Novel taurine-bile acid derivatives inhibitors for TNF-αproduction and inflammasomal activation and preparation method thereof

Abstract

The present invention relates to a novel compound and a method for preparing the same. The compound according to the present invention exhibits inhibitory activity on the production of TNF-α, an inflammatory cytokine generated by an inflammation initiation response, and on the production of IL-1β due to the activation of the inflamed complex, and thus can be developed as a therapeutic agent for inflammatory diseases related thereto.

Description

Technology Field

[0001] The present invention relates to a novel compound that inhibits TNF-α production and the activation of inflammatory complexes, which can be used for the treatment of various inflammatory diseases, and a method for preparing the same. Specifically, the invention relates to a novel compound prepared by reacting a bile acid or a derivative thereof with a taurine derivative. Background Technology

[0003] The causes of inflammation are known to be PAMPs (Pathogen-associated molecular patterns) originating from pathogens and DAMPs (Damage-associated molecular patterns) released from tissues due to tissue damage. Consequently, activated immune cells and other inflammatory mediators produced by cells such as blood vessels engage in a bioprotective response; however, if this response is not properly regulated, it leads to inflammatory diseases.

[0004] Intractable inflammatory diseases have high recurrence rates and require long-term administration for treatment. However, treatments developed to date have failed to satisfy this unmet market demand, necessitating the development of new therapies. Currently, steroids, NSAIDs (non-steroidal anti-inflammatory drugs), antibody therapies, and JAK inhibitors are prescribed for inflammatory diseases; however, steroids are limited to short-term prescriptions due to systemic side effects, while NSAIDs have not demonstrated sufficient efficacy in clinical trials. Additionally, while antibody therapies offer relatively rapid response and allow for long-term administration, they have drawbacks such as injection site side effects, a gradual decline in efficacy due to the formation of neutralizing antibodies in the body, and high patient costs. Although JAK inhibitors exhibit excellent anti-inflammatory efficacy, they pose a risk of increasing severe infections by excessively suppressing T lymphocytes, and cardiovascular side effects and carcinogenic risks have been identified.

[0005] To address this unmet market demand, inflammasome modulators have recently been attracting attention. Inflammasomes, which are central to the body's immune response, play a crucial role in innate defense immunity as part of the immune response to microbial infections and cell damage. Inflammasomes are cytosolic multiprotein oligomers of the innate immune system. Among the many inflammasomes, the abnormal activation of the NLRP3 inflammasome is particularly associated with the onset and exacerbation of various inflammatory diseases, such as ulcerative colitis, gout, multiple sclerosis, arthritis, sepsis, and inflammatory neurological disorders. The NLRP3 inflammasome is also activated by PAMPs from pathogens such as viruses and bacteria, as well as DAMPs such as calcium influx, mitochondrial reactive oxygen species, and extracellular APTs. Activation of the inflammasome promotes not only the activation of gasdermin-D via caspase-1 but also the protein maturation and secretion of pro-IL-1β and pro-IL-18 into IL-1β and IL-18. Impairment in the regulation of inflammasome activation leads to various diseases, including cancer, metabolic diseases, degenerative diseases, and inflammatory diseases.

[0006] There have been numerous past attempts to develop new drugs targeting the NLRP3 inflammasome, a major regulator of inflammatory responses. As it became known that the inflammasome is activated through normal and abnormal pathways composed of pro-caspase, gasdermin D, ASC, NLR proteins, AIM2, IF116, and pyrin, and that dysregulation of the inflammasome during this process leads to various diseases, the development of drugs targeting proteins involved in inflammasome-related signaling began to gain momentum after 2010. Representative inflammasome regulators developed include P2X7 receptor antagonists, NLRP3 inhibitors, and caspase-1 inhibitors.

[0007] Among these, P2X7R is one of the receptors crucial for the activation of the NLRP3 inflammasome. The P2X7 receptor is an ion channel receptor composed of a complex belonging to the P2Xn purine receptor family; stimulation of P2X7 facilitates the extracellular release of potassium ions and the rapid inward transport of calcium and sodium ions. High concentrations of ATP released from necrotic cells act as pro-inflammatory DAMPs, binding to the P2X7 receptor and activating the NLRP3 inflammasome. Ultimately, this leads to the release of potassium ions via the P2X7 receptor and causes intracellular ion imbalance, thereby activating the NLRP3 inflammasome. As such, the P2X7 receptor, which plays a vital role in the activation of the inflammasome, is widely expressed in various immune cells, epidermal cells, and neurons. Since P2X7 receptor signaling activates both the normal and abnormal pathways of NLRP3 activation, the ATP-P2X7 interaction is critical to the activation of the NLRP3 inflammasome.

[0008] Global pharmaceutical companies such as Pfizer, AstraZeneca, and Janssen initiated the development of P2X7 antagonists for indications including rheumatoid arthritis, Crohn's disease, and depression; however, most were discontinued due to insufficient efficacy in clinical trials. Although venture companies subsequently continued development, there were fewer than 10 therapeutic development pipelines targeting P2X7 by 2020. Currently, the only new drug in the clinical stage is 18F-JNJ-64413739, developed by Janssen as a treatment for depression, which has completed Phase 1 trials; other pipelines remain in the preclinical or development stages. As Caspase-1 inhibitors were discontinued in 2020 due to failure to meet efficacy targets and safety concerns, there are currently no global development pipelines for this group. NLRP3 inhibitors are being developed by venture companies such as OLATEC, IMFLAZOME, IFM THERAPETICS, NODTHERA, and AC Immune for indications including osteoarthritis, systolic heart failure, Parkinson's disease, inflammatory bowel disease, and Alzheimer's disease.

[0009] As mentioned above, most of these novel inflammasome modulator drugs have failed to achieve success in clinical trials. This is known to be because the specific drug targets they target alone cannot effectively and simultaneously inhibit the various pro-inflammatory pathways that activate the NLRP3 inflammasome. In other words, the novel inflammasome modulator drugs known to date—such as P2X7 receptor antagonists, NLRP3 inhibitors, and caspase-1 inhibitors—selectively inhibit inflammatory cytokines triggered by inflammatory activity, such as IL-1β and IL-18, but they have limitations in that they cannot inhibit TNF-α, an inflammatory cytokine triggered during the inflammation initiation phase. This is a fundamental limitation of drugs that selectively target only NLRP3 or P2X7; it can be said that pharmacological mechanisms that selectively block only the inflammatory activation phase are insufficient to suppress inflammatory responses through various inflammatory bypass pathways. In other words, numerous clinical studies have reported cases where patient drug responsiveness and anti-inflammatory effects to current novel inflammasome modulators are unsatisfactory due to the alternative activity of compensatory bypass pathways.

[0010] In addition, it has been revealed that due to the genetic redundancy and polymorphisms inherent in NLRP3 and P2X7, current novel inflammasome modulator drugs do not achieve the targeted response rates in actual clinical trials. Because they exist in a group of pseudo-NLRP inflammasomes that have the same protein domain as the NLPR3 inflammasome, this is the reason why novel inflammasome modulator drugs are not demonstrating sufficient efficacy.

[0011] Since hundreds to thousands of SNPs (Single nucleotide polymorphisms) have been identified in P2X7 and NLRP3 proteins, individual genetic diversity is very high, often leading to significant individual variability in drug response rates and efficacy; therefore, it is unlikely that new drugs targeting these proteins will become therapeutic agents with broad efficacy without individual variation. As described above, it can be said that the novel inflammasome-targeting drugs developed to date—such as P2X7 receptor antagonists, NLRP3 inhibitors, and caspase-1 inhibitors—have many limitations in achieving their intended clinical efficacy.

[0012] In this invention, a GPCR19-targeted therapeutic agent that regulates the P2X7R-inflammation complex at an upstream level was developed to overcome the shortcomings of existing novel drugs targeting the inflammation complex. GPCR19 is specifically highly expressed primarily in innate immune cells and selectively induces immune cell-mediated anti-inflammatory effects, thus offering the advantage of low non-specific side effects affecting normal cells. Considering that the target receptors of existing anti-inflammatory steroids are distributed systemically, inducing broad systemic responses in addition to pharmacological actions against the target, and consequently reporting risks of systemic metabolic side effects, increased risk of infection, and high carcinogenicity, it is judged that the novel GPCR19-targeted drug will offer significant advantages in terms of safety.

[0013] Drugs targeting GPCR19 to date include TUDCA, INT-747 (Obeticholic acid, OCA), and INT-777 (S-EMCA). However, the extent to which they efficiently inhibit the inflammasome complex has not been reported in detail. All of these are bile acid derivatives and have been reported as GPCR19 agonists; however, research has primarily focused on their mechanism of inflammation suppression by inhibiting NF-kB through increased cAMP production. Clinical trials are currently underway for TUDCA regarding conditions such as type 2 diabetes, ulcerative colitis, and amyotrophic lateral sclerosis (ALS), while INT-747 is being tested for biliary cirrhosis, non-alcoholic fatty liver disease, and liver cirrhosis. Among the GPCR19 targeted therapies developed to date, there are currently no new drugs with proven efficacy in clinical trials. In the case of the most advanced new drugs, there have been instances where Phase 3 clinical trials targeting inflammatory diseases failed due to low anti-inflammatory efficacy.

[0014] The failure of these GPCR19 targeted therapies stems from overlooking the fact that the complex of P2X7R and GPCR19 regulates the inflammasome. Specifically, new drugs were screened using cell lines that artificially high-expressed GPCR19 without a precise consideration of the anti-inflammatory mechanism of GPCR19; this resulted in small molecule compounds screened through an artificial system that does not correctly reflect the initiation and activation stages of inflammation via GPCR19-P2X7R in vivo. Therefore, the present invention, by improving the drug screening system, has overcome previous failure cases. Based on an understanding of the signaling pathway mediated by the GPCR19-P2X7R-NLRP3 axis, the present invention has invented a small molecule compound with broad anti-inflammatory effects capable of blocking both the initiation and activation stages of inflammation, which can simultaneously inhibit the cAMP pathway and the NRLP pathway.

[0015] Bile acids are known as GPCR19 regulators. Bile acids are amphiphilic molecules possessing both hydrophobic and hydrophilic domains. Examining the process of bile acid production, primary bile acids in the form of cholic acid and chenodeoxycholic acid are produced in the liver using cholesterol as a precursor by cytochrome P450 enzymes. Subsequently, these acids bind to taurine and glycine by hepatocytes to become more hydrophilic, then travel to the intestines where they are converted into secondary bile acids by intestinal microorganisms. Secondary bile acids are reabsorbed into the liver via the hepato-intestinal circulation, travel through blood vessels to various tissues, and perform diverse physiological functions. Specifically, it plays roles such as the digestion of fats through amphiphilic characteristics, the inhibition of the overgrowth of harmful intestinal microorganisms through acidity, and the excretion of cholesterol during intestinal circulation. Furthermore, it is known to transmit signals through receptors such as the nuclear receptor farnesoid X receptor (FXR) and the cell membrane GPCR19. Specifically, bile acids bound to the farnesoid X receptor inhibit gluconeogenesis and lipogenesis genes, thereby suppressing these processes in the liver; conversely, binding to GPCR19 promotes metabolic rate, stimulates insulin secretion, and inhibits cytokine secretion. In particular, because binding to GPCR19 suppresses inflammatory responses,

[0016] Research has been conducted on the treatment of skin, nerve, stomach, intestines, liver, and joint diseases associated with inflammation and autoimmune disorders using bile acids as therapeutic agents.

[0018] Looking at the chemical structure of bile acids, they have a steroid structure with four rings and possess the following chemical formula. Bile acids vary greatly depending on differences in the position, stereochemical position, and number of hydroxyl groups of the hydroxyl group. Major bile acids in the human body include cholic acid, glycocholic acid, deoxycholic acid, and lithocholic acid. Furthermore, bile acids can be modified by the reactivity of hydroxyl or carboxyl groups, and due to their amphiphilicity and chirality, they are utilized in various fields, including not only the pharmaceutical sector but also materials for solution processing, thin films, and surfactants.

[0019]

[0020] Bile acid structure

[0021] Taurine (or 2-aminoethanesulfonic acid) is an organic compound and a type of amino acid found in the cells and tissues of mammals, including humans. Taurine is rarely utilized in protein synthesis and exists mostly in the form of free amino acids; it is present in high concentrations in organs such as the brain, heart, liver, and kidneys, as well as in the skeleton and muscles.

[0022]

[0023] <Taurine Structure>

[0024] Taurine is known to be effective in vascular diseases, such as stabilizing blood pressure and preventing stroke by inhibiting the production of low-density lipoprotein cholesterol, due to its inhibitory effect on the sympathetic nervous system of the brain caused by the structural characteristics of the β-amino acid of the sulfonic acid group. However, since it is difficult to manufacture derivatives or compositions of taurine, it is generally used in its raw state. However, taurine can combine with choline acid, a type of bile acid, to form taurocholic acid, which produces crystalline bile acids involved in the emulsification of fats.

[0025]

[0026] <Structure of Taurocholic Acid>

[0027] In this regard, Korean Registered Patent No. 10-1778687 discloses a deoxycholate-based amphiphilic compound, and Korean Published Patent No. 10-1994-0021065 discloses a taurine-bile acid derivative having a therapeutic effect.

[0028] However, in the case of taurine, it is difficult to form derivatives, so there are almost no derivatives of taurocholic acid, and there is little known therapeutic effect using them. Accordingly, the inventors of the present invention have made efforts to produce an inflammatory complex and a TNF-α production inhibitor that exhibit excellent effects, and as a result, have discovered that compounds formed by covalently bonding a novel bile acid derivative and a taurine derivative can be produced, thereby synthesizing a novel taurine-bile acid derivative compound and revealing its therapeutic use, thus completing the present invention. Prior art literature

[0030] Korean Registered Patent KR 10-1778687, Korean Published Patent KR 10-1994-0021065 The problem to be solved

[0031] The present invention relates to a novel compound capable of simultaneously regulating the GPCR19-P2X7R-NLRP3 signaling pathway and the cAMP signaling pathway, and a method for preparing the same, aiming to solve the problem of low difficulty, yield, and purity in the manufacturing process of conventional compounds containing taurine derivatives.

[0032] In addition, the present invention aims to provide a novel compound capable of being developed as a therapeutic agent by demonstrating that the novel compound synthesized by the method according to the present invention inhibits the production of IL-1β, which is caused by the activation of TNF-α and inflammatory complexes important for the pathology of various inflammatory diseases, thereby exhibiting a useful therapeutic effect. means of solving the problem

[0034] To achieve the above objective, the present invention provides a compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof.

[0035] [General Formula 1]

[0036]

[0037] In the above formula,

[0038] R1, R2, R3, and R4 are each independently H, halo, and C 1-5 Alkyl, OH, or =O, and,

[0039] X is substituted or unsubstituted C 1-10 It is an alkylene,

[0040] Here, if X is substituted, one or more hydrogens are linear or branched C 1-10 Substituted with alkyl, halo, OH, SH, NH2, CONH2, or COOH,

[0041] A is C 1-10 Alkylene, C 1-10 Heteroalkylene, C 1-10 Alkenylene, C 1-5 alkynylene, C 3-8 Cycloalkylene, C 3-8 Heterocycloalkylene, C 6-20Aryllene, C 6-20 Heteroarylene, -NR5R6C(O)-, -OR6, -SR6, -NR5R6, -C(O)R6, -C(O)OR6, -C(O)NR5R6, -CH(R5)(R6), -CH(R5)(OR6), -CH(OR5)(OR6), -CH(R5)(SR6), or -CH(SR5)(SR6);

[0042] R5 is hydrogen, substituted or unsubstituted C 1-10 Alkyl, substituted or unsubstituted C 1-10 Heteroalkyl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 6-20 Heteroaryl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Cycloalkyl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Heterocycloalkyl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Aryl or substituted or unsubstituted C 1-10 Alkyl-C 6-20 It is heteroaryl, and

[0043] Here, if R5 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, =O, OR a , SR a , N(R a )2, or CON(R a It is replaced with )2, and R a is hydrogen or C 1-5 It is alkyl, and

[0044] R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20 Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, substituted or unsubstituted C 6-20Aryllene, or substituted or unsubstituted C 6-20 It is a heteroarylene,

[0045] Here, if R6 is substituted, one or more hydrogens are =O, linear or branched C 1-10 Alkyl, C 0-10 Alkyl-C 6-20 Aril, C 0-10 Alkyl-OH, C 0-10 Alkyl-NH2, C 0-10 Alkyl-SH, or C 0-10 Substituted with alkyl-CONH2;

[0046] Or R5 and R6 together C 3-20 Cycloalkylene, C 3-20 Heterocycloalkylene, C 6-20 Aryllene or C 6-20 Forming heteroarylenes;

[0047] Y directly bonds with A or bonds with R6, and H, -(CH2) n CH3, -(CH2) n COOH, -(CH2) n OH -(CH2) n SO3H, -(CH2) n OSO3H, -(CH2) n PO3H2, -(CH2) n OPO3H2, -(CH2) n SO3NH 2, -(CH2) n CONH2, or -(CH2) n C(O)SO3H, and

[0048] Here, n is an integer from 0 to 10.

[0050] In one aspect of the present invention, R1, R2, R3, and R4 are each independently H, OH, =O, or C 1-5 It is an alkyl.

[0051] In one embodiment of the present invention, R1, R2, R3 and R4 are each independently H or OH, wherein at least one OH is included.

[0052] In one aspect of the present invention, R1, R2, R3, and R4 are each independently H, OH, =O, or C 1-5 It is an alkyl, where at least one =O or C 1-5 It contains alkyl.

[0053] In one embodiment of the present invention, R1, R2, R3 and R4 are each independently H or OH.

[0054] In one embodiment of the present invention, R1, R3 and R4 are OH, and R2 is H.

[0055] In one embodiment of the present invention, R1 and R2 are H, and R3 and R4 are OH.

[0056] In one embodiment of the present invention, R1, R2 and R4 are H, and R3 is OH.

[0057] In one embodiment of the present invention, R1, R2 and R4 are H, and R3 is =O.

[0058] In one embodiment of the present invention, R1 and R3 are OH, and R2 is C2 alkyl.

[0059] In one embodiment of the present invention, R1, R3 and R4 are OH, and R2 is C2 alkyl.

[0060] In one aspect of the present invention, X is a substituted or unsubstituted C 1-4 It is an alkylene, and when substituted, one or more hydrogens are linear or branched C 1-4 It is an alkyl. In one specific embodiment of the present invention, X is an unsubstituted C 1-4 It is an alkylene.

[0061] In one aspect of the present invention, A is -NR5R6C(O)-, -OR6, -SR6, -NR5R6, -C(O)R6, -C(O)OR6, -C(O)NR5R6, -CH(R5)(R6), -CH(R5)(OR6), -CH(OR5)(OR6), -CH(R5)(SR6), or -CH(SR5)(SR6). In a specific aspect of the present invention, A is -NR5R6C(O)-, -C(O)NR5R6, or -CH(R5)(R6).

[0062] In one aspect of the present invention, R5 is hydrogen, substituted or unsubstituted C 1-10 Alkyl, substituted or unsubstituted C 1-10 Heteroalkyl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Aryl or substituted or unsubstituted C 1-10 Alkyl-C 6-20 It is heteroaryl, and

[0063] Here, if R5 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, =O, OR a , SR a , N(R a )2, or CON(R a It is replaced with )2, and R a is hydrogen or C 1-5 It is an alkyl.

[0064] In one aspect of the present invention, R5 is hydrogen, or substituted or unsubstituted C 1-10 It is alkyl, and

[0065] Here, when R5 is substituted, one or more hydrogens are substituted with =O, OH, SH, NH2, or CONH2.

[0066] In one aspect of the present invention, R5 is a substituted or unsubstituted C 3-20Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl or substituted or unsubstituted C 6-20 Arilgo,

[0067] Here, when R5 is substituted, one or more hydrogens are substituted with =O, OH, SH, NH2, or CONH2.

[0068] In one aspect of the present invention, the R5 is an unsubstituted C 3-10 Cycloalkyl, unsubstituted C 3-10 Heterocycloalkyl or unsubstituted C 6-10 It is Aril.

[0069] In one aspect of the present invention, the R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20 Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, or substituted or unsubstituted C 6-20 It is Arilen, and

[0070] Here, if R6 is substituted, one or more hydrogens are =O, linear or branched C 1-10 Alkyl, C 0-10 Alkyl-C 6-20 Aryl or C 0-10 It is substituted with alkyl-OH.

[0071] In one aspect of the present invention, the R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20 Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, or substituted or unsubstituted C 6-20 It is Arilen, and

[0072] Here, if R6 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, C 0-5 Alkyl-OH, C 6-20Aryl or CH2-C 6-20 It is replaced by aryl.

[0073] In one embodiment of the present invention, R6 is a direct connection.

[0074] In one aspect of the present invention, the R6 is a substituted unsubstituted C 1-5 It is an alkylene, wherein R6 is substituted, and one or more hydrogens are linear or branched C 1-5 Alkyl, C 0-3 It is substituted with alkyl-OH, C6-aryl, or CH2-C6-aryl.

[0075] In one aspect of the present invention, the R5 and R6 together form C 3-10 Cycloalkylene, C 3-10 Heterocycloalkylene, C 6-10 Aryllene or C 6-10 It forms heteroarylenides.

[0076] In one aspect of the present invention, R5 and R6 together , , , or forms.

[0077] In one embodiment of the present invention, the Y is H, -(CH2) n CH3, -(CH2) n COOH, -(CH2) n OH, -(CH2) n SO3H or -(CH2) n OSO3H, where n is an integer from 0 to 10.

[0078] In one embodiment of the present invention, the Y is -(CH2) n It is SO3H, and n is an integer from 0 to 5.

[0079] In addition, the present invention provides a pharmaceutical composition for treating inflammatory diseases comprising the above compound or a pharmaceutically acceptable salt thereof. Effects of the invention

[0081] The present invention relates to a novel compound that inhibits TNF-α production and the activity of the inflammatory complex, and a method for preparing the same. Since the compound according to the present invention exhibits useful anti-inflammatory activity, it can be developed as a therapeutic agent for related diseases. Specific details for implementing the invention

[0083] The present invention will be described in detail below.

[0084] In the present invention, the compound represented by General Formula 1 corresponds to a conjugate formed by reacting a bile acid derivative with a taurine derivative. The bile acid derivative refers to a derivative of the following structural formula, and the position of each carbon atom is designated by a commonly used method.

[0085]

[0086] In the present invention, some of the hydrogen atoms substituted on the carbon ring of the bile acid derivative may be substituted with other substituents. For example, when substituted, C 1-5 It can be substituted with alkyl, hydroxy, oxo (=O), etc. Examples of substituted compositions include deoxycholic acid, lithocholic acid, dehydrolithocholic acid, obeticholic acid, INT-777, and cholic acid. However, these are exemplary and are not limited thereto.

[0087] In this specification, “substituted or unsubstituted” means an atom that can be substituted or unsubstituted, “substituted” means a group having one or more substituents, and a substituent means a chemical part covalently bonded to said group. Or, “unsubstituted” means that the chemical part is directly modified in the substituted part without having a substituent.

[0088] In this specification, "halo" refers to elements belonging to Group 17, such as fluorine, chlorine, bromide, iodine, etc.

[0089] In this specification, "alkyl" refers to a chemical portion obtained by removing a hydrogen atom from a carbon atom of an aliphatic or alicyclic, saturated or unsaturated (unsaturated, completely unsaturated) hydrocarbon compound, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, etc.

[0090] In this specification, "alkylene" refers to a divalent chemical part obtained by removing one more hydrogen atom from the alkyl, and does not include one in which two atoms are removed from one carbon.

[0091] In this specification, "heteroalkyl" refers to an alkyl containing one or more heteroatoms, and "heteroalkylene" refers to an alkylene containing one or more heteroatoms.

[0092] In the present invention, "cycloalkyl" refers to a chemical portion obtained by removing a hydrogen atom from a ring alicyclic atom, wherein the alkyl group is a cyclyl group. Examples include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclohexene, etc.

[0093] In this specification, "heterocycloalkyl" means a cycloalkyl comprising one or more heteroatoms.

[0094] In this specification, "aryl" refers to a chemical portion obtained by removing a hydrogen atom from an aromatic ring atom of an aromatic compound having a ring atom.

[0095] In the present invention, "heteroaryl" means an aryl containing one or more heteroatoms. Examples include pyridine, pyrrolyl, quinoline, pyridyl, pyrimidinyl, etc.

[0096] In this specification, "branched type" means having one or more branched forms, and the branching means that it is not limited to carbon and can bond with carbon.

[0097] In this specification, "linear" means not having a branched form.

[0098] In this specification, prefixes (e.g., C 1-12 , C 3-8 (etc.) refers to the number of ring atoms or a range of ring atoms, regardless of whether they are carbon atoms or heteroatoms. For example, the term "C as used herein 3-6 "Heterocycloalkyl" relates to a heterocycloalkyl group having 3 to 6 ring atoms. Additionally, for example, the term "C as used herein 1-10 Alkyl-C 6-20 "Aril" is C 1-10 Alkyl and C 6-20 It refers to a form in which aryls are continuously combined.

[0099] Unless otherwise specifically stated in this specification, isomers are not excluded.

[0101] The present invention relates to a compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof.

[0102] [General Formula 1]

[0103]

[0104] In the above formula,

[0105] R1, R2, R3, and R4 are each independently H, halo, and C 1-5 Alkyl, OH, or =O, and,

[0106] X is substituted or unsubstituted C 1-10 It is an alkylene,

[0107] Here, if X is substituted, one or more hydrogens are linear or branched C 1-10 Substituted with alkyl, halo, OH, SH, NH2, CONH2, or COOH,

[0108] A is C 1-10 Alkylene, C 1-10 Heteroalkylene, C 1-10 Alkenylene, C 1-5 alkynylene, C3-8 Cycloalkylene, C 3-8 Heterocycloalkylene, C 6-20 Aryllene, C 6-20 Heteroarylene, -NR5R6C(O)-, -OR6, -SR6, -NR5R6, -C(O)R6, -C(O)OR6, -C(O)NR5R6, -CH(R5)(R6), -CH(R5)(OR6), -CH(OR5)(OR6), -CH(R5)(SR6), or -CH(SR5)(SR6);

[0109] R5 is hydrogen, substituted or unsubstituted C 1-10 Alkyl, substituted or unsubstituted C 1-10 Heteroalkyl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 6-20 Heteroaryl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Cycloalkyl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Heterocycloalkyl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Aryl or substituted or unsubstituted C 1-10 Alkyl-C 6-20 It is heteroaryl, and

[0110] Here, if R5 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, =O, OR a , SR a , N(R a )2, or CON(R a It is replaced with )2, and R a is hydrogen or C 1-5 It is alkyl, and

[0111] R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, substituted or unsubstituted C 6-20 Aryllene, or substituted or unsubstituted C 6-20 It is a heteroarylene,

[0112] Here, if R6 is substituted, one or more hydrogens are =O, linear or branched C 1-10 Alkyl, C 0-10 Alkyl-C 6-20 Aril, C 0-10 Alkyl-OH, C 0-10 Alkyl-NH2, C 0-10 Alkyl-SH, or C 0-10 Substituted with alkyl-CONH2;

[0113] Or R5 and R6 together C 3-20 Cycloalkylene, C 3-20 Heterocycloalkylene, C 6-20 Aryllene or C 6-20 Forming heteroarylenes;

[0114] Y directly bonds with A or bonds with R6, and H, -(CH2) n CH3, -(CH2) n COOH, -(CH2) n OH -(CH2) n SO3H, -(CH2) n OSO3H, -(CH2) n PO3H2, -(CH2) n OPO3H2, -(CH2) n SO3NH 2, -(CH2) n CONH2, or -(CH2) n C(O)SO3H, and

[0115] Here, n is an integer from 0 to 10.

[0117] In one embodiment of the present invention, general formula 1 can be specifically expressed by the following general formula 2.

[0118] [General Formula 2]

[0119]

[0120] Here, R1, R2, R3, R4, X, A and Y are as defined above.

[0121] In one aspect of the present invention, the compound or a pharmaceutically acceptable salt thereof comprises, more specifically, a compound represented by the following general formula 3.

[0122] [General Formula 3]

[0123]

[0124] In addition, more specifically, the above compound or its pharmaceutically acceptable salt comprises, more specifically, a compound represented by the following general formula 4.

[0125] [General Formula 4]

[0126]

[0127] In the above general formulas 3 and 4, R1, R2, R3, R4, R5, R6, X, and Y are as defined above.

[0129] In one specific embodiment of the present invention, R1, R2, R3, and R4 are each independently H, OH, =O, or C 1-5 It is an alkyl.

[0130] In one embodiment of the present invention, R1, R2, R3 and R4 are each independently H or OH, wherein at least one OH is included.

[0131] In one aspect of the present invention, R1, R2, R3, and R4 are each independently H, OH, =O, or C 1-5 It is an alkyl, where at least one =O or C 1-5 It contains alkyl.

[0132] In one embodiment of the present invention, R1, R2, R3 and R4 are each independently H or OH.

[0133] In one embodiment of the present invention, R3 is OH.

[0134] In one embodiment of the present invention, R1 and R3 are OH.

[0135] In one embodiment of the present invention, R3 is =O.

[0136] In one embodiment of the present invention, R1 and R3 are OH, and R2 is C2 alkyl.

[0137] In one embodiment of the present invention, R1, R3 and R4 are OH, and R2 is C2 alkyl.

[0138] In one embodiment of the present invention, R1, R3 and R4 are OH, and R2 is H.

[0139] In one embodiment of the present invention, R1 and R2 are H, and R3 and R4 are OH.

[0140] In one embodiment of the present invention, R1, R2 and R4 are H, and R3 is OH.

[0141] In one embodiment of the present invention, R1, R2 and R4 are H, and R3 is =O.

[0142] In one embodiment of the present invention, R1 and R3 are OH, R2 is C2 alkyl, and R4 is H.

[0143] In one embodiment of the present invention, R1, R3 and R4 are OH, and R2 is C2 alkyl.

[0144] In one specific embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof comprises a compound represented by the following general formulas 5 to 10, more specifically general formulas 5-2 to 10-2.

[0145] [General Formula 5] [General Formula 5-2]

[0146]

[0147] [General Formula 6] [General Formula 6-2]

[0148]

[0149] [General Formula 7] [General Formula 7-2]

[0150]

[0151] [General Formula 8] [General Formula 8-2]

[0152]

[0153] [General Formula 9] [General Formula 9-2]

[0154]

[0155] [General Formula 10] [General Formula 10-2]

[0156]

[0157] In the above equation, X, A, and Y are as defined above.

[0159] In one aspect of the present invention, X is a substituted or unsubstituted C 1-4 It is an alkylene, and when substituted, one or more hydrogens are linear or branched C 1-4 It is an alkyl.

[0160] In one aspect of the present invention, X is an unsubstituted C 1-4 It is an alkylene.

[0161] In one aspect of the present invention, A is -NR5R6C(O)-, -OR6, -SR6, -NR5R6, -C(O)R6, -C(O)OR6, -C(O)NR5R6, -CH(R5)(R6), -CH(R5)(OR6), -CH(OR5)(OR6), -CH(R5)(SR6), or -CH(SR5)(SR6).

[0162] In one aspect of the present invention, A is -NR5R6C(O)-, -C(O)NR5R6, or -CH(R5)(R6).

[0163] In one aspect of the present invention, R5 is hydrogen, substituted or unsubstituted C 1-10 Alkyl, substituted or unsubstituted C 1-10Heteroalkyl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 1-10 Alkyl-C 6-20 Aryl or substituted or unsubstituted C 1-10 Alkyl-C 6-20 It is heteroaryl, and

[0164] Here, if R5 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, =O, OR a , SR a , N(R a )2, or CON(R a It is replaced with )2, and R a is hydrogen or C 1-5 It is an alkyl.

[0165] In one aspect of the present invention, R5 is hydrogen, or substituted or unsubstituted C 1-10 It is alkyl, and

[0166] Here, when R5 is substituted, one or more hydrogens are substituted with =O, OH, SH, NH2, or CONH2.

[0167] In one aspect of the present invention, R5 is a substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 3-20 Heterocycloalkyl or substituted or unsubstituted C 6-20 Arilgo,

[0168] Here, when R5 is substituted, one or more hydrogens are substituted with =O, OH, SH, NH2, or CONH2.

[0169] In one aspect of the present invention, the R5 is an unsubstituted C 3-10 Cycloalkyl, unsubstituted C 3-10 Heterocycloalkyl or unsubstituted C 6-10 It is Aril.

[0170] In one aspect of the present invention, the R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20 Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, or substituted or unsubstituted C 6-20 It is Arilen, and

[0171] Here, if R6 is substituted, one or more hydrogens are =O, linear or branched C 1-10 Alkyl, C 0-10 Alkyl-C 6-20 Aryl or C 0-10 It is substituted with alkyl-OH.

[0172] In one aspect of the present invention, the R6 is directly bonded, substituted, or unsubstituted C 1-10 Alkylene, substituted or unsubstituted C 1-10 Heteroalkylene, substituted or unsubstituted C 3-20 Cycloalkylene, substituted or unsubstituted C 3-20 Heterocycloalkylene, or substituted or unsubstituted C 6-20 It is Arilen, and

[0173] Here, if R6 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, C 0-5 Alkyl-OH, C 6-20 Aryl or CH2-C 6-20 It is replaced by aryl.

[0174] In one embodiment of the present invention, R6 is a direct connection.

[0175] In one aspect of the present invention, the R6 is a substituted unsubstituted C 1-5 It is an alkylene, and

[0176] Here, if R6 is substituted, one or more hydrogens are linear or branched C 1-5 Alkyl, C 0-3 It is substituted with alkyl-OH, C6-aryl, or CH2-C6-aryl.

[0177] In one aspect of the present invention, the R5 and R6 together form C 3-10 Cycloalkylene, C 3-10 Heterocycloalkylene, C 6-10 Aryllene or C 6-10 It forms heteroarylenides.

[0178] In one aspect of the present invention, R5 and R6 together , , , or forms.

[0179] In one embodiment of the present invention, the Y is H, -(CH2) n CH3, -(CH2) n COOH, -(CH2) n OH, -(CH2) n SO3H or -(CH2) n OSO3H, where n is an integer from 0 to 10.

[0180] In one embodiment of the present invention, the Y is -(CH2) n It is SO3H, and n is an integer from 0 to 5.

[0181] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0182] [The following compounds and their pharmaceutically acceptable salts] (NC10001 ~ NC10019)

[0183] , , , , , , , , , , , , , , , , , , and .

[0185] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0186] [The following compounds and their pharmaceutically acceptable salts] (NC10021 ~ NC10056)

[0187] , , , , , , , , , , , , , , , , , , , , , , and .

[0189] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0190] [The following compounds and their pharmaceutically acceptable salts] (NC10058 ~ NC10093)

[0191] , , , , , , , , , , , , , , , , , , , , , , , , and .

[0193] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0194] [The following compounds and their pharmaceutically acceptable salts] (NC20002 ~ NC20037)

[0195] , , , , , , , , , , , , , , , , , , , , , , , , and .

[0197] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0198] [The following compounds and their pharmaceutically acceptable salts] (NC30002 ~ NC30037)

[0199] , , , , , , , , , , , , , , , , , , , , , , , and .

[0201] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0202] [The following compounds and their pharmaceutically acceptable salts] (NC40002 ~ NC40037)

[0203] , , , , , , , , , , , , , , , , , , , , , , , , and .

[0205] In one specific embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0206] [The following compounds and their pharmaceutically acceptable salts] (NC50002 ~ NC50037)

[0207] , , , , , , , , , , , , , , , , , , , , , , , and .

[0209] The present invention includes not only the compound represented by the above general formula 1, but also all pharmaceutically acceptable salts thereof, and possible solvates, hydrates, racemics, or stereoisomers that can be prepared therefrom.

[0210] In one embodiment of the present invention, the compound represented by General Formula 1 or a pharmaceutically acceptable salt thereof is any one selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof.

[0211] , , , , , , , , , , , , , , , , , , ;

[0212] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

[0213] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

[0214] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

[0215] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

[0216] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ;

[0217] , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0218] (Here, Na + can be replaced with other pharmaceutically acceptable salts)

[0220] The compound represented by General Formula 1 of the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. The acid addition salt is obtained from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromide, hydroiodide, nitrous acid, or phosphoric acid, and non-toxic organic acids such as aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates and alkandioates, aromatic acids, and aliphatic and aromatic sulfonic acids. These pharmaceutically non-toxic salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chloride, bromides, iodides, fluorides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, malieates, butyne-1,4-dioate, hexane-1,6-dioate, benzoates, chlorobenzoates, methyl benzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, and phthalates. Includes terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, etc.

[0221] The acid addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving taurodeoxycholic acid represented by Formula 1 in an excess amount of an aqueous acid solution, and precipitating the salt using a water-miscible organic solvent, for example, methanol, ethanol, acetone, or acetonitrile. Alternatively, it can be prepared by drying the mixture by evaporating the solvent or the excess acid, or by suction filtration of the precipitated salt.

[0222] In addition, pharmaceutically acceptable metal salts can be produced using a base. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess amount of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to produce sodium, potassium, or calcium salts as metal salts, and more specifically, it is suitable to produce sodium salts. In addition, the corresponding silver salt is obtained by reacting the alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0223] In one specific embodiment of the present invention, sodium salt, hydrogen salt, potassium salt, magnesium salt, calcium salt, aluminum salt, chloride, hydrochloride, sulfate, carbonate, nitrate, phosphate, ferrous salt, tartrate, arginine, benzathine salt, chloroprocaine salt, choline salt, diethanolamine salt, ethanolamine, ethylenediamine, histidine, lithium, lysine, meglumine, procaine, triethylamine, Zinc, Acetate, Aspartate, Benzensulfonate, Benzoate, Besylate, Bicarbonate, Bitartrate, Bromine, Camsylate, Citrate, Decanoate, Edetate, Estolate, Esylate, Fumarate, Gluceptate, Gluconate, Glutamate, Glycolate, Glycollylarsanilate, Hexanoate, Hexylresorcinolate, Hydrabamine, Hydroxynaphthoate, Iodide,Composed of isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfonic acid, mucus, napsylate, octanoate, oleate, pamoate, pantothenate, polygalacturonate, propionate, salicylate, stearate, subacetate, succinate, teoclate, tosylate, and trithiodide. It may be a salt selected from the group. In one more specific embodiment of the present invention, the pharmaceutically acceptable salt may be a sodium salt.

[0224] In one embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof may additionally comprise an amino acid, a peptide, a sugar, a polysaccharide, or one or more conjugates thereof.

[0226] In addition, the present invention provides a pharmaceutical composition comprising the above compound or a pharmaceutically acceptable salt thereof.

[0227] In addition, the present invention provides a pharmaceutical composition for treating inflammatory diseases comprising the above compound or a pharmaceutically acceptable salt thereof.

[0228] In one embodiment of the present invention, the pharmaceutical composition may further comprise a pharmaceutically acceptable component. Examples of pharmaceutically acceptable ingredients include ARBs (Angiotensin Receptor Blockers), ACEIs (Angiotensin Converting Enzyme Inhibitors), CCBs (Calcium Channel Blockers), BBs (Beta Blockers), and Diuretics for compositions used to treat essential hypertension; Biguanides, Sulfonyl Urea (SU), Meglitinides, Thiazolidinediones (TZD), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), Sodium Glucose Co-Transporter 2 Inhibitors (SGLT-2i), and GLP-1RAs (Glucagon-Like Peptide 1 Receptor Agonists) for compositions used to treat type 2 diabetes; and Acetaminophens, NSAIDs (Non-Steroidal Anti-Inflammatory Drugs), Penicillins, Cephalosporins, Monobactams, Carbapenems, Polymyxins, Aminoglycosides, and Macrolides for compositions used to treat acute bronchitis. Fluoroquinolones, glycopeptides, HMG-CoA reductase inhibitors (β-hydroxy β-methylglutaryl-CoA reductase inhibitor) for compositions for treating dyslipidemia, PCSK9 inhibitors (Proprotein Convertase Subtilisin / Kexin type 9 inhibitor), fibrates, resins, omega-3, PPI (Proton Pump Inhibitor) for compositions for treating GERD, H1-antagonist, H2-antagonist for compositions for treating allergic rhinitis, corticosteroids,It may further include LTRA (Leukotriene receptor antagonist), α2-agonist, mast cell stabilizer, anticholinergic agents, cholinesterase inhibitor (composition for treating dementia), NMDA receptor antagonist, antipsychotic agents, antidepressant, acetaminophen (composition for treating osteoarthritis), NSAIDs, tramadol, 5-HT3 agonist (composition for treating migraines), ergot alkaloids, etc.

[0229] The route of administration of the compound of the present invention may be administered, for example, by an oral or parenteral route. Here, parenteral refers to a broad route of administration and includes, for example, intravenous, intra-arterial, intraperitoneal, intramuscular, subcutaneous, intranasal, sublingual, intrathecal, inhalation, ocular, rectal, vaginal, and ventricular administration.

[0230] When formulating the above composition, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

[0231] Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, troches, etc., and these solid dosage forms are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, or gelatin, with one or more compounds according to the present invention. In addition, lubricants such as magnesium stirate talc are also used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, or syrups, and may include various excipients, such as humectants, sweeteners, flavorings, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.

[0232] Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, etc.

[0233] Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspension solvents. Witepsol, Macrogol, Tween 61, cocoa paste, laurin paste, glycerol, gelatin, etc. may be used as bases for suppositories.

[0234] The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined based on factors including the type and severity of the patient's disease, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses. It is important to administer an amount that obtains maximum effect with a minimum amount without side effects by taking all of the above-mentioned factors into account, and this can be easily determined by a person skilled in the art.

[0235] Specifically, the effective amount of the compound according to the present invention may vary depending on the patient's age, gender, and weight, and generally, 0.01 mg to 100 mg per kg of body weight, more specifically 0.1 mg to 15 mg per kg of body weight, may be administered daily or every other day, or divided into 1 to 3 doses per day. However, since the dosage may be increased or decreased depending on the route of administration, severity, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0236] In the present invention, the bile acid or its derivative for preparing the compound of General Formula 1 may be any of the following: one isolated from the carcass of an animal, such as a sheep, dog, goat, or rabbit, commercially available, or synthesized.

[0238] The present invention will be explained in detail below through examples and experimental examples.

[0239] However, the following examples and experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following examples and experimental examples.

[0241] <Example 1> Method for preparing a taurine derivative

[0242] <Example 1-1> Preparation of taurine derivative (1)

[0243]

[0244] Sodium vinylsulfonic acid salt 2 amine ( 1 The mixture produced by adding ) was stirred at 100 °C for 48 hours. After cooling, the reaction mixture was concentrated under reduced pressure and coevaporated with acetonitrile to produce a sodium sulfonate compound ( A1 ) obtained.

[0246] <Example 1-2> Preparation of taurine derivative (2)

[0247]

[0248] 2-aminoethanol-1-ol (2-aminoethan-1-ol, 3A mixture of 7.0 mmol of ) and 35.0 mL (35.0 mmol) of potassium hydroxide (1 M in H2O) was heated at 100 °C for 16 hours by adding 2.1 mL (35.0 mmol) of carbon disulfide to the resulting mixture. After cooling to room temperature, the mixture was extracted with dichloromethane (3 × 20 mL). The combined organic layer was dried with sodium sulfate, and the solvent was completely removed under reduced pressure to obtain the thiazolidine-2-thione compound ( B1 ) obtained.

[0249] 7.0 mL (68.5 mmol) of a 30% hydrogen peroxide solution was dissolved in 35.0 mL (928 mmol) of formic acid at 0 °C and stirred at room temperature for 1 hour to obtain peroxyformic acid. The peroxyformic acid solution was cooled back to 0 °C, and 7.0 mmol of the above thiazolidin-2-thione compound was added gradually while stirring the resulting solution, which was then heated to room temperature. After 18 hours, the mixture was concentrated under reduced pressure and co-evaporated with acetonitrile. The obtained raw material was crystallized with ethanol and diethyl ether at 4 °C to obtain pure sulfonic acid. B2 ) obtained.

[0251] <Example 1-3> Preparation of taurine derivatives (3)

[0252]

[0253] 2.08 mL (15.0 mmol) of triethylamine tert-butyl(2-hydroxyethyl)carbamate, 4) was added to a 35 mL solution of dichloromethane containing 10.0 mmol. The mixed solution was cooled to 0 °C, and 0.93 mL (12.0 mmol) of mesyl chloride was added dropwise. The resulting mixture was stirred for 2 hours while slowly heating to room temperature. Saturated sodium bicarbonate was added to separate the layers, and the aqueous layer was extracted with dichloromethane (2 × 30 mL). The combined organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated to obtain 2-((tert-butoxycarbonyl)amino)ethyl methane sulfonate. C1 ) obtained.

[0254] 2.28 g (20.0 mmol) of potassium thioacetate and the above 2-(tert-butoxycarbonyl)amino)ethyl methanesulfonate ( C1 ) 10.0 mmol of dry anhydrous N,N The mixture prepared by dissolving in 50 mL of DMF was stirred at 65 °C for 16 hours. Subsequently, 50 mL of water and 50 mL of ethyl acetate were added to separate the layers. The organic layer was washed with 80% saturated brine (4 x 30 mL). Afterward, the organic layer was dried with sodium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography to obtain S-(2-((tert-butoxycarbonyl)amino)ethyl)ethane thioate, C2 ) obtained.

[0255] 4.25 mL (41.6 mmol) of hydrogen peroxide solution (30%) was dissolved in 20.8 mL (928 mmol) of formic acid at 0 °C and stirred at room temperature for 1 hour to obtain peroxyformic acid. The peroxyformic acid solution was cooled back to 0 °C, and the above S-(2-((tert-butoxycarbonyl)amino)ethyl) ethane thioate ( C2 The solution prepared by adding 4.2 mmol of ) dropwise was stirred and heated to room temperature. After 18 hours, the mixture was reduced in concentration and co-evaporated with ethanol. The residue was washed once each with DCM / EtOH and DCM to obtain pure sulfonic acid ( C3 ) obtained.

[0257] <Example 2> Preparation of Bile Acid Derivatives

[0258] <Example 2-1> Coupling of Cholic Acid Derivative and Taurine Derivative

[0259]

[0260] Cholic acid and its derivatives CA1-7 In 1 mL of dry anhydrous N,N-DMF containing 0.134 mmol, the taurine derivative prepared in <Examples 1-1> to <Examples 1-3> ( A1, B2, C3 0.147 mmol of ) 0.024 mL (0.174 mmol) of triethylamine and 0.043 g (0.0174 mmol) of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) were added, and the mixed solution was stirred at 90°C for 70 minutes. After cooling, the mixture was flushed with Dowex® and rinsed with 4 to 6 mL of methanol. Subsequently, the mixture was concentrated and purified by preparative liquid chromatography-mass spectrometry (LCMS) to obtain compounds (NC10XXX~NC50XXX) containing 2-aminoethanesulfonic acid.

[0262] <Example 2-2> Conversion to Na Salt

[0263]

[0264] The compounds (NC10XXX~NC50XXX) obtained in <Example 2-1> above were dissolved in 1 mL of MeCN / H2O (9:1), and an equal molar amount of an aqueous NaOH solution (0.1 M) was added. The resulting solution was concentrated under vacuum to obtain compounds in the Na-salt state (NC10XXX~NC50XXX , Na-salt ) obtained.

[0266] <Example 3> Preparation of Compound 1

[0267]

[0268] [Compound 1] - NC10001

[0269] Compound 1 was prepared by the preparation method of <Example 1> and <Example 2> above. Specifically, 400 mg (10 mmol) of NaOH was dissolved in 40 mL of 95% ethanol, and 1.11 g (10 mmol) of aminomethanesulfonic acid was added. The mixture was heated to 50 °C and stirred for 30 minutes. After cooling to room temperature, 4.12 g (10.4 mmol) of deoxycholic acid (DCA) and 5.0 g (20.2 mmol) of EEDQ were added. The mixture was washed with 5 mL of ethanol, heated to 40 °C, and stirred for 15 hours. Subsequently, it was cooled to room temperature and stirred for 1 hour. The solvent was evaporated, 50 mL of acetone was added, and ultrasonic waves were applied to obtain a solid. Subsequently, the mixture was filtered and washed with acetone and dried under vacuum for 5 hours to obtain 0.99 g of Compound 1. (Yield 19%)

[0271] <Example 4> Preparation of Compound 2

[0272]

[0273] [Compound 2] - NC10002

[0274] Compound 2 was prepared in the same manner as in the above example using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 1.39 g (10 mmol) of 3-amino-1-propanesulfonic acid, 400 mg (10 mmol) of NaOH, and 5.0 g (20.2 mmol) of EEDQ.

[0276] <Example 5> Preparation of Compound 3

[0277]

[0278] [Compound 3] - NC10003

[0279] Compound 3 was prepared in the same manner as in the above example using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 1.73 g (10 mmol) of 4-aminobenzenesulfonic acid, 400 mg (10 mmol) of NaOH, and 5.0 g (20.2 mmol) of EEDQ.

[0281] <Example 6> Preparation of Compound 4

[0282]

[0283] [Compound 4] - NC10004

[0284] Compound 4 was prepared using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 2.07 g (10 mmol) of 2-(cyclohexylamino)ethanesulfonic acid, 400 mg (10 mmol) of NaOH, and 5.0 g (20.2 mmol) of EEDQ in the same manner as in the above example. (Yield 51%)

[0286] <Example 7> Preparation of Compound 5

[0287]

[0288] [Compound 5] - NC10005

[0289] Compound 5 was prepared using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 1.82 g (10 mmol) of N-(2-acetamido)-2-aminoethanesulfonic acid, 400 mg (10 mmol) of NaOH, and 5.0 g (20.2 mmol) of EEDQ in the same manner as in the above example. (Yield 79.0%)

[0291] <Example 8> Preparation of Compound 6

[0292]

[0293] [Compound 6] - NC10006

[0294] Compound 6 was prepared in the same manner as in the above example using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 2.5 g (10 mmol) of N-methyltaurine sodium salt, 400 mg (10 mmol) of NaOH, and 5.0 g (20.2 mmol) of EEDQ.

[0296] <Example 9> Preparation of Compound 7

[0297]

[0298] [Compound 7] - NC10007

[0299] Compound 7 was prepared in the same manner as in the above example using 4.12 g (10.4 mmol) of deoxycholic acid (DCA), 1.41 g (10 mmol) of 2-aminoethyl hydrogen sulfate, and 5.0 g (20.2 mmol) of EEDQ.

[0301] <Example 10> Preparation of Compound 8

[0302]

[0303] [Compound 8] - NC10008

[0304] Compound 8 was prepared using 0.210 g (0.54 mmol) of deoxycholic acid (DCA), 96.6 mg (0.5 mmol) of 2-(Piperidin-4-yl)ethane-1-sulfonic acid, 20 mg (0.5 mmol) of NaOH, and 0.250 g (1.0 mmol) of EEDQ in the same manner as in the above example. (Yield 74.6%)

[0306] <Example 11> Preparation of Compound 9

[0307]

[0308] [Compound 9] - NC10009

[0309] Compound 9 was prepared using 0.205 g (0.52 mmol) of deoxycholic acid (DCA), 83.1 mg (0.5 mmol) of piperazine-1-sulfonic acid, 20 mg (0.5 mmol) of NaOH, and 0.250 g (1.0 mmol) of EEDQ in the same manner as in the above example. (Yield 56.5%)

[0311] <Example 12> Preparation of Compound 10

[0312]

[0313] [Compound 10] - NC10010

[0314] Compound 10 was prepared using 0.205 g (0.52 mmol) of deoxycholic acid (DCA), 97.1 mg (0.5 mmol) of 2-(piperazin-1-yl)ethane-1-sulfonic acid, 20 mg (0.5 mmol) of NaOH, and 0.250 g (1.0 mmol) of EEDQ in the same manner as in the above example. (Yield 71.1%)

[0316] <Example 13> Preparation of Compound 11

[0317]

[0318] [Compound 11] - NC10011

[0319] Compound 11 was prepared using 0.410 g (1.04 mmol) of deoxycholic acid (DCA), 165 mg (1.0 mmol) of piperidine-4-sulfonic acid, 40 mg (1.0 mmol) of NaOH, and 0.500 g (2.0 mmol) of EEDQ in the same manner as in the above example. (Yield 60.5%)

[0321] <Example 14> Preparation of Compound 12

[0322]

[0323] [Compound 12] - NC10012

[0324] Compound 12 was prepared using 0.200 g (0.53 mmol) of litocholic acid (LCA), 96.2 mg (0.5 mmol) of 2-(piperidin-4-yl)ethane-1-sulfonic acid, 20 mg (0.5 mmol) of NaOH, and 0.250 g (1.01 mmol) of EEDQ in the same manner as in the above example. (Yield 73.2%)

[0326] <Example 15> Preparation of Compound 13

[0327]

[0328] [Compound 13] - NC10013

[0329] Compound 13 was prepared using 0.395 g (1.05 mmol) of litocholic acid (LCA), 141 mg (1.0 mmol) of 2-aminoethyl hydrogen sulfate, 40 mg (1.0 mmol) of NaOH, and 0.507 g (2.05 mmol) of EEDQ in the same manner as in the above example. (Yield 61.3%)

[0331] <Example 16> Preparation of Compound 14

[0332]

[0333] [Compound 14] - NC10014

[0334] Compound 14 was prepared using 0.395 g (1.05 mmol) of litocholic acid (LCA), 139 mg (1.0 mmol) of 3-amino-1-propanesulfonic acid, 40 mg (1.0 mmol) of NaOH, and 0.507 g (2.05 mmol) of EEDQ in the same manner as in the above example. (Yield 86.6%)

[0336] <Example 17> Preparation of Compound 15

[0337]

[0338] [Compound 15] - NC10015

[0339] Compound 15 was prepared using 0.395 g (1.05 mmol) of litocholic acid (LCA), 173 mg (1.0 mmol) of 4-aminobenzenesulfonic acid, 40 mg (1.0 mmol) of NaOH, and 0.505 g (2.05 mmol) of EEDQ in the same manner as in the above example. (Yield 70.4%)

[0341] <Example 18> Preparation of Compound 16

[0342]

[0343] [Compound 16] - NC10016

[0344] Compound 16 was prepared using 0.395 g (1.05 mmol) of litocholic acid (LCA), 207 mg (1.0 mmol) of 2-(cyclohexylamino)ethanesulfonic acid, 40 mg (1.0 mmol) of NaOH, and 0.507 g (2.05 mmol) of EEDQ in the same manner as in the above example. (Yield 66.3%)

[0346] <Example 19> Preparation of Compound 17

[0347]

[0348] [Compound 17] - NC10017

[0349] Compound 9 was prepared by the preparation method of <Example 1> and <Example 2> above. Specifically, 3.92 g (10 mmol) of deoxycholic acid (DCA), 1.42 g (10.5 mmol) of hydroxybenzotriazole (HOBt), and 2.17 g (10.5 mmol) of N,N'-dicyclohexylcarbodiimide (DCC) were mixed with 30 mL of DMF. To the mixture, 1.41 mL (10 mmol) of N,N-diethylethylenediamine and 1.15 mL (10.4 mmol) of N-methylmorpholine (N-MMP) were added. The mixture was heated to 40–45 °C and stirred for 1 day. Afterward, it was cooled to room temperature and filtered and washed with 10 mL of DMF. The solvent was evaporated under reduced pressure, dissolved in 20 mL of 2N HCl and 80 mL of H2O, and washed with 100 mL of ethyl acetate x 2. Subsequently, the solution was neutralized with NaOH until the pH reached 8–9, and then saturated with NaCl. The solution was extracted with 100 mL of dichloromethane x 2, mixed with the organic layer, and dissolved in 10 mL of methanol. Afterward, the solution was dried with Na2SO4, filtered and washed with dichloromethane, and the solvent was evaporated. Subsequently, compound 17 was obtained by sequentially filtering and washing with ethanol, 1N HCl ether, and acetone.

[0351] <Example 20> Preparation of Compound 18

[0352]

[0353] [Compound 18] - NC10018

[0354] Compound 18 was prepared in the same manner as in the above example using 3.92 g (10 mmol) of deoxycholic acid (DCA), 1.42 g (10.5 mmol) of HOBt, 2.17 g (10.5 mmol) of DCC, 1.30 g (10 mmol) of 4-(2-aminoethyl)morpholine, and 1.06 g (10.4 mmol) of N-MMP.

[0356] <Example 21> Preparation of Compound 19

[0357]

[0358] [Compound 19] - NC10019

[0359] Compound 19 was prepared in the same manner as in the above example using 3.92 g (10 mmol) of deoxycholic acid (DCA), 1.42 g (10.5 mmol) of HOBt, 2.17 g (10.5 mmol) of DCC, 1.00 g (10 mmol) of 1-methylpiperazine, and 1.06 g (10.4 mmol) of N-MMP.

[0361] <Example 22> Preparation of Bile Acid Derivatives

[0362] The following bile acid derivatives were prepared in the same manner as the above example, and the specific chemical structural formulas, NMR data, and MS data of the bile acid derivatives are as shown below.

[0364]

[0365] NC10001

[0366] 1 H NMR (400 MHz, DMSO-d6) δ 8.04 (t, J = 6.2 Hz, 1H), 4.45 (s, 1H), 4.22-4.15 (m, 1H), 3.92-3.82 (m, 2H), 3.81-3.76 (m, 1H), 3.41-3.31 (m, 1H), 2.15 (ddd, J= 14.1, 10.6, 5.0 Hz, 1H), 2.00 (ddd, J = 14.1, 10.2, 6.0 Hz, 1H), 1.86-1.41 (m, 10H), 1.40-0.94 (m, 13H), 0.94-0.85 (m, 4H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 25 H 42 NO6S [M-Na] - 484.3, found 484.6.

[0368]

[0369] NC10002

[0370] 1 H NMR (400 MHz, DMSO-d6) δ 7.78 (t, J = 5.6 Hz, 1H), 4.46 (d, J = 4.4 Hz, 1H), 4.19 (d, J = 4.1 Hz, 1H), 3.81-3.74 (m, 1H), 3.47-3.32 (m, 1H), 3.08-3.03 (m, 2H), 2.45-2.37 (m, 2H), 2.12-2.00 (m, 1H), 1.93 (ddd, J = 13.7, 9.6, 6.4 Hz, 1H), 1.86-0.95 (m, 25H), 0.94-0.85 (m, 4H), 0.84 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.6.

[0372]

[0373] NC10003

[0374] 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 7.56-7.47 (m, 4H), 4.47 (d, J = 4.2 Hz, 1H), 4.21 (d, J = 3.9 Hz, 1H), 3.83-3.76 (m, 1H), 3.49-3.38 (m, 1H), 2.34 (ddd, J = 14.1, 9.7, 4.6 Hz, 1H), 2.20 (ddd, J = 14.7, 9.0, 6.5 Hz, 1H), 1.87-1.67 (m, 5H), 1.67-1.41 (m, 5H), 1.41-1.13 (m, 11H), 1.12-0.86 (m, 6H), 0.84 (s, 3H), 0.60 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 44 NO6S [M-Na] - 546.3, found 546.6.

[0376]

[0377] NC10004

[0378] 1 H NMR (400 MHz, DMSO-d6) δ 4.45 (t, J = 4.9 Hz, 1H), 4.20 (d, J = 4.1 Hz, 1H), 4.15-4.07 (m, 0.5H), 3.83-3.76 (m, 1H), 3.57-3.47 (m, 0.5H), 3.46-3.35 (m, 3H), 2.66-2.54 (m, 2H), 2.33-2.11 (m, 2H), 1.86-0.86 (m, 37H), 0.84 (s, 3H), 0.59 (d, J = 1.9 Hz, 3H); LCMS (ESI) m / z calcd for C 32 H 54 NO6S [M-Na] - 580.4, found 580.8.

[0380]

[0381] NC10005

[0382] 1 H NMR (400 MHz, DMSO-d6) δ 7.52 (s, 0.4H) 7.42 (s, 0.6H), 7.11 (s, 0.4H), 6.91 (s, 0.6H), 4.49-4.40 (m, 1H), 4.20 (d, J = 4.1 Hz, 0.6H), 4.18 (d, J = 4.1 Hz, 0.4H), 3.91 (s, 1H), 3.83-3.71 (m, 2H), 3.61-3.51 (m, 1H), 3.49-3.41 (m, 1H), 3.41-3.31 (m, 1H), 2.69-2.65 (m, 1.2H), 2.59-2.56 (m, 0.8H), 2.49-2.38 (m, 0.6H), 2.33-2.21 (m, 0.6H), 2.21-2.10 (m, 0.4H) 2.07-1.97 (m, 0.4H), 1.87-1.41 (m, 10H), 1.40-0.79 (m, 20H), 0.60 (s, 1.8H), 0.59 (s, 1.2H); LCMS (ESI) m / z calcd for C 28 H 47 N2O7S [M-Na] - 555.3, found 555.6.

[0384]

[0385] NC10006

[0386] 1H NMR (400 MHz, DMSO-d6) δ 4.45 (s, 1H), 4.25-4.16 (m, 1H), 3.79 (s, 1H), 3.55-3.41 (m, 2H), 3.40-3.30 (m, 1H), 2.93 (s, 1.5H), 2.75 (s, 1.5H), 2.69-2.62 (m, 1H), 2.60-2.53 (m, 1H), 2.36-2.10 (m, 2H), 1.86-1.70 (m, 4H), 1.68-1.41 (m, 6H), 1.40-1.11 (m, 11H), 1.09-0.85 (m, 6H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.6.

[0388]

[0389] NC10007

[0390] 1 H NMR (400 MHz, DMSO-d6) δ 7.85 (t, J = 5.6 Hz, 1H), 4.45 (d, J = 4.3 Hz, 1H), 4.18 (d, J = 4.1 Hz, 1H), 3.82-3.75 (m, 1H), 3.69 (t, J = 6.1 Hz, 2H), 3.42-3.31 (m, 1H), 3.19 (q, J = 5.9 Hz, 2H), 2.14-2.03 (m, 1H), 1.95 (ddd, J = 13.9, 9.7, 6.3 Hz, 1H), 1.86-1.69 (m, 4H), 1.68-1.40 (m, 6H), 1.40-1.09 (m, 11H), 1.08-0.85 (m, 6H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / zcalcd for C 26 H 44 NO7S [M-Na] - 514.3, found 514.5.

[0392]

[0393] NC10008

[0394] 1 H NMR (400 MHz, DMSO-d6) δ 4.46 (d, J = 4.2 Hz, 1H), 4.34 (d, J = 12.9 Hz, 1H), 4.19 (d, J = 4.0 Hz, 1H), 3.84-3.75 (m, 2H), 3.42-3.30 (m, 1H), 2.98-2.87 (m, 1H), 2.48-2.36 (m, 3H), 2.34-2.22 (m, 1H), 2.22-2.10 (m, 1H), 1.86-1.41 (m, 15H), 1.40-0.85 (m, 19H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.7.

[0396]

[0397] NC10009

[0398] 1 H NMR (400 MHz, DMSO-d6) δ 4.45 (d, J = 4.2 Hz, 1H), 4.19 (d, J = 4.0 Hz, 1H), 3.82-3.75 (m, 1H), 3.48-3.35 (m, 5H), 2.83-2.65 (m, 4H), 2.30 (ddd, J = 15.4, 10.3, 5.2 Hz, 1H), 2.17 (ddd, J= 15.3, 9.9, 5.9 Hz, 1H), 1.86-1.69 (m, 4H), 1.67-1.41 (m, 6H), 1.39-1.12 (m, 11H), 1.10-0.86 (m, 6H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 47 N2O6S [M-Na] - 539.3, found 539.5.

[0400]

[0401] NC10010

[0402] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.94 (m, 1H), 3.61-3.46 (m, 5H), 3.07-2.99 (m, 2H), 2.89-2.82 (m, 2H), 2.56-2.54 (m, 2H), 2.52-2.40 (m, 3H), 2.35-2.27 (m, 1H), 1.96-1.68 (m, 7H), 1.67-1.56 (m, 3H), 1.55-1.23 (m, 11H), 1.22-0.91 (m, 9H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 51 N2O6S [M-Na] - 567.3, found 567.8.

[0404]

[0405] NC10011

[0406] 1 H NMR (500 MHz, CD3OD) δ 4.65-4.55 (m, 1H), 4.06-4.04 (m,1H), 3.97-3.95 (m, 1H), 3.57-3.47 (m, 1H), 3.13 (td, J= 13.2, 2.6 Hz, 1H), 2.90 (tt, J = 11.7, 3.8 Hz, 1H), 2.69-2.60 (m, 1H), 2.52-2.40 (m, 1H), 2.38-2.26 (m, 1H), 2.23-2.08 (m, 2H), 1.95-1.68 (m, 8H), 1.68-1.55 (m, 4H), 1.55-1.23 (m, 11H), 1.22-1.06 (m, 2H), 1.04 (d, J = 6.5 Hz, 3H), 0.98 (td, J = 14.1, 3.3 Hz, 1H), 0.93 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.7.

[0408]

[0409] NC10012

[0410] 1 H NMR (400 MHz, DMSO-d6) δ 4.50 (s, 1H), 4.33 (d, J = 13.1 Hz, 1H), 3.80 (d, J = 13.4 Hz, 1H), 3.53-3.35 (m, 1H), 2.95-2.89 (m, 1H), 2.48-2.36 (m, 3H), 2.35-2.22 (m, 1H), 2.22-2.11 (m, 1H), 1.96-1.87 (m, 1H), 1.85-1.72 (m, 2H), 1.71-1.43 (m, 10H), 1.42-0.77 (m, 26H), 0.60 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO5S [M-Na] - 550.4, found 550.3.

[0412]

[0413] NC10013

[0414] 1 H NMR (500 MHz, CD3OD) δ 4.31-4.26 (m, 1H), 4.05-4.01 (m, 1H), 3.60-3.49 (m, 1H), 3.46-3.42 (m, 1H), 3.23-3.19 (m, 1H), 2.49-2.08 (m, 2H), 2.03-2.00 (m,1H), 1.96-1.70 (m, 5H), 1.66-1.57 (m, 2H), 1.51-1.24 (m, 12H), 1.24-1.05 (m, 5H), 1.03-0.93 (m, 7H), 0.694 (s, 1.5H), 0.691 (s, 1.5H); LCMS (ESI) m / z calcd for C 26 H 44 NO6S [M-Na] - 498.3, found 498.6.

[0416]

[0417] NC10014

[0418] 1 H NMR (400 MHz, DMSO-d6) δ 7.80 (t, J = 5.6 Hz, 1H), 4.49 (d, J = 4.5 Hz, 1H), 3.59-3.24 (m, 1H), 3.05 (q, J = 6.6 Hz, 2H), 2.46-2.37 (m, 2H), 2.11-2.01 (m, 1H), 1.99-1.87 (m, 2H), 1.83-1.43 (m, 9H), 1.41-0.96 (m, 17H), 0.95-0.80 (m, 7H), 0.60 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46NO5S [M-Na] - 496.3, found 496.6.

[0420]

[0421] NC10015

[0422] 1 H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 7.57-7.46 (m, 4H), 4.45 (d, J = 4.5 Hz, 1H), 3.42-3.31 (m, 1H), 2.33 (ddd, J = 14.7, 9.7, 5.2 Hz, 1H), 2.20 (ddd, J = 14.7, 9.3, 6.6 Hz, 1H), 1.97-1.90 (m, 1H), 1.88-1.45 (m, 7H), 1.45-0.97 (m, 17H), 0.97-0.89 (m, 4H), 0.87 (s, 3H), 0.62 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 44 NO5S [M-Na] - 530.3, found 530.7.

[0424]

[0425] NC10016

[0426] 1 H NMR (500 MHz, CD3OD) δ 3.73-3.61 (m, 2H), 3.58-3.47 (m, 1H), 3.08-3.00 (m, 2H), 2.49-2.38 (m, 1H), 2.37-2.25 (m, 1H), 2.05-1.99 (m, 1H), 1.95-1.52 (m, 14H), 1.52-1.05 (m, 21H), 1.04-0.92 (m, 7H), 0.70 (d, J = 4.9 Hz, 3H); LCMS (ESI) m / z calcd for C32 H 54 NO5S [M-Na] - 564.4, found 564.6.

[0428]

[0429] NC10017

[0430] 1 H NMR (500 MHz, CD3OD) δ 3.96 (t, J = 3.0 Hz, 1H), 3.58-3.48 (m, 3H), 3.30-3.22 (m, 6H), 2.32 (ddd, J = 14.0, 10.6, 4.9 Hz, 1H), 2.16 (ddd, J = 14.1, 9.9, 6.2 Hz, 1H), 1.95-1.73 (m, 7H), 1.67-1.56 (m, 3H), 1.56-1.24 (m, 17H), 1.22-1.07 (m, 2H), 1.03 (d, J = 6.4 Hz, 3H), 1.01-0.95 (m, 1H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 55 N2O3[M-Cl] + 491.4, found 491.3.

[0432]

[0433] NC10018

[0434] 1 H NMR (500 MHz, CD3OD) δ 4.12-4.02 (m, 2H), 3.97-3.94 (m, 1H), 3.84-3.73 (m, 2H), 3.65-3.48 (m, 5H), 3.29 (t, J = 6.0 Hz, 2H), 3.23-3.12 (m, 2H), 2.33 (ddd, J= 13.9, 10.6, 4.7 Hz, 1H), 2.22-2.13 (m, 1H), 1.95-1.73 (m, 7H), 1.67-1.55 (m, 3H), 1.55-1.33 (m, 9H), 1.33-1.23 (m, 2H), 1.23-1.07 (m, 2H), 1.05-0.95 (m, 4H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 53 N2O4[M-Cl] + 505.4, found 505.3.

[0436]

[0437] NC10019

[0438] 1 H NMR (500 MHz, CD3OD) δ 4.66 (s, 1H), 4.20 (s, 1H), 3.97-3.95 (m,1H), 3.73-3.36 (m, 4H), 3.28-2.96 (m, 3H), 2.93 (s, 3H), 2.51 (ddd, J = 15.7, 10.9, 5.1 Hz, 1H), 2.36 (ddd, J = 15.6, 10.5, 5.6 Hz, 1H), 1.95-1.70 (m, 7H), 1.68-1.56 (m, 3H), 1.56-1.23 (m, 11H), 1.23-1.06 (m, 2H), 1.04 (d, J = 6.5 Hz, 3H), 1.02-0.95 (m, 1H), 0.94 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 51 N2O3[M-Cl] + 475.4, found 475.3.

[0440]

[0441] NC10021

[0442] 1 H NMR (400 MHz, DMSO-d6) δ 7.79 (t, J = 5.4 Hz, 1H), 4.47 (s, 1H), 4.22 (s, 1H), 3.78 (s, 1H), 3.41-3.29 (m, 1H), 3.12-3.07 (m, 2H), 2.04 (ddd, J = 14.8, 10.1, 5.1 Hz, 1H), 1.97-1.85 (m, 3H), 1.85-1.41 (m, 10H), 1.40-0.93 (m, 13H), 0.93-0.85 (m, 4H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5[M-Na] - 462.3, found 462.2.

[0444]

[0445] NC10022

[0446] 1 H NMR (500 MHz, CD3OD) δ 3.96 (t, J = 3.0 Hz, 1H), 3.58 (t, J = 6.3 Hz, 2H), 3.56-3.49 (m, 1H), 3.25 (td, J = 6.9, 1.1 Hz, 2H), 2.29-2.20 (m, 1H), 2.15-2.05 (m, 1H), 1.95-1.74 (m, 7H), 1.74-1.66 (m, 2H), 1.65-1.56 (m, 3H), 1.56-1.23 (m, 11H), 1.23-1.06 (m, 2H), 1.05-0.94 (m, 4H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46NO4[M-H] - 448.3, found 448.1.

[0447]

[0448] NC10024

[0449] 1H NMR (500 MHz, CD3OD) δ 7.41-7.34 (m, 1H), 7.34-7.19 (m, 4H), 4.74 (s, 1H), 4.63 (s, 1H), 3.99-3.94 (m, 0.5H), 3.93-3.88 (m, 0.5H), 3.83-3.67 (m, 2H), 3.57-3.46 (m, 1H), 3.10-2.96 (m, 2H), 2.62-2.52 (m, 0.5H), 2.52-2.38 (m, 1H), 2.35-2.25 (m, 0.5H), 1.96-1.68 (m, 7H), 1.68-1.03 (m, 18H), 1.02-0.90 (m, 5H), 0.71 (s, 1.5H), 0.67 (s, 1.5H); LCMS (ESI) m / z calcd for C 33 H 50 NO6S [M-Na] - 588.3, found 588.2.

[0451]

[0452] NC10025

[0453] 1 H NMR (500 MHz, CD3OD) δ 3.99-3.93 (m, 1H), 3.89-3.77 (m, 1H), 3.77-3.64 (m, 3H), 3.60-3.44 (m, 3H), 3.15-3.01 (m, 2H), 2.57-2.45 (m, 1H), 2.43-2.30 (m, 1H), 1.96-1.70 (m, 7H), 1.66-1.55 (m, 3H), 1.55-1.24 (m, 11H), 1.23-0.94 (m, 6H), 0.93 (s, 3H), 0.73-0.69 (m, 3H); LCMS (ESI)m / z calcd for C 28 H 48 NO7S [M-Na] - 542.3, found 542.4.

[0456]

[0457] NC10026

[0458] 1 H NMR (500 MHz, CD3OD) δ 4.66-4.56 (m, 0.5H), 4.23-4.13 (m, ,0.5H), 3.99-3.94 (m, 1H), 3.72-3.65 (m, 1H), 3.65-3.58 (m, 1H), 3.57-3.46 (m, 1H), 3.10-3.01 (m, 2H), 2.51-2.40 (m, 1H), 2.38-2.26 (m, 1H), 1.95-1.69 (m, 7H), 1.67-1.57 (m, 3H), 1.55-1.23 (m, 15H), 1.23-1.07 (m, 4H), 1.06-0.94 (m, 4H), 0.934 (s, 1.5H), 0.932 (s, 1.5H), 0.72 (s, 1.5H), 0.71 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.2.

[0460]

[0461] NC10027

[0462] 1 H NMR (500 MHz, CD3OD) δ 4.44 (tt, J = 12.2, 4.0 Hz, 0.5H), 4.06-3.91 (m, 3.5H), 3.77-3.62 (m, 2H), 3.56-3.41 (m, 3H), 3.09-3.01 (m, 2H), 2.54-2.43 (m, 1H), 2.36 (ddd,J = 14.7, 10.2, 5.8 Hz, 1H), 2.05-1.23 (m, 25H), 1.23-1.02 (m, 5H), 1.01-0.94 (m, 1H), 0.935 (s, 1.5H), 0.931 (s, 1.5H), 0.72 (s, 1.5H), 0.71 (s, 1.5H); LCMS (ESI) m / z calcd for C 31 H 52 NO7S [M-Na] - 582.3, found 582.2.

[0464]

[0465] NC10028

[0466] 1 H NMR (500 MHz, CD3OD) δ 5.03 (d, J = 10.6 Hz, 0.4H), 4.43 (d, J = 13.0 Hz, 0.6H), 4.33-4.26 (m, 0.6H), 4.00-3.89 (m, 1.4H), 3.57-3.46 (m, 1H), 3.24 (dd, J = 13.5, 11.1 Hz, 0.6H), 3.01 (td, J = 13.2, 2.7 Hz, 0.4H), 2.83-2.56 (m, 2H), 2.56-2.40 (m, 1H), 2.39-2.21 (m, 2H), 1.96-1.69 (m, 9H), 1.67-1.57 (m, 3H), 1.57-1.24 (m, 12H), 1.23-0.94 (m, 6H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.2.

[0467]

[0468] NC10029

[0469] 1 H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 10.4 Hz, 0.4H), 4.44 (d, J = 13.0 Hz, 0.6H), 4.34-4.27 (m, 0.6H), 3.99-3.89 (m, 1.4H), 3.56-3.46 (m, 1H), 3.23 (dd, J = 13.6, 11.2 Hz, 0.6H), 3.01 (td, J = 13.2, 2.8 Hz, 0.4H), 2.83-2.54 (m, 2H), 2.53-2.24 (m, 3H), 1.95-1.68 (m, 9H), 1.67-1.55 (m, 3H), 1.55-1.23 (m, 12H), 1.23-1.02 (m, 5H), 1.02-0.95 (m, 1H), 0.93 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.2.

[0471]

[0472] NC10031

[0473] 1 H NMR (400 MHz, DMSO-d6) δ 4.45 (d, J = 4.0 Hz, 1H), 4.21 (d, J = 4.0 Hz, 1H), 4.16 (td, J = 8.4, 3.8 Hz, 1H), 4.05-3.96 (m, 1H), 3.85 (t, J= 9.0 Hz, 1H), 3.80-3.71 (m, 2H), 3.44-3.35 (m, 2H), 2.06-1.94 (m, 1H), 1.94-1.40 (m, 11H), 1.40-0.85 (m, 17H), 0.84 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO6S [M-Na] - 510.3, found 510.1.

[0475]

[0476] NC10032

[0477] 1 H NMR (500 MHz, CD3OD) δ 3.95 (t, J = 3.0 Hz, 1H), 3.51 (tt, J = 11.1, 4.6 Hz, 1H), 3.20-3.11 (m, 2H), 2.25-2.16 (m, 1H), 2.10-2.00 (m, 1H), 1.95-1.71 (m, 7H), 1.66-1.23 (m, 20H), 1.23-1.05 (m, 2H), 1.03-0.94 (m, 4H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 48 NO6S [M-Na] - 526.3, found 526.2.

[0479]

[0480] NC10033

[0481] 1 H NMR (500 MHz, CD3OD) δ 7.29-7.22 (m, 4H), 7.22-7.14 (m, 1H), 4.51-4.43 (m, 1H), 3.94 (t, J= 3.0 Hz, 1H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 3.17 (dd, J = 13.6, 6.1 Hz, 1H), 3.04-2.94 (m, 2H), 2.91 (dd, J = 13.7, 7.9 Hz, 1H), 2.18 (ddd, J = 13.8, 10.6, 5.1 Hz, 1H), 2.02 (ddd, J = 13.8, 10.3, 6.2 Hz, 1H), 1.95-1.73 (m, 6H), 1.73-1.32 (m, 12H), 1.31-1.03 (m, 5H), 1.03-0.94 (m, 4H), 0.93 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 50 NO6S [M-Na] - 588.3, found 588.3.

[0483]

[0484] NC10034

[0485] 1 H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 7.5 Hz, 1H), 7.29-7.11 (m, 5H), 4.45 (d, J = 4.3 Hz, 1H), 4.22-4.06 (m, 2H), 3.78 (s, 1H), 3.41-3.31 (m, 1H), 3.13 (dd, J = 13.3, 6.0 Hz, 1H), 2.75 (dd, J = 13.3, 6.9 Hz, 1H), 2.54-2.51 (m, 2H), 2.07-1.94 (m, 1H), 1.93-1.41 (m, 11H), 1.38-0.93 (m, 13H), 0.89 (d, J= 6.5 Hz, 4H), 0.84 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 50 NO6S [M-Na] - 588.3, found 588.3.

[0487]

[0488] NC10035

[0489] 1 H NMR (500 MHz, CD3OD) δ 4.24-4.17 (m, 1H), 3.96 (t, J = 3.0 Hz, 1H), 3.52 (tt, J = 11.1, 4.5 Hz, 1H), 2.98-2.92 (m, 2H), 2.30 (ddd, J = 13.8, 10.5, 5.1 Hz, 1H), 2.16-2.03 (m, 2H), 1.96-1.73 (m, 7H), 1.67-1.23 (m, 14H), 1.23-1.05 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H), 1.01-0.94 (m, 1H), 0.94-0.88 (m, 9H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.2.

[0491]

[0492] NC10036

[0493] 1 H NMR (400 MHz, DMSO-d6) δ 7.46 (d, J = 8.5 Hz, 1H), 4.45 (d, J = 4.3 Hz, 1H), 4.19 (d, J= 4.0 Hz, 1H), 3.98-3.87 (m, 1H), 3.78 (s, 1H), 3.41-3.28 (m, 1H), 2.54-2.51 (m, 2H), 2.14-1.91 (m, 3H), 1.86-1.40 (m, 10H), 1.40-0.85 (m, 17H), 0.84 (s, 3H), 0.75 (d, J = 6.8 Hz, 6H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.2.

[0495]

[0496] NC10037

[0497] 1 H NMR (500 MHz, CD3OD) δ 7.38-7.33 (m, 2H), 7.33-7.26 (m, 2H), 7.24-7.19 (m, 1H), 5.35 (dd, J = 10.0, 3.7 Hz, 1H), 3.97-3.92 (m, 1H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 3.26 (dd, J = 14.3, 10.0 Hz, 1H), 3.10 (dd, J = 14.3, 3.8 Hz, 1H), 2.32 (ddd, J = 13.7, 10.0, 5.0 Hz, 1H), 2.16 (ddd, J = 13.9, 9.6, 6.7 Hz, 1H), 1.95-1.73 (m, 7H), 1.65-1.54 (m, 3H), 1.54-1.03 (m, 13H), 1.02-0.94 (m, 4H), 0.93 (s, 3H), 0.67 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48NO6S [M-Na] - 574.3, found 574.2.

[0498]

[0499] NC10038

[0500] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.27 (m, 4H), 7.24-7.18 (m, 1H), 5.35 (dd, J = 10.0, 3.7 Hz, 1H), 3.97-3.92 (m, 1H), 3.51 (tt, J = 11.1, 4.5 Hz, 1H), 3.26 (dd, J = 14.3, 10.0 Hz, 1H), 3.09 (dd, J = 14.3, 3.7 Hz, 1H), 2.30 (ddd, J = 14.0, 9.6, 4.6 Hz, 1H), 2.18 (ddd, J = 13.7, 8.7, 7.2 Hz, 1H), 1.95-1.73 (m, 7H), 1.64-1.09 (m, 15H), 1.09-0.94 (m, 5H), 0.93 (s, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO6S [M-Na] - 574.3, found 574.2.

[0502]

[0503] NC10039

[0504] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.37 (m, 1H), 3.99-3.93 (m, 1H), 3.59-3.32 (m, 3.5H), 3.02-2.90 (m, 1H), 2.73 (dd, J= 13.3, 10.6 Hz, 0.5H), 2.60-2.51 (m, 0.5H), 2.47-2.28 (m, 2H), 2.21 (ddd, J = 15.1, 10.1, 5.9 Hz, 0.5H), 2.11-1.69 (m, 10H), 1.67-1.23 (m, 14H), 1.23-1.07 (m, 2H), 1.05 (d, J = 6.5 Hz, 1.5H), 1.03 (d, J = 6.5 Hz, 1.5H), 1.01-0.94 (m, 1H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.2.

[0506]

[0507] NC10040

[0508] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.38 (m, 1H), 3.99-3.93 (m, 1H), 3.60-3.33 (m, 3.5H), 3.02-2.90 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.50-2.39 (m, 2H), 2.35 (ddd, J = 15.3, 10.6, 5.1 Hz, 0.5H), 2.23 (ddd, J = 14.6, 10.2, 5.9 Hz, 0.5H), 2.11-1.70 (m, 10H), 1.67-1.23 (m, 14H), 1.23-1.07 (m, 2H), 1.05 (d, J = 6.5 Hz, 1.5 H), 1.03 (d, J= 6.5 Hz, 1.5H), 0.933 (s, 1.5H), 0.931 (s, 1.5H), 1.01-0.95 (m, 1H), 0.933 (s, 1.5H), 0.931 (s, 1.5H), 0.713 (s, 1.5H), 0.711 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.2.

[0510]

[0511] NC10041

[0512] 1 H NMR (400 MHz, DMSO-d6) δ 7.62-7.55 (m, 1H), 4.45 (d, J = 4.3 Hz, 1H), 4.19 (d, J = 3.9 Hz, 1H), 3.78 (s, 1H), 3.41-3.22 (m, 2H), 3.17-3.06 (m, 1H), 2.48-2.41 (m, 1H), 2.06 (ddd, J = 14.5, 9.8, 5.0 Hz, 1H), 2.00-1.88 (m, 1H), 1.86-1.41 (m, 10H), 1.40-0.85 (m, 20H), 0.84 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.2.

[0514]

[0515] NC10042

[0516] 1 H NMR (500 MHz, CD3OD) δ 3.96 (t, J= 3.0 Hz, 1H), 3.59-3.41 (m, 3H), 2.99-2.89 (m, 1H), 2.27 (ddd, J = 13.8, 10.1, 5.0 Hz, 1H), 2.12 (ddd, J = 13.9, 9.7, 6.6 Hz, 1H), 1.95-1.74 (m, 7H), 1.67-1.55 (m, 3H), 1.55-1.24 (m, 14H), 1.22-1.04 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H), 1.01-0.94 (m, 1H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.2.

[0518]

[0519] NC10043

[0520] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.26 (m, 1H), 3.96 (t, J = 3.2 Hz, 1H), 3.76-3.65 (m, 2H), 3.52 (tt, J = 11.1, 4.5 Hz, 1H), 3.14-3.07 (m, 1H), 3.06-2.99 (m, 1H), 2.32-2.25 (m, 1H), 2.17-2.09 (m, 1H), 1.95-1.73 (m, 7H), 1.66-1.55 (m, 3H), 1.55-1.23 (m, 11H), 1.23-1.06 (m, 2H), 1.04-0.94 (m, 4H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] -528.3, found 528.2.

[0522]

[0523] NC10045

[0524] 1 H NMR (400 MHz, DMSO-d6) δ 7.61 (d, J = 4.5 Hz, 1H), 4.45 (d, J = 4.4 Hz, 1H), 4.20 (d, J = 4.0 Hz, 1H), 3.93-3.84 (m, 1H), 3.81-3.75 (m, 1H), 3.41-3.28 (m, 1H), 2.48-2.42 (m, 1H), 2.25-2.13 (m, 1H), 2.08-1.86 (m, 2H), 1.86-1.67 (m, 7H), 1.67-1.41 (m, 6H), 1.41-0.85 (m, 21H), 0.84 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO6S [M-Na] - 552.3, found 552.3.

[0526]

[0527] NC10046

[0528] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.27 (m, 1H), 3.96 (t, J = 3.0 Hz, 1H), 3.51 (tt, J = 11.1, 4.6 Hz, 1H), 2.91 (dt, J = 10.1, 4.0 Hz, 1H), 2.32 (ddd, J = 14.2, 10.2, 5.2 Hz, 1H), 2.25-2.18 (m, 1H), 2.13 (ddd, J= 14.3, 9.9, 6.5 Hz, 1H), 2.07-1.74 (m, 10H), 1.67-1.57 (m, 3H), 1.55-1.23 (m, 15H), 1.22-1.05 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H), 1.00-0.94 (m, 1H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO6S [M-Na] - 552.3, found 552.3.

[0530]

[0531] NC10047

[0532] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.98-3.93 (m, 1H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 3.05 (dd, J = 13.9, 5.5 Hz, 1H), 2.87 (dd, J = 13.9, 7.0 Hz, 1H), 2.23 (ddd, J = 13.8, 10.2, 5.1 Hz, 1H), 2.08 (ddd, J = 13.8, 9.7, 6.5 Hz, 1H), 1.95-1.73 (m, 7H), 1.66-1.57 (m, 3H), 1.57-1.23 (m, 14H), 1.22-1.04 (m, 2H), 1.01 (d, J = 6.5 Hz, 3H), 1.00-0.94 (m, 1H), 0.93 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.2.

[0534]

[0535] NC10048

[0536] 1 H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 7.4 Hz, 1H), 4.45 (d, J = 4.3 Hz, 1H), 4.19 (s, 1H), 4.05-3.91 (m, 1H), 3.78 (s, 1H), 3.41-3.28 (m, 1H), 2.60 (dd, J = 13.4, 4.6 Hz, 1H), 2.45 (dd, J = 13.4, 8.0 Hz, 1H), 2.02 (ddd, J = 14.6, 9.9, 5.1 Hz, 1H), 1.94-1.40 (m, 11H), 1.40-0.85 (m, 20H), 0.84 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.2.

[0538]

[0539] NC10049

[0540] 1 H NMR (500 MHz, CD3OD) δ 4.39-4.31 (m, 1H), 3.96 (t, J = 3.0 Hz, 1H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 3.02 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.3 Hz, 1H), 2.25 (ddd, J = 13.8, 9.9, 5.1 Hz, 1H), 2.10 (ddd, J= 13.7, 9.5, 6.9 Hz, 1H), 1.95-1.74 (m, 7H), 1.73-1.23 (m, 17H), 1.23-1.04 (m, 2H), 1.04-0.95 (m, 4H), 0.95-0.89 (m, 9H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO6S [M-Na] - 554.4, found 554.3.

[0542]

[0543] NC10050

[0544] 1 H NMR (400 MHz, DMSO-d6) δ 7.54 (d, J = 8.6 Hz, 1H), 4.45 (d, J = 4.3 Hz, 1H), 4.18 (d, J = 3.7 Hz, 1H), 4.12-4.01 (m, 1H), 3.78 (s, 1H), 3.41-3.29 (m, 1H), 2.59 (dd, J = 13.5, 4.5 Hz, 1H), 2.46 (dd, J = 13.5, 7.5 Hz, 1H), 2.05-1.86 (m, 2H), 1.83-1.41 (m, 12H), 1.40-0.74 (m, 27H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO6S [M-Na] - 554.4, found 554.3.

[0546]

[0547] NC10051

[0548] 1H NMR (500 MHz, CD3OD) δ 3.97-3.92 (m, 1H), 3.56-3.46 (m, 1H), 3.03 (s, 2H), 2.21 (ddd, J = 13.9, 10.2, 5.0 Hz, 1H), 2.06 (ddd, J = 14.0, 9.7, 6.5 Hz, 1H), 1.94-1.70 (m, 7H), 1.66-1.56 (m, 3H), 1.55-1.22 (m, 11H), 1.22-1.04 (m, 2H), 1.02-0.94 (m, 6H), 0.93 (s, 3H), 0.81-0.76 (m, 2H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO6S [M-Na] - 524.3, found 524.3.

[0550]

[0551] NC10052

[0552] 1 H NMR (400 MHz, DMSO-d6) δ 4.45 (d, J = 4.3 Hz, 1H), 4.22 (d, J = 4.0 Hz, 0.5H), 4.20 (d, J = 3.4 Hz, 0.5H), 3.79 (s, 1H), 3.63-3.30 (m, 4.5H), 3.25-3.14 (m, 1H), 3.13-3.04 (m, 0.5H), 2.26-1.87 (m, 4H), 1.86-1.67 (m, 4H), 1.67-1.41 (m, 6H), 1.40-1.12 (m, 11H), 1.12-0.80 (m, 9H), 0.60 (s, 1.5H), 0.59 (s, 1.5H); LCMS (ESI) m / z calcd for C 28 H 46 NO6S [M-Na]- 524.3, found 524.2.

[0554]

[0555] NC10053

[0556] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.93 (m, 1H), 3.90-3.65 (m, 3H), 3.65-3.40 (m, 3H), 2.47-2.18 (m, 4H), 1.95-1.71 (m, 7H), 1.66-1.56 (m, 3H), 1.56-1.24 (m, 11H), 1.23-1.07 (m, 2H), 1.04 (d, J = 6.4 Hz, 1.5H), 1.03 (d, J = 6.5 Hz, 1.5H), 1.01-0.94 (m, 1H), 0.93 (s, 3H), 0.72 (s, 1.5H), 0.71 (s, 1.5H); LCMS (ESI) m / z calcd for C 28 H 46 NO6S [M-Na] - 524.3, found 524.2.

[0558]

[0559] NC10054

[0560] 1 H NMR (500 MHz, CD3OD) δ 3.99-3.93 (m, 1H), 3.81-3.75 (m, 1H), 3.74-3.68 (m, 1H), 3.60-3.46 (m, 3H), 3.11-3.02 (m, 2H), 2.59-2.33 (m, 4H), 2.31 (s, 3H), 2.29 (s, 3H), 1.95-1.72 (m, 7H), 1.68-1.56 (m, 3H), 1.55-1.23 (m, 11H), 1.23-1.06 (m, 2H), 1.06-1.02 (m, 3H), 0.98 (td, J= 14.2, 3.1 Hz, 1H), 0.93 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 53 N2O6S [M-Na] - 569.4, found 569.3.

[0562]

[0563] NC10055

[0564] 1 H NMR (500 MHz, CD3OD) δ 8.53-8.41 (m, 2H), 7.80-7.76 (m, 0.7H), 7.76-7.72 (m, 0.3H), 7.49-7.45 (m, 0.3H), 7.43-7.38 (m, 0.7H), 4.84 (s, 1H), 4.69-4.65 (m, 1H), 3.96 (t, J = 3.0 Hz, 0.7H), 3.91 (t, J = 3.0 Hz, 0.3H), 3.84-3.69 (m, 2H), 3.56-3.46 (m, 1H), 3.11-3.04 (m, 2H), 2.64-2.54 (m, 0.7H), 2.52-2.39 (m, 1H), 2.36-2.27 (m, 0.3H), 1.95-1.69 (m, 7H), 1.67-1.55 (m, 3H), 1.55-1.31 (m, 9H), 1.32-1.03 (m, 6H), 1.02-0.89 (m, 5H), 0.71 (s, 2H), 0.68 (s, 1H); LCMS (ESI) m / z calcd for C 32 H 49 N2O6S [M-Na] - 589.3, found 589.3.

[0566]

[0567] NC10056

[0568] 1H NMR (500 MHz, CD3OD) δ 7.52-7.46 (m, 2H), 7.45-7.38 (m, 1H), 7.35-7.29 (m, 2H), 4.13-4.06 (m, 2H), 3.85 (t, J = 3.0 Hz, 1H), 3.50 (tt, J = 11.1, 4.6 Hz, 1H), 3.09-3.02 (m, 2H), 2.19-2.09 (m, 1H), 2.03-1.94 (m, 1H), 1.93-1.62 (m, 7H), 1.62-1.34 (m, 10H), 1.32-0.87 (m, 10H), 0.76 (d, J = 6.1 Hz, 3H), 0.63 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO6S [M-Na] - 574.3, found 574.3.

[0570]

[0571] NC10058

[0572] 1 H NMR (500 MHz, CD3OD) δ 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.39 (t, J = 7.0 Hz, 2H), 2.34 (t, J = 7.0 Hz, 2H), 2.22 (ddd, J = 13.8, 10.4, 5.2 Hz, 1H), 2.07 (ddd, J = 13.8, 10.1, 6.4 Hz, 1H), 2.01 (dt, J= 12.5, 3.2 Hz, 1H), 1.95-1.85 (m, 2H), 1.84-1.71 (m, 3H), 1.66-1.57 (m, 2H), 1.51-1.23 (m, 12H), 1.23-1.03 (m, 5H), 1.03-0.93 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO4[M-Na] - 446.3, found 446.3.

[0574]

[0575] NC10059

[0576] 1 H NMR (500 MHz, CD3OD) δ 3.58 (t, J = 6.3 Hz, 2H), 3.56-3.50 (m, 1H), 3.25 (td, J = 6.9, 1.3 Hz, 2H), 2.23 (ddd, J = 13.7, 10.0, 5.2 Hz, 1H), 2.09 (ddd, J = 13.8, 9.7, 6.7 Hz, 1H), 2.02 (dt, J = 12.3, 3.5 Hz, 1H), 1.96-1.85 (m, 1H), 1.85-1.74 (m, 3H), 1.73-1.67 (m, 2H), 1.66-1.56 (m, 2H), 1.51-1.24 (m, 13H), 1.23-1.05 (m, 5H), 1.03-0.92 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO3[M-H] - 432.3, found 432.3.

[0578]

[0579] NC10060

[0580] 1 H NMR (400 MHz, DMSO-d6) δ 4.42 (t, J = 5.6 Hz, 1H), 3.57-3.42 (m, 2H), 3.40-3.27 (m, 1H), 2.93 (s, 1.5H), 2.75 (s, 1.5H), 2.70-2.58 (m, 1H), 2.58-2.52 (m, 1H), 2.37-2.06 (m, 2H), 1.97-1.87 (m, 1H), 1.87-1.73 (m, 2H), 1.72-1.44 (m, 5H), 1.42-0.96 (m, 17H), 0.95-0.81 (m, 7H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5S [M-Na] - 496.3, found 496.2.

[0582]

[0583] NC10061

[0584] 1 H NMR (500 MHz, CD3OD) δ 7.41-7.34 (m, 1H), 7.34-7.20 (m, 4H), 4.79-4.69 (m, 1H), 4.68-4.58 (m, 1H), 3.84-3.68 (m, 2H), 3.57-3.48 (m, 1H), 3.07 (t, J = 7.1 Hz, 1H), 3.05-2.97 (m, 1H), 2.57 (ddd, J = 15.2, 10.3, 5.2 Hz, 0.5H), 2.50-2.33 (m, 1H), 2.27 (ddd, J = 15.4, 10.4, 5.7 Hz, 0.5H), 2.06-1.68 (m, 6H), 1.66-0.85 (m, 26H), 0.70 (s, 1.5H), 0.65 (s, 1.5H); LCMS (ESI) m / z calcd for C33 H 50 NO5S [M-Na] - 572.3, found 572.3.

[0586]

[0587] NC10062

[0588] 1 H NMR (500 MHz, CD3OD) δ 3.89-3.78 (m, 1H), 3.77-3.69 (m, 2H), 3.67 (t, J = 5.7 Hz, 1H), 3.58-3.44 (m, 3H), 3.13-3.04 (m, 2H), 2.55-2.44 (m, 1H), 2.41-2.29 (m, 1H), 2.05-1.99 (m, 1H), 1.98-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.60 (s, 2H), 1.52-1.04 (m, 17H), 1.02-0.94 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 48 NO6S [M-Na] - 526.3, found 526.3.

[0590]

[0591] NC10063

[0592] 1 H NMR (500 MHz, CD3OD) δ 4.66-4.55 (m, 0.5H), 4.21-4.12 (m, 0.5H), 3.72-3.65 (m, 1H), 3.65-3.58 (m, 1H), 3.58-3.47 (m, 1H), 3.10-3.01 (m, 2H), 2.44 (ddd, J= 15.3, 10.5, 5.1 Hz, 1H), 2.37-2.25 (m, 1H), 2.05-1.99 (m, 1H), 1.95-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.66-1.57 (m, 2H), 1.51-1.04 (m, 23H), 1.03-0.93 (m, 7H), 0.70 (s, 1.5H), 0.69 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 50 NO5S [M-Na] - 524.3, found 524.3.

[0594]

[0595] NC10064

[0596] 1 H NMR (500 MHz, CD3OD) δ 4.43 (tt, J = 12.1, 3.9 Hz, 0.5H), 4.06-3.89 (m, 2.5H), 3.75-3.62 (m, 2H), 3.58-3.42 (m, 3H), 3.08-3.01 (m, 2H), 2.53-2.42 (m, 1H), 2.40-2.30 (m, 1H), 2.05-1.85 (m, 5H), 1.85-1.70 (m, 3H), 1.70-1.54 (m, 4H), 1.50-1.04 (m, 17H), 1.03-0.95 (m, 4H), 0.949 (s, 1.5H), 0.945 (s, 1.5H), 0.70 (s, 1.5H), 0.69 (s, 1.5H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.3.

[0598]

[0599] NC10065

[0600] 1 1H NMR (500 MHz, CD3OD) δ 5.05–4.98 (m, 0.4H), 4.42 (d, J = 12.9 Hz, 0.6H), 4.32-4.25 (m, 0.6H), 3.92 (d, J = 12.9 Hz, 0.4H), 3.52 (tt, J = 11.4, 4.3 Hz, 1H), 3.24 (dd, J = 13.5, 11.1 Hz, 0.6H), 3.01 (td, J = 13.2, 2.8 Hz, 0.4H), 2.84-2.56 (m, 2H), 2.56-2.39 (m, 1H), 2.38-2.24 (m, 2H), 2.02 (dt, J = 12.4, 3.1 Hz, 1H), 1.98-1.68 (m, 7H), 1.66-1.57 (m, 2H), 1.54-1.05 (m, 18H), 1.03-0.97 (m, 4H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS(ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0602]

[0603] NC10066

[0604] 1 H NMR (400 MHz, DMSO-d6) δ 4.71 (d, J = 13.6 Hz, 0.5H), 4.42 (s, 1H), 4.28 (d, J = 12.9 Hz, 0.5H), 4.03 (d, J = 13.2 Hz, 0.5H), 3.77 (d, J= 13.3 Hz, 0.5H), 3.41-3.27 (m, 1H), 2.99-2.88 (m, 0.5H), 2.85-2.75 (m, 0.5H), 2.42-2.24 (m, 2.5H), 2.22-2.08 (m, 1.5H), 2.06-1.98 (m, 1H), 1.96-1.89 (m, 1H), 1.83-1.73 (m, 2H), 1.72-1.43 (m, 7H), 1.43-0.96 (m, 18H), 0.94-0.84 (m, 7H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0606]

[0607] NC10067

[0608] 1 H NMR (400 MHz, DMSO-d6) δ 4.45-4.32 (m, 2H), 3.85 (d, J = 13.5 Hz, 1H), 3.41-3.27 (m, 1H), 2.92 (t, J = 12.5 Hz, 1H), 2.47-2.37 (m, 2H), 2.36-2.10 (m, 2H), 1.96-1.72 (m, 5H), 1.72-1.44 (m, 5H), 1.44-0.96 (m, 19H), 0.95-0.82 (m, 7H), 0.61 (s, 3H). ; LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.2.

[0610]

[0611] NC10068

[0612] 1H NMR (500 MHz, CD3OD) δ 4.42 (t, J = 8.8 Hz, 1H), 4.36-4.30 (m, 1H), 4.21-4.11 (m, 2H), 3.85-3.76 (m, 1H), 3.58-3.48 (m, 1H), 2.25-2.12 (m, 1H), 2.11-1.98 (m, 2H), 1.95-1.85 (m, 2H), 1.85-1.69 (m, 3H), 1.65-1.57 (m, 2H), 1.51-1.05 (m, 17H), 1.03-0.98 (m, 1H), 0.96 (d, J = 6.5 Hz, 3H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0614]

[0615] NC10069

[0616] 1 H NMR (500 MHz, CD3OD) δ 3.57-3.48 (m, 1H), 3.21-3.09 (m, 2H), 2.19 (ddd, J = 13.9, 10.3, 5.2 Hz, 1H), 2.08-1.98 (m, 2H), 1.96-1.85 (m, 2H), 1.84-1.71 (m, 3H), 1.67-1.56 (m, 2H), 1.53 (s, 6H), 1.50-1.04 (m, 17H), 1.03-0.92 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 48 NO5S [M-Na] - 510.3, found 510.3.

[0618]

[0619] NC10070

[0620] 1 H NMR (500 MHz, CD3OD) δ 7.29-7.22 (m, 4H), 7.22-7.14 (m, 1H), 4.50-4.42 (m, 1H), 3.58-3.48 (m, 1H), 3.20-3.13 (m, 1H), 3.05-2.95 (m, 2H), 2.92 (dd, J = 13.6, 7.8 Hz, 1H), 2.16 (ddd, J = 13.8, 10.8, 5.1 Hz, 1H), 2.00 (ddd, J = 13.8, 10.5, 6.2 Hz, 2H), 1.96-1.57 (m, 7H), 1.50-1.04 (m, 17H), 1.03-0.95 (m, 1H), 0.94 (s, 3H), 0.92 (d, J = 6.6 Hz, 3H), 0.67 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 50 NO5S [M-Na] - 572.3, found 572.3.

[0622]

[0623] NC10071

[0624] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.22 (m, 4H), 7.22-7.14 (m, 1H), 4.52-4.43 (m, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.16 (dd, J = 13.7, 6.1 Hz, 1H), 3.04-2.93 (m, 2H), 2.91 (dd, J = 13.7, 7.8 Hz, 1H), 2.17 (ddd, J= 13.8, 10.4, 5.1 Hz, 1H), 2.06-1.96 (m, 2H), 1.96-1.55 (m, 7H), 1.51-1.04 (m, 17H), 0.99 (td, J = 14.1, 3.3 Hz, 1H), 0.94 (s, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.66 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 50 NO5S [M-Na] - 572.3, found 572.3.

[0626]

[0627] NC10072

[0628] 1 H NMR (500 MHz, CD3OD) δ 4.23-4.16 (m, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.01-2.90 (m, 2H), 2.28 (ddd, J = 13.7, 10.6, 5.2 Hz, 1H), 2.15-1.98 (m, 3H), 1.97-1.86 (m, 2H), 1.85-1.71 (m, 3H), 1.65-1.56 (m, 2H), 1.51-1.23 (m, 12H), 1.23-1.03 (m, 5H), 1.03-0.88 (m, 13H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO5S [M-Na] - 524.3, found 524.3.

[0630]

[0631] NC10073

[0632] 1H NMR (400 MHz, DMSO-d6) δ 7.46 (d, J = 8.4 Hz, 1H), 4.42 (d, J = 4.6 Hz, 1H), 3.98-3.87 (m, 1H), 3.41-3.27 (m, 1H), 2.55-2.51 (m, 2H), 2.15-1.88 (m, 4H), 1.84-1.72 (m, 2H), 1.72-1.43 (m, 5H), 1.41-0.95 (m, 17H), 0.94-0.82 (m, 7H), 0.76 (s, 3H), 0.74 (s, 3H), 0.60 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO5S [M-Na] - 524.3, found 524.3.

[0634]

[0635] NC10074

[0636] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.27 (m, 4H), 7.24-7.19 (m, 1H), 5.35 (dd, J = 10.0, 3.7 Hz, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.26 (dd, J = 14.3, 10.0 Hz, 1H), 3.09 (dd, J = 14.3, 3.8 Hz, 1H), 2.31 (ddd, J = 13.9, 10.1, 5.4 Hz, 1H), 2.15 (ddd, J = 14.0, 9.8, 6.5 Hz, 1H), 1.99 (dt, J= 12.5, 3.3 Hz, 1H), 1.95-1.71 (m, 5H), 1.66-1.52 (m, 2H), 1.52-1.21 (m, 12H), 1.21-0.90 (m, 12H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO5S [M-Na] - 558.3, found 558.3.

[0638]

[0639] NC10075

[0640] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.26 (m, 4H), 7.24-7.18 (m, 1H), 5.35 (dd, J = 10.1, 3.7 Hz, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.26 (dd, J = 14.3, 10.1 Hz, 1H), 3.09 (dd, J = 14.3, 3.7 Hz, 1H), 2.29 (ddd, J = 14.4, 9.7, 5.0 Hz, 1H), 2.17 (ddd, J = 13.9, 9.2, 7.1 Hz, 1H), 2.00 (dt, J = 12.4, 3.2 Hz, 1H), 1.95-1.71 (m, 5H), 1.65-1.52 (m, 2H), 1.51-0.91 (m, 24H), 0.63 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO5S [M-Na] - 558.3, found 558.3.

[0642]

[0643] NC10076

[0644] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.44 (m, 0.5H), 4.44-4.37 (m, 0.5H), 3.59-3.32 (m, 3.5H), 3.02-2.90 (m, 1H), 2.73 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.55 (ddd, J = 15.3, 10.6, 5.3 Hz, 0.5H), 2.47-2.27 (m, 2H), 2.19 (ddd, J = 14.7, 10.4, 5.8 Hz, 0.5H), 2.11-1.85 (m, 6H), 1.85-1.70 (m, 3H), 1.66-1.56 (m, 2H), 1.50-1.03 (m, 17H), 1.02-0.91 (m, 4H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0646]

[0647] NC10077

[0648] 1 H NMR (500 MHz, CD3OD) δ 4.51-4.44 (m, 0.5H), 4.44-4.37 (m, 0.5H), 3.59-3.32 (m, 3.5H), 3.01-2.90 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.48-2.38 (m, 2H), 2.34 (ddd, J = 15.5, 10.8, 5.2 Hz, 0.5H), 2.21 (ddd, J= 14.7, 10.5, 5.8 Hz, 0.5H), 2.10-1.85 (m, 6H), 1.85-1.71 (m, 3H), 1.67-1.56 (m, 2H), 1.50-1.03 (m, 17H), 1.03-0.96 (m, 4H), 0.95 (s, 3H), 0.694 (s, 1.5H), 0.690 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0650]

[0651] NC10078

[0652] 1 H NMR (500 MHz, CD3OD) δ 3.61-3.48 (m, 2H), 3.44 (dd, J = 13.8, 6.7 Hz, 1H), 3.00-2.90 (m, 1H), 2.25 (ddd, J = 13.9, 10.2, 5.1 Hz, 1H), 2.11 (ddd, J = 13.9, 9.8, 6.7 Hz, 1H), 2.01 (dt, J = 12.4, 3.2 Hz, 1H), 1.96-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.66-1.57 (m, 2H), 1.51-1.24 (m, 15H), 1.23-1.03 (m, 5H), 1.03-0.98 (m, 1H), 0.96 (d, J = 6.6 Hz, 3H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5S [M-Na] - 496.3, found 496.2.

[0654]

[0655] NC10079

[0656] 1 H NMR (500 MHz, CD3OD) δ 3.59-3.49 (m, 2H), 3.46 (dd, J = 13.7, 6.8 Hz, 1H), 2.99-2.89 (m, 1H), 2.26 (ddd, J = 13.9, 10.3, 5.2 Hz, 1H), 2.11 (ddd, J = 14.0, 9.9, 6.6 Hz, 1H), 2.01 (dt, J = 12.4, 3.2 Hz, 1H), 1.96-1.85 (m, 2H), 1.84-1.71 (m, 3H), 1.66-1.56 (m, 2H), 1.51-1.23 (m, 15H), 1.23-1.04 (m, 5H), 1.03-0.98 (m, 1H), 0.96 (d, J = 0.65 Hz, 3H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5S [M-Na] - 496.3, found 496.2.

[0658]

[0659] NC10080

[0660] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.25 (m, 1H), 3.75-3.65 (m, 2H), 3.53 (tt, J= 10.5, 4.6 Hz, 1H), 3.13-3.07 (m, 1H), 3.06-3.00 (m, 1H), 2.32-2.17 (m, 1H), 2.16-1.98 (m, 2H), 1.97-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.67-1.55 (m, 2H), 1.51-1.23 (m, 12H), 1.23-1.04 (m, 5H), 1.03-0.90 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.2.

[0662]

[0663] NC10081

[0664] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.26 (m, 1H), 3.76-3.64 (m, 2H), 3.57-3.48 (m, 1H), 3.14-3.07 (m, 1H), 3.07-2.99 (m, 1H), 2.32-2.17 (m, 1H), 2.16-1.98 (m, 2H), 1.96-1.85 (m, 2H), 1.85-1.72 (m, 3H), 1.66-1.55 (m, 2H), 1.51-1.23 (m, 12H), 1.23-1.04 (m, 5H), 1.03-0.91 (m, 7H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO6S [M-Na] - 512.3, found 512.3.

[0666]

[0667] NC10082

[0668] 1H NMR (500 MHz, CD3OD) δ 4.33-4.27 (m, 1H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 2.91 (dt, J = 10.2, 4.0 Hz, 1H), 2.31-2.19 (m, 2H), 2.15 (ddd, J = 14.1, 9.6, 6.9 Hz, 1H), 2.07-1.85 (m, 6H), 1.84-1.71 (m, 3H), 1.66-1.56 (m, 2H), 1.55-1.24 (m, 16H), 1.23-1.03 (m, 5H), 1.02-0.98 (m, 1H), 0.97 (d, J = 6.6 Hz, 3H), 0.95 (s, 3H), 0.68 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO5S [M-Na] - 536.3, found 536.3.

[0670]

[0671] NC10083

[0672] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.27 (m, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 2.91 (dt, J = 10.1, 4.0 Hz, 1H), 2.31 (ddd, J = 14.2, 10.3, 5.3 Hz, 1H), 2.25-2.18 (m, 1H), 2.12 (ddd, J = 14.3, 10.1, 6.4 Hz, 1H), 2.06-1.85 (m, 6H), 1.84-1.72 (m, 3H), 1.66-1.56 (m, 2H), 1.55-1.24 (m, 16H), 1.24-1.03 (m, 5H), 1.03-0.98 (m, 1H), 0.96 (d, J= 6.5 Hz, 3H), 0.95 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO5S [M-Na] - 536.3, found 536.3.

[0674]

[0675] NC10084

[0676] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.58-3.48 (m, 1H), 3.05 (dd, J = 13.9, 5.5 Hz, 1H), 2.88 (dd, J = 13.9, 7.0 Hz, 1H), 2.22 (ddd, J = 13.8, 10.3, 5.2 Hz, 1H), 2.12-1.98 (m, 2H), 1.96-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.66-1.56 (m, 2H), 1.51-1.24 (m, 15H), 1.23-1.03 (m, 5H), 1.03-0.97 (m, 1H), 0.96 (d, J = 6.5 Hz, 3H), 0.94 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5S [M-Na] - 496.3, found 496.2.

[0678]

[0679] NC10085

[0680] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.53 (tt, J= 11.1, 4.6 Hz, 1H), 3.05 (dd, J = 13.9, 5.6 Hz, 1H), 2.88 (dd, J = 13.9, 6.9 Hz, 1H), 2.22 (ddd, J = 13.8, 10.2, 5.1 Hz, 1H), 2.11-1.98 (m, 2H), 1.96-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.66-1.56 (m, 2H), 1.50-1.24 (m, 15H), 1.23-1.04 (m, 5H), 1.03-0.97 (m, 1H), 0.96 (d, J = 6.5 Hz, 3H), 0.94 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5S [M-Na] - 496.3, found 496.2.

[0681]

[0682] NC10086

[0683] 1 H NMR (500 MHz, CD3OD) δ 4.39-4.30 (m, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.03 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.2 Hz, 1H), 2.23 (ddd, J = 13.8, 9.9, 5.3 Hz, 1H), 2.08 (ddd, J = 13.8, 9.6, 6.8 Hz, 1H), 2.02 (dt, J= 12.4, 3.2 Hz, 1H), 1.96-1.85 (m, 2H), 1.85-1.72 (m, 3H), 1.70-1.52 (m, 5H), 1.51-1.24 (m, 12H), 1.23-1.04 (m, 5H), 1.04-0.89 (m, 13H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO5S [M-Na] - 538.4, found 538.3.

[0685]

[0686] NC10087

[0687] 1 H NMR (500 MHz, CD3OD) δ 4.42-4.33 (m, 1H), 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.01 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.3 Hz, 1H), 2.22 (ddd, J = 14.2, 9.4, 5.1 Hz, 1H), 2.10 (ddd, J = 13.8, 9.0, 7.4 Hz, 1H), 2.01 (dt, J = 12.5, 3.2 Hz, 1H), 1.96-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.71-1.51 (m, 5H), 1.50-1.04 (m, 17H), 1.04-0.89 (m, 13H), 0.68 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO5S [M-Na] - 538.4, found 538.3.

[0689]

[0690] NC10088

[0691] 1 H NMR (500 MHz, CD3OD) δ 3.53 (tt, J = 11.1, 4.6 Hz, 1H), 3.08-2.97 (m, 2H), 2.20 (ddd, J = 14.0, 10.4, 5.2 Hz, 1H), 2.09-1.97 (m, 2H), 1.96-1.85 (m, 2H), 1.85-1.70 (m, 3H), 1.66-1.56 (m, 2H), 1.51-1.23 (m, 12H), 1.22-1.04 (m, 5H), 1.03-0.90 (m, 9H), 0.82-0.76 (m, 2H), 0.68 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO5S [M-Na] - 508.3, found 508.3.

[0693]

[0694] NC10089

[0695] 1 H NMR (500 MHz, CD3OD) δ 3.88-3.65 (m, 3H), 3.65-3.39 (m, 3H), 2.47-2.16 (m, 4H), 2.09-1.99 (m, 1H), 1.95-1.85 (m, 2H), 1.85-1.71 (m, 3H), 1.67-1.56 (m, 2H), 1.53-1.04 (m, 17H), 1.04-0.92 (m, 7H), 0.73-0.65 (m, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO5S [M-Na] - 508.3, found 508.3.

[0697]

[0698] NC10090

[0699] 1 H NMR (400 MHz, DMSO-d6) δ 4.43 (s, 1H), 3.65-3.29 (m, 4.5H), 3.27-3.14 (m, 1H), 3.13-3.04 (m, 0.5H), 2.26-2.14 (m, 1H), 2.14-1.87 (m, 4H), 1.85-1.73 (m, 2H), 1.72-1.44 (m, 5H), 1.43-0.96 (m, 17H), 0.94-0.81 (m, 7H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO5S [M-Na] - 508.3, found 508.3.

[0701]

[0702] NC10091

[0703] 1 H NMR (500 MHz, CD3OD) δ 3.80-3.74 (m, 1H), 3.73-3.68 (m, 1H), 3.59-3.44 (m, 3H), 3.12-3.02 (m, 2H), 2.58-2.22 (m, 10H), 2.02 (dt, J = 12.5, 3.1 Hz, 1H), 1.96-1.85 (m, 2H), 1.84-1.71 (m, 3H), 1.66-1.57 (m, 2H), 1.52-1.05 (m, 17H), 1.03-0.96 (m, 4H), 0.95 (s, 3H), 0.70 (s, 1.5H), 0.69 (s, 1.5H); LCMS (ESI) m / z calcd for C 30 H 53 N2O5S [M-Na] - 553.4, found 553.3.

[0705]

[0706] NC10092

[0707] 1 H NMR (500 MHz, CD3OD) δ 8.52-8.41 (m, 2H), 7.81-7.72 (m, 1H), 7.51-7.37 (m, 1H), 4.86-4.79 (m, 0.6H), 4.72-4.65 (m, 1.4H), 3.84-3.68 (m, 2H), 3.57-3.48 (m, 1H), 3.11-3.02 (m, 2H), 2.63-2.53 (m, 0.3H), 2.34-2.25 (m, 1H), 2.51-2.37 (m, 0.7H), 2.05-1.69 (m, 6H), 1.66-1.54 (m, 2H), 1.52-1.03 (m, 17H), 1.02-0.96 (m, 3H), 0.96-0.92 (m, 3H), 0.86 (d, J = 6.5 Hz, 1H), 0.69 (s, 2H), 0.65 (s, 1H); LCMS (ESI) m / z calcd for C 32 H 49 N2O5S [M-Na] - 573.3, found 573.3.

[0709]

[0710] NC10093

[0711] 1 H NMR (500 MHz, CD3OD) δ 7.53-7.47 (m, 2H), 7.46-7.39 (m, 1H), 7.35-7.29 (m, 2H), 4.13-4.06 (m, 2H), 3.52 (tt, J = 11.1, 4.6 Hz, 1H), 3.09-3.02 (m, 2H), 2.17-2.08 (m, 1H), 2.01-1.83 (m, 3H), 1.83-1.51 (m, 6H), 1.51-0.94 (m, 18H), 0.92 (s, 3H), 0.69 (d, J= 6.0 Hz, 3H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO5S [M-Na] - 558.3, found 558.3.

[0714]

[0715] NC20002

[0716] 1 H NMR (400 MHz, DMSO-d6) δ 7.83 (t, J = 5.6 Hz, 1H), 4.31 (s, 1H), 4.09 (s, 1H), 4.01 (s, 1H), 3.78 (s, 1H), 3.61 (s, 1H), 3.24-3.13 (m, 3H), 2.32 (t, J = 6.9 Hz, 2H), 2.28-1.87 (m, 5H), 1.83-1.55 (m, 6H), 1.51-1.06 (m, 11H), 1.02-0.82 (m, 5H), 0.81 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO6[M-Na] - 478.3, found 478.2.

[0718]

[0719] NC20003

[0720] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.58 (t, J = 6.4 Hz, 2H), 3.41-3.33 (m, 1H), 3.25 (t, J = 7.3 Hz, 2H), 2.33-2.20 (m, 3H), 2.11 (ddd, J= 13.7, 9.5, 6.7 Hz, 1H), 2.04-1.49 (m, 15H), 1.48-1.24 (m, 5H), 1.12 (qd, J = 12.0, 5.8 Hz, 1H), 1.03 (d, J = 6.4 Hz, 3H), 1.02-0.94 (m, 1H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO5[M-H] - 464.3, found 464.1.

[0722]

[0723] NC20004

[0724] 1 H NMR (400 MHz, DMSO-d6) δ 4.30 (s, 1H), 4.12 (s, 1H), 4.01 (s, 1H), 3.79 (s, 1H), 3.61 (s, 1H), 3.56-3.42 (m, 2H), 3.17 (s, 1H), 2.93 (s, 1.5H) 2.75 (s, 1.5H), 2.69-2.60 (m, 1H), 2.58-2.52 (m, 1H), 2.36-2.07 (m, 4H), 2.05-1.94 (m, 1H), 1.85-1.55 (m, 6H), 1.51-1.07 (m, 11H), 1.03-0.82 (m, 5H), 0.81 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] - 528.3, found 528.1.

[0726]

[0727] NC20005

[0728] 1H NMR (500 MHz, CD3OD) δ 7.41-7.34 (m, 1H), 7.34-7.20 (m, 4H), 4.74 (s, 1H), 4.63 (s, 1H), 3.99-3.94 (m, 0.5H) 3.92-3.88 (m, 0.5H), 3.82-3.68 (m, 3H), 3.37 (m, 1H), 3.10-2.96 (m, 2H), 2.63-2.54 (m, 0.5H) 2.52-2.39 (m, 1H), 2.36-2.19 (m, 2.5H), 2.06-1.18 (m, 18H), 1.17-0.88 (m, 8H), 0.72 (s, 1.5H), 0.68 (s, 1.5H); LCMS (ESI) m / z calcd for C 33 H 50 NO7S [M-Na] - 604.3, found 604.2.

[0730]

[0731] NC20006

[0732] 1 H NMR (500 MHz, CD3OD) δ 3.99-3.93 (m, 1H), 3.89-3.82 (m, 1H), 3.82-3.77 (m, 1H), 3.77-3.64 (m, 3H), 3.60-3.52 (m, 1H), 3.51-3.44 (m, 1H), 3.41-3.32 (m, 1H), 3.15-3.04 (m, 2H), 2.55-2.47 (m, 1H), 2.41-2.33 (m, 1H), 2.32-2.23 (m, 2H), 2.04-1.70 (m, 7H), 1.69-1.49 (m, 6H), 1.49-1.27 (m, 5H), 1.17-1.02 (m, 4H), 0.98 (td, J = 14.2, 3.5 Hz, 1H), 0.92 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 28 H48 NO8S [M-Na] - 558.3, found 558.2.

[0734]

[0735] NC20007

[0736] 1 H NMR (400 MHz, DMSO-d6) δ 4.55-4.42 (m, 0.6H), 4.31 (s, 1H), 4.11 (s, 1H), 4.15-3.96 (m, 1.4H), 3.79 (s, 1H), 3.61 (s, 1H), 3.45-3.37 (m, 1H), 3.36-3.27 (m, 1H), 3.17 (s, 1H), 2.67-2.54 (m, 2H), 2.34-2.09 (m, 4H), 2.02-1.94 (m,1H), 1.85-1.55 (m, 6H), 1.51-1.07 (m, 14H), 1.03 (d, J = 6.8, 3H), 0.97-0.94 (m, 1H), 0.93 (d, J = 6.4, 3H), 0.87-0.83 (m, 1H), 0.81 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.2.

[0738]

[0739] NC20008

[0740] 1 H NMR (500 MHz, CD3OD) δ 4.44 (tt, J= 12.1, 3.9 Hz, 0.5H) 4.06-3.91 (m, 3.5H), 3.83-3.77 (m, 1H), 3.75-3.63 (m, 2H), 3.53-3.41 (m, 2H), 3.41-3.32 (m, 1H), 3.08-3.01 (m, 2H), 2.55-2.44 (m, 1H), 2.41-2.21 (m, 3H), 2.06-1.24 (m, 22H), 1.18-1.08 (m, 1H), 1.07-1.05 (m, 3H), 0.98 (tt, J = 14.2, 3.5 Hz, 1H), 0.922 (s, 1.5H), 0.919 (s, 1.5H), 0.73 (s, 1.5H), 0.72 (s, 1.5H); LCMS (ESI) m / z calcd for C 31 H 52 NO8S [M-Na] - 598.3, found 598.2.

[0742]

[0743] NC20009

[0744] 1 H NMR (400 MHz, DMSO-d6) δ 4.72 (d, J = 12.7 Hz, 0.5H), 4.37-4.22 (m, 1.5H), 4.16-4.07 (m, 1H), 4.07-3.95 (m, 1.5H), 3.84-3.70 (m, 1.5H), 3.61 (s, 1H), 3.24-3.11 (m, 1H), 2.99-2.89 (m, 0.5H), 2.86-2.76 (m, 0.5H), 2.42-2.09 (m, 6H), 2.08-1.91 (m, 2H), 1.86-1.07 (m, 20H), 1.01-0.82 (m, 5H), 0.81 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 29 H48 NO7S [M-Na] - 554.3, found 554.2.

[0746]

[0747] NC20010

[0748] 1 H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 9.7 Hz, 0.5H), 4.44 (d, J = 13.3 Hz, 0.5H), 4.34-4.27 (m, 0.5H), 3.98-3.94 (m, 1.5H), 3.82-3.77 (m, 1H), 3.41-3.33 (m, 1H), 3.23 (dd, J = 13.6, 11.2 Hz, 0.5H), 3.01 (td, J = 13.2, 2.8 Hz, 0.5H), 2.84-2.55 (m, 2H), 2.54-2.42 (m, 1H), 2.42-2.21 (m, 4H), 2.07-1.69 (m, 9H), 1.69-1.25 (m, 12H), 1.17-1.08 (m, 1H), 1.06 (d, J = 6.5, 1.5H), 1.04 (d, J = 6.4, 1.5H), 1.02-0.94 (m, 1H), 0.92 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO7S [M-Na] - 554.3, found 554.2.

[0750]

[0751] NC20011

[0752] 1 H NMR (400 MHz, D2O) δ 4.50 (d, J= 13.5 Hz, 1H), 4.15-4.02 (m, 2H), 3.92-3.85 (m, 1H), 3.55-3.44 (m, 1H), 3.20 (t, J = 13.1 Hz, 1H), 3.14-3.03 (m, 1H), 2.78-2.67 (m, 1H), 2.59-2.29 (m, 2H), 2.23-1.22 (m, 24H), 1.22-1.09 (m, 1H), 1.08-0.95 (m, 4H), 0.91 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO7S [M-Na] - 554.3, found 554.2.

[0754]

[0755] NC20012

[0756] 1 H NMR (500 MHz, CD3OD) δ 4.47-4.38 (m, 1H), 4.38-4.31 (m, 1H), 4.21-4.11 (m, 2H), 3.98-3.93 (m, 1H), 3.85-3.76 (m, 2H), 3.41-3.32 (m, 1H), 2.35-2.14 (m, 3H), 2.13-1.69 (m, 8H), 1.69-1.49 (m, 6H), 1.49-1.27 (m, 5H), 1.12 (qd, J = 11.8, 5.3 Hz, 1H), 1.05-0.94 (m, 4H), 0.92 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO7S [M-Na] - 526.3, found 526.1.

[0758]

[0759] NC20013

[0760] 1 H NMR (400 MHz, DMSO-d6) δ 8.15 (s, 1H), 4.31 (d, J = 4.5 Hz, 1H), 4.11 (d, J = 3.4 Hz, 1H), 4.01 (d, J = 3.4 Hz, 1H), 3.78 (s, 1H), 3.61 (s, 1H), 3.23-3.11 (m, 1H), 2.61 (s, 2H), 2.29-2.08 (m, 2H), 2.04-1.91 (m, 2H), 1.90-1.52 (m, 7H), 1.50-1.07 (m, 17H), 1.02-0.82 (m, 5H), 0.81 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 48 NO7S [M-Na] - 542.3, found 542.2.

[0762]

[0763] NC20014

[0764] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.21 (m, 4H), 7.20-7.14 (m, 1H), 4.51-4.42 (m, 1H), 3.95-3.94 (m, 1H), 3.82-3.78 (m, 1H), 3.42-3.34 (m, 1H), 3.21-3.13 (m, 1H), 3.03-2.96 (m, 2H), 2.91 (dd, J = 13.6, 7.8 Hz, 1H), 2.34-2.13 (m, 3H), 2.07-1.92 (m, 3H), 1.92-1.49 (m, 11H), 1.48-1.33 (m, 3H), 1.32-1.18 (m, 2H), 1.16-0.93 (m, 5H), 0.92 (s, 3H), 0.70 (s, 3H); LCMS (ESI) m / zcalcd for C 33 H 50 NO7S [M-Na] - 604.3, found 604.2.

[0766]

[0767] NC20015

[0768] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.22 (m, 4H), 7.22-7.14 (m, 1H), 4.52-4.44 (m, 1H), 3.96-3.91 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.32 (m, 1H), 3.17 (dd, J = 13.6, 6.1 Hz, 1H), 3.03-2.95 (m, 2H), 2.91 (dd, J = 13.7, 7.8 Hz, 1H), 2.34-2.15 (m, 3H), 2.08-1.49 (m, 14H), 1.48-1.19 (m, 5H), 1.16-1.04 (m, 1H), 1.03-0.93 (m, 4H), 0.92 (s, 3H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 50 NO7S [M-Na] - 604.3, found 604.2.

[0770]

[0771] NC20016

[0772] 1H NMR (500 MHz, CD3OD) δ 4.24-4.17 (m, 1H), 3.98-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.33 (m, 1H), 2.99-2.92 (m, 2H), 2.35-2.21 (m, 3H), 2.17-2.04 (m, 2H), 2.03-1.69 (m, 7H), 1.69-1.49 (m, 6H), 1.49-1.27 (m, 5H), 1.17-1.06 (m, 1H), 1.03 (d, J = 6.5 Hz, 3H), 1.02-0.94 (m, 1H), 0.94-0.89 (m, 9H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.2.

[0774]

[0775] NC20017

[0776] 1 H NMR (500 MHz, CD3OD) δ 4.23-4.21 (m, 1H), 3.98-3.92 (m, 1H), 3.83-3.75 (m, 1H), 3.41-3.32 (m, 1H), 2.95 (d, J = 6.1 Hz, 2H), 2.34-2.21 (m, 3H), 2.21-2.12 (m, 1H), 2.12-2.03 (m, 1H), 2.03-1.69 (m, 7H), 1.69-1.49 (m, 6H), 1.49-1.25 (m, 5H), 1.16-1.07 (m, 1H), 1.04 (d, J = 6.4 Hz, 3H), 1.02-0.94 (m, 1H), 0.94-0.89 (m, 9H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50NO7S [M-Na] - 556.3, found 556.2.

[0778]

[0779] NC20018

[0780] 1 H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 6.2 Hz, 1H), 7.29-7.19 (m, 4H), 7.18-7.11 (m, 1H), 5.01-4.92 (m, 1H), 4.31 (d, J = 4.5 Hz, 1H), 4.11 (s, 1H), 4.01 (s, 1H), 3.78 (s, 1H), 3.61 (s, 1H), 3.23-3.11 (m, 1H), 2.85 (dd, J = 13.8, 9.2 Hz, 1H), 2.66 (dd, J = 13.8, 4.2 Hz, 1H), 2.29-2.06 (m, 3H), 2.04-1.89 (m, 2H), 1.85-1.55 (m, 6H), 1.50-1.08 (m, 11H), 0.99-0.82 (m, 5H), 0.81 (s, 3H), 0.57 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO7S [M-Na] - 590.3, found 590.3.

[0782]

[0783] NC20019

[0784] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.27 (m, 4H), 7.24-7.18 (m, 1H), 5.35 (dd, J= 10.0, 3.7 Hz, 1H), 3.96-3.91 (m, 1H), 3.81-3.75 (m, 1H), 3.41-3.32 (m, 1H), 3.26 (dd, J = 14.3, 10.0 Hz, 1H), 3.10 (dd, J = 14.3, 3.7 Hz, 1H), 2.36-2.14 (m, 4H), 2.02-1.48 (m, 13H), 1.48-1.27 (m, 4H), 1.26-1.17 (m, 1H), 1.11-0.94 (m, 5H), 0.92 (s, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO7S [M-Na] - 590.3, found 590.3.

[0786]

[0787] NC20020

[0788] 1 H NMR (400 MHz, DMSO-d6) δ 4.31 (s, 1H), 4.23-4.07 (m, 2H), 4.01 (s, 1H), 3.79 (s, 1H), 3.61 (s, 1H), 3.44-3.27 (m, 1H), 3.26-3.11 (m, 2H), 2.92 (dd, J = 12.7, 2.9 Hz, 0.5H), 2.61-2.52 (m, 0.5H), 2.44-1.91 (m, 7H), 1.91-1.54 (m, 9H), 1.51-1.06 (m, 11H), 1.03-0.82 (m, 5H), 0.81 (s, 3H), 0.59 (s, 1.5H), 0.58 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 48 NO7S [M-Na] - 554.3, found 554.4.

[0790]

[0791] NC20021

[0792] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.38 (m, 1H), 3.99-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.60-3.52 (m, 0.5H), 3.52-3.26 (m, 3H), 3.02-2.92 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.50-2.40 (m, 2H), 2.39-2.19 (m, 3H), 2.11-1.70 (m, 10H), 1.68-1.49 (m, 6H), 1.49-1.25 (m, 5H), 1.17-1.08 (m, 1H), 1.06 (d, J = 6.5 Hz, 1.5H), 1.04 (d, J = 6.5 Hz, 1.5H), 1.02-0.94 (m, 1H), 0.92 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO7S [M-Na] - 554.3, found 554.3.

[0794]

[0795] NC20022

[0796] 1 H NMR (500 MHz, CD3OD) δ 3.99-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.58 (dd, J = 13.8, 6.0 Hz, 1H), 3.43 (dd, J = 13.8, 6.8 Hz, 1H), 3.40-3.32 (m, 1H), 3.00-2.90 (m, 1H), 2.34-2.21 (m, 3H), 2.13 (ddd, J= 13.9, 9.5, 6.8 Hz, 1H), 2.04-1.70 (m, 7H), 1.69-1.49 (m, 6H), 1.47-1.31 (m, 5H), 1.29 (d, J = 6.9 Hz, 3H), 1.17-1.06 (m, 1H), 1.03 (d, J = 6.4 Hz, 3H), 1.01-0.94 (m, 1H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] - 528.3, found 528.2.

[0798]

[0799] NC20023

[0800] 1 H NMR (400 MHz, DMSO-d6) δ 7.63-7.55 (m, 1H), 4.32 (d, J = 4.4 Hz, 1H), 4.10 (d, J = 3.3 Hz, 1H), 4.01 (d, J = 3.3 Hz, 1H), 3.78 (s, 1H), 3.61 (s, 1H), 3.30-3.09 (m, 3H), 2.49-2.42 (m, 1H), 2.28-1.87 (m, 5H), 1.84-1.52 (m, 6H), 1.50-1.08 (m, 11H), 1.02 (d, J = 6.8 Hz, 3H), 0.99-0.82 (m, 5H), 0.80 (s, 3H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] - 528.3, found 528.2.

[0802]

[0803] NC20024

[0804] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.27 (m, 1H), 3.99-3.92 (m, 1H), 3.84-3.77 (m, 1H), 3.75-3.64 (m, 2H), 3.42-3.32 (m, 1H), 3.14-3.06 (m, 1H), 3.05-2.97 (m, 1H), 2.34-2.20 (m, 3H), 2.18-2.03 (m, 1H), 2.03-1.69 (m, 7H), 1.69-1.49 (m, 6H), 1.49-1.25 (m, 5H), 1.17-1.06 (m, 1H), 1.03-1.01 (m, 3H), 1.01-0.93 (m, 1H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO8S [M-Na] - 544.3, found 544.2.

[0806]

[0807] NC20025

[0808] 1 H NMR (500 MHz, CD3OD) δ 4.35-4.27 (m, 1H), 4.00-3.92 (m, 1H), 3.83-3.77 (m, 1H), 3.76-3.64 (m, 2H), 3.41-3.32 (m, 1H), 3.14-3.06 (m, 1H), 3.05-2.98 (m, 1H), 2.34-2.20 (m, 3H), 2.18-2.03 (m, 1H), 2.03-1.69 (m, 7H), 1.69-1.49 (m, 6H), 1.49-1.24 (m, 5H), 1.17-1.06 (m, 1H), 1.03-0.94 (m, 4H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27H 46 NO8S [M-Na] - 544.3, found 544.2.

[0810]

[0811] NC20026

[0812] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.28 (m, 1H), 4.00-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.32 (m, 1H), 2.91 (dt, J = 10.3, 4.0 Hz, 1H), 2.34-2.12 (m, 5H), 2.07-1.69 (m, 10H), 1.68-1.25 (m, 15H), 1.16-1.06 (m, 1H), 1.04 (d, J = 6.4 Hz, 3H), 0.98 (td, J = 14.2, 3.4 Hz, 1H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO7S [M-Na] - 568.3, found 568.3.

[0814]

[0815] NC20027

[0816] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.27 (m, 1H), 3.98-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.32 (m, 1H), 2.91 (dt, J = 10.1, 4.1 Hz, 1H), 2.37-2.18 (m, 4H), 2.14 (ddd, J= 14.2, 9.9, 6.5 Hz, 1H), 2.07-1.70 (m, 10H), 1.69-1.27 (m, 15H), 1.17-1.06 (m, 1H), 1.03 (d, J = 6.5 Hz, 3H), 0.98 (td, J = 14.1, 3.5 Hz, 1H), 0.92 (s, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO7S [M-Na] - 568.3, found 568.3.

[0818]

[0819] NC20028

[0820] 1 H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 7.4 Hz, 1H), 4.31 (d, J = 4.3 Hz, 1H), 4.10 (s, 1H), 4.04-3.91 (m, 2H), 3.78 (s, 1H), 3.61 (s, 1H), 3.24-3.11 (m, 1H), 2.60 (dd, J = 13.4, 4.6 Hz, 1H), 2.48-2.41 (m, 1H), 2.29-2.08 (m, 2H), 2.07-1.52 (m, 9H), 1.52-1.06 (m, 14H), 1.02-0.73 (m, 8H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] - 528.3, found 528.2.

[0822]

[0823] NC20029

[0824] 1H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.99-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.33 (m, 1H), 3.08-3.02 (m, 1H), 2.91-2.84 (m, 1H), 2.34-2.19 (m, 3H), 2.13-2.04 (m, 1H), 2.04-1.69 (m, 7H), 1.69-1.48 (m, 6H), 1.48-1.25 (m, 8H), 1.11 (qd, J = 11.9, 5.8 Hz, 1H), 1.02 (d, J = 6.4 Hz, 3H), 1.01-0.93 (m, 1H), 0.92 (s, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 46 NO7S [M-Na] - 528.3, found 528.2.

[0826]

[0827] NC20030

[0828] 1 H NMR (500 MHz, CD3OD) δ 4.39-4.31 (m, 1H), 3.98-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.32 (m, 1H), 3.03 (dd, J = 14.0, 5.5 Hz, 1H), 2.90 (dd, J = 14.0, 6.3 Hz, 1H), 2.34-2.19 (m, 3H), 2.15-2.05 (m, 1H), 2.04-1.49 (m, 16H), 1.49-1.25 (m, 5H), 1.11 (qd, J = 12.0, 5.7 Hz, 1H), 1.03 (d, J = 6.5 Hz, 3H), 1.01-0.90 (m, 10H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO7S [M-Na] - 570.3, found 570.3.

[0830]

[0831] NC20031

[0832] 1 H NMR (500 MHz, CD3OD) δ 4.42-4.33 (m, 1H), 3.99-3.93 (m, 1H), 3.82-3.77 (m, 1H), 3.41-3.32 (m, 1H), 3.01 (dd, J = 14.0, 5.5 Hz, 1H), 2.90 (dd, J = 14.0, 6.4 Hz, 1H), 2.34-2.19 (m, 3H), 2.17-2.06 (m, 1H), 2.04-1.49 (m, 16H), 1.49-1.23 (m, 5H), 1.10 (qd, J = 12.0, 5.9 Hz, 1H), 1.03 (d, J = 6.5 Hz, 3H), 1.01-0.89 (m, 10H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO7S [M-Na] - 570.3, found 570.3.

[0834]

[0835] NC20032

[0836] 1 H NMR (400 MHz, DMSO-d6) δ 7.78 (s, 1H), 4.31 (d, J = 4.4 Hz, 1H), 4.09 (d, J = 3.4 Hz, 1H), 4.01 (d, J= 3.3 Hz, 1H), 3.77 (s, 1H), 3.61 (s, 1H), 3.22-3.11 (m, 1H), 2.70-2.59 (m, 2H), 2.28-2.08 (m, 2H), 2.04-1.91 (m, 2H), 1.90-1.52 (m, 7H), 1.49-1.06 (m, 11H), 1.01-0.72 (m, 10H), 0.61-0.50 (m, 5H); LCMS (ESI) m / z calcd for C 28 H 46 NO7S [M-Na] - 540.3, found 540.2.

[0838]

[0839] NC20033

[0840] 1 H NMR (500 MHz, CD3OD) δ 3.99-3.93 (m, 1H), 3.89-3.32 (m, 7H), 2.47-2.18 (m, 6H), 2.05-1.70 (m, 7H), 1.69-1.26 (m, 11H), 1.18-0.94 (m, 5H), 0.92 (s, 3H), 0.724 (s, 1.5H), 0.719 (s, 1.5H); LCMS (ESI) m / z calcd for C 28 H 46 NO7S [M-Na] - 540.3, found 540.2.

[0842]

[0843] NC20034

[0844] 1H NMR (500 MHz, CD3OD) δ 3.98-3.93 (m, 1H), 3.89-3.32 (m, 7H), 2.47-2.18 (m, 6H), 2.06-1.70 (m, 7H), 1.70-1.50 (m, 6H), 1.49-1.26 (m, 5H), 1.18-0.95 (m, 5H), 0.92 (s, 3H), 0.723 (s, 1.5H), 0.720 (s, 1.5H); LCMS (ESI) m / z calcd for C 28 H 46 NO7S [M-Na] - 540.3, found 540.2.

[0846]

[0847] NC20035

[0848] 1 H NMR (400 MHz, DMSO-d6) δ 4.30 (s, 1H), 4.12 (s, 1H), 4.01 (s, 1H), 3.79 (s, 1H), 3.61 (s, 1H), 3.54-3.39 (m, 2H), 3.31-3.23 (m, 2H), 3.21-3.12 (m, 1H), 2.70-2.61 (m, 1H), 2.60-2.53 (m, 1H), 2.39-2.06 (m, 12H), 2.03-1.92 (m, 1H), 1.85-1.56 (m, 6H), 1.50-1.07 (m, 11H), 1.01-0.82 (m, 5H), 0.81 (s, 3H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 53 N2O7S [M-Na] - 585.4, found 585.3.

[0850]

[0851] NC20036

[0852] 1H NMR (400 MHz, DMSO-d6) δ 8.51-8.38 (m, 2H), 7.62-7.54 (m, 1H), 7.43-7.29 (m, 1H), 4.65 (s, 0.5H), 4.59-4.45 (m, 1.5H), 4.30 (s, 1H), 4.16-3.97 (m, 2H), 3.82-3.72 (m, 1H), 3.61 (s, 1H), 3.54-3.41 (m, 2H), 3.22-3.11 (m, 1H), 2.69-2.54 (m, 2H), 2.48-2.37 (m, 1H), 2.37-2.07 (m, 3H), 2.04-1.90 (m, 1H), 1.85-1.55 (m, 6H), 1.50-1.07 (m, 11H), 0.96 (d, J = 6.3 Hz, 3H), 0.89-0.73 (m, 5H), 0.62-0.52 (m, 3H); LCMS (ESI) m / z calcd for C 32 H 49 N2O7S [M-Na] - 605.3, found 605.3.

[0854]

[0855] NC20037

[0856] 1 H NMR (500 MHz, CD3OD) δ 7.52-7.46 (m, 2H), 7.44-7.38 (m, 1H), 7.34-7.29 (m, 2H), 4.13-4.06 (m, 2H), 3.87-3.83 (m, 1H), 3.79-3.75 (m, 1H), 3.39-3.33 (m, 1H), 3.09-3.03 (m, 2H), 2.32-2.09 (m, 3H), 2.05-1.87 (m, 3H), 1.82-1.47 (m, 11H), 1.46-1.32 (m, 2H), 1.32-1.14 (m, 3H), 1.13-1.01 (m, 1H), 1.01-0.92 (m, 1H), 0.90 (s, 3H), 0.77 (d, J= 6.1 Hz, 3H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 48 NO7S [M-Na] - 590.3, found 590.3.

[0859]

[0860] NC30002

[0861] 1 H NMR (500 MHz, CD3OD) δ 3.39 (t, J = 7.0 Hz, 2H), 2.82 (d, J = 13.5 Hz, 1H), 2.51-2.40 (m, 1H), 2.34 (t, J = 7.0 Hz, 2H), 2.22 (ddd, J = 13.8, 10.4, 5.2 Hz, 1H), 2.12-2.01 (m, 4H), 1.99-1.86 (m, 2H), 1.82-1.72 (m, 2H), 1.68-1.57 (m, 2H), 1.54-1.07 (m, 15H), 1.04 (s, 3H), 0.96 (d, J = 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 42 NO4[M-Na] - 444.3, found 444.2.

[0863]

[0864] NC30004

[0865] 1H NMR (400 MHz, DMSO-d6) δ 3.57-3.41 (m, 2H), 2.93 (s, 1.5H), 2.82-2.69 (m, 2.5H), 2.69-2.61 (m, 1H), 2.59-2.52 (m, 1H), 2.42-2.06 (m, 3H), 2.01-1.88 (m, 3H), 1.86-1.48 (m, 7H), 1.46-0.99 (m, 14H), 0.95 (s, 3H), 0.89 (d, 3H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0867]

[0868] NC30005

[0869] 1 H NMR (500 MHz, CD3OD) δ 7.41-7.34 (m, 1H), 7.34-7.19 (m, 4H), 4.74 (s, 1H), 4.63 (s, 1H), 3.84-3.69 (m, 2H), 3.07 (t, J = 7.1 Hz, 1H), 3.03-2.98 (m, 1H), 2.90-2.79 (m, 1H), 2.62-2.52 (m, 0.5H), 2.52-2.35 (m, 2H), 2.32-2.20 (m, 0.5H), 2.14-1.70 (m, 8H), 1.69-0.93 (m, 20.5H), 0.86 (d, J = 6.5 Hz, 1.5H), 0.74 (s, 1.5H), 0.69 (s, 1.5H); LCMS (ESI) m / z calcd for C 33 H 48 NO5S [M-Na] - 570.3, found 570.3.

[0871]

[0872] NC30006

[0873] 1 H NMR (500 MHz, CD3OD) δ 3.89-3.79 (m, 1H), 3.76-3.64 (m, 3H), 3.58-3.52 (m, 1H), 3.50-3.45 (m, 1H), 3.13-3.04 (m, 2H), 2.89-2.79 (m, 1H), 2.57-2.41 (m, 2H), 2.41-2.29 (m, 1H), 2.12-2.02 (m, 3H), 1.99-1.88 (m, 3H), 1.83-1.72 (m, 2H), 1.69-1.56 (m, 2H), 1.56-1.08 (m, 14H), 1.05 (s, 3H), 1.02-0.93 (m, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO6S [M-Na] - 524.3, found 524.3.

[0875]

[0876] NC30007

[0877] 1 H NMR (500 MHz, CD3OD) δ 4.66-4.56 (m, 0.5H), 4.23-4.12 (m, 0.5H), 3.71-3.64 (m, 1H), 3.64-3.57 (m, 1H), 3.09-3.02 (m, 2H), 2.84 (td, J= 14.3, 3.7 Hz, 1H), 2.52-2.40 (m, 2H), 2.37-2.26 (m, 1H), 2.13-2.01 (m, 3H), 2.00-1.86 (m, 3H), 1.84-1.71 (m, 2H), 1.69-1.57 (m, 2H), 1.56-1.07 (m, 20H), 1.048 (s, 1.5H), 1.045 (s, 1.5H), 1.02-0.93 (m, 3H), 0.74 (s, 1.5H), 0.73 (s, 1.5H); LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0879]

[0880] NC30008

[0881] 1 H NMR (500 MHz, CD3OD) δ 4.44 (tt, J = 12.1, 3.9 Hz, 0.5H), 4.06-3.90 (m, 2.5H), 3.75-3.61 (m, 2H), 3.53-3.42 (m, 2H), 3.08-3.00 (m, 2H), 2.83 (td, J = 14.2, 3.5 Hz, 1H), 2.54-2.30 (m, 3H), 2.12-2.02 (m, 3H), 2.02-1.84 (m, 5H), 1.83-1.71 (m, 1H), 1.71-1.24 (m, 15H), 1.24-1.08 (m, 4H), 1.05 (s, 1.5H), 1.04 (s, 1.5H), 1.02-0.93 (m, 3H), 0.74 (s, 1.5H), 0.73 (s, 1.5H); LCMS (ESI) m / z calcd for C 31 H 50 NO6S [M-Na] - 564.3, found 564.3.

[0883]

[0884] NC30009

[0885] 1 1H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 10.2 Hz, 0.4H), 4.42 (d, J = 13.3 Hz, 0.6H), 4.32-4.25 (m, 0.6H), 3.92 (d, J = 13.0 Hz, 0.4H), 3.24 (dd, J = 13.5, 11.1 Hz, 0.6H), 3.01 (td, J = 13.2, 2.8 Hz, 0.4H), 2.90-2.57 (m, 3H), 2.56-2.39 (m, 2H), 2.38-2.25 (m, 2H), 2.13-1.99 (m, 3H), 1.99-1.69 (m, 7H), 1.69-1.57 (m, 2H), 1.57-1.24 (m, 11H), 1.24-1.07 (m, 4H), 1.05 (s, 3H), 1.01-0.98 (m, 3H), 0.73 (s, 3H); LCMS(ESI) m / z calcd for C 29 H 46 NO5S [M-Na] - 520.3, found 520.3.

[0887]

[0888] NC30010 (St4-Tau10)

[0889] 1 1H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 9.9 Hz, 0.4H), 4.44 (d, J = 13.0 Hz, 0.6H), 4.33-4.25 (m, 0.6H), 3.92 (d, J = 13.5 Hz, 0.4H), 3.23 (dd, J= 13.5, 11.2 Hz, 0.6H), 3.01 (td, J = 13.2, 2.8 Hz, 0.4H), 2.89-2.55 (m, 3H), 2.52-2.40 (m, 2H), 2.40-2.25 (m, 2H), 2.12-1.99 (m, 3H), 1.99-1.70 (m, 7H), 1.69-1.58 (m, 2H), 1.56-1.24 (m, 11H), 1.24-1.07 (m, 4H), 1.05 (s, 3H), 1.01-0.98 (m, 3H), 0.74 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 46 NO5S [M-Na] - 520.3, found 520.3.

[0891]

[0892] NC30011

[0893] 1 H NMR (400 MHz, DMSO-d6) δ 4.37 (d, J = 12.9 Hz, 1H), 3.85 (d, J = 13.4 Hz, 1H), 2.98-2.87 (m, 1H), 2.81-2.69 (m, 1H), 2.48-2.11 (m, 5H), 2.01-1.67 (m, 9H), 1.67-1.49 (m, 3H), 1.46-1.00 (m, 16H), 0.96 (s, 3H), 0.90 (d, J = 6.5 Hz, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 46 NO5S [M-Na] - 520.3, found 520.2.

[0895]

[0896] NC30012

[0897] 1 H NMR (400 MHz, DMSO-d6) δ 4.16 (td, J = 8.4, 2.3 Hz, 1H), 4.05-3.97 (m, 1H), 3.85 (t, J = 9.0 Hz, 1H), 3.80-3.71 (m, 1H), 3.46-3.38 (m, 1H), 2.75 (t, J = 14.1 Hz, 1H), 2.36 (td, J = 14.7, 5.4 Hz, 1H), 2.05-1.67 (m, 9H), 1.66-1.49 (m, 3H), 1.47-0.99 (m, 14H), 0.96 (s, 3H), 0.88 (d, J = 6.7 Hz, 3H), 0.64 (d, J = 2.0 Hz, 3H); LCMS (ESI) m / z calcd for C 27 H 42 NO5S [M-Na] - 492.3, found 492.2.

[0899]

[0900] NC30013

[0901] 1 H NMR (500 MHz, CD3OD) δ 3.15-3.10 (m, 2H), 2.89-2.80 (m, 1H), 2.52-2.42 (m, 1H), 2.20 (ddd, J = 14.0, 10.3, 5.2 Hz, 1H), 2.13-1.99 (m, 4H), 1.99-1.85 (m, 3H), 1.83-1.71 (m, 2H), 1.68-1.57 (m, 2H), 1.56-1.24 (m, 10H), 1.53 (s, 6H), 1.24-1.07 (m, 4H), 1.04 (s, 3H), 0.96 (d, J = 6.6 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 46 NO5S [M-Na] - 508.3, found 508.3.

[0903]

[0904] NC30014

[0905] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.22 (m, 4H), 7.21-7.14 (m, 1H), 4.50-4.43 (m, 1H), 3.16 (dd, J = 13.6, 6.3 Hz, 1H), 3.04-2.94 (m, 2H), 2.91 (dd, J = 13.6, 7.8 Hz, 1H), 2.88-2.80 (m, 1H), 2.52-2.41 (m, 1H), 2.17 (ddd, J = 13.8, 10.7, 5.2 Hz, 1H), 2.12-1.83 (m, 7H), 1.82-1.75 (m, 1H), 1.73-1.57 (m, 3H), 1.56-1.06 (m, 14H), 1.04 (s, 3H), 0.93 (d, J = 6.6 Hz, 3H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 48 NO5S [M-Na] - 570.3, found 570.3.

[0907]

[0908] NC30015

[0909] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.22 (m, 4H), 7.22-7.14 (m, 1H), 4.52-4.44 (m, 1H), 3.16 (dd, J= 13.6, 6.1 Hz, 1H), 3.03-2.94 (m, 2H), 2.91 (dd, J = 13.6, 7.8 Hz, 1H), 2.88-2.80 (m, 1H), 2.52-2.41 (m, 1H), 2.18 (ddd, J = 13.8, 10.4, 5.1 Hz, 1H), 2.13-1.83 (m, 7H), 1.83-1.75 (m, 1H), 1.74-1.56 (m, 3H), 1.56-1.07 (m, 14H), 1.04 (s, 3H), 0.92 (d, J = 6.6 Hz, 3H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 33 H 48 NO5S [M-Na] - 570.3, found 570.4.

[0911]

[0912] NC30016

[0913] 1 H NMR (500 MHz, CD3OD) δ 4.23-4.16 (m, 1H), 2.96 (dd, J = 6.1, 1.9 Hz, 2H), 2.88-2.80 (m, 1H), 2.52-2.41 (m, 1H), 2.28 (ddd, J = 13.8, 10.6, 5.2 Hz, 1H), 2.15-2.02 (m, 5H), 1.99-1.87 (m, 3H), 1.87-1.75 (m, 2H), 1.69-1.56 (m, 2H), 1.56-1.07 (m, 14H), 1.05 (s, 3H), 0.98 (d, J = 6.6 Hz, 3H), 0.92 (t, J = 6.5 Hz, 6H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48NO5S [M-Na] - 522.3, found 522.3.

[0915]

[0916] NC30017

[0917] 1 H NMR (400 MHz, DMSO-d6) δ 7.47 (d, J = 8.5 Hz, 1H), 3.99-3.88 (m, 1H), 2.75 (t, J = 14.1 Hz, 1H), 2.56-2.51 (m, 2H), 2.36 (td, J = 14.5, 5.3 Hz, 1H), 2.14-1.89 (m, 6H), 1.87-1.62 (m, 5H), 1.62-1.49 (m, 2H), 1.46-0.98 (m, 14H), 0.95 (s, 3H), 0.89 (d, J = 6.5 Hz, 3H), 0.76 (d, J = 6.8 Hz, 6H), 0.63 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO5S [M-Na] - 522.3, found 522.3.

[0919]

[0920] NC30018

[0921] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.27 (m, 4H), 7.24-7.18 (m, 1H), 5.34 (dd, J = 10.0, 3.7 Hz, 1H), 3.26 (dd, J = 14.3, 10.0 Hz, 1H), 3.09 (dd, J = 14.3, 3.8 Hz, 1H), 2.89-2.79 (m, 1H), 2.51-2.41 (m, 1H), 2.31 (ddd,J = 14.0, 10.2, 5.3 Hz, 1H), 2.15 (ddd, J = 14.0, 10.0, 6.5 Hz, 1H), 2.11-2.00 (m, 3H), 2.00-1.84 (m, 3H), 1.83-1.74 (m, 2H), 1.65-1.56 (m, 2H), 1.55-1.06 (m, 14H), 1.04 (s, 3H), 0.95 (d, J = 6.5 Hz, 3H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 46 NO5S [M-Na] - 556.3, found 556.3.

[0923]

[0924] NC30019

[0925] 1 H NMR (500 MHz, CD3OD) δ 7.36-7.27 (m, 4H), 7.24-7.19 (m, 1H), 5.35 (dd, J = 10.1, 3.6 Hz, 1H), 3.26 (dd, J = 14.3, 10.1 Hz, 1H), 3.09 (dd, J = 14.3, 3.7 Hz, 1H), 2.88-2.80 (m, 1H), 2.51-2.41 (m, 1H), 2.30 (ddd, J = 13.8, 9.7, 5.0 Hz, 1H), 2.17 (ddd, J = 13.9, 9.3, 7.1 Hz, 1H), 2.12-2.00 (m, 3H), 1.99-1.83 (m, 3H), 1.83-1.73 (m, 2H), 1.71-1.55 (m, 2H), 1.55-1.06 (m, 14H), 1.05 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.67 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 46 NO5S [M-Na] - 556.3, found 556.3.

[0927]

[0928] NC30020

[0929] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.45 (m, 0.5H), 4.43-4.36 (m, 0.5H), 3.58-3.51 (m, 0.5H), 3.50-3.28 (m, 2H), 3.02-2.90 (m, 1H), 2.85 (td, J = 14.2, 4.1 Hz, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.56 (ddd, J = 15.3, 10.6, 5.3 Hz, 0.5H), 2.51-2.27 (m, 3H), 2.20 (ddd, J = 14.7, 10.4, 5.9 Hz, 0.5H), 2.12-1.87 (m, 9H), 1.85-1.71 (m, 2H), 1.69-1.57 (m, 2H), 1.56-1.07 (m, 14H), 1.05 (s, 1.5H), 1.04 (s, 1.5H), 1.00 (d, J = 6.6 Hz, 1.5H), 0.98 (d, J = 6.6 Hz, 1.5H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 46 NO5S [M-Na] - 520.3, found 520.3.

[0931]

[0932] NC30021

[0933] 1H NMR (400 MHz, DMSO-d6) δ 4.24-4.10 (m, 1H), 3.42-3.27 (m, 1H), 3.27-3.11 (m, 1H), 2.91 (dd, J = 12.7, 2.9 Hz, 0.5H), 2.76 (td, J = 14.1, 6.4 Hz, 1H), 2.60-2.52 (m, 0.5H), 2.43-2.03 (m, 5H), 2.00-1.89 (m, 3H), 1.88-1.48 (m, 10H), 1.47-0.99 (m, 14H), 0.96 (s, 3H), 0.93-0.86 (m, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 46 NO5S [M-Na] - 520.3, found 520.4.

[0935]

[0936] NC30022

[0937] 1 H NMR (500 MHz, CD3OD) δ 3.57 (dd, J = 13.8, 6.1 Hz, 1H), 3.44 (dd, J = 13.8, 6.7 Hz, 1H), 3.00-2.90 (m, 1H), 2.89-2.80 (m, 1H), 2.52-2.41 (m, 1H), 2.26 (ddd, J = 13.9, 10.2, 5.2 Hz, 1H), 2.17-2.02 (m, 4H), 1.99-1.85 (m, 3H), 1.85-1.75 (m, 2H), 1.68-1.57 (m, 2H), 1.57-1.24 (m, 13H), 1.24-1.07 (m, 4H), 1.05 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0939]

[0940] NC30023

[0941] 1 H NMR (400 MHz, DMSO-d6) δ 7.59 (t, J = 5.6 Hz, 1H), 3.28-3.20 (m, 1H), 3.19-3.09 (m, 1H), 2.75 (t, J = 14.1 Hz, 1H), 2.48-2.30 (m, 2H), 2.07 (ddd, J = 14.6, 9.9, 5.2 Hz, 1H), 2.00-1.88 (m, 4H), 1.87-1.49 (m, 7H), 1.47-1.04 (m, 14H), 1.02 (d, J = 6.8 Hz, 3H), 0.96 (s, 3H), 0.88 (d, J = 6.5 Hz, 3H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0943]

[0944] NC30024

[0945] 1H NMR (500 MHz, CD3OD) δ 4.34-4.26 (m, 1H), 3.75-3.64 (m, 2H), 3.14-3.06 (m, 1H), 3.06-2.98 (m, 1H), 2.89-2.79 (m, 1H), 2.51-2.40 (m, 1H), 2.33-2.23 (m, 1H), 2.16-1.99 (m, 4H), 1.99-1.87 (m, 3H), 1.85-1.74 (m, 2H), 1.68-1.56 (m, 2H), 1.56-1.24 (m, 10H), 1.24-1.06 (m, 4H), 1.05 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO6S [M-Na] - 510.3, found 510.2.

[0947]

[0948] NC30025

[0949] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.26 (m, 1H), 3.76-3.65 (m, 2H), 3.13-3.00 (m, 2H), 2.89-2.80 (m, 1H), 2.51-2.40 (m, 1H), 2.32-2.24 (m, 1H), 2.16-2.00 (m, 4H), 1.99-1.86 (m, 3H), 1.85-1.74 (m, 2H), 1.68-1.57 (m, 2H), 1.56-1.24 (m, 10H), 1.24-1.06 (m, 6H), 1.05 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO6S [M-Na] -510.3, found 510.3.

[0951]

[0952] NC30026

[0953] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.28 (m, 1H), 2.91 (dt, J = 10.2, 4.0 Hz, 1H), 2.88-2.80 (m, 1H), 2.52-2.42 (m, 1H), 2.32-1.84 (m, 12H), 1.84-1.74 (m, 2H), 1.69-1.57 (m, 2H), 1.57-1.24 (m, 14H), 1.24-1.06 (m, 4H), 1.04 (s, 3H), 0.98 (d, J = 6.5 Hz, 3H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 48 NO5S [M-Na] - 534.3, found 534.4.

[0955]

[0956] NC30027

[0957] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.26 (m, 1H), 2.91 (dt, J = 10.1, 4.1 Hz, 1H), 2.88-2.80 (m, 1H), 2.51-2.41 (m, 1H), 2.31 (ddd, J = 14.2, 10.4, 5.2 Hz, 1H), 2.26-2.18 (m, 1H), 2.16-1.74 (m, 12H), 1.69-1.57 (m, 2H), 1.57-1.24 (m, 14H), 1.24-1.06 (m, 4H), 1.05 (s, 3H), 0.97 (d, J= 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 48 NO5S [M-Na] - 534.3, found 534.3.

[0959]

[0960] NC30028

[0961] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.26 (m, 1H), 3.05 (dd, J = 13.9, 5.6 Hz, 1H), 2.92-2.80 (m, 2H), 2.52-2.41 (m, 1H), 2.22 (ddd, J = 13.8, 10.3, 5.2 Hz, 1H), 2.13-2.01 (m, 4H), 1.99-1.85 (m, 3H), 1.84-1.74 (m, 2H), 1.68-1.57 (m, 2H), 1.56-1.24 (m, 13H), 1.23-1.07 (m, 4H), 1.05 (s, 3H), 0.97 (d, J = 6.5 Hz, 3H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0963]

[0964] NC30029

[0965] 1 H NMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 7.5 Hz, 1H), 4.04-3.92 (m, 1H), 2.81-2.69 (m, 1H), 2.60 (dd, J= 13.4, 4.6 Hz, 1H), 2.49-2.30 (m, 2H), 2.09-1.48 (m, 12H), 1.47-0.99 (m, 17H), 0.96 (s, 3H), 0.88 (d, J = 6.5 Hz, 3H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 27 H 44 NO5S [M-Na] - 494.3, found 494.2.

[0967]

[0968] NC30030

[0969] 1 H NMR (500 MHz, CD3OD) δ 4.39-4.30 (m, 1H), 3.03 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.2 Hz, 1H), 2.87-2.79 (m, 1H), 2.51-2.40 (m, 1H), 2.24 (ddd, J = 13.8, 9.9, 5.3 Hz, 1H), 2.14-2.02 (m, 4H), 1.99-1.87 (m, 3H), 1.84-1.75 (m, 2H), 1.71-1.24 (m, 15H), 1.23-1.07 (m, 4H), 1.05 (s, 3H), 1.00-0.91 (m, 9H), 0.73 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO5S [M-Na] - 536.3, found 536.3.

[0971]

[0972] NC30031

[0973] 1H NMR (500 MHz, CD3OD) δ 4.42-4.33 (m, 1H), 3.01 (dd, J = 14.1, 5.6 Hz, 1H), 2.94-2.80 (m, 2H), 2.52-2.41 (m, 1H), 2.22 (ddd, J = 14.2, 9.4, 5.2 Hz, 1H), 2.15-2.02 (m, 4H), 1.99-1.85 (m, 3H), 1.85-1.75 (m, 2H), 1.71-1.06 (m, 19H), 1.05 (s, 3H), 1.00-0.91 (m, 9H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO5S [M-Na] - 536.3, found 536.3.

[0975]

[0976] NC30032

[0977] 1 H NMR (500 MHz, CD3OD) δ 3.08-2.97 (m, 2H), 2.88-2.80 (m, 1H), 2.52-2.41 (m, 1H), 2.20 (ddd, J = 14.0, 10.4, 5.2 Hz, 1H), 2.12-2.00 (m, 4H), 1.99-1.86 (m, 3H), 1.83-1.71 (m, 2H), 1.68-1.57 (m, 2H), 1.57-1.24 (m, 10H), 1.23-1.07 (m, 4H), 1.04 (s, 3H), 1.01-0.90 (m, 5H), 0.80-0.76 (m, 2H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 28 H 44 NO5S [M-Na] - 506.3, found 506.2.

[0980]

[0981] NC30033

[0982] 1 H NMR (400 MHz, DMSO-d6) δ 3.65-3.26 (m, 3.5H), 3.25-3.13 (m, 1H), 3.13-3.04 (m, 0.5H), 2.81-2.69 (m, 1H), 2.43-2.30 (m, 1H), 2.27-2.14 (m, 1H), 2.14-1.86 (m, 6H), 1.86-1.50 (m, 7H), 1.46-1.00 (m, 14H), 0.96 (s, 3H), 0.93-0.82 (m, 3H), 0.68-0.60 (m, 3H); LCMS (ESI) m / z calcd for C 28 H 44 NO5S [M-Na] - 506.3, found 506.3.

[0984]

[0985] NC30034

[0986] 1 H NMR (400 MHz, DMSO-d6) δ 3.64-3.30 (m, 3.5H), 3.25-3.15 (m, 1H), 3.12-3.03 (m, 0.5H), 2.81-2.69 (m, 1H), 2.43-2.30 (m, 1H), 2.26-2.14 (m, 1H), 2.14-1.86 (m, 6H), 1.86-1.49 (m, 7H), 1.49-1.00 (m, 14H), 0.96 (s, 3H), 0.92-0.83 (m, 3H), 0.66-0.62 (m, 3H); LCMS (ESI) m / z calcd for C 28 H 44 NO5S [M-Na] - 506.3, found 506.3.

[0988]

[0989] NC30035

[0990] 1 H NMR (400 MHz, DMSO-d6) δ 3.55-3.39 (m, 2H), 3.32-3.22 (m, 2H), 2.82-2.70 (m, 1H), 2.70-2.61 (m, 1.2H), 2.60-2.54 (m, 0.8H), 2.43-2.18 (m, 5H), 2.16 (s, 2.4H), 2.12 (s, 3.6H), 2.00-1.90 (m, 3H), 1.87-1.50 (m, 7H), 1.47-0.99 (m, 14H), 0.96 (s, 3H), 0.91-0.87 (m, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 51 N2O5S [M-Na] - 551.4, found 551.3.

[0992]

[0993] NC30036

[0994] 1 H NMR (500 MHz, CD3OD) δ 8.52-8.42 (m, 2H), 7.80-7.77 (m, 0.6H), 7.77-7.72 (m, 0.4H), 7.50-7.44 (m, 0.4H), 7.43-7.38 (m, 0.6H), 4.84-4.79 (m, 0.8H), 4.71-4.62 (m, 1.2H), 3.82-3.71 (m, 2H), 3.11-3.04 (m, 2H), 2.85-2.78 (m, 1H), 2.63-2.55 (m, 0.6H), 2.51-2.37 (m, 2H), 2.35-2.26 (m, 0.4H), 2.12-1.72 (m, 7H), 1.69-1.56 (m, 2H), 1.55-1.06 (m, 14.6H), 1.05 (s, 1.8H), 1.03 (s, 1.2H), 1.01 (d, J = 6.5 Hz, 1.8H), 0.99-0.93 (m, 0.4H), 0.88 (d, J = 6.5 Hz, 1.2H), 0.74 (s, 1.8H), 0.70 (s, 1.2H); LCMS (ESI) m / z calcd for C 32 H 47 N2O5S [M-Na] - 571.3, found 571.4.

[0996]

[0997] NC30037

[0998] 1 H NMR (500 MHz, CD3OD) δ 7.53-7.47 (m, 2H), 7.46-7.39 (m, 1H), 7.35-7.29 (m, 2H), 4.15-4.05 (m, 2H), 3.09-3.02 (m, 2H), 2.82 (t, J = 14.3 Hz, 1H), 2.43 (td, J = 14.7, 5.6 Hz, 1H), 2.17-2.02 (m, 3H), 2.02-1.85 (m, 4H), 1.82-1.64 (m, 3H), 1.61-0.91 (m, 19H), 0.71 (d, J = 6.2 Hz, 3H), 0.65 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 46 NO5S [M-Na]- 556.3, found 556.3.

[1001]

[1002] NC40002

[1003] 1 H NMR (500 MHz, CD3OD) δ 3.65 (t, J = 2.6 Hz, 1H), 3.39 (t, J = 7.0 Hz, 2H), 3.34-3.26 (m, 1H), 2.34 (t, J = 7.0 Hz, 2H), 2.23 (ddd, J = 13.8, 10.4, 5.2 Hz, 1H), 2.07 (ddd, J = 13.8, 10.0, 6.4 Hz, 1H), 2.00 (dt, J = 12.4, 3.4 Hz, 1H), 1.97-1.68 (m, 7H), 1.64-1.24 (m, 13H), 1.23-1.06 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO5[M-Na] - 490.4, found 490.3.

[1005]

[1006] NC40003

[1007] 1 H NMR (500 MHz, CD3OD) δ 3.65 (t, J = 2.8 Hz, 1H), 3.58 (t, J = 6.3 Hz, 2H), 3.35-3.27 (m, 1H), 3.27-3.22 (m, 2H), 2.24 (ddd, J = 13.7, 10.0, 5.2 Hz, 1H), 2.10 (ddd, J= 13.8, 9.7, 6.7 Hz, 1H), 2.00 (dt, J = 12.5, 3.4 Hz, 1H), 1.97-1.66 (m, 9H), 1.64-1.25 (m, 12H), 1.24-1.06 (m, 3H), 1.06-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO4[M-H] - 476.4, found 476.4.

[1009]

[1010] NC40004

[1011] 1 H NMR (500 MHz, CD3OD) δ 3.84-3.70 (m, 2H), 3.66 (t, J = 2.6 Hz, 1H), 3.35-3.25 (m, 1H), 3.12 (s, 1.5H), 3.09-2.99 (m, 2H), 2.93 (s, 1.5H), 2.52 (ddd, J = 15.6, 10.9, 5.1 Hz, 0.5H), 2.46-2.33 (m, 1H), 2.26 (ddd, J = 15.3, 10.7, 5.7 Hz, 0.5H), 2.04-1.69 (m, 8H), 1.63-1.26 (m, 13H), 1.25-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.3.

[1013]

[1014] NC40005

[1015] 1 H NMR (400 MHz, DMSO-d6) δ 7.41-7.14 (m, 5H), 4.59-4.48 (m, 2H), 4.28 (d, J = 4.8 Hz, 1H), 4.08-4.03 (m, 1H), 3.54-3.39 (m, 3H), 3.17-3.05 (m, 1H), 2.64-2.51 (m, 2H), 2.45-2.10 (m, 2H), 1.97-1.59 (m, 7H), 1.55-0.74 (m, 27H), 0.62 (s, 2H), 0.57 (s, 1H); LCMS (ESI) m / z calcd for C 35 H 54 NO6S [M-Na] - 616.4, found 616.3.

[1017]

[1018] NC40006

[1019] 1 H NMR (500 MHz, CD3OD) δ 3.89-3.78 (m, 1H), 3.78-3.63 (m, 4H), 3.58-3.51 (m, 1H), 3.51-3.43 (m, 1H), 3.35-3.26 (m, 1H), 3.14-3.03 (m, 2H), 2.57-2.44 (m, 1H), 2.42-2.29 (m, 1H), 2.05-1.69 (m, 8H), 1.64-1.25 (m, 13H), 1.25-1.05 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.86 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO7S [M-Na] - 570.3, found 570.4.

[1021]

[1022] NC40007

[1023] 1 H NMR (400 MHz, DMSO-d6) δ 4.55-4.43 (m, 0.5H), 4.29 (t, J = 5.7 Hz, 1H), 4.11-3.98 (m, 1.5H), 3.49 (s, 1H), 3.45-3.37 (m, 1H), 3.37-3.28 (m, 1H), 3.18-3.05 (m, 1H), 2.67-2.55 (m, 2H), 2.34-2.11 (m, 2H), 1.95-1.57 (m, 7H), 1.55-0.94 (m, 23H), 0.93-0.78 (m, 10H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 54 NO6S [M-Na] - 568.4, found 568.4.

[1025]

[1026] NC40008

[1027] 1 H NMR (500 MHz, CD3OD) δ 4.43 (tt, J = 12.1, 3.9 Hz, 0.5H), 4.06-3.90 (m, 2.5H), 3.76-3.62 (m, 3H), 3.53-3.41 (m, 2H), 3.35-3.26 (m, 1H), 3.08-3.01 (m, 2H), 2.54-2.43 (m, 1H), 2.41-2.30 (m, 1H), 2.05-1.64 (m, 11H), 1.64-1.43 (m, 8H), 1.43-1.25 (m, 6H), 1.25-1.06 (m, 3H), 1.06-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.71(s, 1.5H), 0.69 (s, 1.5H); LCMS (ESI) m / z calcd for C33 H 56 NO7S [M-Na] - 610.4, found 610.4.

[1029]

[1030] NC40009

[1031] 1 H NMR (500 MHz, CD3OD) δ 5.05-4.99 (m, 0.5H), 4.43 (d, J = 13.0 Hz, 0.5H), 4.33-4.25 (m, 0.5H), 3.92 (d, J = 13.3 Hz, 0.5H), 3.65 (t, J = 2.7 Hz, 1H), 3.35-3.27 (m, 1H), 3.27-3.20 (m, 0.5H), 3.06-2.96 (m, 0.5H), 2.84-2.56 (m, 2H), 2.56-2.40 (m, 1H), 2.38-2.23 (m, 2H), 2.04-1.69 (m, 10H), 1.64-1.26 (m, 14H), 1.25-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.4.

[1033]

[1034] NC40010

[1035] 1 H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 9.8 Hz, 0.5H), 4.44 (d, J = 13.1 Hz, 0.5H), 4.34-4.26 (m, 0.5H), 3.92 (d, J = 13.2 Hz, 0.5H), 3.66 (t,J = 2.7 Hz, 1H), 3.34-3.26 (m, 1H), 3.23 (dd, J = 13.5, 11.2 Hz, 0.5H), 3.01 (td, J = 13.2, 2.8 Hz, 0.5H), 2.84-2.56 (m, 2H), 2.53-2.41 (m, 1H), 2.41-2.24 (m, 2H), 2.04-1.69 (m, 10H), 1.64-1.25 (m, 14H), 1.24-1.06 (m, 3H), 1.05-0.96 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.4.

[1037]

[1038] NC40011

[1039] 1 H NMR (400 MHz, DMSO-d6) δ 4.37 (d, J = 13.1 Hz, 1H), 4.29 (d, J = 4.7 Hz, 1H), 4.05 (d, J = 4.1 Hz, 1H), 3.86 (d, J = 13.4 Hz, 1H), 3.49 (s, 1H), 3.18-3.05 (m, 1H), 2.98-2.87 (m, 1H), 2.48-2.38 (m, 2H), 2.36-2.10 (m, 2H), 1.98-1.57 (m, 9H), 1.55-1.03 (m, 18H), 1.03-0.75 (m, 11H), 0.61 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.3.

[1041]

[1042] NC40012

[1043] 1 H NMR (500 MHz, CD3OD) δ 4.42 (t, J = 8.8 Hz, 1H), 4.37-4.30 (m, 1H), 4.21-4.11 (m, 2H), 3.85-3.76 (m, 1H), 3.65 (t, J = 2.6 Hz, 1H), 3.35-3.25 (m, 1H), 2.25-2.13 (m, 1H), 2.11-1.97 (m, 2H), 1.97-1.69 (m, 7H), 1.64-1.24 (m, 13H), 1.24-1.06 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO6S [M-Na] - 538.3, found 538.3.

[1045]

[1046] NC40013

[1047] 1 H NMR (500 MHz, CD3OD) δ 3.65 (t, J = 2.7 Hz, 1H), 3.34-3.25 (m, 1H), 3.20-3.10 (m, 2H), 2.20 (ddd, J = 13.9, 10.3, 5.1 Hz, 1H), 2.09-1.68 (m, 9H), 1.64-1.23 (m, 19H), 1.23-1.05 (m, 3H), 1.05-0.94 (m, 4H), 0.93-0.86 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 30 H52 NO6S [M-Na] - 554.4, found 554.3.

[1049]

[1050] NC40014

[1051] 1 H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 7.6 Hz, 1H), 7.29-7.12 (m, 5H), 4.29 (d, J = 4.6 Hz, 1H), 4.19-4.07 (m, 1H), 4.05 (d, J = 5.0 Hz, 1H), 3.50 (s, 1H), 3.18-3.07 (m, 2H), 2.74 (dd, J = 13.4, 7.1 Hz, 1H), 2.53 (d, J = 6.2 Hz, 2H), 2.05-1.94 (m, 1H), 1.93-1.64 (m, 7H), 1.64-0.74 (m, 28H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 35 H 54 NO6S [M-Na] - 616.4, found 616.4.

[1053]

[1054] NC40015

[1055] 1 H NMR (500 MHz, CD3OD) δ 7.30-7.22 (m, 4H), 7.21-7.14 (m, 1H), 4.52-4.43 (m, 1H), 3.65 (t, J = 2.8 Hz, 1H), 3.34-3.26 (m, 1H), 3.16 (dd, J = 13.6, 6.1 Hz, 1H), 3.03-2.94 (m, 2H), 2.91 (dd, J= 13.7, 7.8 Hz, 1H), 2.18 (ddd, J = 13.8, 10.3, 5.1 Hz, 1H), 2.07-1.95 (m, 2H), 1.95-1.65 (m, 7H), 1.64-1.05 (m, 16H), 1.00 (td, J = 14.2, 3.5 Hz, 1H), 0.95-0.85 (m, 9H), 0.67 (s, 3H); LCMS (ESI) m / z calcd for C 35 H 54 NO6S [M-Na] - 616.4, found 616.4.

[1057]

[1058] NC40016

[1059] 1 H NMR (500 MHz, CD3OD) δ 4.24-4.16 (m, 1H), 3.65 (t, J = 2.8 Hz, 1H), 3.35-3.26 (m, 1H), 2.98-2.93 (m, 2H), 2.29 (ddd, J = 13.7, 10.6, 5.1 Hz, 1H), 2.15-2.03 (m, 2H), 2.03-1.69 (m, 8H), 1.63-1.25 (m, 13H), 1.24-1.05 (m, 3H), 1.05-0.96 (m, 4H), 0.95-0.87 (m, 12H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 54 NO6S [M-Na] - 568.4, found 568.4.

[1061]

[1062] NC40017

[1063] 1H NMR (500 MHz, CD3OD) δ 4.25-4.18 (m, 1H), 3.65 (t, J = 2.7 Hz, 1H), 3.35-3.26 (m, 1H), 2.95 (d, J = 6.1 Hz, 2H), 2.26 (ddd, J = 13.7, 9.7, 5.0 Hz, 1H), 2.20-2.04 (m, 2H), 2.04-1.69 (m, 8H), 1.63-1.24 (m, 13H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.95-0.85 (m, 12H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 54 NO6S [M-Na] - 568.4, found 568.4.

[1065]

[1066] NC40018

[1067] 1 H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 6.3 Hz, 1H), 7.29-7.19 (m, 4H), 7.18-7.11 (m, 1H), 5.03-4.93 (m, 1H), 4.29 (d, J = 4.7 Hz, 1H), 4.05 (d, J = 5.0 Hz, 1H), 3.49 (s, 1H), 3.18-3.05 (m, 1H), 2.85 (dd, J = 13.9, 9.1 Hz, 1H), 2.67 (dd, J = 13.8, 4.1 Hz, 1H), 2.17-2.05 (m, 1H), 2.01-1.58 (m, 8H), 1.57-0.74 (m, 27H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 34 H52 NO6S [M-Na] - 602.4, found 602.4.

[1069]

[1070] NC40019

[1071] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.26 (m, 4H), 7.25-7.18 (m, 1H), 5.36 (dd, J = 10.0, 3.7 Hz, 1H), 3.64 (t, J = 2.7 Hz, 1H), 3.34-3.22 (m, 2H), 3.09 (dd, J = 14.3, 3.7 Hz, 1H), 2.30 (ddd, J = 14.3, 9.6, 5.0 Hz, 1H), 2.18 (ddd, J = 13.9, 9.1, 7.2 Hz, 1H), 1.98 (dt, J = 12.4, 3.4 Hz, 1H), 1.95-1.67 (m, 7H), 1.64-1.11 (m, 15H), 1.10-0.99 (m, 2H), 0.97 (d, J = 6.4 Hz, 3H), 0.93-0.87 (m, 6H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 34 H 52 NO6S [M-Na] - 602.4, found 602.4.

[1073]

[1074] NC40020

[1075] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.45 (m, 0.5H), 4.44-4.37 (m, 0.5H), 3.66 (t, J= 2.7 Hz, 1H), 3.58-3.52 (m, 0.5H), 3.50-3.27 (m, 3H), 3.02-2.90 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.56 (ddd, J = 15.3, 10.6, 5.2 Hz, 0.5H), 2.48-2.27 (m, 2H), 2.20 (ddd, J = 14.6, 10.4, 5.9 Hz, 0.5H), 2.11-1.70 (m, 11H), 1.64-1.25 (m, 13H), 1.24-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.4.

[1077]

[1078] NC40021

[1079] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.44 (m, 0.5H), 4.44-4.37 (m, 0.5H), 3.66 (t, J = 2.7 Hz, 1H), 3.58-3.52 (m, 0.5H), 3.51-3.26 (m, 3H), 3.02-2.90 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.49-2.39 (m, 2H), 2.34 (ddd, J = 14.6, 10.8, 5.2 Hz, 0.5H), 2.22 (ddd, J= 14.7, 10.5, 5.8 Hz, 0.5H), 2.11-1.69 (m, 11H), 1.64-1.25 (m, 13H), 1.25-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.701 (s, 1.5H), 0.697 (s, 1.5H); LCMS (ESI) m / z calcd for C 31 H 52 NO6S [M-Na] - 566.4, found 566.3.

[1081]

[1082] NC40022

[1083] 1 H NMR (500 MHz, CD3OD) δ 3.65 (t, J = 2.7 Hz, 1H), 3.57 (dd, J = 13.7, 6.0 Hz, 1H), 3.44 (dd, J = 13.7, 6.8 Hz, 1H), 3.31-3.26 (m, 1H), 3.00-2.90 (m, 1H), 2.26 (ddd, J = 13.9, 10.1, 5.1 Hz, 1H), 2.12 (ddd, J = 13.9, 9.7, 6.7 Hz, 1H), 2.04-1.69 (m, 8H), 1.64-1.25 (m, 16H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.3.

[1085]

[1086] NC40023

[1087] 1 H NMR (400 MHz, DMSO-d6) δ 7.63-7.56 (m, 1H), 4.30 (d, J = 4.6 Hz, 1H), 4.05 (d, J = 5.0 Hz, 1H), 3.49 (s, 1H), 3.30-3.22 (m, 1H), 3.19-3.05 (m, 2H), 2.49-2.41 (m, 1H), 2.13-2.01 (m, 1H), 2.00-1.58 (m, 8H), 1.57-0.74 (m, 30H), 0.59 (s, 3H). ; LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.3.

[1089]

[1090] NC40024

[1091] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.25 (m, 1H), 3.76-3.67 (m, 2H), 3.65 (t, J = 2.6 Hz, 1H), 3.36-3.25 (m, 1H), 3.14-2.99 (m, 2H), 2.33-2.22 (m, 1H), 2.17-2.06 (m, 1H), 2.04-1.70 (m, 8H), 1.63-1.25 (m, 13H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.3.

[1093]

[1094] NC40025

[1095] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.26 (m, 1H), 3.76-3.67 (m, 2H), 3.65 (t, J = 2.6 Hz, 1H), 3.36-3.26 (m, 1H), 3.14-2.99 (m, 2H), 2.32-2.24 (m, 1H), 2.16-2.07 (m, 1H), 2.03-1.68 (m, 8H), 1.65-1.25 (m, 13H), 1.24-1.05 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.3.

[1097]

[1098] NC40026

[1099] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.28 (m, 1H), 3.65 (t, J = 2.6 Hz, 1H), 3.35-3.25 (m, 1H), 2.91 (dt, J = 10.2, 4.0 Hz, 1H), 2.32-2.11 (m, 3H), 2.07-1.69 (m, 11H), 1.64-1.25 (m, 17H), 1.24-1.05 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 54 NO6S [M-Na] - 580.4, found 580.4.

[1101]

[1102] NC40027

[1103] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.26 (m, 1H), 3.65 (t, J = 2.7 Hz, 1H), 3.34-3.26 (m, 1H), 2.91 (dt, J = 10.1, 4.1 Hz, 1H), 2.31 (ddd, J = 14.2, 10.4, 5.2 Hz, 1H), 2.26-2.18 (m, 1H), 2.13 (ddd, J = 14.2, 10.1, 6.3 Hz, 1H), 2.07-1.69 (m, 11H), 1.65-1.25 (m, 17H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 54 NO6S [M-Na] - 580.4, found 580.4.

[1105]

[1106] NC40028

[1107] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.65 (t, J = 2.7 Hz, 1H), 3.35-3.26 (m, 1H), 3.05 (dd, J = 13.9, 5.5 Hz, 1H), 2.88 (dd, J = 13.9, 7.0 Hz, 1H), 2.22 (ddd, J = 13.8, 10.3, 5.2 Hz, 1H), 2.07 (ddd, J= 13.8, 10.0, 6.4 Hz, 1H), 2.03-1.69 (m, 8H), 1.63-1.24 (m, 16H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.3.

[1109]

[1110] NC40029

[1111] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.65 (t, J = 2.7 Hz, 1H), 3.35-3.27 (m, 1H), 3.05 (dd, J = 13.9, 5.6 Hz, 1H), 2.88 (dd, J = 13.9, 6.9 Hz, 1H), 2.23 (ddd, J = 13.8, 10.1, 5.1 Hz, 1H), 2.07 (ddd, J = 13.8, 9.8, 6.6 Hz, 1H), 2.03-1.70 (m, 8H), 1.63-1.25 (m, 16H), 1.24-1.05 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.87 (m, 6H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO6S [M-Na] - 540.3, found 540.3.

[1113]

[1114] NC40030

[1115] 1H NMR (500 MHz, CD3OD) δ 4.39-4.30 (m, 1H), 3.65 (t, J = 2.8 Hz, 1H), 3.35-3.26 (m, 1H), 3.03 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.3 Hz, 1H), 2.24 (ddd, J = 13.8, 10.1, 5.2 Hz, 1H), 2.09 (ddd, J = 13.8, 9.8, 6.7 Hz, 1H), 2.04-1.70 (m, 8H), 1.70-1.24 (m, 16H), 1.23-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.95-0.85 (m, 12H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 56 NO6S [M-Na] - 582.4, found 582.4.

[1117]

[1118] NC40031

[1119] 1 H NMR (500 MHz, CD3OD) δ 4.42-4.33 (m, 1H), 3.65 (t, J = 2.7 Hz, 1H), 3.35-3.26 (m, 1H), 3.01 (dd, J = 14.0, 5.6 Hz, 1H), 2.90 (dd, J = 14.0, 6.3 Hz, 1H), 2.22 (ddd, J = 14.1, 9.3, 5.1 Hz, 1H), 2.11 (ddd, J= 13.7, 9.0, 7.5 Hz, 1H), 2.04-1.70 (m, 8H), 1.70-1.24 (m, 16H), 1.23-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.95-0.86 (m, 12H), 0.69 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 56 NO6S [M-Na] - 582.4, found 582.4.

[1121]

[1122] NC40032

[1123] 1 H NMR (400 MHz, DMSO-d6) δ 7.79 (s, 1H), 4.28 (d, J = 4.7 Hz, 1H), 4.05 (d, J = 5.0 Hz, 1H), 3.49 (s, 1H), 3.17-3.06 (m, 1H), 2.71-2.57 (m, 2H), 2.04-1.55 (m, 9H), 1.55-0.74 (m, 29H), 0.62-0.50 (m, 5H); LCMS (ESI) m / z calcd for C 30 H 50 NO6S [M-Na] - 552.3, found 552.3.

[1125]

[1126] NC40033

[1127] 1H NMR (500 MHz, CD3OD) δ 3.87-3.40 (m, 6H), 3.35-3.24 (m, 1H), 2.47-2.17 (m, 4H), 2.06-1.69 (m, 8H), 1.64-1.25 (m, 13H), 1.24-1.06 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.71 (s, 1.5H), 0.70 (s, 1.5H); LCMS (ESI) m / z calcd for C 30 H 50 NO6S [M-Na] - 552.3, found 552.3.

[1129]

[1130] NC40034

[1131] 1 H NMR (500 MHz, CD3OD) δ 3.87-3.40 (m, 6H), 3.36-3.26 (m, 1H), 2.47-2.17 (m, 4H), 2.04-1.69 (m, 8H), 1.64-1.25 (m, 13H), 1.25-1.06 (m, 3H), 1.05-0.94 (m, 4H), 0.94-0.87 (m, 6H), 0.71 (s, 1.5H), 0.70 (s, 1.5H); LCMS (ESI) m / z calcd for C 30 H 50 NO6S [M-Na] - 552.3, found 552.3.

[1133]

[1134] NC40035

[1135] 1 H NMR (500 MHz, CD3OD) δ 3.81-3.75 (m, 1H), 3.73-3.68 (m, 1H), 3.65 (t, J= 2.7 Hz, 1H), 3.59-3.44 (m, 2H), 3.35-3.27 (m, 1H), 3.11-3.02 (m, 2H), 2.58-2.32 (m, 4H), 2.31 (s, 3H), 2.29 (s, 3H), 2.06-1.68 (m, 8H), 1.65-1.25 (m, 13H), 1.25-1.06 (m, 3H), 1.05-0.95 (m, 4H), 0.94-0.86 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 57 N2O6S [M-Na] - 597.4, found 597.4.

[1137]

[1138] NC40036

[1139] 1 H NMR (500 MHz, CD3OD) δ 8.52-8.41 (m, 2H), 7.81-7.76 (m, 0.6H), 7.76-7.71 (m, 0.4H), 7.51-7.45 (m, 0.4H), 7.43-7.37 (m, 0.6H), 4.84-4.81 (m, 1H), 4.72-7.62 (m, 1H), 3.85-3.70 (m, 2H), 3.68-3.62 (m, 1H), 3.36-3.26 (m, 1H), 3.12-3.03 (m, 2H), 2.64-2.54 (m, 0.6H), 2.51-2.37 (m, 1H), 2.35-2.25 (m, 0.4H), 2.04-1.67 (m, 8H), 1.64-1.05 (m, 16H), 1.05-0.95 (m, 3H), 0.94-0.85 (m, 7H), 0.69 (s, 1.8H), 0.66 (s, 1.2H); LCMS (ESI) m / z calcd for C 34 H 53 N2O6S [M-Na] -617.4, found 617.4.

[1141]

[1142] NC40037

[1143] 1 H NMR (500 MHz, CD3OD) δ 7.53-7.46 (m, 2H), 7.46-7.38 (m, 1H), 7.35-7.29 (m, 2H), 4.13-4.06 (m, 2H), 3.63 (s, 1H), 3.34-3.25 (m, 1H), 3.09-3.02 (m, 2H), 2.17-2.08 (m, 1H), 2.02-1.93 (m, 1H), 1.93-1.64 (m, 8H), 1.62-1.15 (m, 13H), 1.14-0.85 (m, 10H), 0.70 (d, J = 5.9 Hz, 3H), 0.62 (s, 3H); LCMS (ESI) m / z calcd for C 34 H 52 NO6S [M-Na] - 602.4, found 602.4.

[1146]

[1147] NC50002

[1148] 1 H NMR (400 MHz, DMSO-d6) δ 7.83 (t, J = 5.5 Hz, 1H), 4.29 (s, 1H), 4.08 (s, 1H), 3.93 (s, 1H), 3.77 (s, 1H), 3.48 (s, 1H), 3.23-3.16 (m, 2H), 3.15-3.08 (m, 1H), 2.32 (t, J = 6.9 Hz, 2H), 2.14-1.55 (m, 10H), 1.55-1.05 (m, 13H), 1.01-0.70 (m, 11H), 0.58 (s, 3H). ; LCMS (ESI) m / zcalcd for C 29 H 48 NO6[M-Na] - 506.3, found 506.3.

[1150]

[1151] NC50004

[1152] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.93 (m, 1H), 3.86-3.70 (m, 2H), 3.66 (t, J = 2.7 Hz, 1H), 3.35-3.26 (m, 1H), 3.13 (s, 1.5H), 3.08-3.00 (m, 2H), 2.93 (s, 1.5H), 2.53 (ddd, J = 15.4, 10.8, 5.1 Hz, 0.5H), 2.48-2.33 (m, 1H), 2.33-2.15 (m, 1.5H), 2.02 (td, J = 12.1, 7.4 Hz, 1H), 1.97-1.68 (m, 7H), 1.64-1.25 (m, 12H), 1.18-1.08 (m, 1H), 1.08-0.93 (m, 4H), 0.93-0.87 (m, 6H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.3.

[1154]

[1155] NC50005

[1156] 1 H NMR (400 MHz, DMSO-d6) δ 7.42-7.14 (m, 5H), 4.59 (s, 0.6H), 4.56-4.43 (m, 1.4H), 4.29 (d, J = 4.4 Hz, 1H), 4.13 (d, J= 3.4 Hz, 0.7H), 4.06 (d, J = 3.1 Hz, 0.3H), 3.97-3.90 (m, 1H), 3.81 (s, 0.7H), 3.74 (s, 0.3H), 3.54-3.39 (m, 3H), 3.17-3.06 (m, 1H), 2.66-2.54 (m, 2H), 2.46-1.91 (m, 4H), 1.89-1.58 (m, 6H), 1.54-1.04 (m, 13H), 1.02-0.74 (m, 11H), 0.60 (s, 2.1H), 0.56 (s, 0.9H); LCMS (ESI) m / z calcd for C 35 H 54 NO7S [M-Na] - 632.4, found 632.3.

[1158]

[1159] NC50006

[1160] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.94 (m, 1H), 3.90-3.79 (m, 1H), 3.77-3.64 (m, 4H), 3.59-3.53 (m, 1H), 3.52-3.43 (m, 1H), 3.35-3.26 (m, 1H), 3.13-3.04 (m, 2H), 2.58-2.45 (m, 1H), 2.43-2.30 (m, 1H), 2.24-2.15 (m, 1H), 2.05-1.68 (m, 8H), 1.65-1.26 (m, 12H), 1.20-0.94 (m, 5H), 0.94-0.86 (m, 6H), 0.76-0.67 (m, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO8S [M-Na] - 586.3, found 586.4.

[1162]

[1163] NC50007

[1164] 1 H NMR (500 MHz, CD3OD) δ 4.66-4.56 (m, 0.4H) and 4.25-4.13 (m, 0.6H), 3.98-3.93 (m, 1H), 3.72-3.58 (m, 3H), 3.36-3.26 (m, 1H), 3.09-3.02 (m, 2H), 2.51-2.41 (m, 1H), 2.38-2.27 (m, 1H), 2.25-2.15 (m, 1H), 2.08-1.97 (m, 1H), 1.96-1.68 (m, 7H), 1.65-1.23 (m, 16H), 1.20-1.08 (m, 3H), 1.08-0.95 (m, 4H), 0.94-0.86 (m, 6H), 0.723 (s, 1.8H), 0.720 (s, 1.2H); LCMS (ESI) m / z calcd for C 31 H 54 NO7S [M-Na] - 584.4, found 584.4.

[1166]

[1167] NC50008

[1168] 1 H NMR (500 MHz, CD3OD) δ 4.44 (tt, J= 12.1, 3.9 Hz, 0.5H), 4.06-3.91 (m, 3.5H), 3.78-3.69 (m, 1H), 3.69-3.62 (m, 2H), 3.53-3.41 (m, 2H), 3.37-3.24 (m, 1H), 3.09-3.00 (m, 2H), 2.55-2.44 (m, 1H), 2.41-2.31 (m, 1H), 2.25-2.15 (m, 1H), 2.08-1.64 (m, 11H), 1.64-1.25 (m, 13H), 1.17-0.95 (m, 5H), 0.94-0.87 (m, 6H), 0.72 (s, 1.5H), 0.71 (s, 1.5H); LCMS (ESI) m / z calcd for C 33 H 56 NO8S [M-Na] - 626.4, found 626.4.

[1170]

[1171] NC50009

[1172] 1 H NMR (400 MHz, DMSO-d6) δ 4.72 (d, J = 12.5 Hz, 0.5H), 4.34-4.23 (m, 1.5H), 4.15-4.07 (m, 1H), 4.03 (d, J = 13.4 Hz, 0.5H), 3.93 (t, J = 4.9 Hz, 1H), 3.83-3.72 (m, 1.5H), 3.48 (s, 1H), 3.18-3.07 (m, 1H), 3.00-2.89 (m, 0.5H), 2.87-2.75 (m, 0.5H), 2.42-1.92 (m, 7H), 1.90-1.08 (m, 22H), 1.02-0.73 (m, 11H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO7S [M-Na] -582.3, found 582.3.

[1175]

[1176] NC50010

[1177] 1 H NMR (500 MHz, CD3OD) δ 5.02 (d, J = 9.7 Hz, 0.5H), 4.45 (d, J = 12.9 Hz, 0.5H), 4.34-4.28 (m, 0.5H), 3.98-3.90 (m, 1.5H), 3.66 (t, J = 2.7 Hz, 1H), 3.35-3.27 (m, 1H), 3.23 (dd, J = 13.5, 11.2 Hz, 0.5H), 3.01 (td, J = 13.2, 2.8 Hz, 0.5H), 2.79 (tt, J = 11.3, 3.8 Hz, 0.5H), 2.75-2.65 (m, 1H), 2.59 (td, J = 12.6, 2.7 Hz, 0.5H), 2.54-2.26 (m, 3H), 2.20 (td, J = 12.1, 5.2 Hz, 1H), 2.02 (td, J = 11.9, 7.2 Hz, 1H), 1.97-1.67 (m, 9H), 1.64-1.26 (m, 13H), 1.18-1.09 (m, 1H), 1.09-0.95 (m, 4H), 0.95-0.87 (m, 6H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO7S [M-Na] - 582.3, found 582.4.

[1179]

[1180] NC50011

[1181] 1H NMR (400 MHz, DMSO-d6) δ 4.37 (d, J = 13.0 Hz, 1H), 4.29 (d, J = 4.3 Hz, 1H), 4.10 (d, J = 3.4 Hz, 1H), 3.96-3.90 (m, 1H), 3.85 (d, J = 13.5 Hz, 1H), 3.79 (s, 1H), 3.48 (s, 1H), 3.18-3.06 (m, 1H), 2.99-2.87 (m, 1H), 2.48-2.37 (m, 2H), 2.36-2.04 (m, 3H), 2.04-1.55 (m, 9H), 1.54-1.07 (m, 15H), 1.04-0.75 (m, 11H), 0.59 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52 NO7S [M-Na] - 582.3, found 582.3.

[1183]

[1184] NC50012

[1185] 1 H NMR (400 MHz, DMSO-d6) δ 4.30 (d, J = 4.3 Hz, 1H), 4.21-4.09 (m, 2H), 4.05-3.97 (m, 1H), 3.94 (d, J = 4.9 Hz, 1H), 3.85 (t, J = 9.0 Hz, 1H), 3.81-3.71 (m, 2H), 3.48 (s, 1H), 3.45-3.38 (m, 1H), 3.17-3.06 (m, 1H), 2.15-1.06 (m, 23H), 1.00-0.74 (m, 11H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 48 NO7S [M-Na] -554.3, found 554.3.

[1187]

[1188] NC50013

[1189] 1 H NMR (500 MHz, CD3OD) δ 3.97-3.93 (m, 1H), 3.66 (t, J = 2.7 Hz, 1H), 3.35-3.27 (m, 1H), 3.20-3.12 (m, 2H), 2.26-2.15 (m, 2H), 2.10-1.96 (m, 2H), 1.96-1.70 (m, 7H), 1.64-1.24 (m, 18H), 1.12 (qd, J = 12.0, 5.9 Hz, 1H), 1.05-0.95 (m, 4H), 0.91 (d, J = 6.7 Hz, 6H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 52 NO7S [M-Na] - 570.3, found 570.3.

[1191]

[1192] NC50014

[1193] 1 H NMR (500 MHz, CD3OD) δ 7.29-7.22 (m, 4H), 7.21-7.14 (m, 1H), 4.53-4.44 (m, 1H), 3.96-3.91 (m, 1H), 3.66 (t, J = 2.8 Hz, 1H), 3.36-3.26 (m, 1H), 3.16 (dd, J = 13.7, 6.0 Hz, 1H), 3.04-2.95 (m, 2H), 2.88 (dd, J= 13.7, 8.1 Hz, 1H), 2.24-2.13 (m, 2H), 2.07-1.96 (m, 2H), 1.96-1.63 (m, 7H), 1.63-1.18 (m, 12H), 1.17-1.05 (m, 1H), 1.05-0.95 (m, 4H), 0.95-0.86 (m, 6H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 35 H 54 NO7S [M-Na] - 632.4, found 632.4.

[1195]

[1196] NC50015

[1197] 1 H NMR (400 MHz, DMSO-d6) δ 7.70 (d, J = 7.5 Hz, 1H), 7.29-7.11 (m, 5H), 4.29 (d, J = 4.3 Hz, 1H), 4.17-4.06 (m, 2H), 3.93 (d, J = 4.9 Hz, 1H), 3.78 (s, 1H), 3.49 (s, 1H), 3.17-3.07 (m, 2H), 2.75 (dd, J = 13.3, 6.9 Hz, 1H), 2.53-2.51 (m, 2H), 2.15-1.05 (m, 23H), 1.00-0.75 (m, 11H), 0.57 (s, 3H); LCMS (ESI) m / z calcd for C 35 H 54 NO7S [M-Na] - 632.4, found 632.4.

[1200]

[1201] NC50016

[1202] 1H NMR (500 MHz, CD3OD) δ 4.24-4.17 (m, 1H), 3.98-3.93 (m, 1H), 3.66 (t, J = 2.7 Hz, 1H), 3.34-3.27 (m, 1H), 2.98-2.92 (m, 2H), 2.30 (ddd, J = 13.7, 10.5, 5.1 Hz, 1H), 2.24-1.97 (m, 4H), 1.97-1.70 (m, 7H), 1.64-1.26 (m, 12H), 1.12 (qd, J = 12.0, 5.8 Hz, 1H), 1.06-0.95 (m, 4H), 0.95-0.87 (m, 12H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 54 NO7S [M-Na] - 584.4, found 584.4.

[1204]

[1205] NC50017

[1206] 1 H NMR (500 MHz, CD3OD) δ 4.27-4.20 (m, 1H), 3.98-3.93 (m, 1H), 3.66 (t, J = 2.8 Hz, 1H), 3.35-3.27 (m, 1H), 2.97-2.91 (m, 2H), 2.27 (ddd, J = 14.2, 9.6, 4.9 Hz, 1H), 2.23-2.11 (m, 2H), 2.08-1.96 (m, 2H), 1.96-1.69 (m, 7H), 1.65-1.24 (m, 12H), 1.17-1.06 (m, 1H), 1.06-0.96 (m, 4H), 0.95-0.85 (m, 12H), 0.70 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 54 NO7S [M-Na]- 584.4, found 584.3.

[1208]

[1209] NC50018

[1210] 1 H NMR (500 MHz, CD3OD) δ 7.37-7.27 (m, 4H), 7.24-7.18 (m, 1H), 5.34 (dd, J = 9.9, 3.8 Hz, 1H), 3.98-3.92 (m, 1H), 3.66 (d, J = 2.8 Hz, 1H), 3.34-3.29 (m, 1H), 3.29-3.23 (m, 1H), 3.10 (dd, J = 14.3, 3.8 Hz, 1H), 2.32 (ddd, J = 13.8, 10.1, 5.0 Hz, 1H), 2.23-2.12 (m, 2H), 2.05-1.95 (m, 1H), 1.95-1.68 (m, 7H), 1.63-1.20 (m, 12H), 1.15-1.05 (m, 1H), 1.05-0.96 (m, 4H), 0.94-0.85 (m, 6H), 0.68 (s, 3H). ; LCMS (ESI) m / z calcd for C 34 H 52 NO7S [M-Na] - 618.3, found 618.3.

[1212]

[1213] NC50019

[1214] 1 H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J = 6.3 Hz, 1H), 7.28-7.19 (m, 4H), 7.18-7.10 (m, 1H), 5.03-4.94 (m, 1H), 4.30 (d, J = 4.3 Hz, 1H), 4.11 (d, J= 3.5 Hz, 1H), 3.93 (d, J = 4.9 Hz, 1H), 3.79 (s, 1H), 3.48 (s, 1H), 3.17-3.06 (m, 1H), 2.85 (dd, J = 13.9, 9.2 Hz, 1H), 2.67 (dd, J = 13.8, 4.0 Hz, 1H), 2.15-1.91 (m, 4H), 1.90-1.56 (m, 6H), 1.54-1.03 (m, 13H), 0.99-0.75 (m, 11H), 0.56 (s, 3H); LCMS (ESI) m / z calcd for C 34 H 52 NO7S [M-Na] - 618.3, found 618.3.

[1216]

[1217] NC50021

[1218] 1 H NMR (500 MHz, CD3OD) δ 4.52-4.45 (m, 0.5H), 4.45-4.38 (m, 0.5H), 3.99-3.93 (m, 1H), 3.66 (t, J = 2.8 Hz, 1H), 3.59-3.53 (m, 0.5H), 3.51-3.26 (m, 3H), 3.02-2.92 (m, 1H), 2.74 (dd, J = 13.3, 10.6 Hz, 0.5H), 2.50-2.39 (m, 2H), 2.35 (ddd, J = 15.3, 10.6, 5.1 Hz, 0.5H), 2.28-2.15 (m, 1.5H), 2.11-1.70 (m, 11H), 1.64-1.27 (m, 12H), 1.18-0.95 (m, 5H), 0.95-0.86 (m, 6H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 31 H 52NO7S [M-Na] - 582.3, found 582.3.

[1220]

[1221] NC50023

[1222] 1 H NMR (500 MHz, CD3OD) δ 3.97-3.93 (m, 1H), 3.66 (t, J = 2.7 Hz, 1H), 3.58 (dd, J = 13.7, 5.8 Hz, 1H), 3.42 (dd, J = 13.7, 7.2 Hz, 1H), 3.36-3.27 (m, 1H), 2.99-2.90 (m, 1H), 2.28 (ddd, J = 13.8, 10.2, 5.0 Hz, 1H), 2.23-2.08 (m, 2H), 2.01 (td, J = 12.1, 7.4 Hz, 1H), 1.96-1.69 (m, 7H), 1.64-1.47 (m, 6H), 1.47-1.24 (m, 9H), 1.12 (qd, J = 12.1, 5.8 Hz, 1H), 1.05-0.94 (m, 4H), 0.94-0.86 (m, 6H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.2.

[1224]

[1225] NC50024

[1226] 1 H NMR (500 MHz, CD3OD) δ 4.34-4.26 (m, 1H), 3.95 (t, J= 3.0 Hz, 1H), 3.76-3.64 (m, 3H), 3.35-3.27 (m, 1H), 3.14-3.07 (m, 1H), 3.06-2.99 (m, 1H), 2.34-2.24 (m, 1H), 2.24-2.08 (m, 2H), 2.06-1.96 (m, 1H), 1.96-1.70 (m, 7H), 1.64-1.47 (m, 6H), 1.47-1.27 (m, 6H), 1.18-1.07 (m, 1H), 1.06-0.95 (m, 4H), 0.94-0.86 (m, 6H), 0.72 (d, J = 1.1 Hz, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO8S [M-Na] - 572.3, found 572.2.

[1228]

[1229] NC50027

[1230] 1 H NMR (500 MHz, CD3OD) δ 4.33-4.27 (m, 1H), 3.99-3.93 (m, 1H), 3.69-3.64 (m, 1H), 3.34-3.27 (m, 1H), 2.91 (dt, J = 10.1, 4.1 Hz, 1H), 2.33 (ddd, J = 14.2, 10.2, 5.1 Hz, 1H), 2.27-2.09 (m, 3H), 2.06-1.70 (m, 11H), 1.64-1.27 (m, 16H), 1.18-1.06 (m, 1H), 1.06-0.94 (m, 4H), 0.94-0.86 (m, 6H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 54 NO7S [M-Na] - 596.4, found 596.3.

[1232]

[1233] NC50028

[1234] 1 H NMR (400 MHz, DMSO-d6) δ 7.68 (d, J = 7.5 Hz, 1H), 4.30 (d, J = 4.2 Hz, 1H), 4.10 (d, J = 3.4 Hz, 1H), 4.04-3.91 (m, 2H), 3.78 (s, 1H), 3.48 (s, 1H), 3.18-3.06 (m, 1H), 2.60 (dd, J = 13.4, 4.6 Hz, 1H), 2.45 (dd, J = 13.4, 8.0 Hz, 1H), 2.14-1.06 (m, 26H), 1.02-0.74 (m, 11H), 0.58 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.2.

[1236]

[1237] NC50029

[1238] 1 H NMR (500 MHz, CD3OD) δ 4.37-4.27 (m, 1H), 3.97-3.93 (m, 1H), 3.66 (t, J = 2.8 Hz, 1H), 3.34-3.27 (m, 1H), 3.05 (dd, J = 13.9, 5.5 Hz, 1H), 2.88 (dd, J = 13.9, 7.0 Hz, 1H), 2.29-2.15 (m, 2H), 2.13-1.97 (m, 2H), 1.97-1.69 (m, 7H), 1.64-1.47 (m, 6H), 1.47-1.26 (m, 9H), 1.12 (qd, J= 11.9, 5.7 Hz, 1H), 1.05-0.94 (m, 4H), 0.93-0.87 (m, 6H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 29 H 50 NO7S [M-Na] - 556.3, found 556.2.

[1240]

[1241] NC50030

[1242] 1 H NMR (500 MHz, CD3OD) δ 4.39-4.30 (m, 1H), 3.99-3.92 (m, 1H), 3.66 (t, J = 2.6 Hz, 1H), 3.35-3.26 (m, 1H), 3.03 (dd, J = 14.0, 5.5 Hz, 1H), 2.90 (dd, J = 14.0, 6.4 Hz, 1H), 2.30-2.15 (m, 2H), 2.15-2.06 (m, 1H), 2.06-1.97 (m, 1H), 1.97-1.25 (m, 22H), 1.18-1.06 (m, 1H), 1.05-0.85 (m, 16H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 56 NO7S [M-Na] - 598.4, found 598.4.

[1244]

[1245] NC50031

[1246] 1 H NMR (400 MHz, DMSO-d6) δ 7.55 (d, J = 8.6 Hz, 1H), 4.30 (d, J= 4.3 Hz, 1H), 4.13-4.02 (m, 2H), 3.94 (d, J = 4.9 Hz, 1H), 3.78 (s, 1H), 3.48 (s, 1H), 3.17-3.06 (m, 1H), 2.59 (dd, J = 13.5, 4.5 Hz, 1H), 2.49-2.41 (m, 1H), 2.14-1.86 (m, 4H), 1.87-1.05 (m, 22H), 1.03-0.72 (m, 17H), 0.57 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 56 NO7S [M-Na] - 598.4, found 598.4.

[1248]

[1249] NC50032

[1250] 1 H NMR (500 MHz, CD3OD) δ 3.96-3.92 (m, 1H), 3.66 (t, J = 2.7 Hz, 1H), 3.34-3.25 (m, 1H), 3.03 (s, 2H), 2.27-2.14 (m, 2H), 2.11-1.96 (m, 2H), 1.96-1.70 (m, 7H), 1.64-1.24 (m, 12H), 1.11 (qd, J = 12.0, 5.8 Hz, 1H), 1.05-0.86 (m, 12H), 0.81-0.76 (m, 2H), 0.71 (s, 3H); LCMS (ESI) m / z calcd for C 30 H 50 NO7S [M-Na] - 568.3, found 568.3.

[1252]

[1253] NC50033

[1254] 1 H NMR (500 MHz, CD3OD) δ 4.00-3.91 (m, 1H), 3.89-3.40 (m, 6H), 3.36-3.25 (m, 1H), 2.47-2.15 (m, 5H), 2.07-1.97 (m, 1H), 1.97-1.70 (m, 7H), 1.64-1.27 (m, 12H), 1.13 (qd, J = 11.9, 5.3 Hz, 1H), 1.07-0.94 (m, 4H), 0.94-0.86 (m, 6H), 0.73 (s, 1.5H), 0.72 (s, 1.5H); LCMS (ESI) m / z calcd for C 30 H 50 NO7S [M-Na] - 568.3, found 568.3.

[1256]

[1257] NC50034

[1258] 1 H NMR (500 MHz, CD3OD) δ 3.95 (d, J = 2.3 Hz, 1H), 3.88-3.40 (m, 6H), 3.34-3.26 (m, 1H), 2.47-2.15 (m, 5H), 2.08-1.97 (m, 1H), 1.97-1.70 (m, 7H), 1.64-1.26 (m, 12H), 1.13 (qd, J = 11.7, 5.2 Hz, 1H), 1.07-0.93 (m, 4H), 0.93-0.86 (m, 6H), 0.73 (s, 1.5H), 0.72 (s, 1.5H); LCMS (ESI) m / z calcd for C 30 H 50 NO7S [M-Na] - 568.3, found 568.3.

[1260]

[1261] NC50035

[1262] 1 H NMR (500 MHz, CD3OD) δ 3.98-3.93 (m, 1H), 3.81-3.75 (m, 1H), 3.73-3.68 (m, 1H), 3.66 (t, J = 2.8 Hz, 1H), 3.59-3.45 (m, 2H), 3.35-3.27 (m, 1H), 3.11-3.02 (m, 2H), 2.58-2.32 (m, 4H), 2.31 (s, 3H), 2.28 (s, 3H), 2.20 (td, J = 12.3, 5.2 Hz, 1H), 2.02 (td, J = 12.1, 7.4 Hz, 1H), 1.97-1.70 (m, 7H), 1.64-1.27 (m, 12H), 1.18-0.96 (m, 5H), 0.94-0.87 (m, 6H), 0.72 (s, 3H); LCMS (ESI) m / z calcd for C 32 H 57 N2O7S [M-Na] - 613.4, found 613.4.

[1264]

[1265] NC50036

[1266] 1 H NMR (400 MHz, DMSO-d6) δ 8.51-8.40 (m, 2H), 7.62-7.55 (m, 1H), 7.43-7.38 (m, 0.4H), 7.36-7.31 (m, 0.6H), 4.66 (s, 0.4H), 4.59-4.46 (m, 1.6H), 4.29 (d, J= 4.3 Hz, 1H), 4.15-4.05 (m, 1H), 3.97-3.91 (m, 1H), 3.83-3.72 (m, 1H), 3.56-3.38 (m, 3H), 3.18-3.06 (m, 1H), 2.68-2.54 (m, 2H), 2.46-2.37 (m, 1H), 2.37-2.24 (m, 1H), 2.14-1.91 (m, 2H), 1.90-1.57 (m, 6H), 1.56-1.08 (m, 13H), 1.03-0.74 (m, 11H), 0.59 (s, 1.8H), 0.56 (s, 1.2H); LCMS (ESI) m / z calcd for C 34 H 53 N2O7S [M-Na] - 633.4, found 633.4.

[1268]

[1269] NC50037

[1270] 1 H NMR (500 MHz, CD3OD) δ 7.52-7.46 (m, 2H), 7.45-7.38 (m, 1H), 7.35-7.29 (m, 2H), 4.13-4.06 (m, 2H), 3.85 (s, 1H), 3.64 (s, 1H), 3.34-3.25 (m, 1H), 3.09-3.03 (m, 2H), 2.20-2.10 (m, 2H), 2.04-1.65 (m, 9H), 1.60-1.34 (m, 8H), 1.33-1.14 (m, 4H), 1.13-0.84 (m, 8H), 0.77 (d, J = 6.1 Hz, 3H), 0.64 (s, 3H); LCMS (ESI) m / z calcd for C 34 H 52 NO7S [M-Na] - 618.3, found 618.4.

[1273] <Experimental Example 1> Taurine-Bile Acid Derivative Evaluation of anti-inflammatory efficacy 1

[1274] To evaluate anti-inflammatory efficacy, inflammatory responses were induced in J774A.1 (Mouse BALB / c monocyte macrophage cell line) cells derived from mouse macrophages using lipopolysaccharide (LPS) and adenosine triphosphate (LPS+ATP), and the inhibitory effect of taurine-bile acid derivatives on the production of inflammatory cytokines (IL-1β, TNF-α) was measured. After treating J774A.1 cells with 1 μM of taurine-bile acid derivatives, the degree of inhibition of TNF-α secretion was measured in the group induced with LPS, while the degree of inhibition of IL-1β secretion was measured in the group induced with LPS+ATP. The cytokine production inhibitory ability of taurine-bile acid derivatives was expressed as a grade relative to taurodeoxycholic acid, a positive control. The grading criteria are A: greater than 100%, B: 50% or more and 100% or less, C: 20% or more and less than 50%, and D: less than 20%. The measurement results are as shown in Table 1 below.

[1275] Inflammatory cytokine production inhibition grade Compound Code TNF-α production inhibition grade IL-1β production inhibition grade NC10001 D A NC10002 A A NC10003 A A NC10004 C B NC10005 D C NC10006 D B NC10007 B B NC10008 A A NC10009 A A NC10010 A A NC10011 A A NC10012 A A NC10013 D B NC10014 D D NC10015 D D NC10016 A A NC10017 A A NC10018 B C NC10019 D C NC10021 - - NC10022 C B NC10024 D A NC10025 - - NC10026 D A NC10027 D A NC10028 D A NC10029 D A NC10031 D D NC10032 D B NC10033 D B NC10034 - - NC10035 D B NC10036 D A NC10037 D B NC10038 D B NC10039 C B NC10040 D D NC10041 D D NC10042 D D NC10043 D A NC10045 D B NC10046 D B NC10047 D C NC10048 D B NC10049 D A NC10050 D A NC10051 D B NC10052 B B NC10053 B B NC10054 D B NC10055 D B NC10056 C B NC10058 D A NC10059 D A NC10060 D B NC10061 D A NC10062 D A NC10063 D A NC10064 D D NC10065 D A NC10066 D A NC10067 D D NC10068 D A NC10069 D A NC10070 B A NC10071 D A NC10072 D C NC10073 D B NC10074 D A NC10075 D B NC10076 D A NC10077 D A NC10078 D A NC10079 C A NC10080 D A NC10081 A A NC10082 A A NC10083 A A NC10084 D D NC10085 D D NC10086 D D NC10087 A A NC10088 C D NC10089 D C NC10090 D D NC10091 A A NC10092 - - NC10093 - - NC20002 B B NC20003 B C NC20004 D A NC20005 D A NC20006 D A NC20007 D A NC20008 D A NC20009 D D NC20010 D B NC20011 D B NC20012 D A NC20013 D A NC20014 D A NC20015 D A NC20016 D A NC20017 D B NC20018 D D NC20019 D D NC20020 B C NC20021 D D NC20022 D D NC20023 D D NC20024 D C NC20025 D D NC20026 D B NC20027 D A NC20028 D D NC20029 D D NC20030 D D NC20031 D B NC20032 D B NC20033 D C NC20034 D D NC20035 D D NC20036 D D NC20037 D B NC30002 D B NC30004 C C NC30005 - - NC30006 D D NC30007 - - NC30008 D B NC30009 B C NC30010 A B NC30011 D D NC30012 D C NC30013 B B NC30014 D C NC30015 D D NC30016 C C NC30017 D D NC30018 D D NC30019 D D NC30020 D C NC30021 - - NC30022 C C NC30023 A B NC30024 - - NC30025 A D NC30026 - - NC30027 A A NC30028 D D NC30029 D C NC30030 D C NC30031 D C NC30032 - - NC30033 D C NC30034 D D NC30035 A A NC30036 - - NC30037 C A NC40002 D C NC40003 - - NC40004 D B NC40005 - - NC40006 C B NC40007 D B NC40008 A A NC40009 D D NC40010 B D NC40011 D C NC40012 D B NC40013 D A NC40014 D A NC40015 D A NC40016 - - NC40017 D C NC40018 D A NC40019 D A NC40020 D A NC40021 D B NC40022 C C NC40023 D D NC40024 D D NC40025 C C NC40026 - - NC40027 D B NC40028 D B NC40029 D D NC40030 D D NC40031 D D NC40032 D D NC40033 A A NC40034 C A NC40035 D A NC40036 D B NC40037 D C NC50002 - - NC50004 D D NC50005 - - NC50006 D D NC50007 D A NC50008 D A NC50009 - - NC50010 D A NC50011 - - NC50012 D A NC50013 D A NC50014 - - NC50015 D A NC50016 D A NC50017 - - NC50018 D B NC50019 D B NC50021 D C NC50023 - - NC50024 D C NC50027 D C NC50028 D B NC50029 D B NC50030 D B NC50031 D B NC50032 D B NC50033 D C NC50034 D C NC50035 - - NC50036 D D NC50037 D B

[1277] <Experimental Example 2> Taurine-Bile Acid Derivative Evaluation of anti-inflammatory efficacy 2

[1278] To evaluate the anti-inflammatory efficacy, human monocytic cell line U937 cells were differentiated into macrophages using PMA (phorbol 12-myristate 13-acetate), and then an inflammatory response was induced using Pam2CSK4 (Pam2CysSerLys4) or BzATP (2′(3′)-O-(4-Benzoylbenzoyl)adenosine 5′-triphosphate) to measure the inhibitory effect of taurine-bile acid derivatives on the production of inflammatory cytokines (IL-1β, TNF-α). In the experimental group in which U937 cells were differentiated into macrophages using PMA and treated with taurine-bile acid derivatives followed by an inflammatory response induced with Pam2CSK4, the degree of inhibition of TNF-α secretion among cytokines was measured, and in the experimental group in which an inflammatory response was induced with BzATP, the degree of inhibition of IL-1β secretion among cytokines was measured. The cytokine production inhibitory ability of taurine-bile acid derivatives is IC 50 (μM) values ​​were expressed as grades. The grading criteria for TNFα inhibitory ability are A: <0.5, B: 0.5 or more but <1.0, C: 1.0 or more but <2.0, D: 2.0 or more, and the grading criteria for IL-1β inhibitory ability are A: <0.05, B: 0.05 or more but <0.10, C: 0.10 or more but <0.20, D: 0.20 or more. The measurement results are shown in Table 2 below.

[1279] Inflammatory cytokine production inhibition grade Compound Code TNF-α production inhibition grade IL-1β production inhibition grade NC10001 D A NC10002 A A NC10003 A A NC10004 D D NC10005 C C NC10006 B D NC10007 D A NC10008 A A NC10009 A A NC10010 A A NC10011 A A NC10012 A A NC10013 B B NC10014 C A NC10015 D A NC10016 A A NC10017 B A NC10018 D B NC10019 B D NC10021 C B NC10022 B C NC10024 C B NC10025 C B NC10026 C A NC10027 B A NC10028 D B NC10029 D B NC10031 D B NC10032 D B NC10033 B C NC10034 B B NC10035 B D NC10036 D C NC10037 A D NC10038 D B NC10039 B B NC10040 C D NC10041 B D NC10042 B D NC10043 A C NC10045 A B NC10046 A C NC10047 B C NC10048 A B NC10049 A A NC10050 A B NC10051 C B NC10052 C B NC10053 C B NC10054 C B NC10055 C A NC10056 D B NC10058 D A NC10059 C A NC10060 D D NC10061 B C NC10062 B A NC10063 B A NC10064 A A NC10065 C C NC10066 C A NC10067 C D NC10068 A A NC10069 A A NC10070 A A NC10071 A A NC10072 A A NC10073 A B NC10074 A B NC10075 A C NC10076 D B NC10077 A A NC10078 A A NC10079 B A NC10080 B C NC10081 B A NC10082 A A NC10083 B A NC10084 A D NC10085 D D NC10086 A D NC10087 B A NC10088 A D NC10089 A D NC10090 B D NC10091 B A NC10092 D B NC10093 D C NC20002 D C NC20003 - B NC20004 B A NC20005 B B NC20006 C A NC20007 C A NC20008 B B NC20009 D A NC20010 C A NC20011 D B NC20012 B A NC20013 C A NC20014 B A NC20015 A A NC20016 C A NC20017 A D NC20018 C D NC20019 C B NC20020 D A NC20021 C B NC20022 C A NC20023 D B NC20024 A D NC20025 D D NC20026 C C NC20027 D A NC20028 C D NC20029 A B NC20030 A D NC20031 A B NC20032 D A NC20033 C B NC20034 C B NC20035 C B NC20036 B B NC20037 A A NC30002 C C NC30004 C D NC30005 B D NC30006 B D NC30007 A D NC30008 B D NC30009 B D NC30010 B A NC30011 B D NC30012 D D NC30013 B D NC30014 B D NC30015 A D NC30016 A D NC30017 D D NC30018 D D NC30019 C D NC30020 D D NC30021 B B NC30022 D D NC30023 D D NC30024 C D NC30025 C D NC30026 A D NC30027 B A NC30028 B D NC30029 B D NC30030 B D NC30031 B D NC30032 B D NC30033 B B NC30034 B D NC30035 B A NC30036 C D NC30037 D A NC40002 D D NC40003 D D NC40004 D D NC40005 D D NC40006 C D NC40007 C D NC40008 A A NC40009 C C NC40010 B D NC40011 B D NC40012 B D NC40013 C A NC40014 B A NC40015 B B NC40016 B D NC40017 B D NC40018 A A NC40019 C C NC40020 C C NC40021 B D NC40022 B D NC40023 B D NC40024 B D NC40025 B B NC40026 B B NC40027 D D NC40028 C C NC40029 C D NC40030 C D NC40031 C D NC40032 C D NC40033 A A NC40034 A A NC40035 A B NC40036 C B NC40037 B B NC50002 D D NC50004 D C NC50005 C D NC50006 D A NC50007 C B NC50008 B A NC50009 C C NC50010 D C NC50011 D D NC50012 C A NC50013 C A NC50014 B A NC50015 C B NC50016 B B NC50017 C B NC50018 D B NC50019 C D NC50021 B D NC50023 D D NC50024 D D NC50027 C D NC50028 C D NC50029 B D NC50030 D C NC50031 D B NC50032 D B NC50033 C B NC50034 D B NC50035 D D NC50036 D D NC50037 D D

Claims

Claim 1 Any one compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , and . Claim 2 Any one compound selected from the group consisting of the following compounds or a pharmaceutically acceptable salt thereof: , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , , , , , , , , , ; , , , , , , , , , , , , , , , , , , , and .(here, Na + can be replaced with other pharmaceutically acceptable salts) Claim 3 A pharmaceutical composition for treating inflammatory diseases comprising the compound of claim 1 or 2 or a pharmaceutically acceptable salt thereof. Claim 4 delete Claim 5 delete Claim 6 delete Claim 7 delete Claim 8 delete Claim 9 delete Claim 10 delete Claim 11 delete Claim 12 delete Claim 13 delete Claim 14 delete Claim 15 delete Claim 16 delete Claim 17 delete Claim 18 delete Claim 19 delete Claim 20 delete Claim 21 delete Claim 22 delete Claim 23 delete Claim 24 delete Claim 25 delete Claim 26 delete Claim 27 delete Claim 28 delete Claim 29 delete Claim 30 delete Claim 31 delete

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