising an ANOSA compound as described herein, e.g., preferably provided in a suitable container and / or with suitable packaging; and (b) instructions for use, e.g., written instructions on how to administer the compound or composition.

[1161] The written instructions may also include a list of indications for which the active ingredient is a suitable treatment.

[1162] Routes of Administration

[1163] The ANOSA compound or pharmaceutical composition comprising the ANOSA compound may be administered to a subject by any convenient route of administration, whether systemically / peripherally or topically (i.e. , at the site of desired action).

[1164] Routes of administration include, but are not limited to, oral (e.g., by ingestion); buccal; sublingual; transdermal (including, e.g., by a patch, plaster, etc.); transmucosal (including, e.g., by a patch, plaster, etc.); intranasal (e.g., by nasal spray); ocular (e.g., by eyedrops); pulmonary (e.g., by inhalation or insufflation therapy using, e.g., via an aerosol, e.g., through the mouth or nose); rectal (e.g., by suppository or enema); vaginal (e.g., by pessary); parenteral, for example, by injection, including subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, and intrasternal; by implant of a depot or reservoir, for example, subcutaneously or intramuscularly.

[1165] The Subject / Patient

[1166] The subject / patient may be a chordate, a vertebrate, a mammal, a placental mammal, a marsupial (e.g., kangaroo, wombat), a rodent (e.g., a guinea pig, a hamster, a rat, a mouse), murine (e.g., a mouse), a lagomorph (e.g., a rabbit), avian (e.g., a bird), canine (e.g., a dog), feline (e.g., a cat), equine (e.g., a horse), porcine (e.g., a pig), ovine (e.g., a sheep), bovine (e.g., a cow), a primate, simian (e.g., a monkey or ape), a monkey (e.g., marmoset, baboon), an ape (e.g., gorilla, chimpanzee, orangutan, gibbon), or a human.

[1167] Furthermore, the subject / patient may be any of its forms of development, for example, a foetus.

[1168] In one preferred embodiment, the subject / patient is a human. Formulations

[1169] While it is possible for an ANOSA compound to be administered alone, it is preferable to present it as a pharmaceutical formulation (e.g., composition, preparation, medicament) comprising at least one ANOSA compound, as described herein, together with one or more other pharmaceutically acceptable ingredients well known to those skilled in the art, including, but not limited to, pharmaceutically acceptable carriers, diluents, excipients, adjuvants, fillers, buffers, preservatives, anti-oxidants, lubricants, stabilisers, solubilisers, surfactants (e.g., wetting agents), masking agents, colouring agents, flavouring agents, and sweetening agents. The formulation may further comprise other active agents, for example, other therapeutic or prophylactic agents.

[1170] Thus, the present invention further provides pharmaceutical compositions, as defined above, and methods of making a pharmaceutical composition comprising mixing at least one ANOSA compound, as described herein, together with one or more other pharmaceutically acceptable ingredients well known to those skilled in the art, e.g., carriers, diluents, excipients, etc. If formulated as discrete units (e.g., tablets, etc.), each unit contains a predetermined amount (dosage) of the compound.

[1171] The term “pharmaceutically acceptable,” as used herein, pertains to compounds, ingredients, materials, compositions, dosage forms, etc., which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of the subject in question (e.g., human) without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. Each carrier, diluent, excipient, etc. must also be “acceptable” in the sense of being compatible with the other ingredients of the formulation.

[1172] Suitable carriers, diluents, excipients, etc. can be found in standard pharmaceutical texts, for example, Remington's Pharmaceutical Sciences, 18th edition, Mack Publishing Company, Easton, Pa., 1990; and Handbook of Pharmaceutical Excipients, 5th edition, 2005.

[1173] The formulations may be prepared by any methods well known in the art of pharmacy. Such methods include the step of bringing into association the compound with a carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the compound with carriers (e.g., liquid carriers, finely divided solid carrier, etc.), and then shaping the product, if necessary.

[1174] The formulation may be prepared to provide for rapid or slow release; immediate, delayed, timed, or sustained release; or a combination thereof. Formulations may suitably be in the form of liquids, solutions (e.g., aqueous, nonaqueous), suspensions (e.g., aqueous, non-aqueous), emulsions (e.g., oil-in-water, water-in-oil), elixirs, syrups, electuaries, mouthwashes, drops, tablets (including, e.g., coated tablets), granules, powders, lozenges, pastilles, capsules (including, e.g., hard and soft gelatin capsules), cachets, pills, ampoules, boluses, suppositories, pessaries, tinctures, gels, pastes, ointments, creams, lotions, oils, foams, sprays, mists, or aerosols.

[1175] Formulations may suitably be provided as a patch, adhesive plaster, bandage, dressing, or the like which is impregnated with one or more compounds and optionally one or more other pharmaceutically acceptable ingredients, including, for example, penetration, permeation, and absorption enhancers. Formulations may also suitably be provided in the form of a depot or reservoir.

[1176] The compound may be dissolved in, suspended in, or mixed with one or more other pharmaceutically acceptable ingredients. The compound may be presented in a liposome or other micro particulate which is designed to target the compound, for example, to blood components or one or more organs.

[1177] Formulations suitable for oral administration (e.g., by ingestion) include liquids, solutions (e.g., aqueous, non-aqueous), suspensions (e.g., aqueous, non-aqueous), emulsions (e.g., oil-in-water, water-in-oil), elixirs, syrups, electuaries, tablets, granules, powders, capsules, cachets, pills, ampoules, boluses.

[1178] Formulations suitable for buccal administration include mouthwashes, lozenges, pastilles, as well as patches, adhesive plasters, depots, and reservoirs. Lozenges typically comprise the compound in a flavored basis, usually sucrose and acacia or tragacanth. Pastilles typically comprise the compound in an inert matrix, such as gelatin and glycerin, or sucrose and acacia. Mouthwashes typically comprise the compound in a suitable liquid carrier.

[1179] Formulations suitable for sublingual administration include tablets, lozenges, pastilles, capsules, and pills.

[1180] Formulations suitable for oral transmucosal administration include liquids, solutions (e.g., aqueous, non-aqueous), suspensions (e.g., aqueous, non-aqueous), emulsions (e.g., oil- in-water, water-in-oil), mouthwashes, lozenges, pastilles, as well as patches, adhesive plasters, depots, and reservoirs.

[1181] Formulations suitable for non-oral transmucosal administration include liquids, solutions (e.g., aqueous, non-aqueous), suspensions (e.g., aqueous, non-aqueous), emulsions (e.g., oil-in-water, water-in-oil), suppositories, pessaries, gels, pastes, ointments, creams, lotions, oils, as well as patches, adhesive plasters, depots, and reservoirs.

[1182] Formulations suitable for transdermal administration include gels, pastes, ointments, creams, lotions, and oils, as well as patches, adhesive plasters, bandages, dressings, depots, and reservoirs.

[1183] Tablets may be made by conventional means, e.g., compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the compound in a free-flowing form such as a powder or granules, optionally mixed with one or more binders (e.g., povidone, gelatin, acacia, sorbitol, tragacanth, hydroxypropyl methylcellulose); fillers or diluents (e.g., lactose, microcrystalline cellulose, calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc, silica); disintegrants (e.g., sodium starch glycolate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose); surface-active or dispersing or wetting agents (e.g., sodium lauryl sulfate); preservatives (e.g., methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, sorbic acid); flavours, flavour enhancing agents, and sweeteners. Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the compound therein using, for example, hydroxypropyl methylcellulose in varying proportions to provide the desired release profile. Tablets may optionally be provided with a coating, for example, to affect release, for example an enteric coating, to provide release in parts of the gut other than the stomach.

[1184] Ointments are typically prepared from the compound and a paraffinic or a water-miscible ointment base.

[1185] Creams are typically prepared from the compound and an oil-in-water cream base. If desired, the aqueous phase of the cream base may include, for example, at least about 30% w / w of a polyhydric alcohol, i.e. , an alcohol having two or more hydroxyl groups such as propylene glycol, butane-1 ,3-diol, mannitol, sorbitol, glycerol and polyethylene glycol and mixtures thereof. The topical formulations may desirably include a compound which enhances absorption or penetration of the compound through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethyl sulfoxide and related analogues.

[1186] Emulsions are typically prepared from the compound and an oily phase, which may optionally comprise merely an emulsifier (otherwise known as an emulgent), or it may comprise a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabiliser. It is also preferred to include both an oil and a fat. Together, the emulsifier(s) with or without stabiliser(s) make up the so-called emulsifying wax, and the wax together with the oil and / or fat make up the so-called emulsifying ointment base which forms the oily dispersed phase of the cream formulations.

[1187] Suitable emulgents and emulsion stabilisers include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate and sodium lauryl sulfate. The choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the compound in most oils likely to be used in pharmaceutical emulsion formulations may be very low. Thus the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers. Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate or a blend of branched chain esters known as Crodamol CAP may be used, the last three being preferred esters. These may be used alone or in combination depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

[1188] Formulations suitable for intranasal administration, where the carrier is a liquid, include, for example, nasal spray, nasal drops, or by aerosol administration by nebuliser, include aqueous or oily solutions of the compound.

[1189] Formulations suitable for intranasal administration, where the carrier is a solid, include, for example, those presented as a coarse powder having a particle size, for example, in the range of about 20 to about 500 microns which is administered in the manner in which snuff is taken, i.e., by rapid inhalation through the nasal passage from a container of the powder held close up to the nose.

[1190] Formulations suitable for pulmonary administration (e.g., by inhalation or insufflation therapy) include those presented as an aerosol spray from a pressurised pack, with the use of a suitable propellant, such as dichlorodifluoromethane, trichlorofluoromethane, dichoro-tetrafluoroethane, carbon dioxide, or other suitable gases.

[1191] Formulations suitable for ocular administration include eye drops wherein the compound is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the compound.

[1192] Formulations suitable for rectal administration may be presented as a suppository with a suitable base comprising, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols, for example, cocoa butter or a salicylate; or as a solution or suspension for treatment by enema.

[1193] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the compound, such carriers as are known in the art to be appropriate.

[1194] Formulations suitable for parenteral administration (e.g., by injection), include aqueous or non-aqueous, isotonic, pyrogen-free, sterile liquids (e.g., solutions, suspensions), in which the compound is dissolved, suspended, or otherwise provided (e.g., in a liposome or other micro particulate). Such liquids may additionally contain other pharmaceutically acceptable ingredients, such as anti-oxidants, buffers, preservatives, stabilisers, bacteriostats, suspending agents, thickening agents, and solutes which render the formulation isotonic with the blood (or other relevant bodily fluid) of the intended recipient. Examples of excipients include, for example, water, alcohols, polyols, glycerol, vegetable oils, and the like. Examples of suitable isotonic carriers for use in such formulations include Sodium Chloride Injection, Ringer's Solution, or Lactated Ringer's Injection. Typically, the concentration of the compound in the liquid is from about 1 ng / mL to about 10 pg / mL, for example from about 10 ng / mL to about 1 pg / mL. The formulations may be presented in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and may be stored in a freeze-dried (lyophilised) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets.

[1195] Dosage

[1196] It will be appreciated by one of skill in the art that appropriate dosages of the ANOSA compounds, and compositions comprising the ANOSA compounds, can vary from patient to patient. Determining the optimal dosage will generally involve the balancing of the level of therapeutic benefit against any risk or deleterious side effects. The selected dosage level will depend on a variety of factors including, but not limited to, the activity of the particular ANOSA compound, the route of administration, the time of administration, the rate of excretion of the ANOSA compound, the duration of the treatment, other drugs, compounds, and / or materials used in combination, the severity of the disorder, and the species, sex, age, weight, condition, general health, and prior medical history of the patient. The amount of ANOSA compound and route of administration will ultimately be at the discretion of the physician, veterinarian, or clinician, although generally the dosage will be selected to achieve local concentrations at the site of action which achieve the desired effect without causing substantial harmful or deleterious side-effects. Administration can be effected in one dose, continuously or intermittently (e.g., in divided doses at appropriate intervals) throughout the course of treatment. Methods of determining the most effective means and dosage of administration are well known to those of skill in the art and will vary with the formulation used for therapy, the purpose of the therapy, the target cell(s) being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician.

[1197] In general, a suitable dose of the ANOSA compound is in the range of about 0.1 mg to about 5000 mg (more typically about 10 mg to about 3000 mg) per kilogram body weight of the subject per day. Where the compound is a salt, an ester, an amide, a prodrug, or the like, the amount administered is calculated on the basis of the parent compound and so the actual weight to be used is increased proportionately.

[1198] General Chemical

[1199] Methods for the chemical synthesis of ANOSA compounds are described herein may be prepared by techniques known in the art. These and / or other well-known methods may be modified and / or adapted in order to facilitate the synthesis of additional compounds described herein.

[1200] In the following general scheme, where specific reaction conditions like, temperature, duration of reaction, acids, bases, reagents, solvents, coupling agents, etc. are mentioned, it is understood that other reaction conditions like, temperature, duration of reaction, acids, bases, reagents, solvents, coupling agents, etc. may also be used and are therefore included within the scope of this disclosure.

[1201] General Scheme 1

[1202] One of several possible approaches for the synthesis of acylated sulfonimidamide derivatives of formula (D) is illustrated in the scheme shown above. The required sulfonimidamide derivative (A) was prepared and the procedure was part of earlier patent publication Edmund et al., 2021.

[1203] By using this approach, an appropriate sulfonimidamide of formula (A) reacts with acid or its activated form of formula (B) in the presence of base and acid activating agent which are known in the art to give the acylated sulfonimidamide of formula (C). Individual stereoisomers (enantiomers, diastereomers) of formula (C) derivative can be isolated by applying appropriate separation methods which are known in the art, if desired. The product (C) or its isomer can be deprotected using TFA or HCI to give the acyl sulfonimidamide derivative of formula (D). General Scheme 1.2 lnt-L4-2 lnt-L7-2 lnt-L8-2 Synthesis of 4-chlorothiophene-2-sulfonimidamide 2,2,2-trifluoroacetic acid salt, lnt-B-4.23 lnt-B-2.23 lnt-B-3.23 lnt-B-4.23

[1204] Step-1 : 4-Chlorothiophene-2-sulfonamide, lnt-B-2.23, (2.0 g, 10.1 mmol, 1 equiv) was dissolved in dry THF (150 mL). The solution was cooled to 0 °C and 60% NaH (1.21 g, 30.4 mmol, 3 equiv) was slowly added and the mixture was stirred at rt for 30 min.

[1205] Afterwards TBDMS-CI (1.83 g, 12.1 mmol, 1.2 equiv) was added and the mixture was left to stir at rt until completion (8-16h). After completion the mixture was slightly evaporated; water added and extracted with EtOAc 3 times. Combined organic phases were washed with brine, dried over anh. Na2SO4. The solvent was evaporated and crude TBS-protected product lnt-B-3.23 was used in the next step.

[1206] Step-2: Triethylamine (2.81 mL, 20.2 mmol, 2 equiv) was added to a stirred suspension of PhaPCh (5.05 g, 15.2 mmol, 1.5 equiv) in dry CHCI3 (20 mL) under Ar atmosphere. The mixture was stirred for 10 min, then suspension of lnt-B-3.23 (10.1 mmol, 1 equiv) in dry CHCI3 (10 mL) was added to the reaction mixture at 0 °C. The mixture was stirred for 30 min at 0 °C (after ~5 min a clear solution formed), then the reaction mixture was cooled to -78°C and g. NH3 was bubbled at -78°C for 5 min. The mixture was stirred at -78°C for 30 min then warmed to room temperature. The solvent, excess of NH3 and Et3N was removed under reduced pressure to give a crude residue which was dissolved in acetonitrile (ca. 10 mL), and cooled to 0°C. 2,2,2-Trifluoroacetic acid (4.65 mL, 60.7 mmol, 6 equiv) was added and the mixture was stirred at room temperature for 5 min to 1 h (conversion was judged by UPLC / MS). The solvent was removed under reduced pressure to give an oil residue that was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: 0.01 % TFA in H2O / ACN) and direct phase chromatography (EtOAc: PE = 1 :1) to obtain 1.8g (57%) pure lnt-B-4.23 as white solid. The following intermediates in Synthesis Table 1 were made according to the procedure described for lnt-B-4.23: Synthesis of tert-butyl ((S)-1-(((S)-amino(3-chlorophenyl)(oxo)-X6-sulfaneylidene)amino)-

[1207] 4-methyl-1-oxopentan-2-yl)carbamate lnt-A-4.3-Fr-1 and butyl ((S)-1-(((F?)-amino(3-chlorophenyl)(oxo)-X6-sulfaneylidene)amino)-4-methyl-1- oxopentan-2-yl)carbamate lnt-A-4.3-Fr-2

[1208] 3-Chlorobenzenesulfonimidamide 2,2,2-trifluoroacetic acid salt lnt-A-3.3 (780 mg, 2.6 mmol, 1 equiv) was dissolved in dry DMF (15 mL). The solution was cooled to 0 °C and 60% NaH (307.2 mg, 7.7 mmol, 3 equiv) was slowly added. The mixture was stirred for IQ- 15 min then / V-Boc-L-leucine-OSu (840.6 mg, 2.6 mmol, 1 equiv) was added and the mixture was left to stir at rt until completion (8-16h). After completion the mixture was quenched with water and extracted with EtOAc 3 times. Combined organic phases were washed with brine, dried over anh. Na2SO4. The solvent was evaporated and crude residue was purified by column chromatography (EtOAc: PE 1 :2 to EtOAc) or reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O / AON) to obtain 550 mg (53%) of rac-lnt-A-4.3 as mixture of 2 diastereomers. Diastereomers were separated using Chiral prep HPLC: CHIRALPAK IC (250 x 30mm, 5pim), Mobile phase: Heptane-IPA-DCM (65- 15-20), flow rate: 20mL / min to yield 254 mg of S,S-isomer (lnt-A-4.3-Fr-1), retention time: 13.3 min and 263 mg of S,F?-isomer (lnt-A-4.3-Fr-2), retention time: 37.3 min.

[1209] The following intermediates in Synthesis Table 2 were made according to the procedure described for Int-A-4.3-Fr-1 and Int-A-4.3-Fr-2:

[1210] Synthesis of tert-butyl ((S)-1-(((S)-(4-chlorothiophen-2-yl)(oxo)(ureido)-X6- sulfaneylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate triethylamine salt lnt-C-6.0-2

[1211] Triethylamine (0.27 mL, 1.9 mmol, 4 equiv) and TMSNCO (0.13 mL, 0.97 mmol, 2 equiv) was added to the solution of lnt-B-5.23-Fr-2 (200 mg, 0.48 mmol, 1 equiv) in dichloromethane (10 mL). The reaction mixture was stirred for 5 h at rt. Incomplete conversion of lnt-B-5.23-Fr-2 was detected by UPLC / MS and second portion of triethylamine (0.27 mL, 1.9 mmol, 4 equiv) and TMSNCO (0.13 mL, 0.97 mmol, 2 equiv) was added and reaction mixture stirred at rt overnight. The reaction mixture was quenched with MeOH (0.5 mL), solvents were removed under reduced pressure. Crude was residue purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O / ACN) to obtain lnt-C-6.0-2 195mg (72%) as white amorphous solid.

[1212] The following intermediates in Synthesis Table 3 were made according to the procedure described for lnt-C-6.0-2:

[1213] Synthesis of tert-butyl ((S)-1-(((R)-(4-chlorothiophen-2-yl)(3-ethylureido)(oxo)-X6- sulfaneylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate triethylamine salt lnt-C-6.7-1

[1214] Triethylamine (0.14 mL, 0.98 mmol, 4 equiv) and EtNCO (0.040 mL, 0.49 mmol, 2 equiv) was added to the solution of lnt-B-5.23-Fr-1 (100 mg, 0.24 mmol, 1 equiv) in dichloromethane (5 mL). The reaction mixture was stirred for 5 h at rt. The reaction mixture was quenched with MeOH (0.5 mL), solvents removed under reduced pressure. Crude residue was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O / ACN) to obtain lnt-C-6.7-1 82 mg (70%) as colourless oil. The following intermediates in Synthesis Table 4 were made according to the procedure described for lnt-C-6.7-1:

[1215]

[1216] Synthesis of tert-butyl ((S)-1-(( -acetamido(3-chlorophenyl)(oxo)-X6- sulfaneylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate lnt-D-6.0-1

[1217] 60% NaH (70 mg, 1.7 mmol, 3 equiv) was slowly added to solution of lnt-A-4.3-Fr-1 (236 mg, 0.58 mmol, 1 equiv) in THF (10 mL). Afterwards acetyl chloride (0.06 mL, 0.87 mmol, 1 .5 equiv) was added and the reaction mixture was stirred at room temperature for 1 h, then quenched with MeOH (0.5 mL). Solvent was removed under reduced pressure. The crude residue was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O / ACN) to obtain lnt-D-6.0-1 211 mg (81 %) as colourless oil.

[1218] The following intermediates in Synthesis Table 5 were made according to the procedure described for lnt-D-6.0-1:

[1219] Synthesis of tert-butyl ((S)-1-(( -(4-chlorothiophen-2-yl)(oxo)(5-((3aS,4S,6aF?)-2- oxohexahydro-1 H-thienof3,4-d1imidazol-4-yl)pentanamido)-X6-sulfaneylidene)amino)-4- methyl- 1-oxopentan-2-yl)carbamate lnt-D-6.1-1 To a stirred solution of acid lnt-X1 (48.5 mg, 0.20 mmol, 1 equiv) in DMF (20 mL) was added EDCI HCI (45.6 mg, 0.24 mmol, 1.2 equiv), HOBT (29.5 mg, 0.22 mmol, 1.1 eqiuv) followed by lnt-B-5.23-Fr-1 (81.3 mg, 0.20 mmol, 1 equiv). The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure and the residue was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O / ACN) to obtain lnt-D-6.1-1 63 mg (50%) as colourless oil.

[1220] The following intermediates in Synthesis Table 6 were made according to the procedure described for lnt-D-6.1-1 : Synthesis of (S)-2-amino- / \ / -((S)-(4-chlorothiophen-2-yl)(oxo)(ureido)-X6-sulfaneylidene)-4- methylpentanamide 2,2,2-trifluoroacetic acid salt ANQSA-003-2

[1221] TFA (0.4 mL, ~10eq) was added to a solution of lnt-C-6.0-2 (195 mg, 0.35 mmol, 1 equiv) in DCM (15 mL) and the mixture was allowed to stir at room temperature for 30 min to 2h (conversion was judged by UPLC / MS). After complete conversion of starting material the reaction mixture was concentrated under reduce pressure the product was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: 0.01 % TFA in H2O I ACN) to obtain ANOSA-003-2 87 mg (53%) as white amorphous solid.

[1222] The following intermediates in Synthesis Table 7 were made according to the procedure described for ANOSA-003-2:

[1223]

[1224]

[1225]

[1226]

[1227] Synthesis of (S)- / V-((S)-acetamido(3-chlorophenyl)(oxo)-X6-sulfaneylidene)-2-amino-4- lnt-D-6.0-2 ANOSA-004-2

[1228] TFA (0.2 mL, ~10eq) was added to a solution of lnt-D-6.0-2 (287 mg, 0.64 mmol, 1 equiv) in DCM (15 mL) and the mixture was allowed to stir at room temperature for 30 min to 2h

[1229] (conversion was judged by UPLC / MS). After complete conversion of starting material the reaction mixture was concentrated under reduce pressure the product was purified by reversed phase chromatography (C18 silica, gradient 98% to 0%: H2O I ACN) to obtain

[1230] ANOSA-004-2 138 mg (62%) as white amorphous solid. Note: Gradient 98% to 0%: 0.01% TFA in H2O I ACN was used to obtain final products as TFA salts. The following intermediates in Synthesis Table 8 were made according to the procedure described for AN OSA-004-2:

[1231]

[1232] Synthesis of 2-(4-acetamidophenyl)acetic acid (lnt-W1) lnt-W1

[1233] To a solution of 2-(4-aminophenyl)acetic acid (0.50 g, 3.30 mmol) in acetonitrile (8.0 mL), acetic anhydride (0.74 g, 7.27 mmol) was added and the reaction mixture was stirred at room temperature for 8h. After completion of reaction as indicated by TLC, the reaction mixture was concentrated under vacuum. The crude was purified by column chromatography (82 % ethyl acetate / hexane) to give title compound as white solid (0.32 g, 50.07 %). LCMS ESI (m / z): 194.0 (M+H).1H NMR (400 MHz, DMSO-d6) 5 12.11 (s, 1H), 9.88 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 3.48 (s, 2H), 2.02 (s,

[1234] 3H). Synthesis of (R)-2,3-bis((tert-butoxycarbonyl)amino)propanoic acid (lnt-W2)

[1235] (Boc)2), NaOH, Boc

[1236] HO HN-Boc Step-1 HO HN-Boc lnt-W2

[1237] To a solution of sodium hydroxide (0.12 g, 1.47 mmol) and (R)-3-amino-2-((tert- butoxycarbonyl)amino)propanoic acid (0.20 g, 0.98 mmol) in water (1 mL) at 0°C, Boc anhydride (0.32 g, 2.94 mmol) in 1,4-dioxane (2 mL) was added and the reaction mixture was stirred at room temperature for 3h. After completion of reaction as indicated by TLC, the reaction mixture was diluted with 10 % sodium hydroxide solution (10 mL) and washed with diethyl ether (3 x 10 mL). The aqueous layer was acidified to pH=2 using dilute HCI (10 mL) and extracted with diethyl ether (3 x 20 mL). The combined organic layer was washed with water (30 mL), dried over sodium sulfate, and concentrated under vacuum to give title compound as white solid (0.25 g, 86.66 %). LCMS ESI (m / z): 305.8, (M +1).

[1238] Following intermediates (lnt-W3 to W5; in Synthesis Table 9) were prepared using similar reaction protocol as shown in lnt-W2: Synthesis of (S)-3-((tert-butoxycarbonyl)amino)-2-((tert-butyldimethylsilyl)oxy)propanoic acid (lnt-W6) lnt-W6-A1 lnt-W6

[1239] Step-1 : It was prepared using similar reaction condition as shown in lnt-W2 LCMS ESI (m / z): 206.0 (M+1)

[1240] Step-2: To a solution of (S)-3-((tert-butoxycarbonyl)amino)-2-hydroxypropanoic acid (0.10 g, 0.48 mmol) in THF (2 mL), TEA (0.20 mL, 1.46 mmol) was added at 0°C and stirred for 30 min. TBDMS-CI (0.11 g, 0.73 mmol) was added at 0°C and reaction mixture was allowed to stir at 70°C for 2h. After completion of reaction as indicated by TLC, reaction mixture was poured into water and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum to give title compound which was directly used for next step (0.31 g crude).

[1241] Synthesis of 2-(thiazol-2-yl)acetic acid (lnt-W7) lnt-W7

[1242] Step-1 : To a solution of thiazole-2-carbaldehyde (1.0 g, 8.83 mmol) in MeOH (10.0 mL), NaBH4 (0.166 g, 4.41 mmol) was added at 0 °C and reaction mixture was stirred for additional 30 min. After completion of reaction as indicated by TLC, reaction mixture was poured into water and extracted with DCM (3 x 25 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum to give title compound as white solid

[1243] (0.75 g, 74.25%). LCMS ESI (m / z): 116.34 (M+H). Step-2: To a solution of thiazol-2-ylmethanol (0.5 g, 4.34 mmol) in DCM (6 mL), thionyl chloride (0.63 mL, 8.68 mmol) was added and the reaction mixture was stirred at 40°C for 1h. The reaction mixture was cooled to room temperature and concentrated under vacuum to give title compound as brown solid (0.535 g, 92.08%). It was used immediately for the next step without further purification LCMS ESI (m / z): 134.2, 136.2 (M & M+2).

[1244] Step-3: 2-(chloromethyl)thiazole (0.4 g, 2.99 mmol) and trimethylsilyl cyanide (0.75 mL, 5.98 mmol) were added into a solution of TBAF (8.98 mL, 8.98 mmol, 1M in THF) and stirred the reaction mixture at room temperature for 16h. The reaction mixture was concentrated and treated with saturated aqueous sodium bicarbonate (10 mL). The product was extracted with DCM (3 x 20 mL). The combined organic layer was washed with brine (30 mL), dried over anhydrous Na2SO4 and evaporated under vacuum. The crude was purified by using column chromatography (35% ethyl acetate / hexane) to obtain title compound as brown gummy solid (0.085 g, 22.91%). LCMS ESI (m / z): 125.2 (M+1).

[1245] Step-4: To a solution of 2-(thiazol-2-yl)acetonitrile (0.055 g, 0.44 mmol) in dioxane:water (0.5:0.5 mL), KOH (0.074 g, 1.32 mmol) was added and the reaction mixture was heated at 100 °C for 2h. The reaction mixture was concentrated under vacuum and treated with water (10 mL). It was acidified with 1N HCI (pH ~2) and the resulted solid was filtered and washed with water and hexane. The solid was dried under vacuum to give title compound as yellow solid (0.033 g, 52.38%). LCMS ESI (m / z): 143.99 (M+1)

[1246] Synthesis of 2-(3-acetamidophenyl)acetic acid (lnt-W8) lnt-W8-A1 lnt-W8

[1247] Step-1: To a solution of methyl 2-(3-aminophenyl)acetate (0.50 g, 3.02 mmol) in THF (5.00 mL), Et3N (0.8 mL, 6.05 mmol) followed by acetyl chloride (0.28 mL, 3.93 mmol) were added at 0°C and allowed to stir for 1h at room temperature. After completion of reaction as indicated by TLC, the reaction mixture was concentrated under vacuum to give title compound as gummy solid (0.6 g, 95.66 %). LCMS ESI (m / z): 208.28(M+1). Step-2: To a solution of 2-(3-acetamidophenyl)acetate (0.6g, 0.28 mmol) in EtOH:H2O (0.5:0.2 ml), LiOH.H2O (0.06g, 1.44mmol) was added and stirred at 60 °C for 2h. After completion of reaction as indicated by TLC, the reaction mixture was concentrated and then poured into aqueous 1 N HCI (pH ~4). The product was extracted with ethyl acetate (2 x 30 mL). The combined organic layer was dried over Na2SC>4 and evaporated under vacuum to give title compound as white solid (0.23 g, 41 .11 %). LCMS ESI (m / z): 194.23 (M+H).

[1248] Synthesis of tert-butyl ((S)-1-(((S)-amino(5-chlorothiophen-3-yl)(oxo)-X6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate & tert-butyl ((S)-1-(((R)-amino(5-chlorothiophen-3-yl)(oxo)-X6-sulfanylidene)amino)-4- methyl- 1-oxopentan-2-yl)carbamate (lnt-B-5.52-Fr-1 & lnt-B-5.52-Fr-2)

[1249] Step-1 : To a solution of 2,3-dibromothiophene (30g, 124.48 mmol) in AcOH (300 mL) was added NCS (17.52 g, 131.43 mmol) at room temperature and stirred for 2 h at 110 °C. After completion of reaction as indicated by TLC, reaction mixture was poured into aqueous sodium hydroxide and extracted with ethyl acetate (3 x 500 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum (47.5 g Crude). 1 H NMR (400 MHz, CDCI3) 5 6.79 (s, 1 H). Step-2: To a stirred solution of 2,3-dibromo-5-chlorothiophene(lnt-B-2.12-A1) (47.5 g, 172.10 mmol) in AcOH (375 mL) was added Zinc dust (55.35 g, 846.00 mmol) at room temperature and stirred for 16 h at 110 °C. After completion of reaction, the reaction mixture was filtered through Celite. The filtrate was poured into sat. sodium bicarbonate solution and extracted with ethyl acetate (3 x 500 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was used for next step (28g, Crude). 1 H NMR (400 MHz, CDCI3) 5 7.04 (d, J= 1.6, 1 H), 6.87 (d, J= 1 .2, 1 H).

[1250] Step-3: To a stirred solution of 4-bromo-2-chlorothiophene (lnt-B-2.12-A2) (2.0 g, 10.12 mmol) in dioxane (20 mL) was added benzyl mercaptan (1.1 mL, 10.12 mmol) and DIPEA (3.49 mL, 20.20 mmol). The reaction mixture was purged with N2 for 30 min. Xantphos (0.59 g, 1.01 mmol) and Pd3dba3(0.46 g, 0.50 mmol) was added to the reaction mixture and heated at 120 °C for 16 h. After completion of reaction as indicated by TLC, the reaction mixture was filtered through celite. The filtrate was poured into water and extracted with ethyl acetate (3x 100 mL). The combined organic layer was dried over Na3SO4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (0.4% ethyl acetate / hexane) to give 4-(benzylthio)-2-chlorothiophene (1.7 g, 70.83 %). 1 H NMR (400 MHz, CDCI3), 5 7.31-7.22 (m, 5H), 6.83 (d, J= 1.2, 1H), 6.77 (d, J= 1.6, 1 H).

[1251] Step-4: To a stirred solution of 4-(benzylthio)-2-chlorothiophene (lnt-B-2.12-A3) (1.7 g, 7.06 mmol) in acetic acid (34 mL)-water (3.4 mL) was added N-chlorosuccinimide (2.82 g, 21.25 mmol) and stirred for 1 h at room temperature. After completion of reaction as indicated by TLC, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layer was dried over Na3SO4 and evaporated under vacuum. The crude was used for next step (2.5 g crude).

[1252] Step-5: Ammonia gas was purged into THF (10 mL) at -78 °C and added into a solution of 5-chlorothiophene-3-sulfonyl chloride (lnt-B-2.12-A4) (2.5 g, 10.41 mmol) in THF (15 mL), the reaction mixture was stirred for additional 30 min. After completion of reaction as indicated by TLC, reaction mixture was allowed to come at room temperature and evaporated under vacuum. The crude was purified by silica gel column chromatography (35 % ethyl acetate / hexane) to give 5-chlorothiophene-3-sulfonamide (1.0 g, 45.45%) LCMS ESI (m / z): 196.0(M-1) Step-6: To a solution of 5-chlorothiophene-3-sulfonamide (lnt-B-2.12) (3.65 g, 18.46 mmol) in THF (50 mL) was added NaH (60% in mineral oil) (3.69 g, 92.33 mmol) at 0°C and stirred for another 1 h. TBDMS-CI (5.56 g, 36.93 mmol) in THF (50 mL) was added and the reaction mixture was stirred for 1 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (80 mL) and extracted with ethyl acetate (3x 80 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum to give N-(tert-butyldimethylsilyl)-5-chlorothiophene-3- sulfonamide as colourless liquid (7.3 g crude).

[1253] Step-7: To a solution of triphenylphosphine (5.2 g, 19.84 mmol) in chloroform (50 mL) was added Hexachloroethane (5.15 g, 21.83 mmol) and stirred at 70°C for 12 h. DIPEA (8.06 mL, 46.80 mmol) was added and stirred further for 30 min. A solution of N-(tert- butyldimethylsilyl)-5-chlorothiophene-3-sulfonamide (7.3 g, 23.40 mmol) in chloroform (7 mL) was added drop wise at 0°C and allowed to stir the reaction mixture for 30 min. Ammonia gas was purged for 30 min into the reaction mixture. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (120 mL) and extracted with DCM (3x 120 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (17% ethyl acetate / hexane) to obtain N-(tert-butyldimethylsilyl)-5-chlorothiophene-3- sulfonimidamide as white solid (2.8 g, 35.41 % over 2 steps). LCMS ESI (m / z): 311.44, 313.46 (M & M+2).

[1254] Step-8: To a solution of N-(tert-butyldimethylsilyl)-5-chlorothiophene-3-sulfonimidamide (lnt-B-3.12) (2.8 g, 9.00 mmol) in DCM (15 mL) was added 4M HCI in dioxane (2 mL) and stirred at room temperature for 1 h. After completion of reaction, reaction mixture was evaporated under vacuum and crude was triturated with n-pentane and diethyl ether to give 5-chlorothiophene-3-sulfonimidamide hydrochloride as white solid. LCMS ESI (m / z): 197.3, 199.3 (M & M+2). (2.4 g, Quantitative).

[1255] Step-9: To a solution of 5-chlorothiophene-3-sulfonimidamide hydrochloride(lnt-B-4.12) (2.4 g, 12.24 mmol) in DMF (20 mL), NaH (60% in mineral oil) (2.44 g, 61.22 mmol) was added and stirred at 0°C for 1 h, 2,5-dioxopyrrolidin-1-yl (tert-butoxycarbonyl)-L-leucinate (4.42 g, 13.46 mmol) in DMF (10 mL) was added and the resulting reaction mixture was stirred at 0°C for 1 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (80 mL) and extracted with ethyl acetate: THF (9:1) (3x 80 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (27% ethyl acetate / hexane) to obtain lnt-B-5.52 as yellow sticky solid (2.6 g, 51.79 %). LCMS ESI (m / z): 410.6, 412.9 (M & M+2). Further the diastereomers were separated by Chiral prep HPLC (Chiral prep HPLC: CHIRAKPAK IA 250 x 5 mm 5um, Mobile phase: A= Liq CO2, B= 0.1 % DEA in IPA: MTBE (70:30), A:B = 70:30) to give lsomer-1 (lnt-B-5.52-Fr-1): Retention time: 7.20 and lsomer-2 (lnt-B-5.52-Fr-2): Retention time 10.25 min.

[1256] Synthesis of tert-butyl ((S)-1-(((S)-arnino(oxo)(thienof3,2-b1thiophen-3-yl)-X6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate & tert-butyl ((S)-1-(((R)-amino(oxo)(thienof3,2-b1thiophen-3-yl)-X6-sulfanylidene)amino)-4- methyl-1-oxopentan-2-yl)carbamate (lnt-B-5.40-Fr-1 & lnt-B-5.40-Fr-2) lnt-B-5.40-Fr-2 lnt-B-5.40-Fr-1 lnt-B-5.40

[1257] Step-1 : To a solution of 3, 4-dibromothiophene (15 g, 62.00 mmol) in THF (150 mL) was added lithium diisopropylamide (2M in THF) (62 mL, 123.96 mmol) at -78 °C and stirred at -78 °C for 2 h. DMF (5.77 mL, 74.38 mmol) was added dropwise to the reaction mixture and then allowed to stir at room temperature for additional 1 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into NH4CI solution (500 mL) and extracted with ethyl acetate (500 mL). The organic layer was dried over Na2SC>4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography to give 3,4-dibromothiophene-2-carbaldehyde(lnt-Y4-A1) (11 g, 65 %).1 H NMR (400 MHz, DMSO-d6) 5 9.85 (s, 1 H), 8.46 (s, 1 H).

[1258] Step-2: To the solution of 3, 4-dibromothiophene-2-carbaldehyde (lnt-Y4-A1) (11 g, 40.74 mmol) in DMF (110 mL) was added ethyl thioglycolate (6 g, 48.88 mmol), potassium carbonate (17 g, 123.9 mmol) and 18-crown-6 (1 g, 4.03 mmol). The reaction mixture was heated at 70 °C for 2 h. After completion of reaction as indicated by LCMS, the reaction mixture was poured into ice cold water (200 mL). The solid was filtered and washed with water. The residue was dried under vacuum to give 6-bromothieno [3, 2-b] thiophene-2- carboxylate(lnt-Y4-A2) (12.5 g, Quantitative). 1 H NMR (400 MHz, DMSO-d6) 5 8.31 (s, 1 H), 8.12 (s, 1 H), 4.33 (q, J=7.1 Hz, 1 H), 1.32 (t, J=6.8 Hz, 3H).

[1259] Step-3: To a solution of ethyl 6-bromothieno [3, 2-b] thiophene-2-carboxylate (lnt-Y4-A2) (12.5 g, 42.94 mmol) in THF:water (1 :1) (120 mL) was added lithium hydroxide monohydrate (5.4 g, 129.26 mmol) and the reaction mixture was heated at 70 °C for 3 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (200 mL) and acidified with 1 N HCI (pH ~4), the resulted solid was filtered and dried under vacuum to give 6-bromothieno[3,2-b]thiophene-2-carboxylic acid (lnt-Y4-A3) (8.6, 76%). 1 H NMR (400 MHz, DMSO-d6) 5 13.54 (s, 1 H), 8.21 (s, 1 H), 8.08 (s, 1 H).

[1260] Step-4: To a degassed solution of 6-bromothieno[3,2-b]thiophene-2-carboxylic acid (Int- Y4-A3) (4.3 g, 16.34 mmol) in N-Methyl-2-pyrrolidone (45 mL) was added potassium carbonate (0.33 g,2.45 mmol) and silver acetate (0.27 g,1.63 mmol). The reaction mixture was heated at 120 °C for 3 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (200 mL) and extracted with ethyl acetate (2x200 mL). The combined organic layer was washed with brine (4x200 mL), dried over Na2SO4 and evaporated under vacuum. The crude product purified by silica gel column chromatography to give 3-bromothieno[3,2-b]thiophene (lnt-Y4-A4) (3 g, 41.89%). 1 H NMR (400 MHz, DMSO-d6) 5 7.82 (s, 1 H), 7.79 (d, J=5.1 Hz, 1 H), 7.56 (d, J=5.1 Hz, 1 H).

[1261] Step-5: To a degassed solution of 3-bromothieno [3, 2-b]thiophene (lnt-Y4-A4) (3.6 g, 16.43 mmol) and DIPEA (4.25 g, 32.86 mmol) in dioxane (36 mL), xantphos (0.95 g, 1.64 mmol), Pd2dba3 (0.75 g,0.82 mmol) and benzyl mercaptan (2.04 g, 16.43 mmol) were added and heated at 100 °C for 3h. After completion of reaction as indicated by TLC, the reaction mixture was filtered through celite and filtrate was poured into water (100 mL). The product was extracted with ethyl acetate (2x100 mL). The combined organic layer was washed with brine (2x200 mL), dried over Na2SO4 and evaporated under vacuum. The crude product was subjected to silica gel column chromatography to give title compound (lnt-Y4-A5) (3.4 g, 78.86 %). 1H NMR (400 MHz, DMSO-d6) 5 7.71 (d, J=5.2, 1 H), 7.53 (s, 1H), 7.46 (d, J=5.2 Hz, 1H), 7.29-7.21 (m, 5H), 4.23 (s, 2H)

[1262] Step-6: To a stirred solution of 3-(benzylthio)thieno[3,2-b]thiophene (lnt-Y4-A5) (3.4 g, 12.95 mmol) in acetic acid (68 mL) and water (6.8 mL), N-chlorosuccinimide (5.18 g, 38.87 mmol) was added in portions at room temperature. The reaction mixture was stirred for 2 h. After completion of reaction as indicated by TLC, the reaction mixture was evaporated under vacuum and then partitioned between water (150 mL) and ethyl acetate (150 mL). The organic layer was washed with water (150 mL), dried over Na2SO4 and evaporated under vacuum. The crude product was purified with silica gel column chromatography to give title compound (lnt-Y4) (2.9 g, 93.75%).

[1263] Step-7: To a freshly prepared sat. ammonia solution in THF (20 mL), thieno[3,2- b]thiophene-3-sulfonyl chloride (lnt-Y4) (2.9 g, 12.14 mmol) in THF (10 mL) was added at -78 °C. After completion of reaction as indicated by TLC, the reaction mixture was evaporated to dryness and crude was purified by silica gel column chromatography to obtain title compound (lnt-B-2.40) (2 g, 75%) LCMS ESI (m / z): 218.2 (M-H).

[1264] Step-8: To a solution of thieno[3,2-b]thiophene-3-sulfonamide(lnt-B-2.40) (2.7 g, 12.31 mmol) and TEA (6.85 mL, 49.24 mmol) in THF (20 mL) at 0°C, TBDMS-CI (5.56 g, 36.93 mmol) in THF (7 mL) was added. The reaction mixture was allowed to stir at 70° for 3 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (150 mL) and extracted with ethyl acetate (3x 150 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum to give N-(tert- butyldimethylsilyl)thieno[3,2-b]thiophene-3-sulfonamide (7.8 g crude).

[1265] Step-9: To a solution of triphenylphosphine (7.91 g, 30.15 mmol) in chloroform (50 mL), hexachloroethane (7.83 g, 33.16 mmol) was added and stirred at 70°C for 12 h to give fresh PPhaCh. DIPEA (6.87 mL, 40.2 mmol) was added and stirred the reaction mixture for 30 min. A solution of N-(tert-butyldimethylsilyl)thieno[3,2-b]thiophene-3-sulfonamide (15.8 g, 50.64 mmol) in chloroform (10 mL) was added drop wise at 0°C. The resulting reaction mixture was allowed to stir at 0°C for 30 min. Ammonia gas was purged into for 30 min at 0°C. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (150 mL) and extracted with DCM (3x 150 mL). The combined organic layer was dried over Na2SC>4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (17% ethyl acetate / hexane) to obtain N-(tert- butyldimethylsilyl)thieno[3,2-b]thiophene-3-sulfonimidamide (lnt-3.40) (1.0 g, 25 %). LCMS ESI (m / z): 333.5, 334.5 (M & M+2).

[1266] Step-10: To a solution of N-(tert-butyldimethylsilyl)thieno[3,2-b]thiophene-3- sulfonimidamide(lnt-3.40) (1 g, 3.01 mmol) in 1 , 4 dioxane (2 mL), 4M HCI in dioxane (2 mL) was added and stirred at room temperature for 2 h. After completion of reaction, reaction mixture was evaporated under vacuum and triturated with n-pentane and diethyl ether to give thieno[3,2-b]thiophene-3-sulfonimidamide hydrochloride (lnt-4.40) (0.91 g, quantitative). LCMS ESI (m / z): 219.2 (M +1).

[1267] Step-11 : To a solution of thieno[3,2-b]thiophene-3-sulfonimidamide hydrochloride (lnt- 4.40) (0.9 g, 4.12 mmol) in DMF (5 mL) was added NaH (60% in mineral oil) (0.49 g, 12.36 mmol) and stirred at 0°C for 30 min. A solution of 2,5-dioxopyrrolidin-1-yl (tert- butoxycarbonyl)-L-leucinate (1.48 g, 4.53 mmol) in DMF (5 mL) was added to the reaction mixture and stirred for 2 h. After completion of reaction as indicated by TLC, the reaction mixture was poured into water (60 mL) and extracted with ethyl acetate (3x 60 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (38% ethyl acetate / hexane) to obtain lnt-5.40 as yellow sticky solid (0.88 g, 51.76 %). LCMS ESI (m / z): 432.8 (M+1).

[1268] Further the diastereomers were separated by Chiral prep HPLC (YMC CHIRALART CELLULOSE-SC, 250 x 20 mm, S-5pm, Mobile phase: A= n-Heptane, B= IPA: Acetonitrile (70:30), A:B = 90:10) to give lsomer-1 (lnt-5.40-Fr-1): Retention time: 8.90) and lsomer-2 (lnt-5.40-Fr-2): Retention time 23.76 min. Synthesis of tert-butyl ((S)-1-(((R)-(4-chlorothiophen-2-yl)(oxo)(2-(thiophen-2- yl)acetamido)-X6-sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate & tert-butyl ((S)-1-(((S)-(4-chlorothiophen-2-yl)(oxo)(2-(thiophen-2-yl)acetamido)-X6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate

[1269] (lnt-B-6.1-Fr-1 & lnt-B-6.1-Fr-2)

[1270] Step-1 : To a solution of 2-(thiophen-2-yl)acetic acid (0.08 g, 0.56 mmol) in DCM (2.5 mL), EDC.HCI (0.20 g, 1.06 mmol) and DMAP (0.13 g, 1.06 mmol) were added at 0°C and stirred for 10 min. lnt-B-5.23 was added (0.23 g, 0.56 mmol) to the reaction mixture and allowed to stir at room temperature for 1 h. After completion of reaction as indicated by TLC, reaction mixture was poured into water (30 mL) and extracted with DCM (3 x 25 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by flash column chromatography (20 % MeOH / DCM) to give title compound as mixture of isomers (0.18 g, 61.72 %).

[1271] Further the diastereomers were separated by chiral prep HPLC (Column: CHIRALPAK IG 250X20 mm 5pm, Mobile phase: A= liq CO2, B = 0.1% DEA in I PA: MTBE (70:30), A:B = 55:45 to give lsomer-1 (lnt-B-6.1-Fr-1): Retention time: 1.91 min & lsomer-2 (lnt-B-6.1-Fr- 2): Retention time: 4.60 min. The following intermediates were made according to the procedure described for Int-B-

[1272] 6.1 using precursors shown in Synthesis Table 10, below. Respective isomers were separated by chiral prep HPLC purification as per the specification shown in the table under “Analytical data” for the respective intermediate:

[1273]

[1274]

[1275]

[1276]

[1277]

[1278]

[1279]

[1280] Synthesis of di-tert-butyl ((R)-4-(((R)-N'-((tert-butoxycarbonyl)-L-leucyl)-4- chlorothiophene)-2-sulfonoamidimidamido)-4-oxobutane-1 ,3-diyl)dicarbamate (lnt-B-6.29-Fr-1) lnt-W3 lnt-B-6.29-Fr-1 To a solution of (R)-2,4-bis((tert-butoxycarbonyl)amino)butanoic acid (lnt-W3) (0.1 g, 0.31 mmol) in DMF (1 mL) was added DIPEA (0.16 ml , 0.94 mmol), EDC.HCI (0.20 g , 1.06 mmol) and HOBt (0.06 g , 0.47 mmol) at room temperature and stirred for 15 min. Int-B- 5.23-Fr-1 (0.13 g, 0.31 mmol) was added to the reaction mixture and allowed to stir at room temperature for 4 h. After completion of reaction as indicated by TLC, reaction mixture was poured into water (30 mL) and extracted with ethyl acetate (3 x 25 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by reverse phase column chromatography (Water: Acetonitrile, 9:1) to give title compound as sticky solid (0.1 g, 40.34 %). LCMS ESI (m / z): 710.3, 712.2 (M & M+2). Following intermediates were made according to the procedure described for lnt-B-6.29-Fr-1 using precursors shown in Synthesis Table 11 , below:

[1281] Synthesis of tert-butyl ((S)-1-(((R)-((R)-2-((tert-butoxycarbonyl)amino)-3- hydroxypropanamido)(4-chlorothiophen-2-yl)(oxo)-X6-sulfanylidene)amino)-4-methyl-1- oxopentan-2-yl)carbamate (lnt-B-6.38-Fr-1)

[1282] To a solution of (tert-butoxycarbonyl)-D-serine (0.07 g, 0.36 mmol) in DMF (0.5 mL) was added HATLI (0.14 g, 0.36 mmol) and DI PEA (0.12 mL, 0.72 mmol) at 0°C and stirred for 10 min. lnt-B-5.23-Fr-1 (0.10 g, 0.24 mmol) was added to the reaction mixture and stirred further at room temperature for 2 h. After completion of reaction as indicated by TLC, reaction mixture was poured into water (10 mL) and extracted with DCM (3 x 10 mL). The combined organic layer was dried over Na2SC>4 and evaporated under vacuum. The crude was purified by column chromatography (30 % MeOH / DCM) to give title compound as white solid. (0.09 g, 62.09 %). LCMS ESI (m / z): 497.9 (M -Boc).

[1283] Following intermediates were made according to the procedure described for lnt-B-6.38-Fr-1 using intermediate shown in Synthesis Table 12, below:

[1284] Synthesis of tert-butyl ((S)-1-(((R)-(4-chlorothiophen-2-yl)(2-(3,4- dihydroxyphenyl)acetamido)(oxo)-X6-sulfanylidene)amino)-4-methyl-1 -oxopentan-2- vDcarbamate

[1285] (lnt-B-6.42-Fr-1) lnt-B-5.23-Fr-1 lnt-B-6.42-Fr-1

[1286] To a solution of 2-(3,4-dihydroxyphenyl)acetic acid (0.095 g, 0.548 mmol) in acetonitrile (3.0 mL), TEA (0.16 mL, 1.097 mmol) and lnt-B-5.23-Fr-1 (0.15 g, 0.365 mmol) were added at 0°C and stirred for 10 min. T3P (50% Solution in ethyl acetate) (0.46 mL, 0.731 mmol) was added to the reaction mixture and stirred further at room temperature for 1 h. After completion of reaction as indicated by TLC, reaction mixture was poured into water and extracted with DCM (3 x 25 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by column chromatography using (6 % MeOH / DCM) to give title compound as off white solid (0.035 g, 17.50 %). LCMS ESI

[1287] (m / z): 504.8(M-56).

[1288] Syntheiss of tert-butyl ((S)-1-(((R)-benzamido(4-chlorothiophen-2-yl)(oxo)-X6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate & tert-butyl ((S)-1-(((S)-benzamido(4-chlorothiophen-2-yl)(oxo)-X6-sulfanylidene)amino)-4- methyl-1-oxopentan-2-yl)carbamate (lnt-B-6.43-Fr-1 & lnt-B-6.43-Fr-2) lnt-B-6.43-Fr-2

[1289] To a solution of lnt-B-5.23 (0.25 g, 0.60 mmol) in THF (1.5 mL) was added NaH (60% mineral oil) (0.07 g, 1.82 mmol) at 0°C and stirred for 10 min. Then benzoyl chloride (0.13 g, 0.91 mmol) in THF (1 mL) was added to the reaction mixture and allowed to stir at room temperature for 30 min. After completion of reaction as indicated by TLC, reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by column chromatography (5 % MeOH / DCM) to give mixture of isomers (0.27 g, 86.26 %). LCMS ESI (m / z): 514.3, 516.3 (M & M+2). Further the diastereomers were separated by chiral prep HPLC (Column: CHIRALPAK IG 250X20 mm 5pm, Mobile phase: A= Liq CO2, B = 0.1% DEA in I PA: MTBE (70:30), A:B = 60:40 to give lsomer-1 (lnt-B-6.43-Fr-1): Retention time: 1.91 min & lsomer-2 (lnt-B-6.43- Fr-2): Retention time: 4.60 min. Following intermediates were made according to the procedure described above for lnt-B-6.43-Fr-1 and Fr-2 using precursors shown in Synthesis Table 13, below. Respective isomers were separated by chiral prep HPLC purification as per the specification shown in table for respective intermediate:

[1290]

[1291] Synthesis of tert-butyl ((S)-1-(((R)-acetamido(5-chlorothiophen-3-yl)(oxo)-k6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate (lnt-B-6.48-Fr-1) lnt-B-5.52-Fr-1 lnt-6.48-Fr-1

[1292] To a solution of lnt-B-5.52-Fr-1 (0.06 g, 0.15 mmol) in THF (1.0 mL) was added TEA (0.06 mL, 0.45 mmol) at 0°C and stirred for 30 min. After that acetic anhydride was added (0.01 mL, 0.10 mmol) and stirred at room temperature for 1 hr. After completion of reaction as indicated by TLC, reaction mixture was poured into water (30 mL) and extracted with ethyl acetate (3 x 10 mL). The combined organic layer was dried over Na2SC>4 and evaporated under vacuum. The crude was purified by reverse phase column chromatography (Water: acetonitrile, 8:2) to give title compound as white solid. (0.045 g, 68.18%). LCMS ESI (m / z): 452.0, 454.1 (M & M+2)

[1293] Following intermediates were made according to the procedure described for lnt-B-6.48-

[1294] Fr-1 using precursors shown in Synthesis Table 14, below:

[1295] Synthesis of tert-butyl ((S)-1-(((R)-(4-chlorocyclopenta-1 ,4-dien-1-yl)(oxo)(ureido)-X6- sulfanylidene)amino)-4-methyl-1-oxopentan-2-yl)carbamate

[1296] (lnt-B-6.50-Fr-1) lnt-B-5.52-Fr-1 lnt-B-6.50-Fr-1 To a solution of lnt-B-5.52-Fr-1 (0.15 g, 0.36 mmol) in DCM (1.5 mL) was added TEA (0.30 mL, 2.19 mmol) at 0°C and stirred for 30 min. TMS-NCO (0.14 mL, 1.09 mmol) was added to the reaction mixture and allowed to stir at room temperature for 16 h. After completion of reaction indicated by TLC, reaction mixture was poured into water and extracted with DCM (3 x 10 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by reverse phase chromatography (Water: Acetonitrile, 7:3) to give title compound as white solid (0.10 g, 61.81%). LCMS ESI (m / z): 453.9, 455.0 (M & M+2)

[1297] Following intermediates were made according to the procedure described for lnt-B-6.50 using precursors shown in Synthesis Table 15, below:

[1298] Synthesis of (2S)-N-(N-(L-leucyl)-5-chlorothiophene-3-sulfonimidoyl)-2-amino-4- methylpentanamide dihydrochloride lnt-B-4.12 lnt-B-6.52

[1299] To a suspension of 60% NaH (0.12 g, 3.0 mmol) in DMF (3.0 mL), 5-chlorothiophene-3- sulfonimidamide hydrochloride (lnt-B-4.12) (0.2 g, 1.01 mmol) was added at 0 °C and stirred for 1h at same temperature. 2,5-dioxopyrrolidin-1-yl (tert-butoxycarbonyl)-L- leucinate (0.66 g, 2.00 mmol) was added to the reaction mixture and stirred at room temperature for 1h. After completion of reaction as indicated by TLC, reaction mixture was poured into water and extracted with ethyl acetate (2x50 mL). The combined organic layer was dried over Na2SO4 and evaporated under vacuum. The crude was purified by silica gel column chromatography (30 % ethyl acetate / hexane) to give title compound as white solid (0.15 g, 23.69 %). LCMS ESI (m / z): 623.6, 625.5 (M & M+2).

[1300] Synthesis of (S)-2-amino-N-((R)-(2-amino-2-methylpropanamido)(4-chlorothiophen-2- yl)(oxo)-X6-sulfanylidene)-4-methylpentanamide bis(2,2,2-trifluoroacetate)

[1301] (ANQSA-041-1) &

[1302] (S)-2-amino-N-((S)-(2-amino-2-methylpropanamido)(4-chlorothiophen-2-yl)(oxo)-X6- sulfanylidene)-4-methylpentanamide bis(2,2,2-trifluoroacetate)

[1303] (ANQSA-041-2) lnt-B-6.6-Fr-1 ANOSA-041-1

[1304] To a solution of lnt-B-6.6-Fr-1 (75 mg, 0.12 mmol) in 1,4-dioxane (1 mL), 4M HCI in dioxane (1 mL) was added and the reaction mixture was allowed to stir at room temperature for 2h. After completion of reaction as indicated by TLC, reaction mixture was concentrated under vacuum followed by trituration with n-pentane and diethyl ether to give title compound as hydrochloride salt which was further purified by reverse phase prep. HPLC (Column: SUNFIRE Prep C18 OBD, 19 x 250 mm, 5pm, Mobile phase: A= 0.05 % TFA in water, B = Acetonitrile +10% MTBE, A:B = 84:16) to give title compound as TFA salt (21 mg, 28.47 %).

[1305] 1H NMR (400 MHz, DMSO-d6) 5 7.89 (br s, 6H), 7.77 (s, 1 H), 7.47 (d, J= 1.2 Hz, 1 H), 3.55-3.52 (m, 1H), 1.76-1.73 (m, 1H), 1.64-1.60 (m, 1H), 1.48-1.42 (m, 1H), 1.34 (d, J =

[1306] 5.6 Hz, 6H), 0.86 (d, J = 6.4 Hz, 6H). LCMS: 395.8, 397.8 (M & M+2). Purity at 210 nm:

[1307] 95.76 % Similarly, lnt-B-6.6-Fr-2 was treated with 4N HCI as deprotection agent to give ANOSA-041-2. lnt-B-6.6-Fr-2 ANOSA-041-2

[1308] 1 H N MR (400 MHz, DMSO-d6) 5 7.91 (br s, 3H), 7.85 (br s, 3H), 7.76 (d, J= 1.6 Hz, 1 H), 7.46 (s, 1 H), 3.54 (br s, 1 H), 1.76-1.71 (m, 1 H), 1.68-1.61 (m, 1 H), 1.51-1.46 (m, 1 H), 1.35 (s, 3H), 1.33(s, 3H), 0.87 (t, J = 6.0Hz, 6H). LCMS: 395.8, 397.8 (M & M+2).

[1309] Purity at 210 nm: 100.0 %

[1310] Synthesis of (S)-2-amino-N-((R)-(4-chlorothiophen-2-yl)(oxo)(2-(thiophen-2- yl)acetamido)-X6-sulfanylidene)-4-methylpentanamide hydrochloride &

[1311] (S)-2-amino-N-((S)-(4-chlorothiophen-2-yl)(oxo)(2-(thiophen-2-yl)acetamido)-X6- sulfanylidene)-4-methylpentanamide hydrochloride lnt-B-6.1 -Fr-1 & lnt-B-6.1-Fr-2 ANOSA-029-2 To a solution of lnt-B-6.1-Fr-1 (0.08 g, 0.14 mmol) in 1,4-dioxane (1 mL), 4M HCI in dioxane (1 mL) was added and stirred at room temperature for 1h. After completion of reaction as indicated by TLC, reaction mixture was concentrated under reduce pressure followed by trituration with n-pentane and diethyl ether to give title compound as white solid which was further purified by reverse phase Prep. HPLC (Column: SUNFIRE Prep C18 OBD, 19 x 250 mm, 5pm, Mobile phase: A= 0.01% HCI in water, B = Acetonitrile, A:B = 62:38) to give title compound as hydrochloride salt (12 mg, 18.46 %).

[1312] 1H NMR (400 MHz, DMSO-d6) 5 7.90 (br s, 3H), 7.79 (d, J = 1.2 Hz, 1 H), 7.47 (d, J = 1.2 Hz, 1 H), 7.32 (d, J = 5.2 Hz, 1 H), 6.92 - 6.90 (m, 1 H), 6.85 (s, 1 H), 3.65 (s, 2H),3.52- 3.50(m, 1 H), 1.77-1.73 (m, 1H), 1.67-1.62 (m, 1 H), 1.48-1.43 (m, 1 H), 0.88-086 (dd, J = 6.4, 2.0 Hz, 6H). LCMS: 434.8, 436.8 (M+, M+1).

[1313] Similarly lnt-B-6.1-Fr-2 was reacted with 4M HCI in dioxane followed by reverse phase Prep. HPLC (Column: SUNFIRE Prep C18 OBD, 19 x 250 mm, 5pm, Mobile phase: A= 0.01% HCI in water, B = Acetonitrile, A:B = 62:38) to give title compound as hydrochloride salt(12 mg, 25 %).

[1314] 1H NMR (400 MHz, DMSO-d6) 5 7.90 (br s, 3H), 7.79 (s, 1 H), 7.46 (s, 1 H), 7.32 (d, J = 5.2 Hz, 1H), 6.92-6.90 (m, 1H), 6.85 (s, 1 H), 3.65 (s, 2H), 1.76-1.72 (m, 1H), 1.68-1.62 (m, 1H), 1.50 - 1.43 (m, 1H), 0.87 (t, J = 10.8, 5.2 Hz, 6H). LCMS: 434.7, 436.8 (M & M+2).

[1315] Synthesis of (R)-N-((R)-N-(L-leucyl)-4-chlorothiophene-2-sulfonimidoyl)-2,5- diaminopentanamide trihydrochloride (ANOSA-056-1) lnt-B-6.15-Fr-1 ANOSA-056-1

[1316] To a solution of lnt-B-6.15-Fr-1 (0.085 g, 0.11 mmol) in DCM (1 mL) was added triisopropylsilane (0.4 mL), 4M HCI in dioxane (0.8 mL) and stirred at room temperature for 2h. After completion of reaction as indicated by TLC, reaction mixture was concentrated under reduced pressure followed by trituration with n-pentane and diethyl ether to give title compound as white solid which was further purified by reverse phase Prep. HPLC (Column: YMC-PACK ODS-AQ Prep C18-S, 250 X 20mm S-5pm, 12nm, Mobile phase: A= 0.01% HCI in water, B = Acetonitrile, A: B = 87:13) to give title compound as HCI salt (0.017, 27.41 %).

[1317] 1H NMR (400 MHz, DMSO-d6) 5 8.05-7.96 (br s, 9H), 7.78 (d, J = 1.6 Hz, 1H), 7.53 (d, J = 1.6 Hz, 1 H), 3.57 (br s, 2H), 2.78 (br s, 2H), 1.82 - 1.76 (m, 2H), 1.70-1.65 (m, 3H), 1.62-1.59 (m, 1H), 1.52 - 1.45 (m, 1H), 0.87 (d, J = 6.0 Hz, 6H). LCMS ESI (m / z): 424.1, 426.1 (M & M+2). Purity at 210 nm: 100 %

[1318] The following compounds shown in Synthesis Table 16 were made according to the procedure described for compound ANOSA-029-1 & 2 or ANOSA-056-1 using HCI as de-protecting agent:

[1319]

[1320] Mixture of diastereomers

[1321] The following compounds shown in Synthesis Table 17 were prepared according to procedures similar to those described hereinabove:

[1322] Mixture of diastereomers

[1323] Biological Methods

[1324] Study 1 - Enzyme Inhibition

[1325] The aminoacylation reaction catalyzed by aminoacyl-tRNA synthetases (aaRS) takes place in two steps. In the first step, aaRS activates its cognate amino acid with ATP; and in the second step the activated amino acid is loaded to its corresponding tRNA. This reaction can be summarized as follows: aaRS + aa + ATP = aaRS-aa-AMP + PPi aaRS-aa-AMP + tRNA = aa-tRNA + AMP + aaRS wherein: aaRS, aminoacyl-tRNA synthetase; aa, amino acid; aaRS-aa-AMP, enzymebound to aminoacyl-adenylate; AMP, adenosine monophosphate; aa-tRNA, aminoacyl- tRNA, PPi, inorganic pyrophosphate.

[1326] Leucyl-tRNA Synthetase

[1327] Determination of IC50

[1328] The activity of the pathogenic aaRSs was monitored by measuring AMP production using the commercial kit AMP-Glo (Promega, Madison, USA).

[1329] Ligand stock solutions were prepared in 100% DMSO at 10 mM concentration. An assay buffer consisting of 100 mM Tris HCI pH 7.6, 40 mM MgCI, 20 mM KCI and 150 mM NaCI was prepared in dH2O. An enzyme solution containing 72.95 pM LeuRS was prepared in assay buffer to provide 20 nM final assay concentration and 50 nM reservoir concentration for a 1 :2.5 dilution in the assay. A substrate solution was also prepared in assay buffer with 50 mM L-leucine, 10 mM ATP and 100 mg / mL tRNA. A final assay concentration of 500 pM L-leucine, 16.7 pM ATP and 0.5 mg / mL tRNA and reservoir concentration of 833.33 pM L-leucine, 27.83 pM ATP and 0.83 mg / mL tRNA was used for a 1 :1.66 dilution in assay. In a 384-well plate format, ten-point concentration response curves were generated for each compound using a top concentration of 10 pM. The known inhibitor LeuAMS was used as a positive control for the LeuRS assay. 100% DMSO was used as a negative control. The IC50 was calculated based on non-linear regression analysis.

[1330] The data are summarised in the following table.

[1331] Key:

[1332] A < 100 nM; 100 nM < B < 500 nM; 500 nM < C < 2 pM; 2 pM < D < 10 pM; 10 pM < E.

[1333] (*) mixture of diastereomers

[1334] Study 2 - Antibacterial Activity

[1335] Minimum Inhibitory Concentrations (MICs) were determined by the broth micro-dilution method performed according to Clinical Laboratory Standards Institute guidelines. For testing, 5 mg / mL DMSO solutions were prepared by dissolving solids in DMSO. Standard antibiotics were prepared according to CLSI guidelines as 5 mg / mL stock solutions. Upon DMSO stock solutions preparation, the working solutions in MH media were prepared by adding 38.4 μL of stock solution to 1461.6 μL of MH media. Out of these working solutions 100 μL were transferred to wells in the third column of 96-well assay plates. Assay plates were previously filled with 50 μL of MH media in all wells except for the wells in the third column. Upon compounds and antibiotics addition, 50 μL was transferred from the third to the fourth column, then from the fourth to the fifth and so on. In this manner, the compounds and antibiotics were plated in 96-well assay plates in serial two-fold dilutions starting from a top concentration of 256 pg / mL or 64 pg / mL.

[1336] MIC value was determined by visual inspection of bacterial growth within 96-well plates. The first column in which there was no visible growth of bacteria was determined as MIC value for compound or antibiotic tested in that particular row. ATCC strains were used as reference strains for which there is a determined value of MIC values for standard antibiotics. The assay is considered valid when MIC values for standard antibiotics are within CLSI designated range for ATCC strain tested.

[1337] The data are summarised in the following table.

[1338] Key:

[1339] A = E. coli ATCC 25922

[1340] B = E. coli BAA-2469 C = K. pneumoniae ATCC 700603

[1341] D = E. coli BW25113

[1342] E = K. pneumoniae ATCC 43816

[1343] F = P. aeruginosa ATCC 27853

[1344] G = A. baumannii B1931

[1345] Study 3 - Human Cell Viability

[1346] Compounds were assessed for potential non-specific cytotoxic effects against a human hepatic cell line (HepG2 ATCC HB-8065). 96-well plates were seeded with HepG2 cells in concentration of 15,000 cells per well in 100 μL of MEM growth media completed with 1% NEAA and 1% sodium pyruvate. Border wells were filled with 100 μL of sterile PBS. Two days upon cells incubation, the compounds were added. Compound dilutions were prepared in 96-well V-bottom plate in pure DMSO. Growth media from 5 plates were aspirated and replaced with 98.7 μL of fresh growth media. 1.28 μL of compounds prepared in V-bottom plates were transferred with multichannel pipette into test plates (78.1x dilution). Final DMSO concentration was 1.28% per well. In control wells, 1.28 pL of DMSO was added in 98.7 μL of media. Compounds were tested in duplicates. Cells were incubated with compounds for 24 hours when cell viability was assessed by measuring ATP levels. ATP levels were measured by adding 50 μL of CellTiter-Glo reagent to each well and after 5 minutes of incubation luminescence was measured with SpectraMax i3. The potential effect of tested compounds on cell viability was determined by comparing the signal obtained in presence of different concentrations of the compounds with those obtained in the presence of DMSO only. The potential effects were then calculated and presented as IC50 values (μg / mL).

[1347] The data are summarised in the following table.

[1348] The foregoing has described the principles, preferred embodiments, and modes of operation of the present invention. However, the invention should not be construed as limited to the particular embodiments discussed. Instead, the above-described embodiments should be regarded as illustrative rather than restrictive. It should be appreciated that variations may be made in those embodiments by workers skilled in the art without departing from the scope of the present invention. REFERENCES

[1349] A number of publications are cited herein in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below.

[1350] Each of these references is incorporated herein by reference in its entirety into the present disclosure, to the same extent as if each individual reference was specifically and individually indicated to be incorporated by reference.

[1351] Finn et al., 2018, “2-Amino-N-(arylsulfinyl)-acetamide compounds as inhibitors of bacterial aminoacyl-tRNA synthetase”, international (PCT) patent publication number WO 2018 / 065611 A1 published 12 April 2018.

[1352] Gadahk et al., 2012, “Aminoacyl-tRNA synthetase inhibitors as antimicrobial agents: a patent review from 2006 till present”, Expert Opin. Ther. Patents, Vol. 22, No. 12, pp. 1453-1465.

[1353] Hurdle et al., 2005, “Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents”, Antimicrobial Agents and Chemotherapy, Vol. 49, pp. 4821-4833.

[1354] Jirgensons et al., 2016, “Novel N-acyl-sulfonamide derivatives as aminoacyl-tRNA synthetase inhibitors”, international (PCT) patent publication number WO 2016 / 129983 A 1 published 18 August 2016.

[1355] Laupland et al., 2003, “Treatment of staphylococcus aureus colonization and prophylaxis for infection with topical intranasal mupirocin: An evidence-based review”, Clinical Infectious Diseases, Vol. 37, pp. 933-938.

[1356] Ochsner et al., 2007, “Aminoacyl-tRNA synthetases: essential and still promising targets for new anti-infective agents”, Expert Opinion on Investigational Drugs, Vol. 16, pp. 573-593.

[1357] Pham et al., 2014, “Aminoacyl-tRNA synthetases as drug targets in eukaryotic parasites”, I nt. J. Parasitol. Drugs Drug Resist., Vol. 4, Issue 1, pp. 1-13.

[1358] Vondenhoff et al., 2011 , “Aminoacyl-tRNA synthetase inhibitors as potential antibiotics”, Eur. J. Med. Chem., Vol. 46, pp. 5227-5236.

[1359] Edmund et al. 2021 , “2-Amino-N-(amino-oxo-aryl-lambda6-sulfanylidene)acetamide compounds and their therapeutic use”, international (PCT) patent publication number WO 2021 / 123237 A1 published 24 June 2021.

Claims

CLAIMS 1. A compound selected from compounds of the following formula, and pharmaceutically acceptable salts, hydrates, and solvates thereof:wherein: -Y is independently -NRUARUBor -RP; -RUAis independently -H or -RUUA; -RUUAis independently: -RU1, -RU2, -RU3, -RU4, -RU5, -LU-RU2, -LU-RU3, -LU-RU4, -C(=O)-RU4, -LU-RU5, or -C(=O)-RU5; -RU1is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups -RUU2; each -RU2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU3is non-aromatic C3-8heterocyclyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -RU5is C5-10heteroaryl, and is optionally substituted with one or more groups -RUU1and one or more groups -RUU2; each -LU- is linear or branched saturated C1-4alkylene, and is optionally substituted with one group selected from -OH, -ORUL, -NH2, -NHRUL, and -NRUL2; each -RULis independently linear or branched saturated C1-4alkyl; each -RUU1is independently selected from: -RUU, -LUU-OH, -LUU-ORUU, -LUU-NH2, -LUU-NHRUU, -LUU-N(RUU)2, and -LUU-RUM;each -RUU2is independently selected from:-F, -Cl, -Br, -I,-OH, -ORUU,-CF3, -CHF2, -OCF3, -OCHF2,-NH2, -NHRUU, -N(RUU)2, -RUM,-C(=O)OH, -C(=O)ORUU, -OC(=O)RUU,-C(=O)NH2, -C(=O)NHRUU, -C(=O)N(RUU)2, -C(=O)RUM,-NHC(=O)RUU, -NRUNC(=O)RUU,-NHC(=O)NH2, -NHC(=O)NHRUU, -NHC(=O)N(RUU)2, -NHC(=O)RUM, -NRUNC(=O)NH2, -NRUNC(=O)NHRUU, -NRUNC(=O)N(RUU)2, -NRUNC(=O)RUM,-NHC(=O)ORUU, -NRUNC(=O)ORUU,-OC(=O)NH2, -OC(=O)NHRUU, -OC(=O)N(RUU)2, -OC(=O)RUM,-NHC(=NH)NH2,-C(=O)RUU,-S(=O)NH2, -S(=O)NHRUU, -S(=O)N(RUU)2, -S(=O)RUM,-S(=O)2NH2, -S(=O)2NHRUU, -S(=O)2N(RUU)2, -S(=O)2RUM,-NHS(=O)RUU, -NRUNS(=O)RUU,-NHS(=O)2RUU, -NRUNS(=O)2RUU,-S(=O)RUU, -S(=O)2RUU,-SH, -SRUU, -CN, and -NO2; wherein: each -Luu- is linear or branched saturated Ci-4alkylene; each -Ruuis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RUNis linear or branched saturated Ci-4alkyl; each -RUMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:-RUMM, -C(=O)RUMM, -C(=O)ORUMM, and -S(=O)2RUMM; wherein each -RUMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;-RUBis independently -H or -RUUB;-RUUBis independently linear or branched saturated Ci-4alkyl;-Rpis independently:-RP1, -RP2, -RP3, -RP4, -RP5, -LP-RP2, -LP-RP3, -LP-RP4, or -Lp-RP5;-RP1is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups -RPP2; each -RP2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP3is non-aromatic C3-8heterocyclyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -RP5is C5-10heteroaryl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; each -LP- is linear or branched saturated C1-4alkylene, and is optionally substituted with one group selected from -OH, -ORPL, -NH2, -NHRPL, and -NRPL2; each -RPLis independently linear or branched saturated C1-4alkyl; each -RPP1is independently selected from: -RPP, -LPP-OH, -LPP-ORPP, -LPP-NH2, -LPP-NHRPP, -LPP-N(RPP)2, and -LPP-RPM; each -RPP2is independently selected from: -F, -Cl, -Br, -I, -OH, -ORPP, -CF3, -CHF2, -OCF3, -OCHF2, -NH2, -NHRPP, -N(RPP)2, -RPM, -C(=O)OH, -C(=O)ORPP, -OC(=O)RPP, -C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2, -C(=O)RPM, -NHC(=O)RPP, -NRPNC(=O)RPP, -NHC(=O)NH2, -NHC(=O)NHRPP, -NHC(=O)N(RPP)2, -NHC(=O)RPM, -NRPNC(=O)NH2, -NRPNC(=O)NHRPP, -NRPNC(=O)N(RPP)2, -NRPNC(=O)RPM, -NHC(=O)ORPP, -NRPNC(=O)ORPP, -OC(=O)NH2, -OC(=O)NHRPP, -OC(=O)N(RPP)2, -OC(=O)RPM, -NHC(=NH)NH2, -C(=O)RPP, -S(=O)NH2, -S(=O)NHRPP, -S(=O)N(RPP)2, -S(=O)RPM, -S(=O)2NH2, -S(=O)2NHRPP, -S(=O)2N(RPP)2, -S(=O)2RPM, -NHS(=O)RPP, -NRPNS(=O)RPP, -NHS(=O)2RPP, -NRPNS(=O)2RPP, -S(=O)RPP, -S(=O)2RPP,-SH, -SRPP, -CN, and -NO2; wherein: each -LPP- is linear or branched saturated C1-4alkylene; each -RPPis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RPNis linear or branched saturated C1-4alkyl; each -RPMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from: -RPMM, -C(=O)RPMM, -C(=O)ORPMM, and -S(=O)2RPMM; wherein each -RPMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; -RNis independently -H or -RNN; -RNNis independently linear or branched saturated C1-4alkyl; and wherein: -A is independently -ACor -AH; -ACis independently phenyl or naphthyl, and is optionally substituted with one or more substituents -RX; -AHis independently C5-12heteroaryl, and is optionally substituted with one or more substituents -RX; wherein: each -RXis independently selected from: -RXX, -RXXU, -RXXV, -F, -Cl, -Br, -I, -OH, -ORXX, -LXX-OH, -LXX-ORXX, -CF3, -CHF2, -OCF3, -OCHF2, -NH2, -NHRXX, -NRXX2, -RXM, -LXX-NH2, -LXX-NHRXX, -LXX-NRXX2, -LXX-RXM, -C(=O)OH, -C(=O)ORXX, -OC(=O)RXX, -C(=O)NH2, -C(=O)NHRXX, -C(=O)NRXX2, -C(=O)RXM, -NHC(=O)RXX, -NRXNC(=O)RXX,-NHC(=O)NH2, -NHC(=O)NHRXX, -NHC(=O)NRXX2, -NHC(=O)RXM, -NRXNC(=O)NH2, -NRXNC(=O)NHRXX, -NRXNC(=O)NRXX2, -NRXNC(=O)RXM, -NHC(=O)ORXX, -NRXNC(=O)ORXX,-OC(=O)NH2, -OC(=O)NHRXX, -OC(=O)NRXX2, -OC(=O)RXM,-NHC(=NH)NH2,-C(=O)RXX,-S(=O)NH2, -S(=O)NHRXX, -S(=O)NRXX2, -S(=O)RXM,-S(=O)2NH2, -S(=O)2NHRXX, -S(=O)2NRXX2, -S(=O)2RXM,-NHS(=O)RXX, -NRXNS(=O)RXX,-NHS(=O)2RXX, -NRXNS(=O)2RXX,-S(=O)RXX, -S(=O)2RXX,-SH, -SRXX, -CN, and -NO2; and additionally, two adjacent groups -Rx, if present, may together form: -O-CH2-O-, -O-CH2CH2-O-, -CH2-CH2-O-, -CH2-CH2CH2-O-, -CH2-O-CH2-, or -CH2-CH2-O-CH2-; wherein: each -Lxx- is linear or branched saturated Ci-4alkylene; each -R^ is independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -R50^ is independently linear or branched C2-4alkenyl; each -Rxxvis independently linear or branched C2-4alkynyl; each -RXNis linear or branched saturated Ci-4alkyl; each -RXMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:-RXMM, -C(=O)RXMM, -C(=O)ORXMM, and -S(=O)2RXMM; wherein each -RXMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;-R1is independently -H or -R11;-R11is independently -R11Aor -R11B;-R11Ais independently:-RA1, -RA2, -RA3, -RA4, -RA5, -LA-RA2, -LA-RA3, -LA-RA4, or -LA-RA5;-RA1is linear or branched saturated Ci-ealkyl, and is optionally substituted with one or more groups -RAA2;each -RA2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2; each -RA3is non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RM1and one or more groups -RAA2; each -RA4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2; each -RA5is Cs-wheteroaryl, and is optionally substituted with one or more groups -RM1and one or more groups -RM2; each -LA- is linear or branched saturated Ci-4alkylene; each -RM1is independently selected from:-RAA,-L^-OH, -L^-OR™,-L^-NHz, -L^-NHR™, -LAA-N(RAA)2, and -L^-R™; each -RM2is independently selected from:-F, -Cl, -Br, -I,-OH, -OR™,-CF3, -CHF2, -OCF3, -OCHF2,-NH2, -NHR™, -N(R™)2, -RAM,-C(=O)OH, -C(=O)OR™, -OC(=O)RAA,-C(=O)NH2, -C(=O)NHRAA, -C(=O)N(RAA)2, -C(=O)RAM,-NHC(=O)R™, -NRANC(=O)RAA,-NHC(=O)NH2, -NHC(=O)NHRAA, -NHC(=O)N(RAA)2, -NHC(=O)RAM,-NRANC(=O)NH2, -NRANC(=O)NHRAA, -NRANC(=O)N(RAA)2,-NRANC(=O)RAM,-NHC(=O)ORAA, -NRANC(=O)ORAA,-OC(=O)NH2, -OC(=O)NHRAA, -OC(=O)N(RAA)2, -OC(=O)RAM,-NHC(=NH)NH2,-C(=O)R™,-S(=O)NH2, -S(=O)NHRAA, -S(=O)N(RAA)2, -S(=O)RAM,-S(=O)2NH2, -S(=O)2NHRAA, -S(=O)2N(RAA)2, -S(=O)2RAM,-NHS(=O)RAA, -NRANS(=O)RAA,-NHS(=O)2RAA, -NRANS(=O)2RAA,-S(=O)RAA, -S(=O)2RAA,-SH, -SRAA, -ON, and -NO2;wherein: each -LAA- is linear or branched saturated Ci-4alkylene; each -RMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RANis linear or branched saturated Ci-4alkyl; each -RAMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:-RAMM, -C(=O)RAMM, -C(=O)ORAMM, and -S(=O)2RAMM; wherein each -RAMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;-R11Bis independently selected from:-F, -Cl, -Br, -I,-OH, -ORBB,-CF3, -CHF2, -OCF3, -OCHF2,-NH2, -NHRBB, -NRBB2, -RBM,-C(=O)OH, -C(=O)ORBB, -OC(=O)RBB,-C(=O)NH2, -C(=O)NHRBB, -C(=O)NRBB2, -C(=O)RBM,-NHC(=O)RBB, -NRBNC(=O)RBB,-NHC(=O)NH2, -NHC(=O)NHRBB, -NHC(=O)NRBB2, -NHC(=O)RBM,-NRBNC(=O)NH2, -NRBNC(=O)NHRBB, -NRBNC(=O)NRBB2, -NRBNC(=O)RBM, -NHC(=O)ORBB, -NRBNC(=O)ORBB,-OC(=O)NH2, -OC(=O)NHRBB, -OC(=O)NRBB2, -OC(=O)RBM,-NHC(=NH)NH2,-C(=O)RBB,-S(=O)NH2, -S(=O)NHRBB, -S(=O)NRBB2, -S(=O)RBM,-S(=O)2NH2, -S(=O)2NHRBB, -S(=O)2NRBB2, -S(=O)2RBM,-NHS(=O)RBB, -NRBNS(=O)RBB,-NHS(=O)2RBB, -NRBNS(=O)2RBB,-S(=O)RBB, -S(=O)2RBB,-SH, -SRBB, -CN, and -NO2; wherein: each -RBBis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RBNis linear or branched saturated Ci-4alkyl;each -RBMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from: -RBMM, -C(=O)RBMM, -C(=O)ORBMM, and -S(=O)2RBMM; wherein each -RBMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; -R2is independently -H or -R22; -R22is independently -R22Cor -R22D; -R22Cis independently: -RC1, -RC2, -RC3, -RC4, -RC5, -LC-RC2, -LC-RC3, -LC-RC4, or -LC-RC5; -RC1is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups -RCC2; each -RC2is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC3is non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC4is independently phenyl or naphthyl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -RC5is C5-10heteroaryl, and is optionally substituted with one or more groups -RCC1and one or more groups -RCC2; each -LC- is linear or branched saturated C1-4alkylene; each -RCC1is independently selected from: -RCC, -LCC-OH, -LCC-ORCC, -LCC-NH2, -LCC-NHRCC, -LCC-N(RCC)2, and -LCC-RCM; each -RCC2is independently selected from: -F, -Cl, -Br, -I, -OH, -ORCC, -CF3, -CHF2, -OCF3, -OCHF2, -NH2, -NHRCC, -N(RCC)2, -RCM, -C(=O)OH, -C(=O)ORCC, -OC(=O)RCC, -C(=O)NH2, -C(=O)NHRCC, -C(=O)N(RCC)2, -C(=O)RCM, -NHC(=O)RCC, -NRCNC(=O)RCC,-NHC(=O)NH2, -NHC(=O)NHRCC, -NHC(=O)N(RCC)2, -NHC(=O)RCM, -NRCNC(=O)NH2, -NRCNC(=O)NHRCC, -NRCNC(=O)N(RCC)2, -NRCNC(=O)RCM,-NHC(=O)ORcc, -NRCNC(=O)ORCC,-OC(=O)NH2, -OC(=O)NHRCC, -OC(=O)N(RCC)2, -OC(=O)RCM,-NHC(=NH)NH2,-C(=O)RCC,-S(=O)NH2, -S(=O)NHRCC, -S(=O)N(RCC)2, -S(=O)RCM,-S(=O)2NH2, -S(=O)2NHRCC, -S(=O)2N(RCC)2, -S(=O)2RCM,-NHS(=O)RCC, -NRCNS(=O)RCC,-NHS(=O)2RCC, -NRCNS(=O)2RCC,-S(=O)RCC, -S(=O)2RCC,-SH, -SRCC, -CN, and -NO2; wherein: each -Lcc- is linear or branched saturated Ci-4alkylene; each -Rccis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RCNis linear or branched saturated Ci-4alkyl; each -RCMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from:-RCMM, -C(=O)RCMM, -C(=O)ORCMM, and -S(=O)2RCMM; wherein each -RCMMis independently linear or branched saturated Ci-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3;-R22Dis independently selected from:-F, -Cl, -Br, -I,-OH, -ORDD,-CF3, -CHF2, -OCF3, -OCHF2,-NH2, -NHRDD, -NRDD2, -RDM,-C(=O)OH, -C(=O)ORDD, -OC(=O)RDD,-C(=O)NH2, -C(=O)NHRDD, -C(=O)NRDD2, -C(=O)RDM,-NHC(=O)RDD, -NRDNC(=O)RDD,-NHC(=O)NH2, -NHC(=O)NHRDD, -NHC(=O)NRDD2, -NHC(=O)RDM,-NRDNC(=O)NH2, -NRDNC(=O)NHRDD, -NRDNC(=O)NRDD2, -NRDNC(=O)RDM, -NHC(=O)ORDD, -NRDNC(=O)ORDD,-OC(=O)NH2, -OC(=O)NHRDD, -OC(=O)NRDD2, -OC(=O)RDM,-NHC(=NH)NH2, -C(=O)RDD, -S(=O)NH2, -S(=O)NHRDD, -S(=O)NRDD2, -S(=O)RDM, -S(=O)2NH2, -S(=O)2NHRDD, -S(=O)2NRDD2, -S(=O)2RDM, -NHS(=O)RDD, -NRDNS(=O)RDD, -NHS(=O)2RDD, -NRDNS(=O)2RDD, -S(=O)RDD, -S(=O)2RDD, -SH, -SRDD, -CN, and -NO2; wherein: each -RDDis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; each -RDNis linear or branched saturated C1-4alkyl; each -RDMis independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is: optionally substituted with one or more groups selected from: -RDMM, -C(=O)RDMM, -C(=O)ORDMM, and -S(=O)2RDMM; wherein each -RDMMis independently linear or branched saturated C1-4alkyl, phenyl, or -CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from -F, -Cl, -Br, -Me, -OH, -OMe, -CF3, and -OCF3; or -R1and -R2, together with the carbon atom to which they are attached, form a saturated C3-6cycloalkyl or a non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups -RCC2.

2. A compound according to claim 1, wherein -RUAis -RUUA.

3. A compound according to claim 1 or 2, wherein -RUUAis independently: -RU1, -RU2, -RU4, -LU-RU4, or -C(=O)-RU4.

4. A compound according to any one of claims 1-3, wherein -RU1is independently -Me, -Et, or -nPr; and is optionally substituted with one or more groups -RUU2.

5. A compound according to any one of claims 1-4, wherein each -RU2is independently cyclohexyl.

6. A compound according to any one of claims 1-5, wherein each -RU4is phenyl.

7. A compound according to any one of claims 1-6, wherein each -LU- is -CH2-.

8. A compound according to any one of claims 1-7, wherein each -RUU2is independently selected from:-ORUU, -NH2, and -C(=O)OH.

9. A compound according to claim 1 , wherein -RUAis -H.

10. A compound according to any one of claims 1-9, wherein -RUBis -H.

11. A compound according to any one of claims 1-10, wherein -Rpis independently: -RP1, -RP2, -LP-RP3, -LP-RP4, or -Lp-RP5.

12. A compound according to any one of claims 1-11 , wherein -RP1is independently -Me, -Et, -nPr, -iPr, -nBu, -iBu, -sBu, -tBu, -n-pentyl, -s-pentyl, or - / -pentyl; and is optionally substituted with one or more groups -RPP2.

13. A compound according to any one of claims 1-12, wherein -RP1is independently -Me, -Et, or -nPr; and is substituted with one or two groups -RPP2.

14. A compound according to any one of claims 1-13, wherein -RP1is selected from groups of the following structural formula:wherein RP1Ris -Me or -Et and is substituted with one group RPP2.

15. A compound according to any one of claims 1-14, wherein each -RP5is independently:(a) pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is optionally substituted with one or more groups -RPP1and one or more groups -RPP2; or(b) thienyl, thiazolyl, or tetrazolyl.

16. A compound according to any one of claims 1-15, wherein each -RP5is independently thiazolyl optionally substituted with one or more groups RPP1and one or more groups RPP2.

17. A compound according to any one of claims 1-16, wherein each -RP5is independently pyridyl optionally substituted with one or more groups RPP1and one or more groups RPP2.

18. A compound according to any one of claims 1-17, wherein each -RP2is independently cyclopropyl, and is substituted with one group RPP2.

19. A compound according to any one of claims 1-18, wherein each -RP3is independently pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl; or -RP3is (3aS,6aR)-2-oxohexahydro-1 / 7-thieno[3,4-d]imidazolyl.

20. A compound according to any one of claims 1-19, wherein each -RP4is phenyl, and is substituted with one or more groups -RPP2.

21. A compound according to any one of claims 1-17, wherein -Rpis -RP1or -Lp-RP5.

22. A compound according to any one of claims 1-21, wherein -Lp- is independently -CH2CH2- or -CH2-.

23. A compound according to any one of claims 1-22, wherein -Lp- is -CH2-.

24. A compound according to any one of claims 1-23, wherein each -RPP2is independently selected from:-OH, -ORPP,-NH2, -NHRPP, -N(RPP)2,-C(=O)OH, -C(=O)ORPP,-C(=O)NH2, -C(=O)NHRPP, -C(=O)N(RPP)2,-NHC(=O)RPP, -NRPNC(=O)RPP, and -CN.

25. A compound according to any one of claims 1-24, wherein each -RPP2is independently selected from:-OH, -NH2, -NHRPP, -N(RPP)2, and -C(=O)OH.

26. A compound according to any one of claims 1-25, wherein each -RPP2is independently selected from:-OH, -NH2, and -C(=O)OH.

27. A compound according to any one of claims 1-26, wherein each -Rppis -Me.

28. A compound according to any one of claims 1-10, wherein -Y is -NRUARUB.

29. A compound according to any one of claims 1 and 11-27, wherein -Y is -Rp.

30. A compound according to any one of claims 1-29, wherein -RNis -H.

31. A compound according to any one of claims 1-30, wherein -AHis thienyl, thiazolyl, or thienothiophenyl, and is optionally substituted with one or more substituents -Rx.

32. A compound according to any one of claims 1-31, wherein -AHis thien-2-yl or thien-3-yl, and is optionally substituted with one or more substituents -Rx.

33. A compound according to any one of claims 1-31, wherein -AHis thiazol-2-yl and is optionally substituted with one or more substituents -Rx.

34. A compound according to any one of claims 1-31, wherein -AHis thienothiophenyl and is optionally substituted with one or more substituents -Rx.

35. A compound according to any one of claims 1-34, wherein -Acis phenyl and is optionally substituted with one or more substituents -Rx.

36. A compound according to any one of claims 1-34, wherein -Acis:wherein -RX2is -Cl.

37. A compound according to any one of claims 1-31 , 35, and 36, wherein -AHis:wherein -RX4is -Cl.

38. A compound according to any one of claims 1-35, wherein each -Rxis -Cl or -F.

39. A compound according to any one of claims 1-34, and 37 wherein -A is -AH.

40. A compound according to any one of claims 1-30, 35, 36, and 38, wherein -A is -Ac.

41. A compound according to any one of claims 1-40, wherein:-R1is -CH2CH(CH3)2; and-R2is -H.

42. A compound according to any one of claims 1-41, wherein R2is -H, and which is a compound selected from compounds of the following formula, and pharmaceutically acceptable salts, hydrates, and solvates thereof:

43. A compound according to any one of claims 1-42, wherein the sulfur atom which forms part of the sulfonimidamido group is in the configuration shown in the following structural formula:

44. A compound according to any one of claims 1-42, wherein the sulfur atom which forms part of the sulfonimidamido group is in the configuration shown in the following structural formula:

45. A compound according to claim 1 , which is selected from any one of ANOSA-001 to ANOSA-087 and pharmaceutically acceptable salts, hydrates, and solvates thereof.

46. A pharmaceutical composition comprising a compound according to any one of claims 1-45, and a pharmaceutically acceptable carrier or diluent.

47. A method of preparing a pharmaceutical composition comprising the step of mixing a compound according to any one of claims 1-45, and a pharmaceutically acceptable carrier or diluent.

48. A method of inhibiting bacterial aminoacyl-tRNA synthetase, in vitro or in vivo, comprising contacting the synthetase with an effective amount of a compound according to any one of claims 1-45.

49. A method of inhibiting bacterial aminoacyl-tRNA synthetase function in a cell, in vitro or in vivo, comprising contacting the cell with an effective amount of a compound according to any one of claims 1-45.

50. A compound according to any one of claims 1-45, for use in a method of treatment of the human or animal body by therapy.

51. A compound according to any one of claims 1-45, for use in a method of treatment of a disorder of the human or animal body that is ameliorated by the inhibition of bacterial aminoacyl-tRNA synthetase.

52. Use of a compound according to any one of claims 1-45 in the manufacture of a medicament for the treatment of a disorder of the human or animal body that is ameliorated by the inhibition of bacterial aminoacyl-tRNA synthetase.

53. A method of treatment of a disorder of the human or animal body that is ameliorated by the inhibition of bacterial aminoacyl-tRNA synthetase, comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound according to any one of claims 1-45.

54. A compound according to any one of claims 1-45, for use in a method of treatment of a bacterial infection.

55. Use of a compound according to any one of claims 1-45 in the manufacture of a medicament for the treatment of a bacterial infection.

56. A method of treatment of a disorder of the human or animal body, comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound according to any one of claims 1-45, wherein the disorder is a bacterial infection.

57. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are Gram-positive bacteria.

58. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are Gram-negative bacteria.

59. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are aerobic bacteria.

60. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are anaerobic bacteria.

61. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are intracellular bacteria.

62. A compound for use according to claim 54, use according to claim 55, or a method according to claim 56, wherein the bacteria are:Staphylococci, for example S. aureus;Enterococci, for example E. faecalis;Streptococci, for example S. pneumoniae; Haemophilus, for example H. influenza;Moraxella, for example M. catarrhalis-, Klebsiella, for example K. pneumoniae-, Acinetobacter, for example A. baumanir, Pseudomonas, for example P. aeruginosa-, Proteus, for example P. mirabilis-,Neisseria, for example Neisseria gonorrhoeae, Clostridioides, for example Clostridioides difficile; Campylobacter, for example C. jejuni;Salmonella, for example S. typhi;Shigella, for example S. flexneri;Enterobacter, for example E. cloacae;Citrobacter, for example C. freundii;Serratia, for example Serratia marcescens; or Escherichia, for example E. coli.

63. A compound for use according to any one of claims 54 and 57-62, use according to any one of claims 55 and 57-62, or a method according to any one of claims 56-62, wherein the infection is: a central nervous system infection; an external ear infection; an infection of the middle ear, including acute otitis media; an infection of the cranial sinuses; an eye infection; an infection of the oral cavity, including an infection of the teeth, gums, or mucosa; an upper respiratory tract infection; a lower respiratory tract infection; a genitourinary infection; a urinary tract infection; an intra-abdominal infection; a gastrointestinal infection; a gynecological infection; septicemia, a bone or joint infection a skin or skin structure infection; bacterial endocarditis; or a burn infection.