TW201204731A - Pyrrolopyrazine kinase inhibitors - Google Patents

Abstract

The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables Q and R, R2, and R3 are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.

Description

201204731 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to the use of novel pyrrolopyrazine derivatives which are JAK and SYK inhibitors and which selectively inhibit JAK3 and are suitable for use. For the treatment of autoimmune diseases and inflammatory diseases. [Prior Art] Protein kinases constitute one of the largest family of human enzymes, and a variety of different signaling processes are regulated by the addition of a cleavage acid group to proteins; in particular, tyrosine kinases allow protein phosphorylation on the alcohol portion of tyrosine residues. Chemical. The tyrosine kinase family includes members that control cell growth, migration, and differentiation. Abnormal kinase activity is associated with a variety of human diseases' such human diseases include cancer, autoimmune diseases, and inflammatory diseases. Since protein kinases are key regulators of cell signaling, they provide a means of modulating cell function with small molecule inhibitors of kinase activity, making them a good drug design goal. In addition to treating kinase-mediated disease processes, selective and potent inhibitors of kinase activity are also useful for studying cellular signaling processes and identifying other cellular targets of therapeutic importance. JAK (Janus Kinase) is a cytoplasmic protein tyrosine kinase steroid, which includes JAK1, JAK2, JAK3, and TYK2. Each JAK preferentially binds to the intracytoplasmic portion of an individual cytokine receptor/state (10)(10)/· 16 (1998), pp. 293_322). JAK is activated after binding to the ligand and initiates signaling by phosphorylating a cytokine receptor that lacks its intrinsic kinase activity. This phosphorylation produces a docking site at the receptor called the STAT protein (signal transducer and transcriptional activator) at 156090.doc 201204731, and the phosphorylated JAK binds to various STAT proteins. The STAT protein or STAT is a specific DNA sequence that is present in the promoter of a cytokine-responsive gene by acidifying the live H DlsTA binding protein from the SI-amino acid residue # and acting as a signaling molecule and transcription factor (Leonard Et al, (2000), J. Allergy Clin. Immunol. 105: 877-888) ° JAK/STAT signaling with a variety of abnormal immune responses (such as allergies, asthma), autoimmune diseases (such as transplantation (allograft) It is mediated by rejection, rheumatoid arthritis, amyotrophic lateral sclerosis, and multiple sclerosis, and is associated with solid malignant conditions and hematological malignancies such as leukemia and lymphoma. Thus, JAK and STAT are components of multiple possible entangled signal transduction pathways (2000), pp. 5662-5679), which indicates that one of the elements of the JAK-STAT pathway is specifically targeted without interfering with other signals. The transduction path is difficult. JAK kinases (including JAK3) are abundantly expressed in primary leukemia cells of children with acute lymphoblastic white disease (the most common form of childhood cancer), and studies have shown that STAT activation and regulation of cell death in some cells The signal of death is related (Demoulin et al. (1996), Mol. Cell. Biol. 16:4710-6; Jurlander et al., (1997), Blood. 89: 4146-52; Kaneko et al., (1997), Clin·Exp. Immun. 109:185-193; and Nakamura et al. (1996), J. Biol. Chem. 271: 19483-8). It is also known to be important for lymphocyte differentiation, function and survival. JAK3 plays a major role in the function of lymphocytes, macrophages and mast cells. Given the importance of this JAK kinase, compounds that modulate the JAK pathway (comprises 156090.doc 201204731 to compounds that are selective for JAK3) can be used to treat diseases or conditions involving the function of lymphocytes, macrophages or mast cells (Kudlacz Et al., (2004) Am. J. Transplant 4: 51-57; Changelian (2003) Science 302: 875-878). Conditions that target the JAK pathway or modulate JAK kinase (especially JAK3) for therapeutic efficacy include leukemia, lymphoma, transplant rejection (eg, islet transplant rejection, bone marrow transplantation applications (eg, graft versus host disease)), Immune diseases (such as diabetes) and inflammation (such as asthma, allergic reactions). The conditions that may benefit from inhibition of JAK3 are described in more detail below. However, the performance of JAK3 is more limited and controlled than the relatively broad performance of JAK1, JAK2 and Tyk2. Although a variety of cytokine receptors use some JAK (JAK1, JAK2, Tyk2), JAK3 is only used by cytokines containing yc in the receptor. Thus, JAK3 plays a role in the cytokine signaling of the following cytokines, which have been shown to use a common gamma chain to date: IL-2, IL-4, IL-7, IL-9, IL -15 and IL-21. JAK1 interacts with receptors for the cytokines IL-2, IL-4, IL-7, IL-9 and IL-21, while JAK2 interacts with receptors for IL-9 and TNF-ot. After certain cytokines (such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21) bind to their receptors, the receptors are recruited, allowing the combined JAK The cytoplasmic tail of the kinase approaches and promotes acidification of the tyrosine residues on the JAK kinase. This trans-acidification activates the JAK kinase. Animal studies have shown that JAK3 not only plays a key role in the maturation of B lymphocytes and T lymphocytes, but also is required to maintain T cell function in composition. Modulation of immunological activity by this novel mechanism may prove useful for the treatment of T-156090.doc 201204731 cell proliferative disorders, such as transplant rejection and autoimmune diseases. In particular, JAK3 is associated with a variety of biological processes. For example, proliferation and survival of murine mast cells induced by IL-4 and IL-9 have been shown to be dependent on JAK3 signaling and gamma chain signaling (Suzuki et al. (2000), Blood 96: 2172-2180). . JAK3 also plays a key role in IgE receptor-mediated mast cell degranulation (Malaviya et al., (1999), Ugly 1^111· Biophys. Res. Commun. 257:807-813), and inhibition JAK3 kinase has been shown to prevent type I allergic reactions, including systemic allergic reactions (Malaviya # et al, (1999), J. Biol. Chem. 274:27028-27038). JAK3 inhibition has also been shown to produce immunosuppression of allograft rejection (Kirken, (2001), Transpl. Proc. 33: 3268-3270). JAK3 kinase is also involved in the following mechanisms: early and late rheumatoid arthritis (Muller-Ladner et al, (2000), J. Immunal 164:3894-3901); familial amyotrophic lateral sclerosis (Trieu et al, (2000), Biochem Biophys. Res. Commun. 267: 22-25); Leukemia (Sudbeck et al, (1999), Clin. Cancer Res. 5: 1569-1582); ® Mycosis fungoides , a form of T-cell lymphoma (Nielsen et al, (1997), Prac. Natl. Acad. Sci. USA 94:6764-6769); and abnormal cell growth (Yu et al, (1997), J. Immunol. 159: 5206-5210; Catlett-Falcone et al. (1999), Immunity 10: 105-115). JAK3 inhibitors as immunosuppressants have become effective treatments for organ transplantation, xenograft, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, I diabetes and diabetes complications, cancer, asthma, atopic Dermatitis, autoimmune verrucous disorder, ulcerative knot 156090.doc 201204731 Enteritis, Crohn's disease, Alzheimer's disease, leukemia and other adaptations requiring immunosuppression disease. The non-hematopoietic performance of JAK3 has also been reported, but its functional importance needs to be clarified (乂 /wwwwo/. (2002), pp. 2475-2482). Since the bone marrow transplant of SCID is therapeutic (5/oW 103 (2004), pp. 2009-2018), it seems that JAK3 is unlikely to have the necessary non-redundant function in other tissues or organs. Therefore, it is associated with immunosuppressive drugs. The limited distribution of JAK3 is attractive compared to other goals. Agents that act on molecular targets that are limited to the immune system's parameters may produce optimal efficacy: toxicity ratio. Thus, targeting JAK3 will theoretically provide immunosuppression where needed (i.e., provide immunosuppression to cells actively involved in the immune response) without any effect outside of such cell populations. Although defective immune responses have been described in various STAT·/- lines (j. Wd. 44 (1996), pp. 304-311; Cwrr. Ce// 〇// 9 (1997), pp. 233-239 Page), but the widespread distribution of STAT and the lack of such molecules to be enzymatically active by small molecule inhibitors make it not a key target for immunosuppression. Lu SYK (spleen tyrosine kinase) is a non-receptor tyrosine kinase necessary for the activation of b cells via Bcr signaling. SYK activates upon binding to phosphorylated BCR binding to initiate early signaling events after BCR activation. Mice lacking S YK developed early B cell development (Cheng et al. ' Nature 378: 303, 1995; Turner et al, Nature 378: 298, 1995). Therefore, inhibition of SYK enzyme activity in cells is recommended as a method of treating autoimmune diseases via its action on autoantibodies. 156090.doc 201204731 In addition to its role in BCR signaling and B cell activation, SYK also plays a key role in FcsRI-mediated mast cell degranulation and eosinophil activation. Therefore, SYK is associated with allergies (including asthma) (reviewed in Wong et al., Expert Opin Investig Drugs 13:743, 2004). SYK binds to the phosphorylated gamma chain of FcsRI via its SH2 domain and is required for downstream signaling (Taylor et al, Mol. Cell. Biol. 15:4149, 1995). Mast cells lacking SYK exhibit defects in granules, arachidonic acid, and cytokine secretion (Costello et al., Oncogene 13: 2595, 1996). A pharmacological agent that inhibits SYK activity in mast cells also exhibits this phenomenon (Yamamoto et al, J Pharmacol Exp Ther 306: 1174, 2003). Inhibition of antigen-induced eosinophils and neutrophils in an animal asthma model was treated with SYK antisense oligonucleotides (Stenton et al, J Immunol 169:1, 28, 2002). Eosinophils lacking SYK also exhibit reduced activation in response to FcsR stimulation (Lach-Trifilieffe et al, Blood 96: 2506, 2000). Therefore, SYK's small molecule inhibitors will be suitable for the treatment of allergic-induced inflammatory diseases including asthma. Given the expected benefits from many of the conditions involved in the treatment of JAK and/or SYK pathways, it is clear that new compounds that modulate JAK and/or SYK pathways and methods of using such compounds will provide substantial therapeutic benefit to many patients. . Provided herein are novels suitable for treating conditions that target the JAK and/or SYK pathway or inhibit JAK or S YK kinases, particularly JAK3. It is more suitable for the treatment of autoimmune diseases and inflammatory diseases than π and η than V». The novel pyrrolopyrazine derivatives provided herein selectively inhibit jAK3 and are useful for the treatment of autoimmune diseases and inflammatory diseases. The compounds of the present invention modulate the JAK and/or SYK pathway of 156090.doc 201204731 and are novel for the treatment of autoimmune diseases and inflammatory diseases. The preferred compounds selectively inhibit JAK3. For example, the compounds of the present invention inhibit JAK3 and SΥΚ, wherein preferred compounds are selective for JAK3 in JAK kinase and are novel pyrrolopyrazine derivatives suitable for the treatment of autoimmune diseases and inflammatory diseases. The indoleamine linker at position 7 of 5Η-pyrrolo[2,3-b]pyrazine allows the compounds of formula I and guanidine to inhibit the potency of JAK and Syk kinase compared to other portions of 5H-pyrrolo[2 , 3-b] Pyridine was unexpectedly improved. Furthermore, the compounds of the present invention inhibit JAK3 and JAK2, among which the preferred compounds are selective for JAK3 in JAK kinase and are novel pyrrolopyrazine derivatives suitable for the treatment of autoimmune diseases and inflammatory diseases. Similarly, the compounds of the present invention inhibit JAK3 and JAK1, wherein the preferred compounds are selective for JAK3 in JAK kinases and are novel pyrrolopyrazine derivatives suitable for the treatment of autoimmune diseases and inflammatory diseases. SUMMARY OF THE INVENTION The present application provides a compound of formula I,

R is hydrazine, cyano, lower alkyl, R or

156090.doc -10- 201204731 R' is cycloalkyl, heterocycloalkyl, heteroaryl or phenyl, each of which is optionally substituted by one or more R"; each R" is independently halo, hydroxy, Cyano, lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, C(=〇)R"' or S(=〇)2R "; each R&quot ; 'Independently OH or lower alkyl;

Rla&Rlb are each independently hydrazine, hydroxy, dentate, lower alkyl, lower alkenyl, lower alkynyl, lower carbon lialkyl, lower alkoxy, lower alkoxy-based, lower Carboxyhydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, C(=0)R'', S(=0)2R'' or CH2S(=0)2R '·'; R1 e is phenyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Rld; each Rld is independently hydroxy, halo, lower alkyl, low carbon A hydroxyalkyl group, a low carbon dentate group or a lower alkoxy group; R2 is a hydrazine, a hydroxy lower alkyl group, a lower haloalkyl group or a lower carbon yard; R3 is a hydrazine, a hydroxyl group, a cyano group, a cyano group low carbon Alkyl or R3·; each R3 is independently a lower alkyl group, a transcarbocarbyl group, a lower alkoxy group, a lower alkene group, a lower alkovaneoxy group, a phenyl lower alkyl group, a ring The alkyl or % alkyl-based low-carbon alkyl group is optionally substituted with one or more R 3 groups; each R 3 '' is independently lower alkyl, halo, hydroxy, lower alkoxy, lower carbon to alkyl , lower hydroxyalkyl, pendant oxy, amine, cyano, cyano lower carbon, S(=0)2R3&quo t;·, C(=〇)R3·", cycloalkyl, heterocycloalkyl, heteroaryl or heterocycloalkenyl; each R3'" is independently hydrazine, hydroxy or lower alkyl; 156090 .doc -11· 201204731 Q is Q2, Q3 or Q4; Q2 is heterocycloalkyl 'cycloalkyl, cycloalkenyl, heterocycloalkylphenyl, heteroaryl, biaryl or heteroaryl The situation is replaced by one or more (^23; Q24Q2l^Q2e; each Q2b is independently halogen, pendant oxo, thiol, -CN, -sch3, -s(o)2ch3 or -s(=〇 Ch3; each () 2 <: independently Q2d or Q2e; or two Q2a together form a double loop system 'optionally substituted by one or more Q2b4Q2e; each 卩2<1 is independently -〇(Q2e), -S(=0)2(Q2e), _C(=0)N(Q2e)2, -S(〇)2(Q2e), -C( = 〇)(Q2e), -C( = 〇)〇( Q2e), -N(Q2e)C( = 〇)(Q2e), -N(Q2e)C( = 〇)〇(Q2e) or -N(Q2e)C(=〇)N(Q2e)2 ; each Q Independently H or Q2e; each Q2e' is independently lower alkyl, phenyl, benzyl, 5,6,7,8-tetrahydro-naphthalene, lower alkyl, lower alkoxy, Cycloalkyl, cycloalkenyl, heterocycloalkyl, spirocycloheteroalkyl or heteroaryl, optionally by one or more Q2 f is substituted; each () 2 £ is independently Q2g or Q2h; each <^28 is independently a element, a hydroxyl group, a cyano group, a pendant oxy group, -S(= 〇)2(Q2i.), -S( = 〇) 2N(Q2i')2, _C(=〇)〇H, C(=〇)N(Q2i')2 or -C(=0)(Q2i); each Q2h is independently a lower alkyl group, Lower alkenyl, 156090.doc •12· 201204731 low carbon halogen group, low carbon alkoxy group, amine group, phenyl group, benzyl group, cycloalkyl group, heterocycloalkyl group or heteroaryl group, as the case may be One or more Q2i substitutions; and each Q2i is independently dentate, hydroxy, cyano, lower alkyl, lower haloalkyl or lower alkoxy; each Q2i' is independently hydrazine or lower alkyl ;

Q3 is -0-Q3a, -S-Q3a, -C(=0)(Q3a), -0(CH2)mC(=0)(Q3a), -S(=〇)(Q3a), -S(= 0) 2 (Q3a), -N(Q3a)2, -N(Q3a)S(=0)2(Q3a), -N(Q3a)C(=0)(Q3a), -C(=0)N (Q3a)2, N(Q3a)C(=0)N(Q3a)2 or -N(Q3a)(CH2)mC(=0)N(Q3a)2; each ()33 is independently Q3b4Q3c; each m Independently 〇, 1 or 2; each 〇 315 is independently Η; each Q3e is independently lower alkyl, lower carboalkyl, phenyl, 5,6,7,8-tetrahydro-naphthalene, naphthalene , 2,2-dimethyl-2,3-dihydro-benzofuranyl, indanyl, fluorenyl, fluorenyl, cycloalkyl, heterocycloalkyl or heteroaryl, as appropriate Multiple Q3d substitutions; and each (^3 (1 independently of () 36 or (5^; each Q3e is independently dentate, pendant oxy, cyano, hydroxy, -NHS(=〇)2(Q3f) -NHC(=0)(Q3f) 'NHC(=0)N(Q3f)2 or N(Q3f)2; each Q3% site is Η or Q3f'; each Q3f' is independently lower alkyl, lower Carboalkoxy, lower haloalkyl, phenyl, phenyl fluorenyl, cycloalkyl, heterocycloalkyl 156090.doc • 13-201204731 or heteroaryl, optionally substituted by one or more Q3g; Q3g is independently halogen, hydroxy, lower alkyl, low carbon alkyl Low carbon functional group or low carbon alkoxy; Q4 is Q4a4Q4b; Q4a is hydroxyl, halogen or cyano; Q4b is lower alkyl, lower alkoxy, lower alkynyl, lower alkenyl, low carbon a hydroxyalkyl group, an amine group or a lower alkyl group, optionally substituted by one or more Q4e; each 卩^ is independently Q4d4Q4e; each 卩4 (1 is independently i, hydroxy or cyano; each Q4e is independent Is a lower alkyl, lower alkyl-, lower alkoxy, amine, cycloalkyl, phenyl, heterocycloalkyl or heteroaryl group, optionally substituted by one or more Q4f; each Q4f Independently a hydroxy, _, lower alkyl, lower alkenyl, pendant oxy, lower carbyl, lower alkoxy, lower hydroxy or amine group; Not 2-pyrene-2-yl-5H-° ratio η[2,3-15]pyrazine-7-decyl isopropylamine, 2-cyclopropyl-511-pyrrole[ 2,3_b]pyrazine formic acid (4-hydroxy-3,3-dimethyl-butyl)-decylamine, 2-[1-(7-isopropylaminoindolyl-5Η-pyrrolo[2 ,3-b]pyrylene-2-yl)-piperidin-3-yl]-propionic acid second butyl ester, 2-cyclopropyl-5H-" ratio 并[2,3-b]° ratio啩-7- citrate third Mince amine group, 2-cyclohexyl--5H-. Bis-[2,3-b]pyrazine-7-formic acid isopropylamine, 2-cyclohex-1-ylidene-5H-pyrrolo[2,3-b]n ratio p--7- Isopropylamine formate, 2-a-5H-pyrrolo[2,3-b]pyrazine-7-formic acid isopropylamine, 2-156090.doc • 14· 201204731

Isopropyl-5H each [2'3 handsome than spray_7·isopropyl isopropylamine, 2_isopropenyl-5Η·(4) and [2,3.b] Μ _7• formic acid propyl decylamine , fluorenylcyclopentylmethyl-amino)-5Η "Big slightly [2,3 sec. 7 carboxylic acid isopropyl urethane, Π · (7 · isopropylamine 曱 _5H_ntb 并 [ 2,3 刈 耕 耕 _2 _2 _ _2 _ _2 _2 _2 _2 _2 -3- -3- -3- 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 [2,3_b]_ ·7_ f acid isopropyl _, 2 (cyclopentyl _ methyl-amino)-5H-t each [2,3_ ratio, well _7_carboxylic acid isopropyl Amine, 2_ gas-5H-pyrrolo[2'3 handsome ratio tillage_7_isopropenylamine, 2·isopropenyl-5H-[2,3 handsome ratio {7-isopropyl isopropyl hydrazine Amine, 2_isopropyl_ 5H-indolo[2,3 sec- -7-formic acid isopropyl decylamine, 2_cyclohexyl-diyl _ 5H-. (4) and [2,3-b H7-isopropyl decyl decanoate, 2_cyclopropyl_5//_ pyrrolo[2, called pyridinium-7-formic acid (3·hydroxyindole dimethyl-propyl)-bristamine, 2-cyclopropyl-5/f·pyrrolo[2,3_6]pyrazine_7•carboxylic acid ((8)_2_hydroxy-1,2-dimethylpropyl)-decylamine, 2_cyclopropyl_5扒Pyrrolo[2,3_6]pyrrol-7-nonanoic acid dibutyl Indoleamine, 2-cyclohexyl_5H_pyrrolo[2,3-7]pyrazine·7·metholidine isopropylamine, 2-»cephen-2-yl-5ϋΓ-bias[2, 3-3⁄4] 〇 比 p Well-7-decanoic acid (3-hydroxy-2,2-dimercapto-propyl)-decylamine, isopropylaminecarbamyl _ 5Η-»比咯和[2, 3-b]n than cultivable-2-yl)-piperidin-3-yl]-mercapto-amino decanoic acid tert-butyl ester, 2-(3-mercaptoamino-piperidine-indenyl) _5H_pyrrolo[2,3_b]pyrazine_7-isopropyl isopropylamine; [〖-(7·isopropylaminemethanyl-511_pyrrolo[2,3-b]pyrazine- 3-butyl)-piperidinyl]-methyl-amino decanoic acid tert-butyl ester or 2-(3-methylamino-piperidinyl)- 5H•pyrrolo[2,3_b]pyrazine _7 isopropyl decyl citrate; or a pharmaceutically acceptable salt thereof. 156090.doc • 15-201204731 The present application provides a method for treating an inflammatory condition or an autoimmune condition A patient in need thereof is administered a therapeutically effective amount of a hydrazine compound. The present application provides a pharmaceutical composition comprising a mixture of a compound of formula 1 and at least one pharmaceutically acceptable carrier, excipient or diluent.

The phrase "a" or "system" as used herein refers to one or more of the entities; for example, a compound refers to - or a plurality of compounds or at least one compound. Therefore, in this document, the terms "one", "one or more" and "at least one" are used interchangeably. Λ w 73 μ谷驭大广的申申 The broadest definition of each group provided in the patent scope. In all other embodiments set forth below, the broadest definitions provided in the various embodiments of the Substitutes (IV) may be present in the various embodiments. As used in this specification, the term "comprising" should be interpreted as open-ended, whether in a conjunction or in the subject matter of the application. That is, the terms should be interpreted as synonymous with the phrase "土^丹有" or "at least". When used in the context of a method, the term "includes". When the method includes at least the steps but may also include other two substances or compositions, the term "spooning in" or the composition includes at least the features. Or a component, or a compound or component. c may also include other specific names, unless otherwise specifically indicated, as used herein, the term "or J is used in the sense of inclusion of 156090.doc -16-201204731 or", It is not used in the sense of "exclusiveness" of "or". "Independently" is used herein to indicate that a variable is used in either case without regard to the presence or absence of a variable having the same or different definition within the same compound. &# 'In R', appears twice and is defined as Of the compounds "independently carbon or nitrogen", both R" can be carbon, and both R" can be nitrogen or one R" can be carbon and the other nitrogen. When any variable (e.g., R, R, or Q) occurs more than once in any portion or formula depicting and describing a compound used or claimed in the present invention, its definition on each occurrence is independent of each other. Furthermore, combinations of substituents and/or variables are permissible only if such compounds result in stable compounds. The symbol "*" at the end of the key or the "·······" drawn through the key is used to refer to the official base or /, and the other. The point of attachment to the remainder of the molecule to which the functional group or other chemical moiety belongs is divided. So, for example:

MeC(=〇)〇R, R4= *〇 or +< 4 Μ·〇. Plotting the keys into the ring system (as opposed to connecting at different vertices) indicates that the bond can be attached to any suitable ring atom. An event or circumstance as described herein after the term "as appropriate" may, but is not necessarily, to occur, and the description includes the circumstances in which the event or circumstance occurs and the event or circumstance does not occur. For example, "substituting as appropriate" means that the portion substituted by the circumstance may have hydrogen or a substitution of a phrase as used herein to form a double loop, which means that the joint forms a 156090.doc -17-201204731 double loop system, Each of the rings may be composed of 4·7 carbon atoms or 4-7 carbons and heteroatoms, and may be saturated or unsaturated. As used herein, the phrase "forming a spiro ring system" means that two substituents on a single carbon atom are joined together to form a spiro ring system in which the ring formed can be smear of 7 carbons and heteroatoms from 3 to 7 carbon atoms. Composition, and can be saturated or unsaturated. The term "about" is used herein to mean approximation, in scope, rough or approximate. When the term "about" is used in conjunction with a numerical range, it modifies the range such that the boundary extends above and below the stated value. In general, the 〇〇 ’ , ' ' 勺 ' is used herein to modify the value of the deviation value of up to 2% above and below the value. The definitions described herein may be added to form chemically relevant combinations such as "heteroalkylaryl", "dentate alkylheteroaryl", "arylalkylheterocyclyl", "alkyl carbonyl", "alkane" An oxyalkyl group, a "cycloalkylalkyl group" and the like. When the term "alkyl" is used as the suffix of another term, such as "phenylalkyl" or "hydroxyalkyl", it is intended to mean one to two substituents selected from other specifically designated groups. An alkyl group as defined above. Thus, for example, ""phenylalkyl" refers to an alkyl group having one to two phenyl substituents and thus includes phenylhydrazine, phenylethyl and biphenyl. "Alkylaminoalkyl" is an alkyl group having one to two alkylamino substituents. "Hydroxyalkyl group j includes 2-carbylethyl, 2-propylpropyl, 1-(transmethyl)-2-methylpropyl, 2-hydroxybutyl, 2,3-dihydroxybutyl, 2-(Hydroxymethyl), 3-hydroxypropyl, etc. Thus, the term "hydroxyalkyl" as used herein, is used to define one of the heteroalkyl groups defined below. The term -(aryl)alkyl means a substituted alkyl or aralkyl group of 156090.doc -18-201204731. The term (hetero)aryl refers to an aryl or heteroaryl group. The compounds of formula I can exhibit tautomerism. The tautomeric compound may exist in the form of two or more substances which are mutually convertible. The proton transfer tautomeric system is produced by the migration of a hydrogen atom bonded by a common mussel between two atoms. Tautomers generally exist in equilibrium and attempts to separate individual tautomers typically result in a mixture of chemical and physical properties and a mixture of compounds. The position of equilibrium depends on the chemical characteristics within the molecule. For example, in many aliphatic aldehydes and aliphatic ketones (such as acetaldehyde), the keto form predominates; in phenols, the enol form predominates. Common proton transfer tautomers include ketone/enol (-C(=〇)-CH-SC(-OH)=CH-), decylamine/imidic acid (-C(=0)-NH-i5- C(-0H)=N·) and 脒(-C(=NR)-NHC(·NHR)=N-) tautomers. The latter two are especially common in heteroaryl and heterocycles' and the invention encompasses all tautomeric forms of the compounds. The technical and scientific terms used herein have the meaning commonly understood by those skilled in the art to which the invention pertains, unless otherwise defined. Various methods and materials known to those skilled in the art are mentioned herein. Standard references describing the general principles of pharmacology include Goodman and Gilman's 77ie household/mr co/〇gZca/ 1st edition, edition & please

Hill Companies Inc., New York (2001). The invention may be practiced using any suitable materials and/or methods known to those skilled in the art. However, preferred materials and methods are described. Unless otherwise stated, the materials, reagents and analogs mentioned in the following examples and examples are available from commercial sources. The term "mercapto" as used herein denotes a radical of the formula _c(=〇)R, wherein 156090.doc -19 201204431 is R or hydrogen or a lower alkyl group as defined herein. The term "alkylcarbonyl" as used herein denotes a radical of the formula C(=0)R, wherein R is alkyl as defined herein. The term C,.6 fluorenyl refers to a group containing 6 carbon atoms _ C(=0)R. The term "arylcarbonyl," as used herein, refers to a radical of the formula c(=〇)R, wherein R is aryl; as used herein, the term "benzhydryl" is an arylcarbonyl group wherein R is phenyl. "." The term "carbonyl" as used herein means a group of the formula c(=o). The term "tertiary oxy group" as used herein means a group of the formula (=〇) which may be attached to a carbon atom or a hetero atom. The term "hospital group" as used herein denotes an unbranched or branched chain, saturated, monovalent hydrocarbon residue containing from 1 to 1 carbon atoms. The term "lower alkyl" means a straight or branched hydrocarbon residue having from 1 to 6 carbon atoms. As used herein, "C^oalkyl" means an alkyl group consisting of 1 to 1 carbon. Examples of alkyl groups include, but are not limited to, lower alkyl groups including methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl or pentyl, isopentyl, new Butyl, hexyl, heptyl and octyl. When the term "alkyl" is used as the suffix of another term, such as "phenylalkyl J or "hydroxyalkyl", it is meant to be substituted with one to two substituents selected from other specifically designated groups. An alkyl group as defined above. Thus, for example, a silly base group means a group R'R"-, wherein R. is a phenyl group, and ru is a stretching group as defined herein, provided that the point of attachment of the phenyl group moiety is in the alkylene group. Examples of the β-arylalkyl group include, but are not limited to, phenyl fluorenyl, phenylethyl, 3-phenylpropyl. The term "arylalkyl" or "aralkyl" is interpreted similarly with the exception of R being an aryl group. The term "heteroarylalkyl" is interpreted similarly with the exception of R, optionally as aryl or heteroaryl. 156090.doc -20- 201204731 The term "dentate alkyl" as used herein denotes an unbranched or branched alkyl group as defined above wherein one, two, three or more hydrogen atoms are replaced by a halogen . The term "lower carbon dentate" means a straight or branched chain hydrocarbon residue having 1 to 6 carbon atoms in which one, two, three or more hydrogen atoms are replaced by a halogen. Methyl, 1-chloroindenyl, 丨-bromoindolyl, 1-iodomethyl, difluoroindolyl, trifluoromethyl, trichloromethyl, tribromoindolyl, triiodomethyl, 1-fluoroethyl Base, 丨-chloroethyl, 丨-bromoethyl, 丨-iodoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-di Ethyl, 3-bromopropyl or 2,2,2-trifluoroethyl. The term "alkylene" as used herein, unless otherwise indicated, means a divalent saturated straight chain hydrocarbon radical having from 1 to 10 carbon atoms (eg (CH2)n) or a branched chain saturated with from 2 to 10 carbon atoms. A valence hydrocarbon group (for example, _CH]vle_ or •CH2CH(i-Pr)CH2-). Except in the case of a methylene group, the valence of the alkyl group is not bonded to the same atom. Examples of alkylene groups include, but are not limited to, anthracenylene, ethylidene, propyl, 2-methyl-propyl, ι, ι-didecyl-ethyl, butyl, 2- Ethyl butyl. The term "alkoxy" as used herein means _〇-alkyl, wherein alkyl is as defined above, such as decyloxy, ethoxy, n-propoxy, isopropoxy, n-butoxy 'Isobutoxy, tert-butoxy, pentyloxy, hexyloxy' includes isomers thereof. As used herein, "lower oxyalkyl" means an alkoxy group having a "lower alkyl" group as defined previously. As used herein, "Cuo-xyloxy" means _〇-alkyl, wherein alkyl is c11〇. The term "alkyl group" as used herein denotes a alkyl group as defined herein wherein one to three hydrogen atoms on different carbon atoms are replaced by a hydroxyl group. 156090.doc •21· 201204731 The term “cycloalkyl" as used herein refers to a saturated stone and ring containing from 3 to 8 carbon atoms, ie cyclopropyl, cyclobutyl, cyclodecyl, cyclohexyl, ring. Heptyl or cyclooctyl. As used herein, "C37 cycloalkyl" refers to a cycloalkyl group of from 3 to 7 carbons in the carbocyclic ring. The "cycloalkenyl group" means a partially unsaturated carbocyclic ring having 5 to 7 carbon atoms and having a carbon-carbon double bond in the ring unless otherwise specified. By way of example, 'c5.6 cycloalkenyl refers to a cyclic bake group having 5 to 6 member atoms. In some embodiments, the ring of the ring has a carbon-carbon double bond in the ring. In other embodiments, the ring of the ring has more than one carbon-carbon double bond. However, the cycloalkenyl ring is not an aromatic ring. The cycloalkenyl group may be optionally substituted with one or more substituents. Examples of cycloaliphatic groups include, but are not limited to, cyclopentyl and cyclohexyl. The term "dentate" or "dentate" as used herein means fluoro, chloro, imine or basic. The term "amino" as used herein encompasses 2, wherein each R group is independently hydrazine or lower alkyl, wherein lower alkyl is as defined herein. Examples of amine groups include dimethylamino, methylamino and Νη^ "As used herein, the term "aryl" means monocyclic or bicyclic (also known as "biaryl"), substituted or not. Substituted carbocyclic aromatic group. Examples of aryl groups are phenyl, naphthyl and the like. The term "heteroaryl" as used herein means a monocyclic or bicyclic ("heterobiaryl") or tricyclic group having 5 to 18 ring atoms, which has at least one atom containing from four to eight atoms per ring. And one or more ruthenium, osmium or 3 heteroatoms, the remaining ring atoms are carbon aromatic rings, provided that the point of attachment of the heteroaryl group should be 156090.doc -22· 201204731 on the aromatic ring. As is well known to those skilled in the art, the aromatic character y of the heteroaryl ring is in its counterpart. Thus, for the present invention, the heteroaryl group only needs to have a certain degree of aromatic character. Examples of heteroaryl moieties include monocyclic aromatic heterocycles having 5 to 6 ring atoms and 1 to 3 heteroatoms including, but not limited to, pyridinyl, pyrimidinyl, pyridyl, pyrrolyl, pyrazole Base, imidazolyl, fluorenyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl triazoline, triazolyl, thienyl, furyl, thiadiazolyl and

a oxazoline group, optionally substituted by one or more, preferably one or two substituents selected from the group consisting of: cyano, cyano, alkyl, alkoxy, thio, low carbon Substituted thiol, dentate, (tetra), aryl, decyl, aryl, amine, amine, dialkylamino, amine alkyl amide And dialkylamino-based, nitro, decyloxy and carbamoyl, alkylamine T-decyl, dialkylamine-methyl hydrazino, arylamine-brenyl 1 yl (tetra)amine And an arylamino group. Examples of bicyclic moieties (also known as heterozygous moieties) include, but are not limited to, linalyl, decyl, isoindole, and benzoate. Nanji, benzoquinole, benzo. Evil saliva, benzopyrene, benzoquinone and saliva. The ratio is slightly lower than the base n and then the ratio of -n to [2,3-b]. Bipyridine and benzisothiazole. "The term "heterocyclic alkyl", as used herein, unless otherwise indicated, refers to a monovalent saturated cyclic group which consists of one or more two-two to two partial rings or three rings (each ring). a composition having three to eight atoms, and having - or a plurality of ring carbon atoms and - a ring of heteropoly or (d) W, wherein the point of attachment may be via a carbon atom or a hetero atom, optionally independently - or multiple, Preferably - or two or three are selected from the group consisting of 156090.doc • 23-201204731: hydroxy, pendant oxy, cyano, lower alkyl, lower alkoxy, lower alkoxy , alkylthio, ii, i alkyl, hydroxyalkyl, nitro, alkoxycarbonyl, amine, alkylamino, alkylsulfonyl, arylsulfonyl, alkylamino Sulfonyl, arylaminosulfonyl, alkylsulfonylamino, arylsulfonylamino, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonylamino, arylcarbonylamine base. Examples of heterocyclic groups include, but are not limited to, azetidinyl, pyrrolidinyl, hexahydroazetyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, oxazolidinyl, thiazole bites Basis, hetero-causal bite base, °Bi Luobite, 琳琳基, 旅井基, Niangbite base, different ° bow 丨 ° 朵 · 、, dihydroisoquine: Linji, tetrahydro senti , tetrahydrocarbinyl, imidazolinyl, thiomorpholinyl and P quinacridyl. The phrase "organ rejection" includes acute allograft rejection or xenograft rejection and chronic allograft rejection in the setting of vascularization and/or non-vascularization (eg, bone marrow, membrane island cells) grafts. Reaction or xenograft rejection. Inhibitors of JAK and Syk The present invention provides a compound of formula I or I, wherein the conditions are such that when q is cyclopropyl or thienyl, R2 and R3 are fluorenyl or fluorenyl, and R is a, Rib and Rlc* When either of them is hydrazine or methyl, the other is not hydrazine, hydroxy or hydroxymethyl; the limitation is when Q is gas, isopropyl, isopropenyl, piperidinyl, methyl-piperidine 3-yl-amine, methyl-piperidine-3-yl-carbamic acid tert-butyl ester, cyclohexyl, cyclopentyl fluorenyl-amino or cyclohexenyl, and ruler 2 and ruler 3 When hydrazine or methyl group, Rla ' Rib and Ric are not all Η; and 156090.doc •24- 201204731 pyridine is a condition that the compound of formula 1 is not 2-(cyclodecyl-methyl-amino)_5Η· "[2'3'b]pyrazine·7_isopropyl decyl decylamine, 2-gas-; 5Η-pyrrolo[] ratio, well-7-formic acid isopropylamine, 2-isopropene Η-5Η-pyrrolo[,] than well 7-formic acid isopropyl decylamine, 2-isopropyl-5 Η-pyrido-W than well-7-formic acid isopropyl guanamine, 2-cyclohexan- 1-alkenyl-5Η-pyrrolo[,b] than argon-7-formic acid isopropylamine, 2-cyclopropyl-5 open-pyrrolo[2,34]pyridin-7-decanoic acid (3 -hydroxy·2,2-dimethyl- ) 醯 、, 2_cyclopropyl-5/f-pyrrolo[2,3·6]pyrazine_7-carboxylic acid hydroxy-I, dimethyl-propyl)-nonylamine, 2-ring Propyl-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid tert-butylamine, 2-cyclohexyl-5H-pyrrolo[2,3_b]pyrrol-7-formic acid Isopropyl decylamine, 2-thiophen-2-yl-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid (3-hydroxy-2,2-didecyl-propyl)_ Indoleamine, [1-(7-isopropylaminoindolyl-5H-pyrrolo[2,3-b]pyrylene-2-yl)-piperidine-3-yl]-methyl-aminocarboxylic acid Second, 2-(3-methylamino-piperidinyl-yl)-511-pyrrolo[2,3_b] ° ratio -7-isopropyl decyl decylamine; π·(7 · Isopropylamine thiol_5H pyrrolo[2,3-b]pyrylene-2-yl)-piperidine-3-yl]-methyl-amino decanoic acid tert-butyl ester or 2-( 3-methylamino-piperidin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-formic acid isopropylamine; or a pharmaceutically acceptable salt thereof In one variation of I or Γ, R is Η, cyano, R' or

156090.doc •25· 201204731 R' is a cycloalkyl, heterocycloalkyl, heteroaryl or phenyl group, each optionally substituted by one or more R; each R" independently halo, hydroxy' cyanide Base, lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, C(=0)R'" or S(=0)2R".; each R&quot ; 'Independently OH or lower alkyl;

Rla&Rlb are each independently hydrazine, hydroxy, halo, lower alkyl, lower alkenyl, lower alkynyl, lower alkene, lower alkoxy, lower alkoxy, lower carbon Hydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, C(=0)R"', S(=0)2R" or (:Η28(=0)2ΐΓ ;

Rle is phenyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Rld; each Rld is independently hydroxy, cumyl, lower alkyl, lower hydroxyalkyl, lower Carboalkyl or lower alkoxy. In one variation of formula I or hydrazine, r is deuterium, fluorenyl or R'. In one variation of formula I or hydrazine, it is a cycloalkyl, piperidinyl, pyrrolidinyl or tetrahydropyranyl group, each of which is optionally substituted by one or more R.. In one variation of formula I or hydrazine, R2 is deuterium or lower alkyl. In one variation of formula I or hydrazine, R3 is hydrazine, hydroxy, cyano, cyano lower alkyl or R3'; each R3' is independently lower alkyl, hydroxy lower alkyl, lower alkane An oxy group, a low carbon dentate group, a lower carbitoloxy group, a phenyl lower alkyl group or a cycloalkyl lower carbon group, each optionally substituted by one or more R3"; each R3" independently low Carboalkyl,! |, hydroxy, lower alkoxy 156090.doc •26·201204731 base, low carbon dentate, lower hydroxyalkyl, pendant oxy, cyano, cyano lower alkyl, S(=0)2R3 And C(=〇)R3·'', cycloalkyl, heterocycloalkyl, heteroaryl or heterocycloalkenyl; each R3"' is independently hydrazine or lower alkyl. In one variation of formula I or hydrazine, R3 is fluorenyl, cyano, cyano lower alkyl or R3; each R3 is independently lower alkyl, hydroxy lower alkyl, lower alkoxy, lower Carbodentyl, lower carbitoloxy, cycloalkyl or cycloalkyl lower alkyl, each optionally substituted by one or more R3". In one variation of formula I or r, it is a fluorenyl group. In one variation of formula I or hydrazine, 'R2 or R3 is lower alkyl and the other is hydrazine. In one variation of formula I or hydrazine, 'q is cycloalkyl, heterocycloalkyl or heteroaryl' is optionally substituted with one or more Q2a, and R2 or R3 is fluorenyl. In one variation of formula I or hydrazine, 'Rla is lower alkyl, hydroxy, lower carboalkyl, lower alkoxy, cyano or lower hydroxyalkyl. In one variation of formula I or hydrazine, 'Rla is lower alkyl, hydroxy, lower haloalkyl, lower alkoxy, cyano or lower hydroxyalkyl, and Q is cycloalkyl, heterocycle Alkyl or heteroaryl, each optionally substituted by one or more Q2a. 0 In a variation of formula I or hydrazine, 'Rla is lower alkyl, hydroxy, lower haloalkyl, lower alkoxy, Cyano or lower hydroxyalkyl, and R2 or R3 is fluorenyl. In one variation of formula I or hydrazine, 'Rla is lower alkyl, hydroxy, lower 156090.doc 27-201204731 carbon dentate, lower alkoxy, cyano or lower hydroxyalkyl, Q is a ring Alkyl, heterocycloalkyl or heteroaryl, each optionally substituted by one or more Q2a, and R2 or R3 is a fluorenyl group. In one variation of formula I or hydrazine, Rib is a lower alkyl or lower haloalkyl. In one variation of formula I or hydrazine, Rib is lower alkyl or lower haloalkyl' and R a is lower alkyl, hydroxy, lower carbonyl, lower alkoxy, cyano Or low carbon base base. In one variation of formula I or hydrazine, Rib is lower alkyl or lower haloalkyl and Q is cycloalkyl, heterocycloalkyl or heteroaryl, each optionally substituted by one or more Q2a In one variation of formula I or hydrazine, Rib is lower alkyl or lower haloalkyl, and R2 or R3 is methyl. In one variation of formula I or hydrazine, Rib is lower alkyl or lower haloalkyl 'Rla is lower alkyl, hydroxy, lower haloalkyl, lower alkoxy, cyano or lower carbon The hydroxyalkyl group 'Q is a cycloalkyl group, a heterocycloalkyl group or a heteroaryl group, each optionally substituted by one or more Q2a, and R2 or R3 is a fluorenyl group. In one variation of formula I or hydrazine, the ruthenium is hydrazine, hydroxy or lower alkyl. In one variation of formula I or hydrazine, Rle is hydrazine, hydroxy or lower alkyl, and R1 a is a lower carbon alkyl group, a hydroxyl group, a lower carbon group, a lower alkoxy group, a cyano group or a lower carbon. Base base. In one variation of formula I or hydrazine, hydroxy or lower alkyl, and Q is cyclohetero, heterocycloalkyl or heteroaryl, each optionally substituted by one or more Q2a. 156090.doc •28- 201204731 In a variation of Formula I or ’, '111. Is a hydroxyl group or a lower alkyl group, and R2 or R3 is a fluorenyl group. In one variation of formula I or hydrazine, 'Rle is hydrazine, hydroxy or lower alkyl, and Rla is lower alkyl, hydroxy, lower carboxy, lower alkoxy, cyano or lower hydroxyalkyl And Q is a cycloalkyl, heterocycloalkyl or heteroaryl group, each optionally substituted by one or more Q2a, and R2 or R3 is a fluorenyl group. In one variation of formula I or hydrazine, R1a&Rlb together form a spirocycloalkyl or spiroheterocycloalkyl group. In a variation of Formula 1 or 1 ', Q is Q2, Q3 or Q4; Q is a cycloalkyl group, a ring-dense group, a guanidine group, a sputum group, a thiophene group, a 0-pyridyl group, Pyrazolyl or dihydropyranyl, optionally substituted by one or more Qh; 卩2& independently 卩2 (1 or Q2e; each Q2, site is -C(=0)N(Q2e)2 or -C(=0)(Q2e)-; each Q21 site is Η or Q2e, Φ Each Q2e is independently a lower alkyl, phenyl, phenyl fluorenyl, 5,6,7,8-tetrahydro-naphthalene, Lower halohaloalkyl, lower alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl, spirocycloheteroalkyl or heteroaryl, optionally substituted by one or more Q2f; each 023⁄4 Q2g or Q2h; each Q2g is independently _ 素, hydroxy, cyano, pendant oxy ' -s (= 〇) 2 (Q2i,), -S (=0) 2N (Q2i') 2, -C (= 0) OH, C( = 〇)N(Q2i')2 or _C( = 〇)(Q2i); each Q h is independently low carbon burnt, low carbon dilute, low carbon halogen 156090.doc -29 · 201204731 alkyl, lower alkoxy, amino, phenyl, benzyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q2i; and each Q2i is independently Halogen, hydroxyl, cyano, lower alkane , low carbon or alkyl alkoxy; Q3 is -0-Q3a, -N(Q3a)2 or -N(Q3a)(CH2)mC(=0)N(Q3a)2; each 卩3" Independently Η or Q3c; each m is independently 0, 1 or 2; each Q3e is independently a low carbon burn group, a low carbon li base, a phenyl group, a 5,6,7,8-tetrazine-ca, Cai, 2,2-dimethyl-2,3-dinitro-benzocarbonyl, indanyl, fluorenyl, fluorenyl, cycloalkyl, heterocycloalkyl or heteroaryl, as appropriate Substituted by one or more Q3d; and each Q3d is independently a pixel, a pendant oxy group, a cyano group, a hydroxyl group, -NHS(=0)2(Q3f), -NHC(=0)(Q3f), NHC (=0 N(Q3f)2 or N(Q3f)2; each Q3% is Η or Q3f_; each Q3f' is independently lower alkyl, lower alkoxy, lower haloalkyl, phenyl, phenyl a group, a cycloalkyl group, a heterocycloalkyl group or a heteroaryl group, optionally substituted by one or more Q3g; and each Q3g is independently a dentate, a hydroxyl group, a lower alkyl group, a lower hydroxyalkyl group, a low carbon picture Alkyl or lower alkoxy; Q4 is (343 or 941); (43 is halogen or cyano; Q4b is lower alkyl, lower alkenyl or lower haloalkyl; 156090.doc • 30- 201204731 In a variant of the formula i or I, Cyclopropyl, thienyl or pyrazolyl. In one variation of Formula I or Γ form, (^ cyclopropyl, thienyl or. The azole group is optionally substituted by one or more Q2e. The present application provides a compound of formula I',

R is hydrazine, cyano, R or f is cycloalkyl, heterocycloalkyl, heteroaryl or phenyl, each of which is optionally substituted by one or more R" ^ is _ group, hydroxy group, cyano group , lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, C(=0)R··· or S(=〇)2r "; f is OH Or lower alkyl;

Rla, 11115 and 111 (: each independently η, hydroxy, i-based, lower alkyl, lower alkenyl, lower alkynyl, lower carboalkyl, lower alkoxy, lower carbo-oxygen Base, lower hydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, cycloalkyl, heterocycloalkyl, C(=0)R" or 156090.doc 201204731 s(=o)2r "; R2 is H or lower alkyl; R3 is hydrazine, hydroxy, cyano, cyano lower alkyl or R3'; R3' is lower alkyl, hydroxy lower alkane a group, a lower alkoxy group, a lower haloalkyl group, a lower halo alkoxy group, a phenyl lower alkyl group or a cycloalkyl lower alkyl group, each optionally substituted by one or more R3"; each R3" Independently lower alkyl, halo, hydroxy, lower alkoxy, lower haloalkyl, lower hydroxyalkyl, pendant oxy, cyano, cyano lower alkyl, S(=0 2R3..., C(=0)R3"', cycloalkyl, heterocycloalkyl 'heteroaryl or heterocycloalkenyl; R3"' is hydrazine or lower alkyl; Q is Q2, Q3 or Q4; Q2 is heterocycloalkyl, cycloalkyl, cycloalkenyl, heterocycloalkylphenyl, heteroaryl, biaryl or heterobiaryl , optionally substituted by one or more Q2a; 023 is Q2b4Q2e; Q2b is halogen, pendant oxy, hydroxy, -CN, -SCH3, -S(〇)2CH3 or -S(=〇)CH3; Q2e is Q2<^Q2e; or two Q2a - form a double loop system, which is replaced by one or more Q2b4Q2e as appropriate; Q2 <%-0(Q2e), -S(=0)2(Q2e), -C(=0)N (Q2e)2, -S(〇)2(Q2e), -C(=〇)(Q2e), _c(=0)0(Q2e), -N(Q2e)C(=〇)(Q2e), • N(Q2e)C(=0)0(Q2e) or -N(Q2e)C(=0)N(Q2e)2; each 卩26 is independently H or Q2e'; 156090.doc -32- 201204731 each Q2e 'Independently, lower alkyl, phenyl, benzoinyl, lower haloalkyl, lower alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl or heteroaryl, as appropriate Substituted by a plurality of Q2f; Q2g is halogen, hydroxy, cyano, pendant oxy or -C(=0)(Q2h); Q2h is lower alkyl, lower haloalkyl, lower decyloxy, amine, Phenyl, benzyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q' and Q2i is halo, thiol, cyano, lower carbyl, lower alkane Base or lower alkoxy; Q3 is -0-Q3a, _S-Q3a, -C(=0)(Q3a), -OCCH^CpOXQ33) -S(=〇)(Q3a), -S(=〇)2(Q3a), -N(Q3a)2, -N(Q3a)S(=0)2(Q3a), -N(Q3a)C( =0)(Q3a), _C(=〇)N(Q3a)2, N(Q3a)C(=〇)N(Q3a)2 or -N(Q3a)(CH2)mC(=〇)N(Q3a) 2; each Q3a is independently Q3b or Q3c; m is 0, 1 or 2; Q3b is Η; Q3e is lower alkyl, lower carbon, alkyl, phenyl, cycloalkyl, heterocycloalkyl or heteroaryl a group, optionally substituted by one or more Q3d; and each 卩3 <1 is independently; 卩> is halogen or hydroxy; Q3f is lower alkyl, lower alkoxy, lower ii alkyl, benzene a group, a cycloalkyl group, a heterocycloalkyl group or a heteroaryl group, optionally substituted by 156090.doc -33·201204731 or a plurality of Q3g; and each Q3g is independently a hydroxyl group, a hydroxyl group, a lower alkyl group, a lower carbon Hydroxyalkyl, lower alkyl or lower alkoxy; Q4 is Q4a4Q4b; Q4a is hydroxy, halogen or cyano; Q4b is lower alkyl, lower alkoxy, lower alkynyl, lower olefinic , a lower hydroxyalkyl, an amine or a lower alkyl i-alkyl, optionally substituted by one or more Q4e; Q4<^Q4<^Q4e; φ each Q4d is independently halogen, hydroxy or cyano; each Q4e is independently Lower alkyl, lower carbon-alkyl , a lower alkoxy group, an amine group, a cycloalkyl group, a phenyl group, a heterocycloalkyl group or a heteroaryl group, optionally substituted by one or more Q 4f; each Q is independently a thiol, a halogen, a low carbon burn a base, a low carbon, a pendant oxy, a lower alkoxy group, a lower alkoxy group, a lower hydroxyalkyl group or an amine group; the limitation is that when Q is a cyclopropyl or thienyl group, R2 and R3 are Η or 曱 _ base ' and any two of R, Rib and Rlc are fluorene or methyl and the other is not hydrazine, hydroxy or hydroxy fluorenyl; and the limitation is that when q is gas, isopropyl, Isopropyl base, mouth base bite, methyl ketone 3 base-amine, methyl 〇 ° 定 -3--3-amino-amino carboxylic acid tert-butyl vinegar, cyclohexyl cyclopentyl-methyl amine Or a cyclohexyl group, and when R2 and r3 are hydrazine or methyl, R", not all hydrazine; or a pharmaceutically acceptable salt thereof. 156090.doc -34. 201204731 The present invention provides a method of treating an inflammatory condition or an autoimmune condition, which comprises administering a therapeutically effective amount of a compound of formula (4) to a patient in need thereof. The present invention provides the above method, which further comprises administering another therapeutic agent selected from the group consisting of a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulator or an immunosuppressive agent, a neurotrophic factor, and a cardiovascular treatment. An agent for a disease, an agent for treating diabetes, or an agent for treating an immunodeficiency disorder. The present application provides a method of treating an inflammatory condition comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 丨 or 〗. The present invention provides a method of treating rheumatoid arthritis comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula [or j]. The present application provides a method of treating asthma comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 1 or hydrazine. The present application provides a method of inhibiting a T cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula 1 or 11. The present invention provides a method of inhibiting a tau cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I or Formula. The present application provides the above method wherein the proliferative disorder is cancer. The present invention provides a method of treating a B cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula or formula. The present application provides a method of treating an immune disorder, including lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, type I diabetes, complications of organ transplantation, xenograft, diabetes, cancer, asthma, Atopic dermatitis, autoimmune verrucous disorder, ulcer 156090.doc -35- 201204731 colitis, Crohn's disease, Alzheimer's disease and leukemia, the method involves patients in need A compound that is administered in a therapeutically effective amount. The present invention provides for the prevention or treatment of all forms of organ rejection (including acute allograft rejection or xenograft rejection and chronic allograft rejection or xenograft rejection) of vascularized or non-vascularized grafts. A method comprising administering a compound of formula I or r to a patient in need thereof. The present application provides a method of inhibiting JAK3 activity comprising administering a compound of Formula I or guanidine, wherein the compound exhibits a concentration of 50 micromolar or less than 50 micromolar in a biochemical assay of JAK3 activity in vitro. 50 value. The present application provides the above method wherein the compound exhibits an IC5 〇 value below the concentration of moxigen or a concentration of 1 〇〇Nemo in the in vitro biochemical detection of JAK3 activity. The present invention provides the above method, wherein the compound exhibits an IC5Q value of 1 〇Nemo concentration or 1 〇Nemo concentration in an in vitro JAK3 activity biochemical assay. The present application provides a method of inhibiting SYK activity comprising administering a compound of Formula I or I wherein the compound exhibits a concentration of 50 micromolar or less than 50 micromolar in an in vitro syk activity bioassay assay. Ic5 depreciation. The present invention provides the above method, wherein the compound exhibits an IC5G value of 10 〇Nemo concentration or 1 〇〇Nemo concentration in an in vitro SYK activity biochemical assay. 156090.doc -36-201204731 The present application provides the above method, wherein the compound exhibits an IC5 〇 value of 1 〇Nemo concentration or 1 〇Nemo concentration in an in vitro SYK activity biochemical assay. The present invention provides a method of treating an inflammatory condition comprising co-administering to a patient in need thereof a therapeutically effective amount of an anti-inflammatory compound and a compound of the formula or formula. The present invention provides a method of treating an immune disorder comprising co-administering to a patient in need thereof a therapeutically effective amount of an immunosuppressant compound and a compound of formula I or guanidine. The present application provides a pharmaceutical composition comprising a mixture of a compound of formula I or I and at least one pharmaceutically acceptable carrier, excipient or diluent. The present invention provides the pharmaceutical compound of the above formula 1 or 1, which further comprises another therapeutic agent selected from the group consisting of a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulator or an immunosuppressive agent, a neurotrophic factor, An agent for treating cardiovascular diseases, an agent for treating diabetes, and an agent for treating an immunodeficiency disorder. The present invention provides the above compounds suitable for the treatment of inflammatory conditions or autoimmune conditions. The present invention provides a compound 0 suitable for treating any of the above conditions. The present invention provides a use of a compound of formula I or guanidine in the manufacture of a medicament for the treatment of an inflammatory condition. The present application provides the use of a compound of the formula in the manufacture of a medicament for treatment from a 156090.doc • 37-201204731 immunological disorder. The present application provides a compound or method as described herein. Examples of representative compounds encompassed by the present invention and which are within the scope of the present invention are provided in the following table. The examples and the preparations are provided to enable those skilled in the art to understand and practice the present invention, and should not be construed as limiting the scope of the invention. In general, the nomenclature used in the present application is based on AUTONOMTM version 4.0, a Beilstein Institute computerized system for generating IUPAC system nomenclature. If there is a discrepancy between the structure and the name given to the structure, then the structure will prevail. In addition, if the stereochemistry of a structure or a portion of a structure is not indicated by, for example, bold or dashed lines, the structure or portion of the structure is understood to encompass all stereoisomers thereof. Table I depicts exemplary compounds of Formula I. Table I. Numbered structure system name MP 1-1 Br 2-bromo-5//·° ratio slightly [2,3-6] pyridin-7-a 248.0-acid (3-hydroxy-2,2-di 250.0 Methyl-propyl)-nonylamine 1-2 2-cyclopent-1-enyl-5H-pyrrolo[2,3-0]pyrene ratio 0 well-7-carboxylic acid ((S)-2-hydroxyl -1,2-dimercapto-propyl)-nonylamine 156090.doc -38 - 201204731 1-3

2-isopropenyl-5H-0 piroxime [2,3-ό]° ratio tillage-7-decanoic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)-guanamine 1-4

Guang 2-didecylamino-5/ί-pyrrolo[2,3-6]pyrazine-7-decanoic acid (3-hydroxy-2,2-dimercapto-propyl)-decylamine 222.0- 224.0

1-5

2-isopropyl-5·ίΓ-0 is more than 2[3,3-6]. Specific tillage-7-formic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-guanamine 1-6

2-cyclopentyl-5//-pyrrolo[2,3-6]» than argon-7-decanoic acid ((S)-2-hydroxy-1,2-dimercapto-propyl> decylamine

1-7

2-cyclohex-1-ylidene-5//·pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-2-yl-1,2-dimethyl-propyl )-guanamine 1-8

2-Cyclopropyl-5//-pyrrole is each [2,3-6]. Specific tillage-7-isopropyl hydrazide 156090.doc -39- >300- 201204731 1-9

2-cyclopropyl-5//-pyrrolo[2,3-6]indole pent-7-decanoic acid (2-decyloxy-1-methyl-ethyl)-decylamine 238.0- 240.0 1- 10

0 2-° ratio slightly bite-1 -yl-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid (3-hydroxy-2,2-dimercapto-propyl)-oxime Amine 220.0-222.0 1-11

2-Cyclohexyl-5//·0 ratio 咯[2,3-6]. Bikoujing-7-formic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-nonylamine 1-12 1-13

2-cyclopropyl-5//-pyrrolo[2,3-6]'^ than 啩-7-carboxylic acid (3-hydroxy-1,1-dimethyl-butyl)-nonylamine 2-cyclopropyl -5-5//-pyrrolo[2,3-punch ratio well 7-formic acid (2-cyano-ethyl)-decylamine 230.0- 232.0 236.0- 238.0 156090.doc -40- 201204731 1-14

〇c 2-(3,3-Dimethylpyrrolidin-1-yl)-5i/-port ratio 0 and [2,3-6] mouth ratio tillage-7-formic acid (3-hydroxy-2, 2-Dimercapto-propyl)-nonylamine 223.0- 225.0 1-15

NH d

OH 2-phenylamino-5i/-° ratio 0 [2,3-6] 〇 耕 -7-decanoic acid (3-hydroxy-2,2-dimercapto-propyl)-decylamine 280.0- 282.0 1-16

2-(indenylJ-anthracenyl-amino)-5//-pyrrolo[2,3-6]pyridin-7-decanoic acid (3-hydroxy-2,2-dimercapto-propyl Base)-bristamine 270- 275 1-17

2-cyclopropyl-5//-pyrrolo[2,3-6]° ratio tillage-7-decanoic acid [2-hydroxy-1 -(2-trans-ethyl-ethyl)-2-mercapto-propyl Base]-bristamine 195- 198 1-18

2-thiophen-2-yl-57f-indolo[2,3-6]° ratio tillage-7-formic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)-decylamine 156090.doc -41 - 201204731 1-19

2-Cyclopropyl-5//·pyrrolo[2,3-punch ratio•• Well-7-decanoic acid (1-cyclopropyl-ethyl)-decylamine 269- 272 1-20 1-21

2-(2-indolyl-° ratio -4-yl)-5//-n ratio [2,3-6]. Specific tillage-7-decanoic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-decylamine 2-(6-mercapto-0-bite-3-3-pyrylene[2 ,3-6]« 比耕-7-carboxylic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)-nonylamine 1-22

2-cyclopropyl-5//·pyrrolo[2,3-6]. Specific tillage-7-decanoic acid ((S)-second butyl)-nonylamine 280.0- 282.0 1-23

2-Cyclopropyl-5//-pyrrolo[2,3-6]indole-7-carboxylic acid ((S)-l,2,2-tridecyl-propyl)-decylamine>300- 156090.doc • 42- 201204731 1-24

2-cyclopropyl-5//-pyrrolo[2,3-6]. Specific tillage-7-decanoic acid ((S)-2-hydroxy-1-isopropyl-2-methyl-propyl)-nonylamine 232.0- 234.0 1-25

2-cyclopropyl-5//-pyrolo[2,3-6]° cultivating -7-decanoic acid ((S)-l,2-dimethyl-propyl)-decylamine 281.0- 283.0 1-26 1-27

2-cyclopropyl-5//-pyrrolo[2,3-6]. Specific spray -7-formic acid (l-ethyl-propyl)-decylamine 245- 246 N, 2-cyclopropyl-5//-pyrrolo[2,3-6]° cultivating -7-decanoic acid (2-Didecylamino-1-methyl-ethyl)-guanamine 225- 229 1-28

2-cyclopropyl-5//-pyrrolo[2,3-6]» than argon-7-cyanate cyanoguanidino- guanamine 240.0- 242.0 156090.doc -43- 201204731 1-29

2-cyclopropyl-5i/-pyrrolo[2,3-6].口井井-7-decanoic acid ((S)-l-ethyl-2-yl-2-methyl-propyl)-nitramine 229.0- 231.0 1-30

2-cyclopropyl-5//-pyrrole and [2,3-6]° ratio tillage-7-formic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)- Amine 269.0- 271.0

2-cyclopropyl-5//-pyrrolo[2,3-6]n ratio ^ well-7-decanoic acid ((lS,2S)-2-hydroxy-l,2-dimethyl-butyl) - guanamine 243.0- 245.0

1-32

2-cyclopropyl-5//-pyrrolo[2,3-6]"Special spray-7-formic acid ((S)-l-cyclohexyl-ethyl)-decylamine 246- 249 1-33

2-cyclopropyl-57/-pyrrolo-; 2,3-punch ratio well-7-decanoic acid (3-cyanopropyl)-nitramine 232.0- 234.0

1-34

2-cyclopropyl-5//-pyrrolo[2,3-6]'^^^^-7-carboxylic acid ((lS52R)-2-yl-l-2-dimethyl-butyl) - Stearic amine 262.0- 264.0 156090.doc • 44- 201204731 1-35

2-Trifluoromethyl-5//-0 ratio argon [2,3-6] ° cultivable-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine 221.0- 223.0 1-36

2-vinyl-5if-pyridyl 0 each [2,3-6]° ratio 0 well-7-formic acid (3-hydroxy-2,2-dimercapto-propyl)-decylamine

1-37

2-cyclopropyl-5//·° ratio [[2,3-punching ratio tillage-7-formic acid [(S)-l-(1 dan-"biazol-3-yl)-ethyl] - guanamine 1-38

2-cyclopropyl-5//-pyrrolo[2,3-6]« specific tillage-7-decanoic acid ((1S,2S)-3-cyclopropyl-2-yl-1,2-di Mercapto-propyl)-bristamine

1-39

2-ethyl-5//.0 piroxime [2,3-crushed cultivable-7-carboxylic acid (3-hydroxy-2,2-dimercapto-propyl)-indoleamine 1-40

OH 2-cyclopropyl-5//-pyrrolo[2,3-6]«bi -7-carboxylic acid ((S)-l-hydroxyindolyl-propyl)-decylamine 250- 252 156090.doc -45- 201204731 1-41

2-cyclopropyl-5/ί·11-pyrolo[2,3-6]吼'well-7-carboxylic acid ((R)-2-hydroxy-1-indolyl-ethyl)-guanamine 265- 268 1-42

2-Cyclopropyl-5//-pyrrolo[2,3-6]indole-well-7-decanoic acid (3-hydroxy-U-didecyl-propyl)-guanamine 250.0- 252.0 1-43

OH 2-((lR,2R)-2-methyl-cyclopropyl)-5//-0 piroxi[2,3-6]0 than argon-7-decanoic acid (3-hydroxy-2, 2-dimethyl-propyl)-guanamine

1-44

2-cyclopropyl-5//-pyrrolo[2,3-6]» than argon-7-decanoic acid ((R)-l-ethyl-2-yl-2-yl-propyl) - guanamine 218.0- 220.0

1-45

2-cyclopropyl-5·ί^-0 ratio 咯[2,3-punching ratio -7-decanoic acid (2-hydroxy-1,1-dimethyl-ethyl)-decylamine 293.0- 295.0 156090.doc -46- 201204731 1-46

2-((lR, 2S)-2-indenyl-cyclopropyl)-5//-. More than 0 each [2, 3-6]. Specific tillage-7-formic acid (3-hydroxy-2,2·didecyl-propyl)-nonylamine 244.0- 246.0 1-47

2-cyclopropyl-57/-pyrrolo[2,3-6]» than well -7-formic acid ((S)-l-hydroxyindenyl-2,2-dimercapto-propyl)-oxime Amine 259.0- 261.0 1-48

2-cyclopropyl-5//·° pyrrolo[2,3-6]» than argon-7-decanoic acid ((lS,2R)-3-cyclopropyl-2-hydroxy-1,2- Dimercapto-propyl)-nonylamine 1-49

pT S>〇H/P

2-cyclopropyl-5/f-pyrrolo[2,3-rushed tillage-7-decanoic acid [(S)-l-(l-yl-1-yl-ethyl)-pentyl] ** Stear amine 170.0- 172.0 1-50 : BH. , 2-cyclopropyl-5//·0 pyrrolo[2,3-6]吼井-7-decanoic acid (2-decyloxy-2-mercapto-propyl)-nonylamine 259.0- 262.0 156090.doc -47- 201204731 1-51

2-Cyclopropyl-5//-pyrrolo[2,3·冲比井-7-decanoic acid-1-hydroxymethyl-ethyl)-guanamine 255.0- 256.7 1-52

ΟΗ 2-Cyclopropyl-5//-pyrrolo[2,3-6]. Specific tillage-7-decanoic acid ((R)-l-hydroxyhydrazino-2,2-dimercapto-propyl)-nitramine 270.0- 273.0 1-53

2-cyclopropyl-5//-° ratio slightly [2,3-punch ratio tillage-7-formic acid ((1S,2R)- 280.0-3,3,3-trifluoro-2-hydroxy 283.0 base- 1,2-dimercapto-propyl)-guanamine

1-54

2-cyclopropyl-5//·0 is more than [2,3-6]-specific tillage-7-decanoic acid ((S)-3,3,3-trifluoro-1,2,2-three Mercapto-propyl)-nonylamine >300-

1-55

2-cyclopropyl-5·//-0-pyrolo[2,3-6]indole-p--7-carboxylic acid (2,2-dimethyl-propyl)-decylamine 156090.doc •48- 201204731

OH 1-56

2-cyclopropyl-5//-0-pyrolo[2,3-6]» than argon-7-decanoic acid ((R)-l-hydroxydecyl-2-methyl-propyl)-hydrazine Amine 250.0- 253.0 1-57

The 2-cyclopropyl-57 ί·0 ratio is [2, 3-6]. Bikoujing-7-formic acid ((S)-2-hydroxy-1-indolyl-ethyl)-guanamine 274.0- 276.0

1-58

2-cyclopropyl-5//-0 ratio » each [2,3-6]° ratio tillage-7-decanoic acid ((R)-l-hydroxyindolyl-propyl)-nonylamine 250.0- 253.0 1-59

2-cyclopropyl-5//-pyrrolo[2,3-6]"specific tillage-7-decanoic acid (3-methoxy-2,2-dimercapto-propyl)-S&amine 230.0- 232.0 1-60

2-cyclopropyl-5//-° ratio is [2,3-6]. Bikoujing-7-formic acid ((R)-l-cyclohexyl-ethyl)-guanamine 253.0- 255.0 156090.doc -49- 201204731 1-61

2-cyclopropyl-5//·° ratio is [2,3-6]. ''• Well-7-decanoic acid (2-cyano-1,2,2-trimethyl-ethyl)-decylamine 295.0- 297.0 1-62 HN^\V % 2-cyclopropyl-5/ /·0 ratio of [2,3-6]° cultivating -7-decanoic acid ((ΙΟ-ΐ, 2,2-trimethyl-propyl)-decylamine 298.0- 300.0 1-63

2-cyclopropyl-5//-° ratio of each [2,3-ό]° ratio 11 well-7-decanoic acid ((1S, 2S)-3,3,3-trifluoro-2-hydroxyl -1,2-dimercapto-propyl)-nonylamine 290.0- 292.0 1-64

2-cyclopropyl-5//-°Pylo-P,3-&]° ratio p-well-7-formic acid ((R)-l-methoxymethyl-2,2-didecyl- Propyl)-guanamine 265- 270 1-65 2-cyclopropyl-5/f-pyridyl 0 each [2,3-δ]° ratio p well-7-formic acid ((S)-l-methoxy Base thiol-2,2-dimercapto-propyl)-nonylamine 268.0- 270.0 156090.doc -50· 201204731 1-66

2-cyclopropyl-5//-pyrrolo[2,3-δ]° ratio tillage-7-formic acid ((R)-l-phenyl-ethyl)-nonylamine 278.0- 280.0 1-67

2-cyclopropyl-5//·0 ratio 咯[2,3-punching ratio -7-decanoic acid ((3)-phenylphenyl-ethyl)-linamide 272.0- 274.0

1-68

2-cyclopropyl-5//·0 ratio 咯[2,3-6]«比耕-7-decanoic acid (3-hydroxy-butyl> guanamine 228.0- 230.0 1-69

2-cyclopropyl-5//-0 ratio 咯[2,3-6]^^ ratio '^井-7-formic acid (3-hydroxy-2-indolyl-propyl)-bristamine 252.0- 254.0

1-70

2-cyclopropyl-5/f-pyrrolo[2,3-6]° morphine-7-indole ratio 0 2-yl-ethyl)-decylamine 217.0- 219.0 156090.doc -51 - 201204731 1- 71

OH 2-cyclopropyl-5//-pyrrolo[2,3-6]° ratio tillage-7-decanoic acid (3-hydroxy-1,2,2-trimethyl-propyl)-decylamine 268.0 - 270.0 1-72

2-0 ratio °-2-yl-5//-0 ratio 0 and [2,3-6]0 ratio tillage-7-formic acid ((S)-1,2,2·trimethyl-propane Base) - guanamine > 300-

1-73

2-cyclopropyl-5//·° ratio is [2,3-6].啩-7-decanoic acid ((3) small cyclopropyl-2-alkyl-2-mercapto-propyl)-nonylamine 238.0- 240.0 1-74

2-cyclopropyl-5//·0 piroxi[2,3-punch ratio well-7-carboxylic acid ((R)-l-cyclopropyl-2-yl-2-yl-propyl-propyl ) - guanamine 235.0- 237.0

1-75 2-cyclopropyl-57/-0 pyrrolo[2,3-6]» than 啩-7-decanoic acid (1-cyclohexyl-propyl)-decylamine 208.0-210.0 156090.doc - 52- 201204731 1-76

2-cyclopropyl-5·ί/~° ratio is [2,3-6]. Specific tillage-7-decanoic acid ((R) small cyanoguanidino-2,2-dimercapto-propyl)-nonylamine 259.0- 261.0 1-77

The 2-cyclopropyl-5·//-° ratio is [2, 3-6]. Specific tillage-7-formic acid ((S)-l-cyanomethyl-2,2-dimethyl-propyl)-guanamine 258.0- 260.0

1-78

2-cyclopropyl-5//-pyrrolo[2,3-6]° Trulli-7-decanoic acid (cyclohexyl-cyclopropyl-methyl)-nonylamine 174.0- 176.0 1-79

2-cyclopropyl-5//-° ratio is [2,3-6]. Specific tillage-7-formic acid (2-hydroxy-l,l,2-trimethyl-propyl)-nonylamine 270.0- 273.0 1-80 2-cyclopropyl-5·ί/*0 ratio 咯[2 ,3-6]»比耕-7-carboxylic acid dicyclopropylmethyl-decylamine 224.0- 226.0 156090.doc -53 - 201204731 1-81

2-cyclopropyl-5//·0 is more than [2,3-6]n than spray _ 7-decanoic acid (2-cyano-1 -cyclopropyl-2,2-didecyl-B Base) - guanamine 230.0- 232.0 1-82

2-cyclopropyl-5/ί-pyrrolo[2,3-6]. Specific tillage-7-decanoic acid [(R)-l-(l-carbamic-cyclopentyl)-ethyl]-nonylamine 287.0- 290.0 1-83

2-cyclopropyl-5//-0 ratio 咯[2,3-punch ratio ρ well-7-decanoic acid ((1R,2R)-2-hydroxy-1,2-didecyl-butyl) - guanamine 245.0- 247.0

1-84

2-cyclopropyl-5//-° ratio of [2,3-6]« than -7-carboxylic acid ((1R, 2R)-2-hydroxy-1,2-didecyl-pentyl) - guanamine 222.0- 224.0 1-85

2-cyclopropyl-5-open-oxo-[2,3-6]° ratio well-7-decanoic acid [1·(tetrahydro-π-decano-4-yl)-ethyl]-醯Amine 260.0- 262.0

156090.doc -54- 201204731 1-86

2-cyclopropyl-5F-pyrrolo[2,3-6]. Specific tillage-7-decanoic acid ((R)-2-cyano-1,2,2-_rL.methyl-ethyl)-nonylamine 278.0- 281.0 1-87

2-3⁄4 propyl-5//-0 ratio 咯[2,3-6].口井井-7-decanoic acid ((5)-2-cyano-1,2,2-trimethyl-ethyl)-nonylamine 277.0- 279.0

1-88

2-cyclopropyl-5//-pyrrolo[2,3-6]. Specific tillage-7-decanoic acid ((1S,2R,3S)-1-cyclohexylmethyl-3-cyclopropyl-2,3-dihydroxy-propyl)-decylamine 1-89

2-cyclopropyl-5//-° ratio of [2,3-δ]η to argon-7-decanoic acid (1-cyano-2-indolyl-propyl)-indoleamine

1-90

2-cyclopropyl-5//-10 ratio 咯[2,3-6]. Specific tillage-7-formic acid (cyano-cyclopropyl-indenyl)-guanamine 156090.doc -55- 201204731 1-91

2-cyclopropyl-5//·° ratio [[2,3-rushing than 啩-7-decanoic acid ((1R,2R)-3- 3-yl-2-yl-1,2-diindole Base-propyl)-guanamine 234.0- 236.0 1-92

3-cyclopropyl-3-[(2-cyclopropyl-5/ί-pyrrolo[2,3-6]. specific tillage-7-carbonyl)-amino]-2,2-didecyl- Propionic acid 265.0- 267.0 1-93

2-cyclopropyl-5//-pyrroloindole, 3-6]»pyrone-7-carboxylic acid (2-hydroxy-2-indolyl-1-trifluoromethyl-propyl)-decylamine 258.0- 260.0 1-94

2-cyclopropyl-5//·0 pyrrolo[2,3-punching ratio -7-carboxylic acid ((S)-l-cyclohexyl-2-yl-2-yl-propyl)- Guanamine 251.0- 253.0 1-95

2-cyclopropyl-5//-pyrrolo[2,3-6].比"井-7-decanoic acid (1-cyclopentyl-ethyl)-nitramine 156090.doc -56- 201204731 1-96 2-phenoxy-5//-pyrrolo[2,3-6] . Specific tillage-7-decanoic acid (1-cyclopropyl-ethyl)-nonylamine 242.0- 245.0 1-97

2-cyclopropyl-5·ί/~0 ratio 咯[2,3-6]. Specific tillage-7-formic acid [(S)-l-(l-hydroxy-cyclopentyl)-ethyl]-nonylamine 292.0- 294.0

1-98

2-cyclopropyl-5//-pyrrolo[2,3-crushed tillage-7-formic acid (3-decanesulfonyl-2,2-dimercapto-propyl)-decylamine 206.0- 208.0 1-99

2-(1-ethyl-1//-pyrazol-4-yl)-5//-pyrrolo[2,3-punch ratio beer-7-decanoic acid ((R)-2-hydroxy-1, 2-dimercapto-propyl;)-nonylamine 270.0- 272.0 1-100

2-cyclopropyl-5//-pyridinium [2,3-6]° ratio 11 Well-7-carboxylic acid [(R)-l-(l-cyano-cyclopentyl)-ethyl]- Guanamine 220.0- 223.0 156090.doc -57- 201204731 1-101

OH 2-cyclopropyl-5//-0 ratio argon [2,3-6]° cultivating -7-decanoic acid [(S)-l-(l-cyano-cyclodecyl)-ethyl ]-guanamine 220.0- 223.0 1-102

2-(1-mercapto-1//-pyridin-2-ylidene-4-ylpyrolo[2,3-6]«比耕-7-decanoic acid ((R)-2-hydroxy-1,2- Dimercapto-propyl)-nonylamine 285.0- 288.0

1-103

OH 2-0 cephen-2-yl-5//· 0 to 0 each [2,3-6]0 than argon-7-decanoic acid ((R)-2-hydroxy-1,2-di Base-propyl)-bristamine 272.0- 275.0 1-104

2-cyclopropyl-5//·0 ratio slightly [2,3-punch ratio] well-7-decanoic acid [(R)-cyclopropyl-(1-carbyl-cyclodecyl)-fluorenyl ]-nonylamine 195.0- 197.0

1-105

V/=\ F 2-(2,4-dioxa-phenoxy)-57/-°pyrho[2,3-6]pyrazine-7-decanoic acid (1-cyclopropyl-ethyl Guanamine 156090.doc -58- 201204731 1-106

2-cyclopropyl-5//·0 pirodi[2,3-6]» than 啼-7-decanoic acid (2-cyano·1-cyclopropyl-ethyl)-decylamine 230.0- 232.0 1-107 2-cyclopropyl-5//-° ratio [2,3-crushed tillage-7-formic acid cyclohexylfluorenyl-bristamine 284.2- 284.7

1-108 1-109

1-110

2-cyclopropyl-5/ί"-0-pyrolo[2,3-6]» than argon-7-decanoic acid (1-decanesulfonyl-piperidin-3-ylmethyl)-hydrazine Amine 2-cyclopropyl-5//-0-pyrolo[2,3-crushed tillage-7-formic acid (1-mercaptopyrrolidine-3-ylindenyl)-nonylamine 2-(3 ,6-Dihydro-2//-piperidin-4-yl)-5//-° ratio 0 and [2,3-6]0 than -7-decanoic acid ((R)-2-hydroxyl -1,2-dimercapto-propyl)-guanamine

247.6- 248.4〇C 248.0- 249.0 156090.doc -59- 201204731 I-lll 1-112

2-thiazol-2-yl-57/-. Biluo[2,3-6]0 is more than -7-decanoic acid ((R)-2-hydroxy-1,2-dimercapto-propyl)-nonylamine 2-0 than bit-2-yl -5//· 0 ratio of each [2,3-6]° cultivating -7-decanoic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-decylamine 1- 113

2-(4-Any-phenoxy)-57/-n ratio of argonium [2,3-6]0 to argon-7-decanoic acid (1-cyclopropyl-ethyl group > decylamine

1-114

2-(2-D-phenoxy)-5i/-° than s-[2,3-6]' whistle-7-decanoic acid (1-cyclopropyl-ethyl)-decylamine

1-115

2-cyano-57/-pyrrolo[2,3-crushed tillage-7-decanoic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-nitramine 156090.doc • 60· 201204731 1-116

2-phenoxy-5i/-.比和和[2,3-6]^比耕-7-carboxylic acid ((R)-2-hydroxy-1,2-dimercapto-propyl)-guanamine 1-117

2-cyclopropyl-5//*° ratio [2,3-ό]吼耕-7-decanoic acid [(R)-l-(l-cyano-cyclohexyl)-ethyl]-oxime Amine 1-118

2-cyclopropyl-5·/ί·α ratio[2,3-punch ratio spray-7-decanoic acid [(S)-l-(l-cyano-cyclohexyl)-ethyl]-oxime Amine 1-119

2-phenoxy-5//-« ratio 0 each [2,3-ό]°Λ-7-7-isopropyl hydrazide 263- 265 1-120

2-phenoxy-5//·° ratio [[2,3-6]"t^井-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)- Guanamine 270- 273 156090.doc -61 - 201204731 1-121

2-phenoxy-5//-.倍比和[2,3-6]» 比耕-227-7-decanoic acid ((S)-second 229 butyl)-nonylamine 1-122

The 2-phenoxy-5//-° ratio is [2,3-6]. Specific tillage-7-formic acid ((S)-l,2-dimercapto-propyl)-nonylamine 234- 235 1-123

2-phenoxy-5//-° ratio 咯[2,3-ό]° 啩-227-7-decanoic acid ((S)-l-ring 230 hexyl-ethyl)-nitramine

1-124

2-(2,4-dioxa-phenoxypyrazine P,3-6]pyrazine-7-decanoic acid ((R)-l-cyclohexyl-ethyl)-nitramine 233.0- 235.0 1- 125

2-(2,4-Bismo-phenoxy)-5//-pyrrolo[2,3-6]« specific tillage-7-曱224.0-acid ((S)-2-hydroxy· 226.0 1, 2-dimercapto-propyl)-guanamine

1-126

2-(2,4-Dilacyl-phenoxy)-5//-.倍比和[2,3-6]» 比耕-7-曱 acid ((R)-secondyl)-guanamine 246.0- 248.0 156090.doc -62- 201204731 1-127

2-(2,4-Difluoro-phenoxy)-5//-° ratio of [2,3-δ]° to plough-7-formic acid ((R)-l,2-didecyl- Propyl)-guanamine 235.0- 237.0 1-128 1-129

2-phenoxy-5//-pyrrolo[2,3-6]pyridin-7-decanoic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)-guanamine 2 -phenoxy-5//-"bibromo[2,3-flush ratio _-7-carboxylic acid ((R) small cyclohexyl-ethyl)-decylamine 232-233 231-232

1-130

2-phenoxy-5//-.比和和[2,3-6]»比'^井-7-carboxylic acid ((R)-l,2,2-trimethyl-propyl)-nitramine 273- 274 1-131

2-phenoxy-5//-吼 咯[2,3-δ]. Specific tillage-7-formic acid ethylguanamine 230-232 156090.doc -63- 201204731 1-132

The 2-(2,4-difluoro-phenoxy)-57/-° ratio is slightly [2,3-6]. Specific tillage-7-isopropyl isopropylamine 1-133

2-(2,4-Difluoro-phenoxy)-5 ugly-.咯和和 [2,3-6]吼耕-7-曱 acid ((S)-1,2,2-trimethyl-propyl)-guanamine 1-134

2-(2,4-difluoro-phenoxypyrolo[2,3-6]indole argon-7-decanoic acid ((R)-1,2,2-tridecyl-propyl)- Guanamine 1-135

2-cyclopropyl-5//·pyrrolo[2,3-6]» ratio-well 7-decanoic acid ((R)-2-cyano-1 -cyclopropyl-ethyl)-decylamine 1 -136

2-cyclopropyl-5//~π ratio 咯[2,3-rushing ratio tillage-7-formic acid (1-ethylindenyl-pyrylene-3-ylmethyl)-nitramine 198.4- 199.1 1- 137

2-cyclopropyl-57/-pyrrolo[2,3-crushed tillage-7-formic acid (1-ethylindolyl-to-1α-dec-3-ylmethyl)-decylamine 233.8- 235.0 156090.doc -64- 201204731 1-138

2-(1-ethyl-1//-pyrazol-4-yl)-5i/-pyrrolo[2,3-6]"specific tillage-7-decanoic acid [(S)-1-(1 -hydroxy-cyclopentyl)-ethyl]-nonylamine 1-139

2-(1-Mercapto-1//-pyrazol-4-yl)-5//-pyrrolo[2,3-6]. Specific tillage-7-formic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-decylamine

1-140 2-(1-Methyl-1//-pyrazole-4-ylpyrolo[2,3-6]"Big Geng-7-formic acid ((S)-l-cyclohexyl-B Base)-nonylamine 1-141

ΝΛ 2-(1-mercapto-1//-pyrazol-4-yl)-5//-pyrrolo[2,3-rushing tillage-7-decanoic acid ((S)-l,2,2 -tridecyl-propyl)-nonylamine 296- 297 1-142

2-thiophen-2-yl-5//-πpyrolo[2,3-6]° ratio ρ well-7-decanoic acid ((S)-1,2,2-trimethyl-propyl) - guanamine 311- 312 156090.doc -65- >300201204731 1-143 1-144

2-(4-Trifluoromethyl-phenyl)-5//-pyrrolo[2,3 clock ratio 'well-7-decanoic acid ((S)-l,2,2-trimethyl-propyl - indoleamine 2-cyclopropyl 0 each [2,3-ό]β ratio 11 well-7-carboxylic acid ((S)-3-indole-burning-based 1,2,2-tridecyl- Propyl)-guanamine 232- 234 1-145

α 2-[1-(3-Gas-phenyl)-17/-imidazol-4-yl]-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S) -l,2,2-trimethyl-propyl)-nonylamine 337- 339 1-146

2-[1-(3-Trifluoromethyl-phenyl)-1//-imidazol-4-yl]-5//-pyrrolo[2,3-6]° than argon-7-nonanoic acid ( (S)-l,2,2-trimethyl-propyl)-guanamine 332- 333 1-147

2-[1-(5-Gas-2-a-phenyl)-1//-imidazol-4-yl]-5//-° ratio P, 3-6]. Specific tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 337-339 156090.doc -66- 201204731 1-148

2-[l-(2-Fluoro-5-indenyl-phenyl)-1//-imidazol-4-yl]-5//-pyrrolo[2,3-6]. Specific tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 331- 332 1-149

2-[1-(2-Fluoro-5-trifluoromethyl-phenyl)-1//-imidazol-4-yl]-5//·-pyrrolo[2,3-6]pyrazine-7 -capric acid ((S)-l,2,2-tridecyl-propyl)-nonylamine>300 1-150

2-(1-m-phenylphenyl-li/-imidazol-4-yl)-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2 -trimethyl-propyl)-guanamine 314- 316

1-151

2-[l-(3-ethyl-phenyl)-1//-imidazol-4-yl]-5/f-. More than [2,3-6].啩-7-曱 acid ((S)-l,2,2-trimethyl-propyl)-decylamine 284- 287 156090.doc -67- 201204731 1-153

2-[l-(3-isopropyl-phenyl)-1//-imidazol-4-yl]-5//-° 嘻 242- [2,3-6]° 啼-7-曱245 acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 2-[1-(3- ritriyl-phenyl)-1//-imidazol-4-yl ]-5/ί-pyrrolo[2,3-punching ratio 226_ 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

1-154

2-(l,3-Dimercapto-1//-pyrazol-4-yl)-5//-pyrrolo[2,3-6]pyrrole-7-decanoic acid ((S)-2-曱oxy-1-methyl-ethyl)-nonylamine 1-155

2-(5-ethylamine-mercapto-phen-2-yl)-5//-pyrrolo[2,3-6] ° than tillage-7-decanoic acid ((S)-l, 2, 2 -trimethyl-propyl)-guanamine

1-156

2-(5-isopropylaminoindenyl-thiophen-2-yl)-5/^pyrho[2,3-6]» than argon-7-decanoic acid ((S)-l, 2, 2-trimethyl-propyl)-guanamine 156090.doc -68 - 201204731 1-157

2-(5-茗三rylaminoindenyl-thiophen-2-ylpyrolo[2,3-ό]° than 啩-7-carboxylic acid ((S)-l,2,2-tridecyl -propyl)-nonylamine 1-158

2-[5·(1-indolyl-2-°°°-1-yl-ethylaminemethanyl)-thiophen-2-yl]pyrho[2,3-6]pyrr. Well-7-decanoic acid ((S)-1,2,2-trimethyl-propyl)-nonylamine 1-159

2-{5-[2-(4-Fluoro-phenyl)-1-indolyl-ethylamine decyl]-thiophen-2-yl b-5//-pyrrolo[2,3-pumping -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

1-160

2-(5-diethylaminecarbazyl-11-cephen-2-ylpyrolo[2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2-three Methyl-propyl)-nonylamine 1-161

2-[5-(4-indolyl-pipeline-1-carbonyl)-thiophen-2-yl]-5//-pyrrolo[2,3-crushed tillage-7-decanoic acid ((3)-1, 2,2-trimethyl-propyl)-guanamine 156090.doc -69 201204731 1-162

2-[5-((R)-l-cyclopropyl-ethylamine decyl)-11 cephen-2-yl]-5//-pyrrolo[2,3-6]pyrene-7 -formic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-163

2-[1-(3-vinyl-phenyl)-1//-imidazol-4-yl]-5//·11 is more than B and 253-[2,3-6]pyrazine-7-曱257 acid ((S)-l,2,2-trimethyl-propyl)-guanamine

1-164

2-{5-[(Acridine-3-ylindenyl)-aminoindenyl]-n-cephen-2-yl}-5//-pyrrolo[2,3-6]pyrazine-7- Formic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-165

2-{5-[(°°°-4-ylmethyl)-amine sulfhydryl]-11 cephen-2-yl}-57/-pyrrolo[2,3-ό]0 to 11 well -7-formic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

1-166

2-{5-[(° ratio bit-2-ylmethyl)-amine sulfhydryl]-11 cephen-2-yl}-pyrrolo[2,3-6]0 to 11 well-7-formic acid ((S)-l,2,2-Trimethyl-propyl)-decylamine 156090.doc -70- 201204731 1-167

2-[5-(4-cyano-piperidines small carbonyl)-thiophen-2-yl]-5//·D Biluo[2,3-6]° ratio p well-7-decanoic acid (( S)-l,2,2-trimethyl-propyl)-nonylamine 1-168

2-[5-(cyclopentyl decyl-amine-carbamoyl)-thiophen-2-yl]-5//-pyrrole and [2,3-6]° than argon-7-decanoic acid (( S)-l,2,2-trimethyl-propyl)-guanamine

1-169

2-[5-((R)-2-Hydroxy-1 -mercapto-ethylaminecarbamimidyl)-thiophen-2-yl]-5//-° ratio P, 3-6].啩-7-曱 acid ((S)-l,2,2-trimethyl-propyl)-guanamine 1-170

2-[5-((R)-l-indolyl-2-phenyl-ethylaminemethanyl)-thiophen-2-yl]-5//-pyrrolo P,3-6]pyrazine- 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-171

2-[5-(1-Pyridin-3-yl-ethylaminecarbamimidyl)-porphin-2-yl]-5//-° ratio [2,3-6]. Ratio 11 Well-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 156090.doc -71 201204731 1-172

2-[5-(Actylmethyl-amine-carbamoyl)-thiophen-2-yl]-57/-pyrrolo[2,3-6]"Compared tillage-7-decanoic acid ((S)- l,2,2-Trimethyl-propyl)-nonylamine 1-173

2-[5-(2-Aminosulfonyl-ethylaminoindenyl)-porphin-2-yl]-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid (( S)-l,2,2-trimethyl-propyl)-nonylamine 1-174

2-[5-(2-imidazol-1-yl-1-methyl-ethylaminoindolyl)-thiophen-2-yl]-5//-. Ratio of [2,3-6]° to well -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

1-175

2-[5-(4-hydroxy-4-methyl-slightly bite-1-rebase)-°cephen-2-yl]-5i/-pyrrolo[2,3-6]0 ratio p well- 7-formic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

1-176

2-[5-(1-indolyl-2-0 ratio. 1,4-yl-ethylaminemethanyl)-thiophen-2-yl]-5/ί-pyrrolo[2,3-6] » Beyond -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -72- 201204731 1-177

2-[5-(7-azabicyclo[2.2.1]heptan-7-yl-yl)-11-cephen-2-yl]-5//-°pyrho-p,3-6]pyridyl Plowing -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-178

2-[5-(3-Cyano-azetidin-1-carbonyl)-°cephen-2-yl]-5//-» bis-[2,3-6]pyr- 0 well- 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

1-179 1-180

2-[5-(3-Aminoindolyl-cyclohexanexan-1-yl)-. Cephtho-2_yl]-5//-. Bisino[2,3-6]吼耕-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine 2- [5-(azetidin- 1-amino)-03⁄4 phen-2-yl]-5//-pyrrolo P,3-6]n than tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl Base)-nonylamine 1-181

,2-[5-(2,6-dimethyl-pyro--1-reyl)-n-cephen-2-yl]-57/-pyrrolo[2,3-6]0 than p- 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine 156090.doc -73- 201204731 1-182 Ο

L-{5-[7-((S)-1,2,2-Trimethyl-propylamine fluorenyl)·pyrrolo[2,3-6]0 ratio p--2-yl]- Dextran-2-meryl}-0-pyridin-4-indole

2-[5-(4-Ethylideneamino-π-bottom-1-rebase)-°cephen-2-yl]-5//-° ratio of [2,3-ό]° '• Well-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-184

2-[5-(4-indolyl-phenylhydrazinylfluorenyl)-porphin-2-yl]-5//· 0 to 0 and [2,3-6]0 to 啩-7- Capric acid ((S)-1,2,2-trimethyl-propyl)-decylamine

1-185 1-186

2-[5-(4-H-Benzylaminoindenyl)-thiophen-2-yl]-5//-. Bis-[2,3-6]〇 ratio 'well-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-bristamine 2-[5-(2,3- Dioxo-phenylhydrazinyl fluorenyl)· 吩 -2--2-yl]-5//-pyrrolo[2,3-ό]0 than plough-7-formic acid ((S)-l,2,2 -trimethyl-propyl)-guanamine

156090.doc -74- 201204731 1-187

2-[5-(2-indolyl-phenylhydrazinylfluorenyl)-thiophen-2-yl]-5//-° ratio 0 and [2,3-6]° ratio tillage-7-formic acid ((S)-1,2,2-trimethyl-propyl)-nonylamine 1-188

2-[5-(2,6-difluoro-benzoindolino)-decenophen-2-yl]-5//-pyrrolo[2,3-decanoic acid ((S)-l , 2,2-trimethyl-propyl)-nonylamine 1-189

2-[5-(2-Ga-6-H-phenylhydrazinylfluorenyl)-03⁄4-phen-2-yl]-5//-pyrrolo[2,3-6]° ratio Well-7 -Citrate ((S)-l,2,2-trimethyl-propyl)-nitramine

1-190

2-[5-(2-indolyl-cyclohexylamine fluorenyl)-thiophen-2-yl]-5//-° ratio 0 and [2,3-6]° 啩-7-decanoic acid ((S)-1,2,2-trimethyl-propyl)-guanamine 156090.doc -75- 201204731 1-191 1-192

2-[5-((lS,2R)-2-phenyl-cyclopropylaminemethanyl)-thiophen-2-yl]-5//-吼 并[2,3-6]° -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 2-{5-[(4-methyl-thiophen-2-ylmethyl)-amine oxime ]]-thiophen-2-yl}-5-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

1-193

2-{5-[(5-fluorenyl-indol-2-ylindenyl)-aminecarboxylidene]-thiophen-2-yl}-5--"pyrho[2,3-6] ° Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-194 1-195

2-[5-(adamantan-1-ylaminoindolyl)-thiophen-2-yl]-5i/-pyrrolo[2,3-crushed tillage-7-formic acid ((S)-l,2 ,2-trimethyl-propyl)-nonylamine 2-{5-[1-(4-fluoro-phenyl)-ethylaminemethanyl]-15-cement-2-yl}-5// -pyrrolo[2,3-6]» than argon-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

156090.doc -76- 201204731 1-196 1-197

2-[5-(decyloxy-indolyl-amine-carbamoyl)-thiophen-2-yl]-5//-pyrrolo[2,3-crushed tillage-7-decanoic acid ((S)- l,2,2-trimethyl-propyl)-nonylamine 2-(5-nonyloxyamine fluorenyl-thiophen-2-yl)-5/fn ratio [2,3-6]&quot Specific ratio of -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

1-198 1-199

2-(5-prop-2-ynylaminoindolyl-thiophen-2-yl)-5-indole-pyrrolopyrene, 3-δ]« 比耕-7-decanoic acid ((S)-l , 2,2-trimethyl-propyl)-nonylamine 2-{5-[(R)-2-(3//-imidazol-4-yl)-1-indenyl-ethylamine fluorenyl ]Sentene-2·yl}-5//-pyrrolo[2,3-6]"#11 Well-7-carboxylic acid ((S)-l,2,2-tridecyl-propyl)- Guanamine

1-200

2-[5-(5,6,7,8-tetrazine-cai-2-ylaminoindolyl)-thiophen-2-yl]pyrho[2,3-ό]° than tillage-7- Capric acid ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -77- 201204731 1-201 1-202

P

2-(5-Phenylaminomercapto-n-secen-2-yl)-5//-pyrrolo[2,3-6]pyridin-7-carboxylic acid ((S)-l,2, 2-trimethyl-propyl)-guanamine 2-[5-((R)-l-p-nonylphenyl-ethylamine oxime)-嗟-phen-2-yl]-5//-» Bis-[2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 1-203

2-[5-(2-methoxy-phenylhydrazinocarbamimidyl)-indol-2-yl]-5 from pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S) -l,2,2-trimethyl-propyl)-nonylamine 1-204

2-[5-(2,5-dimethoxy-phenylhydrazinocarbyl)-03⁄4-phen-2-yl]-5//-"bibromo[2,3-6]° ratio Plough-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine 1-205

2-{5-[(4-Gas-Benzyl)-methyl-aminocarbamimidyl]-11 thiophene-2-yl}-5//-pyrrolo[2,3-carboxylic acid ((S) -l,2,2-trimethyl-propyl)-guanamine 156090.doc -78- 201204731 1-206

2-[5-(3-decyloxy-phenylhydrazinylfluorenyl)-〇cephen-2-yl]-5//-pyrrolo[2,3-6] ° ratio 11 well-7- Capric acid ((S)-l,2,2-trimethyl-propyl)-decylamine

1-207 1-208

2-[5-(3-Trifluoromethyl-benzoylamine fluorenyl)-thiophen-2-yl]-5/^ is more than [2,3-6]. Specific tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 2-[5-(2-gas-4-vorvyl-phenylaminoindenyl)-°塞 phen-2-yl]-5·ί/~ ° piroxi[2,3-6]° cultivating -7-decanoic acid ((S)-1,2,2-tridecyl-propyl) - guanamine 1-209

2-[5-((R)-l,2,2-trimethyl-propylamino)-thiophen-2-yl]-5//-pyrrolo[2,3-6]pyrazine -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

2-[5-(2,2-Dimercapto-propylaminemethanyl)-indol-2-yl]-5/ί-pyrrolo[2,3-ό]0 is compared to hydrazine-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -79- 201204731 1-211

1-212

2-[5-((R)-2-methanesulfonyl-1-methyl-ethylaminemethanyl)-thiophen-2-yl]-57f-0pyrho[2,3-6] ° ratio tillage-7-formic acid ((S)-1,2,2-trimethyl-propyl)-bristamine 2-[5-(1,1-di- oxo-hexanitro-1 into 6- Thiopiperazin-4-ylaminemethanyl)-thiophen-2-yl]-57/-»birtho[2,3-6]» than argon-7-decanoic acid ((S)-l, 2,2-trimethyl-propyl)-nonylamine 1-213

2-[5-(1,1-di-l-oxy-1 λ6-thio-indol-4-yl)-infrared-2-yl]-5-butyr-[2,3-cylinder -7-formic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-214

2-[5-(2-Methoxy-1·indolyl-ethylamine fluorenyl)-thiophen-2-yl]-5//-. More than [2,3-δ]. Specific tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -80 - 201204731 1-215

2-(5-Aminyl-thiophen-2-yl)-5//-° ratio 0 and [2,3-6]° ratio tillage-7-decanoic acid ((S)-1,2, 2-trimethyl-propyl)-nonylamine 1-216

1-217

2-[5-(3,3,3-trifluoro-propylaminemethanyl)-thiophen-2-yl]-5/f-0 piroxi[2,3-6]° - citric acid ((S)-1,2,2-trimethyl-propyl)-nonylamine 2-[5-(2-oxa-6-aza-spiro[3.3]heptane-6- Kesenophen-2-yl]-5//·0 is more than [2,3-6]. than argon-7-decanoic acid ((S)-l,2,2-tridecyl-propyl) - guanamine

1-218

2-[5-(3,3-bis-hydroxyindenyl-azetidin-1-carbonyl)-thiophen-2-yl]-5//·pyrrolo[2,3-6]" ^^井-7-Citrate ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -81- 201204731 1-219

HN

2-[4-Methyl-5-(tetrazo-n- ace-4-ylamine fluorenyl)-thiophen-2-yl] is slightly more than [2,3-6]. Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nonylamine 1-220

2-[5-(1,1-di- oxo-1λ6-thiomorpholine-4-carbonyl)-4-indolyl-α-cephen-2-yl]-5//-pyrrolo[2, 3-ό]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

1-221

2-[4-amily-5-(2-oxa-6-aza-spiro[3.3]heptane-6-carbonyl)_<Icephen-2-yl]-5/f-pyrrolo[ 2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2-tridecyl-propyl)-bristamine 1-222

2-[5-(3,3-bis-hydroxymethyl-azetidin-1-yl)-4-methyl-thiophen-2-yl]-5--- 3-6]° than tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

156090.doc -82 · 201204731 1-223 1-224

2-[5-(tetrazine-pyridin-4-ylaminoindolyl)-thiophen-2-yl]-5//-° ratio 0 and [2,3-6]〇比耕-7- Capric acid ((3)-2-cyano-1,2,2-trimethylethyl)-guanamine oxime 2-[5-(piperidin-1-carbonyl)- sultin-2-yl] -5/ί-pyrrolo[2,3-6]pyridin-7-carboxylic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl) acetamide 253- 257 1- 225

2-[5-(tetrahydro- bottom 0-alkyl-4-ylamino)-thiophen-2-yl]-5/ί-0 than the mouth and [2,3-ό]° than the whistle-7- Citrate ((S)-1,2,2-trimethyl-propyl)-nonylamine 333- 334

1-226

2-(5-phenylhydrazinyl aryl-7-cephen-2-ylpyrolo[2,3-6]. Ratio-well-7-formic acid ((S)-l,2,2-three Mercapto-propyl)·guanamine 225- 226 156090.doc -83 - 201204731 1-227

2-[5-(3-indolyl-benzylaminoindolyl)-thiophen-2-yl]-5//-°piro[2,3-δ]α than plough-7-formic acid ( (S)-1,2,2-trimethyl-propyl)-nonylamine 1-228 1-229

2-(3-cyano-phenoxy)-57/-pyrrolo[2,3-6]° ratio tillage-7-formic acid isopropylamine 2-(3-decyloxy-phenoxy) -5//~°Biluo[2,3-6]° Tillage-7-Isopropylguanidate 1-230

2-(3-Trifluoromethoxy-phenoxy)-5//-0 ratio 0 and [2,3-6]0 ratio tillage-7-formic acid isopropylamine 1-231

2-(3-Tertibutyl-phenoxy)-5//-pyrrolo[2,3-leaf than well-7-isopropyl isopropylamine 1-232

2-m-tolyloxy-5/f-pyrrolo[2,3-6]pyrazine-7-decanoic acid isopropyl guanamine 156090.doc -84- 201204731 1-233

2-(3-ethyl-phenoxylpyrrolo[2,3-6]° than argon-7-isopropyl decylamine 1-234

2-(3-isopropyl-phenoxy)-5/f-pyrrolo[2,3-6]' than argon-7-formic acid isopropyl guanamine

1-235

2-(3-Trifluoromethyl-phenoxy)-5//-pyrrolo[2,3-6] ° than argon-7-isopropyl decylamine 1-236

2-(2-Trifluoromethyl-phenoxy)-5//-pyrrolo[2,3-punching ratio tillage-7-isopropyl isopropyl hydrazine

1-237

2-(2-phenylhydrazino-phenoxypyrrolo and P,3-6]pyrazine-7-carboxylic acid isopropylamine 1-238

2-(2-Ethyl-phenoxy)-5//-pyrrolo[2,3-indole]pyridin-7-decyl isopropylamine 156090.doc -85 - 201204731 1-239

2-(5,6,7,8-tetrahydro-cai-1-yloxy)-5//-pyrrolo[2,3-6]pyrrol-7-formic acid isopropylamine 1-240

2-(5,6,7,8-tetrazole-naphthalen-2-yloxy)-57/-pyrrolo[2,3-6]pyrazine-7-formic acid isopropylamine 1-241

2-(Cai-1-yloxy)-5//-pyrrolo[2,3-6]° ratio tillage-7-formic acid isopropylamine

1-242

2-(Ginger-2-yloxy)-5//-pyrrolo[2,3-6]pyrazine-7-decyl isopropyl decylamine 1-243

2-(3-Chloro-phenoxy)-5/f-pyrrolo[2,3-6]pyrrole-7-decanoic acid isopropyl decylamine

1-244

2-(3-Gas-phenoxy)-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid ethyl decylamine 1-245

2-(3-Cyano-phenoxy)-5//-° piroxi[2,3-6]. Specific tillage-7-decanoic acid ethyl guanamine 156090.doc • 86 - 201204731 1-246

2-(3-Trifluoromethoxy-phenoxy)-5i/_ ° ratio of each [2,3-6]0 ratio arbutin-7-decanoate ethyl decyl 1-247

2-(3-t-butyl-phenoxyl-pyrrolo[2,3-punching ratio tillage-7-decanoic acid ethylguanamine

1-248

2-m-tolyloxy-pyrolo[2,3-indene]pyrrol-7-formic acid ethyl decylamine 1-249

2-(3-Ethyl-phenoxy)-5/ί-η ratio is [2,3-6]. Specific tillage-7-decanoic acid ethyl guanamine 1-250

2-(3-isopropyl-phenoxy)-5//-pyrrolo[2,3-6]° cultivating -7-decanoic acid ethyl decyl 1-251

2-(3-Trifluorodecyl-phenoxy)-5//-pyrrole each [2,3-6]° ratio 11 well-7-ethyl decanoate 1-252

2-o-phenoxy-5//-pyrrolo[2,3-6]pyrazine-7-decyl isopropyl decylamine 156090.doc -87- 201204731 1-253

2-(2-Trifluoromethoxy-phenoxy)-5//-0 ratio 0 and [2,3-6]〇 ratio 啩-7-decanoic acid isopropylamine 1-254

2-(2,2-Dimethyl-2,3-dihydro-benzofuran-7-yloxy)-5//-pyrrolo[2,3-ό]0 than tillage-7-decanoic acid Isopropyl urethane 1-255

2-(2-Chloro-phenoxy)-5//-pyrrolo[2,3-6]pyridin-7-formic acid isopropyl decylamine

1-256

2-(2-methoxy-phenoxy)-5lepyrrolo[2,3-6]« than isopropyl-7-decanoate 1-257

2-o-phenoxy-5//-quot;bibromo[2,3-6]pyrrol-7-formic acid ethyl decylamine

2-(3,5-Dimethoxy-stanoyloxy)-5//-° ratio is [2,3-6]. Ratio _-7-isopropyl hydrazide 156090.doc _ 88 · 201204731 1-259

2-(5,6,7,8-tetrazo-naphthalen-1-yloxy)-5//·pyrrolo[2,3-6]pyrrol-7-formic acid ethyl decylamine 1-260

2-(5,6,7,8-tetrahydro-naphthalen-2-yloxy)-5//-pyrrolo[2,3-δ]pyridin-7-decanoic acid ethyl amide

1-261

2-(Cai-1-yloxy)-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid ethyl decylamine 1-262

2-(%-2-yloxy)-5/f-pyrrolo[2,3-6]pyrrol-7-formic acid ethyl amide 1-263

2-(3,5-dimethoxy-phenoxy)-5/ί-η ratio 0 each [2,3-ό]β ratio p well-7-decanoic acid ethyl phthalamide 1-264

2-(3-decyloxy-phenoxy)-57/-° ratio and [2,3-6]' than argon-7-formate ethyl decylamine 1-265 156090.doc

2-(2-Chloro-phenoxy)-5//-pyrrolo[2,3-6]pyrrol-7-decanoic acid ethyl decylamine 201204731 1-266

2-(4-cyano-phenoxy)-5//-. More than [2,3-6]. Specific tillage-7-isopropyl isopropylamine 1-267 1-268

2-(4-cyano-phenoxy)-5//-° ratio of [2,3-6]pyrazine-7-carboxylic acid ethylguanamine 2-((R)-3-decanesulfonate Stearic amine-segmentation _ 5-yloxy)-5//-pyrrolo[2,3-crushed tillage-7-formic acid isopropyl guanamine

1-269

2-((R)-3-Ethylideneamino-indan-5-yloxy)-5/ί-pyrrolo[2,3-6]«pyrylene-7-isopropyl decylamine 1-270

2-((R)-3-methanesulfonylamino-pumpy-5-yloxy)-5/f-pyrrolo[2,3-punch than well-7-formic acid ethylguanamine

1-271

2-((R)-3-Ethylamino-indan-5-yloxypyrolo[2,3-6]indole ratio tillage-7-decanoic acid ethyl decyl 156090.doc -90 - 201204731 1-272

2-(1//-吲哚-6-yloxy)-5//-pyrrolo[2,3-6]n than argon-7-isopropyl decylamine 1-273

吲哚-6-yloxy)-5//-n ratio and [2,3-6]" than cultivating -7-decanoic acid ethyl decylamine

1-274

2-(1//-吲哚-4-yloxy)-5-indole-pyrrole and [2,3-6]"specific tillage-7-isopropyl decyl phthalate 1-275

2-(1//-吲哚-4-yloxy)-5/ί-° ratio and [2,3-6]. Specific tillage-7-decanoic acid ethyl phthalamide 1-276

2-(1-mercapto-1//-吲D--6-yloxy)-5-pyrrolo[2,3-6] ° than argon-7-isopropyl decylamine 1- 277

2-(1//-吲哚-5-yloxy)-57/-pyrrole[2,3-6]« specific tillage-7-isopropyl decyl phthalate 1-278

2-(6-fluorenyl-° ratio bit-2-yloxypyrrolo[2,3-crushed tillage-7-isopropyl isopropylamine 156090.doc -91 - 201204731 1-279

2-(4,6-Dimercapto-pyridin-2-yloxy)-5//-pyrrolo[2,3-6]pyrazine-7-formic acid isopropylamine 1-280

2-(2-mercapto-0-bite-3-yloxy)-5//·pyrrolo[2,3-crushing argon-7-isopropyl isopropyl hydrazine 1-281 1-282

2-((R)-3-Amino-pump-5-yloxy)-5/7-pyrrolo[2,3-6]pyridin-7-carboxylic acid isopropylguanamine 2-(( R)-3-propenylamino-pump-5-yloxy>5//-pyrrolo P,3-6]pyrazine-7-isopropyl decyl decylamine

1-283

2-{(R)-3-[(tetrahydro-π-decano-4-yl)-amino]-indan-5-yloxy}-5//-pyrrolo[2,3-6 Pyridin-7-isopropyl decyl citrate

1-284

2-[(R)-3-(cyclopropane-yl-amino)-p--5-yloxy]-5//-pyrrolo[2,3-6]0 than phenyl-7-decanoic acid Isopropyl decylamine 156090.doc -92- 201204731 1-285

2-[(R)-3-(2,2-dimethyl-propionylamino)-pump-5-yloxy]-5//-n ratio [2,3-6] ° 耕-7-formic acid isopropylamine 1-286

2-((R)-3-phenylhydrazinoamino-p--5-yloxy)-5//-indole-[2,3-crushed -7-decanoic acid isopropyl Guanamine

1-287

2-((R)-3-Ethylamino-??-p--5-yloxy)-5/f-pyrrolo[2,3-6]» than argon-7-decanoic acid ((S )-l,2,2-trimethyl-propyl)-nonylamine 1-288

2-((S)-3-Ethylamino-p--5-yloxypyrrolo[2,3-6]° than argon-7-isopropyl decyl decylamine

1-289

2-((S)-3-Amino-pump-5-yloxy)-5//-pyrrolo[2,3-6]pyrazine-7-decyl isopropylamine 1-290

2-(Fly-5-yloxy)-5//-.咯比和[2,3-6]吼耕-7-isopropyl decyl amide 156090.doc -93 - 201204731 1-291 1-292

2-((R)-l-ethinylamino-?p--5-yloxy)-5//-pyrrolo[2,3-flush ratio 11 well-7-decanoic acid ((S) -l,2,2-trimethyl-propyl)-nonylamine 2-[(R)-3-(3-indolyl-glycosyl)-p--5-yloxy]-5//- ° ratio is [2, 3-6]. Ratio _-7-isopropyl hydrazide citrate 1-293

2-(3-Pyly-Sp-pan-5-yloxy)-5i/-pyrrolo[2,3-6]. Bikou well-7-isopropyl hydrazide

1-294

2-((R)-3-Ethylamino-pyridyl P--5-yloxy)-5//-pyrrolo[2,3-6]' than argon-7-decanoic acid ((R )-l-cyclopropyl-ethyl)-nonylamine 1-295

2-((R)-3-Ethylamino-indan-5-yloxypyrazine, 3-6]pyrazine-7-decanoic acid ((S)-l-cyclopropyl- Ethyl)-bristamine

1-296

2-((R)-3-Ethylamino-indan-5-yloxypyrolo[2,34]' than argon-7-decanoic acid ((S)-second butyl)-醯amine 156090.doc •94- 201204731 1-297

2-(3-Sideoxy-indole-5-yloxy)-5i/-indolo[2,3-6]pyridin-7-formic acid isopropylamine 1-298

2-((R)-3-Ethylamino-pump-5-yloxy)-5//-° ratio [2,3-punching ratio tillage-7-carboxylic acid (atmosphere-oxime) Base-mercapto)-guanamine

1-299

2-((R)-3-ureido-indolyl-5-yloxy)-5//-. Bis-[2,3-6]pyrazine-7-isopropyl decyl phthalamide 1-300

1-301

2-(2-Ethylamino-indan-5-yloxy)-5//-indolo[2,3-6]» than argon-7-formic acid isopropylamine 2-( (R)-3-hydrazinoamino-p--5-yloxy)-5//-pyrrolo[2,3-6]° cultivating ·7· isopropyl decyl citrate 1- 302

2-(1//-茚-5-yloxy)-5//-° pyrrolo[2,3-6]pyridin-7-isopropyl decyl phthalate 156090.doc -95- 201204731 1-303

2_((R)-3-Hydroxy-indole-5-yloxy)-5//-pyrrolo[2,3-6]pyrazine-7-formic acid isopropylamine 1-304

2-((S)-3-hydroxy-inden-5-yloxy)-5-pyrido[2,3-6]pyridin-7-formic acid isopropylamine 1-305

2-((R)-l-amino-pump-5-yloxy)-5//-» berbolo[2,3-6]pyridin-7-decanoic acid ((S)-l , 2,2-trimethyl-propyl)-nonylamine 1-306

2-((R)-8-ethenylamino-5,6,7,8-tetrazine-cai-2-yloxypyrolo[2,3-crushed tillage-7-decanoic acid ( (S)-l,2,2-trimethyl-propyl)-guanamine 1-307

2-((R)-8-Amino-5,6,7,8-tetrazole-cain-2-yloxy)-5//-pyrrolo[2,3-leaf tillage-7-曱Acid ((S)-l,2,2-trimethyl-propyl)-decylamine 156090.doc -96- 201204731 1-308

2-((R)-8-Ethylamino-5,6,7,8-tetrahydro-naphthalen-2-yloxypyrolo[2,3·δ]. 比口井-7- Capric acid ((R)-l-cyclopropyl-ethyl)-bristamine 1-309

2-((R)-8-carbamimidino-5,6,7,8-tetrazine-cai-2-yloxypyrolo[2,3-6]» 耕-7-曱Acid ((R)-l-cyclopropyl-ethyl)-bristamine 1-310

2-((R)-8-amino-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-5//-pyrrolo[2,3-6]" -7-decanoic acid ((R)-l-cyclopropyl-ethyl)-decylamine

1-311

Η 2-((R)-3-Ethylamino-indole P-5-yloxy)-5//-° ratio 134- and [2,3-ό].啩-7- 143 Dicyclopropyl decyl decyl phthalate 156090.doc -97- 201204731

1-312

1-313((R)-l-Ethylamino-indan-5-yloxypyrrolo[2,3-6]pyrazine-7-carboxylic acid ((R)-l-cyclopropane 2-ethyl)-nonylamine 2-((R)-8-ethinylamino-5,6,7,8-tetrazine-cai-2-yloxy)-5if-indole-pyrrolo[ 2,3-6]"tb 啼.7·capric acid ((S)-2-methoxy-1-methyl-ethyl)-nitramine The following schemes, preparations and examples illustrate compounds within the scope of the invention The preparations and biological evaluations are provided below to provide a clearer understanding and practice of the present invention, which should not be construed as limiting the scope of the invention, but merely as a description and representation thereof. U.S. Application No. 12/378,837, filed on February 20, 2009, U.S. Application No. 12/378,869, filed on February 20, 2009, February 20, 2009 U.S. Application No. 12/378,971, February 20, 2009, U.S. Application No. 12/3,8,977, and U.S. Application No. 12/3,78,978, filed on February 20, 2009 It is disclosed in the present disclosure. The various applications are hereby incorporated by reference in their entirety. Shu case and process as mentioned below and provides procedures for the synthesis of the disclosure and examples synthesized as described before to be able to incorporate more of the following general structural formula I partially included in the position 156090.doc -98- 201204731 Q:

For example, U.S. Patent Application Serial No. 12/378,837, the disclosure of which is incorporated herein by reference in its entirety, the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of the entire disclosure of Carboxyhydroxyalkyl, amine or lower haloalkyl, each optionally substituted. For example, 'U.S. Application Serial No. 12/378,869 discloses pyrrolopyrazine compounds' wherein Q may be a phenyl group substituted with two substituents which together form a heterocyclic or heteroaryl ring system, each Replaced as appropriate. For example, U.S. Application Serial No. 12/378,971 discloses pyrrolopyrazine compounds wherein Q can be -0-Q3a, -S-Q3a, -C(=0)(Q3a), 〇(CH2)mC ( =0) (Q3a), -S(=〇)(Q3a), -S(=0)2(Q3a), -N(Q3a)2, • _N(Q3a)S(=0)2(Q3a), -N(Q3a)C(=0)(Q3a), -C(=〇)N(Q3a)2 or _N(Q)C(=0)N(Q3a)2, where 111 is 〇, i or 2 And each Q3a may independently be substituted with a lower alkyl group, a lower alkyl group, a phenyl group, a cycloalkyl group, a heterocycloalkyl group or a heteroaryl group, or hydrazine. For example, U.S. Application Serial No. 12/378,977 discloses pyrrole. The ratio of spray & matter, wherein Q can be phenyl or fluorenyl, each optionally substituted. For example, U.S. Patent Application Serial No. 12/378,978, the disclosure of which is incorporated herein by reference in its entirety, the disclosure of the entire disclosure of the disclosure of the disclosure of the disclosure of the disclosure of Replaced. The synthetic details of the procedures and examples provided in Scheme 1 and hereinafter are described as being capable of incorporating the synthesis of the portions included in the general structure described above at positions R, R2 and R3. A representative method for preparing the compounds of the invention is outlined in Scheme 1 below: Scheme 1

156090.doc -100· 201204731 As shown in the above Scheme 1, R may be hydrazine, cyano, R' or ^Rlb R' may be cycloalkyl, heterocycloalkyl or phenyl, each of which may be Or a plurality of R'' substitutions; R" may be halo, hydroxy, cyano, lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, C(= 0) R"' or S(= 0)2R'"; R' ' may be OH, lower alkyl, lower alkoxy, lower _alkyl, lower hydroxyalkyl, cycloalkyl or Amine; Rla, 1111) and 111<: independently hydrazine, hydroxy, halo, lower alkyl, lower alkenyl, lower alkynyl, lower carbyl, lower alkoxy, lower carbon Alkoxy, lower hydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, cycloalkyl, heterocycloalkyl, C(=0)R... or S(=0)2R'"; or Rla&Rlb- to form a spirocycloalkyl or spiroheterocycloalkyl group, each of which may optionally be substituted by one or more R3'; R2 may be deuterated or lower alkyl ; R3 can be anthracene, lower alkyl, hydroxy, hydroxy lower alkyl, lower alkoxy, lower haloxyalkyl, lower carbon# An oxy group, a phenyl group, a phenyl lower alkyl group, a cycloalkyl group, a cycloalkyl lower alkyl group, a cyano group, a cyano lower alkyl group or a heterocycloalkyl group; or R3 together form a spiro ring system, Each may optionally be substituted by one or more R 3 '; each R 3 may independently be lower alkyl, halo, hydroxy, lower alkoxy, lower carboalkyl, lower hydroxyalkyl, pendant oxy, Cyano, cyano lower alkyl, S(=0)2R3", C(=0)R3', cycloalkyl, heterocycloalkyl, heteroaryl or heterocycloalkenyl; R3' can be deuterium or Lower alkyl; Q can be Q2, Q3 or Q4; Q2 can be 156090.doc -101 - 201204731 Heterocycloalkyl, cycloalkyl, cycloaliphatic, heterocycloalkylphenyl, heteroaryl, hydrazine Or a heterobiaryl group, optionally substituted by one or more Q2a; Q2a may be Q2b or Q2c; Q2b may be halogen, pendant oxy, hydroxy, -CN, -SCH3, -s(o)2ch3 or -s (=o)ch3 ; Q2c can be Q2£^Q2e; or two Q2a - form a double loop system, optionally replaced by one or more 卩215 or 02<:;〇2<1 can be -0(Q2e) , -S(=0)2(Q2e), -C(=0)N(Q2e)2, -S(0)2(Q2e), -C( = 0)(Q2e), -C( = 0) 0(Q2e), -N(Q2e)C( = 0)(Q2e) -N(Q2e)C(=0)0(Q2e) or -N(Q2e)C(=0)N(Q2e)2; each Q2e may independently be H or Q2e_; each Q2e' may independently be low carbon Alkyl, phenyl, benzyl, lower haloalkyl, lower alkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q2f; Q2f It may be Q2g4 Q2h; ()28 may be halogen, hydroxy, cyano, pendant oxy or -C(=0)(Q2h); Q2h may be lower alkyl, lower alkyl, lower alkoxy , an amine group, a phenyl group, a phenyl fluorenyl group, a cycloalkyl group, a heterocycloalkyl group or a heteroaryl group, optionally substituted by one or more Q 2 i ; and Q 2 i may be _ s, hydroxy, cyano, lower alkyl , a lower halohaloalkyl group or a lower alkoxy group; Q3 may be -0-Q3a, -S-Q3a, -C(=0)(Q3a), -0(CH2)mC(=0)(Q3a), -S(=0)(Q3a), -S(=0)2(Q3a), -N(Q3a)2, -N(Q3a)S(=0)2(Q3a), -N(Q3a)C( =0)(Q3a), -C(=〇)N(Q3a)2, N(Q3a)C(=0)N(Q3a)2 or -N(Q3a)(CH2)mC(=0)N(Q3a 2; each Q3a may independently be Q3b or Q3e; m may be 0, 1 or 2; Q3b may be H; Q3e may be a low carbon group, a low carbon halogen group, a phenyl group, a cycloalkyl group, a hetero Cycloalkyl or heteroaryl, as appropriate by one or more Q 3d substituted; and each Q3d may independently be Q3e or Q3f; Q3e may be halogen or hydroxyl; Q3f may be lower alkyl, lower alkoxy, lower alkyl, phenyl, cycloalkyl, heterocyclic An alkyl or heteroaryl group, which is substituted by one or more Q3g in the case of 156090.doc -102-201204731; and each oxime 38 may independently be a dentate, a hydroxyl group, a low carbon alkyl group, a low carbon base group, Low carbon oxime or low carbon alkoxy; Q4 may be <3" or Q4b; 卩 "may be hydroxy, halogen or cyano; () 415 may be lower alkyl, lower alkoxy, lower a carbynyl group, a lower alkenyl group, a lower hydroxyalkyl group, an amine group or a lower carbon dentate group, optionally substituted by one or more q4c; Q4e may be 卩4<1 or (^46; each 卩4 £ 1 can independently be halogen, hydroxy or cyanide

a group, each Q may independently be a low carbon group, a low carbon group, a low carbon alkoxy group, an amine group, a cycloalkyl group, a phenyl group, a heterocycloalkyl group or a heteroaryl group, optionally one or more Substituted by Q4f; each (/£ can independently be hydroxy, dentate, lower alkyl, lower alkenyl, pendant oxy, lower _alkyl, lower alkoxy, lower hydroxyalkyl or amine a restriction; if the ring is propyl or thienyl, R2 and R3 are fluorene or methyl, and any one of Rla, Rlb lc and R is hydrazine or methyl, the other cannot be hydrazine, Hydroxyl hydrazine | . η孙社丞 or hydroxymethyl, and the restriction is when Q is gas, isopropyl, isopropylisopropenyl, piperidinyl, cyclohexyl or cyclohexenyl' and R and R3 are Η Or 甲 拄 pla lb , H. When flying methyl, R ' Rlb and ruler are not all procedures. The following procedure details the chemical synthesis used to provide intermediates such as the procedure. Procedure 1. Preparations disclosed in the examples Final combination

156090.doc 201204731 Step 1 Partial suspension of 2-di-5H "Biloze[2,3-b]» flavonoids (5.0 g, 25.2 匪〇1) in 14-monohexane (100 mL) 2 〇M Na〇H aqueous solution (25 mL, 50.0 mmol) and 37% aqueous furfural (19 mL, 252 mmol) was added. The dark homogeneous mixture was stirred overnight at room temperature. The aqueous layer was neutralized with EtOAc (2x). EtOAc (EtOAc) The organic solid was extracted with hot 10% MeOH/EtOAc (3.times.ss.sssssssssssssssssssssssssssssssssssssssssssssssssssssssssss Hydroxymercapto-pyrrolo[2 3_b]pyrazine-5-yl)sterol. Step 2 to (2-bromo-7-hydroxymethyl-pyrrolo[2,3-b]pyrazine-5-yl) Methanol (5.65 g,

21.9 mmol) A solution of 2·〇 M NaOH (33 mL, 66 mmol) was added to a suspension in THF (150 mL). The homogeneous reaction mixture was stirred overnight and then the organic phase was removed under reduced pressure. The aqueous residue was brought to pH 4 with a 1. 〇 M HCl aqueous solution. The resulting precipitate was collected via suction and washed with EtOAc to afford 3. The filtrate was extracted with EtOAc (2x)EtOAc. The total yield was 4.60 g (92%) (2_ bromo-5H-"bilo[2,3-b]. than cultivable-7-yl) sterol. Step 3 Prepare a stock of 156 090.doc • 104· 201204731 by carefully adding concentrated H 2 SO 4 (2.3 mL) to Cr03 (2.67 g), followed by dilution with H 2 至 to 1 〇 mL. 2.67 1^)» to a slow suspension of (2-bromo-511-pyrrolo[2,3_13]. plough-7-yl) sterol (4.6 g, 20.1 mmol) in acetone (300 mL) Jones reagent (9 mL '24.0 mmol) was added. During the addition, the starting material gradually dissolved and formed a thick green precipitate. The reaction mixture was stirred for 5 minutes, then quenched with i-PrOH (2 mL) > The filtrate was concentrated to give 4·76 g of 2-bromo-5H- as a yellow solid. The ratio of [2,3-b]pyrazine-7-furfural was used without further purification. Here. Add NaH (60o/〇, in mineral oil, 1.2 g, 30.1 mmol) to the solution of this solid in DMF (50 mL), stir the reaction mixture for 3 min at room temperature, then cool back and slowly. Add 2-((trimethyldecyl)ethoxymethyl gas (4.3 mL, 24.1 mmol). EtOAc (3 mL) The combined organic phases were washed with H.sub.2 (3.sub.3) and brine, then dried and concentrated with <RTI ID=0.0>>> 53%) 2_bromo-5-(2-trimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyr-7-carbaldehyde as a yellow solid. Procedure 2.

Dissolve 2-bromo-5-(2-trimethyldecylalkylethoxymethyl)_5Η·pyrrolo[2,3-b]pyrazine-7-furaldehyde (3.11 g, 8.74 mmol) in a flask The mixture was cooled in dioxane 156090.doc -105.201204731 (120 mL) and H2O (30 mL) at 0 °C. Add the amine acid (5.09 g, 52.4 mmol), then add sodium sulfite (1_28 g, 11.4 mmol) and potassium dihydrogen phosphate (14.3 g, 104.9 mmol) in H20 (75 mL) over 15 min. Solution. The mixture was allowed to warm to room temperature over 2 hours. The resulting yellow solid was filtered, washed with EtOAc and EtOAc. The filtrate was then extracted with EtOAc and EtOAc (EtOAc) A total of 3.71 g of 2-bromo-5-(2-trimethyldecyl ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a yellow solid was obtained. Procedure 3

Step 1 Flush with 2-argon-5-(2-trimethylglycine-ethoxymethyl)_5h_debido and [2,3-b]0 than well-7-brown (0.33) g, 〇.93 mmol), cyclopropyl@Phenic acid (0.12 g ' 1.39 mmol), tricyclohexylphosphine (0.026 g, 〇.〇 9 mmol), acetic acid (Π) (〇.01 g, 0.046 mmol) And a mixture of tripotassium citrate (0.63 g, 2.97 mmol) in 4 mL of toluene and 0.5 mL of water for 5 minutes, followed by heating at 100 ° C for 18 hours. The cooled mixture was filtered through a pad of celite and washed with EtOAc. The residue was purified by EtOAc (EtOAc/EtOAc) elute elute elute elut elut elut elut elut 2-trimethylsulfonyl-ethoxycarbonyl)_5H-indolo[2,3-b]indole-7-formaldehyde. Step 2 Under 〇C, 2-cyclopropyl-5-(2-trimethylsulfanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrrol-7-furfural (0.24 g, 0.75 mmol) A solution of sulfonic acid (0.44 g, 4.54 mmol) was added to a solution of 1,4-dioxane (10 mL) and water (2 mL). 0.09 g, 0.98 mmol) and a solution of potassium dihydrogenate (1.22 g, 9·0 mmol) in 6 mL of water. After the addition, the reaction mixture was allowed to warm to room temperature and stirred for 2 hr then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate The residue was triturated with hexane to give EtOAc (EtOAc m.) Pyrrolo[2,3-b]. Than cultivating -7-decanoic acid. Procedure 4

Step 1 to 2-Moet 5-((2·(tridecyldecyl)ethoxy)indolyl)_5H-0pyrolo[2,3_b] 〇 耕-7-furfural (1.33 g, 3.73 mmol) And 1-ethyl-4-(4,4,5,5-tetradecyl-1,3,2-dioxaboromid-2-yl)-1Η-pyrazole (995 mg, 4.48 mmol) Add 156090.doc -107- 201204731 卩咐113?)4(0.22§'〇.19 111111〇1) and 2.〇]^〖2(:03 aqueous solution (5.6 ml ' 11.2 mmol) to the solution in ihDMEGO mL) The reaction mixture was degassed by bubbling N2 for 15 minutes, then heated overnight at 100 ° C. The resulting maroon reaction mixture was cooled and diluted with &amp; 0, then extracted with EtOAc (2x). The organic phase was concentrated and purified <RTI ID=0.0>: </RTI> </RTI> <RTI ID=0.0> 1Η-»Bizozol-4-yl)-5-((2-(tridecyldecyl)ethoxy)indolyl)_5Η·pyrrolo[2,3-b]pyridin-7-carboxaldehyde. Step 2 2-(1-Ethyl-1H-pyrazol-4-yl)-5-((2-(trimethyldecyl)ethoxy)methyl)-5H-0 pirin at 〇 °C And [2,3-b]pyrazine-7-brown (1.12 g, 3.01 mmo) l) Amine acid (1.76 g, 18.1 mmol) was added to a solution of 1,4-dioxane (50 mL) and H2O (10 mL), then NaC102 (0-44 g, 3_92 mmol) and a solution of KH2P 〇4 (4.92 g, 36.2 mmol) in H.sub.2 (30 mL). The ice bath was removed and the yellow turbid reaction mixture was stirred at room temperature for 2.5 hr. 2x) Extraction. The combined organic layers were dried with EtOAc EtOAcjjjjjjjjjj ·1Η·pyrazol-4-yl)-5-((2-(trimethyldecyl)ethoxy)indolyl)-5H-«bibromo[3,2-b]-specific tillage-7 - Formic acid. Pharmaceutical compositions and administration The compounds of the present invention can be formulated into a variety of oral administration forms and carriers. Oral administration can be used as tablets, coated tablets, dragees, hard gelatin capsules and soft 156090.doc -108- 201204731 In the form of a capsule, solution, emulsion, syrup or suspension. The compounds of the invention are also effective when administered by other routes of administration, and other routes of administration include continuous (intravenous drip) Topical parenteral, intramuscular, intravenous, subcutaneous (which may include penetration enhancers), buccal, nasal, inhalation, and suppository administration, as well as other routes of administration. The preferred mode of administration is generally an oral administration using a convenient daily dosing regimen which is adjusted depending on the degree of the disease and the patient's response to the active ingredient.

The compounds of the present invention, as well as the pharmaceutically acceptable salts thereof, may be combined with one or more %, carriers or diluents to form a pharmaceutical composition and unit dosage form. The pharmaceutical compositions and unit dosage forms may contain conventional ingredients in the ordinary proportions, with or without other active compounds or ingredients, and the unit dosage form may contain any suitable effective amount of the active ingredient equivalent to the intended daily dosage range to be employed. The pharmaceutical composition can be used in the form of a solid, such as a lozenge or filled capsule, a semi-solid, a powder, a sustained release formulation; or a liquid such as a liquid, suspension, emulsion, boat or filled capsule for administration Oral use; or suppository for rectal or vaginal administration; or sterile injection for parenteral use. Typical formulations contain from about 5% to about the active compound (w/w). The term "formulation" or "dosage form" is intended to include both solid and liquid formulations of the active compound and those skilled in the art will appreciate that the active ingredient may be present in separate formulations depending on the target organ or tissue and the desired dosage and It depends on the parameters. The term "excipients and generally safe, non-toxic, and biologically acceptable, and including veterinary" as used herein means that it is suitable for the preparation of pharmaceutical combinations and other uses which are not unsuitable for use and for human medical use. Accepted 156090.doc 201204731 by the job agent. The compounds of the present invention can be administered alone, but are generally administered in admixture with a suitable pharmaceutical, diluent or carrier selected according to the intended route of administration and standard pharmaceutical practice. Formal, pharmaceutically acceptable means that it is suitable for the preparation of a pharmaceutical composition that is safe, non-toxic and not biologically or otherwise unsuitable and includes materials acceptable for veterinary and human medical use. The "pharmaceutically acceptable salt" form of the active ingredient may also initially impart a suitable pharmacokinetic property to the active ingredient which is not in a non-salt form and may even positively affect the active ingredient's therapeutic activity in vivo. Effectiveness. The "pharmaceutically acceptable salt" of the phrase compound means a salt which is pharmaceutically acceptable and which has the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or acid addition salts with organic acids such as the following: acetic acid , propionic acid, caproic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, cis-butanic acid, fumaric acid, tartaric acid, citric acid, benzene Formic acid, 3_(4-hydroxybenzyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, sylvestre, 1,2-ethane--26 acid, 2-ionyl-burning acid, Benzoic acid, 4-gas benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-indolyl sulfonic acid, camphorsulfonic acid, 4-mercaptobicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, Portuguese Glycolic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid and Similar to an acid; or (2) a salt formed when an acidic proton present in a parent compound is replaced by a metal ion (eg, an alkali metal ion, an alkaline earth metal ion, or an aluminum ion); or with 156090.doc -11 0-201204731 A salt formed by the organic test (such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine and the like). Solid form preparations include powders, lozenges, pills, capsules, cachets, suppositories, and dispersible granules. The solid carrier can be one or more substances which may also act as release agents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, lozenge disintegrating agents or encapsulating materials. In powders, the carrier is generally a finely divided solid which is a mixture with the finely divided active component. In the tablet, the active component is typically admixed with a suitable ratio of carrier having the necessary binding ability and compacted to the desired shape and size. Suitable carriers include, but are not limited to, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, low Melting point 蠛, cocoa butter and the like. The solid form preparation may contain, in addition to the active ingredient, a coloring agent, a flavoring agent, a stabilizer, a buffering agent, an artificial and natural sweetener, a dispersing agent, a thickening agent, a solubilizing agent, and the like. Liquid formulations are also suitable for oral administration, including liquid emulsions, syrups, elixirs, aqueous solutions and aqueous suspensions. It includes solid form preparations which are intended to be converted into liquid form preparations by the use of hydrazine. The rolling liquid can be prepared in the form of a solution, for example, in the form of an aqueous solution of propylene glycol, or may contain an emulsifier such as lecithin, sorbitan monooleate or gum arabic. The aqueous solution can be prepared by dissolving the active component in water and adding suitable colorants, odorants, stabilizers, and bulking agents. Aqueous suspensions can be prepared by dispersing the finely divided active component in water together with a viscous material such as natural or synthetic gum, resin, methylcellulose, sodium carboxymethylcellulose, and other well known suspending agents. 156090.doc • 111· 201204731 The compounds of the invention may be formulated for parenteral administration (for example by injection, such as bolus injection or continuous infusion), and may be provided in unit dosage form in ampoules, prefilled syringes, small volume infusion containers. Or provided in a multi-dose container with a preservative added. The composition may take the form of, for example, a suspension, solution or emulsion in an oily or aqueous vehicle, such as a solution in aqueous polyethylene glycol. Examples of oily or non-aqueous vehicles, diluents, solvents or vehicles include propylene glycol, polyethylene glycol, vegetable oils (such as olive oil), and injectable organic esters (such as ethyl oleate), and may contain formulating agents, such as Preservatives, wetting agents, emulsifying or suspending agents, stabilizers and/or dispersing cold agents. Alternatively, the active ingredient may be in the form of a powder obtained by sterile separation of sterile solids or by lyophilization from solution, reconstituted with a suitable vehicle (for example, sterile non-pyrogenic water) before use. The compounds of the invention may be formulated for topical administration to the epidermis in the form of an ointment, cream or lotion, or in the form of a transdermal patch. Ointments and creams may, for example, be formulated with a suitable thickening and/or gelling agent in an aqueous or oily base. The lotion may be formulated with an aqueous or oily base and will generally contain one or more emulsifying, stabilizing, dispersing, suspending, thickening or coloring agents. Formulations for topical administration in the mouth include: buccal agents which contain the active agent in a flavoring base (usually sucrose and acacia or tragacanth); tablets which are in an inert base such as gelatin and glycerin Or sucrose and gum arabic) comprising an active ingredient; and a mouthwash comprising the active ingredient in a suitable liquid carrier. The compounds of the invention may be formulated for administration as a suppository. First, a low melting wax such as a mixture of fatty acid glycerides or cocoa butter is melted, and the active component is uniformly dispersed by stirring, for example, by 156090.doc -112·201204731. The molten homogeneous mixture is then poured into a mold of suitable size to allow it to cool and solidify. The compounds of the invention may be formulated for vaginal administration. A pessary, cotton ball, cream, gel, paste, foam or spray containing a carrier known in the art in addition to the active ingredient is suitable. The compounds of the invention may be formulated for nasal administration. The solution or suspension can be applied directly to the nasal cavity by conventional means, e.g., using a dropper, pipette or spray. Formulations may be provided in single or multiple doses. In the case of the latter dropper or inhalation, this can be achieved by the patient administering a suitable predetermined amount of solution or suspension. In the case of a nebulizer, this can be achieved, for example, by means of a metered mist spray pump. The compounds of the invention may be formulated for aerosol administration, especially to the respiratory tract and include intranasal administration. The compound generally has a small particle size of, for example, about five (5) microns or less than five (5) microns. The particle size can be obtained by methods known in the art, for example by micronization. The active ingredient is provided in a pressurized pack together with a suitable propellant such as a chlorofluorocarbon (CFC) such as di-halogenated difluoromethane, tri-fluorofluoromethane or dichlorotetrafluoroethane, or carbon dioxide or other suitable gas. Aerosols should also contain a surfactant (such as lecithin). The drug dose can be controlled by a metering valve. Alternatively, the active ingredient may be presented in the form of a powder, such as a powder mixture in a suitable powder base such as lactose, starch, starch derivatives (such as hydroxypropylf-based cellulose) and polyvinylpyrrolidine (PVP). The powder carrier will form a gel in the nasal cavity. The powder composition may be provided in unit dosage form, e.g., in a capsule or cartridge such as gelatin or blister pack, wherein the powder may be administered by means of an inhaler from the capsule 156090.doc • 113-201204731 capsule or cartridge. When desired, the formulation can be prepared using a casing suitable for sustained or controlled release of the active ingredient. For example, the compounds of the invention may be formulated in a transdermal or subcutaneous drug delivery device. Such delivery systems are suitable when sustained release of the compound is desired and when patient compliance with the treatment regimen is critical. The compounds in the transdermal delivery system are typically attached to a skin-adhesive solid carrier. The related compound may also be combined with a penetration enhancer such as Azone (l-dodecylaza-cycloheptan-2-one). The sustained release delivery system can be inserted subcutaneously into the subdermis by surgery or injection. Subepidermal implants encapsulate the compound in a lipid soluble membrane (e.g., polyoxyxene rubber) or a biodegradable polymer (e.g., polyplactic acid). Suitable formulations as well as pharmaceutical carriers, diluents and excipients are described in Remington: The Science and Practice of Pharmacy 1995, edited by E. W. Martin, Mack Publishing C〇mpany, 19th edition, East〇n,

In Pennsylvania. A skilled worker will be able to modify the formulation without the teachings of the present invention, without causing instability or damage to the composition of the invention, and to provide a variety of formulations for a particular route of administration. In order to make the compounds of the present invention more soluble in water or other vehicles, modifications to such compounds are readily accomplished, for example, by minor modifications (salt formulations, S-dissolving, etc.), which are fully within the skill of the art. Within the scope. Modification of the route of administration of a particular compound &amp; dosing regimen to control the pharmacokinetics of the compounds of the invention to produce maximum beneficial effects in the patient is also complete 156090.doc -114· 201204731 is within the general skill of the art. The term "therapeutically effective amount" as used herein means the amount required to alleviate the symptoms of an individual's disease. The dosage in each particular case can be adjusted to individual needs. The dosage may vary within a wide range depending on a number of factors, such as the severity of the condition to be treated, the age and general health of the patient, the other drug being treated, the route and form of administration, and the preferences of the physician concerned. experience. For oral administration, the appropriate dose per dose in monotherapy and/or combination therapy should be from about 0 01 mg to about 1,000 mg per kilogram of body weight per day. Preferably, the dose per dose is from about 1 mg to about 500 mg per kilogram of body weight per day, more preferably from about 1 to about 丨〇〇 mg per kilogram of body weight per day, and most preferably from 10 mg to about 1 part per kilogram of body weight per day. Meg Therefore, for administration to a 70 kg person, the dose should range from about 7 111 § to 7 g per day. The dose per dose can be administered in a single dose or in divided doses, usually three to five doses per day. In general, treatment is initiated with a smaller dose that is less than the optimal dose of the compound. Thereafter, the dose is increased in small increments until the individual patient achieves the best results. Those of ordinary skill in the treatment of the diseases described herein should be able to determine the therapeutically effective amount of the compound of the present invention for a given disease and patient, without undue experimentation, based on personal knowledge, experience, and disclosure of the present invention. The pharmaceutical preparation is preferably in a unit dosage form. In this dosage form, the preparation is subdivided into unit doses containing appropriate quantities of the active ingredient. The unit dosage form can be a package preparation such as a packaged tablet, a capsule, and a powder in a vial or ampule, and the gastric package contains a separate amount of the formulation. In addition, the unit dosage form can be a capsule, a lozenge, a cachet or a mouth-containing spin itself, or it can be in the form of a package formed by any of these unit dosage forms 156090.doc • 115-201204731. Indications and treatments The novel pyrrole provided in this article. Specific cultivating derivatives selectively inhibit jAK3 and are suitable for the treatment of autoimmune diseases and inflammatory diseases. The compounds of the invention modulate the JAK and/or SYK pathway and are novel &lt;RTI ID=0.0&gt;&gt;&gt;&lt;/RTI&gt; For example, the compound of the present invention inhibits jak3 and SYK, wherein the preferred compound is selective for JAK3 in JAK kinase and is a novel pyrrolopyrazine derivative suitable for the treatment of autoimmune diseases and inflammatory diseases. The 5Η-° ratio of [2,3-b]° to the 7-position of the guanamine linker allows the compound to inhibit the efficacy of JAK and Syk kinase compared to other parts of the 511- The ground[2,3_b]D was unexpectedly improved than the ploughing. Furthermore, the compounds of the present invention inhibit JAK3 and JAK2, among which preferred compounds are selective for JAK3 in JAK kinase and are novel pyrrolopyrazole derivatives suitable for the treatment of autoimmune diseases and inflammatory diseases. Similarly, the compounds of the present invention inhibit JAK3 and JAK1, wherein the preferred compounds are selective for IAK3 in JAK kinase, and 1 is a novel lysine-to-P ratio for the treatment of autoimmune diseases and inflammatory diseases. derivative. The present application provides a method of treating an inflammatory condition or an autoimmune condition, which comprises administering a therapeutically effective amount of a compound to a patient in need thereof. The present invention provides the above method, which comprises the step of administering another therapeutic agent: chemotherapeutic or anti-proliferative, anti-inflammatory, immunomodulatory or immunosuppressive, neurotrophic, cardiovascular 156090.doc • 116· 201204731 Pharmacy, an agent for treating diabetes or an agent for treating an immunodeficiency disorder. The present application provides a method of treating an inflammatory condition comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or r. The present application provides a method of inhibiting a T cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or hydrazine. The present application provides a method of inhibiting a T cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or hydrazine. The present application provides the above method wherein the proliferative disorder is cancer. The present application provides a method of treating a B cell proliferative disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula. The present application provides a method of treating an immune disorder, including lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, type I diabetes, complications of organ transplantation, xenograft, diabetes, cancer, asthma, Atopic dermatitis, autoimmune sputum gland disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, and leukemia, the method comprising administering a therapeutically effective amount to a patient in need thereof I or a compound of hydrazine. The present invention provides for the prevention or treatment of all forms of organ rejection, such as acute allograft rejection or xenograft rejection and chronic allograft rejection or xenograft rejection, such as tubular or non-i tube grafts. A method of reacting comprising administering a compound of formula I or hydrazine to a patient in need thereof. The present application provides a method for inhibiting JAK3 activity comprising administering a compound of Formula I or guanidine wherein the compound exhibits a concentration of 50 micromolar or less than 50 micromolar in a biochemical assay of JAK3 activity in vitro. .doc -117- 201204731 1. 5 depreciation. The present invention provides the above method, wherein the compound exhibits an IC50 value of (10) nanomolar concentration or (10) nanomolar concentration in an in vitro MK3 active biochemical assay. The present invention provides the above method, wherein the compound exhibits a 1 () Naimer concentration or a WN molar concentration of 1 (: 5 〇 value) in an in vitro JAK3 activity biochemical assay. The present application provides a A method of inhibiting SYK activity, comprising administering a compound of Formula I or I, wherein the compound exhibits a concentration of 50 micromolar or less than 50 micromolar in an in vitro biochemical assay of SYK activity. Values. The above method is provided wherein the compound exhibits (10) a concentration of IC5 or a concentration of IC5 below the concentration of Naimer in an in vitro biochemical assay of SYK activity. The present application provides the above method, wherein the compound is in vitro SYK An IC50 value indicative of a concentration of 1 nanomolar or a concentration of 1 nanomolar in an active biochemical assay. The present invention provides a method of treating an inflammatory condition comprising co-administering a therapeutically effective amount to a patient in need thereof An anti-inflammatory compound and a compound of formula I or I. The present invention provides a method of treating an immune condition comprising co-administering to a patient in need thereof An immunosuppressant compound and a compound of formula I or oxime. The following examples illustrate the preparation and biological evaluation of compounds within the scope of the invention 156090.doc 201204731. These examples and preparations are provided below to familiarize themselves with the art. The invention may be more clearly understood and practiced, and should not be construed as limiting the scope of the invention, but only as its description and representative. [Embodiment] Examples Abbreviations commonly used abbreviations include: Acetyl (Ac), Azo- Bis-isobutyronitrile (AIBN), atmospheric pressure (Atm), 9-borabicyclo[3.3.1]decane (9-BBN or BBN), third butoxycarbonyl (Boc), pyrocarbonate di-third Butyl ester or boc anhydride (B0C20), benzyl (Bn), butyl (Bu), CAS-No. (CASRN), benzomethoxycarbonyl (CBZ or Z), carbonyl diimidazole (CDI), M- Diazabicyclo[2.2.2]octane (DABCO), diethylaminosulfur trifluoride (DAST), dibenzylideneacetone (dba), 1,5-diazabicyclo[4.3.0壬-5-ene (DBN), 1,8-diazabicyclo[5·4·0]undec-7-ene (DBU), N,NL dicyclohexylcarbodiimide (DCC), 1 ,2-di-ethane (DCE) , dioxane (DCM), diethyl azodicarboxylate (DEAD), diisopropyl azodicarboxylate (DIAD), diisobutylaluminum hydride (DIBAL or DIBAL-H), diisopropyl Ethylethylamine (DIPEA), N,N-dimethylacetamide (DMA), 4-N,N-dimethylaminopyridine (DMAP), N,N-didecylguanamine (DMF) Dioxane sulfoxide (DMSO), 1,1'-bis-(diphenylphosphino)ethane (dppe), hydrazine, bismuth-bis-(diphenylphosphino)ferrocene (dppf), 1 -(3-didecylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), ethyl (Et), ethyl acetate (EtOAc), ethanol (EtOH), 2-ethoxy Ethyl 2H-quinoline-1-decanoate (EEDQ), diethyl ether (Et20), hexafluorophosphate 0-(7-azabenzotriazol-1-yl)-fluorene, hydrazine, Ν'Ν' - 四156090.doc •119- 201204731 TU 锞 (HATU), acetic acid (HOAc), 1-N-hydroxybenzotriazole (HOBt), high pressure liquid chromatography (HPLC), isopropanol (IPA), Lithium hexamethylene diazoxide (LiHMDS), decyl alcohol (MeOH), melting point (mp or MP), MeS02- (mesyl or Ms), methyl (Me), acetonitrile (MeCN), M-benzoic acid (MCPBA), mass spectrometry (ms or MS), Methyl third butyl ether (MTBE), N-bromosuccinimide (NBS), N-formic anhydride (NCA), N-gas diimenimine (NCS), N-methylmorpholine (NMM) ), N-decylpyrrolidone (NMP), pyridinium chlorochromate (PCC), pyridinium dichromate (PDC), phenyl (Ph), propyl (Pr), isopropyl (i-Pr) ), pounds per square inch (psi), &quot;pyridyl (pyr), room temperature (rt or RT), 2-(trimethylsulfanyl)ethoxy sulfhydryl (SEMC1), tert-butyl Mercaptoalkyl or ί-BuMe2Si (TBDMS), triethylamine (TEA or Et3N), 2,2,6,6-tetramethylpiperidine 1-oxy (TEMPO), triflate or CF3S02 -(Tf), trifluoroacetic acid (TFA), 1, bismuth-bis-2,2,6,6-tetramethylheptane-2,6-dione (TMHD), bismuth tetrafluoroborate-benzotriene Zin-1-yl-indole, hydrazine, hydrazine, Ν'-tetramethylguanidine (TBTU), thin layer chromatography (TLC), tetrahydrofuran (THF), trimethyldecyl or Me3Si (TMS), monohydrate P-toluenesulfonic acid (TsOH or pTsOH), 4-Me-C6H4S02- or toluenesulfonyl (Ts), N-amino phthalate-N-formic anhydride (UNCA). When used in the alkyl moiety, the conventional nomenclature including the initial ("), the different (i), the second (iec-), the third (ieri-), and the neo (neo) has its usual meaning. (J. Rigaudy and D. P. Klesney, Ogam'c less, IUPAC 1979 Pergamon Press, Oxford.). Example 1. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid [(R)-l-(l-hydroxy-cyclo-120-156090.doc 201204731 pentyl) -ethyl]-guanamine

Step 1 Slowly add allylmagnesium bromide μ Et20 solution to a solution of Boc-D-alanine methyl ester (2.03 g, 10.0 mm 〇l) in THF (20 mL) at 〇 ° C, 35 mL ' 35.0 mmol). The resulting white syrup was stirred under EtOAc (1 hr) and then stirred at room temperature for 2 hr. The reaction mixture was cooled to EtOAc EtOAc (EtOAc) The organic phase was dried over MgSO 4 and concentrated to give a viscous oil. The oil was dissolved in CH2C12 (200 mL) and Grubbs 2nd generation catalyst (0_17 g ' 0.2 mmol). The maroon reaction mixture was heated overnight under reflux. Additional amount of catalyst (0.085 g, 0.1 mmol) was added and heating was continued for 6 hours. The reaction mixture was concentrated and chromatographed by SiO 2 (10% to 40% EtOAc / Purification of the alkane to give the titled [(R)-1-(1-hydroxycyclopent-3-enyl)-ethyl]-carbamic acid tert-butyl ester as a pale brown oil. Step 2 to [(R)-1-(1-Hydroxycyclopent-3-enyl)-ethyl]-carbamic acid tert-butyl ester (0.62 g, 2-7 mmol) in MeOH (20 mL) Add 1% Pd/carbon (65 mg) to the solution. Stir the reaction mixture overnight in H2 atmosphere (1 atm), I56090.doc -121 - 201204731 followed by diatomaceous earth Filtration, EtOAc (EtOAc) EtOAc (EtOAc) The above oil was dissolved in 1.0 M HCl in MeOH (10 mL) and stirred at room temperature overnight. The mixture was concentrated to give 218 mg (50%) Amino-ethylcyclopentanol hydrochloride as a hygroscopic white solid. Step 4 Combine 2-cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl) in a flask -5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.36 mmol), 1-((R)-1-amino-ethyl)-cyclopentanol hydrochloride (70 Mg, 0.43 mmol), EDC (77 mg, 0.40 mmol) and HOBt (54 mg, 0.40 mmol). DMF (2 mL) and i_Pr2NEt (0.16 mL, 0.90 mmol) were then added. The reaction mixture was stirred at room temperature. After 4 hours, it was then quenched with H20 and EtOAc (EtOAc) (EtOAc) (EtOAc) (EtOAc) 2-cyclopropyl-5-(2-trimethylglycine ethoxymethyl)-5H-° Than &quot; each [2,3·b]. Specific tillage-7-decanoic acid [(R)-l-(l-hydroxy-cyclopentyl)-ethyl]-guanamine. Step 5 To 2-cyclopropyl-5-(2-trimethyldecylethoxyethoxymethyl)·5Η_pyrolo[2,3-b]» than tillage-7-formic acid [(R)- To the solution of l-(l-hydroxy-cyclopentyl)-ethyl]-decylamine (153 mg '0.34 mmol) in CH2C12 (3 mL) The reaction mixture was stirred for 3 hours and then concentrated. The residue was dissolved in 156090.doc -122 - 201204731 CH2C12 (5 mL) and ethyldiamine (1 mL) was added. The reaction mixture was stirred for 1 hour and then concentrated. The residue was triturated with 10% MeOH / EtOAc. The obtained white solid was collected by filtration to give 73 mg (68%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-i-(i-hydroxy- Cyclopentylethyl]-decylamine MS: (M+H)+=315^Hi=287.0-290.0. Example 2· 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine- 7-formic acid [(S)-l-(1-hydroxy-cyclopentyl)-ethyl]-decylamine

Prepared according to the procedure outlined in Example 1, using Boc-L-alanine decyl ester in place of Boc-D-alanine methyl ester in step 1. MS: (M+H)+=315; melting point 292.0-294.0.

Example 3· 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-l,2,2-trimethylpropyl)-decylamine

156090.doc • 123- 201204731 According to the procedure outlined in step 4_5, substituting (8) &lt; 2 propylamine for 1 L-amine 'ethyl}cyclopentanol hydrochloride to prepare - (M+H)+= 287; melting point &gt; 300. Prepare MS·X 4. Fluoride 1'2'2-dimethyl-propyl urethane

Step 1 To a solution of 3,3,3-trifluoro-2,2-dimethylpropanoic acid (25 g, 16 〇 〇 1) in di-methane (35 mL) was added N, 〇• dimethyl Base the amine hydrochloride (234 g'24 _ol), N-methylmorphine (4.9 mL, 45 _〇ι) μ via benzo oxadiazole hydrate (2.45 g, 16 mmoip vigorously stir the mixture for 5 minutes, Then, 丨-ethyl_3_(3-dimethylaminopropyl)carbodiimide hydrochloride (5·22 g, 27.2 mmol) was added in portions. The mixture was stirred for 72 hours. The crude material was dissolved in 4%. The aqueous solution of HC1 (150 mL) and dichloromethane (15 mL) were transferred to a separatory funnel. The methane phase was collected and continuously washed with an equal volume of 5% aqueous sodium hydrogen hydride solution and brine solution. The aqueous phase was back-extracted with chloromethane (2 x 80 mL). The organic phase was combined, dried (MgSO4), filtered, and carefully reduced on a rotary evaporator. Filtered through a short cerium oxide in a dichloromethane (20 mL) The crude residue was taken under a semi-vacuum. </ RTI> <RTI ID=0.0># </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> Step 2 Under argon (balloon) to 3,3,3-trifluoro-N-decyloxy-2,2,N-trimethyl-propanol (1.25 g' 6.3 mmol) in tetrahydrofuran Add a 3 Μ solution of methylmagnesium bromide in acetamidine (4.2 ml, 12.6 mmol) in a cold (ice bath, 〇C) solution in mp (10 mL). Stir the mixture to ambient temperature. After overnight, it was then quenched by the addition of saturated aqueous ammonium sulphate (15 mL). Water (20 mL) and diethyl ether (25 mL) were added and the mixture was shaken in a sep. funnel. Washing. The aqueous phase was back-extracted with diethyl ether (2×25 mL). The combined organic phases were dried over magnesium sulfate and filtered. The solvent was removed by careful evaporation. The residue was dissolved in anhydrous dichloromethane (2 mL) The solvent was taken up (repeated once more). A clear flowing oil was obtained (assuming 6 mmol) which was dried over molecular sieves and used directly in the next step. Step 3 Titanium ethoxide (IV) under argon atmosphere (1) _〇6 mL, 5.1 mmol) and (R)_(+)-2-methyl-2-propanesulfinamide (303 mg, 2.5 mmol) in a mixture of anhydrous tetrazole (5 mL) Add 4,4,4- Fluorine 3,3·didecyl-butane 2_嗣 (1/2 of the substance in step 2, assuming 3 mmol). The material was heated to 75 ° C for 18 hours. The mixture was cooled to -45 ° C and passed through A 1-butyl side lithium hydride (L-selectride) (1 M THF solution, 8 mL, 8 mmol) was added dropwise. After 5 minutes of charging, the cooling bath was removed and the material was stirred for 3 hours. The mixture was cooled in an ice bath and methanol was added dropwise until bubbling ceased to quench the substance and brine (10 mL) was added to give a solid. 156090.doc -125 - 201204731 Ocean: filtered through a celite plug 1 acetic acid The ethyl ester is thoroughly washed. Collect; consider the solution and wash with equal volume of brine 1 acetic acid ethyl acetate (2 (10) back extraction of the aqueous phase. Combine the organic phase, use sulfur - dry, filter and evaporate. Pass through the heart of the cerium oxide column chromatography (3 〇 g The residue was purified by EtOAc (EtOAc) elute elute 2. Trimethyl propyl) decylamine (7 〇 (4). Step 4 2-methyl-propan-2-densine ((8)_3,3,3_trioxy-trimethyl-propyl)- The amine (7 〇 mg, 〇 27 〇 1) was dissolved in 3 % by weight of hydrochloric acid in ethanol (1 mL) t and the solution was added for 2 hours. The volatiles were evaporated and the residue was dissolved in 2 gas. Flashing (15 mL). The solvent was evaporated again and the material was evaporated EtOAcjjjjjjjjjjj Can be used. Step 5 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyrazine_7·f acid ((s)_3 3,3 trifluoro 1,2,2-trimethyl-propyl) · Amine amine. According to the procedure outlined in Example j, (, (S)-3,3,3 -three gas-12 2-: ® i τ- πρ* 5 rolling, Z, Z Methyl propylamine hydrochloride was prepared instead of ((8) small amino-ethyl)cyclopentanol hydrochloride. Milk (M+H)+=341; melting point &gt;3〇〇. Example 5. 2-ring Propyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy·!丨2-yl-propyl)-bristamine 156090.doc -126- 201204731

Step 1 In a round bottom flask, N-Boc-aminoisobutyric acid (1.20 g, 5.90 mmol) was dissolved in di-methane (22 mL) and Me. The (tridecylalkyl)diazomethane (2 〇M hexane solution, 5 〇 mL, 1 〇 〇 mmol) was added dropwise and the reaction mixture was stirred at room temperature for 2.5 hours. The reaction mixture was quenched with a small amount of acetic acid and concentrated under reduced pressure. The residue was dissolved in dioxane and washed with a saturated aqueous NazCO3. The aqueous layer was extracted with dioxane, and the combined organic phases were dried over Na.sub.4. Step 2 Slowly add bismuth bromide magnesium (3〇μ) to a solution of methyl N-Boc-aminoisobutyrate (〇·6〇g, 2.76 mmol) in THF (20 mL) at 〇 °C. Ether solution '3.6 mL '1〇·8 mm〇i). The reaction mixture was stirred at 〇 °c for 1 hour and then stirred at room temperature for 5 hours. Cool the reaction back to 〇. (: and quenched with a saturated aqueous solution of ΝΗβΙ, followed by extraction with Et 〇Ac (2×). The combined organic phases were washed with water and brine, then dried over Na 2 〇 4 and concentrated. The residue was purified by dissolving 〇% to 2% EtOAc / hexanes to give the titled (2-hydroxy-1,1,2-trimethyl-propyl)-amino group as a white solid. Third butyl formate. Step 3 156090.doc -127- 201204731 Dissolve (2-hydroxy-1,1,2-trimethyl-propyl)-aminodecanoic acid tert-butyl ester in a round bottom flask The reaction mixture was stirred at 50 ° C for 4 h then cooled to rt and concentrated to give 70 mg (99%) Base 2,3_didecyl-butan-2-ol hydrochloride. Step 4 2_Cyclopropyl-5H·pyrrolo[2,3_b]pyrazine_7-carboxylic acid (2-hydroxy-trimethyl- Propyl)-guanamine. According to the procedure outlined in Example 丨Step 4_5, 3-amino-2,3-dimethyl-but-2-ol hydrochloride was used instead of amino-ethyl)-tert. Preparation of alkoxide Sst salt"MS: (M+H)+=303; melting point = 270.0_ 273.0 ° Example 6. 2-Cyclopropyl -5H- pyrrolo [2,3-b] pyrazol farming -7- Yue acid ((S) -2- cyano-1,2,2-trimethyl - ethyl) - Amides

Step 1 2-Methyl-propane-2·sulfinamide (2 〇〇 g, i6 5 mm〇1) was dissolved in CH2C12 (7.0 mL) in a flask. Acetaldehyde (6.7 μm mL, 119 mmol), MgS〇4 (4.79 g, 39.8 mmol) and pyridinium tosylate (100 mg, 0.398 mmol) were added. The reaction mixture was stirred at room temperature overnight, filtered 156090.doc: 128·201204731 and concentrated to give 2.48 g of 2-mercapto-propane-2_sulfinic acid (E)-ethylethenamine as a brown oil. It can be used without further purification. Step 2 Isobutyronitrile (0.91 mL, 10.2 mmol) was dissolved in THF (20 mL) and cooled at -78. LiHMDS (1.0 M in THF, 11.2 mL, 11.2 mmol) was added and the mixture was stirred at -78 °C for 30 min. A solution of 2-mercapto-propane-2-sulfinic acid (E)-ethylene decylamine (1.00 g, 6.8 mmol) in THF (5.0 mL) was slowly added. The mixture was stirred at -78 °C for 2 hours and at 0 °C for 2 hours, then warmed to room temperature overnight. The reaction mixture was quenched with aq. Washed with brine. The combined organic phases were dried over MgSO 4 and concentrated. The residue was purified by EtOAc (20-100% EtOAc (EtOAc) Acid (2-cyano-1,2,2-tridecyl-ethyl)-bristamine. Step 3 2-Mercapto-propane-2-sulfinic acid (2-cyano-1,2,2 -Trimethyl-ethyl)-guanamine (714 mg ' 3.30 mmol) was dissolved in 0.70 M EtOAc (10.0 mL) and stirred at room temperature for 2 hr. Base-2,2-methyl-butyronitrile hydrochloride' can be used without further purification. Step 4 Combine 2-cyclopropyl-5-(2-tridecylfluorenyl ethoxylate) in a flask Methyl)_ 5H·0 is more than [2,3-b]D than 11 well-7-formic acid (200 mg, 0.60 mmol), 3-amino-2,2-methyl-butyronitrile Acid salt (223 mg, 1.50 mmol), 156090.doc • 129-201204731 EDC (264 mg, 1.38 mmol) and HOBt (186 mg, 1.38 mmol). Continued addition of DMF (4.0 mL) and i-Pr2NEt (0.33 mL) , 1.92 mmol). The reaction mixture was stirred at room temperature for 1 hr then concentrated. The residue was purified by EtOAc (20-100% EtOAc/hexane) Separation of the enantiomers by HPLC (Chiralcel OJ-H, hexanes / EtOH) afforded 63 mg (24%) of 2-cyclopropyl-5-(2-trisyl) --ethoxy hydrazinobipiro[2,3-b]&quot; than plough-7-formic acid ((S)-2-cyano-1,2,2-tridecyl-ethyl)-醯Amine and 67 mg (26%) of 2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxyindenyl)-5H-pyrrolo[2,3-b]pyridine as a colorless viscous oil Plough-7-formic acid ((R)-2-cyano-1,2,2-trimethylethyl) guanamine. Step 5 2-Cyclopropyl-5-(2-three in a flask Mercaptoalkyl-ethoxymethyl)_ 5H-pyrrolo[2,3-b]pyridin-7-decanoic acid ((S)-2-cyano-1,2,2-trimethyl- Ethyl)-decylamine (63 mg, 0.146 mmol) was dissolved in CH2C12 (1. 5 mL) and TFA (0.50 mL) was added. The reaction mixture was stirred for 2 hr and concentrated. The residue was dissolved in CH; 2 C12 (2.5 mL) Then, ethylenediamine (〇.5〇mL ' 7.48 mmol) was added and the mixture was stirred overnight at room temperature. The reaction mixture was then concentrated and chromatographed by 8 丨〇 2 (20-10 〇% £1 〇8 (: /hexane)purification of the residue' to give 32.5 mg (75%) of 2-cyclopropyl as a white powder. 5H-pyrrolo[2,3-b]&quot; specific tillage-7-decanoic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-guanidine. MS: (M+H)+=298. Example 7. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)_2-cyano-1,2,2-tridecyl-ethyl)-醯amine 156090.doc •130- 201204731

According to the procedure outlined in Step 5 of Example 6, using 2-cyclopropyl-5-(2-trimethylsulfonyl-ethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine-7 -formic acid ((R)-2-cyano-1,2,2-trimethyl-ethyl)-decylamine in place of 2_cyclopropyl_5_(2_trimethyldecyl-ethoxylated) -5H-pyrrolo[2,3-b]indole-7-carboxylic acid ((S)-2-cyano-i,2,2-trimethyl-ethyl)-decylamine was prepared. Ms: (M+H)+=298. Example 8. 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyridin-7-decanoic acid [(s)1(1 cyanylcyclopentyl)-ethyl]-decylamine and 2_cyclopropane _5H_pyrrolo[2,3_b]pyridin-7-decanoic acid [(R)-i-(i-cyano-cyclopentyl)-ethyl]-decylamine

Prepared according to the procedure outlined in Example 6 using cyclopentanephthalonitrile in place of isobutyronitrile. Step 4 separates the enantiomers by preparative palmitic hplc. (s)-Enantiomer MS: (M+H)+= 324; m.p. 220.0. (R)-Enantiomers ^48: (] \4 + 11) + = 324; melting point 220.0 - 223.0. 156090.doc -131 - 201204731 Example 9. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid [(S)-l-(l-cyano-cyclohexyl) -ethyl]-nonylamine and 2-cyclopropyl-5H-pyrrolo[2,3-1?]° ratio __7_carboxylic acid [(R)-l-(l-cyano-cyclohexyl)-B Amidoxime

Prepared by substituting cyclohexanecarbonitrile for isobutyronitrile according to the procedure outlined in the examples. Step 4 separates the enantiomers by preparative versus palmitic hPLc. (S)-Enantiomer MS: (Μ+Η)+=338. (R)-Enantiomer MS: (M+H)+=338 ° Example 10. 2-Cyclopropyl·5Η_° ratio [[2,3# ratio β井_7_carboxylic acid Π • (four Hydrogen-pyran-4-yl)ethyl]-decylamine

Step 1 At 〇 ° C, to tetrahydropyran, using a jun (5.00 g, 43.8 mmol)

In the solution in EhCHlOO mL), methylmagnesium bromide (3.0 M Et20 156090.doc -132 - 201204731 solution, 18·9 mL ' 56.9 mmol) was added dropwise. The reaction mixture was allowed to warm to rt and stirred overnight. The mixture was quenched with 50% saturated NHjCl. The organic extract was washed with aq. aq. EtOAc (EtOAc EtOAc). Step 2 The oil from Step 1 was dissolved in CH2C12 (50 mL) and triethylamine (9.8 mL &apos; The mixture was cooled to EtOAc and a solution of decane sulphide (4.07 mL &apos; 52.6 mmol The reaction mixture was allowed to warm to rt and stirred overnight. The mixture was quenched with H20 and the aqueous layer was extracted with CH2C12. The combined organic phases were washed with 1 M EtOAc, EtOAc (EtOAc) (EtOAc m. -4_base) _ ethyl ester. Step 3 Add sodium azide (624) to a solution of 1-(tetrahydro-pyran-4-yl)-ethyl sulfonate (1. g, 4.80 mmol) in DMF (10.0 mL). Mg, 9.60 mmol)' and the mixture was held overnight at 70C. The reaction mixture was cooled to room temperature and HW was added. The aqueous layer was extracted with EtOAc. EtOAc (EtOAc m.) Piper. Step 4 The oil from Step 3 was dissolved in MeOH (10 mL) and 10% Pd / carbon (40 mg). The mixture was stirred at Hz atmosphere (1 atm) for 1.5 h then filtered and evaporated to give </RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; -ethylamine. Step 5 2_Cyclopropyl-5Η-»Biloze[2,3-b]«&gt; Ratio 11 Well-7-carboxylic acid [1-(tetrahydroendanyl-4-yl)-ethyl]-decylamine . According to the procedure outlined in Step 4 of Example 1, 2-cyclopropyl-5Η-&quot;Biloxi[2,3-b] «Compound-7-carboxylic acid instead of 2-cyclopropyl-5-(2) -Trimethylsulfonyl-ethoxymethyl)_5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid and replaced with 1-(tetrahydropyran-4-yl)-ethylamine 1-((R)-1-Amino-ethyl)-cyclopentanol hydrochloride was prepared. MS: (M+H)+= 315; m.p. Example 11. 2-Bromo-5H-. Bis[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-guanamine.

Step 1 Suspension of 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3_b]pyridin-7-carboxylic acid (2·〇g, 5.39 mmol) In 36 mL of acetonitrile. Add N'N_diisopropylethylamine (2.8 mL, 16.2 mmol), bismuth tetrafluoroborate-benzotriazol-1-yl-N,N,N,,N,·tetramethylguanidine (1.9 g) , 5.93 mmol) and 3-amino-2,2-dimethyl-propan-1-ol (0.56 g, 5.39 mmol), and the reaction mixture was stirred for 1.5 h. Water and ethyl acetate were added and the layers were separated. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers of 156090.doc - 134 - 201204731 were washed with sodium sulphate, dried over sodium sulfate and concentrated. The residue was purified by EtOAc (EtOAc/EtOAc) toield °Biluo[2,3-b]° ratio tillage-7-formic acid (3-hydroxy-2,2-dimethyl-propyl)-bristamine. Step 2

According to the procedure outlined in Step 5 of Example 1, 2•Bromo·5_(2_tridecyldecyl-ethoxycarbonyl)·5Η-pyrrolo[2,3-b]pyrazine-7-曱Acid (3-hydroxy-2,2-didecyl-propyl)-decylamine in place of 2-cyclopropyl-5-(2-trimethyldecyloxyethoxy)-5H-«Bilo [2,3-b]. Than farming _7_ citrate [(r)]·. ·Hydroxy-cyclopentyl)-ethyl]-nonylamine to prepare 2-bromo-5H-° ratio η[2,3-b]° ratio p well 7-decanoic acid (3-carbyl-2, 2. Dimethyl-propyl)-decylamine. (M+H)+=328; melting point = 248.0-250.0. Example 12 2-Cyclopropyl-5H-pyrrolo[2,3b]pyrazine-7-decanoic acid (3_nonanesulfonyl 2,2-dimethyl-propyl)-decylamine

Step 1 2-Bromo-5-(2-tridecyldecyl-ethoxycarbonyl)-5H-pyrrolo[2 3 b]pyrazine-7-decanoic acid (2.0 g, 5.39 mmol) was suspended in 36 In 5% acetonitrile. N,N-isopropylethylamine (2.8 mL ' 16.2 mmol), tetrafluorofolic acid 〇 156090.doc -135- 201204731 and triazol-1-yl-N,N,N,,N, -Tetramethylhydrazine (1·9 g, 5.93 mmol) and 3-amino-2,2·dimethyl-propan-1-ol (〇·56 g, 5.39 mmol), and stirring the reaction mixture 1.5 Water and ethyl acetate were added and the layers were separated. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers were washed with sodium sulfate and dried over sodium sulfate. The residue was purified by silica gel chromatography (EtOAc / hexane) toield: </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ;Luo[2,3-b]0 is better than well-7_decanoic acid (3-carbyl-2,2-dimethyl-propyl)-bristamine. Step 2 2-Bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[23_b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimethyl • Propyl) amide (〇47 g, 〇2 mmol) was dissolved in 4.9 mL of hydrazine and 0.25 mL of water. The solution was flushed with argon and added with acetic acid (12 mg '0.05 mmol), tricyclohexylphosphine (29 mg, 0.102 mmol), cyclopropylfolic acid (0·114 g, 1 33 mm〇1) and phosphoric acid. Tripotassium (〇·76 g '3.57 mmol). At 1〇〇. The reaction was stirred under stirring for 16 hours and then cooled to room temperature. The aqueous solution of sodium hydrogencarbonate and acetic acid were added and the layers were separated. The aqueous layer was extracted with EtOAc (EtOAc)EtOAc. Purification of the residue by gelatin chromatography (MeOH/CH.sub.2Cl.sub.2) afforded 0.34 g (79%) of 2-cyclopropyl-5-(2-trimethyl-stone-ethoxyl-yl)- 5H-° [2,3-b]0 than p-well-7-carboxylic acid (3-hydroxy-2,2-dimercapto-propyl)-guanamine. Step 3 2-Cyclopropyl-5-(2-trimethylsulfonyl-ethoxymethyl)_5Η_0pyrrolo[2,34]pyrazine-7-carboxylic acid (3-hydroxy-2,2 -Dimethyl-propyl)-decylamine (〇.34 156090.doc • 136·201204731 g, 0.81 mmol) was dissolved in 4 mL of CH2C12 and cooled in an ice bath. N,N-Diisopropylethylamine (〇·2 ΐ mL, 1.2 mmol) was added, followed by the slow addition of decanesulfonium (0.076 mL, 0.97 mmol). The reaction mixture was allowed to warm to room temperature over 16 hours. Ethyl acetate and aqueous hydrochloric acid were added and the layers were separated. The aqueous layer was extracted with EtOAc. EtOAc (EtOAc)曱 矽 矽 _ _ ethoxymethyl) _5H ·. 比 并 [23b] n than plough-7-yl]-amino}-2,2-dimethyl-propyl ester Step 4 will be A 3-{[2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyroxy-7-carbonyl]-amine Base}-2,2-dimethyl-propyl ester (0.28 g '0.56 mmol) was dissolved in 8 mL of DMF. Add sodium thiomethoxide (157 mg, 2.24 mmol) to seal the reaction vessel and in a microwave reactor The mixture was stirred for 30 minutes at 100 C. Aqueous sodium argonate solution and dioxane were added and the layers were separated. The aqueous layer was extracted with dioxane (2x), and the combined organic layers were washed with water and sodium carbonate solution, followed by sulfuric acid. The sodium was dried and evaporated. The residue was purified mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj Methyl) _5H_. Bis[2,3b] pyridin-7-decanoic acid (2,2-dimethyl-3-methylthio-propyl)-decylamine. 5 2-Cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid (2,2-dimethyl) _3_Methylthio-propyl)-decylamine (102 mg '0.226 mmol) was dissolved in 0.9 mL of THF. Slowly added potassium persulfate (0.418 g '0.682 mmol) dissolved in 0.9 mL of H2 156090.doc -137- 201204731 and the mixture was stirred at room temperature for 16 hours. Ethyl acetate and water were added to the mixture. The layers were separated and washed with ethyl acetate (3×). The combined organic layers were dried with sodium sulfate and evaporated <~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Base alkyl-ethoxymethyl)_5H-pyrrolo[2,3_b]pyrazine-7-carboxylic acid (3-methanesulfonyl-2,2-dimethyl-propyl)-guanamine. Step 6 2-cyclopropyl-5H-pyrrolo[2,3b]pyrazine-7-carboxylic acid (3-methanesulfonyl-2,2-dimethyl-propyl)-decylamine. Step 5 according to Example 1. The procedure outlined is '2- lysylpropyl 5-(2-didecylcarbolyl-ethoxymethyl)-5H-°piro[2,3-b]pyrazine-7- Tannic acid 3-decanesulfonyl-2,2-dimercapto-propyl)-guanamine instead of 2-cyclopropyl-5-(2-trimethyldecyloxyethoxy)-5H-pyrrole [2,3-b]. Manufactured by MS-(M+H)+ 351, melting point = 206.0-208.0. Example 13. 2-(3,3-Dimethyl-pyrrole.dine-1-yl)-511-pyrido[2,3-13]. Specific tillage-7-decanoic acid (3-carbyl-2,2-dimethyl-propyl)-nitramine

Step 1 156090.doc 138- 201204731 2-Bromo-5-(2-tridecylfluorenyl-ethoxycarbonyl)_5H_n-Big[2,3_b]pyrazine-7-carboxylic acid (3-hydroxyl) -2,2-Dimethyl-propyl)-decylamine (0.15 g, 〇33 mmol) was dissolved in 3.3 mL of dimethyl sulfoxide and then rinsed with argon. Potassium carbonate (0.113 g, 0.82 mmol), 3,3-dimethylpyrrolidine (0.16 g, 1.64 mmol), DL-proline (11 mg, 0.098 mmol) were added followed by copper iodide (1) ( 9 mg, 0.049 mmol). The reactants were sealed and at 1 Torr. Stir for 16 hours in an oil bath to cool the reaction and add water and ethyl acetate. The layers were separated&apos; and the organic layer was extracted once more with ethyl acetate. The combined organic layers were washed with water and a saturated aqueous solution of sodium sulfate, dried over sodium sulfate and evaporated. The obtained residue was purified by silica gel chromatography (methanol / methylene chloride) to afford 13 g (83%) of 2-(3,3-didecyl-pyrrolidine-i-yl)·5-(2_3 Methyl decyl _ ethoxylated hydrazino) -5 Η - ° than 嘻 [2, 3-1)] ° ratio "• Well-7-decanoic acid (3-carbyl-2,2-dimercapto- Propyl)-guanamine. (Μ+Η)+=476. Step 2 2-(3,3-Dimercapto-pyrrolidin-1-yl)-5-(2-tridecylfluorenyl-ethoxyindolyl)-5H-pyrrolo[2,3-b Pyridin-7-decanoic acid (3-hydroxy-2,2-dimercaptopropyl)-decylamine (0.13 g, 0.27 mmol) was dissolved in 1.3 ml of fermentation. Subsequently, 1.7 ml of a 6 M aqueous HCl solution was slowly added, followed by stirring the reaction in a heating block at 9 ° C for 30 minutes. The reaction was cooled, sodium bicarbonate solution was added and then extracted twice with ethyl acetate. The combined organic layers were washed with a sodium chloride solution, dried over sodium sulfate and concentrated. The residue obtained was redissolved in 1 mL of ethanol and sodium acetate (0.73 g, 5.4 mmol) was added. The reaction was allowed to react at 60 ° C for 16 hours. After cooling, water was added and the solution was extracted three times with ethyl acetate. The combined organic layers were washed with a sodium sulphate solution and dried over sodium sulfate 156090.doc. The residue was purified by EtOAc (MeOH/MeOH) to afford 51 mg (54%) of 2-(3,3-di-di- yl-pyrrolidine yl) _5H-pyrrolo[2, 3_ b]pyridin-7-carboxylic acid (3, hydroxy-2,2-didecyl-propyl decylamine. Ms: (M+H) = 346 'hyun point = 223 〇 225 〇; elemental analysis: calculated value c 69.59, Η 7·88, N 20.27, experimental value c 69 22, Η 7.70, N 20.07. Example 14. 2-Dimercaptoamino-5Η-η ratio 咯[2,3_b]pyrazine_7_ Capric acid (3_hydroxy-2,2-dimethyl-propyl)-decylamine

Replace dimethylamine hydrochloride with 3,3_ according to the procedure outlined in Example 13.

Dimethyl group 0 is prepared by a little acridine. MS: (M+H)+=292; mp=222.0-224.0 〇

Example 15. 2_Pyrrolidin-1-yl-; 5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-methyl-propyl)-nitramine

Η 0 156090.doc •140- 201204731 Methyl According to the procedure outlined in Example 13, a pyrrole bite was used instead of 3,3_Bilo. MS: (M+H)+=318; refining point=220.0-222.0 Example 16. Diterpene 2-phenylamino-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxyl) _2,2_ propyl-propyl)-guanamine

The ratio was prepared by substituting aniline for each of 3,3-dimethylhydrazine according to the procedure outlined in Example 13. 1^8: (]^+print +=340; melting point = 280.0-282.0. Example 17. Formic acid

2_(mercaptoamine fluorenyl-amino)_5H_pyrrolo[2,3_b]pyrazine_7·(3-carbyl-2,2-dimercapto-propyl)-decylamine Step 1 156090.doc

-141 - 201204731 According to the procedure outlined in Step 1 of Example 13, using 2_amino-N-methylacetamide instead of 3'3-methylpyrrolidine to prepare 2·(methylamine-methyl fluorenyl) Methyl-amino)-5-(2-trimethyldecyl-ethoxymethyl&quot;Η·π ratio[23b] pyridin-7-formic acid (3·hydroxy-2,2_2 Methyl-propyl)-guanamine. Step 2 2-(Methylamine-methylmethylmethyl, yl)·5·(2·trimethylglycine-ethoxymethyl)-5Η-pyrrole [2,3-b]pyrazine-7-formic acid (3-hydroxy-2,2-dimercapto-propyl)-decylamine (90 mg, 0.193 mmol) dissolved in 2 ml of 1 fluorinated tetrabutyl In a solution of THF, the solution was stirred at 60 ° C for 24 hours. After cooling the reaction, 'the sodium bicarbonate solution was added and the reaction was extracted three times with ethyl acetate. The combined organic layer was washed with a gasified sodium solution over sulfuric acid. The sodium was dried and concentrated. The residue was purified by silica gel chromatography (EtOAc/EtOAc/EtOAc) to yield 15 mg (21%) of 2-(methylamine carbazinylamino) _5H. [2 3_b]pyridin-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine. MS: (M+H)+=335; mp=270.0-275.0. 18. 2-Trifluoromethyl-5H-° ratio σ[2,3-b]n ratio tillage-7-formic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine

Step 1 156090.doc -142· 201204731 2-Bromo-5·(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ( 3-Hydroxy-2,2-dimethyl-propyl)-decylamine (0.5 g, 1.08 mmol) was dissolved in 5 mL of dichloromethane. Add N,N-diisopropylethylamine (1.5 ml '8_7 mmol) and cool the reaction in an ice bath. Slowly add 2-trimethylsulfanyl ethoxymethyl gas (0·39 ml, 2.18 mmol) The reaction was stirred at room temperature for 16 hours. A dilute aqueous solution of HC1 and ethyl acetate were added. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with a sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to afford &lt;RTI ID=0.0&gt; -5 H-0 ratio slightly [2,3 -b]0 ratio p well-7-carboxylic acid [2,2 - fluorenyl-3-(2-dioxyl sulphate-ethoxy methoxy group) )-propyl]-bristamine. Step 2 2-Bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine_7·decanoic acid [2,2-dimethyl 3-(2-tridecyldecyl-ethoxycarbonyl)-propyl]-decylamine (0.18 g, 0.306 mmol) dissolved in 0.6 ml of N,N-dimethylacetamide . The solution was purged with argon and then cooled in an ice bath. Copper (116 mg, 1.83 mmol) and dibromodifluoromethane (〇·ι 13 m Bu 1.22 mmol) were added, and the reaction vessel was sealed and stirred at i ° ° C for μ hours. After cooling, a sodium hydrogencarbonate solution and ethyl acetate were added to the reaction mixture. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with a sodium sulfate solution and dried over sodium sulfate. After concentration, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to afford 41 mg (23%) of 2-trifluoromethyl-5-(2-trimethyl decyl-ethoxymethyl )_511_pyrrolo[2,34]pyridin 156090.doc -143- 201204731 Plowing-7-formic acid [2,2-dimethyl-3-(2-trimethyldecyl-ethoxyoxy) -propyl]-guanamine. (Μ+Η)+=577 » Step 3 2-2-Dimethylmethyl-5-(2-trimethylphosphoryl-ethoxymethyl)-5H-ntbn each [2,3-b] Pyridine_7_carboxylic acid [2,2-dimethyl]3(3-trimethyldecyl-ethoxyoxy)-propyl]-decylamine (41 mg, 0.17 mmol) dissolved In 0.4 ml of sterol. 0.5 ml of a 6 M aqueous HCl solution was then slowly added, and the reaction was stirred at 90 ° C for 45 minutes in a heating block. The reaction was cooled, a sodium bicarbonate solution was added and then extracted twice with ethyl acetate. The combined organic layers were washed with a sodium chloride solution, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (methanol / dihexane) to yield 15.7 mg (70%) of 2-trifluoromethyl-5H-pyrrolo[2,3-b]pyrimin-7-carboxylic acid (3) _hydroxy-2,2-dimercapto-propyl decylamine. MS: (M+H)+= 317; mp=221.0-223.0 » Example 19. 2-cyclopropyl-5Η-»比比和[2 ,3-b]»比耕-7-decanoic acid (2-decyloxy-2-indolyl-propyl)-guanamine

Substituting 2-methoxy-2-mercaptopropylamine for 3-amino-2,2-dimethyl-propan-indole-ol in step 1 according to the procedure outlined in steps 12-2 and 6 of Example 12. To prepare. MS: (Μ+Η)+=289; m.p. = 259.0-262.0. 156090.doc •144· 201204731 Example 20. 2-Cyclopropyl-5H-0 is more than [2,3-b]D than p-well-7-methyl (3-yl-propyl)-bristamine Gas based, 2,2 hyperthyroidism

According to the procedure outlined in Example 4, Step 4-5, TM 2,2- oxypropylamine replaces 1-((R)-1-amino-ethyl)·cyclopentanyl-3, 曱% (M+H)+=303; melting point=230.0-232.0. Take it for preparation. Example 21. Acid dicyclopropyl fluorenyl-2-cyclopropyl- each [2,3-b]n ratio 11 well-7-methylamine

Substituting dicyclopropylmethylamine hydrochloride for 3-amino-2,2-dimercapto-propanol-ol based on the procedure outlined in steps 12 and 6 of Example 12 preparation. MS: (M+H)+= 297; mp. Example 22. 156090.doc -145- 201204731 2-Cyclopropyl-5H-n-pyrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-l-methoxymethyl-2, 2-·monomethyl-propyl)-bristamine

Step 1 R-second leucine (0 23 g' 1.96 mmol) and di-tert-butyl dicarbonate (0.85 g, 3.9 mm 〇i) were dissolved in 10 ml of dioxane and stirred for 3 days. Subsequently, an aqueous HCl solution and ethyl acetate were added, and the layers were separated and the aqueous layer was extracted once again with ethyl acetate. The combined organic layer was washed with EtOAc (EtOAc) (EtOAc) _Wi-based methyl 2,2 dimethyl-propyl)-aminobutyric acid tert-butyl ester. Step 2 ((R)-l-hydroxyindenyl-2,2-didecyl-propylaminocarboxylic acid tert-butyl ester (〇.38g, ΚΜππηοΐ) was dissolved in nml of acetonitrile, and iodine was added continuously. Burn (1.6 ml ' 26.1 mm〇l) and silver oxide (0.65 g, 2 78; as 0% CW·K//, prepared on page 386). Cover the reaction flask to block light and heat the reactants under reflux 24 Hours. Add the dish (6.4 ml) and silver oxide (0.65 g) one by one, and then continue heating until the reaction is completed by reverse phase LC/MS using standard 156090.doc •146·201204731. The reaction mixture was filtered and washed with ethyl acetate. EtOAc was evaporated. Base 2,2-dimethyl-propyl)-amino decanoic acid tert-butyl ester. Step 3

Dissolve ((R)-l-decyloxyindenyl 2,2-dimercapto-propyl)-tert-butyl methacrylate (0.28 g 'I·2 mmol) in 6 ml of dichloromethane Medium and then cooled in an ice bath. 4 ml of trifluoroacetic acid was added and the reaction was stirred to room temperature. The reaction solution was evaporated to give trifluoroacetic acid (Ry-decyloxy 2,2-dimethyl-propylamine, which was used without further purification. Step 4 was carried out according to the procedure outlined in Step 4-5 Tri-acetic acid (8) beryllyloxy fluorenyl-2,2--methyl--3C, n*. JUL. "代代-1-Amino-ethyl"-cyclopentyl hydrochloride to prepare 2_ ring propyl_5H_ oxo[2,3-b]pyrazine-7-decanoic acid ((R)-l-methoxyindolyl 2 2 bis (μ+Ηλ+_.17 . ^ methyl· Propyl)-guanamine. MS: (M+H) -317, you point = 2 Example 23. - oxime oxime 2-cyclopropyl · 5 Η • (d) and [2, 3 zhong &quot;_7_ formic acid Called 2,2_dimercapto-propylamine I r\

156090.doc • 147-201204731 Prepared according to the procedure outlined in Example 22, substituting s_third leucine for &amp; • third leucine. MS: (m+h)+=317; m.p. = 268 〇 _27 〇 〇. Example 24. 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyridyl, well_7_carboxylic acid (1_cyclohexyl-propyl decylamine)

Step 1 2-Mercapto-2-propanesulfinamide (5 〇g, 41 2 mm 〇1), cyclohexanefurfural (9.9 nU '82.5 mmol), pyridinium sulfonate (0.52 g) , 2.06 mmol) and 25 g of magnesium sulfate were combined with 70 ml of dichloromethane in a flask. The reaction mixture was stirred for 16 hours then filtered through Celite. After evaporation, the residue was purified by silica gel chromatography (diethyl ether/hexane) to afford 7 79 g (87%) of 2-methyl-propane-2-sulfonic acid 1-cyclohexyl-methyleneamine. Step 2 2-Methyl-propane-2-sulfinic acid 1·cyclohexyl-methylene decylamine (0.5 g, 2.3 mmol) was dissolved in 12 mL diethyl ether. The reaction solution was cooled to _40. (: and add ethylmagnesium bromide (3 Μ ether solution, 1.5 ml, 4.5 mmol) and mix the reaction to 25 ° C. Continue to add ammonium chloride solution and ethyl acetate, separate the layers and reuse The aqueous layer was extracted twice with ethyl acetate. The combined organic layer was washed with sodium sulfate solution, dried over sodium sulfate and concentrated to give 0.45 g (85%;) 2 156 090.doc s 148 · 201204731 曱 · · ' Ether-2-rylic acid (1-cyclohexyl-propyl)-decylamine β Step 3 2-Indolyl-propane-2-sulfinic acid (1-cyclohexyl-propyl)-decylamine (0.45 g 1.95 mmol) was dissolved in 1 ml of methanol, and 1 mi of a solution of 4 μl of HCl in 1,4-dioxane was added. The reaction solution was stirred for 30 minutes, and diethyl ether was added to the solution to evaporate the reaction solvent to form a sediment. The solid was filtered, washed with hexane and dried to give &lt;RTI ID=0.0&gt;&gt;

2-ring was prepared according to the procedure outlined in Example 4, Steps 4-5, substituting the azo- propylamine salt to replace 1-((R)_1.amino-ethyl)-cyclo &amp; alkoxide. Propyl-5H-compound [2,3 external ratio. Well_7_carboxylic acid (1) cyclohexyl-propyl urethane. MS: (Μ+ΗΓ=327; dissolved meal g_2ig (); elemental analysis: calculated value C 69.91, Η 8.03, N 17.16, experimental value. μ", Η ή 16.97. 5 Shell Example 25. 2-Cyclopropyl The material is followed by 3_b]"_7_f acid (cyclohexyl-cyclopropylmethyl)-decylamine

Prepared according to the procedure outlined in Example 24, in step 2, by substituting cyclopropyl I56090.doc-149-201204731 for the substitution of desertified ethyl magnesium. MS: (M+H)+=339; m.p. 174.0-176.0; Elemental analysis·calculated value: 7 〇.98, Η 7.74, N 16.55, experimental value c 70.68, Η 7.54, Ν 16.46» Example 26. 2_ Cyclopropyl-5Η-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l-cyanomethyl-2,2-dimercapto-propyl)-decylamine

Step 1 Dissolve ((R)-l-hydroxyindenyl 2,2-dimethyl-propyl)-aminobutyl methacrylate (Example 22, Step 1; 0.157 g, 7.2 mmol) in 2 Ml in tetrahydrofuran. Diethylamine (〇·13 ml, 0.935 mmol) was added and the reaction was cooled in an ice bath. Methane sulfonium gas (0.073 ml, 〇.935 mm 〇1) was slowly added and the reaction was stirred to 25 ° C over 16 hours. Dioxane and water were added and the layers were separated. The aqueous layer was extracted once more with a second gas, then the combined organic layer was washed with sodium chloride and dried over sodium sulfate. After evaporation, 21 g (83%) of (R)-2-tert-butoxycarbonylamino-3,3-didecyl-butyl sulfonate was obtained. Step 2 Dissolve (R)-2-tert-butoxycarbonylamino-3,3,3-dimethyl-butane vinegar (0.21 g, 0.71 mmol) in 2 ml of N,N-didecyl In the guanamine. Add 156090.doc -150- 201204731 Add pulverized sodium cyanide (1 〇 4 mg ' 2 · 13 mmol) and mix the mixture for 4 days at 35 ° C. Add water and ethyl acetate and separate the layers. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with water and sodium sulfate and then dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to afford 0.1 g (62%) of ((S)-l-cyanoindenyl 2, 2-didecyl-propyl) - Amino decanoic acid tertidine. Step 3 Cool ((S)-1-cyanononyl 2,2-dimethyl-propyl)-carbamic acid 2 butyl ester (0.1 g, 0.44 mmol) in ice bath and add cold 4 A solution of M HCl in 1,4-dioxane to dissolve the ester. After 1 hour, the reaction solution was carefully evaporated to give (S)-3-amino-4,4-dimercapto-pentanonitrile hydrochloride, which was used without further purification. Step 4 Substituting (s)_3_Amino-4-heart dimethyl-valeronitrile hydrochloride for hydrazine-"magic-indole-amino-ethyl" according to the procedure outlined in Example 4, Steps 4-5 Preparation of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid by cyclopentanol hydrochloride ((8)_丨_cyanomethyl_2,2·dimethyl _ propyl) _ guanamine. MS: (M + H) + = 312 melting point = 258.0-260.0 〇 Example 27. 2-cyclopropyl-5 Η-pyrrolo[2,3-b] 吼耕-7-carboxylic acid ((R)-l-cyanomethyl 2,2-diindenyl-propyl)-decylamine 156090.doc -151 · 201204731

According to the procedure of Example 23 in Example 26, ((S)-l-hydroxymethyl-2,2-dimercapto-propyl)-carbamic acid di Duo-D-S曰 was substituted ((尺 卜 卜 hydroxymethyl 2,2-didecyl-propyl)-carbamic acid second butyl phthalate is also prepared by 弟 弟 丁 丁 曰 。 。 Μ Μ Μ Η 。 。 。 。 Μ Μ Μ Μ Μ Μ 。 。 。 ; ; ; ; ; ; ; 259.0-261.0. Example 28. 2-Cyclopropyl-5H-. The ratio is slightly [2, qing than spray _7_ decanoic acid (2_yl 2, fluorenyl-trifluoromethyl-propyl)-hydrazine amine

Step 1 3,3,3-Trifluoropropylalanine methyl ester hydrochloride (1. g, 5.16 mmol) was dissolved in 26 ml of chloroform. Diethylamine (0.72 ml, 5.16 mmol) was added and the reaction was cooled in ice. Di-tert-butyl dicarbonate (2.2 g, 10.3 mmol) was slowly added and the reaction was stirred for 18 hours. Ethyl acetate and an ammonium sulfate solution were added, and the layers were separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with EtOAc EtOAc EtOAc EtOAc. After evaporation, the residue was purified by silica gel chromatography to afford EtOAc (EtOAc) Step 2 2-Tertiyloxycarbonylamino-3,3,3-trifluoro-propionic acid decyl ester (0.16 g, 0.55 mmol) was dissolved in 5 mL of THF and then cooled in ice. Gasified bismuth magnesium (3. Μ Μ ether solution, 0.73 ml, 2.18 mmol) was added dropwise to the solution, followed by stirring for 16 hours. An ammonium chloride solution and ethyl acetate were added to the reaction mixture, and the layers were separated. The aqueous layer was extracted once more with ethyl acetate and the combined organic layers were washed with sodium sulfate. Drying over sodium sulfate and evaporation gave 0.11 g of &lt;RTI ID=0.0&gt;&gt; Step 3 The (3-hydroxy-2-methyl-1-trifluoromethyl-propyl)-carbamic acid tert-butyl ester (0.11 g, 0.43 mmol) was cooled in an ice bath and cold 4 M HCl was added. After the 1,4-dioxane solution was dissolved for 1 hour, the reaction solution was carefully evaporated to give 3-amino-4,4,4-tri U-methyl-butan-2-ol hydrochloride. It can be used without further purification. Step 4 Replace the amine group with ethyl 3-amino-4,4,4-trifluoro-2-indolyl-butan-2-ol hydrochloride according to the procedure outlined in Example 4, Steps 4-5. _cyclopentanol hydrochloride to prepare 2-cyclopropyl-5H_pyrrolo[2,3b]pyrazine_7-decanoic acid (2-hydroxy-2-indenyl-1-trifluoromethyl) Base) _ guanamine. MS: (M+H)+=343; melting point = 258.0·260·0. 156090.doc -153- 201204731 Example 29. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid ((yq cyclohexyl_2.hydroxy-2-methyl-propyl) )--bristamine

Step 1 Dissolve (S)-amino-cyclohexyl-acetic acid hydrochloride (1. g, 5 16 〇丨) in 17 ml of 2:1 1,4-dioxane: water in an ice bath cool down. A sodium hydroxide solution (10.4 ml of 1 M aqueous solution) and solid sodium hydrogencarbonate (0.43 g, 5.16 mmol) were slowly added to the reaction solution. Dibutyl succinate diacetate (1.68 g ' 7.74 mmol) was added and the reaction mixture was stirred for 16 h. The partially evaporated reaction mixture was then dissolved in ethyl acetate and water and neutralized to pH 2 with hydrogen sulfate / sulphate. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined ethyl acetate layer was washed with a sodium sulfate solution, dried over sodium sulfate and evaporated to give &lt;RTI ID=0.0&gt;&gt;&gt; Step 2: Dissolve (s)-t-butoxycarbonylamino-cyclohexyl-acetic acid (1.52 g, 516 mmol) in 39 ml of toluene and 11 ml of decyl alcohol. Slowly add trimethyldecyl diazonium. (2_0 hexane solution, 12.9 ml, 25.8 mm 〇 1) i 156090.doc -154 - 201204731 The reaction mixture was stirred for 16 hours. The reaction was evaporated to give a solid, which was purified eluted eluted eluted elut elut . Step 3 Substituting (s) • tert-butoxycarbonylamino-cyclohexyl-acetic acid decyl ester for 2_t-butoxycarbonylamino group _ 3,3 according to the procedure outlined in Example 28, Steps 2-4 , 3-difluoro-propionic acid decyl ester to prepare 2-cyclopropyl-5H_pyrrolo[2,3b]pyrazine-7-carboxylic acid ((S)-l-cyclohexyl-2-hydroxymethylpropyl ) _ guanamine. Ms: (M+H)+=357; mp=251.0-253. Example 30. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine·7-carboxylic acid ((R)_2-cyano-cyclopropyl-ethyl)-g-padamine

Step 1 As in Example 24, step 1 'replaces 2-mercapto-2-propanesulfinamide with (R)-2-mercaptopropan-2-ylidene amide, and replaces cyclohexanal with cyclopropanal Alkylfurfural is used to prepare (R)-2-mercapto-propane-2-pyrroic acid 1-cyclopropyl-methylene-branched amine. Step 2 Dissolve (R)-2-methyl-propan-2-olene acid i_cyclopropyl-methylene decylamine (ο" 156090.doc -155- 201204731 g ' 1.73 mmol) in 17 ml Tetrahydrogen is in the middle. A tetrabutyl sulfonate (0.58 g, 1.73 mmol, as prepared in 5w//. Tpw. 2003, 76 (77), 2191) was added, and the reaction solution was cooled in a dry ice/acetone bath. Trimethyl sulphate acetonitrile (0.356 ml, 2.6 mmol) was added dropwise and the mixture was stirred for 2 hr. An ammonium chloride solution was added to the reaction solution at about 〇 ° C. Ethyl acetate and more water were added, the layers were separated&apos; and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (ethyl acetate / hexane) to afford 0.14 g (3 8%) of (R)-N-((R)-2-cyano-1-cyclopropyl Base)-2-mercaptopropene-2-diamide. Step 3 Substituting 2-(R)-N-((R)-2-cyano-1-cyclopropylethyl)-2-methylpropane-2-sulfinamide for Example 2-Step 3-4 ' Methyl-propane-2-sulfinic acid (1-cyclohexyl-propyl)-guanamine to prepare 2-cyclopropyl-5H-° ratio [2,3-b]D to p-well-7- Capric acid ((R)-2-cyano-cyclopropyl-ethyl)-decylamine. MS: (M+H)+=296; [a]D = -23. Example 31. 2-Cyclopropyl-5H-° ratio of [2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyano-1-cyclopropylethyl)- Guanamine

156090.doc -156· 201204731 Substituting (S)-(-)-t-butylsulfinamide for (R)-2-mercaptopropane_2_sulfinamide according to the procedure outlined in Example 30 To prepare. MS: (M+H)+= 296; [A]D=23.7; Example 32.

Step 1 Slowly add methylmagnesium bromide (3.0 M Et20 solution ' 28.7 mL) to a solution of Boc-D-ethyl galactinate (5.00 g, 24.6 mmol) in THF (10 mL) at 〇 °C. , 86.1 mmol). The resulting white slurry was stirred at 〇 ° C for 1 hour' and then stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated aq. The combined organic phases were washed with brine and dried over MgSO 4 to yield 4.93 g (99%) of (())-hydroxy-1,2-didecyl-propyl ) _ amino citrate third vinegar. Step 2: ((R)-2-Hydroxy-1,2-dimethyl-propyl)-aminocarboxylic acid tert-butyl ester

(4.93 g, 24.2 mmol) was dissolved in ι·〇μ HC1 (150 mL) and stirred at 50 ° C for 4 hrs to give 4 〇1 g as a light brown solid (R) _3 _ 2-Methyl-butan-2-ol hydrochloride, which was used without further purification. 156090.doc -157· 201204731 Step 3 Combine 2-bromo-5-(2-trimethyldecyloxyethoxymethyl)-5H-0 in a flask to ratio [2,3-b]0 11 Well-7-formic acid (3.25 g, 8_74 mmol), (R)-3-amino-2-mercapto-butan-2-ol hydrochloride (3.05 g, 21.9 mmol), EDC (3.85 g ' 20.1 Methyl) and HOBt (2.72 g, 20.1 mmol). DMF (50 mL) and i-Pr2NEt (4.87 mL, 28.0 mmol) were then added. The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was purified by EtOAc EtOAc (EtOAc) elute -5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-decylamine. Step 4 'In the pressure tube', 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (( R)-2-Hydroxy-1,2-dimercapto-propyl)-chiral amine (120 mg '0.26 mmol) and 1-ethyl-1H-pyrazole-4-tanning acid pinacol ester (70 mg '0.32 mmol) was dissolved in DME (2.0 mL). K2C〇3 aqueous solution (2.0 Μ, 0.39 mL, 0·78 mmol) and Pd(PPh3)4 (15 mg '0.013 mmol) were added and the mixture was degassed with a gentle n2 stream for 15 min. The tube was then sealed and heated at 90 °C for 3 hours. The reaction mixture was cooled to rt EtOAc (EtOAc)EtOAc. The organic extract was washed with brine and dried over MgSO 4 and concentrated. Purification of the residue by EtOAc (2 EtOAc EtOAc) elute 4-yl)-5-(2-tridecyldecyl-ethoxymethyl)-5H-&quot;bi-[2,3-b]pyridin-7-decanoic acid ((R)- 2-Hydroxy-1,2-dimercapto-propyl)-bristamine. 156090.doc •158- 201204731 Step 5 To 2-(1-Ethyl-1H-pyrazole-4-yl)-5-(2-trimethyldecylalkylethoxymethyl)-5H-pyrrolo[2, 3-b] Pyridin-7-decanoic acid hydroxydimethyl-propyl)-nonylamine was added to a solution of CH2C12 (2.25 mL). The reaction mixture was stirred for 2.5 hours and concentrated. The residue was dissolved in CH2C12 (3.75 mL), and ethylenediamine (〇75 mL, 112 〇1) was added.

The mixture was stirred overnight at room temperature. The reaction mixture was concentrated and the residue was purified EtOAcjjjjjjjjjjjjjj _4-Base)-5Η-β ratio each [2,3_b]pyridin-7-carboxylic acid ((R)-2-hydroxy-i,2-dimethyl-propyl)-guanamine. MS: 343 (M+H)?; mp. Example 33. 2-(1-Methyl-1H-0 ratio. Sit-4-yl)_5Η-α ratio succinct [2,3-b]. Bi N-7-carboxylic acid ((R)-2-hydroxy-1,2-dimercapto-propyl decylamine

According to the procedure outlined in Example 4, Steps 4-5, substituting Diethyl-1H-pyridin-4-1 phthalic acid pinacol vinegar for 1-ethyl-1 -11 is more than salivation. Prepared by alcoholic vinegar. MS: (M+H)+= 329; mp 285. 〇-288 〇. Example 34. 156090.doc •159- 201204731 2-Thien-2-yl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy·1,2-dimethyl Base-propyl)-guanamine

In accordance with the procedure outlined in Example 4, Steps 4-5, thiophene-2-furanoic acid was used in place of 1-ethyl-1Η-indole. Take -4- tartic acid which is prepared by using alcoholic vinegar. ]viS: (M+H)+=331; melting point 272.0-275.0. Example 35. 2-(3,6-Dihydro-2H-n-endan-4-yl)-5H-indolo[2,3-b]0 than argon-7-decanoic acid ((R)-2 -hydroxy-1,2-dimethyl-propyl;)-decylamine

Substituting 3,6-dihydro-2-indolepiperidin-4-yl-acid pinacol ester for 1-ethyl-1H-pyrazole_4_tanning acid according to the procedure outlined in Example 4, Steps 4-5 The pinacol ester is prepared. MS: (M+H)+=331. Example 36. 2_. Plug. Sit-2-yl-D and [2,3-b]» than "• well formic acid ((r)_2_transcarbyl_ 1,2-156090.doc • 160- 201204731 dimethyl-propyl)- Amine

Step 1 In a pressure tube, 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3b]pyrazine-7-decanoic acid ((R) 2-Hydroxy-1,2-dimercapto-propyl)-decylamine (120 mg '0.26 mmol) and 2-tributylstannylthiazole (〇.1〇niL '0.32 mmol) dissolved in DMF (2.0 mL) )in. Add to

Pd(PPh3)4 (15.2 mg '0.013 mmol) and copper iodide (1) (1 〇. 〇 mg, 0.052 mmol) were sealed and heated at 80 ° C for 1.5 hours. The reaction mixture was cooled and concentrated. Purification of the residue by SiO 2 chromatography (0-10% MeOH/CH.sub.2Cl.sub.2) afforded &lt;RTI ID=0.0&gt;&gt;Methyl)-5H-«bibromo[2,3-b]&quot;Bi-indus-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-decylamine. Step 2 2-° Retraz-2-yl-5H-pyridox[2,3-b]0 to p-well-7-carboxylic acid ((R)-2-hydroxy-I2-dimethyl-propylhydrazine Amine. According to the procedure outlined in Step 5, Example 32, 2-thiazol-2-yl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b] Pyridin-7-formic acid ((R)-2-hydroxy-1,2-dimercapto-propyl)-decylamine in place of 2-(1-ethyl-1H-pyrazol-4-yl)-5- (2-trimethyldecylalkyl-ethoxyl 156090.doc •161- 201204731 methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1 Prepared by using 2-dimethyl-propyl)-guanamine. MS: (M+H)+= 332. Example 37. 2-pyridine-2-yl-5H-pyrrolo[2,3-b]pyridin Carb-7-formic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-decylamine

Prepared according to the procedure outlined in Example 36, using 2-(tributylstannyl)pyridine instead of 2-tributylstannylthiazole. Ms: (M+H)+=326. Example 38. 2-Amino-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)·2·hydroxy-1,2-dimercapto-propyl)-nitramine

Step 1 In a microwave tube, 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-511_〇 〇[2,3b]pyrazine-7·decanoic acid (R)-2-hydroxy-1,2-dimercapto-propanyl 156090.doc 201204731 base)-bristamine (250 mg, 0.55 mmol), zinc cyanide (97 mg '0.82 mmol) and Pd(PPh3)4 (191 mg, 0.165 mmol) was combined in DMF (5.0 mL) and heated at 140 ° C for 15 min. Evaporation of the reaction mixture and purification by EtOAc EtOAc (EtOAc:EtOAc) -ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)-2-hydroxy-1,2-dimercapto-propyl)-decylamine . Step 2 2-Cyano-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)-2-hydroxy-1,2-didecyl-propyl)-guanamine. According to the procedure outlined in Step 5, Example 32, 2-cyano-5-(2-tridecyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b] ° ratio ** Well-7-decanoic acid ((R)-2-yl-1,2-dimethyl-propyl)-nitramine instead of 2_(ι·ethyl-1Η-°Λ. sit-4-yl)- 5-(2-trimethylglycine-ethoxycarbonyl)_ 5 Η_pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl Prepared by benzyl-propylamine. MS: (Μ+Η)+=274. Example 39. 2-Cyclopenta-1-indolyl-5H-nit ox[2,3-b]° ratio η well-7-decanoic acid (〇2-经美_ 1,2-didecyl- Propyl)-guanamine

According to the procedure outlined in Example 3-5, steps 3-5, in step 3, (s) _ 156090.doc -163· 201204731 3-amino-2-methyl-butan-2-ol hydrochloride (7Wr£) z/7e&lt;iro«·· da/wweiry 1995, 671) substituting (R)-3-amino-2-methyl-butan-2-ol hydrochloride and using cyclopentene-oxime in step 4 The base acid is prepared by substituting 丨_ethyl_丨η-pyrazole_4_tanoic acid ester. MS: (M+H)+=315. Example 40· 2-Cyclopentyl-5Η_»pyrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-decylamine

From 2-cyclopent-1-enyl-5H-pyrrolo[;2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)_ Indoleamine (Example 39) was used at 10 °/ under a hydrogen atmosphere of 40 psi. The /carbon treatment was carried out for 24 hours. The reaction mixture was filtered through celite and a Whatman syringe filter, and the product was purified by wet-milling with ethyl acetate. MS: (M+H)+=3 17. Example 41. 2-Isopropenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-nitramine

156090.doc -164- 201204731 According to the procedure outlined in Example 32, steps 3-5, in step 3, (s)-3-amino-2-methyl-butan-2-ol hydrochloride (10).j 1995, (5,671) replaces (R)-3-amino-2-methyl-butan-2-ol hydrochloride and in step 4 uses 2·isopropenyl-4,4,5,5-four The methyl-[ι,3,2]diboron taste was prepared by substituting the ethyl 1-indole-pyrazole-4-carboxyl pinacol ester. Ms: (Μ+Η)+=289. Example 42. 2-Isopropyl-5Η-0 ratio slightly [2,3-b]° ratio tillage_7_carboxylic acid ((S)-2-yl-indole, 2-dimethyl-propyl) - guanamine

By 2-isopropenyl-5Η-pyrrolo[2,3_b]pyrazine-7-carboxylic acid ((S)_2.hydroxyl 1,2-didecyl-propyl)-decylamine (Example 41) Prepared overnight at 10% psi / 1⁄4 under a hydrogen atmosphere of 4 psi. The reaction mixture was filtered through celite and Whatman syringe filter, and the product was purified by crystallised from ethyl acetate. MS: (M+H)+=291. Example 43. 2-Cyclohex-1-enyl-5H-pyrrolo[2,3_b]pyrazine_7-carboxylic acid ((s)-2-hydroxy- 込2-dimethyl-propyl)-decylamine 156090.doc -165 - 201204731

According to the procedure outlined in Example 3-5, steps 3-5, in step 3, (s)-3-amino-2-methyl-butan-2-allate hydrochloride 1995, (5, 671) was substituted (R). _3_Amino-2-indolyl-but-2-ol hydrochloride, and in step 4, 丨_ethyl_1 η- is replaced by cyclohexanyl-1 _yl-based acid. It is prepared by using an alcohol ester than a salt. MS: (Μ+Η)+=329. Example 44. 2-Cyclohexyl-5Η-&quot; 比比和[2,3-b]° ratio of phenyl-7-formic acid ((S)-2-yl-1,2-dimethyl-propyl) - brewing amine

By 2-cyclohex-1-enyl-5Η-pyrrolo[2,3_b]pyrazine_7_carboxylic acid "8)_2-hydroxy-1,2.dimethyl-propyl)-nonylamine Prepared by treatment with 10% carbon/carbon for 48 hours under a hydrogen atmosphere. The reaction mixture was filtered through celite and Whatman syringe filter and purified by crystallization from ethyl acetate. MS: (M +H)+=331. 156090.doc -166 - 201204731 Example 45. 2_Thien-2-yl-5H-pyrrolo[2,3_b]pyrazine_7_f acid ((S)-2-yl-1 ,2-dimethyl-propyl)-guanamine

Substituting (S)-3-aminomethyl-butan-2-ol hydrochloride 1995, i 671) for (R)-3-amine according to the procedure outlined in Example 3-5, Steps 3-5 Benzyl-2-methyl-2-butanol hydrochloride and in step 4 replaced with 4,4,5,5-tetradecyl-2-thiophen-2-yl-[H2]dioxaborom -Ethyl-1H-pyrazole-4-tanoic acid pinacol ester was prepared. The catalyst used in the step 4 is Pd(dppf)Cl2 and the solvent is stupid. Ms: (M+H)+=331. Example 46. • 2-(2-Mercaptopyridin-4-yl)-5H-pyrrolo[2,3_b]pyrazine_7•decanoic acid ((s)_2_yl-1,2-indenyl -propyl)_bristamine hydrochloride

156090.doc • 167-201204731 According to the procedure outlined in Example 32, steps 3-5, in step 3, (s)-3-amino-2-mercapto-butan-2-ol hydrochloride (reira/) Iec/rof 1995, 671) replaces (R)-3-amino-2-mercapto-butan-2-ol hydrochloride and in step 4 2-methyl-4-(4,4,5, 5-Tetramethyl-[1,3,2]diborate-type 2·yl)_pyridine was prepared by substituting 1-ethyl-1 fluorene-pyrazole-4-tanoic acid pinacol ester. The catalyst used in step 4 is PdKdba)3 and the solvent is toluene. The hydrochloride salt was prepared by dissolving the free test in boiling dioxane and treating with 4 M HCl in dioxane. MS: (Μ+Η)+=340. Example 47. 2-(6-Methyl-0-0-but-3-yl)-5Η-° ratio slightly [2,3-b]0 ratio ρ Well-7-carboxylic acid ((§)_2_ 经- 1,2-dimethyl-propyl)-guanamine hydrochloride

According to the procedure outlined in Example 3-5, steps 3-5, in step 3, (s)-3-amino-2-methyl-butan-2-ol hydrochloride (73⁄4b Me (10). The lower price 1995, 乂671) replaces (R)-3-amino-2-mercapto-butan-2-ol hydrochloride and in step 4 2-methyl-5-(4,4,5, 5-Tetramethyl-[1,3,2]dioxan-2-yl)-pyridine was prepared by substituting 1-ethyl-1H-pyrazole-4-carboxylic acid ester. The catalyst used in step 4 is PKdba)3 and the solvent is toluene. The hydrochloride salt was prepared by dissolving free test 156090.doc -168 · 201204731 in boiling dioxane and treating with 4 M HCl in dioxane. MS: (M+H)+=340. Example 48. 2-Vinyl-511-0 vs. '1 each [2, 3-1)] 〇 ratio 1» well-7-carboxylic acid (3-carbyl-2,2-dimethyl-propyl) - guanamine

Step 1 Substituting 3-amino-2,2-dimercapto-propan-1-ol for (R)-3-amino-2-indenyl-butan-2 according to the procedure outlined in Step 3, Example 32 - alkoxide hydrochloride to prepare 2-&gt; odor-5-(2-dimercapto-stone-ethoxymethyl)_5H-° than hydrazine and [2,3-b]n ratio tillage-7- Capric acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine. Step 2 Combine 2-bromo-5-(2-tridecylfluorenyl-ethoxyindenyl)_ 511-〇 in the pressure tube and each [2,3-13] 〇 耕-7-formic acid (3-carbyl-2,2-dimethyl-propyl)-bristamine (250 mg, 0.55 mmol), potassium trifluoroborate (11 mg, 0.83 mmol), cesium carbonate (627 mg, 1.90) Methyl), Pd(dppf)Cl2 (22 mg, 0.03 mmol), THF (1.8 mL) and water (〇·2 mL). The tube was purged with argon, sealed and heated at 85 ° C overnight. The solvent was evaporated and the crude residue was purified eluting elut elut _2_Vinyl·5Η_^ 156090.doc -169- 201204731 Cyclo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine. Step 3 According to the procedure outlined in Step 5, Example 5, 5-(2-trimethyldecyl-ethoxymethyl)-2-vinyl-5H-pyrrolo[2,3-b]pyridinium_ 7_carboxylic acid (3_hydroxy-2,2-dimercapto-propyl)-decylamine instead, (丨-ethyl_1H_pyrazole-4-yl)_ 5-(2-didecylfluorenyl-B Preparation of 2_vinyl _ 5H by oxoyl)_5H_pyrrolo[2,3_b]pyrazine-7_carboxylic acid ((R)-2-hydroxy-l,2-dimethyl-propyl)-decylamine Pyrrolo[2,3-b]pyridin-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine. MS: (M+H)+=275 Example 49. 2-Ethyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (3-hydroxy-2,2-diindenyl) Base

From 2-vinyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (3-hydroxy-2,2-dimethyl-propyl)-bristamine by hydrogen at 50 psi Prepared overnight with 10% palladium on carbon in an atmosphere. The reaction mixture was filtered through celite and a Whatman syringe filter, and the product was purified by wet-milling with ethyl acetate. MS: (M+H)+=277. Example 50. 2-(2,2-Dimethyl-cyclopropyl)-5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid (3-hydroxy 156090.doc-170·201204731 base-2 ,2-dimethyl-propyl)-bristamine

Substituting 3-amino-2,2-dimercapto-propan-1-ol for (R)_3_amino-2-indolinyl-butan-2-allate according to the procedure outlined in Step 3, Example 32 Acid salt to prepare 2_bromotrimethylsulfonyl-ethenylmethyl)-5H-pyrrolo[2,3_b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimercapto-propylhydrazine) Amine. Step 2 Combine 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3_b]pyrazine_7_decanoic acid in a pressure tube (3_ Hydroxy 2,2-dimercapto-propyl)-decylamine (1 〇〇 mg, 0.22 mmol), (2,2-dimercapto-cyclopropyl)·potassium trifluoroborate (58 mg, 〇· 33 mmol), barium carbonate (251 mg, 〇.77 mm〇1),

Pd(dppf)Cl2 (18 mg' 0.02 mmol), THF (0.75 mL) and water (0.25 mL). The tube was flushed with argon, sealed and heated at EtOAc EtOAc (EtOAc). -(2,2-dimethyl-cyclopropyl)_5_(2_trimethyl-stone-ethoxycarbonyl)-5H-0 ratio slightly [2,3-b]. _Phenyl-2,2-dimercapto-propyl)-guanamine. Step 3 156090.doc -171· 201204731 According to the procedure outlined in Step 5 of Example 32, replace the ethylenediamine with i N sodium hydroxide. Preparation of 2-(2,2-dimethyl-cyclopropyl)·5Η_pyrrolo[2,3__ well 7-曱S^(3-carbyl-2,2-monomethyl-propyl) Amine. MS: (Μ+Η)+=317; mp=261.0-263.0. Example 51. 2-((trans)-2-methyl-cyclopropyl)_5 并 并 [2,3 bp ratio _7 carboxylic acid ( 3•transyl-2,2-dimethyl-propyl)-decylamine

Step 1 Mix anti--1 propylene small decanoic acid (10) g' 11.6 mmol) at room temperature with pinacol (1·5 g, 12.8 _01) and sulphuric acid (0.7 g, 5.8 mmol) in the mystery (23 Dissolved in mL) for 1 hour, then concentrated to give, ο,%

2 ((E)-Propyl)-[1,3,2]dioxypyrimidine, which was used without further purification. Step 2 Under nitrogen, 4,4,5,5,methyl-2-UE)-propenyl Hl,3,2]dioxy-paste (1·9 g 'U'6 mm〇1 'Step 1 Crude material) In a solution of toluene (11.6 mL), carefully add hydrazine, hydrazine, and add diethyl ether (1. 丨Μ toluene solution, 10 5 mL » 11.6 mmol), » » m, A burn (1 · 3 mL, 16. 2 mmol). The reaction mixture was stirred for 4 hours at 5 ° ° C 156090.doc -172 · 201204731. Further diethylzinc (丨丨M toluene solution, 10-5 mL, 11.6 mmol) and diiodomethane (1.3 m) L, 162 mm 〇1) were added and heating was continued overnight. The reaction was cooled and 1 〇 M HCi (25 mL) and saturated NaHC 〇 3 (100 mL) were then. The reaction was filtered and the filtrate was extracted with diethyl ether (2 &lt;&gt;&lt;&gt;&gt; The combined organic phases are washed with water, dried over sodium sulfate and concentrated to give 4,4,5,5-tetradecyl-2-((trans)-2-fyl-cyclopropyldioxole. The purity was determined to be 80% by NMR analysis, and the isolated product was used without further purification.

To 4,4,5,5-tetradecyl-2-((trans)-2-methyl-cyclopropyl)-1^,3,2]dioxaborazole (2.0 g, 11 mmol, step 2 A solution of 2 (6_0 via '77111111〇1) in water (7.7 111111〇1) was added to a solution of EtOAc (40 mL). The reaction mixture was stirred at room temperature overnight then concentrated. The residue was extracted with acetonitrile (3×). The combined organic phases were concentrated and the residue was triturated with diethyl ether. The resulting solid was collected via filtration and washed with diethyl ether. 787 mg (44 ° / 〇 ' 3 steps) of trans-2-l-trifluoroborate (2-methylcyclopropane) was isolated and its purity was determined by NMR analysis. It is 80%. The main pollutants are similar to dilute hydrocarbons. It can be used without further purification. Step 4 Prepare 2 according to the procedure outlined in Example 2, Step 2, by substituting trans-_2-methylcyclopropane-1- 1-octanoate potassium (2,2-didecyl-cyclopropyltrifluoroborate) - ((trans)-2-methyl-cyclopropyl)-5-(2-trimethyldecyl-ethoxymethyl)_ 5H-pyrrolo[2,3-b]indole-7- Formic acid (3-hydroxy-2,2-dimethyl-propyl)-hydrazine 156090.doc •173· 201204731 Amine. Step 5 Prepare 2-((reverse) according to the escape of ethylenediamine in Example 5, Step 5 _2•A: in / order, replacing 1·7-formic acid with 3-N sodium hydroxide (3-hydroxy-2,2/two'% two groups)_5H pyrrole [2,3_b]° ratio (M+H )+=303 〇,~methylpropyl)-guanamine. MS: Λ Example 52. 2-((cis)-2-methyl-cyclopropyl)·5

Η 咯 并 [2,3-b]pyridine•• Well base-2,2-dimethyl-propyl)-decylamine

According to the footbed field description outlined in Example 51, using cis-1-propenyl-1-yl-acid

Prepared by substituting trans-1-propen-1-yl acid. MS: (M+H)+==3〇3. Example 53. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine·7·carboxylic acid ((Ryu)-trimethyl-propyl)-decylamine

156090.doc -174· 201204731 Prepared according to the procedure outlined in Example 1 Steps 4-5, using propylamine instead of 1-((R)-1-amino-ethyl)-cyclopentanol hydrochloride. Ms. (M+H)+=287; melting point=298.0-300.0 实例 Example 54. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine·7·isopropyl decylamine

Step 1 to 2_cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)·5Η_pyrrolo[2,3-b]pyrazine-7-decanoic acid (0.20 g, 0.59 Ethyl acetate (0.14 g '0.72 mmol), 4-(dimethylamino)pyrene (888 g, 0.72 mmol) and isopropylamine (0.042 g, 0.72 mmol) in CH2C12 (5 mL) ). The reaction mixture was stirred at room temperature overnight then diluted with H.sub.2 and extracted with ch.sub.2. The combined organic phases were washed with brine, dried over Na 2 EtOAc &EtOAc. The residue was purified by EtOAc (3%EtOAcEtOAcEtOAc) elute Methyl)-5H-pyrrolo[2,3-b]pyrazine-7-isopropyl decylamine. Step 2 To 2-cyclopropyl-5-(2-tridecyldecyl-ethoxylated pyrrolo[2,3-b] nb plough-7-formic acid isopropyl decylamine (〇.18 g) , 0.48 mmol) in a solution of 156090.doc • 175-201204731 CH2C 2 (5 mL) was added trifluoroacetic acid (1 〇 mL). The reaction mixture was stirred at room temperature overnight and then concentrated. to

MeOH (10 mL) was added with EtOAc (2 mL) and Et.sub.3 (2 mL). The reaction mixture was stirred at room temperature overnight and then concentrated. The residue was purified by EtOAc EtOAc (EtOAc (EtOAcMeOHMeOH) Plowing -7-isopropyl decyl citrate. MS: (M+H)+=245; melting point &gt;3〇〇.〇. Example 55. 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyrazine_7-decanoic acid (2.methoxy-4-methyl-luethyl)-decylamine

Prepared according to the procedure outlined in Example 54 using 2-amino-1-methoxypropane as the isopropylamine. MS: (M+H)+= 275; m.p. = 238.0-24. Example 56. propyl·5Η-°pyrolo[2,3-b]pyridin-7-decanoic acid (3-hydroxy-1,1-dimercapto-butyl)-decylamine

156090.doc -176- 201204731 Prepared according to the procedure outlined in Example 54, using 4-amino-4-methyl-pent-2-ol instead of isopropylamine. MS: (M+H)+=303; refining point = 230.0-232.0. Example 57. 2-Cyclopropyl-5H-pyrrolo[2,3-b]n ratio tillage-7-formic acid (2-cyanoethyl)-decylamine

Step 1 2-Cyclopropyl-5-(2-trimethyldecyloxyethyloxy)- 5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.26 g, 0.77 mmol Trifluoroacetic acid (1.5 mL) was added to a solution of CH2C12 (10 mL). The reaction mixture was stirred overnight at room temperature then concentrated. The residue was dissolved in Me〇H (10 mL) and H.sub.2 (1 mL) and EtsN (2 mL). The reaction mixture was stirred at room temperature overnight, then concentrated and dried under high vacuum to afford &lt;RTI ID=0.0&gt; Ready to use. Step 2 To a solution of 2-cyclopropyl-511-pyrrolo[2,3-1)]pyrazine-7-carboxylic acid (0.156 £, 0.77 mmol, crude material from step 1) in CH.sub.2Cl.sub.2 (1 mL) EDC (0.176 g, 0.92 mmol), 4-(dimethylamino)pyridine (o.ll g, 0·92 mmol) and 3-aminopropionitrile (0.065 g, 0.92 mmol) were added. The reaction mixture was stirred overnight at room temperature then diluted with H.sub.2 and extracted with CH.sub.2 C.sub.2. 156090.doc • 177· 201204731 The combined organic phases were washed with brine, dried over NajEtOAc and concentrated. The residue was wet-milled with 5 (mEt 〇H/Et.sub.2) to give yd. 59 g (3%) as a pale white solid, 2·cyclopropyl-5H-pyrrolo[2,3_b]pyrinoic acid (2_ Cyanoethyl)-guanamine. MS: (M+Hr=256; Hyun = 236 〇 〇 〇 58 58. 2-cyclopropyl each [2, 3 external ratio only _7_ formic acid nitrogen Glutamine

Aminoacetonitrile in place of 3-aminopropane = 240.0-242.0 制备 Prepared from the nitrile according to the procedure outlined in Example 57. MS: (M &gt; H) + = 242; melting point Example S9. 2-cyclopropyl-5H-pyridine °[2,3.b; Kt7_carboxylic acid (3-cyanopropyl)

Replacement of 3-aminol with 4-aminobutyronitrile. Melting point = 232.0-234.0. Prepared according to the procedure outlined in Example 57, propionitrile. Ms: (M+H)+==27〇; Example 60. 156090.doc -178· 201204731 裒propyl ratio 嘻[2,3-bJn ratio tillage_7_formic acid ((S)-l-ethyl · 2_ mercaptomethyl-propyl) decylamine

• Prepared according to the procedure outlined in Example 54 using (S)-3.amino-2-methyl-pent-2-ol hydrochloride instead of isopropylamine. MS: (M+H)+= 303; m.p. Example 61. 2-3⁄4 propyl-5H-.咯 并 [2,3_b]n than spray _7 formic acid (3_ mercapto-u-didecyl-propyl)-decylamine

Prepared according to the procedure outlined in Example 54 using 3-amino-3-methyl-butan-1-ol instead of isopropylamine. MS: (M+H)+= 289; mp. Example 62. 2_Cyclopropyl-5H-°pyrho[2,3-b]pyrazine-7-carboxylic acid ((S)-l-hydroxyindenyl-2,2-dimethyl-propyl) - guanamine 156090.doc -179- 201204731

A propylamine 4 heart program was prepared by substituting (s)-third leucine for j-endoamine. MS: (M+m+, H) - 303; m.p. = 259.0-261.0. Example 63. 2-Cyclopropyl-5H-pyrroloindole 2 ^ ki 1 ,·3·*13]11 ratio tillage_7-decanoic acid (2-hydroxy-1-hydroxymethyl-ethyl)·decylamine

3-Aminopropionitrile to prepare 256.7, substituting 2-amino-1,3-propanediol for (M+H)+=277; melting point = 255.0 - Example 64. 2-cyclopropyl-5 〇 嚷 &amp; ρ 1 Open L2,3-b]^Plant-7-formic acid ((R)-l-hydroxymethyl-2,2-dimethyl-propyl)-decylamine 156090.doc 201204731

Prepared by substituting (R)-third leucine for isopropylamine according to the n田 n?, 哲 4 &lt; 裎 order outlined in Example 54. MS: (M+FH+-^, VM+hi) -303; melting point = 27〇 273 273 〇. Example 65. 2-Cyclopropyl-5Η·[[,3,3,4,7-f-acid ((r)]------methyl-2-yl-propyl)-decylamine

Prepared according to the procedure outlined in Example 54 using D-prolinol instead of isopropylamine. 1^:(]^+1'1)+=289; Melting point=250.0-253.0 » Example 66. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S ) 2 -hydroxy-1-methyl-ethyl)-decylamine 156090.doc .181 - 201204731

Prepared according to the procedure outlined in Example 54 using L-propane instead of isopropylamine. 1^: (] \ 4 + 11) + = 261; melting point: = 274.0-276.0. Example 67. 2-Cyclopropyl-5H·lado[2,3_b]0 ratio tillage_7_carboxylic acid ((R)1 benzylidenepropyl)-decylamine

Prepare according to the procedure outlined in Example 54 by substituting (R)_(_)_2_amino-indole-butanol for isopropylamine to 8:(]^+11)+=275; melting point=250.0-253.0 . Example 68. 2-Cyclopropyl-5H_°piro[2,3_b]pyrazine_7-formic acid ((8)-丨cyclohexylethyl)-decylamine

156090.doc • 182·201204731, prepared according to the procedure outlined in Example 54, using (R)_(_)]-cyclohexylethylamine in place of isopropylamine. Ms: (M+H)+=3 13 ; melting point = 253.0-255.0. Example 69· 2 cyclopropyl-5H-pyridinium [2,3_1)]° ratio tillage-7-formic acid (2-cyano-1,2,2-triterpene)

Base-ethyl)-bristamine

Step 1. Add methane to a solution of 3-hydroxy-3-indolyl-2-butanone (1.9 g, 18.6 mmol) and Et3N (3.9 mL '27.9 mmol) in CH2Cl2 (20 mL). A solution of sulfonium chloride (1.6 mL, 20.5 mmol) in CH2Cl2 (1 mL). It was scrambled for 2 hours at room temperature, then poured into water and extracted with ch2C12. The organic phase was washed with a 10% aqueous HCl solution and a 5% aqueous NaH.sub. Base-propyl ester. Step 2 To a solution of 1,1-dimethyl-2-oxo-propane S (1.8 g, 1 mmol) in DMSO (10 mL) was added NaCN (1.47 g, 30 mmol) ). The reaction mixture was stirred overnight at 45 ° C, then quenched with water and extracted with EtOAc. The combined organic phases were washed with brine, dried over EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc Nitrile, which was used without further purification. Step 3 Add ammonium acetate (3.64 g, 47.2 and NaCNBH3) to a solution of 2,2. dimethyl-3. oxo-butyronitrile (0.52 g, 4.72 mm 〇i) in Me 〇H (10 mL). (0-296 g, 4.72 mmol). The reaction mixture was stirred at room temperature for 5 days, then cooled to dryness with EtOAc EtOAc EtOAc EtOAc EtOAc Extracted with CH2Cl2. The aqueous layer was made basic (pH = 1 〇) with concentrated NH4OH, then extracted with CH2C12. The organic layer was dried over MgSO 4 and concentrated to give 0.031 g _2,2-Dimercaptobutyronitrile. Step 4 Prepare 2-cyclopropyl-5H_pyrrole according to the procedure outlined in Example 54 by substituting 1,3-amino-2,2-didecylbutyronitrile for isopropylamine. [2,3_b]pyrazine f 1^-6 〇MS: (M+H)+=298 ; refining point=295.0-297.0 » Example 70. propyl 5H-pyrrolo[2,3_b]pyp well _7_carboxylic acid (3-hydroxytrimethyl-propyl)-guanamine

156090.doc •184·201204731 Step 1 Prepare 2,2-dimethyl-3-oxo-butyric acid ethyl ester according to the procedure reported in ·/· dw. CAew. 1988,//0,1539. Step 2

To a solution of 2,2-dimethyl-3-oxo-butyric acid in ethyl acetate (0.74 g, 4.67 mmol) in MeOH (10 mL), EtOAc (3. &lt;RTI ID=0.0&gt;&gt; (0.29 g ' 4.67 mmol). The reaction mixture was stirred at room temperature overnight, then cooled to 0 ° C, slowly treated with concentrated HC1 until ph = 2, and stirred at room temperature for 15 min. The reaction mixture was concentrated and diluted with water. The residue was extracted with CH.sub.2Cl.sub.2. -2,2-Dimercapto-butyric acid ethyl ester, which can be used without further purification. Step 3 to 3-amino-2,2-dimethyl-butyric acid ethyl ester at -78 °C 0.18 g, 1.1 mmol), slowly added LiAlH4 (1.0 Μ THF solution '1.2 mL '1 · 2 mmol) in a solution of anhydrous THF (3 mL). The mixture was warmed to room temperature and mixed for 2 hours, then water The organic phase was dried and concentrated with CH.sub.2Cl.sub.sup.ss.sssssssssssssssssssssssssssssssssssssssssssss Can be used. Step 4 According to the real The procedure outlined in 54 is to prepare 2-cyclopropyl-5Η- by using 3-amino-2,2-didecyl-but-1-ol instead of isopropylamine. Bis-[2,3-b] Pyridin-7-indole (3-hydroxy·ι, 2,2-trimethyl-propyl)-decylamine. MS: (M+H)+=3〇3; 156090.doc -185· 201204731 Point = 228.0-270.0. Example 71. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-t-butyl)-decylamine

Prepared by substituting (S)-(+)-2-aminobutane for isopropylamine according to the procedure outlined in Example 54. MS: (M+H)+= 259; mp 280. Example 72. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1-isopropyl-2-methyl-propyl)_ Guanamine

Step 1 Add N-Boc-L, alumic acid methyl vinegar (1 5 g, 6 49 _〇1) to THF (1 〇 中 曱 曱 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 (3.0 MEt20 solution, 9.3 mL ' 27.9 mmol). The reaction mixture was allowed to stand overnight at room temperature, then quenched with water and extracted with CH2C1. The dried organic phase was 156090.doc • 186-201204731 organic phase and concentrated to give 1.71 g of ((s)_2_hydroxyq-isopropyl-2-indolyl-propyl) as a colorless oil. Tert-butyl carbamic acid, which can be used without further purification. Step 2: ((S)-2-Hydroxy-1-isopropyl-2-methyl-propyl)-aminocarboxylic acid tert-butyl ester (1.71 g 'the crude material of step 1) was dissolved in hydrochloric acid (1 〇) μ Me〇H solution, 20 mL, 20 mmol). The solution was stirred at room temperature overnight, then concentrated <RTI ID=0.0></RTI> &lt;RTI ID=0.0&gt;&gt;&gt; 2-Alkyl hydrochloride salt which was used without further purification. Step 3 To 2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxymethyl)_5H-pyrrolo[2,3-b]. Trifluoroacetic acid (1 mL) was added to a solution of &lt;RTI ID=0.0&gt;&gt;&gt; The reaction mixture was stirred at room temperature for 2 hours' then concentrated. The residue was dissolved in dmF (5 mL), and EtOAc (s), 3-amino-2'4-dimethyl-pentan-2-ol hydrochloride (1 mg, 0.36 mmol) , B〇P (160 mg, 0.36 mmol) and Et3N (0.21 mL, 1.5 mmol). The reaction mixture was stirred at room temperature overnight then diluted with EtOAc EtOAc (EtOAc)EtOAc. The organic layer was dried and concentrated. The residue was purified by EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc Pyridin-7-decanoic acid ((S)-2-hydroxy-1-isopropyl-2-methyl-propyl)-guanamine. MS: (M+H)+= 317; mp. Example 73. 156090.doc • 187·201204731 2-Cyclopropyl-5Η-»Biloxi[23b]pyrrolin-7carboxylic acid ((8)_12 dimethylpropanoguanamine

Substituting (s)-(+)_3_methyl-2-butylamine for (S)-3-amino-2,4-dimethyl-pentan-2-ol according to the procedure outlined in Step 3, Example 72 Hydrochloride is prepared. MS: (Μ+Η)+=273; mp=281.0-283.0. Example 74. 2-Cyclopropyl-5Η-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)-2-hydroxy-indole, 2·didecyl-propyl decylamine

Prepared according to the procedure outlined in Example 72, substituting N-Boc-D-methyl sulphate for N-Boc-L- decyl decyl ester. MS: (M+H)+=289; mp=269.0- 271·0 ° Example 75. 2-Cyclopropyl-5Η-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((R)-l-ethyl-2-hydroxy-2-methyl- Propyl)-SS amine 156090.doc • 188 - 201204731

OH was prepared according to the procedure outlined in Example 72, substituting &lt;RTI ID=0.0&gt;0&gt; MS:

(M+H)+=303; m.p. = 218.0-222.0. Example 76. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (2-hydroxy 4,1 ·methyl-ethyl)-decylamine

Prepared by substituting 2-aminomercapto ipropanol for (S)-3-amino-2,4-dimethyl-pentan-2-ol hydrochloride according to the procedure outlined in Step 3, Example 72. MS: (M+H)+= 275; melting point = 293.0-295.0. Example 77. 2_Cyclopropyl-5H-pyrrolo[2,3_b]pyrazole-7-carboxylic acid [(s)_1(1_hydroxy&lt; decyl-ethyl)-pentyl]-decylamine I56090. Doc 201204731

Prepared according to the procedure outlined in Example 72, substituting N-Boc-L--methyl-glycinate for methyl N-Boc-L-prolyl. MS: (M+H)+ = 331; m.p. = 170.0-172.0.

Example 78. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-cyclopropyl-ethyl)-decylamine

Prepared according to the procedure outlined in Example 54 propylamine. MS: (M+H)+=27l; </ RTI> </ RTI> </ RTI> <RTIgt;

Example 79. • Formic acid (1-ethyl-propyl)-nonylamine Cyclopropyl sputum sputum each [2,3 external ratio _7

156090.doc • 190-201204731 Prepared according to the procedure outlined in Example 54 using 1-ethylpropylamine instead of isopropylamine. MS: (Μ+Η)+=27·5 . υ ' Melting point = 245.0-246.0. Example 80. 2-Cyclopropyl-5Η-. Ηη和^^’·^1)]«»比耕_7_carboxylic acid (2_didecylamino}-

Methyl-ethyl)-guanamine

Prepared according to the procedure outlined in Example 54 using dimethylamino-2-phenylamine as the isopropylamine. Ms: (M+H)+=288; melting point = 225 Ο· 〇. Example 81. 2 ί-propyl-5H-D than hydrazino each [2,3_b]pyrene bromide_7_carboxylic acid ((8) small cyclohexylethyl)-guanamine

Prepared by substituting isopropylamine with (8)·(+)]-cyclohexylethylamine according to the procedure outlined in Baye. Ms: (m+h)+=313; melting point. Ο· 〇. Example 82. Alumina 5H-. Bis-[2,3_b]pyrazine_7-formic acid ((R)_2_hydroxybap 156090.doc -191 - 201204731 base-ethyl)-decylamine

Prepared according to the procedure outlined in Example 54 using D-propylamine instead of isopropylamine. ]\48: (]^+11)+=261; melting point = 265.0-268.0.

Example 83. 2-% propyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l-hydroxymethyl-propyl)-nitramine

(S)-(+)-2-Amino-1-butanol; melting point = 250.0-252.0. Prepared by substituting isopropylamine according to the procedure outlined in Example 54. Ms: (m + h) + = 275 Example 84. 2 cyclopropyl-5H-pyrrolo[2,3 b]pyrazine_7-formic acid methyl decylamine 156090.doc -192- 201204731

Prepared according to the procedure outlined in Example 54 using methylamine hydrochloride instead of isopropylamine. MS: (M+H)+= 217; m.p. = 283. Example 8S. 2-Cyclopropyl-5Η-. Bis-[2,3-b] 吼7_carboxylic acid (2,2-dimethyl-propyl)-decylamine

Prepared according to the procedure outlined in Example 54 using 2,2-dimethyl-propylamine in place of isopropylamine. MS: (M+H)+=273. Example 8 6. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [2-hydroxy-1-(2-hydroxy-ethyl)-2-indolyl-propyl ]-guanamine

156090.doc • 193·201204731 Step 1 Under 〇C, (tetrazol-2-oxo-3-β-f-butyl)-amino decanoic acid terpene vinegar (2.1 g, 10.4 mmol) in THF ( Methylmagnesium bromide (3.0 M Et20 solution, 14.5 mL '43.5 mmol) was slowly added to the solution in 12 mL). The reaction mixture was stirred overnight at rt then carefully quenched with water. The mixture was rinsed with CHKh via the Shixiazao soil transition mixture. The filtrate was washed with brine, dried over sodium sulfate and concentrated to give &lt;RTI ID=0.0&gt;&&&&&&&&&&&&&& The tert-butyl phthalate was used without further purification. Step 2 In a microwave vial, 2-hydroxy-1-(2-hydroxy-ethyl)-2-methyl-propyl]-aminomethyl-fee-di-(1QQ mg 'G 43 was dissolved in hexafluoro Isopropyl alcohol (5 mL). The vial was sealed and heated under microwave irradiation for 1 hour under 15 Torr. The solvent was removed in vacuo to afford &lt;RTI ID=0.0&gt; Base-pentane-1,4-diol, which can be used without further purification. Step 3 Preparation of formic acid [2-hydroxylhydroxy(M+H)+=319 according to the diol as outlined in Example 54 instead of isopropylamine; Melting point = 195

Procedure using 3-amino-4-methyl-pentan-indole, 4-cyanopropyl-5H-pyrrolo[2,3-b]pyr-7-ethyl)-2-methyl -propyl]-guanamine. MS: • 0-198.0. Example 87. 2-Cyclopropyl-5H- to D[2,3-b]pyridin-7-carboxylic acid [(S)-l-(lH-pyrazol-3-yl)-ethyl]- Guanamine 156090.doc -194- 201204731

Step 1 Prepare 2-cyclopropyl-5-(2-tri) by substituting (S)-l-(lH-pyrazol-3-yl)-ethylamine for isopropylamine according to the procedure outlined in Step 1 of Example 54 Methyl decyl-ethoxymethyl)-5H-n is more than [2,3-b]. Specific tillage-7-formic acid [(S)-l-(lH-&lt;^oxa-3-yl)-ethyl]-decylamine. Step 2 To 2-cyclopropyl-5-(2-tridecyldecyl-ethoxyindenyl)-5H-pyrrolo[2,3_b]pyry&quot; well-7-decanoic acid [(S)-l To a solution of (lH.pyrazol-3-yl)-ethyl]-decylamine (230 mg &lt;RTI ID=0.0&gt; The reaction mixture was stirred at room temperature for 4 hours and then heated at 80 ° C overnight. The reaction was cooled to room temperature and k.sub.2 s.sub.3 (2 g). The reaction was stirred overnight at room temperature then concentrated. The residue was diluted with water and extracted with EtOAc. Dryed and concentrated by \^8〇4. The residue was wet-milled with £1 (8/hexane) to give 130 mg (81%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7·carboxylic acid [(S)- 1-(lH-pyrazol-3-yl)-ethyl]-decylamine. MS: (M+H)+= 297. Example 88. 2-cyclopropyl-5H-. -b]. Specific tillage-7-decanoic acid ((R)-l-phenyl-ethyl)_ decylamine 156090.doc -195· 201204731

Prepared by substituting (R)-(+)-phenylethylamine for isopropylamine according to the procedure outlined in Example 54. In step 2, 1.0 M NaOH and THF were used instead of MeOH, H20 &amp; Et3N MS: (M+H) + = 307 ^j^a = 278.0-280.0. Example 89. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyr-7-decanoic acid ((S)-l-phenyl-ethyl)-decylamine

Prepared according to the procedure outlined in Example 54 using (S)-(-)-l-phenylethylamine instead of isopropylamine. In step 2, MeOH, H20 and Et3N were replaced with 1.0 M NaOH and THF. MS: (M+H)+= 307; mp=272.0-274.0. Example 90. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-butyl)-decylamine 156090.doc •196·201204731

OH was replaced by 4-amino-2-butanol in place of isopropyl NaOH and THF instead of MeOH, melting point = 228.0-230.0. Prepared according to the procedure outlined in Example 54 for the amine. In step 2, use 1〇 Μ h2o and Et3Ne ms: (m+h), 275;

Example 91. Lacyl propyl-5H-pyrrolo[2,3_b]pyrinoic acid (3hydroxy-2-indolyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 54 using 3-amino-2-methyl-1-propanol instead of isopropylamine. In step 2, 1.0 M NaOH and THF were used instead of Me〇H, H2C^Et3N»MS: (M+H)+=275^&gt;^a=252.0-254.0. Example 92. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyr 51 well-7-carboxylic acid (1-pyridyl-2-ylethyl)-decylamine 156090.doc •197· 201204731

Prepared according to the procedure outlined in Example 54 by substituting i-pyridine-2-yl-ethylamine for isopropylamine. Replace with 1.0 M NaOH and THF in step 2.

MeOH, H20 and Et3N. MS: (M+H)+= 308; mp. Example 93. 2-. Bis-2-yl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethyl

Base-propyl)-guanamine

Step 1 To 2-bromo-5-(2-tridecyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyridin-7-decanoate (105 mg, 0.27 Methyl)Pd(PPh3)4 (16 mg, 0.014 mmol) was added to a solution in THF (1 mL). The reaction mixture was degassed with argon, followed by the addition of 2-pyridyl bromide (0-5 M THF, 1.3 5 mL, 0.675 mmol). The reaction mixture was heated at 50 ° C overnight. It was cooled to room temperature, quenched with aq. The organic layer was dried over MgSO 4 and concentrated. Chromatography by SiO 2 (1% to 10% 156090.doc •198· 201204731

Purification of the residue by MeOH / EtOAc (EtOAc) (EtOAc (EtOAc) Cultivated methyl -7-decanoate, which contains some small amounts of impurities. Step 2 to 2-pyridin-2-yl-5-(2-trimethylsulfonyl-ethoxycarbonyl)_5H_pyrrolo[2,3-b] than well-7-decanoic acid An aqueous solution of i 〇M Na0H (1 〇 mL) was added to a solution of EtOAc (2.5 mL). The reaction mixture was stirred overnight at room temperature. The reaction was neutralized with a 1.0 M aqueous HCl solution to pH = 7 °. The obtained precipitate was collected by filtration, then dissolved in 1% MeOH / CH.sub.2, dried and concentrated to give 65 mg of 2-pyridine-2 as a yellow oil. -yl-5 gas 2_trimethyldecylalkyl-ethoxycarbonyl)_5H_pyrrolo[2,3-b]pyrazine-7.nonanoic acid. Step 3 According to the procedure outlined in Example 54, the ratio of 2_pyridine_2_yl·5_(2_trimethyl-stone-ethoxymethyl)_5H-° is slightly [2, 3-1?] °Compared to well-7-nonanoic acid instead of 2-cyclopropyl-5-(2-tridecylsulfanylethoxymethyl)_5Η·ηpyrho[2,3_b]pyrazine-7-曱Acid, and using (δ)·122_trimethyl-propylamine instead of isopropylamine to prepare 2·0 to 0-den-2-yl_5Η-° ratio 嘻[2,3-b]° ratio 11 well-7 - decanoic acid ((S)-l, 2,2-trimethyl-propyl)-guanamine. In step 2, MeOH, H2 hydrazine and Et3N were replaced with L0 M Na0H and THF. MS: (M+H)+=324; melting point &gt;3〇〇 〇. Example 94 2-Cyclopropyl-5H.pyrrolo[2,3_b]pyrazine_7-decanoic acid ((yq.cyclopropyl_2-hydroxy-2-methyl-propyl)-decylamine 156090.doc •199- 201204731

(S)-Cyclopropyl-((S)-l-phenyl-ethylamino)-acetic acid was prepared from cyprodinil according to the procedure outlined in US6191306. Step 2 Slowly to a suspension of (S)-cyclopropyl-((S)-l-phenyl-ethylamino)-acetic acid (〇.5〇g, 2.28 mmol) in MeOH (20 mL) Add (triterpene base) to diazo-methyl (2.0 M Et20 solution, 5.0 mL, 10 mmol) while periodically adjusting the temperature using an ice bath. Stir the reaction mixture at room temperature for 1 hour, then pour into NaHC. 〇3 in aqueous solution and extracted with CH2Cl2 (3x). The combined organic phases were dried over EtOAc (EtOAc) (EtOAcjjjjjjjj The vinegar was used without further purification. Step 3 To a solution of (S)-cyclopropyl-((S)-l-phenyl-ethylamino)-acetic acid decyl ester (0.42 g, 1.8 mmol) in THF (8 mL) Bromomethyl town (3.0 M Et2 solution, 1.5 mL, 4.5 mmol) was added slowly. The reaction mixture was quenched with EtOAc (2x). The combined organic phases were dried over MgS 4 and concentrated. The residue was purified by EtOAc EtOAc (EtOAc:EtOAc) 156090.doc -200- 201204731 ((S)-l-phenyl-ethylamino)-propan-2-ol. Step 4 To (S)-l-cyclopropyl-2-methyl-l-((s)-l-phenylethylamino)-propan-2-ol (0.25 g, 1.07 mmol) in MeOH 20% Pd(OH)2/carbon (30 mg) was added to the solution in (8 mL). The reaction mixture was stirred at 112 atmosphere (1 atm, balloon) for 18 s then filtered over celite and rinsed with Et EtOAc. Concentration of the filtrate gave 0.16 g of (s)-l-amino-1-cyclopropyl-2-indole-propan-2-ol, as a pale yellow oil, which was used without further purification. Step 5 Combine 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (150 mg, 0.74 mmol), (S)-l-amino-1- Cyclopropyl-2-mercapto-propan-2-ol (115 mg '0.89 mmol), EDC (155 mg, 0.81 mmol) and HOBt (109 mg, 0·81 mmol). Then continue to add DMF (2 mL) and ^

Pr2NEt (0.19 mL, 11.11 mm〇i). The reaction mixture was stirred at rt EtOAc (3×). The combined organic phases were washed with h20 (3x) and then dried over MgSO 4 and concentrated. The residue was purified by EtOAc EtOAc (EtOAc) elute 2,3_b]pyridyl-7-carboxylic acid ((S)-l-cyclopropyl-2-yl-2-methyl-propyl)-decylamine. MS: (M+H)+= 315; mp. Example 95. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyridine• Well-7-decanoic acid ((R)-i_cyclopropyl_2-hydroxy-2-methyl-propyl Base)-decylamine 156090.doc •201 · 201204731

Step 1 To N-Boc-D-cyclopropylglycine at 0 ° C (〇 5〇 g, 2 u

Add slowly to the solution in MeOH (2 〇mL) (trimethyl sulphate 2 ==) in the mixture (2.0 M Et20 solution, 5. 〇mL, 10 mm 〇1) 疋 甲 } 搅拌 隹 温 温 温 温The mixture was quenched with a small amount of EtOAc (EtOAc) EtOAc (EtOAc). Step 2 Slowly add methyl bromide to a solution of N-Boc-D-cyclopropylglycolate (〇% ^ S ' -2*32 mmol) in THF (10 mL) at 〇 °C Zhenling ether solution, 2.7 mL, 8.1 mmol). The reaction mixture was stirred with EtOAc (EtOAc) (EtOAc)EtOAc. The residue was purified by chromatography on 24 g of EtOAc (EtOAc) eluted eluted eluted elut elut elut elut elut Cyclopropyl-2-yl-2-methyl-propyl)-aminodecanoic acid tert-butyl ester. Step 3. In a round bottom flask ((R)-l-cyclopropyl-2-hydroxy-2-methyl-propyl)-amine 156090.doc • 202- 201204731 tert-butyl carboxylic acid (0.44 g) , 1.92 mmol) was dissolved in 1.0 M HCl in MeOH (10.0 mL, 1 〇·〇mmol). The reaction mixture was stirred for 4 hours, then cooled to room temperature and concentrated to give (D)-l-aminocyclopropyl-2-methyl-propane as a pale pink solid. _2_alcohol hydrochloride. Step 4 2-Cyclopropyl_5H- was combined in a flask.嘻 嘻 [2,3-b] ° ratio tillage-7-formic acid (150 mg '0.74 mmol), (8) small amine cumyl propyl 2-methyl-propan-2-ol hydrochloride (147 mg) '0.89 mmol), EDC (155 mg, 0,81 mmol) and HOBt (109 mg, 0.81 mm〇i). Subsequently, DMF (2 mL) and i-Pr2NEt (0.32 mL, 1.85 mnu^) were added. The reaction mixture was stirred at room temperature overnight then quenched with EtOAc (EtOAc)EtOAc. The combined organic phases were washed with Η 2 〇 (3 χ), then dried over Mgs 〇 4 and concentrated. The residue was triturated with EtOAc / EtOAc (EtOAc:EtOAc) Cyclopropyl 2-hydroxy-2-methyl-propyl)-guanamine. 8:(1^+11)+=315; melting point = 235.0-237.0. Example 96. 2-Cyclopropyl-5H -pyrrolo[2,3_b]pyrazine_7_carboxylic acid (2-cyanocyclopropyl-2,2-dimethyl-ethyl)-nitramine

Step 1 156090.doc •203 · 201204731 Add LiHMDS (1.0 M THF solution, 4.8 mL, 4.8 mmol) to a solution of isobutyronitrile (0.30 g, 4.35 mmol) in THF (8 mL). . The light yellow reaction mixture was stirred at -78 °C for 30 minutes, then 2-mercapto-propane-2-sulfinic acid 1-cyclopropyl-arylene-(E)-ylguanamine (0.50 g, 2.90) was slowly added. Methyl) [Prepared according to W02008/147800] in THF (2 mL). The reaction mixture was stirred at -78 &lt;0&gt;C for 2 h then quenched with saturated aq. The mixture was diluted with water and extracted with EtOAc (2x). The combined organic phases were dried over MgSO4 and concentrated to give &lt;RTI ID=0.0&gt;&gt;&gt; Base-ethyl)-bristamine. Step 2 2 -Methylpropan-2-deacetylate (2-carbyl-1 -cyclopropyl-2,2*didecyl-ethyl)-decylamine (0.70 g, 2.90) at room temperature To a solution of MeOH (5 mL), EtOAc (EtOAc) The reaction mixture was stirred at room temperature for 15 min then concentrated to give 0.45 g (yield: EtOAc/EtOAc) Nitrile hydrochloride. Step 3 Combining 2-cyclopropyl-5-((2-(trimethyldecyl)ethoxy)indolyl)-5H-pyrrolo[2,3-b]pyrazine-7-oxime in a flask Acid (120 mg, 0.36 mmol), 3-amino-3-cyclopropyl-2,2-didecyl-propanenitrile hydrochloride (75 mg, 0.43 mmol), HOBt (54 mg, 0.40 mmol) EDC (77 mg, 0·40 mmol). DMF (2 mL) and diisopropylethylamine (0.16 mL, 0.90 mmol) were then added. The reaction mixture was stirred at rt EtOAc then EtOAc (EtOAc) The combined organic phases were washed with water (3 Torr) then dried over MgSO 4 and concentrated. The residue was purified by EtOAc (3% to EtOAc /EtOAc) elute Mercaptoalkyl-ethoxymethyl)_5H_pyrrolo[23_b]pyrazine-7-carboxylic acid (2-cyano-1-cyclopropyl-2,2-dimethyl-ethyl)-醯amine. Step 4

2-Cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H_pyrrolo[2,3_b]pyrazine-7-carboxylic acid (2-cyano-1-cyclopropyl) To a solution of -2,2-dimethyl-ethyl)-decylamine (110 mg &lt;RTI ID=0.0&gt;0&gt; The yellow reaction mixture was stirred for 3 h then concentrated. The residue was redissolved in MeOH (8 mL) and water (1 mL) and diamine (1 mL). The reaction mixture was stirred at room temperature overnight then concentrated. The residue was purified by EtOAc EtOAc EtOAc (EtOAc) Bis[2,3-b]pyrazine-7-decanoic acid (2-cyano-^cyclopropyl-2,2-dimethyl-ethyl)-decylamine. MS: (M+H)+=324; mp=23 〇 232 232 〇. Example 97. 3-Cyclopropyl-3-[(2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7.carbonyl)amino]-2,2-didecyl- Propionic acid

156090.doc -205- 201204731 Step 1 Add LiHMDS (1.0 M THF solution, 12.7 mL, 12·) to a solution of methyl isobutyrate (1.18 g, 11.5 mmol) in THF (15 mL). 7 mmol). The light yellow reaction mixture was stirred at _78 for 3 Torr, followed by the slow addition of 2-mercapto-propane-2-sulfinic acid 1-cyclopropyl-arylene-(indole)-yl decylamine (1.0 g' 5.8) Methyl) [Prepared according to W05008/147800] in THF (5 mL). The reaction mixture was stirred at -78 °C for 2 h, then warmed to room temperature over 1 h and was quenched with sat. The mixture was diluted with water and extracted with EtOAc (2x). The combined organic phases were dried over MgSO 4 and concentrated. Purification of the residue by EtOAc (3% to 50%EtOAcEtOAcEtOAc) 3-(2-Methyl-propane-2-sulfinylideneamino)- decanoate. Step 2 To 3-cyclopropyl-2,2-dimercapto-3-(2-methyl-propan-2-ylideneamino)-propionic acid at room temperature (1.15 g, 4.17 mmol) A solution of 4.0 M HCl in dioxane (2.1 mL, 8.4 mmol) was added to a solution. The reaction mixture was stirred at room temperature for 30 minutes and then the residue was evaporated to give EtOAc (m. Acid salt. Step 3 Combining 2-cyclopropyl-5-((2-(trimethyldecyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-formic acid in a flask (200 mg, 0.60 mmol), 3-amino-3-cyclopropyl-2,2-dimethyl-propionic acid decyl ester hydrochloride (150 mg, 0.72 mmol), HOBt (90 mg, 0.66 mmol) And EDC (127 mg, 156090.doc • 206· 201204731 0.66 mmol). Subsequently, DMF (3 mL) and diisopropylethylamine (〇·26 mL, 1.50 mmol) were added. The reaction mixture was stirred with EtOAc EtOAc (EtOAc) The combined organic phases were washed with water (3 Torr) and then dried over MgSCU and concentrated. The residue was purified by EtOAc EtOAc EtOAc (EtOAc) -(2-tridecyldecyloxyethyloxy)-5H-pyrrolo[2,3-b]pyrrol-7-carbonyl]-amino}-2,2-dimethylpropionic acid Methyl ester. Step 4 to 3-cyclopropyl-3-{[2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxyindolyl)-5H-pyrrolo[2,3-b]pyrazine To a solution of methyl -7-carbonyl]-amino}-2,2-dimethyl-propanoate (110 mg '0.23 mmol) in CH. The yellow reaction mixture was stirred for 3 h then concentrated. The residue was redissolved in CH2C12 (4 mL) and EtOAc (0.5 mL). The reaction mixture was stirred at room temperature for 1 hour and then concentrated. The residue was purified by EtOAc EtOAc (EtOAc:EtOAc) -5H-pyrrolo[2,3-13]&lt;«pyrano-7-carbonyl)-amino]-2,2-dimercapto-propionic acid methyl ester. Step 5 3-Cyclopropyl-3-[(2-cyclopropyl-5H-pyrrolo[2,3-b]pyr-11]-7-carbonyl)-amino]-2,2-dimethyl A sample of decyl propionate (56 mg, 0.157 mmol) was dissolved in MeOH (1.5 mL), THF (1.5 mL) and H2O (0.75 mL). Subsequently, LiOH.H 2 O (20 mg, 0.471 mmol) was added and stirred at 50 ° C for 18 hours. Cool to room temperature and concentrate. The residue was diluted with water and acidified to pH = 4 using 156090.doc: 207· 201204731 1.0 M HCl. The mixture was extracted with EtOAc (2×). The combined organics were dried <RTI ID=0.0>(M </RTI> <RTI ID=0.0></RTI> to <RTIgt; b] pyridin-7-carbonyl)-amino]-2,2-dimethyl-propionic acid. MS: (M+H)+= 343; m.p.=265.0-267.0 〇 Example 98. The 2-cyclopropyl-5H-n ratio is slightly [2,3_b]. Specific spray _7_carboxylic acid (1_cyclodecyl-ethyl)

Prepared according to the procedure for the ((R)-l-amino-ethyl)-cyclopentanolate salt of Example 1 Step 4-5, using 1-cyclopentylethylamine in place of the 1-acid salt. MS: (M+H)+=299. Example 99 Citrate ((1S,2R,3S)-1-cyclohexyl-propyl)-nonylamine 2-cyclopropyl-5H-t each [2,3 exophage 1 methyl-3 -cyclopropyl

156090.doc 208. 201204731 According to the procedure outlined in Example 1, Step 4-.5, using (is,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-buty-I,2-di Prepared in the alcohol 2〇05,/5, 3292] instead of 1-((R)-1-amino-ethyl)-cyclopentanol hydrochloride. MS: (M+H)+=413. Example 100. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-cyano-2-indenyl-propyl)-decylamine

Replacing 1-((R)-1-amino-ethyl)-cyclopentanol hydrochloride with 2-amino-3_methylbutyronitrile according to the procedure outlined in Example 4, Steps 4-5 preparation. Ms: (M+H)+=284. Example 101. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyridinium-7-decanoic acid (cyano-cyclopropylindolyl)-nitramine

156090.doc •209· 201204731 Replacement of hydroxycyclopentyl)-ethyl with (cyano-cyclopropyl-methyl)-amino decanoic acid tert-butyl ester according to the procedure outlined in Example 1, Steps 3-5 Prepared by -3-butyl carbamic acid. MS: (M+H)+=282. Example 102. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid [(R)-cyclopropyl-(buhydroxy-cyclopentyl)-indenyl]-decylamine

Step 1 (R)-Cyclopropyl-((R)-l-phenyl-ethylamino)-acetic acid was prepared from cyclopropanecarbaldehyde according to the procedure outlined in US 6,191,306. Step 2 Slowly add to a suspension of (R)-cyclopropyl-((R)-i-phenyl-ethylaminoacetic acid (0.50 g ' 2.28 mmol) in MeOH (20 mL) at 0 °C Thionine chloride (1.66 mL '22.8 mmol). The reaction mixture was stirred at room temperature for 4 hours, then heated to 6 ° C overnight. The reaction was cooled to room temperature and concentrated. The residue was diluted with water and 1.0 M NaOH It was brought to pH = 9. After extraction with Et 2 hydrazine (2x), the organic phase was dried over MgSO 4 and concentrated to give 0.37 g (70%) of (R)·cyclopropyl-((R) Phenyl-ethylamino)-acetic acid decyl acetate, which can be used without further purification. Step 3 156090.doc •210-201204731 Under (R)-cyclopropyl-((幻-^) Benzyl-ethylamino)acetate (0-37 g, 1.58 mm 〇l) in THF (12 mL) was slowly added with propylmagnesium bromide (1.0 M Et2 〇 solution, 5 5 mL) 5·5 mm〇1). The resulting white slurry was stirred under 〇〇c for 1 hour, then at room temperature for 3 hours. The reaction mixture was cooled to hydrazine and quenched with saturated aqueous NH4C1 then diluted with H.sub.2. And extracted with Et0Ac. Washed with ha The combined organics were dried with EtOAc EtOAc (EtOAc) 4_[(11)_cyclopropyl-((R)-l-phenyl-ethylamino)-indenyl]-heptan-1,6-di-di- 4-ol. Step 4 to 4-[( R)-cyclopropyl-((R)-l-phenyl-ethylamino)-indenyl]-heptyl-16-dien-4-ol (0.37 g '1.3 mmol) in decylbenzene (40 mL) Giraff's second generation catalyst (0.044 g, 0.05 mmol) was added to the solution. The maroon reaction mixture was heated overnight at 1 Torr. The reaction mixture was concentrated and chromatographed by Si 〇 2 (20% to 50%) Purification by EtOAc / hexanes to give 134 mg (40%) of 1-[(R)-cyclopropyl-((R)-l-phenyl-ethylamino)methyl] Cyclopenta-3-enol] Step 5 To 1-[(R)-cyclopropyl-((R)-l-phenyl-ethylamino)-indolyl]-cyclopentenol (134 mg' 0.52 Methyl) 20% Pd(OH) 2 / carbon (20 mg) was added to a solution of MeOH (8 mL). The reaction mixture was stirred overnight under H.sub.2 atmosphere (1 atm). Rinse with EtO Ac. Concentrate the filtrate to give 74 mg (90%) of light brown Oily 1-((R)-amino-cyclopropyl-methyl)-cyclopentanol. 156090.doc -211 - 201204731 Step 6 Prepare 2-cyclopropane C by substituting isopropylamine-cyclopropyl-indenyl-cyclopentanol for isopropylamine according to the procedure outlined in Example 1, Steps 4-5. _5Η·η比咯[2'3-b]pyrazine-7-carboxylic acid [(R)-cyclopropyl-(1hydroxycyclopentyl)-methyl]-decylamine. MS: (M+ H) += 341 ; melting point = 195 〇 197 〇. Example 103. 2-cyclopropyl·5Η_&quot; bis-[2,3-b]pyr _7-carboxylic acid ((lS,2S)-2- Methyl-dimethyl-butyl)-decylamine

Step 1 Cool N-(t-butoxycarbonyl)_L_alanine _Ν·_τ oxy-Ν'-methyl decylamine (5·49 g ' 23.64 mmol) in anhydrous THF under argon atmosphere Solution in 〇〇ml) to -25 °C. A solution of methylmagnesium bromide (22 ml, 66 mmol, 3 Μ ether solution) was added thereto. The mixture was stirred at _2 rc for 1 hour and then warmed to ambient temperature overnight. The mixture was cooled in an ice bath and treated with aq. Water (6 〇 mL) and ethyl acetate (60 mL) were added and the mixture was shaken in a sep. funnel. The Sa phase of acetic acid was collected and the strips were washed continuously with 2 x 120 ml of water. The aqueous phase was back extracted with ethyl acetate (mL). The organic phases were combined, dried (MgSO4) filtered and concentrated on EtOAc s. The crude material was purified by EtOAc (EtOAc) eluting eluting - Aminobutyl citrate. 4 NMR (300 MHz, gas-like) δ ppm 1.35 (d, /= 7.2 Hz, 3 Η) 1.44 (s, 9 Η) 1.61 (s, 3 Η) 4.28-4.37 (m,1 Η) 5.27 ( Br s, 1 H). Step 2 Under argon ((S)-l-methyl-2-oxo-propyl)-tert-butyl carbamate (600 mg, 3.2 mmol) in tetrahydrofurfuran (20 mL)冷 Μ Μ solution (9.6 ml, 9.6 mmol) of ethylmagnesium bromide in diethyl ether was added dropwise in a cold (ice bath, 〇 ° C) solution. The material was stirred at (TC) for 20 minutes, then warmed to ambient temperature overnight. 0.5N aqueous solution of hydrochloric acid (60 ml, aqueous solution) and ethyl acetate (60^1) was added and the mixture was shaken in a separatory funnel. The extract was washed with brine (60 mL). The aqueous phase was back-extracted with ethyl acetate (2×40 mL) and the organic phase was combined, dried over magnesium sulfate and filtered. The solvent was stripped and filtered through a short gelatin plug. % acetic acid / hexane dissolving to give 630 mg of yellow butyl semi-viscous oil ((1S,2S)_2_yl-1,2-diyl-butyl)-amino carboxylic acid tert-butyl ester ( Main diastereomer: 3:1 mixture) (M+H)+=218. Step 3 to ((lS,2S)-2-hydroxy-1,2-didecyl-butylaminocarboxylic acid A solution of the third butyl ester (620 mg, 3.2 mmol) in anhydrous dichloromethane (4 ml) was added dropwise with trifluoroacetic acid (4 ml) 0 and the flask was capped and stirred for about 3 min. The volatiles were stripped, the obtained product was dissolved in toluene (25 mi), and the solvent was again stripped on a rotary evaporator. This was repeated once again at 156090.doc •213·201204731 The remaining part of the pump is vacuumed, and the product of viscous brown red oil (2S, 3S)-2-amino-3-mercapto-penta- 3_ol = gas 岬A G acid salt was used which was used in the next step without further purification. Step 4 Step 2 (2S,3S)-2.Amino-3-mercapto-pentanol tris-acetate and 2 -cyclopropyl-5-(2-didecyldecyl-ethenylmethyl)5Η-π-pyrolo[2,3_b]pyridin-7-carboxylic acid under the conditions shown in Step 4 of Example 1. The reaction yields 2 cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)_5H-0 pyrrolo[^^pyrazine-7-decanoic acid ((lS,2S)-2-hydroxy- 1,2-Dimethyl-butyl)- decylamine. Step 5 Step 2 of the procedure described in Step 5 of Example 1 to remove the cyclopropyl _5_(2_trimethylsulfonyl-ethoxyl group) Methyl)-5Η-°Biloze[2,3-b]° ratio tillage-7-formic acid ((lS,2S)-2-yl-1,2-dimethyl-butyl)-nitramine The protecting group is obtained as a white crystalline solid in 2-cyclopropyl-5H-° ratio [2,3-b] ° 11 well-7-decanoic acid ((lS,2S)-2-hydroxy- 1,2-didecyl-butyl)-decylamine. MS: (M+H)+=303; mp=243.0-245.0. Example 104. 2-cyclopropyl -5H- pyrrolo [2,3-b] pyridine 7-carboxylic acid Geng ((1 S, 2R) -2- hydroxy - 1,2-dimethyl-butyl) - · Amides

201204731 Prepared according to the procedure outlined in Example 103, replacing methyl magnesium bromide with ethyl magnesium bromide in step 1 and replacing ethyl magnesium bromide with methyl magnesium bromide in step 2. The product of Step 2 is a 3:2 mixture of diastereomers, primarily in the desired (1S, 2R) configuration. The final product contained 18% (1S, 2S) diastereomers. MS: (M+H)+= 303; mp=262.0-264.0. Example 105.

2-cyclopropyl-5H-pyrrolo[2,3-b]. Specific tillage-7-formic acid ((lS,2S)-3-cyclopropyl-2-hydroxy-1,2-dimethyl-propyl)-decylamine

Step 1 Prepare ((lS, 2S)-2-hydroxy-1,2 dimethyl-pentan-4-) by replacing allyl magnesium bromide with bromoallyl magnesium bromide according to the procedure outlined in Step 2, Example 103. Alkenyl)-tert-butyl carbamic acid. Step 2 was replaced with (0128)-2-hydroxy-1,2-didecyl-pent-4-enyl)-carbamic acid tert-butyl ester according to the procedure outlined in Step 3, Example 103 ((18,28) Preparation of (2S,3S)-2-amino-3-mercaptohexyl-5-thin-3 by tert-butyl 2-hydroxy-1,2-dimethyl-butyl)-amino decanoate - alcohol trigas acetate. 156090.doc •215- 201204731 Step 3 Replace with (2S,3S)-2-amino-3-indolyl-5-en-3-ol trifluoroacetate according to the procedure outlined in Step 4, Example 103 (2S,3S)-2-Amino-3-methyl-pentan-3-ol trifluoroacetate to prepare 2-cyclopropyl-5-(2-trimethyldecyl-ethoxyindenyl)- 5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((lS,2S)-2-hydroxy-1,2-didecyl-pent-4-enyl)-decylamine. Step 4 To 2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxycarbonyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((lS,2S)- Addition of acetic acid to a solution of 2-hydroxy-1,2-didecyl-pent-4-enyl)-decylamine (98 mg, 0.23 mmol) in tetrahydrofuran (2 mL) and diethyl ether (5 mL) (5 mg, catalytic) and the mixture was cooled in an ice bath. A diazomethane solution (6-8 mL, 0.5 Μ ether solution) was added dropwise, and the material was allowed to stand for 30 minutes while cooling and occasionally stirring. Then, a diazo sulphur solution (4 mL) was added under occasional mixing. After 10 minutes, the filtrate was thoroughly washed with ethyl acetate through the celite. The volatiles were evaporated to give 132 mg of crude 2-cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-[2,3-b]pyrazine-7-carboxylic acid ((l, 2S)-3-Cyclopropyl-2-hydroxy-1,2-dimethyl-propyl)-guanamine, which was used in the next step without further purification. Step 5 According to the procedure outlined in Step 5 of Example 103, using 2-cyclopropyl·5_(2-dimethylcarbamate-ethoxymethyl)-5Η-0 to compare each ((18,28) -3-cyclopropyl-2-yl-1,2-dimercapto-propyl)-decylamine in place of 2-cyclopropyl-5-(2-trimethylsulfanyl-ethoxymethyl) )-5Η-°Biloze[2,3-b]indole _-7-carboxylic acid ((lS,2S)-2-hydroxy-1,2-dimethyl-butyl)-decylamine to prepare 2_ 156090.doc •216- 201204731 Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((lS,2S)-3-cyclopropyl_2_hydroxy-1,2-di Mercapto-propyl)-guanamine. The product was isolated as a pale yellow solid. MS: (M+H)+=329. Example 106· 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((ls,2R)-3-cyclopropyl-2-yl-pyridyl-1,2-di Mercaptopropylamine

Step 1 Prepare ((S)-l-indolyl-2-oxo-pent-4-enyl) by replacing allylmagnesium bromide with methylmagnesium bromide according to the procedure outlined in Step 1 of Example 103. )_T-butyl carbamic acid. Step 2 Prepare ((lS,2R)-2-hydroxy-1,2 dimethyl-pent-4-ene by substituting lanthanum bromide for ethylmagnesium bromide according to the procedure outlined in Step 2 of Example 103. Base) · Tert-butyl amide. Step 3 Substituting ((lS,2R)-2-hydroxy-1,2-dimethyl-pent-4-enyl)-aminodecanoic acid tert-butyl ester according to the procedure outlined in Step 3, Example 103 ( (1S,2S)_2_ 156090.doc •217- 201204731 Preparation of (2S,3R)-2-amino-3- by mercapto-1,2-didecyl-butyl)-carbamic acid terpene vinegar Mercaptohex-5-en-3-ol trifluoroacetate. Step 4 Substituting (2S,3R)_2-amino-3-cyanohex-5-en-3-ol trifluoroacetate for (2S,3S)_2-amine according to the procedure outlined in Step 4, Example 103 Preparation of 2•cyclopropyl_5(2_tridecylfluorenyl-ethoxyindolyl)-5H-pyrrolo[2,3_b] by _3_fluorenyl-pent-3-ol trifluoroacetate Pyridine_7_decanoic acid ((1S, 2R)_2_yl-1,2-dimethyl-pent-4-enyl)-decylamine. Step 5 φ according to the procedure outlined in Step 4 of Example 105, using 2_cyclopropyl_5_(2_trimethylsulfonyl-ethoxyindolyl)-5Η-αpyrrolo[2,3- b]° than cultivable -7-formic acid ((lS, 2R)-2-yl-1,2-monomethyl-pentyl-4-yl) hydrazine instead of 2_cyclopropyl-5-(2 -tridecylalkyl-ethoxymethyl)_5H_pyrrolo[2,3_b]pyrazine-7-carboxylic acid ((lS,2S)-2-hydroxy·ι,2-dimethyl-penta-4 Preparation of 2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxyindenyl)-5Η-pyrrolo[2,3-b]pyr 11 well-7-formic acid ((lS, 2R)-3-cyclopropyl-2-hydroxy-1,2-dimercapto-propyl)-guanamine. Step 6 According to the procedure outlined in Example 1, Step 3, using 2-cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3- b] pyridin-7-formic acid ((lS,2R)-3-cyclopropyl-2-hydroxy-1,2-dimethyl-propyl)·decylamine instead of 2-cyclopropyl-5-(2 -tridecylalkyl-ethoxymethyl)-5H-indolo[2,3-b]pyridin-7-carboxylic acid ((lS,2S)-2-hydroxy-1,2-didecyl) -butyl)-guanamine to prepare 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((lS,2R)-3-cyclopropyl-2-156090. Doc -218· 201204731 Hydroxy-1,2-dimercapto-propyl)-decylamine. MS: (M+H)+=329. Example 107. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((lS,2R)-3,3,3- = fluoro-2-hydroxy-l,2 -dimercapto-propyl)-guanamine

According to Andres, JM; Pedrosa, R.; Perez_Encabo, a. Five Mr 乂 (9rg. C/iem. 2004, 1558-1566 and its references by (s)-2-diphenylguanidino-propyl Preparation of (2R,3S)-3-amino-1,l,l-trifluoro-2-indolyl-butan-2-ol by aldehyde. According to the procedure outlined in Example 4, Step 4-5, (2R, 3S) _ 3-Amino-1,1,1-trifluoro-2-methyl-butan-2-ol is substituted for "((r)"-aminoethyl)-cyclopentanol hydrochloride to prepare 2_ ring propyl_5H_pyrrolo[2,3_b]pyrazine_#7-decanoic acid ((18,211)_3,3,3-trifluoro-2-hydroxy-1,2-dimethyl-propyl)-醯Amine::\18:(]\/[+11)=343; Hyun=28〇.〇_283.0. Example 108. 2_Cyclopropyl-5H-. Bisino[2,3_b]n than brown _7_ decanoic acid ((1s, 2S)_3,3,3_5 fluoro-2-hydroxy-i,2_didecyl-propyl)-decylamine 156090.doc -219- 201204731

Step 1 (S)-2-Dibenzylamino-N-methoxy-N-methyl-propanamide (492 mg, 1.57 mmol) under argon at 〇 ° C (ice) ) [synthesis described in

Josop Bonjoch et al., 2006, &lt;52, 9166-9173] was dissolved in anhydrous tetrahydrofuran (1 〇 mL). The 3 Μ solution (2.1 mL, 6.3 mmol) of the desertified sulfhydryl group was added via dropwise addition and was in hydrazine. The reaction mixture was stirred for 3 hours under the arm. A saturated aqueous solution (2 mL, aqueous solution) was added, followed by water (40 mL) and ethyl acetate (60 mL). The mixture was transferred to a separatory funnel and shaken. The ethyl acetate phase was collected and washed with brine (6 mL). The aqueous phase was back-extracted with ethyl acetate (2 x 40 mL), dried <RTI ID=0.0> The residue was dissolved in dichloromethane and filtered through a EtOAc EtOAc EtOAc EtOAc EtOAc. (M+H)+=268. Step 2 Add fluorination to a solution of (S)-3-benzhydryl-butan-2-one (4 mg, 1.5 mm 〇l) in anhydrous pentane (7 mL) Tetrabutyl sulphide 156090.doc • 220· 201204731 solution (0.08 mL '1.0 μ THF solution), and the reaction mixture was cooled to 0 ° C (ice bath) under argon atmosphere. Triamyl (trifluoromethyl) oxacyclohexane (0.35 mL, 2.25 mmol) was added via a dropwise addition and was at 0. (: stirring for 30 minutes. Add saturated ammonium hydride solution (20 mL, aqueous solution) and strip most of the solvent on a rotary evaporator. Dissolve the residue in diethyl ether (4 mL) and water (40 mL) and transfer To the separatory funnel, the mixture was shaken, the ether phase was collected and washed with brine. The aqueous phase was back-extracted with _ (2 x 30 mL), combined, dried over magnesium sulfate, filtered and stripped to give crude s. The material was purified by preparative TLC (EtOAc (EtOAc) elute elute elut And a solution of tetra-N-butylammonium chloride (Q. 4 mL, 1. THF THF solution) was added. The material was stirred for 1 hour, followed by treatment as described above. The crude product was dissolved in di-methane and passed through a short Filtration of ruthenium dioxide plug. Stripping solvent' gives the desired (2S,3S)_3_diphenylmethylamino-1,1,1-trifluoro-2-indenyl group as a clear, semi-viscous oil. Butan-2-ol. (M+H)+=338 » Step 3 (2S,3S)-3-Diphenyldecylamino-trifluoro-2-methyl-butan-2-ol (130 mg, 0.42 mmol) dissolved Pelman's catalyst (40 mg) was added to methanol (4 mi). The flask was evacuated and placed under a helium balloon. The mixture was mixed overnight and then filtered through a Shisaizao plug. Rinse thoroughly with methanol. Add hydrochloric acid solution (15 ml, about 50% ethanol solution) to the material. Strip the solvent on a rotary evaporator to give (2S,3S)-3-amino-1 as an off-white solid. , U_Trifluoro-2-methyl-2-butan-2-ol hydrochloride (82 mg) 'can be used without further purification. 156090.doc -221· 201204731 Step 4 According to Example 1 Step 4·5 The procedure outlined, substituting (28,38)_3_amino-1,1,1-dioxa-2-methyl-butan-2-ol hydrochloride for the amine-ethyl)-cyclopentanolate Acid salt to prepare 2_cyclopropyl_5H_pyrrolo[2,3_b]pyrazine_7_carboxylic acid ((18,23)-3,3,3-trifluoro-2-hydroxy-1,2_2 Methyl propyl) amide. MS: (M+H)=343;;^^=29〇.〇_292.0. Example 109. 2-Cyclopropyl-5H-.咯和[2,3_b]pyrazine·7_carboxylic acid ((1R,2R)_2_hydroxy-1,2·dimethyl-butyl)-decylamine

According to the procedure outlined in Example 103, n-(third butoxycarbonyl)-D-alanine _n'-decyloxy-N,-mercaptodecylamine was substituted for N- in the step 1. Preparation of butoxycarbonyl)-L-alanine_N,-methoxy-oxime-methylamine. The product of Step 2 is the diastereomer 4: hydrazine mixture, primarily in the desired (1R, 2R) configuration. In step 3, the protecting group Boc group is removed using Hcl/MeOH instead of TFA. After step 4, the diastereomers were separated using preparative HpLC. River 8: (] ^ + 11) + = 303; melting point = 245.0-247_0. Example 110. 2-Cyclopropyl-5H-° ratio each [2,3-b]. Specific tillage-7-formic acid ((lR,2R)-2-yl-1,2-di-decyl-pentyl)-nonylamine 156090.doc -222- 201204731

Substituting N-(third butoxycarbonyl)-D-alanine-N-methoxy-N--mercaptoamine for N- (third) according to the procedure outlined in Example 103 Butoxycarbonyl)-L-alanine-Ν'-methoxy-indole-methylamine is prepared in step 2 by replacing propylmagnesium bromide with ethylmagnesium bromide. The product of Step 2 is a 4:1 mixture of diastereomers, primarily in the desired (ir, 2R) configuration. In step 3, the protecting group Boc group was removed using HCl/MeOH instead of TFA. After step 4, the diastereomers were separated using preparative HPLC. MS: (M+H)+=3 17; m.p. = 222.0-224.0. Example 111. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((lR,2R)-3-cyano-2-hydroxy-1,2-didecyl) -propyl)-guanamine

Step 1 Substituting N-(t-butoxycarbonyl)-D-alanine-Ν'-decyloxy-N,-methylguanamine for N- (third) according to the procedure outlined in Step 1 of Example 21. Preparation of ((R)-i-methyl-2-oxooxyl by butoxy 156090.doc -223· 201204731 benzyl)-L-alanine·Ν·-methoxy-N,-methyl decylamine -propyl). tert-butyl carbamic acid. Step 2 To a solution of acetonitrile (0.50 mL, 9.5 mmol) in THF (25 mL), bis(trimethylsulfonyl)amine lithium (1 〇M THF solution, 9·5 mL) ' 9.5 mmol). The reaction mixture was stirred at -78 ° C for 30 minutes, followed by dropwise addition of ((R)-l-methyl-2-oxo-propyl)-amino decanoic acid.

A solution of butyl ester (400 mg, 2.1 mmol) in THF (5 mL). The reaction mixture was stirred at -78 °C for 2 h then quenched with saturated aqueous NH4C1 and warmed to room temperature. The mixture was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate and concentrated. Purification of the residue by chromatography eluting with EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc ((lR, 2R)-3-cyano-2-hydroxy-1,2-dimethyl-propyl)-carbamic acid tert-butyl ester. Step 3 Dissolve ((lR,2R)-3-cyano-2-hydroxy-1,2-dimercaptopropyl)-aminodecanoic acid dibutyl ester (180 mg, 0.78 mmol) in hydrochloric acid ( 1〇Me〇H^ solution, 5 mL, 5 mmol)*. The solution was stirred overnight at rt then concentrated to give (3,,,,,,,,,,,,,,,,,, use. Step 4 Substituting (3R,4R)_4_amino-3-hydroxy-3-indolyl-valeronitrile hydrochloride for the amino group-ethyl) ring according to the procedure outlined in Example 4, Steps 4-5 156156090.doc -224- 201204731 Alkyl hydrochloride to prepare 2-cyclopropyl-5H-pyrrolo[2,3_b]pyrazine-7-carboxylic acid ((lR,2R)-3-cyano-2-hydroxyl -1,2-dimethyl-propyl)-decylamine. MS: (1^+11)+= 314; mp=234.0-236.0. Example 112. 2-Cyclopropyl-5Η-°piro[2,3-b]pyrazine-7-decanoic acid cyclohexyldecyl-decylamine

step 1

To 2-cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]° ratio p--7-decanoic acid (80 mg, 0.24 Methyl) 1,1,-carbonyldiimidazole (47 mg, 0.29 mmol) was added to a solution in THF (2 mL). The reaction mixture was stirred at 60 &lt;0&gt;C for 45 min then cooled to rt and EtOAc (0.31 mL, &lt The reaction mixture was stirred at rt EtOAc (EtOAc) The combined organic layers were washed with water and brine then dried over sodium sulfate. Purification of the residue by chromatography eluting with EtOAc / EtOAc EtOAc EtOAc EtOAc EtOAc夕alkyl-ethoxy fluorenyl)_5H-pyridoxine ro q than the [2,3-b]pyridinium-7-decanoic acid ring? Indole-ylamine. The procedure outlined in Step 2 of Example 2 was carried out according to the procedure of Example 1, step 5 using 2-cyclopropyl_5_(2-tri-156090.doc-225·201204731 methyldecyl-ethoxymethyl)-5H-pyrrole And [2,3-b]pyrazine-7-decanoic acid cyclohexylmethyl-decylamine in place of 2-cyclopropyl-5-(2-tridecyldecylalkylethoxyindolyl)-5H-pyrrole [2,3-b]pyridin-7-decanoic acid hydroxy·cyclopentyl)-ethyl]-nonylamine to prepare 2-cyclopropyl-5H-° ratio η[2,3_b]pyrazine- 7-Cyclohexyldecyl-decylamine. MS: (M+H)+= 299; m.p. KS. Biluo[2,3-b]pyrazine-7-formic acid (1_methanesulfonyl-oxen-3-ylmethyl)-decylamine

Step 1 Feed a 10 mL round bottom flask with 2_cyclopropyltrimethyldecylalkyl)ethoxy)methyl)_5H-pyrrolo[2,3-b]° than argon-7-decanoic acid (250) Mg, 0.75 mmol), 3-(aminomethyl v^n-Boc-piperidine (241 mg, 1.12 mmol), HOBT (lll mg, 0.82 mmol) and EDC (158 mg, 0·82 mmol). Dmf (3.3 mL) and N,N-diisopropylethylamine (0·20 mL ' 1.12 mmol) were added </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; Extraction with Et2O (2x50 mL). Wash the combined organic layers twice with 156090.doc -226 - 201204731 H2 and wash once with brine, then dry over NazSO4, filtered and concentrated" by chromatography on 24 g SiO 2 use

The residue was purified with EtOAc EtOAc (EtOAc:EtOAc:EtOAc 3-Ethyl fluorenyl)-5H-pyrrolo[2,3-13]° ratio tillicin-7-carbonyl]-amino}-indenyl)-piperidine-1 -decanoic acid tert-butyl ester. Step 2 3-({[2-cyclopropyl-5-(2-tridecylfluorenyl-ethoxymethyl)-5H-°) in a 25 mL round bottom flask [2,3- b]n than argon-7-carbonyl]-amino}-mercapto)-piperidine-1-furic acid tert-butyl ester (0.39 g, 0.74 mmol) was dissolved in MeOH (6.0 mL). The solution was cooled to 〇 ° C and ethyl acetate (1.05 mL, 14-8 mmol) was added dropwise over 10 min. • The ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 hours. The solvent was evaporated at rt and the residue was dried <RTI ID=0.0></RTI> to </RTI> </RTI> </RTI> </RTI> _5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (piperidin-3-ylindenyl)-guanamine hydrochloride. Step 3 2-Cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7- in a 15 mL round bottom flask Citrate (piperidin-3-ylmethyl)-guanamine hydrochloride (160 mg '0_34 mmol) was dissolved in CH2C12 (3 mL) and cooled to 0. Triethylamine (0.11 mL, 0.75 mmol) and decanesulfonium (0.032 mL '0.41 mmol) were added. The reaction mixture was stirred at room temperature for 7 hr then diluted with EtOAc EtOAc (EtOAc) The aqueous layer was extracted with CH.sub.2Cl.sub.2 (25 mL). The residue was purified by EtOAc / EtOAc (EtOAc:EtOAc) -trimethylsulfate-ethoxymethyl)_5h_pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methanesulfonyl-piperidinyl)-decylamine Step 4 In a 10 mL round bottom flask, 2-cyclopropyl-5-(2-trimethylsulfanyl-ethoxymethylpyrolo[2,3-b]pyridin-7-decanoic acid (1) - decanesulfonyl _0 底 -3- mercapto) decylamine (159 mg, 0.32 mmol) was dissolved in CH2C12 (1.3 mL). Difluoroacetic acid (1·0 mL, ΐ3·0 mmol) And the residue was dissolved in toluene (3 mL), concentrated and dried under high vacuum. The residue was dissolved in CH2C12 (1.3 mL). Ethylenediamine (L3 mL, 19.3 mmol) was added. The reaction mixture was stirred at room temperature for 2.5 hours, then h2 hydrazine and EtOAc were added, and the obtained suspension was filtered, washed with η 2 〇 and Et 〇 A ( Drying down to give 59 mg (50%) of 2_cyclopropyl_5H_pyrrole as a pale yellow solid [2,3-b]pyrazine-7-formic acid (ι_methanesulfonylpiperidine-3-ylmethylguanamine. MS: (M+H)+=378; Hyun=247.6-248.4. Example 114. 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (1-ethylindenyl-piperidine-3-yl)-decylamine 156090.doc-228 - 201204731

Step 1 3-({[2-cyclopropyl-5-(2-trimethylsulfanyl-ethoxycarbonyl)-5H-») in a 25 mL round bottom flask [2,3 -b] η is more soluble in MeOH (6.0 mL) than argon-7-carbonyl]-aminopyridylmethyl)-O-O-butyl-1 - formazan-dibutylamine (0.39 g, 0.74 mmol). The solution was cooled to 〇 ° C and ethyl acetate (1.05 mL, 14.8 mmol) was added dropwise over 1 Torr. The ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 hours. The solvent was evaporated at room temperature and the residue was dried under high vacuum to afford 339 g (98%) of y. _5H-° 〇[2,3-b]0 than well-7-formic acid (piperidin-3-ylindenyl)-guanamine hydrochloride. Step 2 2-Cyclopropyl-5-(2.3-trimethylsulfonyl-ethoxymethyl)-5-pyrrolo[2,3-b]pyrazine-7- in a 15 mL round bottom flask Capric acid (piperidin-3-ylindenyl)-decylamine hydrochloride (175 mg '0.38 mmol, from Example 3 1 Step 2) was dissolved in CH2C12 (3 mL) and cooled to EtOAc. Triethylamine (0.12 mL, 0.83 mmol) and acetonitrile (0.032 mL, 0.45 mmol) were then added. The reaction mixture was stirred at room temperature for 7.5 hours, then diluted with 30 mL of CH.sub.2 C.sub.2 and washed with 156090.doc - 229 - 201204731 water (5 mL). The aqueous layer was taken up in <RTI ID=0.0># </ RTI> </ RTI> <RTIgt; By chromatography on 8 g 8丨02

The residue was purified with EtOAc / EtOAc (EtOAc (EtOAc) (2-trimethyldecyl-ethoxycarbonyl)-5H-pyrolo[2,3-b]&quot; ratio 11 well-7-carboxylic acid (1-ethylindenyl-piperidin-3-yl) Sulfhydryl) - guanamine. Step 3 According to the procedure outlined in Step 4 of Example 113, 2-cyclopropyl-5-(2-trimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3-b] Pyridin-7-decanoic acid (1-ethylhydrazine base -3-ylindenyl)-guanamine instead of 2-cyclopropyl-5-(2-trimethylsulfanyl-ethoxymethyl)- 5H-0 is greater than 0 and [2,3-b]. Preparation of 2-cyclopropyl-5H_pyrrolo[2,3-b]pyrazine-p-p--7-formic acid (1-indolesulfonyl-piperidin-3-ylmethyl)-decylamine 7-Formic acid (i-ethinylpiperidine-3-ylmethyl)-decylamine. MS: (M+H)+=342; melting point = 198.4-199.1. Example 115. 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyrazine·7•decanoic acid (1_methanesulfonyl-pyridyl 0-decyl-3-ylmethyl)-nitramine

156090.doc •230-201204731 Step 1 Feed a 10 mL round bottom flask with 2-cyclopropyl-5-((2-(tridecyldecyl)ethoxy)methyl)-5H-pyrrole[ 2,3-b]pyrazine-7-decanoic acid (260 mg, 0.78 mmol), 3-(aminomethyl)-1-N-Boc-pyrrolidine (234 mg, 1.17 mmol), HOBT (116 mg , 0.86 mmol) and EDC (164 mg, 0.86 mmol). DMF (3.4 mL) and N,N-diisopropylethylamine (0.20 mL, 1.12 mmol) were then added. The yellow reaction mixture was stirred with EtOAc (EtOAc)EtOAc. The combined organic layers were washed twice with HzO and once with brine then filtered and concentrated with Naj. The residue was purified by EtOAc / EtOAc (EtOAc:EtOAc) 5-(2-tridecylsulfanyl-ethoxymethyl)-5H-° ratio [2,3-b] ° ratio whisperazine-7-amino]-amino}-methyl) Pyrrolidin-1-decanoic acid tert-butyl ester. Step 2 According to the procedure outlined in Steps 2-4 of Example 113, 3-({[2-cyclopropyl-^ 5-(2-tridecyl)-stone-ethoxyl-yl-n-[2] , 3-b]»比'• Well-7. carbonyl]-amino}-mercapto)-pyrrolidine-1-decanoic acid tert-butyl ester instead of 3-({[2-cyclopropyl-5-( 2-trimethyldecyl-ethoxycarbonyl)-5H-«bido[2,3-b]»prefers to 11--7-yl-amino]-amino}-indenyl)-. Preparation of 2--1-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (1-methanesulfonyl-pyrrole biting _ 3 - fluorenyl)-guanamine. MS: (M+H)+= 364; mp=248.0-249.0. Example 116. 2-cyclopropyl-5H-0 ratio slightly [2,3-b]0 ratio ρ井-7-carboxylic acid (1-ethylidene ratio η each. 定_156090.doc -231- 201204731 3-ylmethyl)-guanamine

According to the procedure outlined in Example 114, 3_({[2_cyclopropyl_5_(2_tridecylfluorenyl-ethoxycarbonyl)-[2,3_b]. ]_amino}-mercapto)-pyrrolidine-1_decanoic acid tert-butyl ester instead of 3_({[2 cyclopropyl_5_(2-tridecylfluorenyl-ethoxymethyl)_5H_pyrrole And [2,31;)]pyridinium-7-carbonyl]-amino}-indenyl)-piperidine-1·decanoic acid tert-butyl ester was prepared. MS: (M+H)+= 328; mp=233.8-235.0. Example 117. 2-Phenoxy-5H-pyrrolo[2,3-b]pyrazine_7-carboxylic acid (1•cyclopropyl-ethyl)-indoleamine

Step 1 Stir 2-bromo-5-(2·trimethyldecyl-ethoxymethyl hsH-n ratio 156090.doc •232· 201204731 [2,3-b]0 to 0 well-7- Formic acid (0-276 g, 0.741 mmol), 7 mL of dioxane, 4-dimethylamino 0-position (0.0850 g, 0.696 mmol), 1-cyclopropylethylamine (0.151 g, 1.77) A solution of (1 mmol) and (3-didecylamino-propyl)-ethyl-carbodiimide (0.285 g ' 1.49 mmol) for 20 h then concentrated to a yellow oil. Between ethyl acetate and 1 〇mL of 10% citric acid solution, and the organic layer was washed sequentially with 10 mL of water and 10 mL of saturated aqueous NaCl solution; dried over MgSO4, filtered and concentrated to a yellow oil. Analysis (〇-&gt; 33% EtOAc/hexanes) afforded 0.190 g (yield: 58%) of 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrole as a white solid. And [2,3-b]pyrazine-7-decanoic acid (1-cyclopropyl-ethyl)-decylamine Step 2 Stir 2-bromo in a sealed tube at 150 ° C under nitrogen 5-(2-trimethyldecyl-ethoxycarbonyl)-5H-pyrrolo[2,3-b]indole plough-7-carboxylic acid (1-cyclopropyl-ethyl)-decylamine ( 0.092 g, 0.21 0 mmol), phenol (0.0246 g, 0.261 mmol), K3P〇4 (〇.1〇6 g, 0.498 mmol), [2'-(di-t-butyl-phosphino)-biphenyl-2-yl a mixture of di-mercapto-amine (0.0036 g, 0.011 mmol), Pd(OAc) 2 (〇.〇〇18 g, 0.0080 mmol) and 2 mL of hydrazine for 38 hours, then cooled and partitioned into 10 mL of ethyl acetate The residue was combined with 10 mL EtOAc (EtOAc)EtOAc. Obtained 0.047 g (46%) of 2- phenoxy-5-(2-tridecyl decyl-ethoxymethyl)-5H-n ratio [2,3-bp] as a pale yellow oil. Specific cultivating -7-decanoic acid (1-cyclopropyl-ethyl)-guanamine. Step 3 156090.doc -233 · 201204731 Mix 2-phenoxy-5-(2-trimethyl sulphate · B Oxymethyl)5h_〇 略和[2,3-b]pyrazine-7-carboxylic acid (1_cyclopropyl-ethylamine (〇〇47 〇ι〇5 mmoi) in i mL dichloride A solution of methyl chloride in trifluoroacetic acid for 2 hours, followed by concentration and addition of toluene afforded a yellow residue. The residue was treated with 6 mL of dioxane and 0.6 mL of ethylenediamine. The resulting solution was stirred for a few hours, 'and then partitioned between 10 mL of ethyl acetate and 5 mL of water. The aqueous layer was extracted with 1 mL of ethyl acetate (yield) and the combined organic layers were concentrated to a solid crystal column chromatography (20-&gt; 100% EtOAc/hexanes) to give 〇〇 24 g (7 %) 2-phenoxy-5 oxime and [2,3.b] (cyclopropylethyl)-decylamine as a yellow solid. MS: (M+H)+= 323; mp = 242. 〇 245. Example 118. 2-(2'4-Difluoro-phenoxy)-5-p-pyrolo[2,3_b]n-pyridyl-7-carboxylic acid (1-cyclopropyl-ethyl)-decylamine

F was prepared in step 2 using 2,4-difluorobenzene in accordance with the procedure outlined in Example 117. MS: (M+H)+=359. Example 119. 2-(4 Luphenoxy)-5H-W and [2,3 exo 7-decanoic acid (1 cyclopropyl-ethyl)·nitramine 156090.doc •234· 201204731

F

Prepared according to the procedure outlined in Example 117, in step 2, using 4-methanol as a substitute for phenol. MS: (M+H)+=341.

Example 120. 2-(2-Fluoro-phenoxy)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (b-cyclohexyl-ethyl)-decylamine

F

Prepared in step 2 with 2-fluorophenol instead of phenol according to the procedure outlined in Example 117. MS: (M+H)+=341. Example 121. 2-Benzyloxy-5H-. Biluo[2,3-b]° ratio 11 Well-7-formic acid ((r)_2-yl-1,2-didecyl-propyl)-nitramine 156090.doc -235 - 201204731

According to the procedure outlined in Steps 2-3 of Example 117, using 2_bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-»pyr-[2,3_b]D _7_Citrate 2-hydroxy-1,2-dimethyl-propyl)·guanamine [from Example 32, Step 3] instead of 2_bromo-5-(2-tridecylfluorenyl-ethoxymethyl) _5H_pyrrolo[2,3_b]pyrazine-7-carboxylic acid (1-%propyl-ethyl)-decylamine was prepared.ms: (M+H)+=341 ° Example 122. 2-Benzene Oxy-5-pyrido[2,3-b]pyrazine-7-formic acid isopropylamine

Step 1: 2 -Bromo-5-(2-tridecylfluorenyl-ethoxyindenyl)_5仏pyrrolo[2,3-13] was added to the sealed tube under nitrogen at 150 °C. . Specific tillage-7-formaldehyde (3.29 g, 9.23 mmol), phenol (1.04 g, 11.08 mmol), Κ3Ρ04 (3.92 g, 18.46 mmol), [2'-(di-t-butyl-phosphinoalkyl) Biphenyl-2-yl]-didecyl-amine (0.157 g, 0.46 mmol), Pd(〇Ac) 2 (0.1〇3 g, 0.46 156090.doc • 236-201204731 mmol) and degassed toluene ( A mixture of 50 mL) was overnight. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate and water. The aqueous layer was extracted with EtOAc (EtOAc)EtOAc. The residue was purified by EtOAc EtOAc EtOAc (EtOAc) -(2-trimethylsulfonyl-ethoxycarbonyl)-5H-° 〇[2,3-1&gt;]0 ratio"* well-7-曱. Step 2 by Cr03( 2.67 g) Prepare a stock solution of Jones reagent (2.67 Μ) by carefully adding concentrated h2S04 (2.3 mL) and then diluting to 1 〇mL with HzO. To 2-phenoxy-5-(2-triterpene) at 〇 °C矽 矽 - 乙 乙 乙 ) · 〇 〇 〇 〇 〇 〇 2 2 2 2 2 2 2 2 2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 (2.35, 6.37 mmol) in acetone (75 mL) The solution was stirred with EtOAc (5 mL, EtOAc (EtOAc). The filtrate was washed with cold water (3x) and brine, then dried and concentrated with EtOAc EtOAc EtOAc EtOAc (EtOAc) 2-Phenoxy-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid as a pale yellow solid. Step 3To 2-phenoxy-5-(2-tridecylfluorenyl-ethoxyindenyl)-5H_pyrrolo[2,3-b]0 than p-well-7-decanoic acid (〇·ιΐ5 g, 0.30 mmol), 4-dimethylamine-based pyridine (0.048 g, 0.39 mmol) and (3-dimethylamino-propyl)-ethylcarbodiimide (0.075 g, 0.39 mmol) To a solution of CH2C12 (2 mL) was added isopropylamine (0.023 g, 0.39 mmol) in CH2C12 (0.5 mL) 156 090. doc - 237 - 201204731. The reaction mixture was stirred overnight at room temperature and then quenched with water. And extracted with ethyl acetate (3X). The organic layer was washed with water and a saturated aqueous solution of NaCI and dried over MgSCU, filtered and concentrated to give 2 phenoxy _5_(2_trimethyl decyl-ethoxy fluorenyl -5H-pyrrolo[2,3-b]pyrazine-7-isopropyl decylamine, which can be used without further purification. Step 4 to 2-phenoxy-5-(Step 3) 2-trimethyldecyl-ethoxymethyl)_ 5H-. Addition of hydrazino[2,3-b]pyrazine-7-formic acid isopropylamine in CH2C12 (0.7 mL) Trifluoroacetic acid (0.7 mL). The reaction mixture was stirred at room temperature overnight and then concentrated. THF. The residue was stirred for 2 hours with EtOAc (3 mL) and then concentrated. The residue was partitioned between ethyl acetate and water and aqueous layer was evaporated. The combined organic layers were dried over a pad of EtOAc and concentrated. The residue was purified by EtOAc EtOAc EtOAc EtOAc (EtOAc) [2,3-b]pyrazine-7-decyl isopropylamine. ;\18: (14+11)+=297; melting point = 263.0-265.0. Example 123. 2-Phenoxy-5H-0 piroxi[2,3-b]. Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)

156090.doc -238- 201204731 Prepared in step 3 by replacing the isopropylamine with onhs methyl-propylamine according to the procedure outlined in Example 122. MS: (M+H)+=339; mp=270.0-273.0 ° Example 124. 2-phenoxy-5H-pyrrolo[2,3_b]pyrazine-7-decanoic acid ((S)-second Amine

Prepared in step 3 by replacing the isopropylamine with a second butanamine according to the procedure outlined in Example 122. Ms·(M+H)+=31l; melting point=227〇_ 229.0 ° Example 125.

2 phenyloxy-5Η-»比比和[2,3_b]D ratio -7-7-decanoic acid ((8) dimethyl-propyl)-guanamine

According to the procedure outlined in Example 122, +Sum, in step 3, use (S)-l,2-two

Mercapto-propylamine was prepared in place of the iso-diamine I J makeup. MS: (M+H)+=325; mp 156090.doc - 239 - 201204731 = 234.0-235.0 ° Example 126. 2-Phenoxy-5H-pyrrolo[2,3-b]pyrazine_7_曱Acid ((S)-l-cyclohexyl-ethyl)-decylamine

Prepared in step 3 by substituting (s)-(+)cyclohexylethylamine for isopropylamine according to the procedure outlined in Example 122. MS: (M+H)+= 365; m.p. Example 127. 2-Phenoxy-5H-pyrrolo[2,3-b]pyridin-7-decanoic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-decylamine

Prepared in step 3 by substituting (s)-3-amino-1-2-methyl-butan-2-ol for isopropylamine according to the procedure outlined in Example 122. MS: (M+H)+=341; melting point=232.0-232.0 〇Example 128. 156090.doc 240· 201204731 2-phenoxy-5H-- ratio η[2,3_b]pyr _7_ Formic acid ((R)-l-cyclohexyl-ethyl)·nitramine

Prepared in step 3 by substituting (R)-(-)-1 -cyclohexylethylamine for isopropylamine according to the procedure outlined in Example 122. MS: (M+H)+=365; m.p. = 231.0 - 232.0 °. Example 129. 2-phenoxy-5H- 〇tb-[2,3-b]pyridin-7-carboxylic acid ((R)- l,2,2-trimethyl-propyl)-guanamine

Prepared in step 3 by substituting (R)-i,2,2-trimethyl-propylamine for isopropylamine according to the procedure outlined in Example 122. MS: (M+H)+= 339; m.p.=273.0-274.0.. Example 130. 2-phenoxy-5H-indolo[2,3-b]pyrazine-7-carboxylic acid ethyl decylamine 156090. Doc -241 - 201204731 hn^An^

Q H

'A was prepared according to the procedure outlined in Example 122 using a 7 % aqueous solution of ethylamine in place of isopropylamine in step 3. Ms: (m+h)+=283; Hyun=23〇 〇_ 232.0 〇 Example 131.

2-(2,4-difluorophenoxy)_511_[2,3_b]am formic acid isopropylamine

F According to the procedure outlined in Example 122, at the step! It is prepared by using 2,4·difluorophenol instead of phenol. MS: (M+H)+=333. Example 132. 2-(2,4-Difluorodecyloxy)_5-p-butyr[2,3-subequal 呶7-carboxylic acid (10)_ 1,2,2-tridecyl-propyl)-decylamine 156090. Doc •242· 201204731

1 in 2,4-difluoro-p-methyl-propylamine instead of

According to the procedure outlined in Example 122, the phenol was substituted for the phenol in the step and was prepared in step 3 with propylamine. MS: (M+H)+=375. Example 133. (2,4-Difluoro-phenoxy)_511 "called and [2,3 succinic acid called 1,2,2.trimethyl-propyl)-decylamine

F. According to the procedure outlined in Example 12 2, the thiol-propylamine substitution step 2 is substituted for phenol with 2,4-difluorobenzene, and is used in step 3 with τ, both propylamine. MS: (M+H)+=375. Example 134. 2-(2,4-Difluoro-phenoxy)-5H-pyrrolin "9 1 L '3_b]° 啩-7-decanoic acid ethyl decylamine 156090.doc -243- 201204731 Ο

F Prepared according to the procedure outlined in Example 122 'in the step' with 2,4-difluorophenol in place of benzophenone and in step 3 with ethylamine instead of isopropylamine. ^ MS: (M+H)+=319 . Example 135. 2-(2,4-Difluoro-phenoxy)-5H-pyrrolo[2,3-b]pyr-7-nonanoic acid ((S)-l-cyclohexyl-ethyl )--bristamine

F. Prepared according to the procedure outlined in Example 122, in which the phenol was replaced with 2,4-difluorophenol in step 1, and in step 3, (SH+)-l-cyclohexylethylamine was used in place of the isopropylamine. ]\^:(]^+11)+=401; Melting point=233.0-23 5.0 » Example 136. 2-(2,4-Difluoro-phenoxy)-5H-&quot; 比比和[2,3 -b]&quot;specific tillage_7_formic acid ((R)-l-cyclohexyl-ethyl)-decylamine 156090.doc -244- 201204731

According to the procedure outlined in Example 122, in step 1, 2,4-difluorophenol was used in place of phenol, and in step 3, cyclohexylethylamine was used in place of

Prepare with propylamine. MS: (M+H)+=40l. k*, mp=233.0-235.0. Example 137· 2-(2,4-Difluoro-phenoxy ratio ‘Bahab[2,3-b]pyrazine-7-carboxylic acid ((R)-butyl-butyl)-nitramine

According to the procedure outlined in Example 122, phenol was replaced with 2,4-difluorophenol in step ,, and in step 3, (R)-second butylamine was used instead of isopropylamine. MS: (M+H)+=347; mp = 246 〇 248. Example 138. 2-(2,4-Fluoro-phenoxypyrolo[2,3_b]pyrazine_7-decanoic acid ((s)-2_hydroxy-1,2-dimethyl-propyl) _ 醯amine 156090.doc -245· 201204731

Substituting 2,4-difluorophenol for phenol' in step 1 and substituting (S)-3-amino-2-methyl-butan-2-ol in step 3 according to the procedure outlined in Example 122 Prepared with isopropylamine. MS: (M+H)+= 377; mp. Example 139. 2-(2,4-Difluoro-phenoxy)_5H-n than argon[2,3-b]° than argon-7-formic acid ((R)-1,2-dimethyl- Propyl)

According to the procedure outlined in Example 122, phenol was replaced with 2,4-difluorophenol in step ,, and in step 3, (R)-i,2-dimethyl-propylamine was used in place of isopropylamine. MS: (M+H)+= 361; melting point = 235.0-237.0. Example 140. 2-(1-ethyl-ΙΗ-α ratio. Sodium-4-yl)-5H-n ratio slightly [2,3-b]° than plough-7-formic acid [(S)-l- (l-radio-cyclopentyl)-ethyl]-bristamine 156090.doc -246- 201204731

According to the procedure outlined in Example i, in the step 丨, B〇c_L_ methionine ester was substituted for Boc-D-alanine decyl ester, and in step 4, 2_(丨·ethyl-1H-pyrazole- 4-yl)-5-(2-trimethyldecyl ethoxymethyl)_5H_pyrrolo[2,3-b]pyridinic acid instead of 2·cyclopropyl_5_(2_tridecyl)矽alkyl-ethoxymethyl)_5H-. More than argon [2,3-b] 0 is prepared by cultivating citric acid. MS: (M+H)+=369 ° Example 141. 2-Cyclopropyl·5Η-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyano-1,2 , 2_ trimethyl-ethyl)-decylamine

Step 1 (R)-2-Methyl-propanol-2_ succinimide (4.00 g, 33.0 mmol) was dissolved in CH2C12 (14.0 mL). Acetaldehyde (16.7 mL, 297 mmol), MgS04 (11.9 g, 99.0 mmol) and pyridinium sulfonate (415 mg, 1.65 mmol) were added. The reaction mixture was stirred at room temperature overnight, filtered and concentrated to give crystals of crystals ofsssssssssssssssssssssssssssssssssssssssssssssss Amine which was used without further purification. Step 2 Isobutyronitrile (6.39 g, 92.4 mmol) was dissolved in diethyl ether (190 mL) and cooled at -78 °C. NaHMDS (1.0 M in THF solution, 99.0 mL '99.0 mmol) was added and mixture was stirred at -78 °C for 30 min. Slowly adding (R)-2-methyl-propane-2-sulfinic acid (E)·ethylene decylamine (the crude material of Step 1 , 5.21 g, 33.0 mmol) in THF (5 0.0 mL) . The mixture was stirred at -781 for 2 hours and then warmed to room temperature overnight. The reaction mixture was quenched with aq. The combined organic phases were washed with brine, dried over EtOAc EtOAc. The residue was purified by EtOAc (20-100% EtOAc (EtOAc): -2-sulfinic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-guanamine. Step 3 (R)-2-indenyl-propane-2-arylene Sulfonic acid (2-cyano-1,2,2-trimethylethyl)-decylamine (2.93 g, 13.6 mmol) was dissolved in MeOH and HCl (4.0 Μ 1,4- dioxin) was added. 6.8 mL ' 27.2 mmol). The reaction mixture was stirred at room temperature for 1 h then diluted to give 1.90 g (94%) of (S)-3-amino-2,2-dimethyl as a white solid. - butyronitrile hydrochloride, which can be used without further purification. Step 4 According to Procedure 4, in step 1, 1-methyl-4-(4,4,5,5·tetramethyl-1,3 ,2-dioxaboron-2-yl)-1Η-pyrazole instead of 1-ethyl·4-(4,4,5,5-tetramethyl-1,3,2-dioxaborene-2 -yl)-1Η-pyrazole to prepare 2-(1-methyl-1Η-pyridyl 156090.doc • 248-201204731. sit-4-yl)-5-(2-trimethyl sulphide-ethoxy Methyl)_5 Η-0 piroxime [2,3-b]pyrazine-7-decanoic acid. Step 5 Combine in the flask 2 - (1 - fluorenyl-1 Η -0 ratio ° sit -4 -5·(2-trimethylsulfonic acid-ethoxymethyl)-5Η-&quot;bibromo[2,3-b]pyrazine-7-carboxylic acid (120 mg, 0.32 mmol), ( S)-3-Amino-2,2-dimercaptobutyronitrile hydrochloride (72 mg, 0.48 mmol), EDC (142 mg '0.74 mmol) and HOBt (125 mg, 0.74 mmol). (4.0 mL) and i-Pr2NEt (0.39 mL, 2·25 mmol). The mixture was stirred at room temperature for 18 h then quenched with EtOAc EtOAc EtOAc EtOAc The saturated NaCl-purged organic phase was then dried over EtOAc (EtOAc) elute elute 2·(ΐ_曱-iH-carbazole·4-yl)-5-(2-trimethyldecyl-ethoxymethyl)_5H_pyrrolo[2,3_b]pyrazine_7_carboxylic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-decylamine. Step 6 2-(1-methyl-1H-. than sal-4-yl) in a flask -5-(2-trimethyl-stone-ethoxymethyl)-5H-. Bisolo[2,3-b]pyrazine-7-decanoic acid ((S)-2-cyano-1,2,2-dimethyl-ethyl)-decylamine (150 mg, 0.32 mmol) Dissolved in CH2C12 (2.25 mL) and added TFA (0 75 mL). The reaction mixture was stirred for 2 hours and concentrated. The residue was dissolved in EtOAc / EtOAc / EtOAc (EtOAc:EtOAc) The reaction mixture was then concentrated and the residue was purified EtOAcjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj _ 156090.doc •249· 201204731 5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid ((S)-2-cyano_12 2_ = ' '-T-ethyl)-decylamine . MS: (M+H)+=338. Example 142. 2-(1-Mercapto-1H-pyrazol-4-yl)-5Η·pyrrolo[2,3-b]pyrrolecarboxylic acid ((S)-l-cyclohexyl-ethyl)- amine

N Substituting (s) _ (+)-1-cyclohexylethylamine for 1-((R)-1-amino-ethyl) in step 4 according to the procedure outlined in Example 4, Steps 4-5 Cyclopentanol hydrochloride and using 2-(1-methyl-1H-pyrazol-4-yl)-5-(2-trimethyldecyl-ethoxycarbonyl)-5H-&quot;咯[2,3-b]pyr, well-7-nonanoic acid instead of 2-cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3 -b] Pyridine-7-formic acid was prepared. MS: (M+H)+=353. Example 143. 2-(1-Mercapto-1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((8)-1,2,2-three Mercapto-propyl)-guanamine

Step 1 156090.doc -250- 201204731 2-Bromo-5-(2-tridecyldecyl-ethoxymethyl)-5H-° ratio [2,3-b]°*p well- 7-carboxylic acid (1.5 g, 4·8 mmol) was partially dissolved in dichloromethane (40 mL). 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (1.54 g, 8.06 mmol), 4-didecylaminopyridine (0.49 g, 4 mmol) N,N-Diisopropylethylamine (1.4 mL, 8.06 mmol) and (S)-3,3-dimethylbutan-2-amine (0.49 g, 4.8 mmol). The reaction mixture was diluted with a HCl solution, and the aqueous layer was extracted twice with methylene chloride. The combined organic layers were washed with sodium bicarbonate, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (ethyl acetate /hexane) to afford 1.23 g (yield: EtOAc) Pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l,2,2-tridecyl-propyl)-guanamine. Step 2 A mixture of 1,4-dioxane (1.8 mL) and water (0.4 mL) was flushed with argon in a microwave vial. 2-Bromo-5-(2-tridecyldecyl-ethoxycarbonyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-l, 2,2-trimethyl-propyl)-decylamine (100 mg '0.22 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2] Oxygen side imino-2-yl)-lH-Dito sitting (50 mg, 0.24 mmol), hydrazine (triphenylphosphine) | £ (12.7 mg, 0.011 mmol) and carbonated (91 mg, 0.66 mmol) » sealed vial And heating in a microwave reactor at 14 (rc for 1 hour. The reaction was cooled and water, sodium bicarbonate solution and acetic acid were added. The aqueous layer was extracted twice with ethyl acetate then washed with brine. The organic layer was dried with sodium sulfate and evaporated. EtOAcjjjjjjjj ))-5-(2-dimercapto-stone-ethoxyl-yl)-5H-° than 〇[2,3-b]&quot;Bijing-7-A 156090.doc -251 · 201204731 Acid ((S)-l,2,2-trimethyl-propyl)-decylamine. Step 3 2-(1-Methyl-1H-pyrazol-4-yl)-5-(2-tri Methyl decyl-ethoxylated hydrazino)-511-pyrrolo[2,3_13]pyr 51 well _7_carboxylic acid (( 8) _1,2,2_tridecyl-propyl)-decylamine (87 mg, 0.19 mmol) was dissolved in dichloromethane (1 mL) and then stirred in ice bath. 6·6 mL) and the ice bath was removed. The reaction was stirred for 3 h then cooled in an ice-bath. A sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layer was washed with brine. Dry over sodium sulfate and concentrate. The residue was dissolved in anhydrous ethyl acetate (8 mL) and sodium acetate (313 mg, 3 8 mm 〇1) was added. The reaction mixture was stirred at 60 ° C for 20 hours, then cooled and water was added. Ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. EtOAc EtOAc EtOAc. (l-mercapto-1H-pyrazole·4·yl)-5H-pyrrolo[2,3-b]. Tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl ))·醢amine. MS: (M+H)+=327; m.p. = 296-297 ° C. Example 144. 2-°-s-phen-2-yl-5H-. b]0 than "• Well-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

V NH 156090.doc .252· 201204731 In accordance with the procedure outlined in Example 143, Steps 2-3, in step 2, replace 1-methyl-4-(4,4,5, with thiophen-2-ylfolic acid It is prepared by 5-tetradecyl-[1,3,2]dioxanol)-1Η-°. MS: (M+H)+= 329; m.p. Example 145. 2-(4-Trifluoromethyl-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)_ 1,2,2-tridecyl- Propyl)

Substituting 4·(difluoroindolyl)phenylg-phenic acid for 丨_曱yl_4_(4,4,5,5-tetramethyl) according to the procedure outlined in Steps 2-3 of Example 143 Monoborohydride-2-yl)-iH-pyrazole was prepared. MS: (M+H)+= 391; m.p. &gt; 300. (:. Example 146. 2-Cyclopropyl-5H-pyrrolo[2,3_b]pyrazine·7-carboxylic acid ((s)_3_nonanesulfonyl-1,2,2-trimethyl-propyl Guanamine

156090.doc -253 201204731 Step 1 (S)-3-(Tertidinoxycarbonylamino)butyric acid (1.0 g, 4.9 mmol) was dissolved in EtOAc (EtOAc) (EtOAc) The solution was cooled in an ice/water bath&apos; and trimethyldecyl diazomethane (2 hexane solution, 12.3 mL, 24.6 mmc) was slowly added. The reaction was stirred at 20 ° C for 18 hours then concentrated. The residue was adsorbed onto silica gel and purified by silica gel chromatography (ethyl acetate / hexanes) to yield 1.06 g (99%) of (S)-3-t-butoxycarbonylamino-butyric acid methyl ester. Step 2 (S)-3-Tertoxycarbonylamino-butyric acid methyl ester (1 〇 6 g, 29 mmol) was dissolved in THF (29 mL) and stirred in a dry ice/acetone bath. Add butyl lithium solution (2 6 alkane solution, 4.2 mL, 1 〇) to each of the flasks by cooling to a dry ice/acetone bath in isopropylamine (1.54 mL, 10.8 mmol) in THF (4 mL) 8 mmol) to prepare lithium diisopropylamide, followed by stirring for 45 minutes. A solution of lithium diisopropylamide was added to the ester solution via cannula over 20 minutes, and the reaction was stirred at dry ice/acetone temperature. Minutes. Iodine (0-7 mL, 10 8 mm 〇1) a was added to the reaction mixture, and the mixture was stirred for 2 hr. Additional methyl iodide (〇 7 rainbow, 1 〇 8 mmol) was added over 20 minutes, then the reaction was allowed to warm to EtOAc over 16 hr. Ammonium chloride solution was added, and the mixture was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography (diethyl ether /hexane) to afford s. 49 g (39%) of (s) 3 3 -butoxyaminoamino-2,2-dimethyl-butyric acid . Step 3 156090.doc -254- 201204731 (S)-3-Tertoxycarbonylamino-2,2-dimethyl-butyrate (0.47 g, 1.92 mmol) was dissolved in THF (11 mL) ) and cooled to -35 ° C. Hydrogenation (1.0 M THF solution, 1.9 mL, 1.9 mmol) was added dropwise. The reactants were mixed and the temperature gradually reached 51 after 2 hours. Then continue to add about 75 pL of water, 120 pL of 10% NaOH solution and 190 μl of water. The resulting solid was triturated with diethyl ether and evaporated to give &lt;RTI ID=0.0&gt;&gt; Butyl ester. Step 4: ((S)-3-Phenyl-1,2,2-tridecyl-propyl)-aminocarboxylic acid tert-butyl ester (244 mg, 1.12 mmol) was dissolved in dioxane (7.5 mL) And stir in an ice bath. Trifluoroacetic acid (3.5 mL) was slowly added, and the reaction was allowed to warm to room temperature and then stirred for 1 hour, then evaporated to dryness to give (s) _ _ _ _ _ _ Trifluoroacetate salt was used without further purification. Step 5 (S)-3-Amino-2,2-dimethyl-butan-1-ol trifluoroacetate (crude of Step 4) was dissolved in acetonitrile (3.75 mL)*. Add 2_cyclopropyl_5_(2_trimethylcalcene-ethoxymethyl)5H-dehydrazino[2,3-b]»比1»井_7·曱酸(25〇 Mg, 0.75 mmol) and bismuth tetrafluoroborate-benzotriazole_丨_yl_N,N,N,,N,_ra methylhydrazine (361 mg ' 1.12 mmol) and N,N_diisopropyl B Amine (46 mL, 2.62 mmol), and the mixture was stirred at room temperature for 18 hr. Water and ethyl acetate were added, the layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate Purification of the residue by gelatin chromatography (ethyl acetate / di-methane) afforded 13 〇 156 090. doc • 255 · 201204731 mg (40%) 2-cyclopropyl-5-(2-trimethyldecyl- Ethoxymethyl)_5h 〇 咯 并 [2,3-b]pyrazine-7-decanoic acid ((S)-3-hydroxy 4,2,2-trimethyl-propyl)-decylamine. Step 6 2-Cyclopropyl-5-(2-trimethyldecyl-ethoxyindenyl)-511 oxime is each [2, 3-1 &gt;]. More than '&gt; Well-7-decanoic acid ((8)-3-hydroxy-1,2,2-trimethyl-propyl)-decylamine (0.13 g '0.3 mmol) dissolved in 1.5 mL of di-methane And in the ice bath ^ but. N,N-Diisopropylethylamine (0.08 mL, 0.45 mm 〇1) was added, followed by the slow addition of hydrazine-burning helium (0.041 mL, 0.36 mmol). The reaction was allowed to warm to room temperature over 5 hours. A vaporized ammonium solution was added to the reaction, followed by extraction three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated to afford s[upsilon] </RTI> <RTIgt; </RTI> <RTIgt; </RTI> </RTI> <RTIgt; ) -5H-0 is more than D [2, 3-1 &gt;] ° ratio '&gt; Well-7-yl}-amino}-2,2-dimercapto-butyl ester, which is not further purified Ready to use. Step 7: (S)-3-{[2-Cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-n ratio in the microwave vial [ 2,3-b]&quot;Biprop-7-carbonyl]-amino}-2,2-dimethyl-butyl ester (the crude material from step 6) was dissolved in DMF (3 mL). Sodium decyl thiolate (0.2 g, 2.8 mmol) and 0.3 mL of water were added continuously. The vial was sealed and heated in a microwave reactor at ll 〇e C for 1 hour. The reaction was cooled and poured into ethyl acetate and sodium bicarbonate solution. The aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with EtOAc (EtOAc m. 2-trimethylsulfonyl-ethoxy 156090.doc -256- 201204731 methyl--5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-l,2,2 - Triterpene-3-3-methylthio-propyl)-bristamine. Step 8 2-Cyclopropyl-5-(2-tridecyldecyl-ethoxycarbonyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l , 2,2-Trisyl-3-mercaptothio-propyl)-decylamine (45 mg '0.097 mmol) was dissolved in THF (0-35 mL). Potassium perhydromonosulfate (0.18 g, 0.29 mmol) suspended in THF (1.3 mL) was added and the reaction was stirred for 5 hrs then stored in a freezer overnight. Add water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with sodium bicarbonate solution, dried over sodium sulfate and evaporated to give &lt;RTI ID=0.&gt;&gt;&gt; More than cultivating -7-decanoic acid ((S)-3-nonanesulfonyl-1,2,2-trimethyl-propyl)-decylamine, which was used without further purification. Step 9 2_Cyclopropyl-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyridin-7-decanoic acid. ((S)-3-nonanesulfonyl-1,2,2-trimethyl-propyl)-decylamine (45 mg, 0.097 mmol) was dissolved in dioxane (〇_7 mL). It was then stirred in an ice bath. Trifluoroacetic acid (〇. 3 mL) was added slowly and the ice bath was removed. The reaction was stirred for 3 hours then cooled again in an ice bath. Sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate The residue was dissolved in water-free ethanol (4 mL) and sodium acetate ( 159 mg, 1. The reaction mixture was stirred at 60 C for 16 hours' then cooled and water and ethyl acetate were added. The aqueous layer was extracted twice more with ethyl acetate and then washed with brine, EtOAc EtOAc EtOAc EtOAc EtOAc. The residue was purified by EtOAc (MeOH/EtOAc) toield of 17g (47%) of 2- </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; )-3-Methanesulfonyl 4,2,2-trimethyl-propyl) decylamine. MS: (M+H)+= 365; m.p. = 232. (:. Example 147. 2-[1-(3-Phenylphenyl)-1Η-π米0坐-4-yl]-5H-n 〇[2,3-b]° ratio p well- 7 -decanoic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

Step 1 4-Magh-1H-methanol (1.0 g' 5.16 mmol) was dissolved in THF (32 mL). Copper TMEDA catalyst (480 mg, 1.03 mmol, Aldrich) and 3-chlorobenzimate (0.56 g' 3.6 mmol) were added. Oxygen was bubbled through the reaction mixture for 20 minutes, then the mixture was stirred for 9 minutes. An additional 0.28 g of 3-chlorophenyl-acid was added, followed by oxygen bubbling for an additional 2 minutes and stirring at room temperature for 75 minutes followed by the addition of 0.28 g of 3-oxophenyl-acid, followed by an additional 20 minutes of oxygen bubbling. Then, it was stirred at room temperature for 2 hours. The reaction mixture was filtered through a pad of EtOAc (EtOAc) EtOAc (EtOAc) -111-. Meter. sit. 156090.doc •258- 201204731 Step 2

4-iodo-1-(3-phenylphenyl)-iH-imidazole (〇.76 g, 2 5 mm 〇1) was dissolved in anhydrous THF (13 mL). Gasified isopropyl magnesium (2 〇 Μ ΤΗρ solution, 1.56 mL, 3.12 mmol) was added dropwise. The reaction was stirred at room temperature for 1 hour. Tributylstannyl chloride (0.71 mL, 2.6 mmol) was added slowly. The gasification solution and ethyl acetate were added after the completion of the reaction by TLC. The aqueous layer was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried and evaporated. The residue was purified by EtOAc (EtOAc/EtOAc/EtOAc) . Step 3 2-Bromo-5-(2-tridecylfluorenyl-ethoxymethyl)-511_11 is conjugated to [2,3_b]. Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine (1 mg, 0.19 mmol) and 1-(3-phenylphenyl)-4- Tributylstannyl·1Η-imidazole (107 mg, 0-229 mmol) was dissolved in DMF (1.9 mL) and the reaction mixture was eluted with Ar gas. Further, hydrazine (diphenylphosphine) (11 mg, 0.010 mmol) and copper iodide (1) (7 mg, 0.03 8 mmol) were added, and the reaction was sealed at 1 Torr. Stir in an oil bath for 2 hours. The reaction was cooled and water, ethyl acetate and sodium bicarbonate solution were added. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine then dried over sodium sulfate. The residue was purified by EtOAc (EtOAc/EtOAc) toield 2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-l,2,2-tridecyl-propyl ) - guanamine. (M+H)+=553. 156090.doc ,259-201204731 Step 4 2-[l-(3-Gas-phenyl)-indole-imidazole. 4-yl]5-(2-trimethyldecyl-ethoxycarbonyl)-5Η- Pyrrolo[2,3-b]pyridin-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-bristamine (145 mg' 〇·26 mmol) dissolved in di-methane (1.6 mL) in 'then stirring in an ice bath. Trifluoroacetic acid (〇 8 mL) was added slowly and the ice bath was removed. The reaction was stirred for 2.5 hours and then cooled in an ice bath. A sodium bicarbonate solution was added, and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate dried The residue was dissolved in absolute ethanol (1 mL) and sodium acetate (430 mg, 5.24 mmol) was then evaporated. The aqueous layer was extracted twice with EtOAc then EtOAc EtOAc. The residue was purified by silica gel chromatography (MeOH/di-methane) to afford &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&& Bilopro[2,3-b]0 is compared to p-well-7-formic acid ((S)-l,2,2-tridecyl-propyl)-guanamine. MS: (M+H)+ = 423; m.p. = 337 - 339. Example 148. 2-[1-(3-Trifluoromethylphenyl)-iH-imidazol-4-yl]-5H-indolo[2,3-b]pyrazine-7-carboxylic acid ((s) -l,2,2-trimethyl-propyl)-guanamine

156090.doc • 260·201204731 Prepared in step 1 by replacing the 3-chlorophenyl-acid with 3-(trifluoromethyl)phenyl-acid according to the procedure outlined in Example 147. MS: (M+Na)+=479; melting point = 332-333 〇C. Example 149. 2-[1-(5-Gas-2-fluorophenyl)_111_imidazole_4_yl]_511_pyrrolo[2,3_^pyrid-7-carboxylic acid ((S)-i, 2 , 2-trimethyl-propyl)-decylamine according to Example 147

The procedure outlined is based on the substitution of a 3-carboxylic acid to form a point = 337-33 9 ° C. Example ISO. In step 1, use 2-fluoro-5-gas stupid MS: (M+Na)+=463; dissolve

Plowing -7·-°. Sodium-4-yl]-5H-° 〇[2,3-b]° ratio Trimethyl-propyl)-guanamine

The procedure outlined is prepared according to Example 147 by substituting 2-fluoro-5-mercapto 156090.doc-261. 201204731 phenyl lysine for 3-phenylphenyl-acid in step 1. MS: (M+Na)+=443; m.p. = 331 - 332. Example 151. 2-[1-(2-Fluoro-5-trifluorodecylphenyl)-1Η-imidazol-4-yl]-5Η-»bi-[2,3-b]pyrazine-7- Capric acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 1 by substituting 2-fluoro-5-(trifluorodecyl)phenyl-p-piconic acid for 3-p-phenylphenyl acid according to the procedure outlined in Example 147. MS: (M+Na)+= 497; m.p. &lt;3 00. Example 152. 2-(1-(3-methylphenyl)_1H-imidazole_4_yl)_5H_D than s-[2,3_b]eth argonic acid ((S)-l,2,2-triterpene Base-propyl)

Prepared according to the procedure outlined in Example 147, in step 1, using 3-methylphenyl group as an under-replacement of 3-hydroxyphenyl-ternic acid. Ms: (M+Na)+=425; melting point 156090.doc 201204731 =314-316〇C. Example 153. 2-(1-(3-Ethyl)-H-imidazo[2,3-end 7-formic acid ((S)-l,2,2-tridecyl-propyl)-醯amine

Prepared according to the procedure outlined in Example 147 by substituting 3-ethylphenyl-ternic acid for 3--phenylphenyl-acid. MS: (M+Na)+= 439; m.p. = 284-287 〇 C 0 </RTI> 154. 2-[1-(3-isopropylphenyl)-methane-imidazole_4_yl]_5H_n ratio [23]氺]〇比耕-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

N N

Prepared according to the procedure outlined in Example 147, substituting 3-isopropylphenyl-acid for 3- phenyl phenyl-p- acid in step 1 : (M+Na)+=453; 245〇C. 156090.doc •263 - 201204731 Example 155. 2-[l-(3-Secondylphenyl)_ih-imidazole_4_yl]_5H_pyrrolo[2 3 b]^ 耕-7-decanoic acid ( (S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 1 by substituting 3 tert-butylphenyl phthalic acid for 3-chlorophenyl-hydroxy acid according to the procedure outlined in Example 147. MS: (M+H)+=445; m.p. = 226-228 〇C 0 </RTI> 156. 2-[1-(3-(Ethylphenyl)-ih- imidazolyl] _5H_D than s-[23-b]I^ Plough-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 1 by substituting 3-vinylphenyl-acid for 3-phenylphenyl-acid according to the procedure outlined in Example 147. MS: (M+H)+= 415; m.p. = 253-257. Example 157. 156090.doc •264·201204731 2-(l,3-Dimethyl-1H-pyrazol-4-yl)-5H-°pyrho[2,3-b]pyrazine-7-formic acid ((S)-2-methoxy-1-indolyl-ethyl)-decylamine

Step 1 1,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborin-2-yl)-1Η- in a 25 mL pressure vessel Pyrazole (439 mg, 1.98 mmol), gasification clock (52 mg, 1.23 mmol) and 2-bromo-5-(2-trimethyl-stone-ethoxymethyl)-5H-0 [2,3-b]n was combined with p-well-7-decanoic acid (440 mg, 1.23 mmol) in ethanol (7 mL) and carbamide (7 mL), and the mixture was washed with n. Tripotassium citrate (917 mg ' 4.32 mmol) was dissolved in 4 mL of water and added to the mixture. After purging with N2, the gasified bis(triphenylphosphine)palladium (11) (87 mg, 0.12 mmol) was added, and the vessel was capped and stirred at 60-65 ° C for 20 hours. The cooled reactants were then diluted with ethyl acetate and water. The organic layer was washed with brine and dried and evaporated. The crude material was purified by flash chromatography (jjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj methyl_1H_pyrazole_4_yl)_5·(2-didecylsulfonyl-ethoxyindenyl)·5 Η-»Bilobut[2,3-b]° ratio tillage-7 - furfural. Step 2 2-(1,3-Dimercapto-1H-pyrazol-4-yl)-5-(2-trimethylhydrazine 156090.doc -265- 201204731 alkyl-ethoxylate at 5 C Methyl)-5Η-π ratio slightly [2,3-1]°° in p-well-7-曱 (440 mg, 1.18 mmol) in 1,4-dioxane (20 mL) A solution of amine sulfonic acid (690 mg, 7.11 mm 〇l) in water (7 mL) was added. A solution of NaC102 (139 mg, 1.54 mmol) and KH2P〇4 (161 mg, 1 _ 18 mmol) in water (4 mL) was then slowly added over 5 min. The ice bath was removed and the κ color 浑/蜀 reaction mixture was allowed to stand at room temperature for 2 hours. Half of the solvent was evaporated, the residue was poured into brine and extracted with EtOAc EtOAc EtOAc The combined organic phases were washed with brine and concentrated. The residue was purified by EtOAc (EtOAc) elut elut elut elut elut elut elut -1H-.Bizozol-4-yl)-5-(2-trimethyl-stone-ethoxycarbonyl)_5H-n than argonium [2,3-b]° . Step 3 In a round bottom flask, (S)-(+)-l-decyloxy-2-propylamine (23.2 pL, 0.22 mmol), N,N-diisopropylethylamine (38 μΐ^, 0.22 mmol And HATU (83 mg, 0.22 mmol) and 2-(1,3-dimethyl-1H-pyrazol-4-yl)-5-(2-trimethyldecyloxyethoxy)-5H -. More than [2,3_b]n was combined with plough-7-formic acid (85 mg '0.22 mmol) and DMF (10 mL) and stirred at room temperature for 20 hours. The reaction mixture was diluted with EtOAc (EtOAc)EtOAc. The combined organic phases were washed with brine and concentrated. The residue was purified by silica gel chromatography (MeOH/di-methane) to afford 2-(1,3-didecyl-1H-pyrazol-4-yl)-5-(2-trimethyl decyl-ethyl Oxymethyl)_5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-2-methoxy-1-methyl-ethyl)-bristamine. 156090.doc -266 - 201204731 Step 4 2·(1,3-Dimercapto-1H-pyrazol-4-yl)_5H-pyrrolo[2,3-b]pyridin-7-decanoic acid ((S )-2-methoxy-1-indolyl-ethyl)-guanamine. According to the procedure outlined in Step 5 of Example 1, '2-(1,3 - fluorenyl-1 Η-° ratio of sial-4-yl)-5-(2-trimethyl sulphate-ethoxy fluorenyl) )-5Η-π ratio slightly [2,3-b]° ratio p well-7-formic acid ((S)_ 2-methoxy-1-methyl-ethyl)-decylamine instead of 2-cyclopropyl -5-(2-trimethylsulfanyloxycarbonyl)-5H-° ratio 0 and [2,3-b] ° ratio p-well-7-formic acid [(R)-i_(i · Prepared by benzyl-cyclopentyl)-ethyl]-bristamine. MS: (M+H)+=329. Lu 158. 2-(5-Ethylaminoindolyl-s-phen-2-yl)-5H-. Ratio π and [2,3-b]° ratio 11 well-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Step 1 To the pressure tube, 2-bromo-5-(2-tridecyldecyl-ethoxymethyl)_5^[_pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S) -1,2,2-Trimethyl-propyl)-decylamine (500 mg ' 1.10 mmol) was added to a stirred solution of 4:1 dioxane / water (15 mL). Cef-5-nonionate (274 mg, 1.76 mmol) and K2C03 (455 mg '3 · 29 mmol). The reaction mixture was flushed with argon for 15 minutes, then PdCl2dppf.CH2Cl2 (90 mg, 0.11 mmol). The tube was sealed and heated at 120 °C for 18 hours, then cooled to room temperature and partitioned between water and Et.Ac 156090.doc • 267-201204731. The organic layer was dried over NazSCU and evaporated under reduced pressure. The crude residue was purified by EtOAc EtOAc EtOAc EtOAc (EtOAc) Base)· 5-(2-tridecyl-decyl-ethoxymethyl)-5H-° ratio 0 and [2,3-b]0 ratio p-well-7-decanoic acid ((S)- l,2,2-Trimethyl-propyl)-guanamine. LC-MS: 487 (M+H)+. Step 2 to 2-(5-Mercapto-β-cephen-2-yl)-5-(2-trimethyl-stone-ethoxycarbonyl)-5H-pyrrolo[2,3-b] Pyridin-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine (1.5 g, 3.09 mmol) in 1:1 dioxane/water (50 mL) Amine acid (1.8 g ' 18.51 mmol), sodium sulfite (0.36 g, 4.01 mmol) and KH 2 P 〇 4 (5.04 g, 37.03 mmol) were added to the mixing solution. The reaction mixture was stirred at 25 &lt;0&gt;C for 30 h then partitioned between water and EtOAc. through

The organic layer was dried over Na~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ _5_(2·trimethylsulfonyl-ethoxycarbonyl)-5H-pyrrolo[2,3-b]pyrrol-2-yl]-thiophen-2-indoleic acid without further purification Ready to use. [e-MS: 503 [M+H]+. Step 3 to 5-[7-((S)-l,2,2-tridecyl-propylaminecarbamyl)_5_(2·trimethylsulfonyl-ethoxymethyl)-5H- Add a triethylamine (0.22 mL) to a stirred solution of succinyl-2-methyl]-deuterophene-2-carboxylic acid (200 mg, 0.40 mmol) in THF. 1.6 mmol), PyBOP (416 mg, 0.80 mmol) and ethylamine (2.0 M THF solution '0.90 mL, 1.80 mmol). The reaction mixture was stirred at 25 ° C for 18 hours and then partitioned between water and Et0Ac. The organic layer was dried and evaporated under reduced pressure. </ RTI> </ RTI> 156090.doc - 268 - 201204731. The crude residue was purified by EtOAc EtOAc EtOAc (EtOAc) ·5_(2_Trimethyldecyl ethoxymethyl)-5 Η-pyrrolo[2,3-b]pyrazine_7_carboxylic acid ((S)-l,2,2-trimethyl- Propyl)-bristamine. LC-MS: 530 [M+H]+. Step 4

Heating 2-(5-ethylamine-mercapto-thiophen-2-yl)-5-(2·trimethylsulfonyl-ethoxymethyl)_5H-pyrrolo[2,3-b at 60 °C a stirred solution of pyridin-7-formic acid ((S)·i,2,2-dimethyl-propyl decylamine (150 mg, 0.28 mmol) in AcOH solution of 〇M HC1 for 3 hours. The reaction mixture was concentrated under reduced pressure. EtOAc m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m m Concentration by compression. The crude residue was purified by EtOAc EtOAc EtOAc (EtOAc) -5H-pyrrolo[2,3_b]pyrazine·7·decanoic acid ((s)_1,2,2-diindolyl-propyl)-guanamine. MS: (M+H)+=400. Example 159. 2-(5·Isopropylamine thiol-thiophene-2-yl)_5Η_pyrrolo[2,3_b]pyrazine_7_ decanoic acid ((S)-l,2,2-trimethyl Base-propyl) amide

156090.doc 201204731 Prepared in step 3 with isopropylamine in place of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=414. Example 160. 2-(5-Tertibutylaminocarbamimidyl-thienyl)_5H-npyrho[2,3_b]pyrazine-7-decanoic acid ((S)-l,2,2-three Mercapto-propyl)

Prepared in step 3 using a third butylamine in place of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=428. Example 161. 2-[5-(1-Mercapto-2-pyrazol-1-yl-ethylamine-mercaptothiophene-2-yl]-5H-pyrrolo[2,3-b]pyrazine_7 -formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

According to the procedure outlined in Example 158, the thiol_2_ was used in step 3. Bizol-1-yl-ethylamine was prepared in place of ethylamine. MS: (M+H)+=480. Example 162. 156090.doc • 270- 201204731 2-{5-[2-(4-Fluoro-phenyl)-1-indenyl-ethylamine-methylhydrazino]-thiophene-2-yl}_ 5H-pyrrole And [2,3-b]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl decylamine

Prepared according to the procedure outlined in Example 158, using 2-(4-fluoro-phenyl)-1-indolyl-ethylamine instead of ethylamine in step 3. MS: (Μ+Η)+=5〇δ. Example 163. 2-(5-Diethylamine-carbamoyl-thienyl)-5H-pyrrolo[2,3-b]pyr-7-nonanoic acid ((S)-l,2,2-trimethyl _propyl) _ guanamine

Prepared in step 3 by replacing diethylamine with diethylamine according to the procedure outlined in Example 158. MS: (M+H)+=428. Example 164. 2 [5 (4 f [2j3_b] 〇 tt 11 well formic acid ((S)-l, 2, 2_trimethyl-propyl) _ _ _ 156090.doc -271- 201204731

Prepared according to the procedure outlined in Example 158, in step 3, using 1-mercaptopiped instead of ethylamine. MS: (M+H)+=455. Example 165. 2-[5-((R)-l-cyclopropylethylamine-mercaptothiophene-2-yl]_5Η_β-pyrolo[2,3-b]pyrazine-7-decanoic acid (out Trimethyl-propyl decylamine r\

Prepared according to the procedure outlined in Example 158, using (R) 1 cyclopropylethylamine in place of ethylamine in step 3. MS: (M+h)+=440. Example 166. 2 {5-[(〇 咬-3-yl-f-yl)-amine 曱 基 】

156090.doc • 272·201204731 Prepared in step 3 by replacing 3-ethylamine with 3-(aminomethyl)pyridine according to the procedure outlined in Example 158. MS: (M+H)+=463. Example 167. 2-{5-[(Pyridin-4-ylmethyl)-aminemethanyl]-thiophen-2-yl}-5H-pyrrolo[2,3-b]pyrazine_7_decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 158, substituting 4-(aminomethyl) 0-pyridine for the ethylamine in step 3. MS: (M+H)+=463. Example 168. 2-{5-[(pyridin-2-ylindenyl)-aminoindenyl]-thiophen-2-yl}-511-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared by substituting 2-(aminomethyl)pyridine for ethylamine in step 3 according to the procedure outlined in Example 158. MS: (M+H)+=463. Example 169. 156090.doc -273· 201204731 2-[5-(4-Cyano-D-Chen-1-yl)-Phenyl-2-yl]-5H-%n[2,3_b] «i ratio tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 158 in step 3 by substituting e.g. MS: (M+H)+=465. Example 170. 2-[5-(Cyclopentylmercapto-amineindolyl)-thiophene-2-yl]_51^pyridinium[2 3_b] &quot; than tillage-7-decanoic acid ((S) -l,2,2-trimethyl-propyl)-decylamine

Prepared by substituting cyclopentylmethylamine for ethylamine in step 3 according to the procedure outlined in Example 158. MS: (M+H)+=454. Example 171. 2-[5-((R)-2-Synyl-indenyl-ethylaminoindenyl)-porphin-2-yl]_5Hpyrrolo[2'3-b]t well-7 - trimethyl propyl propyl propyl acetate 156090.doc • 274· 201204731

Prepared in step 3 by substituting (R) - 2 -aminopropan-1-ol for ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=430. Example 172. 2-[5-((R)-1-Methyl-2-phenyl-ethylaminemethyl)-[cephen-2-yl]_5H-.pyrho[2,3- b]pyrazine-7-decanoic acid tridecyl propyl) guanamine

The procedure 'prepared in step 3 with (R)-l-indenylamine. MS: (M+H)+=490.

Substituting the 2-phenylethylamine hydrochloride as outlined in Example 158 for the Example 173. 2-[5·(1-Pyridin-3-yl-ethylaminemethanyl)·thiophene_2_ [ 2,3-b]» than tillage-7-decanoic acid ((S)-l, 2, 2

Base]-5Η-σϋ σ each methyl-propyl)-guanamine 156090.doc -275- 201204731 According to the procedure outlined in Example 158, 1-pyridin-3-yl-ethylamine is used in step 3. Prepared instead of ethylamine. Ms: (m + h) + = 477. Example 174. 2 [5 (cyanomethyl-aminoindolyl)thienyl]pyrrolo[2,3_b]pyrimidin-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl )

Prepared according to the procedure outlined in Example 158, in step 3, using the amino-ethyl-ethylamine. The surface protecting group removal in step 4 was achieved using a TBA1^THF solution 〇M THF solution) under reflux for 16 hours followed by treatment with ethylenediamine. MS: (M+H)+=411. Example 175. 2-[5-(2-Aminosulfonyl-ethylaminemethylmercapto)-thiophene-2-yl]_5h_pyrrolo[2,3 oxime _7_carboxylic acid trimethyl-propyl Base)

Prepared according to the procedure outlined in Example 158, using 2-Aminoethyl 156090.doc •276·201204731 alkanesulfonamide instead of ethylamine in step 3, using THF solution in TBAF (1·〇Μ THF solution) The SEM protecting group removal in step 4 was achieved by refluxing for 16 hours followed by treatment with ethylenediamine. MS: (M+H)+=479. Example 176. 2-[5-(2-Myryl-1-yl-1-indenyl-ethylaminoindolyl)_0-septene-2-yl]_5-pyrrolo[2,3-b] Pyridine. Well-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 1 58 by substituting 2-imidazole-i-yl-1-mercaptoethylamine for ethylamine in step 3. MS: (M+H)+=480. Example 177.

2-[5-(4-Hydroxy-4-methyl·piperidine-hydrazinyl)-thiophene-2-yl]_511_pyrrolo[2,3-b]pyrazine-7-decanoic acid (on, Trimethyl-propyl decylamine

According to the procedure outlined in Example 158, in Example 3, hydrazine was prepared by replacing the ethylamine with hydrazine-piperidin-4-ol hydrochloride. Ms: (m+h)+=47〇. 156090.doc •277· 201204731 Example 178. 2-[5-(l-Methyl-2-d-But-2-yl-ethylamine oxime)_嗟 _2_2_基]_5H-pyrrole [2,3-b]pyrazine-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared in step 3 by substituting 1-methyl-2-pyridin-2-yl-ethylamine for ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=491. Example 179. 2-[5-(7-Azabicyclo[2.2.1]heptane-7-carbonyl)-thiophen-2-yl]-511-pyrrolo[2,3-b]. Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 3 with 7-azabicyclo[2.2.1]heptane hydrochloride instead of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=452. Example 180. 2-[5-(3-Cyano-azetidin-i-remediate)-porphin-2-yl]-5 H-° ratio π and [2,3-b]pyrr Plough-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine 156090.doc -278- 201204731

Prepared according to the procedure outlined in Example 158, substituting az. The SEM protecting group removal in step 4 was achieved using THF solution of TBAF (1. 〇 μ THF solution) under reflux for 16 hours followed by treatment with ethylenediamine. MS: (Μ+Η)+=437. Example 181. 2-[5-(3-Aminocarboxylidene-azetidinyl)- sin-2-yl]·5Η. Bilo and [2,3-b]pyrazine-7-carboxylic acid ((S)-l,2,2-tridecyl-propyl decylamine

Separation was performed as another product of Example 180, Step 4. MS: (M+H)+=455. Example 182. 2-[5_(Azetidin-1-carbonyl)-thiophene-2-yl]_5H-pyrrolo[2,3-b]pyr-7-carboxylic acid ((S)-l,2 ,2-trimethyl-propyl)-guanamine 156090.doc • 279- 201204731

Prepared according to the procedure outlined in Example 158, substituting az. The SEM protecting group removal in step 4 was achieved using a THF solution of TBAF (1.0 M in THF) under reflux for 16 hours followed by treatment with ethylenediamine. MS: (Μ+Η)+=412. Example 183. 2-[5-(2,6-Dimethylpyridin-1-yl)-porphin-2-yl]-511-11 piroxi[2,3-b]pyrazine-7 -formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared in step 3 with 2,6-dimethylpiperidine in place of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=468. Example 184. l-{5-[7-((S)-l,2,2-tridecyl-propylamine-branthyl)_5H-0 ratio 0 each [2 3*&gt; b]pyrazine -2-yl]-thiophene-2-carbonyl}-piperidine-4-decanoic acid 156090.doc •280· 201204731

Prepared in step 3 by substituting methyl piperidine-4-methylformate for ethylamine according to the procedure outlined in Example 158. The methyl ester is hydrolyzed to the acid after coupling. MS: (M+H)+=484. Example 185. 2-[5-(4-Ethylamino)-N-pyridinyl carbonyl-based phenyl-2-yl]-5H-pyrrolo[2,3-1)]pyrazine-7-carboxylic acid (3 )-1,2,2-trimethyl-propyl)-decylamine

Prepared in step 3 using N-piperidin-4-yl-acetamide instead of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=497. Example 186. 2-[5-(4-Methylphenylhydrazinylcarbinyl)-thiophen-2-yl]-5H-pyrrolo[2,3_b]pyrazine-7-decanoic acid ((S) _l,2,2-trimethyl-propyl)-decylamine 156090.doc • 281 - 201204731

Prepared according to the procedure outlined in Example 158, using 4-mercaptobenzylamine in place of ethylamine in step 3. MS: (M+H)+=476. Example 187. 2-[5-(4-Fluorobenzylaminecarbamyl)-thiophene-2-yl]-5H-pyrrolo[2,3-b]pyridin-7-carboxylic acid ((S)- l,2,2-trimethyl-propyl)-nitramine

Prepared according to the procedure outlined in Example 158, using sub- benzylamine instead of ethylamine in step 3. MS: (M+H)+=480. Example 188. 2-[5-(2,3-Dibenzophenanthrylcarbenyl)-thiophene, 2-phenyl]-5. Bis-[2'3m7-carboxylic acid ((sww-trimethyl-propyl)-nitramine

156090.doc •282· 201204731 Prepared in step 3 by replacing the ethylamine with 2,3·dioxalinamide according to the procedure outlined in Example 158. Ms: (Μ+Η)+=531. Example 189. 2-[5-(2-Methylphenylhydrazinylmethyl)-yl.塞 1 1 Μ] Μ·pyrrolo b]° than morphine formic acid ((8)], 2,2-trimethyl-propyl) decylamine

Prepared according to the procedure outlined in Example 15 8 in step 3 by replacing the ethylamine with 2-methylthiomethylamine. MS: (Μ+Η)+=476. Example 190. 2-[5-(2,6-Dilacylbenzylamine sulfhydryl)_«»cerebrene-2-yl]_5Η-β ratio 11 and [2,3-b] -7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 3 using 2,6-difluoromethaneamine in place of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=498. Example 191. 156090.doc -283-201204731 2-[5-(2-Gas-6-fluorobenzylaminecarbamyl)-propenyl]_5H-° ratio [2,3-b]. Specific tillage-7-formic acid ((S)-1,2,2-trimethyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 158 in step 3 by replacing the ethylamine with 2- _ _ _ _ benzene benzylamine. MS: (M+H)+=515 » Example 192. 2-[5-(2-Mercaptocyclohexylaminemethanyl)·thiophene-2-yl]_51^ ratio slightly [2 % bp than tillage - 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

Prepared in step 3 using 2-methylcyclohexylamine in place of ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=468. Example 193. 2-[5-((lS,2R)-2-phenylcyclopropylaminemethanyl)·thiophene-2-yl]_51^_1]Biha[2,3-b]pyrazine -7-decanoic acid ((S)-l,2,2-trimethyl-propyl decylamine 156090.doc •284- 201204731

Phenylcyclopropylamine hydrochloride was prepared in place of ethylamine. Ms: (m + h) + = 488. Example 194.

2-{5-[(4.methylnonphen-2-ylmethyl)-amine-branthyl], phen-2-a}511 〇 洛 洛 并 [2,3 仲 末 7-carboxylic acid ((8) ten - trisyl-propyl)

Prepared according to the procedure outlined in Example 158, substituting (4-methylthiophen-2-yl)-nonylamine for ethylamine in step 3. The SEM protecting group removal in step 4 was achieved using a THF solution of TBAF (M THF solution) for 16 hours under reflux followed by treatment with ethylenediamine. Then: (Μ+Η)+=482. Example 195. 2_{5-[(5-Methylfuran-2-ylindenyl)-amine fluorenyl]-thiophene-2·yl b 5Η_pyrrolo[2,3-b]pyrazine-7- Formic acid (out trimethyl-propyl) amide 156090.doc -285 · 201204731 Μ r ·

Prepared according to the procedure outlined in Example 158, substituting ethyl-2-amine). The THF solution was used for 16 hours under reflux followed by removal of the SEM protecting group from step 4. Ms: (m + h) + = 466. Example 196. In step 3, (5-mercaptofuran TBAF in THF solution (1.0 ethylenediamine treatment to achieve step 2·[5_(金冈(四)·1-ylamine 曱)) -5H』比略和[2,3_b] than well 7曱酉夂((8)],〗 〖·三曱基_propyl)_醯amine

Prepared according to the procedure outlined in Example 158, using adamantane-bromoamine hydrochloride instead of ethylamine in step 3. MS: (M+H)+=5〇4. Example 197. 2-{5-[1-(4-Fluoro-phenyl)-ethylamine fluorenyl]-thiophene-2-yl 2 5 Η ππ-[2,3-b]pyrazine-7- Formic acid (on, trimethyl-propyl decylamine 156090.doc •286· 201204731

Prepared according to the procedure outlined in Example 158, substituting 1-(4- phenylphenyl)-ethylamine for ethylamine in step 3. MS: (M+H)+=494. Example 198.

2-[5-(Methoxymethylaminecarbamyl)-°cephen-2-yl]-5H-D is more than '1 each [2,3_bJ. Specific tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared in step 3 by substituting N, 〇-dimethylhydroxylamine hydrochloride for ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=4丨6. Example 199. 2-(5-Methoxyaminodecylthiophene-2-yl)_511_pyridinium[2,3_b]pyrazine·7_carboxylic acid ((S)-l,2,2-triterpene Base-propyl)

156090.doc -287-201204731 Prepared according to the procedure outlined in Example 158, in step 3, using hydrazine-methyl instead of ethylamine. MS: (M+H)+=402. Example 200. 2-(5-Propan-2-carbylamine-mercapto-thiophene-2-yl)-5-indole-[bibino[2 3-b].啩-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

Prepared according to the procedure outlined in Example 158, using a propargylamine in place of ethylamine in step 3: MS: (M+H)+=410. Example 201. 2-{5-[(R)-2-(3H-imidazol-4-yl)-1-methyl-ethylamine decyl]-thiophene-2-yl}-511-pyrrolo[2 ,3-b]吼耕-7-decanoic acid ((S)-1,2,2-trimethyl-propyl)-decylamine

Prepared in step 3 by substituting (r) - 2 - (3h - imidazolyl-4-yl)-1-mercaptoethylamine dihydrochloride for ethylamine according to the procedure outlined in Example 158. Ms: 156090.doc • 288-201204731 (M+H)+=480 ° Example 202. 2-[5-(5,6,7,8-tetrahydronaphthalene-2-ylaminemethanyl)_thiophene_ 2_基]_5H•pyrrolo[2,3-b]吼h-7-decanoic acid ((8)_1ί2,2_trimethylpropyl)-nitramine

Prepared according to the procedure outlined in Example 158, using hydrazine, ??-tetrahydronaphthalen-2-amine instead of ethylamine in step 3. MS: (Μ+Η)+=5〇2. Example 203. 2-(5-Phenylaminoindolyl- porphinyl-2-yl)5Η·〇比和和[2,3_b]pyridin·厂甲l((S)-l,2,2- Triterpene-propyl)

Substituting aniline for B in step 3 was prepared according to the procedure outlined in Example 158. MS: (M+H)+=448. Example 204. Alkyl)-porphin-2-yl]-5H-. Biha 156090.doc 201204731 and [2,3-b]pyrh-7-carboxylic acid trimethyl-propyl)-guanamine

Prepared in step 3 by substituting (R)_丨_(bucket-methylphenyl)-ethylamine for ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=490. Example 205. 2-[5-(2-Methoxybenzylaminocarbamoyl)-oxet-2-yl]_5 仏〇 π[2,3-b]吼耕-7-carboxylic acid (ο.,,,Trimethyl-propyl) decylamine

Prepared according to the procedure outlined in Example 158, in step 3 using 2-methoxybenzylamine in place of ethylamine. MS: (M+H)+=492. Example 206. 2-[5_(2,5-Dimethoxyphenanthrylaminomethane)-thiophen-2-yl]-5H-pyrrolo[2,3-b]pyrazine_7_decanoic acid ((shut•trimethyl·propyl)_decylamine 156090.doc -290- 201204731 η

The program, in step 3, uses 2,5. MS: (Μ+Η)+=522. Dioxane was prepared according to the phenyl hydrazine amine as outlined in Example 158 instead of ethylamine.

2-{5_[(4-fluorophenylindenyl)~methyl-amine-methylidene]•(4)·2·基卜5t and [2,3 handsome than 7-carboxylic acid ((8) trimethyl-propyl) amine

Prepared according to the procedure outlined in Example 158, in the step 3, substituting ethylamine. MS: (Μ+Η)+=494. Example 208. 2-[5-(3-Methoxybenzylaminoindenyl)-thiophene-2.yl]-5Η-. Ratio of [2,3-1)]° to -7-decanoic acid ((8)-1,2,2-trimethyl-propyl)-decylamine

Vy ijO^o 156090.doc • 291 · 201204731 Prepared according to the procedure outlined in Example 158, in step 3, using 3-methoxybenzophenone instead of ethylamine. Ms: (M+H)+=492. Soil example 209. Tri-gas methyl-methylamine hydrazine base)·« ··2·基]_5H “比” each ^ J ^ Λ.Λ. 9^ [2,3-b]t well·7·formic acid ((SM, 2, 2 trimethyl-propyl)_nitramine

Prepared in step 3 by substituting 3 - trifluoromethyl benzylamine for ethylamine according to the procedure outlined in Example 158. MS: (M+H)+=530. Example 210. 2-[5-(2-Ga-4-iodophenylaminemethanyl)-thiophene-2-yl]-5H-pyrrolo[2 3 bp than tillage-7-decanoic acid ((S) -l,2,2-trimethyl-propyl)-decylamine

Alkyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrylene-2-yl]-thiophene-2-methyl 156090.doc -292· 201204731 acid (150 mg, 0.30 mm〇l To a stirred solution of anhydrous pyridine was added HATU (228 mg '0.60 mmol) and 2-chloro-4-indoleaniline (38 mg, 15 mmol). The reaction mixture was stirred at room temperature for 72 hr then evaporated under reduced pressure and partitioned between water and EtOAc. The organic layer was dried over NaaSO4 and concentrated. The crude residue was purified by EtOAc EtOAc EtOAc (EtOAc) -thiophen-2-yl]-5-(2-tridecylfluorenyl-ethoxyindolyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l,2 , 2-trimethyl-propyl)-guanamine.

Step 2 2-[5-(2-Chloro-4-iodophenylaminomethane)-thiophene-2-yl]_5h_pyrrolo[2,3-b]. Than cultivating -7-decanoic acid trimethyl-propyl) amide. According to the procedure outlined in Step 4 of Example 170, 2-[5-(2-carb-4-iodo-phenylamine-mercapto)-inden-2-yl]-5-(2-trimethyl)矽alkyl-ethoxymethyl)-5H-pyrido[2,3-1)]pyrene _7-decanoic acid ((8)_1,2,2_trimethyl-propyl)_醯Amine instead of 2-(5-ethylaminemethylmercapto-thiophene-2-yl)_5_(2_trimethyldecyl-ethoxycarbonyl)-5H-D than s-[2,3-b] Pyridine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine was prepared. MS: (M+H)+=608. Example 211. 2-[5-((R)-l,2,2-tridecyl-propylaminoindolyl)-thiophene-2-yl]_5Hpyrrolo[2,3-b]pyp well ·7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

156090.doc •293· 201204731 Step 1 Stir 5-[7-((S)-l,2,2-trimethyl-propylaminecarbamyl)_5_(2-trimethyldecyl) at room temperature _Ethoxymethyl)_5Hpyrrolo[2,3_b0t__2_yl]·°Cet-2-carboxylic acid (0.042 g' 0.084 mmol), 2 mL anhydrous dioxane, (R)_3,3-methyl Butan-2-amine (〇.〇25 mL, 0.19 mmol), 4-dimethylamino 0-bite (0.012 g, 0.101 mmol) and N-(3-didecylaminopropyl)-Ν A solution of ethyl carbodiimide hydrochloride (〇〇37 g, 〇19〇mm〇1) for 4 hours. Add two gas methane (1 〇 mL), and wash the solution sequentially with 1 〇 mL 1 μ citric acid solution, 10 mL water, 1 〇 mL 10% NaOH solution and 1 〇 mL water, then dry with NaJO4, filter and concentrate. , 〇〇74 g (&gt;100%) is a yellow film-like trimethyl-propylamine-methyl sulfhydryl)-- phenyl-2-yl]-5-(2-trimethyl sulphate-B The oxymethyl group is a mixture of [2,3-b]pyrylene-7-formic acid trimethyl-propyl)-guanamine which can be used without further purification. MS: (M+Na)+=608 » Step 2 The above-prepared crude 2-[5-((R)-l,2,2-tridecyl-propylaminecarbamyl) was stirred at room temperature. Thiophen-2-yl]-5-(2-tridecylfluorenyl-ethoxymethyl)_ 5H-pyrrolo[2,3_b]pyrrole-7-decanoic acid tridecylpropyl) decylamine, A solution of 1 mL of CHaCh and 1 mL of trifluoroacetic acid for 2 hours was then concentrated to a yellow residue. To the residue was added 〇·5 mL of dioxane and 0.5 mL of ethylenediamine. The yellow solution was stirred for 90 minutes and then partitioned between 1 〇 mL of acetic acid and 5 mL of water. The aqueous layer was extracted with 1 mL of ethyl acetate. The combined organic layers were dried <RTI ID=0.0>: </RTI> <RTIgt; Column chromatography (80-1〇〇%£1〇(:/hexane), 〇.〇18§(46%, two steps) 156090.doc •294· 201204731 Light yellow solid 2- [5-((R)-l,2,2-Trimethyl-propylaminemethanyl)-thiophen-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-l,2,2-Trimethyl-propyl)-guanamine. MS: (M+Na)+= 478. Example 212. 2-[5-(2,2-dimethyl- Propylamine-mercapto)-thiophen-2-yl]-5H-pyrrolo[2,3-b]pyr-7-nonanoic acid ((S)-l,2,2-tridecyl-propyl )-guanamine

Prepared in step 1 with 2,2-dimethyl-propylamine in place of (R)-3,3-dimethylbutan-2-amine according to the procedure outlined in Example 211. MS: (M+Na)+=464. Example 213. 2-[5-((R)-2-nonanesulfonyl-1-methyl-ethylamine decyl)-thiophene-2·yl]-5H_〇fcL-[2, 3_b]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

According to the procedure outlined in Example 158, in step 3, (R)·Bu (methyl 156090.doc -295· 201204731 醯 )) propan-2-amine hydrochloride was used instead of ethylamine to prepare β continuation. The SEM protecting group removal in step 4 was carried out with tfa and CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=492. Example 214. 2-[5-(1,1-Di-Ethyl-hexahydro-1-thioxo)-4-ylaminocarbamoyl)-septin-2-yl]-5-pyrrole [2,3-b]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Prepared according to the procedure outlined in Example 158, substituting (1, 丨-dioxosyltetrahydro-2H-thiopiperazin-4-yl)amine hydrochloride for the ethylamine in step 3. The SEM protecting group removal in step 4 was continued with TFA and CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=504. Example 215. 2-[5-(1,1-Di-Sideoxy-1-thiomorpholine-4-carbonyl)-thiophen-2-yl μ5Η d than bromo[2,3-b]pyridin- 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-nitramine

156090.doc -296- 201204731 Prepared according to the procedure outlined in Example 1 5 8 in step 3 by replacing the ethylamine with 1 1 thiomorpholine. The &apos;-dioxo was continued with step 4A and removed with Τρ CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=490 » T sulfhydryl example 216. 2-[5-(2-methoxy-1-methylethylamine amide) thiophene 2 yl]&quot;* 5 Η - and [2,3-b]pyrazine-7-formic acid ((S)-l,2,2-trimethacillyl W ^ T丞-propyl)-decylamine

制备 Prepared according to the procedure outlined in Example 1 58 by substituting b-propan-2-amine for ethylamine in 少少乡3. Step 4φ + was carried out with TFA CH 2 Cl 2 /MeOH/NH 4 OH (80:19:1). Long Ding &lt; sem protection base

Remove. MS: (M+H)+=444. &quot; Soil Example 217. 2-(5-Aminomethylmercapto-indol-2-yl)-5H-0 to 0 and [2,3-b]° than well-7-decanoic acid ((S) -l,2,2-trimethyl-propyl)-guanamine

156090.doc -297· 201204731 Prepared according to the procedure outlined in Example 158, using 1,1,1-trifluoropropan-2-amine in place of ethylamine in step 3. It is presumed that the title compound is derived from the initially formed 1,1,1-trifluoro-2-propylamine or the impure 1,1,1-tris-propyl-2-amine starting material. The SEM protecting group removal in step 4 was carried out using TFA and CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=372. Example 218. 2-[5-(3,3,3-Trifluoropropylaminemethanyl)-sole-2-yl]_511-° ratio (1 each [2,3- b] pyridin- 7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

According to the procedure outlined in Example 158, use 333 _ three in step 3.

Remove. MS: (M+H)+=468. Example 219.

11 each [2,3-b]pyridin-7--formic acid ((S)-l,2,2·trimethyl-propyl)-guanamine

156090.doc -298·201204731, prepared in step 3 with 2-oxa-6-azaamine. Step-removal was carried out by using TFA and replacing the SEM protecting group CH2Cl2/Me〇H/NH4OH (80:19:1) in step 4 according to the procedure outlined in Example 158. . MS: (M+H)+=454. Example 220. 2-[5-(3,3-bis(tetra)indolyl-cyclohexane?········································· -7-carboxylic acid ((8)-yis-trimethyl-propyl)-decylamine

Separation as a by-product of Step 4 of Example 219. MS: (M+H)+=472. Example 221. 2-[4-Methyl-5-(tetrahydropyran-4-ylamine oxime)_thiophene-2-yl]_511_pyrrole φ and [2,3_b]pyrazine_7_曱Acid ((s)_1,2,2·trimethyl-propyl)·guanamine

The base 4-methyl group was used in step 1 according to the procedure outlined in Example 158. Desphen-2-ylfolic acid replaces 2-indenyl. This is prepared by the use of tetra-argon-2H-piperidin-4-amine hydrochloride in place of ethylamine in Step 3 156090.doc •299·201204731. The SEM protecting group removal in step 4 was continued with TFA and CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=470. Example 222. 2-[5-(1,1-Pentyloxy-1 -thio-infrared-4-pyryl)-4-methyl-porphin-2-yl]-5H-pyrrolo[2 , 3-b]pyridin-7-formic acid trimethylpropyl)_

Substituting 5-methylmercapto-4-methylthiophen-2-ylnic acid for 2-methylmercaptothiophene-5-folic acid in step 丨 according to the procedure outlined in Example 158, and using ι in step 3 , ι-dithiomorpholine is prepared in place of ethylamine. The SEM protecting group removal in step 4 was carried out by continuing to use TFA and CH2Cl2/Me〇H/NH4〇H (8〇:19:1). MS: (M+H)+=504. Example 223.

]]-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid tridecyl-propyl) 156090.doc -300- 201204731

According to the procedure outlined in Example 158, in the step, 5-nonyl-4-methylthiophen-2-yl-acid was substituted for 2-mercaptothiophene-5-gmin acid, and in step 3, 2- Oxa-6-azaspiro[3.3]heptane hemioxalate was prepared in place of ethylamine. The SEM protecting group removal in step 4 was continued with TFA and CH2Cl2/MeOH/NH4OH (80:19:1). MS: (M+H)+=468. Example 224. 2-[5-(3,3-Dihydroxyindenyl-azetidin-1-carbonyl)-4-methyl-thiophen-2-yl]-5H-. Bis-[2,3-b]indole-7-decanoic acid ((S)_l,2,2-trimethyl-propyl)-decylamine

Separation as a by-product of Step 4 of Example 223. MS: (M-H)-=484. Example 225. 2-[5-(tetrahydro d-butan-4-ylamine fluorenyl)_°cephen-2-yl]-5Η-β ratio σ[2,3-b]〇 ratio ρ Well_7_Cyanoacetic acid-1,2,2-trimethyl-ethyl)-bristamine 156090.doc -301 - 201204731

Step 1 (S)-3-Amino-2,2-dimercapto-butyronitrile hydrochloride was prepared according to Step 1-3 of Example 141. Step 2 Combine 2 -Molybdenum-5-(2-trimethylglycine ethoxymethyl)-5H-° in the case of burning and compare [2,3-b]0 to argon-7-decanoic acid ( 1.10 g' 2.95 mmol), (S)-3-amino-2,2-dimethyl-butyronitrile hydrochloride (439 mg, 2.95 mmol), EDC (1.30 g, 6.80 mmol) and HOBt (1.15 g) , 6.80 mmol). DMF (27 mL) and i-Pr2NEt (3.6 mL, 20.7 mmol) were added. The reaction mixture was stirred at room temperature for 1.5 hr then quenched with water andEtOAc. Use 10. The organic phase was washed with citric acid, saturated NaHC03, saturated LiCl and saturated NaCl, then dried and concentrated with MgSO 4 . The residue was purified by EtOAc EtOAc EtOAc (EtOAc) Methyl)_5H_pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S)-2.cyano-1,2,2-tridecyl-ethyl)-decylamine. Step 3 According to the procedure outlined in Example 1 58, in step 1 2__________2曱-mercaptoalkyl-ethoxymethyl)_5H-pyrrolo[2,3-b]pyrazine -7-decanoic acid ((S)-2·cyano-1,2,2·tridecyl-ethyl)_decylamine instead of 2_bromo_5_(2_trimethyl 156090.doc •302· 201204731矽alkyl-ethoxymethyl)_511-»Birtho[2,3-13]° Trulli-7-carboxylic acid ((8)-1,2,2-trimethyl-propyl)-guanamine And in step 3, 4-(5·(tetrahydropyran-4-ylaminecarbamyl)_ sultane is prepared by replacing tetraethylamine with tetrahydro-21^-«-pyran-4-amine hydrochloride. 2-base]_5Η_. More than [2,3_b]pyrazine_7_carboxylic acid ((S)_2-cyano-1,2,2-trimethyl-ethyl)-guanamine. The SEM protecting group removal in step 4 was continued with TFA and ethylenediamine. MS: (Μ+Η)+=467. Example 226. 2-[5-(Piperidine-1-carbonyl)-thiophene-2-yl]-5-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyano) -ΐ,2,2·tridecyl-ethyl decylamine

According to the procedure outlined in Example 158, in step 1, 2-bromo-5-(2-dimethyl-stone-ethoxycarbonyl)-5H-indole was used to compare [2,3_b]n. Bijing-7-formic acid ((S)-2-cyano-1,2,2-tridecyl-ethyl)-decylamine instead of 2·bromo-5_(2_trimethylsulfonyl-ethoxy曱 ))-5 H- ° is more than [2,3_b] ° than phenyl-7-formic acid (Ο-ΐ'2,2-trimethyl-propyl)-decylamine, and in step 3 Prepared by piperidine instead of ethylamine. The SEM protecting group removal in step 4 was continued with TFA and CH2Cl2/MeOH/NH4(R) (90:9:1). MS: (M+H)+=467; melting point = 253. 257. Example 227. 2-[5-(Tetrahydro-piperazin-4-ylaminoindolyl)-thienyl]_5Η·pyrrolo 156090.doc 201204731 [2,3-b]. Specific tillage-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine

Step 1 2-Bromo-5-(2-tridecyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((S) in a microwave vial -l,2,2-Trimethyl-propyl)-decylamine (100 mg '0.22 mmol) was dissolved in 5:1 dioxane / water (6 mL). The vial was flushed with argon, followed by the addition of 5-(methoxycarbonyl)thiophene-2-ylpyrrolic acid (45 mg, 0.24 mmol), Na2CO3 (70 mg, 0.66 mmol) and Pd(PPh3)4 (13 mg , 0·011 mm〇l). The vial was sealed and heated in a microwave reactor at 140 °C for 1 hour. In addition, a certain amount of 5-(methoxycarbonyl) °-cephen-2-yl-acid (23 mg '0.12 mmol) and Pd(PPh3) 4 (6 mg, 0.005 mmol) were added, and in a microwave reactor at 14 The reaction was heated again for 1 hour at 〇t. The reaction was repeated on the same scale and the crude reaction mixture was combined and partitioned between water and EtOAc. Saturated NaHC.sub.3 was added and the aqueous layer was extracted with EtOAc (2x). The combined organic layers were washed with brine then dried over Na.sub.4 and evaporated. The crude residue was purified by EtOAc EtOAc (EtOAc) elute Methylmercapto)-5-(2-dimethylmethylalkylethoxyphenyl)_5h_d is a methylpyrazine-2-yl J-thiophene-2-carboxylate. 156090.doc •304. 201204731 Step 2 5-[7-((S)-l,2,2-Trimethyl-propylaminemethanyl)-5-(2-tridecylfluorenyl-B Methyloxymethyl)-5H-pyrrolo[2,3-b]pyrylene-2-yl]-thiophene-2-carboxylate (90 mg, 0.17 mmol) was dissolved in THF (1 mL) and dec. 0.5 mL). A solution of gas oxidized (29 mg, 0.70 mmol) in water (1 mL) was slowly added. The solution was stirred for 2 hours. Then water and ethyl acetate were added. The pH was adjusted to 3, the layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layer was washed with brine <RTI ID=0.0> Methyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrylene-2-yl]-thiophene-2-carboxylic acid, which was used without further purification. Step 3 5-[7-((S)-l,2,2-Trimethyl-propylaminemethanyl)_5_(2_trimethylsulfanyl-ethoxyindolyl)-5H- &quot;比比和[2,3-b]. Tr.-2-yl]-thiophene-2-carboxylic acid (87 mg '0.17 mm〇i), benzotriazole-mercapto-N,N,N',N'-tetradecyl fluorene tetrafluoroborate 61 mg, 〇19 mm〇1) and N,N diisopropylethylamine (0.10 mL, 0.52 mmol) were dissolved in acetonitrile (17 mL). Tetrahydro-2H-pyran-4-amine hydrochloride (26 mg, 〇 19 mm 〇 1) was added, and the mixture was stirred at room temperature for 18 hr. Water, dilute HC1 solution and ethyl acetate were added, and the layers were separated. The aqueous layer was extracted twice with acetic acid. The crude residue was purified by EtOAc (EtOAc) (EtOAc) 2_基]_5_(2_tridecylsulfanyl-ethoxyindenyl)·5Η “Biloze[2,3_b]t well·7-formic acid ((8)·^2 trimethyl _ 156090.doc •305 - 201204731 propyl)-guanamine. Step 4 2-[5-(Tetrahydro-piperidylamine thiol)thiophene-2-yl]·5_(2·trimethyldecyl-ethoxyl )5Η-η比比和[2,3-b]D ratio tillage_7_formic acid ((s)_ 1,2,2-dimethyl-propyl)·decylamine (8〇mg, 〇137 Mm 〇 1) dissolved in dichlorohydrazine (1 mL), followed by stirring in an ice bath. Slowly add trifluoroacetic acid (0.4 mL) and remove the ice bath. Stir the reaction for 3 hours, then cool in ice bath. The sodium bicarbonate solution was added, and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in anhydrous ethanol (6 mL) and sodium acetate was added. (224 mg, 2.7 mmol). The mixture was stirred at 60 ° C for 20 hours. The reaction was cooled and water and ethyl acetate were added. The aqueous layer was extracted twice with ethyl acetate. EtOAc (EtOAc m. %) 5-[5-(tetrahydro-piperidylamine sulfhydryl)-thiophen-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ((",,,,-trimethyl-propyl-polyamine. MS: (M+H)+=456; melting point = 333-334. (3. Example 228. 2-(5-benzoinyl) Aminomethyl-thiophene-2-yl)_5H_pyrrolo[2,3_b]pyridin-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine

156090.doc 0 •306· 201204731 Step 1 Dissolve 0 captopril acid (0.5 g, 2·9 mmol) in THF (12 mL). Add 1, fluorene-carbonyl dimethine. The reaction was stirred (0.47 g, 2 9 mm 〇l) and the reaction was allowed to stand at room temperature for 1 hour. Benzylamine (〇 32 mL, 2.9 mmol) was slowly added and the reaction was stirred for 18 hours. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed with a chlorinated solution, dried over sodium sulfate and evaporated to give &lt;RTI ID=0.0&gt;&gt;&gt; Na)+=284. Step 2 In a microwave vial, 2-but-5-(2-trimethyl-stone-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid (( S)-l,2,2-Trimethyl-propyl)-decylamine (100 mg '0.22 mmol) was dissolved in 5:1 dioxane / water (6 mL). The vial was purged with argon&apos; followed by the addition of 5-(benzylammonium)thiophene-2-carboxylic acid (86 mg, 0.33 mmol), Na2CO3 (70 mg, 0.66 mmol) and

Pd(PPh3)4 (13 mg '0.011 mmol). The vial was sealed and heated in a microwave reactor at 150 °C for 0.5 hours. In addition, a certain amount of 5-(phenylhydrazinyl fluorenyl) °-cephen-2-yl-tanning acid (40 mg, 0.15 mmol) and Pd(PPh3)4 (6 mg, 0.005 mmol) were added in the microwave. The reaction was heated again at 140 ° C for 1 hour in the reactor. The reaction mixture was cooled and partitioned between water and EtOAc. Saturated NaHC.sub.3 was added and the aqueous layer was extracted with EtOAc (2x). The combined organic layers were washed with brine, then dried over NazSO4 and evaporated. The crude residue was purified by EtOAc EtOAc EtOAc (EtOAc) 5-(2-trimethylsulfanyl-ethoxymethyl)-5Η-° ratio η[2,3-b] ° ratio 156090.doc • 307- 201204731 Well·7-formic acid ((s )-i, 2,2-trimethyl-propyl)-guanamine. Step 3 2-(5-Benzylaminoindenyl-thiophen-2-yl)_5_(2-trimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3_b]pyrazine _7_Tridecyl-propyl) decylamine (65 mg, 011 mm 〇1) was dissolved in dichloromethane (〇 8 mL), followed by stirring in an ice bath. Add trifluoroacetic acid 4 slowly and remove the ice bath. The reaction was stirred for 3 hours then cooled in an ice bath. A sodium hydrogen carbonate solution was added, and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was dissolved in dry ethanol (7 rnL) and sodium acetate (18 〇 mg, 2.2 mmol) was added. The mixture was simmered at 60 C for 2 hrs. The reaction was cooled and water and ethyl acetate were added. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The crude residue was purified by EtOAc (EtOAc/EtOAc) )_5H_pyrrolo[2,3-13]pyrazine-7-carboxylic acid ((!5)-1,2,2-tridecyl-propyl)-decylamine. River 8: (M+H)+=462; melting point = 225-226. (:. Example 229. 2-[5-(3-Cyanobenzoylaminocarbazyl)-thiophene-2-yl]_5H_„pyrho[2,3_b]pyrazine-7-carboxylic acid (( s)-i,2,2-trimethyl-propyl)-guanamine

0 156090.doc -308 · 201204731 Prepared according to the procedure outlined in Example 228, in step 1, using 3-cyanobenzylamine instead of benzoguanamine. MS: (M+H)+ = 487; m.p. = 171 - 174. Example 230. 2-(3-Cyano-p-oxy)_5Η_Π比比和[2,3_b]n ratio tillage_7-formic acid isopropylamine

Step 1 2-Bromo-5-(2-trimethyldecyl-ethoxymethyl)_5H-pyrido[2,3-b]pyridin-7-decyl isopropyl hydrazine in a pressure tube Add 3-cyanophenol (87 mg, 〇73 mmol), K3P〇4 (204 mg, 0.96 mmol) and 2-second to the stirred solution of the amine (200 mg, 0.48 mmol) in toluene (5 mL) Butylphosphino _ 2'-(N'N-didecylamino)biphenyl (24 mg, 〇.〇7 mm〇i). The reaction mixture was thoroughly purged with argon for 20 minutes, followed by the addition of Pd(〇Ac) 2U1 mg, • 〇·05 mm〇l). The tube was sealed and the reaction mixture was dried with EtOAc EtOAc (EtOAc) The combined organic layers were washed with brine, dried over anhydrous Na. The residue was purified by column chromatography eluting with EtOAc EtOAc (EtOAc) eluting eluting 3-cyano-phenoxy)-5-(2-trimethylsulfanyl-ethoxyphenyl)-5H-pyrrolo[2,3-b]pyrrol-7-decanoic acid isopropyl Guanamine. Step 2 156090.doc •309· 201204731 Heating 2-(3-cyano-phenoxy)-5-(2-tridecylfluorenyl-ethoxyindolyl)-5H-pyrrole at 65 °C [2,3-b] A stirred solution of pyridin-7-isopropyl decylamine (160 mg '〇_3 5 mmol) in 1.0 M EtOAc (5 mL) EtOAc. The reaction mixture was concentrated under reduced pressure and the residue was evaporated, mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj At 25. (The reaction mixture was stirred for 18 hours, then concentrated under reduced pressure. EtOAc EtOAc m. Cyanophenoxy) 5H-&quot; bis-[2,3-b]pyrazine-7-formic acid isopropylamine. MS: (M+H)+=322. Example 231. 2-( 3-methoxyphenoxy)-5H-» ratio slightly [2,3-b]n than argon-7-decyl isopropylamine

0 - Prepared in step 1 by replacing 3-cyanophenol with 3-methoxyphenol in accordance with the procedure outlined in Example 230. MS: (M+H)+=327. Example 232. 2-(3-Trifluoromethoxyphenoxy)_5H-° ratio [2,3-b]. Bijing-7-isopropyl decyl phthalate 201204731

Prepared according to the procedure outlined in Example 230, substituting 3-(trifluoromethoxy)phenol for 3-cyanophenol in the step oxime. MS: (M+H)+=381. Example 233. ® 2-(3-Butylphenoxy)-5H-pyrrolo[2,3_b]pyrazine_7-formic acid isopropylguanamine

According to the procedure outlined in Example 230, 3_t-butyl is used in step 1.

Phenol is prepared by substituting 3-cyanophenol. MS: (M+H)+=353. Example 234. Methylphenoxy)_5H_pyrrolo[2,3_b]pyrrol_7_isopropyl decyl decylamine

156090.doc -311 - 201204731 Prepared according to the procedure outlined in Example 230, in step 1, by replacing the 3-alkenyl phenol with 3- benzyl benzene. MS: (M+H)+=3 11. Example 235. 2. (3-Ethylphenoxy)_5H_ and [2,3 secondary ratio „and_7_carboxylic acid isopropylamine

Prepared according to the procedure outlined in Example 230, using 3-ethylbenzene in the next step instead of 3-cyanophenol. MS: (M+H)+=325. Example 236. 2-(3-Isopropylphenoxy)_5H-indolo[2,3_b]pyrylene·7-formic acid isopropyl decylamine

According to the procedure outlined in Example 230, in the step (4), 3-cyanobenzene was used instead of 3-cyanophenol to prepare "MS: (Μ + Η) + = 339. Example 237. 2-(3-Tris-decylphenoxy)·5Η·pyrrolo[2,3_b]pyr? _ isopropyl guanamine 156090.doc -312- 201204731

According to the procedure of the pepper in Example 230, +. ^ ^, the procedure was followed in the first step by replacing 3-cyanophenol with 3-(trifluoromethyl)phenol. MS: (M+H) = 365. Example 238.

2 (2-fluoromethylphenoxy) each [2,3_leaf ratio p well_7_decanoic acid isopropylamine

Prepared in step 1 with 2-(trifluoromethyl)benzene in place of 3-cyanophenol according to the procedure outlined in Example 230. MS: (M+H)+=365. Example 239. 2-(2-Benzylphenyloxy)_5H-.倍比和[2,3-b]&quot;比耕-7-isopropyl decyl citrate

156090.doc • 313-201204731 Prepared according to the procedure outlined in Example 230, in the step [instead of 2-cyanophenol in place of 3-cyanophenol. MS: (M+H)+=3 87. Example 240. 2-(2-Ethylphenoxy)_5H-pyrrolo[2,3-b]pyrazine-7·isopropyl hydrazide hydrazine

N N

Prepared according to the procedure outlined in Example 230, in step 1, using 2-ethylphenol instead of 3-. Ms: (m+H)+=325. Example 241. 2-(5'6,7'8-tetrahydronaphthyloxy)_5H•pyrrolo[2,3 ton]pyrazine_7_decanoic acid Isopropylamine

Prepared according to the procedure outlined in Example 230 using 5,6,7,8-tetrahydronaphthalene small (tetra) 3 cyanobenzene. Ms: (m+h)+=35i. Example 242. (,6,7,8 tetrahydronaphthalen-2-yloxy)_5Η·〇比嘻[2,3-b] Wells Small formic acid Isopropylamine 156090.doc •314· 201204731

Prepared in step 1 with 5,6,7,8-tetrahydronaphthalen-2-ol in place of 3-cyanophenol according to the procedure outlined in Example 230. Ms: (M+H)+=351. Example 243.

2_(naphthalen-1-yloxy)-5H-. More than [2,3_b]n than _7_ isopropyl decyl decanoate

Prepared according to the procedure outlined in Example 230, in step 1, substituting naphthalocyanine for 3-cyanogen. Ms: (m+H)+=347. Example 244. 2 (Naphthalene-2-yloxy)n each [2, 3 minutes final 7-formic acid isopropylamine

The e Ms was prepared in step 1 using naphthalen-2-phenol in accordance with the procedure outlined in Example 230, 156090.doc-315-201204731, 3-cyanophenol: (m+h)+=347. Example 245. 2-(3-Vephenoxy)_5H-w[2,3_b]i^soparaglycol isopropylamine

Prepared according to the procedure outlined in Example 230, using 3- oxophenol instead of 3-cyanobenzene in the step oxime. Ms: (m+h)+=332. Example 246. 2-(3-Vephenoxy)_5H-pyrrolo[2,3_b]pyrazine_7-formic acid ethylguanamine

According to the procedure outlined in Example 230, in step 1, 2•bromo-5_(2-dimethylindenyl-ethoxymethyl)_5Hpyrrolo[2,3_b]pyrazine_7_decanoic acid B was used in step 1. Alkylamine replaces 2-act-5-(2-trimethyldecyl-ethoxyphenyl)_5H_„ than 11 and [2,3-b]n than argon-7-decyl isopropyl hydrazine Amine, and 3 - chlorophenol was used instead of 3 - cyanide to prepare ^ MS: (Μ + Η) + = 318. Example 247. 2-(3-Cyano-p-oxy)·5Η-〇比洛和[2 , 3-b]° than tillage-7·formic acid ethylguanamine 156090.doc 201204731

CN According to the procedure outlined in Example 230, in the step i, 2-bromo-5-(2-trimethylsulfanyl-ethoxymethyl)-5Η-π&amp; 0 each [2, 3 -b]«Comparatively, 2-bromo-5-(2-trimethyl-stone-ethoxylated thiol)_5H-° ratio of each of the 2,3-b ]&quot; Prepared by cultivating -7-isopropyl isopropylamine. MS: (M+H)+=308. Example 248. 2-(3-Trimethoxymethoxyphenyl)-5H-° than Haha[2,3-b]° Ratio Well-7-Acetyl Ethylamine

According to the procedure outlined in Example 230, in step 1, 2-bromo-5-(2-trimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3-b]fluorene was used. Replacing 2-bromo-5-(2-tridecyldecyl-ethoxymethyl)·5Η•pyrrolo[2,3-b]pyrazine-7- Isopropyl decanoate is prepared by substituting 3-(cyanooxy)phenol for 3-cyanophenol. MS: (M+H)+=367. Example 249. 156090.doc 317-201204731 2-(3-Thryl T-phenoxy) each [2,3-sec-(tetra)_7-carboxylic acid ethyl decylamine 0

According to the procedure outlined in Example 230, in step 1, 2·bromo-5-(2-trimethylglycolyl-ethoxymethyl)_5H"Bilo#[2,3_b]吼_7-formic acid B was used. Alkylamine replaces 2-di-5-(2_tridecyl(tetra)yl-ethenylmethyl(tetra)-pyrene-[2,3-zhong&quot;-7-formic acid isopropylamine, 33 _T-butyl phenylhydrazine instead of 3 · gas is basically prepared. ms: (m + H) + = 33 9. Example 250. 2-(3-methylphenoxy) _5 Η _β ratio 咯 [2, 3_b Pyridine formate

0 hn^V^n^ K H

According to the procedure outlined in Example 230, in step 1, 2_bromo-5-(2-dimethyl-stone-ethoxymethyl)-5H-n is used in the ratio of 2,3_b]D. Ethyl decyl formate replaces 2-&gt; odor _5_(2·trimethyl sulphate-ethoxymethyl)_5Η_ηΛ succinct [2,3-b]t well _7·τ isopropyl decyl amide And prepared by replacing 3 - cyanophenol with 3 曱 base. MS: (Μ+Η)+=297. Example 251. 156090.doc -318- 201204731 2-(3-Ethylphenoxy)-5H-° ratio 咯[2,3-b]. Specific tillage-7-formic acid ethylguanamine

According to the procedure outlined in Example 230, in step 1, 2_ ____(2_ 曱 石 夕 - ethoxy-ethoxymethyl)-5H-° piroxi[2,3-b]°« Ip well-7-formic acid•ethyl decylamine replaces 2_bromo-5-(2-tridecylfluorenyl-ethoxymethyl)_5H_pyrrolo[2,3-b]pyrazine-7-曱Isopropyl decylamine was prepared and replaced with 3-ethylphenol in place of 3-cyanophenol. MS: (M+H)+=311. Example 252. 2-(3-Isopropyloxy)_5H-° ratio [2,3-1?]° ratio well-7-decanoic acid ethylguanamine

According to the procedure outlined in Example 230, in the step oxime, 2-bromo-5-(2-dimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3_b]pyrazine_7-decanoic acid ethyl was used. Indoleamine replaces 2-bromo-5((2·tridecyloxyalkyl)ethoxymethyl)_5Η_^ ρ and [2,3-15]° ratio -7-7-isopropyl decyl decylamine, And using 3 · isopropyl benzene instead of 3- cyan is basically prepared. Ms: (Μ+Η)+=325. Example 253. 156090.doc -319· 201204731 2-(3-Difluoromethylphenoxy)-5H-pyrrolo[2,3-b]pyridinium-7-decanoic acid ethylguanamine

According to the procedure outlined in Example 230, in step 1, 2_bromo-5-(2-dithiocarbazide-ethoxymethyl)_5Η-ηBilo[2,3_b]» - Ethyl decylamine is substituted for 2-bromo-5-(2-tridecyldecyl-ethoxyindenyl)-5 penspiro[2,3-b]. It was prepared by substituting -7-formic acid isopropylamine and replacing 3-cyanophenol with 3-(trifluoromethyl)phenol. MS: (μ+η)+=351. Example 254. 2-(2-Methylphenoxy)-5Η·pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropyl decylamine

Prepared in step 1 by replacing 2-cyanophenol with 2-methylphenol according to the procedure outlined in Example 230. MS: (M+H)+=311. Example 255. 2-(2-Difluoromethoxyphenoxy)pyrolo[2,3-b]0 than tillage-7-formic acid isopropylamine 156090.doc -320- 201204731

λ/ Prepared according to the procedure outlined in Example 230, using 2-(trifluoromethoxy)phenol instead of 3-cyanophenol in the step 丨. MS: (Μ+Η)+=381. Example 256. 2-(2,2-Dimercapto-2,3-dihydrobenzofuran-7-yloxy)_5Η-pyrrolo[2,3-b]n is isopropyl-7-carboxylic acid isopropyl Base amine

〇MS was prepared according to the procedure outlined in Example 230, using 2,2-dimercapto-2,3-dihydro-7-hydroxy-benzofuran instead of 3-cyanophenol in the step :: (M+ H)+=367 = Example 257. 2-(2-Chlorophenoxy)-5H-n than arden[2,3_b]pyrazine_7-formic acid isopropyl decylamine

CI 156090.doc -321-201204731 Prepared according to the procedure outlined in Example 230, using 2-chlorophenol instead of 3-cyanophenol in the step oxime. MS: (M+H)+=332. Example 258. 2-(2-Methoxyphenoxy)-5H-pyrrolo[2,3_b]pyrazine_7-carboxylic acid isopropyl

The guanamine was prepared according to the procedure outlined in Example 230 by substituting methoxybenzene for the 3-cyanophenol in the step oxime. MS: (M+H)+=327. Example 259. 2-(2-Methylphenoxy)·5Η, each [2,3 帅比啡_7_甲酉曼ethylenylamine 0 HN^V^N ～ Μ Η

According to the procedure outlined in Example 230, in step 1, 2_bromo-5-(2·trimethyldecyl-ethoxymethyl)_511_pyrrolo[2,3_b]pyrazine_7_formic acid B was used. Alkylamine instead of 2-wet_5_(2_trimethylglyoxime-ethoxyl group)_511_debido[2,3-b]^b$-7-f acid isopropyl decylamine 'And prepared with 2-methylphenol instead of 3-cyano. MS: (M+H)+=297. 156090.doc -322- 201204731 Example 260. 2-(3,5-Dimethoxyphenoxy)·5Η-. Specific ratio of [2,3-b]° to -7-formic acid isopropylamine

Prepared in step 1 by substituting 3,5-dimethoxyphenol for 3-cyanophenol according to the procedure outlined in Example 230. MS: (m+h)+=3 5 7. Example 261. 2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)-511-pyrrolo[2,3-15]pyrazine-7-carboxylic acid ethyl ethamine

According to the procedure outlined in Example 230, in step 1, 2-bromo-5-(2-dimethylindenyl-ethoxymethyl)-5H_pyrrolo[2,3_b]pyridin-7-formic acid B was used. Replacement of 2-bromo-5-(2-tridecylfluorenyl-ethoxyindenyl)-51{_pyrrolo[2,3-b]pyrazine-7-decyl isopropyl decylamine with guanidinium It was prepared by substituting 5,6,7,8-tetrahydronaphthalene-1-phenol for 3-cyanophenol. MS: (M+H)+=337. 156090.doc •323 - 201204731 Example 262. 2-(5'6,7,8-tetrahydronaphthalen-2-yloxy)·5Η_0 piroxi[2,3b]〇n7-carboxylic acid ethyl decylamine

According to the procedure outlined in Example 230, in step 1, 2·bromo-5·(2-trimethylsulfanyl-ethoxymethyl). 〇 略 并 [2,3 b]D than the brown · 7-formic acid ethyl guanamine in place of 2-bromo-5-(2-trimethylsulfonyl-ethoxymethyl)_5Η-pyrolo[2,3-b]tt7·isopropyl cumylamine, and It was prepared by substituting 5,6,7,8-tetrahydronaphthalene-2-phenol for 3-cyanophenol. MS: (M+H)+=337. Example 263. Acid ethyl guanamine 2-(naphthalene-buyloxy)-5H-pyrrolo[2,3_b]pyrazole_7_A 0

N N

Trimethyldecyl-ethoxymethyl)_5H_pyrrolo[23b]pyrazine_7-decanoic acid ethyl hydrazine instead of 2_ desert·5·(2-tris-yl(tetra)yl-ethoxy fluorenyl ) -5H-port ratio is slightly [2,3-b] than well 7-formic acid isopropylguanamine, and is prepared by substituting naphthalene as a substitute for I56090.doc •324·201204731 phenol. Ms: (M+H)+=333. Example 264. 2_(Naphthalen-2-yloxy)_5H_^ bromo[2,3_b]pyrazine·7-formic acid ethyl guanamine 〇

According to the procedure outlined in Example 230, in step 1, 2-bromo-5-(2-dimethyldecyl-ethoxymethyl)_5Η•pyrrolo[2,3b]pyrazine_7-formic acid was used. Ethyl decylamine replaces 2-bromo-5-(2-tridecylfluorenyl-ethoxyindenyl)-5H-n-pyrolo[2,3-b]pyridin--7-decanoic acid isopropyl The base amine is prepared by substituting naphthalene-2-phenol for 3-cyano. MS: (M+H)+=333. Example 265. 2-(3,5-Dimethoxyphenoxy)_5Η_declozolo[2,3_b]indole ratio tillage_7_carboxylic acid ethyl

According to the procedure outlined in Example 230, in step 1, 2_bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazole 11 was used - Substituting 2-bromoformic acid ethyl guanamine for 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyridyl 156090.doc -325- 201204731 oxo[2,3-b]pyridin It was prepared by cultivating _7_isopropyl decyl decanoate and replacing 3 - cyanophenol with 3,5-dimethoxy phenol. MS: (M+H)+=343. Example 266. 2-(3-Methoxyphenoxy)-5H-0 ratio slightly [2,3-b]° ratio tillage-7-formic acid ethyl decylamine

According to the procedure outlined in Example 230, in step}, bromo-5-(2-dimethylindenyl-ethoxyindenyl)·5Η_pyrrolo[2,3_b]pyrazine_7_formic acid B was used in step}. Replacement of 2-bromo-5-(2-tri-f-decyl-ethoxymethyl)-511-pyrrolo[2,3-b]pyrazine-7-decyl isopropyl decylamine with guanidinium Prepared by replacing 3-cyanophenol with 3-methoxyphenol. MS: (M+H)+=313. Example 267. 2-(2-Vephenoxy)-5m B each [2,3_b]pyrazine_7-formic acid ethylguanamine 0

According to the procedure outlined in Example 230, in step 1, the ratio of 2·bromo-5-(2 methyl sulphate-ethoxymethyl, smectite, 0, and [2,3-b]e was used.耕-7-甲_ 156090.doc -326- 201204731 Ethyl decylamine replaces 2_bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H-u ratio [2,3 -b]pyrazine _7·isopropyl decyl citrate' and prepared by replacing 2 - phenol with cyanobenzene. MS: (M+H)+=318. Example 268. 2_(4-cyanide Phenoxy group)-5Η·η ratio 咯[2,3 handsome ratio „well_7_isopropyl decyl amide

CN was prepared according to the procedure outlined in Example 230 using cyanophenol in place of 3-cyanophenol in the step 丨. Ms: (Μ+Η)+=322. Example 269. 2-(4-Cyanophenoxy)_511_対[2,3 hrs vs. _ethyl formate

CN According to the procedure outlined in Example 230, in the step 丨, 2_bromo-5-(2_trimethyl-stone-acetoxy-indenyl)-5-pyrene and [2,3-b]t- 7-formic acid ethyl guanamine replaces 2-moiety three f-based sulphur-based ethoxymethyl) Qin. The ratio of 'and U,3-b]t well _7_ isopropyl acetamide was prepared and replaced with 4-cyanobenzene to replace 3-cyanophenol. Ms: (m+H)+=3〇8. Example 270. 156090.doc 327·201204731 2-((R)-3-nonanesulfonylaminoindan-5-yloxy)-5H-»pyrrolo[2,3_b]pyrazine-7 -Isopropylamine formate

Step 1 To a solution of (R)-3-aminoindan-5-ol (1 mg, 0.67 mmol) in THF (4 mL) 〇6〇mmol) and triethylamine (o.ii mL, 〇·8〇mmol). The reaction mixture was stirred at room temperature for 18 hours, then the solvent was evaporated. The residue was partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc. The residue was purified by silica gel chromatography using Et EtOAc / hexanes as solvent (yield: </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Tert-butyl phthalate. Step 2 To 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5H_pyrrolo[2,3_b] than well-7-formic acid isopropylamine (250 mg, 0.60) Add ((r)_6·hydroxyindane-fluorenyl) to a stirred solution in toluene (5 mL), dimethyl succinate (190 mg, 0.78 mmol), Κ3ΡΟ4 (250 mg, 1.20 mmol) and 2-di-t-butylphosphine*_2,_(n,n-dimethylamino)biphenyl (41 mg '〇· 12 mmol). The reaction mixture was thoroughly purged with argon for 20 minutes, and Pd(OAc) 2 (13 mg, 0·06 mmol) was added after 156090.doc - 328 - 201204731. The reaction mixture was heated at <RTI ID=0.0></RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; The combined organic layers were washed with brine, dried over anhydrous Na. The residue was purified by silica gel (100-200 mesh) column chromatography using 20-60% EtOAc /hexanes [7-Isopropylamine indanyl-5-(2-tridecylfluorenyl-ethoxyindolyl)-5H-pyrrolo[2,3-b]pyridin-2-yloxy]- Indole-l-yl}-amino decanoic acid · third butyl g. Step 3 to {(R)-6-[7-isopropylaminecarbazide-5-(2-trimethylsulfanyl-ethoxymethyl)-5H-° at 〇 °C And [2,3-b]. Specific cultivating 2-ethyloxy]-indan_ι_yl}-tert-butyl carbamate (45〇111§'0.77 111〇1) in a stirred solution in anhydrous 1^0 called 10 mL) Ethyl hydrazine (1 〇 9 mL, ι 5 46 mmol) was added dropwise. After the addition, the mixture was allowed to warm to room temperature and was stirred for 2 hours. The reaction mixture was concentrated under reduced pressure and at room temperature to afford 2-((())-amino-------- 5-yloxy). The group of ethoxylated hydrazino)-5Η-»pyrolo[2,3_b]pyrazine-7-decyl isopropyl decylamine hydrochloride was used without further purification. Step 4: 2-((R)-3-Amino-pump-5-yloxy)·5_(2·trimethylsulfanyl-ethoxyindolyl)-5Η-pyrrole at 0 C And [2,3-b]pyridin-7-decyl isopropyl decylamine hydrochloride (200 mg, 0.38 mmol) in a stirred solution of dichloromethane (8 mL) Ethylethylamine (0.29 mL, h66 mm 〇1) and methane sulfonium (0.038 mL, 0.49 mmol). The reaction mixture was stirred at EtOAc ( EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc. The residue was purified by column chromatography using EtOAc/hexanes as a solvent to give a solvent (yield: 170 mg (73%) as a gray solid. Amino-p--5-yloxy)-5-(2-trimethylsulfanyl-ethoxymethyl)-5H-0 is more than [2,3-b]0 7-Isopropylamine decanoate. Step 5 to 2-((R)-3-methyl-decylamino-indanyl-5-yloxy)_5_(2_trimethyl-stone-alkyl-B Oxymethyl)-5Η-&lt;Ό each [2,3-b]° than argon-7-isopropyl decylamine (170 mg, 0.30 mmol) in anhydrous THF (5 mL) Tetrabutylammonium fluoride (1.0 M THF solution, 6.0 mL, 6 mmol) and ethylenediamine (0.40 mL, 6.0 mmol) were added to the stirred solution. The reaction mixture was heated under reflux for 18 hours, then cooled to room temperature and quenched with water. It was extracted and extracted with ethyl acetate (3 &lt;&lt;&gt;). The combined organic phases were dried over NazSCU and concentrated. Column chromatography using 2-5% MeOH/CH.sub.2Cl.sub.2 as eluting solvent to purify residue to afford 43 mg (34%) as a white solid. 5-(yloxy)_5H-° piroxi[2,3-b]°fc till -7-formic acid isopropylamine MS: (M+H)+=430. Example 271. 2-(( R)-3-Ethylaminoindaninyl _5_yloxy)·5Η_0 pyrrolo[2,3_b] cultivating -7-isopropyl cuminamide 156090.doc •330· 201204731

Prepared according to the procedure outlined in Example 270, in step 4, replacing the methanesulfonyl chloride and diisopropylethylamine with acetic acid and cockroach. ·: _)+ = 394. Example 272. 2-((R)-3-decanesulfonylaminoindan-5-yloxy)_5Η_πpyrho[2,3 b] ° than argon-7-decanoate ethylguanamine 〇

According to the procedure outlined in Example 270, in step 2, 2_ _________ _ _ _ _ _ _ _ ethoxymethyl)-5H-n pirox [2,3-b] ° Replacement of 2-bromo-5-(2-trimethylsulfanyl-ethoxymethyl)_5η_πpyrho[2,3-b]咐·"-7 - Isopropylamine formate is prepared. MS: (M+H)+=416. Example 273. 156090.doc •331 · 201204731 2-((R)-3·Ethylaminoindanin-5_yloxy)_5H-pyrrolo[2,3-b]»比耕-7- Ethyl decyl citrate

According to the procedure outlined in Example 270, 2-mer-5-(2-trimethylsulfonyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine was used in step 2. 7-formic acid ethyl guanamine in place of 2-bromo-5-(2-tridecylfluorenyl-ethoxyindolyl) oxo[2,3-b]pyrazine-7-formic acid isopropyl guanamine, And in step 4, acetic anhydride and pyridine are used instead of methanesulfonium chloride and diisopropylethylamine. MS: (M+H)+=380. Example 274. 2_(1Η-° 丨 丨 朵 -6-6-yloxy)-511-° ratio [2,3-b]. Ratio °-7-formic acid isopropylamine

Μ Step 1 Add 6-butane dicarbonate (19 mL, 9 向) to 6-glycol (0.40 g, 3.00 mmol) in MeCN (15 mL) 156090.doc •332· 201204731. Mm 〇 1), DMAP (0.184 g '1.5 mmol) and triethylamine (1 2 mL, 9 〇〇 mmol) ^ The reaction mixture was stirred at 25 ° C for 16 hours, then the solvent was completely distilled off. The residue was purified by silica gel (100-200 mesh) column chromatography using EtOAc EtOAc / EtOAc (hexane) Butoxycarbonyloxy_吲哚_dic acid tert-butyl ester. Step 2 Add 6-second butoxycarbonyloxy-indole-carboxylic acid tert-butyl ester (丨〇吕, • 3.00 mm〇1) to a stirred solution of di-methane (2〇mL) Morpholine (7.8 mL, 90·1 mm〇l). The reaction mixture was stirred at 25 °C for 2 hrs, then the solvent was completely distilled off. The residue was purified by column chromatography using 10-20% EtOAc / hexanes eluting solvent to afford EtOAc (35 g) The base is called 丨 π _ 1 _ formic acid third vinegar. Step 3 to 2·bromo-5-(2-tridecylfluorenyl-ethoxymethyl)_5Hpyrrolo[2,3_lub]pyrazine-7-decyl isopropyl decylamine (550 mg, 1.33 mmol) 6-hydroxyindole-indole-tert-butyl tributyl acrylate (466 mg, 2.00 mmol), K3P〇4 (564 mg, 2 66 mm) in a solution of hydrazine (1 mL) 〇1)&2_di-tert-butylphosphino-2'-(N,N-didecylamino)biphenyl (136 mg, 〇4〇mmol) ° thoroughly purge the reaction mixture with argon 2 〇 min, then add Pd (OAc 〇 2 (5 8 mg ' 0.26 mm 〇 i). Heat the reaction mixture at 14 ° ° (: 18 hours), then cool to room temperature, quench with water (2 〇 mL) and use Extracted with EtOAc (3×1 mL), EtOAc (EtOAc) (EtOAcjjjjjjjj The residue was purified using 20-60% EtOAc/hexanes eluted eluted eluted Erythryl ethoxycarbonyl)-5H-° piroxime [2,3-b]° ratio isopropyl decyl citrate. Step 4 〇°C to 2-(1Η-吲哚-6-yloxy)-5-(2-trimethyldecyl-ethoxymethyl)-5H-.pyrho[2,3-b Add a solution of trimethylacetic acid (1 mL) to a stirred solution of sulphonic acid sulphonic acid (63 mg, 0.135 mmol) in dioxane (5 mL). After a few hours, the solvent was removed under reduced pressure. The residue was dissolved in i: 1 MeOH / di-methane (5 mL) and ethyldiamine (2 mL) was added at room temperature. The reaction mixture was stirred for 18 hours and then concentrated under reduced pressure. The crude residue was purified by preparative hplc to give 3.8 mg (8%) of 2-(lH-indol-6-yloxy)-5H- &quot;比 并 [2,3-b]pyrazine-7-isopropyl decyl decylamine MS: (M+H)+=336. Example 275. 2-(1Η-吲哚-6-yloxy )_5H-pyrrolo[2,3-b]pyrazine-7-decanoic acid ethylamine

According to the procedure outlined in Example 274, in step 3, 2-bromo-5-(2-methyl-stone-ethoxymethyl)-5H-pyrrolo[2,3-b]pyridin was used. Plough-7-formic acid 156090.doc 201204731 Ethyl decylamine replaces 2-bromo-5-(2-tridecylfluorenyl-ethoxyindolyl)-511_pyridyl 11 each [2,3-b]. Prepared by cultivating _7_isopropyl decylamine. mS: (M+H)+=322. Example 276. 2-(1Η-Indol-4-yloxy)-5H-pyrrolo[2,3-b]pyridin-7-decanoic acid isopropylamine

Prepared in step 1 with 4-hydroxyindole instead of 6_ via the base according to the procedure outlined in Example 274. MS: (M+H)+=336. Example 277. 2-(1Η-吲哚_4-yloxy)·5η·pyrrolo[2,3_b]pyrazine_7-decanoic acid ethyl decylamine 0

According to the procedure outlined in Example 274, in step 1, 4 hydroxy hydrazine was substituted for 6 _ hydrazine hydrazine, and in step 3, 2-bromo-5-(2-trimethyl decyl- 156090 was used. .doc •335 · 201204731 Ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ethyl decylamine in place of 2-bromo-5-(2-trimethyldecyl) Ethoxymethyl)·5Ηpyrrolo[2313]indole is prepared as well as 7-formic acid isopropylguanamine. MS: (Μ+Η)+=322. Example 278. 2-(1-Indolyl-1Η-吲哚-6-yloxy)_5Η_0pyrolo[2,3_b]pyrazine_7-isopropyl decylamine

Step 1 Add 2_(1H_吲哚_6_yloxy) to a stirred suspension of NaH (60o/〇 in mineral oil, 36 mg, 0.90 mmol) in anhydrous DMF (10 mL). -5-(2-tridecylfluorenyl-ethoxycarbonyl)_5H_0pyrho[23b] 0 than argon-7-isopropyl decyl citrate (275 mg, 0.59 mmol) in anhydrous DMF ( Solution in 5 mL). The reaction mixture was stirred at 25 ° C for 30 minutes, then cooled to 0 ° C and iododecane (44, 0.70 mm )l) was slowly added. The reaction mixture was stirred at 25 ° C for 3 hours, then DMF was distilled off. The crude residue was purified by silica gel column chromatography eluting with 7% ethyl acetate to give 2-(1-mercapto-1H-indole-6- as a yellow oil. The group oxy)-5-(2-trimethylsulfanyl-ethoxymethyl)-5H-° ratio η is [2,3-b]. Bijing-7-decanoic acid isopropylamine. Step 2 156090.doc •336- 201204731 to 2-(1-methyl-1H-indole-6-yloxy)_5_(2·tris-decylalkyl-ethoxymethyl)-5Η-pyrrole [2,3-b] Pyridinium 7-isopropyl decyl decanoate (16 mg, 0.33 mmol) in tetrahydrofuran fluoride (1.0 M THF solution) in a stirred solution of anhydrous THF (5 mL) , 6.6 mL, 6·6 mm 〇 1) and ethylenediamine (0.44 mL, 6.6 mmol). The reaction mixture was heated with EtOAc (4×). The combined organic phases were dried over Na 2 EtOAc and concentrated. The residue was purified by column chromatography using 2-6% MeOH/CHAh as solvent (yield: 59 mg (52%) as a pale yellow solid. 1H-Indol-6-yloxy)-5H-pyrrolo[2,3-b]pyrazine-7-isopropyl isopropylamine. MS: (M+H)+=350. Example 279. 2-(1Η-吲哚-5-yloxy)-5Η·吼-[2,3-b]pyrazine-7-decyl isopropyl decylamine

Step 1 To a stirred solution of 5-hydroxyindole, 7 5 〇 mm 〇 1) in MeCN (35 mL) was added ditributyl dicarbonate (4.9 g, 22.5 mmol), DMAP (0.46 g). , 3.75 mmol) and triethylamine (3.2 mL ' 22.5 mmoip were given the reaction mixture for 16 hours at 25 ° C, then completely steamed crane 156090.doc -337 · 201204731 solvent. With silicone (100-200 mesh) tube Column chromatography using 10-20% EtOAc/hexanes as a solvent to purify the residue to give 2.5 g (1%) as a colorless oil. The third butyl acid ester. Step 2 To a stirred solution of 5 -t-butoxycarbonyloxy-indole-1-carboxylic acid tert-butyl ester (15 g, 4-50 mmol) in dichloromethane (30 mL) Add morpholine (11_8 mL '135 mmol). The reaction mixture was stirred at 25 ° C for 16 hours, then the solvent was completely distilled off. The column was chromatographed using 10-20% EtOAc / The residue was purified as a solvent eluting to afford EtOAc (yield: </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 2-trimethyldecyl-ethoxy oxime _5H_0 Add 5-hydroxyindole to a stirred solution of bromo[2,3-b]pyridin-7-carboxylic acid isopropyl guanamine (1 mg, 0.24 mmol) in DMF (4 mL) 1-butyric acid tert-butyl ester (68 mg, 0.29 mmol) and Cs2C03 (235 mg, 0.72 mmol). The vial was sealed and heated in a microwave reactor for 1 hour at 12 ° C. Quenched with water (20 mL) The reaction was quenched and extracted with EtOAc (EtOAc) (EtOAc)EtOAc. The residue was purified with EtOAc / EtOAc (EtOAc) elute Oxymethyl)_5H-pyrrolo[2,3-b]pyrazine_7-isopropenyl decylamine Step 4 to 2-(1Η-吲哚-5-yloxy)-5-(2 -trimethyldecyl-ethoxy oxime 156090.doc -338- 201204731 yl)-5H-n ratio argon[2,3-b]t well _7·isopropyl guanidinium amide (6 ,, 〇i3 mmol) To a stirred solution of anhydrous THF (4 mL) was added tetrabutylammonium fluoride (1·0 M THF solution 2.6 mL, 2.6 mmol). The reaction mixture was heated under reflux for 16 h then cooled to rt.

(4χ) Extraction "The combined organic phases were dried over Na2S〇4 and concentrated. The crude residue was purified by column chromatography using MeOH/EtOAc (EtOAc) eluting [2,3-b]0 is more than argon-7-isopropyl decyl decylamine. Ms: (M+H)+=336. Example 280. 2-(6-Methyl.pyridin-2-yloxy)-5H-pyrrolo[2,3-b]indole Trulli-7-formic acid isopropyl decylamine

Step 1 To the pressure tube, 2-bromo-5-(2-trimethyldecyl-ethoxymethyl)-5Η-α-pyrolo[2,3-b]pyridin-7-decanoate 6-Methylpyridine-2-ol (115 mg, 1.05 mmol) and Cs2C03 (342 mg, 1.05 mmol) were added to a stirred solution of EtOAc (EtOAc, EtOAc (EtOAc) The tube was sealed and heated at 140 ° C for 18 hours. The reaction was cooled with EtOAc (EtOAc)EtOAc. The combined organic layers were washed with brine, dried over Na~~~ The residue was purified by silica gel (100-200 mesh) column layer 156090.doc - 339 - 201204731 using 20-60% EtOAc/hexanes as solvent. 2-(6-Methylpyridin-2-yloxy)-5-(2-tridecylfluorenyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine_7_ Isopropylamine citrate. Step 4 To 2-(6-fluorenyl "bipyridin-2-yloxy)-5-(2-tridecylfluorenyl-ethoxymethyl)-5H-pyrrolo[2,3-b] To a stirred solution of pyridin-7-formic acid isopropylamine (16 mg, 0.36 mmol) in anhydrous THF (4 mL) was added THF (1.0 M THF solution ' 7.2 mL ' 7.2 mmol) and Ethylenediamine (0.48 mL, 7.2 mmol). The reaction mixture was heated under reflux for 16 hr then cooled to EtOAc EtOAc. The combined organic phases were dried over <RTI ID=0.0># </ </RTI> &amp; The residue was purified by column chromatography using EtOAc EtOAc EtOAc EtOAc (EtOAc) -Piloluene [2,3-1?]0 is more than argon-7-isopropyl decyl decylamine. ;^8: (1^+印+=312. Example 281. 2-(4,6-Dimercaptopyridine-2-yloxy)_5H-pyrrolo[2,3-b]pyrazine-7- Isopropylamine decanoate

156090.doc • 340- 201204731 Pyridin-2-ol is prepared in place of 6-methylpyridine·2·alcohol. MS: (M+H)+=326. Example 282. 2-(2-Methylpyridin-3-yloxy)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamine

Prepared according to the procedure outlined in Example 280 in step 1 using 2-methylpyridin-3-ol instead of 6-mercaptopyridine-2-ol. MS: (M+H)+=312. Example 283. 2-((R)-3-Aminoindan-5-yloxy)·5Η-pyrrolo[2,3-b]pyrazine isopropyl decylamine

MS was prepared according to the procedure outlined in Example 270, but with the exception of step 4: (M+H)+=352. Example 284. 2-((R)-3-Prodecylaminoindol-5-yloxy)_5Η·»Byrolo[2,3_b]ntb 11 Well-7-Isopropylguanidate 156090.doc 341 - 201204731

Prepared according to the procedure outlined in Example 270, using chlorohydrin and pyridin in place of methyl sulfonium and diisopropylethylamine in step 4. Ms: (Μ+Η)+=4〇8 ο Example 285. 2-{(R)-3-[(tetrahydropyran-4-ylcarbonyl)amino]-indan_5_yloxybu 5η _ η each [2,3-b] pyridin-7-isopropyl decyl decylamine

Prepared according to the procedure outlined in Example 270, substituting tetrahydropyran 4-base gas and pyridine for methanesulfonium chloride and diisopropylethylamine in step 4. MS: (M+H)+=464. Example 286. 2-[(R)-3-(cyclopropanecarbonyl-amino)--(5-yloxy)- 5 Η 比 [ [2,3-b]pyridin-7-carboxylic acid isopropyl Baseline 156090.doc -342· 201204731

According to the example outlined in Example 270

Gas and pyridine instead of decanesulfonium gas - in step 4, cyclopropanecarbonyl (M+H) + = 420. Isopropylethylamine was prepared. MS: Example 287. 2 and 3-(2, =methyl, base) ^ _5_ yloxy] _ 洛 洛 [2,3 卞 卞 卞 异丙 异丙 酿 酿 酿

r\

Prepared according to the procedure outlined in Example 270, in step 4 using trimethyl ethane oxime and pyridine instead of decane sulfonium chloride and diisopropylethylamine. MS: (M+H)+=436. Example 288. 2-((R)-3-Benzenylamino-p--5-yloxy)-5H-. More than [2,3-b].比耕-7-Isopropyl decylamine 156090.doc •343 - 201204731

ο

Prepared according to the procedure outlined in Example 270, in the step, using phenylhydrazine hydrazine and hydrazine and diisopropylethylamine. MS: (Μ+Η)+=456. Example 289. 2-((R)-3-Ethylaminoindaninyl-5-yloxy)5Η ιι比比和[2 3 ^^pyran-7-carboxylic acid ((S)-l,2 ,2-trimethyl-propyl)-decylamine

According to the procedure outlined in Example 270, in step 2, 2-bromo-5-(2-methylcyanoalkyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7 was used. -formic acid ((S)-l,2,2-dimethyl-propyl)-decylamine in place of 2_bromo-5-(2-trimethyldecyl-ethoxymethyl)·5Η-pyrrolo[ 2,3-b]pyridin-7-isopropyl decyl decylamine' was prepared in step 4 by replacing decanesulfonium and diisopropylethylamine with acetamidine chloride and pyridine. MS: (Μ+Η)+=436. Example 290. 156090.doc •344·201204731 2_((S)-3-Ethylamino-based (6-yloxy)_5Η-° ratio [[2,3-^&gt;]° ratio _ -7-isopropyl guanamine

According to the procedure outlined in Example 270, (s) 3 amine-based nod-5-ol was substituted for (R)-3-amino-p--5-ol in step ,, and in step 4 Gas and sputum. The eMS was prepared by replacing the brewing gas with diisopropylethylamine: (M+H)+=394. Example 291. 2-((S)-3-Amino-p--5-yloxy)-5 Η "Bisto[2,3 b]e than Flavor-7-Isopropyl Ammonium

According to the procedure outlined in Example 270, (R)-3-amino-based -5-alcohol was replaced in step 1 with (s)_3_aminophenanthrene-5-ol, and step 4 was omitted for preparation. MS: (M+H)+=352. Example 292. -7-Isopropylguanidate 2-(Fly-5-yloxy)-5H-pyrrolo 156090.doc -345- 201204731

According to the procedure outlined in steps 2 and 5 of Example 270, in place 2, ((R)·6-hydroxyindan-1-yl)-aminobutyric acid tert-butylate was replaced with indole-5-ol. preparation. MS: (M+H)+=337. Example 293. 2-((R)-l-Ethylaminoindanin-5_yloxy)_5Hpyrrolo[23 ton]pyrazine-7-f acid ((S)-l,2,2 -trimethyl-propyl)-decylamine

According to the procedure outlined in Example 270, (r) "amino"-indan-5-alcohol hydrochloride was substituted for (r)_3_aminoindan-5-alcohol in step 1, used in step 2. Bromine 5 (2 曱 石 夕 夕 _ ethoxymethyl group d and [2, 3 _ 匕] 〇 ratio

Prepared by diisopropylethylamine. MS: (M+H)+=436. Example 294. 弁[2,3-bJ&quot; Ratio 2_((R)-1 -Ethylaminosyl Xuemaniyloxy)_5H♦ each [2,3-b]pyrene than -7-formic acid ((s)_second butyl)_ guanamine 156090.doc -346- 201204731

Step 1 To the pressure tube, 2-bromo-5-(2-tridecyldecyl-ethoxycarbonyl)-5H-pyrrole and [2,3-b] 0 to -7-decanoic acid· (〇2 5 g, 0.70 mmol) was added to (3) (3,6,6-hydroxyindane-1-yl)-aminobutyric acid tert-butyl ester (0.209 g, 0.84 mmol) in a solution of benzene. 2-tert-butylphosphino-2'-(N,N-dimethylamino)biphenyl (0.072 g, 0.210 mmol) and Κ3Ρ〇4 (〇.298 g, 1.404 mmol). The reaction was flushed with nitrogen for 20 min and Pd ([Lambda]) &lt;2&gt; The tube was sealed and mixed at 90 ° C for 16 hours. The reaction was cooled and the solvent was evaporated under vacuum. Purification of the crude residue by using EtOAc / hexanes (10-15%) as a solvent eluting </ RTI> </ RTI> </ RTI> <RTIgt; )_6-[7_methylmercapto_5_(2-tridecylfluorenyl-ethoxymethyl)_5Η-α is more than [2,3-b]» than t-but-2-yloxy]- Indole-1-yl}-amino decanoic acid third vinegar. LC-MS: (M+H)+=525. Step 2 Under 〇C to {(R)-6-[7-carbamimid-5-(2-trimethyldecyl-ethoxymethyl)-5H-n ratio [2,3_b] 0 is more slowly added to the stirred solution of the second solution of chlorinated 2-1-yloxy]-indan-pyridyl decanoic acid (1.0 g, 丨·91 m〇l) in decyl alcohol ( 2.71 mL, 38.1 mmol). The reaction mixture 1 was stirred under a clock, followed by stirring at 251 for 2 hours. Evaporation of the solvent under reduced pressure at room temperature afforded 2_((R)_3•amine indane_5-yloxy 156090.doc •347-201204731 base)-5-(2-trimethyl) The hydrazinyl-ethoxymethyl)_5H-pyrrolo[2313]pyrazine-7-indole hydrochloride salt was used without further purification. Step 3 Neutralize 2-((R)-3-aminoindan-5-yloxy)·5_(2_trimethyldecyl-) with 0-bit (0.671 g, 8.492 mmol) under 〇C Stirring solution of ethoxylated oxime)_5H_0pyrolo[2,3-b]pyrimidin-7-carbaldehyde hydrochloride (0.19 g, 2.12 mmol) in dichloromethane to PH=7 And at 0. (: stir for 20 minutes. Add

Ac2O (0.325 g, 3.18 mmol) was stirred at 25 ° C for 16 h. The solvent was evaporated under reduced pressure and the crude residue was purified eluting with EtOAc/hexane (1 - 15%) as solvent. %) is a pale yellow solid of N](R)_6_[7_methylmercapto_5_(2-trimethyldecyloxyethyloxy)- 5H-pyrrolo[23_b]pyridin-2-yloxy Base]-indan-1-yl acetamide. LC-MS: (M+H)+=467. Step 4 To N-{(R)-6-[7-Mercapto-5-(2-trimethyldecyl-ethoxymethyl 5H-pyrrolo[2,3-b]pyridin-2 · Addition of NH2SO3H (0.56 g, 5.80 mmol) and NaCl〇2 to a stirred solution of oxyl]-indanyl acetamide (ο. &quot; g ' 0.97 mmol) in dioxane (10 mL) (0.114 g, 1.25 mmol) and ΚΗ2Ρ04 (1·57 g ' 11.592 mmol) in water (5 mL). The mixture was stirred at 25 ° C for 16 h then diluted with water and EtOAc (3×50 mL) The combined organic layers were dried <RTI ID=0.0>(~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ -5-(2-Trimethyl-stone-ethoxymethyl)_5h_pyrrolo[2,3-b]pyrazine-7-carboxylic acid, which can be used without further purification. 156090.doc •348 · 201204731 Step 5 to 2-((R)_3_Ethylaminoindan-5-yloxy)-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[ 2,3-b]pyrazine-7-decanoic acid (0.20 g, 〇·41 mmol) was added to a stirred solution of di-methane (1 mL) in a continuous addition of (S)-l-second butylamine ( 0.033 g, 0.46 mmol) And HATU (175 mg, 0.49 mmol). Diisopropylethylamine (0.21 mL, 1.23 mmol) was added at EtOAc. The mixture was stirred at 25 ° C for 12 h then quenched with water and dichloromethane The organic layer was dried over Na 2 SO 4 and concentrated under reduced pressure. The crude residue was purified by column chromatography eluting with EtOAc (100-200 mesh) to give 0.12 g (540 / 〇) as a yellow viscous solid. 2-((R)_3-Ethylideneamino-p--5-yloxy)-5-(2-trimethyldecyl-ethoxymethyl)-5H-pyrrolo[2,3 -b] pyridinic acid ((S)-t-butyl) decylamine. Step 6 Heating 2-((R)-3-acetamidoamineindan-5-yloxy at 65 °C )_5_(2_ dimethyl sulphate-ethoxy fluorenyl)-5H-° than hydrazine [2,3-b]° ratio tillage-7-decanoic acid Lu ((S)_ second butyl a stirred solution of decylamine (0.12 g, 0-22 mmol) in EtOAc (EtOAc) (EtOAc) Ethylenediamine (20.0 eq.) was added in 1) and below. The reaction mixture was stirred at 251 for 18 hours, then completely distilled under reduced pressure. Solvent, and the crude residue was purified by EtOAc/EtOAc (EtOAc) (EtOAc) 2_((幻_3_Ethylaminoindan-5-yloxy)-5H-pyrrolo[2,3_b]. Specific tillage-7-decanoic acid ((S)-second butyl)-guanamine. MS: (M+H)+=408. 156090.doc •349· 201204731 Example 295. 2-((R)-l-Ethylamino Bp-5-yloxy)-5Η -° ratio 弁[2,3- b]0 ratio Plough-7-decanoic acid ((R)-l-cyclopropyl-ethyl)-decylamine

Prepared in step 5 by substituting (R)-l-cyclopropyl-ethylamine for (S)-l-t-butylamine according to the procedure outlined in Example 294. MS: (M+H)+=420. Example 296. 2-((R)-l-Ethylaminoindolino-5-yloxy)-5H-° than bromo[2,3-b]° Trulli-7-carboxylic acid ((S )-l-cyclopropyl-ethyl)-guanamine

Prepared in step 5 by substituting (S)-l-cyclopropyl-ethylamine for (S)-l-t-butylamine according to the procedure outlined in Example 294. MS: (M+H)+=420. JAK assay information for determination of Janus kinase (JAK) inhibitory IC5G values: The enzymes and peptides used are as follows: JAK1: recombinant human kinase domain from Invitrogen (catalog number PV4774) JAK3: from Millipore (catalog number 14 -629) or a recombinant human kinase domain prepared. JAK2: Recombinant Human Kinase Domain from Millipore (Catalog No. 14-640) 156090.doc -350- 201204731 Substrate: n-terminal biotinylated conjugated peptide derived from the activation loop of JAK1 where the peptide is The detection conditions for the sequence of organisms are as follows:

Detection buffer. JAK kinase buffer: 50 mM Hepes [pH 7.2], 10 mM MgCl2, 1 mM DTT, 1 mg/ml BSA. Detection is carried out in this buffer. Detection format: The kinase activity of all three JAK kinases was measured using a radioactive endpoint assay and using trace amounts of 33p_ATP. Detection was carried out in a 96-well polypropylene plate. Experimental method: All concentrations were final concentrations in the reaction mixture and all incubations were carried out at room temperature. The detection steps are as follows: Use 100°/. DMSO typically serially dilutes the compound 10 times at a starting concentration of i mM. The final concentration of DMSO in the reaction was 1%. The compound was preincubated with the enzyme (0.5 nM JAK3 (commercially available), 0.2 nM JAK3 (prepared), 1 nM JAK2, 5 nM JAK1) for 10 minutes. The reaction was initiated by the addition of a mixture of two receptors (ATP and peptide premixed in JAK kinase buffer). In the JAK2/JAK3 assay, ATP and peptide were used at concentrations of 1.5 μΜ and 50 μΜ, respectively. The JAK1 assay was performed at an ATP concentration of 10 μΜ and a peptide concentration of 50 μΜ. The detection time of JAK2 and JAK3 is 20 minutes. The JAK1 assay was performed for 40 minutes. The reaction was stopped for all three enzymes by adding 0.5 M EDTA to a final concentration of 100 mM. Transfer 25 μΐ of the reacted reaction to 150 μΐ of a 96-well 1.2 μm MultiScreen-BV filter plate. 7.5% (ν/ν) agarose beads containing coated antibiotic 156090.doc -351 - 201204731 nystatin The granules were free of MgCl2 and CaCl2 and contained a slurry of 1 mM phosphate buffered physiological saline of 50 mM EDTA. After incubation for 30 minutes, the beads were washed under vacuum with the following buffer: 3 to 4 washes with 200 μΐ 2 M NaCl. Wash 3 to 4 times with 200 μΐ 2 M NaCl plus 1% (ν/ν) phosphoric acid. Wash the Su for 1 time with water. The washed plates were dried in an oven at 60 ° C for 1 to 2 hours. 70 μM Microscint 20 scintillation fluid was added to each well of the tarsal plate and after at least 30 minutes of incubation, the radioactivity count was measured in a Perkin-Elmer microplate flash counter. The representative IC50 values are shown in Table II below: Table II. Compound Ic50 h-jak3 (810-1124) • sff9-c: no additive (μΜ) 1-1 0.22486 1-2 0.00523 1-3 0.01219 1-4 0.03485 1-5 0.30171 1-6 0.12621 1-7 0.00451 1-8 0.04879 1-9 0.01960 1-10 0.03433 1-11 0.15173 1-12 0.19236 1-13 0.43629 1-14 0.40877 1-15 0.00749 1-16 0.45888 1- 17 0.08448 1-18 0.00305 1-19 0.00614 1-20 0.02977 1-21 0.04500 1-22 0.00590 1-24 0.17964 1-25 0.00673 1-26 0.00408 1-27 0.93386 1-28 0.68064 1-29 ' 0.05427 1-30 0.01905 1-31 0.03948 1-32 0.02008 1-33 0.49272 1-34 0.03643 1-35 1.03872 1-36 0.03361 1-37 0.02204 1-38 0.11500 1-39 0.30185 1-40 0.12828 Ml 0.11153 M2 0.13101 1-43 0.12077 - 352- 156090.doc 201204731

1-44 0.04604 Ι·45 0.20773 1-46 0.22824 1-47 0.34309 1-48 0.11565 1-49 0.45253 1-50 0.00903 1-51 0.41420 1-52 0.01107 1-53 0.00838 1-54 0.00546 1-55 0.02940 1- 56 0.00984 1-57 0.21673 1-58 0.03768 1-59 0.05887 1-60 0.01505 1-61 0.00257 1-62 0.00746 1-63 0.03047 1-64 0.03513 1-65 0.26197 1-66 0.04997 1-67 0.42702 1-68 0.35826 1-69 0.14348 1-70 0.08700 1-71 0.00380 1-72 0.01000 1-73 0.09242 1-74 0.02706 1-75 0.06867 1-76 0.13209 1-77 0.01367 1-78 0.07861 1-79 0.04069 1-80 0.00390 1- 81 0.01599 1-82 0.01516 1-83 0.04725 1-84 0.06514 1-85 0.07251 1-86 0.03919 1-87 0.00182 1-88 1.41346 1-89 0.01339 1-90 0.01454 1-91 0.03868 1-92 0.09507 1-93 0.05784 1-94 0.87751 1-95 0.00999 1-96 0.02595 1-97 0.01804 1-98 0.01113 1-99 0.00661 1-100 0.03846 1-101 0.01203 1-102 0.01032 1-103 0,00725 1-104 0.01632 1-105 0.10280 1-106 0.01475 1-107 0.06129 1-108 0.16295 1-109 0.23090 1-110 0.04545 Mil 0.27573 1-112 0.08615 M13 0.03568 1-114 0.0 6343 1-115 3.30096 1-116 0.68209 1-117 0.02677 1-118 0.14998 1-119 . 0.15058 1-120 0.02436 1-121 0.05950 1-122 0.06382 1-123 1.33371 1-124 0.44223 1-125 0.50236 1-126 0.19021 1-127 0.14283 1-128 0.21127 1-129 0.22225 1-130 0.65874 1-131 1.02865 1-132 0.41477 . 1-133 0.15380 156090.doc •353 · 201204731 1-134 0.89130 1-135 0.02064 1-136 0.28345 1- 137 0.34633 1-138 0.00501 1-139 0.00055 1-140 0.00088 1-141 0.00019 Μ 42 0.00018 1-143 0.00628 . 1-144 0.00340 1-145 0.00461 Μ 46 0.01312 1-147 0.00246 1-148 0.00325 1-149 0.00299 1 -150 0.00512 1-151 0.01244 Μ 52 0.02528 1-153 0.07538 1-155 0.00032 1-156 0.00035 1-157 0.00043 1-158 0.00032 1-159 0.00053 1-160 0.00032 1-161 0.00032 1-162 0.00032 1-163 0.00300 1-164 0.00032 1-165 0.00017 1-166 0.00011 1-167 0.00032 1-168 0.00022 1-169 0.00029 1-170 0.00058 Μ71 0.00023 1-172 0.00014 1-173 0.00020 1-174 0.00022 1-175 0.00010 1-176 0.00046 1-177 0.00032 1-178 0.00032 1-179 0.00032 1-180 0.00032 1-181 0.00062 1-182 0.00032 1-183 0.00032 1-184 0.00032 1-185 0.00032 1-186 0.00046 1-187 0.00046 1-188 0.00041 M89 0.00060 1-190 0.00069 1-191 0.00055 1-192 0.00040 1-193 0.00042 1-194 0.00134 1-195 0.00046 1-196 0.00047 1-197 0.00032 1-198 0.00054 1-199 0.00065 1-200 0.00073 1-201 0.00057 1-202 0.00052 1-203 0.00040 1-204 0.00056 1- 205 0.00076 1-206 0.00032 1-207 0.00073 1-209 0.00047 1-210 0.00071 1-211 - 0.00022 1-212 0.00016 1-213 0.00011 1-214 0.00028 1-215 0.00021 1-216 0.00018 1-217 0.00011 1-218 0.00013 1-219 0.00024 1-220 0.00023 1-221 0.00008 1-222 0.00011 1-223 0.00091 1-224 0.00036 1-225 0.00019 354- 156090.doc 201204731

1-226 0.00050 1-227 0.01056 1-228 0.61869 1-229 0.18371 1-230 2.61358 1-231 4.22410 1-232 0.17718 1-233 0.40678 1-234 0.97958 1-235 0.78443 1-236 2.96483 1-237 5.35592 1- 238 3.84823 1-239 5.19661 1-240 0.31533 1-241 0.67717 1-242 1.17718 1-243 0.30967 1-244 1.07179 1-245 3.30868 1-246 3.45523 1-247 6.45564 1-248 1.03367 1-249 1.59120 1-250 4.58553 1-251 4.03349 1-252 0.91369 1-253 2.17078 1-254 2.98880 1-255 0.38180 1-256 0.93054 1-257 2.74335 1-258 0.24613 1-259 6.70858 1-260 1.52760 1-261 2.98802 1-262 1.87094 1- 263 2.34964 1-264 0.81002 1-265 1.10243 1-266 0.38114 1-267 2.35818 1-268 0.15540 1-269 0.08561 1-270 0.73976 1-271 1.27124 1-272 0.02931 1-273 0.46951 1-274 0.35325 1-275 0.62606 1-276 0.57423 1-277 0.22900 1-278 0.49109 1-279 1.10872 1-280 3.97752 1-281 0.13848 1-282 0.12540 1-283 0.05667 1-284 0.04997 1-285 0.23431 1-286 0.15244 1-287 0.02015 1- 288 0.29715 1-289 0.53285 1-290 0.26103 1-291 0.03697 1-292 0.091 74 1-293 0.16189 1-294 0.01234 1-295 0.00964 1-296 . 0.02288 1-297 0.57324 1-298 0.38682 1-299 0.14336 1-300 0.19924 1-301 0.11839 1-302 0.15723 1-303 0.13997 1-304 0.15495 156090.doc - 355 - 201204731 SYK assay for determining spleen tyrosine kinase (SYK) inhibitory IC5G values: The SYK kinase assay is a standard kinase assay suitable for 96-well plate formats. This assay was performed in a 96-well format with IC5G values determined using 8 samples representing 1 〇 half log dilution and 40 μί reactant volume. The assay measures the amount of incorporation of radiolabeled ΡγΑΤΡ from the biotinylated peptide receptor (biotin-1 laa DY*E) at the N-terminus of the naturally occurring phosphate receptor consensus sequence. The phosphorylated product was detected after termination of the reaction with EDTA and addition of streptavidin coated beads. Representative results are shown in Table II above. Detection plate: 96-well Multiscreen 0.65 μπι filter plate (Millipore catalog number: MADVNOB10) Anti-proteomycin coated beads: Streptavidin SepharoseTM, suspension 5.0 mL, diluted with 50 mM EDTA/PBS (1:100), ( Amersham, Cat. No.: 17-5113-01) Compound: 10 mM in 100% disulfoxide (DMSO), final concentration: 0.003-100 μM in 10% DMSO. Compound enzyme: spleen tyrosine kinase aa 360 -635 of SYKRPA purified truncated construct, stock solution 1 mg/mL, MW: 31.2 KDa, final concentration: 0.0005 μΜ. Peptide 1: Biotin-labeled peptides were derived from the naturally occurring phosphate receptor consensus sequence (Biotin-EPEGDYEEVLE), a special order of QCB, stock solution 20 mM, final concentration: 5.0 μΜ. ΑΤΡ : adenosine-5,-triphosphate 20 mM (ROCHE catalog number: 93302720), 156090.doc -356- 201204731 Final concentration: 20 μΜ Buffer: HEPES: 2-hydroxyethyl peptin-2-ethane Sulfonic acid (Sigma, catalog number: H-3375), final concentration: 50 mM HEPES (pH 7.5) BSA: bovine serum albumin fraction V, no fatty acids (Roche Diagnostics GmbH, catalog number: 9100221), diluted to a final concentration of 0.1 %

EDTA: EDTA stock solution 500 mM, (GIBCO, catalog number: 15575-038), final concentration: 〇.1 mM

DTT : 1,4-dithiothreitol (Roche Diagnostics GmbH, catalog number: 197777), final concentration: 1 mM

MgCl2x6H20 : MERCK, catalog number: 105833.1000, final concentration: 10 mM assay dilution buffer (ADB): 50 mM HEPES, 0.1 mM EGTA, 0.1 mM sodium vanadate, 0.1 mM β-glycerophosphate, 10 mM MgCl2, 1 mM DTT '0.1% BSA (pH 7.5) Bead Wash Buffer: 10 g/L PBS (phosphate buffered saline) containing 2M NaCl + 1% phosphoric acid. Experimental method: 26 pL ADB diluted purified recombinant human SYK360-635 [0.5 nM] and 4 pL l〇x concentration of test compound [usually 100 μΜ-0.003 μΜ] in [10%] Mix in DMSO and incubate the mixture for 10 minutes at room temperature. The kinase reaction was initiated by the addition of 10 pL of a 4x receptor mixture containing DYE peptide receptor [〇 μΜ or 5 μΜ], ΑΤΡ [20 μΜ], and 33ΡγΑΤΡ [2 μ Ci/rxn]. After incubation for 15 minutes at 30 ° C, transfer 25 μί reaction sample to 156090.doc •357, 201204731 to 96-well 0.65 μπι Millipore MADVNOB membrane/plate containing 200 pL 5 mM EDTA and 20% Streptococcus mutans The reaction was terminated by coating the pbs of the beads. Unbound radionucleosides were washed under vacuum with 3 x 250 pL 2 M NaCl; 2 x 250 μί 2 Μ NaCl + 1% phosphoric acid; 1 x 250 μί Η20. After the last wash, the film/plate was transferred to an adaptor plate 'heat drying at 60 ° C for 15 minutes, adding 5 〇pL scintillation mixture to each well' and in the top counter after 4 hours Count the amount of radioactivity. Percent inhibition was calculated based on the ratio of uninhibited enzyme: % inhibition = 100 / (1 + (IC5 〇 / inhibitor concentration) η). The IC5 threshold is calculated using the XLfit software (ID Business Solution Ltd" Guilford, Surrey, uk using a non-linear curve fitting method. The above invention has been described in considerable detail by way of illustration and example for clarity and understanding. It is to be understood that changes and modifications may be made within the scope of the appended claims. The scope of the invention is therefore intended to be illustrative and not restrictive. The scope of the patent application and the equivalents of the equivalents of the scope of the claims are to be determined by the following claims. All patents, patents, and publications cited in this application are hereby In this article, the degree of citation is as individual instructions in individual patents, patents, or public cases. 156090.doc .358-

Claims (1)

201204731 VII. Patent application scope: ι· A compound of formula I, 1 where: R is hydrazine, cyano, low carbon ray, R or f is cycloalkyl, heterocycloalkyl, heteroaryl or phenyl, each optionally substituted by one or more R&quot;; each R&quot; is independently halo, hydroxy, cyano, lower alkyl, Lower haloalkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, c(=o)r &quot; or s(=o)2r '; each R'&quot; independently OH or low Carboalkyl; Rla&amp;Rlb are each independently hydrazine, hydroxy, dentyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkyl, lower alkoxy, lower alkoxy Base, lower hydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, C(=0)R·', S(=0)2R&quot;' or CH2S(= 0) 2R_' ; Rle is phenyl 'cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Rld; each Rld is independently hydroxy, halo, lower alkyl, low carbon Hydroxyalkyl, lower carboalkyl or lower alkoxy; 156090.doc 201204731 R2 is hydrazine, hydroxy lower alkyl, lower haloalkyl or lower alkyl; R3 is hydrazine, hydroxy, cyano, Cyano lower alkyl or r3·; each R3' is independently lower alkyl, lower hydroxy a base, a lower alkoxy group, a lower alkene, a lower alkoxy, a phenyl lower alkyl, a cycloalkyl or a cycloalkyl lower alkyl, each optionally having one or more R 3 ' 'Substituent; each R3&quot; is independently lower alkyl, halo, hydroxy, lower alkoxy, lower decyl, lower hydroxyalkyl, pendant oxy, amine, cyano, cyano Carboxyalkyl, S(=0)2R3&quot;', C(=0)R3'&quot;, cycloalkyl, heterocycloalkyl, heteroaryl or heterocycloalkenyl; each R3' is independently hydrazine, hydroxy Or low carbon alkyl; Q is Q2, Q3 or Q4; Q2 is heterocycloalkyl, cycloalkyl, cycloalkenyl, heterocycloalkylphenyl, heteroaryl, biaryl or heteroaryl, The situation is replaced by one or more Q2a; 卩2&amp; is 卩215 or Q2c; each Q2b is independently halogen, pendant oxy, hydroxy, -CN, -SCH3, -s(o)2ch3 or -S(=0) CH3; each Q2e is independently Q2d4Q2e; or two Q2a together form a double loop system, optionally substituted by one or more Q2b or Q2e; each 卩2 (1 is independently -〇(Q2e), -S(=0 ) 2(Q2e), -C(=0)N(Q2e)2, -S(0)2(Q2e), _c(=〇)(Q2e), -C(=0)0(Q2e), -N (Q2e)C(=0)(Q2 e), -N(Q2e)C(=〇)〇(Q2e) or -N(Q2e)C(=0)N(Q2e)2; each 卩26 is independently H or Q2e; 156090.doc -2 - 201204731 Each Q2e' is independently lower alkyl, phenyl, benzoinyl, 5,6'7,8-tetrahydro-naphthalene, lower alkyl, lower alkoxy, cyclohexyl, cyclo Alkenyl, heterocycloalkyl, spirocycloheteroalkyl or heteroaryl is optionally substituted by one or more Q2f; each 023⁄4 is Q2g or Q2h; each Q2g is independently halogen, thiol, cyano Side oxy, -S( = 0)2(Q2i,), -S( = 0)2N(Q2i')2, -C(=0)〇H, C(=0)N(Q2i')2 or -C(=0)(Q2i); each Q2h is independently lower alkyl, lower alkenyl, lower alkyl, lower alkoxy, amine, phenyl, methyl, cycloalkyl a heterocycloalkyl or heteroaryl group, optionally substituted by one or more Q2i; and each Q21 is independently i, hydroxy, cyano, lower alkyl, lower haloalkyl or lower alkoxy Each Q2i' is independently hydrazine or lower alkyl; Q3 is -0-Q3a, _S-Q3a, _c(=0)(Q3a), -0(CH2)mC(=0)(Q3a), -S (=〇)(Q3a), -S(=〇)2(Q3a), _N(Q3a)2, -N(Q3a)S(=0)2(Q3a), -N(Q3a)C( = 〇) (Q3a), _C( = 〇)N(Q3a)2, N(Q3a)c( = 〇)N(Q3a)2 or -N(Q3a)(CH2)mC(=〇)N(Q3a)2 ; each site is Q3b or Each m is independently 〇, i or 2; each 卩 315 is independently Η; each Q3e is independently lower alkyl, lower _alkyl, phenyl, 5,6,7,8-tetrahydro- Naphthalene, naphthalene, 2,2-dimethyl-2,3-dihydro-benzofuran 156090.doc 201204731 喊基,茚满基, 茚基, U弓丨βτ朵基, cycloalkyl, heterocyclic The base or heteroaryl group is optionally substituted with one or more Q3d; and each Q3d is independently Q3e4Q3f; each Q3e is independently a _ s, a oxy group, an aryl group, a thiol group, a -NHS (=0) 2 ( Q3f), _NHC(=0)(Q3f), NHC(=0)N(Q3f)2 or N(Q3f)2; each Q3% is Η or Q3f·; each Q3r is independently lower alkyl, lower Carboalkoxy, lower alkyl, phenyl, benzyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q3g; and each Q3g is independently _, Hydroxy, lower alkyl 'lower hydroxyalkyl, lower _alkyl or lower alkoxy; Q4 is Q4a4Q4b; Q4a is hydroxy, halogen or cyano; Q4b is lower alkyl, lower alkoxy , low carbon alkynyl, low a carboxyalkenyl group, a lower hydroxyalkyl group, an amine group or a lower alkyl group, optionally substituted by one or more Q4e; each Q4e is independently Q4d4Q4e; each Q4d is independently halogen, hydroxy or cyano; each Q4e Independently a lower alkyl, lower alkene, lower alkoxy, amine, cycloalkyl, phenyl, heterocycloalkyl or heteroaryl group, optionally substituted with one or more Q4f; 156090 .doc -4 - 201204731 Each Q4f is independently hydroxy, halo, lower alkyl, lower alkenyl, pendant oxy, lower carbon functional, lower alkoxy, lower carbyl or amine The restriction is that the compound of formula I is not 2-thiophen-2-yl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamine, 2-cyclopropyl-5H-pyrrole And [2,3-b] pyridin-7-decanoic acid (4-hydroxy-3,3-dimethyl-butyl)-decylamine, 2-[l-(7-isopropylamine) -5H-°Biluo[2,3-b]° ratio p-well-2-yl)-pyrylene-3-yl]-propionic acid tert-butyl, 2-cyclopropyl-5H-α ratio 3⁄4S·和[2,3-b]I^ is more than t^ well-7-carboxylic acid tert-butylamine, 2-cyclohexyl-5H-pyrrolo[2,3-b]pyrazine-7·carboxylic acid Propyl decylamine, 2-cyclohex-1-ylidene-5 Hn, piroxime [2, 3-b]0 to 11 well-7-isopropyl isopropylamine, 2-chloro-5H-° ratio slightly [2, 3-1] ° ° ° well-7-decanoic acid isopropyl Amine, 2-isopropyl-5 H-° than hydrazine [2,3-b] ° than spur _7-formic acid isopropyl amide, 2-isopropyl-5-pyrene-β piroxime [2 ,3-b]η ratio '• Well-7-isopropyl decylamine, 2-(cyclodecyl-fluorenyl-amino)-5Η-ηpiro[2,3-b]n 〇 Well _7_ isopropyl decylamine, [1-(7-isopropylamine fluorenyl-5H-pyrolo[2,3-b]. Till-butyl-2-yl)-0-b--3-yl]-mercapto-aminocarboxylic acid tert-butyl ester, 2_(3_decylamino-ββ唆_1_基比嘻[2, 3-b] ° 啩·7·isopropyl decyl decanoate, 2-(cyclopentyl-methyl-amino)-5 Η-pyrolo[2,3-b]&quot; than spray_7 _ isopropyl formate, chloro π each [2,3-b] »&gt; ratio 井·7·isopropyl decyl citrate, 2-isopropenyl-5Η-pyrrolo[2,3 -b]pyrazine formate isopropylamine, 2-isopropyl-5H-pyrrolo[2,3-b]pyrazine_7-isopropyl isopropylamine, 2-cyclohex-1-ene 5-H-pyrrolo[2,3-b]pyrazine_7·isopropyl decyl decylamine, 2-cyclopropyl-5//-° piroxime [2,3-6]° spray · 7_decanoic acid (3_carbyl 2,2-dimercapto-propyl)-decylamine, 2_cyclopropyl-5/f-pyrrole [2,3_ypy 156090.doc 201204731 &quot; Well-7·formic acid ((s)_2-hydroxyl,2-dimethyl-propyl)-decylamine, 2-cyclopropyl-5//-0 ratio slightly [2,3-6] ° ratio of tillage-7-decanoic acid tert-butylamine, 2-cyclohexyl-5H-.pyrolo[2,3-b]pyr. well-7-isopropyl decylamine, 2-thiophene -2-yl-5孖-pyrrolo[2,3-do]pyrho-7-decanoic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine, [1-(7- Isopropyl Mercapto-5H-pyrrolo[2,3-b]pyrylene-2-yl)-piperidine-3-yl]-mercapto-aminocarboxylic acid tert-butyl ester, 2-(3-methylamino)- Piperidine-1-yl)-5H-»pyrolo[2,3-b]pyrazine-7-isopropyl decylamine; [1-(7-isopropylaminecarbamyl-5H) -pyrrolo[2,3-b]pyridin-2-yl)-piperidin-3-yl]-methyl-amino decanoic acid tert-butyl ester or 2-(3-methylaminopiperidine) a -1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-decyl isopropyl decylamine; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein R' is cycloalkyl, heterocycloalkyl, heteroaryl or stupid, each of which is optionally substituted by one or more R&quot;; R is a dentate group, a hydroxyl group, a cyano group, a lower alkyl group, a low carbon tooth Alkyl, lower alkoxy, lower hydroxyalkyl, cycloalkyl, C(=0)R'·· or s(=o)2r·&quot;; R is OH or a lower carbon group; Rla, Rlb and Rlc are each independently hydrazine, hydroxy, halo, lower alkyl, lower alkenyl, lower alkynyl, lower carboalkyl, lower alkoxy, lower haloxyalkoxy, lower carbon Hydroxyalkyl, amine, lower alkylamino, lower dialkylamino, cyano, cycloalkyl Heterocycloalkyl, C(=0)R'&quot; or S(=〇)2R_&quot;; 156090.doc 201204731 R2 is hydrazine or lower alkyl; R3 is hydrazine, hydroxy, cyano, cyano lower alkane Or R3'; R3_ is lower alkyl, hydroxy lower alkyl, lower alkoxy, lower haloalkyl, lower carbon||alkoxy, phenyl lower alkyl or cycloalkyl lower The alkylalkyl group is optionally substituted by one or more R3&quot;; each R3&quot; is independently a lower alkyl, a functional group, a hydroxyl group, a lower alkoxy group, a lower carbon functional group, a lower carbon base group. , pendant oxy, aryl, cyano lower alkyl, S(=0)2R3&quot;', C(=0)R3&quot;', cycloalkane, heterocycloalkyl, heteroaryl or heterocycloalkenyl R3 is hydrazine or a low carbon alkyl group; Q is Q2, Q3 or Q4; Q2 is heterocycloalkyl, cycloalkyl, cycloalkenyl, heterocycloalkylphenyl, heteroaryl, biaryl or hetero Biaryl, as the case may be substituted by one or more () 23; 卩 23 is (^215 or (52 (:; Q2b is halogen, pendant oxy, hydroxy, -CN, -SCH3, ® -S(0) 2CH3^-S(=0)CH3; Q2e is Q2d4Q2e; or two Q2a together form a double loop system' as the case passes one or more Q2b or Q2C Generation; Q2c%-0(Q2e), -S(=0)2(Q2e), -C(=〇)N(Q2e)2, -S(〇)2(Q2e), -C( = 〇)( Q2e), _C( = 〇)〇(Q2e), -N(Q2e)C( = 〇)(Q2e), -N(Q2e)C( = 〇)〇(Q2e)4 -N(Q2e)C(= 0) N(Q2e)2; 156090.doc 201204731 Each (^2£ is independently Η or Q2e·; each Q2e' is independently lower alkyl, phenyl, benzyl, lower alkyl, lower Carboalkoxy, cycloalkyl, cycloalkenyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q2f; Q2g is dentate, hydroxy, cyano, pendant oxy or -C(= 0) (Q2h); Q2h is lower alkyl, lower ii alkyl, lower alkoxy, amine, phenyl, phenyl, cycloalkyl, heterocycloalkyl or heteroaryl, as appropriate Substituted by one or more Q2i; and Q2i is halogen, hydroxy, cyano, lower alkyl, lower alkyl or lower alkoxy; Q3 is -0-Q3a, -S-Q3a, -C( =0) (Q3a), -〇(CH2)mC(=0)(Q3a), -S(=〇)(Q3a), -S(=0)2(Q3a), -N(Q3a)2, _N (Q3a)S(=0)2(Q3a), -N(Q3a)C(=0)(Q3a), -C(=0)N(Q3a)2, N(Q3a)C(=0)N(( Q3a) 2 or -N(Q3a)(CH2)mC(=0)N(Q3a)2; each site is Q3b or Q3e; m is 0, 1 or 2; Q 3bSH ; Q3c is lower alkyl, lower haloalkyl, phenyl, cycloalkyl, heterocycloalkyl or heteroaryl, optionally substituted by one or more Q3d; and each (^3(| independently) Is 〇 (36 or Q3f; 156090.doc 201204731 (5> is halogen or hydroxy; Q3f is lower alkyl, lower alkoxy, lower haloalkyl, strepto, cycloalkyl, heterocycloalkyl or a heteroaryl group, optionally substituted by one or more Q3g; and each Q3g is independently dentate, hydroxy, lower alkyl, lower hydroxyalkyl, lower alkyl or lower alkoxy; Q4 is Q4a4Q4b; Q4a is hydroxy, halogen or cyano; Q4b is lower alkyl, lower alkoxy, lower alkynyl, lower alkenyl, lower hydroxyalkyl, amine or lower alkyl, depending on The condition is replaced by one or more Q4e; Q4eSQ4d4Q4e; each Q4d is independently a halogen, a trans- or a gas group; each Q4e is independently a low-carbon alkyl group, a low-carbon tooth-burning group, a low-carbon alkoxy group, an amine group, a cycloalkyl, phenyl, heterocycloalkyl or heteroaryl group, optionally substituted by one or more Q4f; each Q4f is independently hydroxy, halo, lower alkyl, lower alkenyl, pendant oxy a lower carbon dentate group, a lower alkoxy group, a lower hydroxyalkyl group or an amine group; v, with the proviso that when Q is a cyclopropyl group or a decyl group, R 2 and R 3 are fluorenyl or fluorenyl groups, and Rla, When either of Rlb&amp;RiC is a fluorenyl group, the other is not a hydrazine, a hydroxy group or a hydroxymethyl group; and the limitation is that when Q is a gas, an isopropyl group, an isopropenyl group, a piperidinyl group, a methyl group - ketone-3-yl-amine, fluorenyl-piperidine _3_yl-amino decanoic acid tert-butyl 156090.doc -9- 201204731 decyl hexyl, J-pentyl methyl-amino group or When R2 and R3 are oxime or methyl, Rla, R]b and R1C are not all H; or a pharmaceutically acceptable salt thereof. 3. A compound according to claim 1 or 2 wherein 9 is cycloalkyl, heterocycloalkyl or heteroaryl&apos;, each optionally substituted by one or more Qh. 4. A compound according to claim 1 or 2 wherein R2 or R3 is lower alkyl and the other is hydrazine. 5. The compound of claim 1 or 2 wherein R2 and R3 are both fluorenyl. 6. The compound of claim 2 or 2 wherein Rh is lower alkyl, hydroxy, lower carboxy, lower alkoxy, cyano or lower hydroxyalkyl. 7. A compound according to claim 2 or 2, wherein Rla is methyl. 8. The compound of claim 1 or 2, wherein Rlb is methyl. 9. A compound according to claim 2 or 2, which is a lower alkyl group, a hydroxyl group, a lower hydroxyalkyl group, a lower alkoxy group, a lower alkyl group, a cyano group or a methane group. 10. The compound of claim 1 or 2, wherein 111 &lt;: is a ^1, hydroxy or lower alkyl group. 11. The compound of claim 1 or 2, wherein 111 &lt;: is a thiol or a hydroxy group. 12. A compound according to claim 2 or 2, wherein the compound is classified as a lower alkyl group or a lower alkyl alkane group. 13. The compound of claim 1 or 2 wherein Rla and Rib together form a spirocycloalkyl or spiroheterocycloalkyl group. 14. A compound according to claim 1 or 2, wherein Q is cyclopropyl, thienyl or pyrazolyl, each optionally substituted by one or more Q2a. 156090.doc • 10-201204731 15. The compound of claim 1 which is selected from the group consisting of: 2 / odor 5 / ί-pyrrolopyrazine _7_ formic acid (3 hydroxy _2, 2 _ Methyl-propyl)-guanamine; 2-cyclopenta-1-yl-5-p-pyrolo[2,3_6]pyridinic acid ((8)_2hydroxyl''2--methyl-propyl)- Amine; 2-isopropenyl-5//-pyrrolo[2,3_6]pyrrole_7_carboxylic acid ((s)_2_hydroxy-1,2_-mercapto-propyl)-decylamine; Aminoamino-5if-pyrrolocarboxylic acid (3-hydroxy-2,2·dimethyl-propyl)-bristamine; 2-isopropyl-5/ί-pyrrolo[2,3-do]pyrazine _7_capric acid ((s)_2_hydroxy_ι,2_didecyl-propyl)-bristamine; 2-cyclopentyl-5/ί-pyrrolo[2,3_6]pyrazine_7_曱Acid ((s)_2_hydroxyl, 2_monodecyl-propyl)-bristamine; 2-cyclohex-1-enyl-5孖-pyrrolo[2,3_qpyrrole_7_decanoic acid (( s)_2_hydroxy-1,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-5H-pyrrolo[2,3-fc]pyrrole_7-decyl isopropyl decylamine 2-cyclopropyl-5ϋΓ-pyrrolo[2,3-6]pyrazine-7-decanoic acid (2-decyloxy-1-indenyl-ethyl)-bristamine; 2-° ratio bite -1-yl-5Η- 〇 D D each [2, 3_5] 咕ντ well_7_carboxylic acid (3-carbyl·2,2-dimethyl-propyl)-bristamine; 2-cyclohexyl-577-pyrrolo[2,3-6]pyrazine-7 -formic acid ((S)-2-hydroxy-1,2·didecyl-propyl)-guanamine; 2-cyclopropyl-5if-pyrrolo[2,3-6]pyridin-7-decanoic acid (3-hydroxy-1,1-dimethyl-butyl)-decylamine; 156090.doc •11- 201204731 2-cyclopropyl-5/ί-° ratio slightly [2,3-6]° Plough-7-formic acid (2·cyano-ethyl)-decylamine; 2-(3,3-dimercapto-pyrrolidinyl-1-yl)_5 ugly-pyrrolo[2,3_do]pyrazine _7_carboxylic acid (3-hydroxy-2,2-diindenyl, propyl)-decylamine; 2-phenylamino-5//-pyrrolo[2,3-6]pyrazine-7-formic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine; 2-(methylamine-mercaptodecylaminopyrrolo[2,3 juvenile] than tillage_7_甲6* _(3-transyl-2,2-methyl-propyl)-bristamine; 2-cyclopropyl_57/_pyrrolo[2,3 work]pyrazine-7-decanoic acid [2-hydroxyl 1-(2-hydroxy-ethyl)-2-methyl-propyl]-guanamine; 2-thiophen-2-yl-5//-pyrrolo[2,3-pyridin-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ( 1-ring --ethyl)_ decylamine; 2-(2-amididyl-4-yl)_5 is better than [2,3-6]0 than cultivable-7-carboxylic acid ((S)-2-hydroxy· l,2-Dimethyl-propyl)-decylamine; 2-(6-fluorenyl-pyridin-3-yl)_5 ugly-pyrrolo[2,3-6]pyrazine-7-decanoic acid (( S)_ 2-hydroxy-1,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-5//-pyridyl"[2,3-6]&quot; 比口井-7 -formic acid ((!5)_second butyl)_ decylamine; 2-cyclopropyl-5//-pyrrolo[2,3_do]pyrazine_7_carboxylic acid ((S)-l,2 ,2-trimethyl-propyl)-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-2-hydroxy·1_ Isopropyl-2-methyl-propyl)-decylamine; 156090.doc •12- 201204731 2-cyclopropyl-5 ugly-0 than haha [2,3-6]. Specific tillage-7-decanoic acid ((8)-1,2-dimethyl-propyl)-guanamine; 2-cyclopropyl-5 open-pyrrolo[2,3-Z&gt;]pyrazole-7 -formic acid (1-ethyl-propyl)-decylamine; 2-cyclopropyl-5/ί-pyrrolo[2,3-6]pyrazine-7-decanoic acid (2-didecylamino)- 1-methyl-ethyl)-bristamine; 2-cyclopropyl-5/ί^pyrho[2,3-6]pyrazine-7-carboxylic acid cyanomethyl-decylamine; 2-cyclopropyl -5 ugly-pyrrolo[2,3-0]pyrazine-7-carboxylic acid ((S)-l-ethyl-2-hydroxy-2-alkyl-propyl)-bristamine; 2-cyclopropyl -5-ί-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((R)-2-hydroxy-1,2-dimercapto-propyl)-bristamine; 2-cyclopropane -5-/-pyrrolo[2,3-Z&gt;]pyrazine-7-decanoic acid ((lS,2S)-2-hydroxy-1.2-didecyl-butyl)-bristamine; 2 - J Propyl propyl-5 // ° ratio slightly [2,3-Z&gt;]n ratio p well-7-formic acid ((S)-l-cyclohexyl-ethyl)-guanamine; 2-cyclopropyl- 5//-° ratio of [2,3-6]pyridine•well-7-decanoic acid (3-cyano-propyl)-indoleamine; 2-cyclopropyl-57/-pyridinium [2,3-6]. Ratio &gt;1 well-7-decanoic acid ((18,2)^)-2-hydroxy·1.2-didecyl-butyl)-guanamine; 2-tris-methyl--5//-° ratio η Each [2,3-△]! ratio ρ well-7-formic acid (3-transyl-2,2-dimercapto-propyl)-decylamine; 2-vinyl-5 ugly-pyrrolo[2 , 3-6] pyridin-7-formic acid (3-hydroxy-2,2-dimercapto-propyl)-guanamine; 2-cyclopropyl-5 ugly-pyrrolo[2,3·6]pyridinium Plough-7-formic acid [(s)_丨兴1^-pyrazole-156090.doc •13-201204731 3-yl)-ethyl]-guanamine; 2-cyclopropyl-5 ugly-pyrrolo[2 ,3_6]pyrazine_7_carboxylic acid ((1S,2S)_3_cyclopropyl-2-hydroxy-1,2-dimercapto-propyl)-decylamine; 2-ethyl-5//~0比略和[2,3-办]〇比1»井_7-decanoic acid (3-carbyl-2,2-dimethyl-propyl)-decylamine; 2-cyclopropylpyrrolo[2 , 34] pyridinium-7-decanoic acid ((S)-l-hydroxyindolyl-propyl)-guanamine; 2-cyclopropyl-5//-. More than [2,3-6]pyrazine-7-decanoic acid ((R)-2-hydroxyindolyl-ethyl)-guanamine; 2-cyclopropyl-5-open-. Biluo[2,34]pyrazine-7-carboxylic acid (3-hydroxy-l,l-dimercaptopropyl)-decylamine; 2-((lR,2R)-2-indenyl-cyclic Propyl)_5 ugly-pyrrolo[2,3_y 0 ratio tillage_7_carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-5孖-pyrrole [2,34]pyrazine_7_carboxylic acid ((R)_i_ethyl_2-hydroxy-2-indolyl-propyl)-guanamine; 2-cyclopropyl-5-pyrrolo[2, 3-&amp;]pyrazine_7-formic acid (2-hydroxy-l,i-dimethyl-ethyl)-guanamine; 2-((lR,2S)-2-methyl-cyclopropyl)_5 //_pyrrolo[2,3 work]pyridinic acid (3-hydroxy-2,2-didecyl-propyl)-decylamine; 2-cyclopropyl-5i/-pyrrolo[2,3- 6] Pyridin-7-formic acid ((S)-l-hydroxymethyl-2,2-dimethyl-propyl)-guanamine; 2-cyclopropyl-5F-pyrrolo[2,3-do Pyridinium 7-decanoic acid ((^,211)-3-cyclopropylhydroxy-1,2-dimethyl-propyl)-decylamine; 2, cyclopropyl-5/f-pyrrolo[ 2,3-6]pyrazine_7-decanoic acid [(8)-1-(1-hydroxy_1_ 156090.doc •14-201204731 decyl-ethyl)-pentyl]-bristamine; 2-ring Propyl-5仏pyrrolo[2,3_6]pyrazine_7_decanoic acid (2-decyloxy-2-indolyl-propyl)-bristamine; 2-cyclopropyl-5 ugly-. Comparative [[2,3 6]pyrazine_7_carboxylic acid (2-hydroxyl-indole-hydroxyindolyl-ethyl)-bristamine; 2-cyclopropyl-5/ί-. Biha and [2,3_6]pyrazine_7_decanoic acid ((8) sulfhydryl- 2,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-5//-pyrrole Pyridin _7 decanoic acid ((1S, 2R)_3,3,3-difluoro-2-hydroxy-1,2-dimercapto-propyl)-decylamine; 2-cyclopropyl-5/ί-pyrrole And [2,3_do]pyrazine_7_carboxylic acid ((s)_3,3,3-trifluoro-1,2,2-trimethyl-propyl)-bristamine; 2-3⁄4 propyl- 5/ί-pyrrolo[2,3· phantomin 7_carboxylic acid (2,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-5 ugly-pyrrolo[2,3- 6] pyridinium 7-formic acid ((R)-l-hydroxyindenyl-2-indolyl-propyl)-bristamine; 2-cyclopropyl-5//-pyrrolo[2,3·6] Pyridin _7_decanoic acid ((s)_2-hydroxymethyl-ethyl)-guanamine; 2--propylpropyl-5//-.倍比和[2,3_外比味_7_carboxylic acid ((尺)_1_经基曱基-propyl)-guanamine; 2-cyclopropyl-5i/-pyrrolo[2,3-6 Pyridin_7_carboxylic acid (3-decyloxy-2,2-dimethyl-propyl)-decylamine; 2-3⁄4 propyl-5//-pyrrolo[^-...pyridin-^曱 “ 尺 环 环 环 环 环 ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ^,之义三i56090.doc -15· 201204731 decyl-ethyl)-guanamine; 2-cyclopropyl-5i/-pyrrolo[2,3-6]pyr p-formic acid ((R)-1 '2,2-Dimercapto-propyl)-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-do]pyrinoic acid ((1S,2S)·3,3,3 -: fluoro-2-hydroxy-1,2-dimethyl-propyl)-decylamine; 2_cyclopropyl_5孖-pyrrolo[2,3-6]° than tillage-7-formic acid (( R)_1_methoxymethyl-2,2-dimercapto-propyl)-bristamine; 2_cyclopropyl_5^-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-1_nonyloxyindenyl-2,2-dimercapto-propyl)-oxime Amine; 2-cyclopropyl_5 ugly-pyrrolo[2,3-6]pyrazine·7-carboxylic acid ((foot)_1_phenyl-ethyl)-decylamine; 2·cyclopropyl_5 _pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-l-phenyl-ethyl)-decylamine; 2-cyclopropyl-5/ί-pyrrolo[2,3 -6] pyridin-7-decanoic acid (3-hydroxy-butyl decylamine; 2_cyclopropyl-5i/-pyrrolo[2,3 work]pyrazine-7-carboxylic acid (3-hydroxy-2-hydrazino-propyl)-guanamine; 2-cyclopropyl-5 ugly-pyrrole And [2,3-6]pyridinium-7-decanoic acid (丨_pyridin-2-ylethyl)-bristamine; 2_cyclopropyl-5//-pyrrolo[2,3·ά]pyridin Plough ·7·formic acid (3•hydroxymethyl-propyl)-decylamine; ' ' 2-pyridin-2-yl-577-pyrrolo[2,3-&]pyrazine_7 thiol-propyl )-decylamine; 2-cyclopropyl-methyl t-[2,3-sec-(tetra)-7-carboxylic acid ((8) succinylpropyl^ 156090.doc -16-201204731)-2-yl-propyl)-decylamine 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid cyclopropyl-2_hydroxy-2-indolyl-propyl)-decylamine; 2-cyclopropyl -5//-° ratio &lt;» each [2, 3-6]. Ratio _-7-formic acid (i-cyclohexyl-propyl)·guanamine; 2-cyclopropyl-5i/-pyrrolo[2,3-6]pyridin-7-decanoic acid ((R)_i_ Cyanomethyl-2-2.2-dimethyl-propyl)-bristamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-l -Cyanoguanidino-2,2-dimethyl-propyl)-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyridin-7-decanoic acid (cyclohexyl-ring Propyl-methyl)-guanamine; 2-cyclopropyl-5//-.比略和[2,3-Z)]n ratio tillage·7-formic acid (2-hydroxy-l,i,2-trimethyl-propyl)-decylamine; 2-cyclopropyl-5H-pyrrole ρ,34]pyrazine_7_carboxylic acid dicyclopropylmethyl-decylamine; 2-cyclopropyl-5&quot;-pyrrolo[2,3-6]pyrazine_7-carboxylic acid (2-cyano- 1-cyclopropyl-2,2-dimethyl-ethyl)-bristamine; 2·cyclopropyl-5//-pyrrolo[2,3-6]pyrazine_7-carboxylic acid [(R) -l-(l-hydroxy-cyclopentyl)-ethyl]-decylamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine_7_carboxylic acid ((lR,2R) 2-hydroxy-1,2-dimercapto-butyl)-bristamine; 2-cyclopropyl-5//-D ratio slightly [2,3-6]. π Well _7_carboxylic acid ((lR, 2R)-2-yl-1,2-dimercapto-pentyl)-bristamine; 2-cyclopropyl-5open-D ratio η[2 , 3-6] «&gt;ratio?&gt; Well_7_中酸Π-(tetra argon. South-4_ 156090.doc 201204731 base)-ethyl]-bristamine; 2-cyclopropyl-57/ -pyrrolo[2,3-6]pyridin-7-carboxylic acid ((R)-2-cyano-1,2,2-trimethyl-ethyl)-bristamine; 2-cyclopropyl-hydrazine -pyrrolo[2,3-6]pyridin-7-carboxylic acid ((S)-2-cyano-1,2,2-tridecyl-ethyl)-guanamine; 2-cyclopropyl-5 /ί-pyrrolo[2,3·δ]pyrazine-7-carboxylic acid ((13,211,33)-1_cyclohexyldecyl-3-cyclopropyl-2,3-dihydroxypropyl)-fluorene Amine; 2-cyclopropyl-5//-° ratio slightly [2,3-6]0 ratio tillage-7-formic acid (1-cyanononyl-propyl decylamine; 2-cyclopropyl-5 //-° is more than [2,3-6]. than arable-7-formic acid (cyano-cyclopropyl-methyl)-guanamine; 2-cyclopropyl-5-pyrrolo[2, 3.·Flashpyrazine·7_decanoic acid ((lR, 2R)-3-cyano-2-p-yl-1,2-dimercapto-propyl)·enamine; 3-cyclopropyl-3- [(2-Cyclopropylpyrrolo[2,3-6]pyrazine-7-carbonyl)-amino]-2,2-dimercapto-propionic acid; 2-cyclopropyl-5 ugly-pyrrolo [2,3-Z&gt;]pyrion _7 _ formic acid (L-hydroxy-2-methyl-1-trimethyl-propyl)-bristamine; 2_cyclopropyl_5 ugly-pyrrolo[2,3-6]pyridin-7-carboxylic acid ( (s)_i_cyclohexyl-2-yl-2-methyl-propyl)-guanamine; 2-cyclopropyl-5/ί-pyrrolo[2,3·6]pyridin-7-carboxylic acid (1-cyclopentylethyl) decylamine; 2-phenoxy-5 good-° ratio 咯[2,3-do] 〇 耕 _7·carboxylic acid (丨_cyclopropyl-ethyl _ 醯 ;; 2-cyclopropyl-57/-pyrrolo[2,3-6]pyrazine-7-decanoic acid [(s)_i_(i-hydroxy- 156090.doc -18· 201204731 cyclopentyl )-ethyl]-bristamine; 2_cyclopropyl _5 Ρ 洛 洛 洛 [2,3·6]. than __7_carboxylic acid (3_甲烧烧基_ 2,2-didecyl-prop ))-nonylamine; 2-(ι-ethyl m4-yl)_5-open-pyrrolo[2,3_small 卞7-carboxylic acid ((R)-2-|%-based-1,2-anthracene Base-propyl)-bristamine; 2-cyclopropyl-5//-(iv) and [2,3 secondary ratio „well_7_carboxylic acid [(rh (i-nitro-cyclodecyl)-ethyl] amine; 2-cyclopropyl-5/^ ratios are combined [2,3_化„well_7_carboxylic acid [(8) small (1_yl-cyclopentyl)-ethyl]-decylamine; 2-(1 -mercapto m4-yl)-5-pyrrolo[2,3_6]pyridin-7-decanoic acid ((R)-2-yl-1,2-dimethyl-propyl)-bristamine; 2- Benzene 1 _5β· Μ # [2,3_6] f acid ((r)_2-trans-yl-1,2-dimercapto-propyl)-bristamine; 2-cyclopropyl-5P piroxime [2,3♦pyrino-7carboxylic acid [(R)cyclopropylhydroxy-cyclopentyl)-indolyl]-guanamine; 2-(2,4-difluoro-phenoxy)-57/-pyrrole And [2, 3_ ratio _ well _7_ formic acid (1_cyclopropyl-ethyl)-decylamine; 2-cyclopropyl-5/^ piroxime [2,3- small pycnolate _7 _Citrate (2-cyano-small-propyl-ethyl)-decylamine; 2-cyclopropyl-5&quot;-pyrrolo[2,3-6]pyridin-7-decanoic acid cyclohexyl fluorenyl hydrazine Amine; 2-cyclopropyl-5open-pyrrolo[2,3·ό]. Specific tillage _7_decanoic acid (1_methanesulfonyl-pyridin-3-ylmethyl)-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine_ 7_carboxylic acid (丨_methanesulfonyl group _ 156090.doc •19· 201204731 pyrrolidin-3-ylmethyl)-guanamine; 2-(3,6-dihydro-2//-pyranyl_4_ Base)-5//-pyrrolo[2,3-do]pyrazine-7-carboxylic acid ((R)-2-yl-1,2-dimethyl-propyl)-bristamine; 2-0 Plug 0 sit-2-yl-5/ί-0 ratio 0 and [2,3-έ]〇 ratio p well_7_carboxylic acid ((R)-2-yl-1,2-dimethyl- Propyl)-decylamine; 2-indenyl-2-yl-5//-pyrrolo[2,3-6]. Specific tillage _7_decanoic acid ((foot)-2-yl-1,2-dimethyl-propyl)-guanamine; 2-(4-fluoro-phenoxy)-5-pyrrolo[ 2,3-6]pyrazine-7-formic acid (1-cyclopropyl-ethyl)-guanamine; 2-(2-fluoro-phenoxy)-5//-»pyrylene [2 34] Pyridin _7• formic acid (丨_cyclopropyl-ethyl)-guanamine; 2_cyano L each [2,3-小比崎·7_carboxylic acid ((R)_2_经基·^一Dimethyl-propyl)-guanamine; 2-phenoxy-5 ugly-n ratio [2,3-6]. Specific cultivating · 7_carboxylic acid ((R)_2_hydroxy-1 1,2-dimethyl-propyl)-decylamine; 2-cyclopropyl-shaking each [2,3_small than the _7_carboxylic acid [ (8) small (ι_ aryl-cyclohexyl)-ethyl]-guanamine; 2-cyclopropyl-5//-pyrrolo[2,3_6]pyridin-7-carboxylic acid [(s)_i (i cyanide Base — cyclohexyl)-ethyl]-guanamine; 2-phenoxy-5/ί-° ratio is slightly [2, 3-6].比乌井·7_ f acid isopropylamine; 2-phenoxy-5//-pyrrolo[2,3-6]pyrazine_7_carboxylic acid ((8)tridecyl-propyl)-guanamine ; 2-phenoxy-5 oxime ratio slightly and ^ small than call Qiao 曱 (8) - second butyl broad amide; 156090.doc • 20· 201204731 2-phenoxy-5 ugly-pyrrolo[2,3 -6]pyrazine-7-decanoic acid ((S)-l,2-dimethyl-propyl)-decylamine; 2-phenoxy-5//-pyrrolo[2,3-6]pyridinium Plough-7-formic acid ((S)-l-cyclohexyl-ethyl)-guanamine; 2-(2,4-difluoro-phenoxy)-5 ugly-° ratio [2,3-6 ]. Specific tillage-7-formic acid ((R)-1_dehexyl-ethyl)-bristamine, 2-(2,4-difluoro-phenoxy)-5open-fluorenyl [2,3-6 ]. Specific tillage-7-decanoic acid ((8)-2-yl-1,2-dimercapto-propyl)-decylamine; • 2-(2,4-difluoro-phenoxy)-5 -pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((R)-t-butyl)-decylamine; 2-(2,4-difluoro-phenoxy)-5-anthracene And [2,3-6] 吼耕-7-decanoic acid ((11)-1,2-dimercapto-propyl)-guanamine; 2-phenoxy-5//-pyrrolo[2, 3-6]° ratio tillage-7-formic acid ((S)-2-hydroxy-1,2-dimercapto-propyl)-guanamine; 2-phenoxy-5//-pyrrolo[2, 3-6] pyridin-7-formic acid ((R)-l-cyclohexyl-ethyl)-decylamine; ® 2-phenoxy-5 ugly-pyrrolo[2,3-6]pyrazine-7 -capric acid ((11)-1,2,2-trimethyl-propyl)-decylamine; 2-phenoxy-5//-pyrrolo[2,3-6]pyridin-7-carboxylic acid Ethyl decylamine; 2-(2,4-difluoro-phenoxy)-5//-pyrrolo[2,3-6]pyrazine-7-decanoic acid isopropylamine, 2-(2 ,4-difluoro-phenoxypyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-decylamine; 2-(2 , 4-difluoro-phenoxypyrolo[2,3_6]. Tillage-7-decanoic acid ((R)-156090.doc •21 - 201204731 1,2,2-trimethyl-propyl) - guanamine; 2-cyclopropyl-5//-pyrrolo[2,3-6]pyrazine-7- Formic acid ((R)_2-cyano + cyclopropyl-ethyl)-decylamine; 2-cyclopropyl bilobo[2,3-6]. Ratio -7-7-decanoic acid (1_ethylhydrazine) _ 〇 bottom bite _ 3- mercapto) - guanamine; 2-cyclopropyl-5 open-oxime [2, 34]. Compared with 4-7-carboxylic acid (1-ethyl fluorenyl _n 嘻唆3--3-indenyl)-bristamine; 2-(1-ethyl-1 ugly-pyrazol-4-yl)-5 ugly-pyrrolo[2,3-6]pyridin-7-carboxylic acid [( S)-l-(l-trans-cyclopentyl)-ethyl]-bristamine; 2-(1-mercapto-1/f-pyrazol-4-yl)-5 ugly-pyrrolo[2 ,3-6]pyrazine_7_carboxylic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl)-guanamine; 2-(1-methyl-1//- Pyrazol-4-yl)-5//-pyrrolo[2,34]pyrazine_7_carboxylic acid ((s)_i-cyclohexyl-ethyl)-bristamine; 2-(1-mercapto-1 //-pyrazol-4-ylpyrrolo[2,3-0]pyrazine_7_carboxylic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-thiophene- 2-based _5 ugly-pyrrolo[2,3-do]pyrazine-7-carboxylic acid ((s)^ 2 2 dimethyl-propyl)-decylamine; 2-(4·trifluoromethyl)- Phenylpyrrolo[2,3 work]pyrazine_7_decanoic acid (〇1,2,2-trimethyl-propyl)-decylamine; 2-cyclopropyl-5 ugly-pyrrolo[2, 3-6]pyrazine-7-formic acid ((s)-3-methanesulfonyl-1,2,2-trimethyl -propyl)·decalamine; 2-[1-(3-gas-phenyl)-1 ugly-imidazole_4_yl]·5 ft-pyrrolo[2,3_6]n than cyano-7-formic acid ( (S)-l,2,2-trimethyl-propyl)-bristamine; 2-[1-(3-trifluoromethyl-phenyl)-1-do-imidazole-4-yl]-5//pyrrole And [2 3_ 156090.doc •22- 201204731 6]pyrazine-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[1-(5-gas -2-fluoro-phenyl)-1//-imidazole _4_yl]-5/ί-吼 并 [2,3-6] ° ratio &lt;* well-7-decanoic acid ((S)- l,2,2-trimethyl-propyl)-decylamine; 2-[1-(2-1-5.indolyl-stupyl)-1 good_ 〇米唾_4_基]-5/ί -0 is 0 and each [2,3-έ]pyrazine-7-decanoic acid ((S)-l,2,2-trimercaptopropyl)-decylamine; 2-[1-(2-gas -5-Trifluoromethyl-phenylmethane 嗤4·yl]·5//·. Ratio p [2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-(1-m-phenylene-phenyl- 1/f-imidazole _4_yl)_5 good _ 吼 并 [2,3_έ] pyridin _7_ decanoic acid ((S)-l, 2, 2-trimethyl-propyl) amide; 2_ [1-(3·Ethyl-phenyl)-1//-mi. Sit _4_base] than 嘻 and [2, 3_ do]. Specific -7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[1-(3-isopropyl-phenyl)-17/-imidazole-4 -基]-5//-° ratio slightly [2,3-6] 吼耕-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2- [1-(3-襄三7&quot; base-stupid)_ι//__imidazolyl]_5 ugly ratio [2,3_6]» than arable-7-decanoic acid ((S)-l, 2, 2-trimethyl-propyl)-guanamine; 2-(1,3-dimethyl-indole/f-pyrazole-4-yl)_5-pyrrolo[2,3-6]pyrazine_ 7_ decanoic acid ((S)-2-decyloxy-1-indenyl-ethyl)-decylamine; 2-(5-ethylaminemethantyl-thiophene-2-yl)_5//_pyrrole [2,3_6]pyrazine_7·formic acid ((S)-l,2,2-trimethyl-propyl)-bristamine; 2-(5-isopropylaminemethanyl-thiophene_2_ )5__pyrrolo[2,3_6]pyridin-7-carboxylic acid ((S)-l,2,2-tridecyl-propyl)-decylamine; 2-(5-#三Τ' group Aminomethylthiophene-2-ylpyrrolo[2,3_]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[ 5-(1-methyl-2-pyrazole·!_yl·ethylaminemethanyl)_thiophene-2-yl]·156090.doc -23- 201204731 5开-&lt;·比略和[ 2,3-do]pyrazine_7_formic acid ((s)·^』· Trimethyl-propyl) decylamine; 2-{5-[2-(4-fluoro-phenyl)-1-methyl-ethylaminemethyl hydrazino]-thiophene-2- yl b 5//- »Bilo and [2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2·trimethyl-propyl)·decylamine; 2·(5-ethylamine A Styrene-D-cetin-2-yl)-5//~° ratio B and [2,3-&amp;] η ratio p well _ 7-formic acid ((S)-l, 2, 2-trim --propyl)-guanamine; 2-[5-(4-methyl-piperidin-1-carbonyl)-thiophene-2-yl]-5/fn ratio slightly [2,3 ό]. Plough-7-formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-((R)-l-cyclopropyl-ethylamine fluorenyl) _thiophene·2_yl]_5开_„Biloze[2,3-6]pyridin-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[1-(3-Ethyl-phenylmethane. Sodium-4-yl) is more than 嘻[2,3_办] Pyrrion _7-carboxylic acid ((S)-l,2,2-three Methyl-propyl)-decylamine; 2-{5-[(pyridin-3-ylmethyl)-aminecarbamimidyl]-thiophen-2-yl}-5 and - are more than 0 [2, 3-6] pyridin-7-decanoic acid ((S)-l,2,2-trimethyl-propyl decylamine; 2-{5-[(. ratio. -4--4-ylindenyl)-amine-mercapto]-porphin- 2-ylpyridinium [2,3]pyrazine_7_carboxylic acid ((S)-l,2,2-triterpene --propyl decylamine; 2-{5-[(° ratio 0 2-1 曱 曱 ))-amine fluorenyl]- porphin 2 - kibido [2, 3 gong] pyrolysis - 7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-bristamine; 2-[5-(4-cyano-based -1-amino)-° phenan-2 -基]-5//·°Biluo[2,3-6] pyridin-7·formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2·[ ·(cyclopentyl decyl-amine carbhydryl)-thiophene~2-yl]-5-pyrido[2,3_6]0 to 11--7-carboxylic acid ((S)-1,2, 2-trimethyl-propyl)-bristamine; 2-[5-((R)-2-alkyl-1-methyl-ethylamine methyl)-porphin-2-yl]_5 tablets _ 156090.doc -24- 201204731 0 than 嘻[2,3-6]吼啼-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2_[5 -((RM-Mercapto-2-phenyl-ethylaminecarbamimidyl)-thiophen-2-yl]_5仏° ratio slightly [2,3-6]pyrazine-7-decanoic acid ((S )-l,2,2-trimethyl-propyl)-decylamine; 2 [5 (1-n ratio η定_3_yl-ethylamine methyl)] _ _ 2 _ base]_ 5 pay _ n ratio slightly [2,3-6] ° than tillage-7-decanoic acid ((S)-l, 2, 2-three Yl - propyl) - Amides; 2-[5-(cyanomethyl-amine-mercaptothiophene-2-ylpyrrolo[2,3 6] ° ratio &quot;well-7-decanoic acid ((8)-1,2,2-three Methyl-propyl)-nonylamine; 2-[5-(2-aminosulfonyl-ethylamine-methyl thiol thiophene 2_*]_5 ugly _pyridyl^[2,3-6]° ratio Plough-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-(2-imidazolyl-yl-ethylamine decyl)-thiophene _2_基]_5 丑比洛和[2,3-6]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[5 -(4-hydroxy-4-methyl-trans--1-carbonyl)-°cephen-2-yl]-5/ί-α is more than [2,3-6]pyrazine-7-carboxylic acid ( (S)-l,2,2-trimethyl-propyl decylamine; 2-[5-(1-methyl-2-° ratio hexane-2-yl-ethylamine oxime)-congestion Phen-2-yl-_ 5/ί-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; [5-(7-Azabicyclo[2.2.1]heptane-7-carbonyl)-thiophene-2-yl]-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid (( S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-(3-cyano-azetidin-1-carbonyl)-thiophen-2-yl]-5 /ί-pyrrolo[2,3-6] » 比ρ井-7-甲2-[5-(3-Aminocarboxylic acid^((8)-1,2,2-trimium) -propyl)-guanamine; _azetidin-1-M-yl)-thiophen-2-yl]-5--. Ratio 156090.doc -25- 201204731 咯[2,3-δ]pyrr Pentyl 7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2_[5弋azetidin-1-carbonyl)-thienyl]_5-pyrrolo [2,3_δ] 0 to 咕7 formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2_t^(2'6-diamidino-piperidine-bucarbonyl) Thiophene-2-yl]_5 uglypyrrolo[2,34]° than tillage ~7_carboxylic acid ((S)-l,2,2·trimethyl-propyl)-decylamine; "[7~(( S)-1,2,2-trimethyl-propylamine fluorenyl each [2'3~6]° ratio _-2-yl]-thiophene-2-carbonyl}-piperidine-4-anthracene Acid; 2-[5-(4-acetamidoamino-piperidine-hydrazino-carbonyl)-thiophene-2-ylpyrrolo[2,3-6]%, well_7_decanoic acid ((8) _1,2,2_tridecyl-propyl)-decylamine; 2-[5-(4-methyl-benzylaminoindolyl)-thiophene-2-yl]_5-pyridyl [2'3-6]° ratio tillage-7-formic acid ((S)-l,2,2-tridecyl-propyl)·guanamine; 2·[5_(4-fluoro-benzoguanamine A醯基)- 叹 基 基]_5 丑_pyrrolo[2,3_ 刎pyridin-7-carboxylic acid ((s)-^, · trimethyl-propyl) _ decylamine; 2-[5-(2 , 3- Dioxo-phenylhydrazinyl fluorenyl) 〇 〇 _2 _ _ _ 。 。 。 。 。 。. Ratio p [2,3-6]pyrazine-7·decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[5-(2-methyl -benzoylaminemethanyl)-thiophene-2-yl]_5 good_pyrolo[2,3-δ]pyrazine-7_carboxylic acid tridecyl-propyl)-decylamine; 2-[5 -(2,6-difluoro-benzylaminecarbamyl)-. Phenyl-2-yl]_5 good_pyrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-decylamine; 2- [5-(2-Ga-6-fluoro-benzoguanamine fluorenyl)-.塞 _2 _ _ _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- [5-(2-Methyl-cyclohexylaminecarbamyl)-°Cet-2-7-yl]·5-open π-pyridyl[2,3-6]pyrazine-7-decanoic acid (0) 4,2,2-trimethyl-propyl)-decylamine; 2-[5-((lS,2R)-2·phenyl-cyclopropylamineyl)-n-cepan-2-yl] _5仏156090.doc -26 - 201204731 Pyrrolo[2,3-6]pyrazine-7-decanoic acid trimethyl-propyl)-decylamine; 2-{5-[(4-methyl-thiophene- 2-ylmethyl)-amine-methylmercaptothiophene-2•kib-5//_pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((8)-1,2,2-trimethyl _-propyl)- guanamine; 2-{5-[(5-methyl-furan-2-ylmethyl)-aminoindenyl]-thiophene-2-yl-5//-pyrrolo[2 , 3-6] pyridin-7-decanoic acid ((s)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-(adamantan-1-ylamine fluorenyl) ) _ thiophene-2·yl]-57/-pyrrolo[2,3-acylpyrazine-7-decanoic acid ((S)-l,2,2-tridecyl-propyl decylamine; 2-{ 5-[1-(4-Fluoro-phenyl)-ethylaminemethanyl]-thiophene-2-ylhydrazide-5-Pylo-[2,3-6]pyrazine-7-carboxylic acid (( S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-(decyloxy- Mercapto-amine-carbamoyl)-thiophene-2-yl]_5 ugly-pyrrolo[2,3-Z&gt;]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl- Propyl)-nonylamine; 2-(5-methoxyaminemethantyl-thiophene-2-yl)_5ii-pyrrolo[2,3-6]pyrazine-7-brew ((S)-l , 2,2-trimethyl-propyl)-bristamine; 2-(5-prop-2-ynylaminoindolylthiophene-2-yl)_5//_pyrrolo[2,3 6] Pyridin-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-{5-[(R)-2-(3 open-imidazol-4-yl) ) mercapto-ethylamine-mercapto]thiophen-2-yl}-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethyl --propyl)-decylamine; 2-[5-(5,6,7,8-tetrahydro-naphthalene-2-ylamino)-thiophene-2-yl-5pyrrolo[2, 3 work] pyridin _7-formic acid ((shut tridecyl-propyl decylamine; 2-(5-phenylaminoindolyl-thiophene-2-yl)_5孖_pyrrolo[2,3] Pyridin _7_ 156090.doc -27- 201204731 citric acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-((R)-l-p-tolyl -ethylaminoindenyl)-thiophen-2-yl]-5//-. Bis[2,3-6]pyrh-7-nonanoic acid ((S)-l,2,2-tridecyl-propyl)-decylamine; 2-[5-(2-methoxyl) -Benzylamine fluorenyl)-thiophen-2-yl]-5//-. Bis-[2,3-gong]pyrazine-7-decanoic acid ((3)-1,2,2-trimethyl-propyl)-guanamine; 2-[5-(2,5-dioxin) Oxy-benzoylaminemethanyl)-thiophen-2-yl]pyrolo[2,3-0]pyrazine-7-decanoic acid ((S)-l,2,2-tridecyl- Propyl)-nonylamine; 2-{5-[(4-fluoro-phenylhydrazino)-methyl-aminoindolyl]-thiophen-2-yl}-5//-pyrrolo[2,3- 6]pyridin-7-decanoic acid ((8)-1,2,2-trimethyl-propyl)-decylamine; 2-[5-(3-methoxy-benzylaminecarbamyl) - thiophen-2-yl]-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((3)-1,2,2-tridecyl-propyl)-decylamine; 2-[5-(3-Trifluoromethyl-benzylaminoindolyl)-thiophen-2-yl]-5^-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S )-l,2,2-tridecyl-propyl)-guanamine; 2-[5-(2- gas-4-indole-phenylamine)-*cephen-2-yl]- 5 ° piroxi[2,3-έ]pyrazine-7-carboxylic acid ((S)-1,2,2-trimethyl-propyl)-guanamine; 2-[5-((R)- l,2,2-Trimethyl-propylaminemethanyl)-thiophen-2-yl]-577-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-l, 2,2-trimethyl-propyl)-guanamine; 2-[5-(2,2-dimethyl-propylaminemethanyl)-thiophen-2-yl]-5//-pyrrole [2,3-do]pyrazine-7-decanoic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-[5-((R)-2-methane Sulfhydryl-1-indenyl-ethylamine-mercapto)-thiophen-2-yl]-57/-pyrrolo[2,3-0]pyrazine-7-carboxylic acid ((S)-l,2 , 2-trimethyl-propyl)-guanamine; 2-[5-(1,1-di-oxy-hexahydro-1λ6-thiopiperazin-4-ylamino)- 156090. Doc •28· 201204731 Thiophen-2-yl]-5if-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((s)-l,2,2-tridecyl-propyl)-醯Amine; 2-[5-(1,1-di- oxo-1 human 6-thio- phenanthrene-4-yl)- porphin-2-yl]_ 5 ugly-pyrrolo[2,3 Pyridinium-7-formic acid trimethyl-propyl)-guanamine; 2-[5-(2-methoxy-1-methyl-ethylamine decyl)_D-septene-2-yl]_5 ugly 〇 〇 咯 [ [2,3-6] pyridin-7 -decanoic acid ((S)_1,2,2-trimethylpropyl)-decylamine; 2-(5-aminoindolylthiophene-2-yl)_5 ugly-pyrrolo[2,3_ft] Pyridin_7_decanoic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[5-(3,3,3-trifluoro-propylaminemethanyl) )_thiophene_2•yl]_5//_pyrrolo[2,3-seven-pyrazine_7_decanoic acid ((SH,2,2_tridecyl-propyl)-decylamine; 2-[5- (2-oxa-6-aza-spiro[3 3]heptane_6-carbonylthiophene-2-diyl-di-[2,3-secretary 7-carboxylic acid ((8)-U,2-trimethyl) -propyl)-bristamine; 2-[5-(3,3-bis-hydroxyindenyl-azaindole oxetane-1-carbonyl)-thiophen-2-yl. Biordo[2,3_Z&gt ;]pyrazine_7-A-text ((S)-l,2,2-trimethyl-propyl)_g amine; carbamide-thiol)-thiophene-2-yl]-5-acid (S)-l,2,2-trimethyl-propyl)_醯2-[4-methyl-5-(tetrahydro-nivine oxime 0 洛和[2,3-办] mouth ratio p well _7_Methylamine; 2 [5 (1,1 - oxo-u, thiomorpholine carbonyl) _4·methyl-thiophene 2 _ ib 5 / ^ each [2,3 · heart ~ · formic acid眺(1)-trimethyl-propyl)-nitramine 2 [4 methyl _5_(2_oxa-6_aza snail [3.3] ng _6· fluorenyl) - sold pheno - 156090.doc • 29· 201204731 2-based]-5//- ° 比比和[2,3-Z&gt;]pyrazine-7-carboxylic acid ((S)-l,2,2-trimethylpropylamine; 2-[5-(3,3-bis- Hydroxymethyl-azetidin-^carbonyl)_4_methyl-porphin-2-yl]-5//-pyrrolo[2,3-6]pyrazine-7-carboxylic acid ((S)- l,2,2-trimethyl-propyl)-guanamine; 2-[5-(tetrahydro-piperazin-4-ylaminecarbamimidyl)-thiophene-2-yl]-57/-pyrrole [2,3-0]pyrazine-7-decanoic acid ((S)-2-cyano-1,2,2-trimethyl-ethyl) decylamine; 2-[5-(piperidine- 1-carbonyl)-thienyl]-5/f-pyrrolo[2,3-6]pyrazine-7-decanoic acid ((S)-2-cyano-1,2,2-trimethyl-B 2-[5-(tetrahydro-piperazin-4-ylaminemethylmercaptothiophene-2-yl]-5 ft-pyrrolo[2,3-6]pyridin-7-decanoic acid ((S)-1,2,2-trimethyl-propyl)-decylamine; 2-(5-present methylamine-mercaptothiophene-2·基比略和[2,3_办] 0 呼 7-carboxylic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-[5-(3-cyano-benzoguanamine fluorenyl) thiophene _2_基]_5开_〇比咯和[2,3-办]pyrazine-7-decanoic acid (S) -l, 2,2- trimethyl-propyl) - _ Amides; 2- (3 - cyano - present) -5 ugly _〇 than each of p and [2,3 do]. 〇井井_7_Isopropyl decyl phthalate; 2-(3-decyloxy-phenoxy)-5/7-indolepyrrolo[2,3·6]pyridinium-7-formic acid Propyl decylamine; 2_(3_difluorodecyloxy-benyloxy)-5//-*&gt; ratio „各[2,3_办]. Specific tillage _7_isopropyl isopropyl hydrazine Amine; 2-(3-Nong 2 7&quot; base-presentoxy piroxi[2,3_do]0 isopropyl decylamine; 156090.doc •30- 201204731 2-metaphenoxy- 5//-° ratio [2,3-6]»pyr- -7 isopropyl decyl phthalate; 2-(3-ethyl-phenoxy)-5//-° bilu [2,3-6]〇比井_7_isopropyl decyl decanoate; 2-(3-isopropyl-phenoxy group B and [2,3-6]n than well-7- Isopropylamine formate; 2-(3-trifluoromethyl-phenoxy)-5 ugly-.pyrho[2,3-6]pyrazine-7-decyl isopropylamine; Collapse ^ 2-(2-di-parent! fluorenyl-benyloxy)-5 i/- ° than 〇[2,3-do]n _ 7 _ isopropyl decyl amide; 2- (2-Benzyl-benoxy)-5 //. Ratio of [2,3-6]π ratio to ρ well_7_isopropyl decyl phthalate; 2-(2-ethyl-ben Oxy)·5 ° ratio slightly [2,3-6]° than well-7-formic acid isopropylamine; 2-(5,6,7,8-tetrahydro-naphthalene-1-yloxy) )-5 ft-pyrrolo[2,3-&amp;]pyrazine_7_isopropyl decylamine; ® 2-(5,6,7,8-tetrahydro-naphthalen-2-yloxy)_57 /-pyrrolo[2,3 work]pyrazine-7·isopropyl decylamine; 2-(naphthalene-1-yloxypyroxy[2,3 work]. Specific tillage _7_isopropyl formate Baseline amine; 2-(naphthalen-2-yloxy)-5//-° ratio '» each [2,3-6] 〇 _7_ isopropyl decylamine; 2-(3 -Chloro-presentoxy-biha-[2,3-6]» than _7-formic acid isopropylamine; 156090.doc -31· 201204731 2-(3-chloro-benoxy)-5/ /- 0 is more than B and [2,3-do]. Compared with "» well_7-formic acid ethyl decylamine; 2-(3-carbyl-presentoxy)-5//-° ratio p and [2,3-6] n-pyro- _7_ decanoic acid ethyl tyranamine; 2-(3-dimethoxy-p-oxy)-5//·-〇 嘻 嘻 [2,3_ ] 比 比 _ _ 7-formic acid ethyl decylamine; 2- (3- 茗 tridecyl - phenoxy) - 5 fluoren [2, 3 ά β ] β than till _7_ formic acid ethyl guanamine ; 2_ m-tolyloxy-5/f-pyrrolo[2,3-6]pyrrolin-7-formic acid ethylguanamine; 2-(3-ethyl-phenoxypyrrolo[2,3_6] Pyridoxine ethyl decylamine; 2-(3-isopropyl-phenoxy)_5-open pyrrolopyrene _7-decanoic acid ethyl decylamine; 2-(3- Difluoromethyl-phenoxy)_5 ugly ratio slightly [2,3_do]n ratio tillage_7·formic acid ethylguanamine; 2-o-tolyloxy-5//-pyrrolo[2,3 -6]pyrazine_7_isopropyl decylamine; 2-(2-difluoromethoxy-phenoxy)_5 ft-pyrrolo[2,3_6]d than argon-7 carboxylic acid isopropyl Guanidine; 2-(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)_5孖-pyrrolo[2,3-6]pyrazine-7-carboxylic acid Propyl decylamine; 2-(2- gas-phenoxypyrrolo[2,3 work] pyridinium-7-formic acid isopropylamine; 2-(2.methoxy-phenoxy)_5/ /_pyrrolo[2,3 work]pyrazine_7•isopropyl isopropyl 156090.doc •32· 201204731 base amide; 2-o-tolyloxy-5i/-pyrrolo[2,3_6]pyrazine Acid ethyl decylamine; 2-(3,5--methoxy-benyloxy)_5-open-. More than 11 each [2,3_do] 0 to 11 well _7_ isopropyl decylamine; 2-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)_5// _nBiluo[2,3_6] β ratio tillage_7_ decanoic acid ethyl decylamine; 2-(5,6,7,8-tetrahydro-naphthalen-2-yloxy ratio „各[2,3_&amp ;]. than the cultivation of ethyl formate; Ethyl decylamine; 2-(3·decyloxy-phenoxy)-5i/-pyrrolo[23_6]pyridinium-7-decanoic acid ethylguanamine; 2-(2-a-phenoxy)- 5/f- η is more than [2,3-6]pyridinium; 2-(4-cyano-phenoxy)-5 ugly-&quot; ratio η[2,3-6je ratio spray_ 7 ethyl hydrazine formate - isopropyl decylamine; 2-(4 · cyano-phenoxy) _ 5 吼 吼 并 [2, 3_6]. Specific amine; 2-((R)-3-nonanesulfonylamino-pump-5-yloxy[2,3-6]pyrazine-7-decyl isopropylamine; -7 - Ethyl decyloxy)-5-.比比和156090.doc •33· 201204731 2-((R)-3-Ethylamino-indan-5-yloxy)-5//-pyrrolo[2,3-6] pyridin -7-Isopropyl decylamine; 2-((R)-3 -methyl succinylamino-p--5-yloxy)-5 //· β 嘻 嘻 [2,3- 6]pyridin-7-decanoic acid ethyl decylamine; 2-((R)-3-ethylenylamino group••Fly-5-yloxyl ratio slightly [2 3] pyro__7_ Ethylguanidinium formate; 2-(1/^吲哚-6-yloxy)-5open-°Biloze[2,3-6]'1 ratio tillage_7-formic acid isopropylamine; 2-(1 _°°°°丨°朵-6-yloxy)-5//-° ratio 0 and [2,3-6]. Ratio &gt; well _7·ethyl formate; 2-(1//&gt;-'»丨丨&lt;1-4-yloxy)-5//'-'1 than "» each [2,3-6]° ratio '»井_ 7_isopropyl decyl decanoate; 2-(1//- 吲哚-4-yloxy)-5 ft-pyrrolo[2,3-6]pyrazine_7-formic acid ethyl decylamine; 2-(1-methyl-1//-吲哚-6-yloxy)-5-pyrrolo[2,34]n than isopropyl myristate; 2-( l/f- 〇 丨 丨 朵 朵 朵 朵 -5 -5 丨 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 2- 2- 2- 2- 2- 2- 2- Base) -5//-0 than Luo and [one - do not call - - Isopropyl decylamine; 2·(4,6-dimethyl-0-buty-2-yloxy)-5//-° ratio 2[2,3_6]〇 ratio p well formic acid isopropyl Indoleamine; 2_(2·methyl-0 is more than -3-yloxy)_5 tablets &quot; 0 to 0 each [2,3-6]. Compared with 〇7_ isopropyl decylamine; 156090.doc -34- 201204731 2-((R)-3-Amino-indan-5-yloxy)_5Ugly-pyrrolo[2,3_6]pyrazine_7_Isopropyl citrate ; 2-((R)-3-propyl-arylamino-p--5-yloxy)-5//- η ratio π each [2, do] pyridin-7-isopropyl isopropyl hydrazine Amine; 2-{(R)-3-[(tetrahydro-piperidin-4-carbonyl)-amino]-indan-5-yloxybu 5//·pyrrolo[2,3-6] Pyridin-7-isopropyl decylamine; 2-[(R)-3-(cyclopropanecarbonyl-amino)_indan_5_yloxy]_5/i_Dtb B and [2,3 work Pyridin-7-isopropyl decylamine; [(R)~3 -(2,2-monomethyl-propyl-arylamino)-p--5-yloxy]_5 pyrrolo[ 2,3 work] pyridin-7-isopropyl decyl phthalate; 2_((R)-3 - this arylamino group - knowing -5 - oxy group ratio slightly [2 3_ do] pyridine Plough-7-isopropyl decylamine; 2_((R)_3-ethyl-arylamino-chid-5-yloxy)_5 ratio slightly [2] pyrin-7 Formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-((S)-3-ethoxyethylamino- ip-5-yloxy)-5 / / ° ratio slightly [2 3 - do] pyridin-7 · isopropyl decyl phthalate; 2- ((S)-3-amino-indan-5-yloxypyrylene [2, 3-6] pyridinium 7-isopropyl decyl decanoate; 2-(indan-5-yloxy)-5 ugly-pyrrolo[2,3-Ζ&gt;]pyrazine-7-decanoic acid Isopropyl decylamine; 2-((R)-l-ethinylamino-indan-5-yloxypyrrolo[2,3_^pyridin-7-decanoic acid ((S)-l, 2,2-trimethyl-propyl)-decylamine; 2-[(R)-3-(3-methyl-ureido)-indan-5-yloxy]-5 ugly-.咯 并 [2,3_ έ]0 than argon-7-formic acid isopropyl amide; 156090.doc '35- 201204731 2-(3-carbyl-indan-5-yloxy)-5// -0 to n each [2,3-6]° ratio &lt;» well _7·isopropyl guanidinium amide; 2-((R)-3-ethylenylamino-p--5-yl Gas base) -5 / / ~ n ratio π each [2 3] pyridin-7-carboxylic acid ((R)-l-cyclopropyl-ethyl) amide; 2-((R)-3 -Ethylamino-pumpy-5-yloxy)-5//- η 比洛和[2 3办] Pyrignin-7-formic acid ((S)-l-cyclopropyl-ethyl) - decylamine; 2-((R)-3-ethylenylamino··indan-5-yloxy)-5//-° 嘻[2 3] pyridin-7-carboxylic acid ( (S)-t-butyl)-guanamine; 2-(3-o-oxy-indan-5-yloxy)-5 ugly-pyrrolo[2,3-6]pyrazine·7_ Isopropylamine formate; 2_((R)-3·ethinylamino-indan_5·yloxy)-5 ugly-pyrido[2 3 6]pyrazine-7-carboxylic acid (cyanide) -methyl-methyl)-guanamine; 2-((R)-3-ureido-indan-5-yloxy)-5/ί-° ratio [2,3-£&gt; ] 〇 „ _ well _7 isopropyl decyl formate; 2- (2-ethyl arylamino-p--5-yloxy)-5 / / - ° Biluo [2,3_6]. Plowing _ 7-isopropyl decylamine; 2- ((R)_3-mercaptoamino-indan-5-yloxy ratio η each [2 3_办] pyridin-7-formic acid isopropyl guanamine; 2-(177-茚-5 - oxypyrrolo[2,3-6]pyrazine_7-isopropyl decylamine; 2-((R)-3-hydroxy-indan-5-yloxy)_5-pyrrole And [2,3_6]pyrazine_7 isopropyl decylamine; 2-((S)-3-hydroxy-indan-5-yloxy)_5open_„比比和[2,34]pyrr Ignition of isopropyl decylamine; 156090.doc -36 - 201204731 2-((1〇-1-amino-indan-5-yloxy)-5---pyrylene [2,3 -6]pyrazine-7_ formic acid ((S)-l,2,2-trimethyl-propyl)-guanamine; 2-((R)-8-ethinylamino-5,6,7 ,8-tetrahydro-naphthalen-2-yloxy)-5//-° ratio of [2,3-6]pyrazine-7-decanoic acid ((S)-l,2,2·3 -propyl)-guanamine; 2-((R)-8-amino-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-5β-indolo[2,3 -6]. Tillage-7-formic acid ((S)-l,2,2-trimethyl-propyl)-decylamine; 2-((R)-8-ethenylamino-5,6 , 7,8-tetrahydro-naphthalen-2-yloxypyrolo[2,3-6]pyrazine-7-decanoic acid ((R)-l.cyclopropyl-ethyl)-decylamine; 2-((1〇-8-Mercaptoamino-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-5//-. Bis-[2,3-6]pyrazine-7-decanoic acid ((R)-l-cyclopropyl-ethyl)-decylamine; 2_((R)_8-amino-5,6,7 ,8-tetrazine-cai-2-yloxyβ ratio °[[^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ -Ethyl mercaptoindolino-5-yloxypyrolo[2,3-6] ° ratio tillage-7-carboxylic acid dicyclopropylindenyl-decylamine; 2-((R)-l - Ethylamino-indan-5-yloxy)-5//-la-[2,3-do] 0-plough-7-decanoic acid ((R)-l-cyclopropyl-B And decylamine; and 2-((R)-8-ethylamido-5,6,7,8-tetrahydro-naphthalen-2-yloxy)-5//-pyrrolo[2 , 34] pyridin-7-decanoic acid ((S)-2·decyloxy-1-mercapto-ethyl)·decylamine. 16_—Use of a compound according to any one of claims 1 to 15 And a medicament for the treatment of an inflammatory condition or an autoimmune condition. 17. The use of claim 16, wherein the drug is used in combination with or further comprises another therapeutic agent. The further therapeutic agent is selected from the group consisting of a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulator or an immunosuppressive 156090.doc-37-201204731 agent, a trophic factor, An agent for treating a cardiovascular disease or a medicament for treating an immunodeficiency disorder. The use of the compound according to any one of items 1 to 15 for the preparation of a medicament for treating rheumatoid arthritis 19. The use of a compound of any one of the claims n5 for the manufacture of a medicament for the treatment of asthma. 20. The use of a compound according to any one of claims 1 to 15 For the preparation of a medicament for treating an immune disorder, including lupus cerebral rickets, rheumatoid arthritis, psoriasis, type j diabetes, complications of organ transplantation, xenograft, diabetes, cancer, snarl And ectopic ί dermatitis, autoimmune nail climbing, vine occupation, ulcerative colon: inflammation, 'Cr. ron's disease (Cr〇hn, s diSease), Alzheimer's disease (Alzheimer's disease) And leukemia. A pharmaceutical composition comprising a mixture of a compound according to any one of claims j to 5 with at least one pharmaceutically acceptable carrier, excipient or diluent. As for the doctor of the 21st a composition further comprising another therapeutic agent selected from the group consisting of a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating cardiovascular diseases, an agent for treating diabetes, and An agent for the treatment of an immunodeficiency disorder. 23. A compound according to claim 1 or 2 for use in the treatment of an inflammatory condition or an autoimmune condition. 24. A compound according to claim 1 or 2 for use in the treatment of any of the conditions as recited in claim 7, 2 or 22. 156090.doc 38· 201204731 IV. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbolic symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please reveal the best display invention. Characteristic chemical formula: 156090.doc