Malt1 inhibitors

Abstract

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the inhibition of MALT1.

Description

[0001] MALT1 INHIBITORS FIELD OF THE INVENTION The present invention relates to a novel compound that is a MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) inhibitor. The compound may be useful for the treatment of a disease, syndrome, condition, or disorder, particularly a MALT1-related disease, syndrome, condition, or disorder, including but not limited to, cancer and immunological diseases. The invention also relates to pharmaceutical compositions comprising one or more of such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds or pharmaceutical compositions for the treatment of cancer and autoimmunological diseases, syndromes, disorders, or conditions associated with MALT1 inhibitors. BACKGROUND OF THE INVENTION MALT1 (mucosa-associated lymphoid tissue lymphoma translocation 1) is a key mediator of the classical NF^B signaling pathway. MALT1 is the only human paracaspase and transduces signals from the B cell receptor (BCR) and T cell receptor (TCR). MALT1 is the active subunit of the CBM complex which is formed upon receptor activation. The CBM complex consists of multiple subunits of three proteins: CARD11 (caspase recruitment domain family member 11), BCL10 (B-cell CLL / Lymphoma 10) and MALT1. MALT1 affects NF^B signaling by two mechanisms: firstly, MALT1 functions as a scaffolding protein and recruits NF^B signaling proteins such as TRAF6, TAB-TAK1 or NEMO-IKKα / ^; and secondly, MALT1, as a cysteine protease, cleaves and thereby deactivates negative regulators of NF^B signaling, such as RelB, A20 or CYLD. The ultimate endpoint of MALT1 activity is the nuclear translocation of the NF^B transcription factor complex and activation of NF^B signaling. Constitutive activation of NF^B signaling is the hallmark of ABC-DLBCL (Diffuse Large B cell Lymphoma of the Activated B Cell-like subtype), the more aggressive form of DLBCL. DLBCL is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for approximately 25% of lymphoma cases while ABC-DLBCL comprises approximately 40% of DLBCL. NF^B pathway activation is driven by mutations of signaling components, such as CD79A / B, CARD11, MYD88 or A20, in ABC-DLBCL patients. The use of BTK inhibitors, for example Ibrutinib, provides clinical proof-of-concept that inhibiting NF^B signaling in ABC-DLBCL is efficacious. MALT1 is downstream of BTK in the NF^B signaling pathway and a MALT1 inhibitor could target ABC-DLBCL patients not responding to Ibrutinib, mainly patients with CARD11 mutations, as well as treat patients that acquired resistance to Ibrutinib. Small molecule tool compound inhibitors of MALT1 protease have demonstrated efficacy in preclinical models of ABC-DLBCL. Interestingly, covalent catalytic site and allosteric inhibitors of MALT1 protease function have been described, suggesting that inhibitors of this protease may be useful as pharmaceutical agents. The chromosomal translocation creating the API2-MALT1 fusion oncoprotein is the most common mutation identified in MALT (mucosa-associated lymphoid tissue) lymphoma. API2-MALT1 is a potent activator of the NF^B pathway. API2-MALT1 mimics ligand-bound TNF receptor, promotes TRAF2-dependent ubiquitination of RIP1 which acts as a scaffold for activating canonical NF^B signaling. Furthermore, API2-MALT1 has been shown to cleave and generate a stable, constitutively active fragment of NF^B-inducing kinase (NIK) thereby activating the non-canonical NF^B pathway. In addition to lymphomas, MALT1 has been shown to play a critical role in innate and adaptive immunity. MALT1 protease inhibitor can attenuate disease onset and progression of mouse experimental allergic encephalomyelitis, a mouse model of multiple sclerosis. Mice expressing catalytically inactive MALT1 mutant showed loss of marginal zone B cells and B1 B cells and general immune deficiency characterized as decreased T and B cell activation and proliferation. However, those mice also developed spontaneous multi-organ autoimmune inflammation at the age of 9 to 10 weeks. It is still poorly understood why MALT1 protease dead knock-in mice show a break of tolerance while conventional MALT1 KO mice do not. One hypothesis suggests the unbalanced immune homeostasis in MALT1 protease dead knock- in mice may be caused by incomplete deficiency in T and B cell but severe deficiency of immunoregulatory cells. Similarly, MALT deficiency in humans has been associated with combined immunodeficiency disorder. Given the difference between genetic mutation and pharmacological inhibition, a phenotype of MALT1 protease dead knock-in mice might not resemble that of patients treated with MALT1 protease inhibitors. A reduction of immunosuppressive T cells by MALT1 protease inhibition may be beneficial to cancer patients by potentially increasing antitumor immunity. Thus, MALT1 inhibitors of the present invention may provide a therapeutic benefit to patients suffering from cancer and / or immunological diseases. SUMMARY OF THE INVENTION The present invention is directed to compounds of Formula (I) and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl; R2represents halo; n is 0, 1 or 2; R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, -CF3, Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, -C(=O)-Het3b, and ; or Raand R are taken together to form together with the nitrogen atom to which they are attached Het2; Cy1represents C3-6cycloalkyl; or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of halo, -OH, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; Het1represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het1represents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7-S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het2represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het2represents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, Het6, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, Het4and -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, Het4, or -C(=O)-C3-6cycloalkyl; Het3arepresents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het3arepresents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het3brepresents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het3brepresents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, C1-4alkyl, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het4represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het5represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het6represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); R4aand R4beach independently represent hydrogen, C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl-O-C1-4alkyl; R4cand R4deach independently represent C1-4alkyl or -O-C1-4alkyl; R5represents hydrogen or halo; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl or C3-6cycloalkyl, each optionally substituted with one, two or three halo substituents; p1 and p2 each independently are 1, 2 or 3; and the pharmaceutically acceptable salts thereof. The present invention is also directed to compounds of Formula (A) and R1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl; R2represents halo; n is 0, 1 or 2; R5represents hydrogen or halo; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; and the pharmaceutically acceptable salts thereof. All references to “compound(s) of Formula (I)” and “compound(s) of Formula (A)”, in the context of this invention, might also refer to a solvate or a pharmaceutically acceptable salt form thereof, even if not explicitly referred to, and are included in the scope of the present invention. It will be clear this also applies to subgroups of Formula (I) and Formula (A). The compounds of Formula (I) and compounds of Formula (A) may exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and it is intended that the invention embrace both solvated and unsolvated forms. As used herein, bonds shown only as solid lines and not as solid wedged or hashed wedged bonds, hashed or bold bonds, or otherwise indicated as having a particular configuration (e.g. by a stereodescriptor such as R, S, ‘R or S’, ‘S or R’, trans, cis) around one or more atoms, contemplate each possible stereoisomer (stereoisomeric form), or mixture of two or more stereoisomers. Where the stereochemistry of any particular chiral atom is not specified in the structures shown herein, then all possible stereoisomers are contemplated and included as the compounds of the invention, either as a pure stereoisomer or as a mixture of two or more stereoisomers. Hereinbefore and hereinafter, the term “compound(s) of Formula (I)” is also meant to include the tautomers and the stereoisomeric forms (stereoisomers; for example enantiomers and diastereomers) thereof, even if not explicitly referred to. However, where stereochemistry, as mentioned in the previous paragraph, is specified by bonds which are shown as solid wedged or hashed wedged bonds, hashed or bold bonds, or are otherwise indicated as having a particular configuration (e.g. R, S, ‘R or S’, ‘S or R’, trans, cis), then that stereoisomer is so specified and defined. It will be clear this also applies to subgroups of Formula (I). It will be clear this also applies to corresponding compounds of Formula (A). In the context of this invention it should be understood that bonds shown as solid lines but indicated with a stereodescriptor, mean that such a stereocenter is specified and defined according to the stereodescriptor. In the context of this invention it should be understood that bonds shown as solid lines but indicated with ‘R or S’ or ‘S or R’, are used to indicate that such a stereocenter is chirally pure but with unknown configuration (pure stereoisomers and enantiomerically pure, but absolute stereochemistry undetermined on stereocenter indicated with ‘R or S’ or ‘S or R’). Substituents on bivalent cyclic saturated (for example a cyclopropyl moiety) or partially saturated radicals may have either the cis- or trans-configuration. Terms like ‘trans A’ or ‘trans B’ mean that one particular trans form was obtained but that the absolute stereochemistry was undetermined. It will be clear for a skilled person that a hashed bond and a bold bond on a 1,3- disubstituted cyclobutyl moiety as shown below: , whereby X1and X2represent substituents, on the cyclobutyl moiety have trans-configuration. It will be clear for a skilled person that the bold bonds on a 1,3-disubstituted cyclobutyl moiety as shown below: , whereby X1and X2represent substituents, on the cyclobutyl moiety have cis-configuration. It will be clear for a skilled person that a hashed bond and a bold bond on a 1,4- disubstituted cyclohexyl moiety as shown below: , whereby X1and X2represent substituents, indica on the cyclohexyl moiety have trans-configuration. It will be clear for a skilled person that the bold bonds on a 1,4-disubstituted cyclohexyl moiety as shown below: , whereby X1and X2represent substituents, the cyclohexyl moiety have cis-configuration. Atropisomers (or atropoisomers) are stereoisomers which have a particular spatial configuration, resulting from a restricted rotation about a single bond, due to large steric hindrance. All atropisomeric forms of the compounds of Formula (I) are intended to be included within the scope of the present invention. If a compound contains a double bond, the substituents may be in the E or the Z configuration. Therefore, the invention and the term “compound(s) of Formula (I)” is also meant to include enantiomers, atropisomers, diastereomers, racemates, E isomers, Z isomers, cis isomers, trans isomers and mixtures thereof, whenever chemically possible. It will be clear this also applies to compounds of Formula (A). The meaning of all those terms, i.e. enantiomers, atropisomers, diastereomers, racemates, E isomers, Z isomers, cis isomers, trans isomers and mixtures thereof are known to the skilled person. The configuration is specified in line with standard priority rules according to the Cahn-Ingold-Prelog system. The term “compound(s) of the (present) invention” or “compound(s) according to the (present) invention” as used herein, is meant to include the compounds of Formula (I) or Formula (A) including tautomers and stereoisomeric forms, the pharmaceutically acceptable salt forms, and the solvates thereof. The present invention also provides a pharmaceutical composition comprising, consisting of and / or consisting essentially of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and / or a pharmaceutically acceptable diluent and a compound of Formula (I). It will be clear this also applies to compounds of Formula (A). Also provided are processes for making a pharmaceutical composition comprising, consisting of, and / or consisting essentially of admixing a compound of Formula (I), and a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and / or a pharmaceutically acceptable diluent. It will be clear this also applies to compounds of Formula (A). The present invention further provides methods for treating or ameliorating a disease, syndrome, condition, or disorder in a subject, including a mammal and / or human in which the disease, syndrome, or condition is affected by the inhibition of MALT1, including but not limited to, cancer and / or immunological diseases, using a compound of Formula (I). It will be clear this also applies to compounds of Formula (A). The present invention also is directed to the use of any of the compounds described herein in the preparation of a medicament wherein the medicament is prepared for treating a disease, syndrome, condition, or disorder that is affected by the inhibition of MALT1, such as cancer and / or immunological diseases. The present invention is also directed to the preparation of compounds of Formula (I) that act as an inhibitor of MALT1. The present invention is also directed to the preparation of compounds of Formula (A) that act as an inhibitor of MALT1. Exemplifying the invention are methods of treating a disease, syndrome, condition, or disorder mediated by MALT1, using a compound of Formula (I). In particular said disease, syndrome, condition, or disorder mediated by MALT1 is selected from the group consisting of lymphomas, leukemias, carcinomas, and sarcomas, e.g. non-Hodgkin’s lymphoma (NHL (including B-cell NHL)), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphoma, T-cell lymphoma, Hodgkin’s lymphoma, Burkitt’s lymphoma, multiple myeloma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia, lymphoblastic T cell leukemia, chronic myelogenous leukemia (CML), hairy-cell leukemia, acute lymphoblastic T cell leukemia, plasmacytoma, immunoblastic large cell leukemia, megakaryoblastic leukemia, acute megakaryocytic leukemia, promyelocytic leukemia, erytholeukemia, brain (gliomas), glioblastomas, breast cancer, colorectal / colon cancer, prostate cancer, lung cancer including non-small-cell, gastric cancer, endometrial cancer, melanoma, pancreatic cancer, liver cancer, kidney cancer, squamous cell carcinoma, ovarian cancer, sarcoma, osteosarcoma, thyroid cancer, bladder cancer, head and neck cancer, testicular cancer, Ewing’s sarcoma, rhabdomyosarcoma, medulloblastoma, neuroblastoma, cervical cancer, renal cancer, urothelial cancer, vulval cancer, esophageal cancer, salivary gland cancer, nasopharangeal cancer, buccal cancer, cancer of the mouth, and GIST (gastrointestinal stromal tumor), comprising, consisting of, and / or consisting essentially of, administering to a subject in need thereof a therapeutically effective amount of any of the compounds or pharmaceutical compositions described in the present invention. In another embodiment, the disease, syndrome, condition, or disorder mediated by MALT1 is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and mucosa-associated lymphoid tissue (MALT) lymphoma. An embodiment of the present invention is directed to a compound of Formula (I) for (use in) the treatment of immunological diseases that are affected by the inhibition of MALT1, including but not limited to, autoimmune and inflammatory disorders, e.g. arthritis, inflammatory bowel disease, gastritis, ankylosing spondylitis, ulcerative colitis, pancreatits, Crohn’s disease, celiac disease, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, rheumatic fever, gout, organ or transplact rejection, chronic allograft rejection, acute or chronic graft-versus-host disease, dermatitis including atopic, dermatomyositis, psoriasis, Behcet’s diseases, uveitis, myasthenia gravis, Grave’s disease, Hashimoto thyroiditis, Sjorgen’s syndrome, blistering disorders, antibody-mediated vasculitis syndromes, immune-complex vasculitides, allergic disorders, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pneumonia, pulmonary diseases including oedema, embolism, fibrosis, sarcoidosis, hypertension and emphysema, silicosis, respiratory failure, acute respiratory distress syndrome, BENTA disease, berylliosis, and polymyositis. In another embodiment, the present invention is directed to a compound of Formula (I) for (use in) the treatment of a disease, syndrome, condition, or disorder affected by inhibition of MALT1, selected from the group consisting of rheumatoid arthritis (RA), psoritic arthritis (PsA), psorisis (Pso), ulcerative colitis (UC), Crohn’s disease, systemic lupus erythematosus (SLE), asthma, and chronic obstructive pulmonary disease (COPD). In an alternate embodiment, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is selected from non-Hodgkin’s lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma, mantle cell lymphoma (MCL), follicular lymphoma (FL), transformed follicular lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. In yet another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is lymphoma. In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is the activated B cell like (ABC) subtype of diffuse large B- cell lymphoma (DLBCL). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is germinal center B cell like (GCB) subtype of diffuse large B-cell lymphoma (DLBCL). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is non-germinal center B cell like (non-GCB) subtype of diffuse large B-cell lymphoma (DLBCL). In an additional embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is chronic lymphocytic leukemia (CLL). In another embodiment, the disorder or condition small lymphocytic lymphoma (SLL). In another embodiment of the invention, the lymphoma is MALT lymphoma. In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is Waldenström macroglobulinemia (WM). In yet another embodiment, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and mucosa-associated lymphoid tissue (MALT) lymphoma. In an alternate embodiment, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is non-Hodgkin’s lymphoma (NHL). In a further embodiment, the non- Hodgkin’s lymphoma (NHL) is B-cell NHL. In another embodiment, the non-Hodgkin’s lymphoma (NHL) is relapsed / refractory B-cell NHL. In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is selected from the group consisting of relapsed / refractory non-germinal center B cell like (non-GCB) subtype of diffuse large B-cell lymphoma (DLBCL), relapsed / refractory Waldenström macroglobulinemia (WM), relapsed / refractory mantle cell lymphoma (MCL), relapsed / refractory follicular lymphoma (FL), and relapsed / refractory mucosa-associated lymphoid tissue (MALT) lymphoma. In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is relapsed / refractory non-germinal center B cell like (non- GCB) subtype of diffuse large B-cell lymphoma (DLBCL). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is relapsed / refractory Waldenström macroglobulinemia (WM). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is relapsed / refractory mantle cell lymphoma (MCL). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is relapsed / refractory follicular lymphoma (FL). In another embodiment of the invention, the disease, syndrome, condition, or disorder affected by inhibition of MALT1 is relapsed / refractory mucosa-associated lymphoid tissue (MALT) lymphoma. Compounds of Formula (I) may be used for the treatment of immunological diseases including, but not limited to, autoimmune and inflammatory disorders, e.g. sepsis-related acute lung injury (ALI), acute respiratory distress syndrome (ARDS), arthritis, rheumatoid arthritis (RA), psoriatic arthritis (PsA), inflammatory bowel disease, gastritis, ankylosing spondylitis, ulcerative colitis, pancreatitis, Crohn’s disease, celiac disease, multiple sclerosis, systemic lupus erythematosus, lupus nephritis, rheumatic fever, gout, organ or transplant rejection, chronic allograft rejection, acute or chronic graft-versus-host disease, dermatitis including atopic, dermatomyositis, psoriasis, Behcet’s diseases, uveitis, myasthenia gravis, Grave’s disease, Hashimoto thyroiditis, Sjorgen’s syndrome, blistering disorders, antibody-mediated vasculitis syndromes, immune-complex vasculitides, allergic disorders, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pneumonia, pulmonary diseases including oedema, embolism, fibrosis, sarcoidosis, hypertension and emphysema, silicosis, respiratory failure, acute respiratory distress syndrome, BENTA disease, berylliosis, and polymyositis. In another embodiment of the present invention, the compounds of the present invention may be employed in combination with one or more other medicinal agents, more particularly with other anti-cancer agents, e.g. chemotherapeutic, anti-proliferative or immunomodulating agents, or with adjuvants in cancer therapy, e.g. immunosuppressive or anti-inflammatory agents. Possible combinations of the compounds of the present invention may include, but are not limited to, BTK (Bruton’s tyrosine kinase) inhibitors such as ibrutinib, SYK inhibitors, PKC inhibitors, PI3K pathway inhibitors, BCL family inhibitors, JAK inhibitors, PIM kinase inhibitors, rituximab or other B cell antigen-binding antibodies, as well as immune cell redirection agents (e.g. blinatumomab or CAR T-cells) and immunomodulatory agents such as daratumumab, anti-PD1 antibodies, and anti-PD-L1 antibodies. It will be appreciated that variations to the foregoing embodiments of the invention can be made while still falling within the scope of the invention. Each feature disclosed in this specification, unless stated otherwise, may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. All possible combinations of the above-indicated embodiments are considered to be embraced within the scope of this invention. In another embodiment, the present invention is directed to a compound of Formula (I) for (use in) the treatment of said disease, syndrome, condition, or disorder affected by the inhibition of MALT1. In another embodiment, the present invention is directed to a composition comprising a compound of Formula (I) for (use in) the treatment of said disease, syndrome, condition, or disorder affected by inhibition of MALT1. In another embodiment, the present invention is directed to methods of treating said disease, syndrome, condition, or disorder mediated by MALT1. Another embodiment of the present invention is directed to a pharmaceutical composition comprising a compound of Formula (I) and uses thereof as described in any of the other embodiments. DETAILED DESCRIPTION OF THE INVENTION With reference to substituents, the term “independently” refers to the situation where several substituents are selected independently from each other and may be the same or different from each other. The term “about” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. Unless explicitly stated otherwise within the Examples or elsewhere in the Specification in the context of a particular assay, result or embodiment, “about” means within one standard deviation per the practice in the art, or a range of up to 5%, whichever is larger. The transitional terms “comprising,” “consisting essentially of,” and “consisting of” are intended to connote their generally accepted meanings in the patent vernacular; that is, (i) “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; (ii) “consisting of” excludes any element, step, or ingredient not specified in the claim; and (iii) “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention. Embodiments described in terms of the phrase “comprising” (or its equivalents) also provide as embodiments those independently described in terms of “consisting of” and “consisting essentially of.” The prefix ‘Cx-y’ (where x and y are integers) as used herein refers to the number of carbon atoms in a given group. Thus, a C1-4alkyl group contains from 1 to 4 carbon atoms, and so on. The term ‘C1-4alkyl’ as used herein as a group or part of a group represents a straight or branched chain saturated hydrocarbon radical having from 1 to 4 carbon atoms, such as methyl, ethyl, n- propyl, isopropyl, n-butyl, s-butyl, t-butyl and the like. The term ‘C3-6cycloalkyl’ as used herein as a group or part of a group defines a saturated, cyclic hydrocarbon radical having from 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Fused bicycles or fused bicyclic groups, are two cycles that share two atoms and the bond between these atoms. Spiro bicycles or spiro bicyclic groups, are two cycles that are joined at a single atom. Bridged bicycles or bridged bicyclic groups, are two cycles that share more than two atoms. The term ‘C6-10carbobicyclic’ as used herein as a group or part of a group defines a saturated, bicyclic hydrocarbon radical having from 6 to 10 carbon atoms. C6-10carbobicyclic can be fused, spiro or bridged, such as spiro[3.3]heptanyl and bicyclo[1.1.1]pentanyl. The term ‘monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one two or three heteroatoms each independently selected from O, S, and N’, defines a C-linked fully saturated, monocyclic radical having from 4 to 7 ring members in total (including the heteroatoms) containing one, two or three heteroatoms each independently selected from O, S, and N, such as for example C-linked azetidinyl, C-linked oxetanyl, C-linked pyrrolidinyl, C- linked tetrayhydrothiophenyl, C-linked tetrahydrofuranyl, C-linked morpholinyl, C-linked 1,4- oxathianyl, C-linked thiazinanyl, C-linked tetrahydropyranyl, C-linked tetrahydrothiopyranyl, C-linked pyrazolidinyl, C-linked isothiazolidinyl, C-linked oxazolidinyl, and C-linked piperidinyl. Bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl groups can be fused, spiro or bridged. The term ‘bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N’, defines a C-linked fully saturated, bicyclic radical having from 6 to 11 ring members in total (including the heteroatoms) containing one, two or three heteroatoms each independently selected from O, S, and N, such as for example: , , The term ‘monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N’, defines a N-linked fully saturated, monocyclic radical having from 4 to 7 ring members in total (including the heteroatoms) containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N, such as for example N-linked azetidinyl, N-linked pyrrolidinyl, N-linked morpholinyl, N-linked thiazinanyl, N-linked pyrazolidinyl, N-linked isothiazolidinyl, N-linked oxazolidinyl, N-linked thiomorpholinyl, N-linked piperazinyl, N- linked thiazolidinyl, N-linked azepanyl, N-linked thiadiazepanyl, and N-linked piperidinyl. Bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl groups can be fused, spiro or bridged. The term ‘bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N- atom and optionally one or two heteroatoms each independently selected from O, S, and N’, defines a N-linked fully saturated, bicyclic radical having from 6 to 11 ring members in total (including the heteroatoms) containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N, such as for example: , . Unless otherwise specified or clear from the context, cyclic moieties such as fully saturated heterocyclyl goups, can be attached to the remainder of the molecule of Formula (I) through any available ring carbon atom (C-linked) or nitrogen atom (N-linked). C-linked means attached to the remainder of the molecule through any available carbon atom. N-linked means attached to the remainder of the molecule through any available nitrogen atom. The term “halogen” or “halo” refers to fluorine, chlorine, bromine and iodine atoms. A skilled person will understand R2is absent when n is 0. It will be clear for the skilled person that S(=O)2or SO2represents a sulfonyl moiety. It will be clear for the skilled person that a group such as -S(=O)(=NH)-C1-4alkyl represents . be clear for the skilled person that a group such as -S(=O)(=NH)-R (with R being any substituent) represents . It will be clear for the skilled person that a group such as -N=S(=O)-(C1-4alkyl)2 represents . for the skilled person that a group such as -NH-(C=O)-C1-4alkyl represents . r the skilled person that a group such as -NH-(C=O)-C3-6cycloalkyl represents . It will be clear for the skilled person that a group such as -NH-(SO2)-C1-4alkyl represents . clear for the skilled person that a group such as -NH-(SO2)-R (with R being any substituent) represents . Whenever substituents are represented by chemical structure, “---” represents the bond of attachment to the remainder of the molecule of Formula (I) or (A). When any variable occurs more than one time in any constituent, each definition is independent. When any variable occurs more than one time in any formula (e.g. Formula (I)), each definition is independent. The skilled person will understand that in general, whenever the term ‘substituted’ is used in the present invention, it is meant, unless otherwise indicated or clear from the context, to indicate that one or more hydrogens, in particular from 1 to 4 hydrogens, more in particular from 1 to 3 hydrogens, preferably 1 or 2 hydrogens, more preferably 1 hydrogen, on the atom or radical indicated in the expression using ‘substituted’ are replaced with a selection from the indicated group, provided that the normal valency is not exceeded, and that the substitution results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture (isolation after a reaction e.g. purification by silica gel chromatography). The skilled person will understand that the term ‘optionally substituted’ means that the atom or radical indicated in the expression using ‘optionally substituted’ may or may not be substituted (this means substituted or unsubstituted respectively). Lines drawn from substituents into ring systems indicate that the bond may be attached to any of the suitable ring atoms. The stereodescriptor label “R” or “(R)” at a stereocenter designates that the stereocenter is purely of the R-configuration as defined in the art; likewise, the stereodescriptor label “S” or “(S)” means that the stereocenter is purely of the S-configuration. A compound containing one stereocenter drawn without a stereo bond designation is a mixture of two stereoisomers unless otherwise indicated (for example via a stereodescriptor). A compound containing two stereocenters both drawn without stereo bond designations is a mixture of four diastereomers unless otherwise indicated (for example via stereodescriptors). Unlabeled stereocenters drawn without stereo bond designations are mixtures of the R- and S- configurations. For unlabeled stereocenters drawn with stereo bond designations, the absolute stereochemistry is as depicted. Hereinbefore and hereinafter, the term “compound(s) of Formula (I)” is meant to include the stereoisomers thereof and the tautomeric forms thereof. However, where stereochemistry, as mentioned in the previous paragraph, is specified by bonds which are shown as solid wedged or hashed wedged bonds, or are otherwise indicated as having a particular configuration (e.g. R, S), then that stereoisomer is so specified and defined. It will be clear this also applies to subgroups of Formula (I). Unless otherwise noted, it is intended that the definition of any substituent or variable at a particular location in a molecule be independent of its definitions elsewhere in that molecule. It is understood that substituents and substitution patterns on the compounds of the present invention can be selected by one of ordinary skill in the art to provide compounds that are chemically stable enough to isolate and that can be synthesized by methods set forth herein in combination with techniques known in the art. The term “subject” refers to an animal, preferably a mammal, most preferably a human, who has been the object of treatment, observation or experiment. The term “therapeutically effective amount” refers to an amount of an active compound or pharmaceutical agent, including a compound of the present invention, which elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, including reduction or inhibition of an enzyme or a protein activity, or ameliorating symptioms, alleviating conditions, slowing or delaying disease progression, or preventing a disease. In one embodiment, the term “therapeutically effective amount” refers to the amount of a compound of the present invention that, when administered to a subject, is effective to (1) at least partially alleviate, inhibit, prevent, and / or ameliorate a condition, or a disorder or a disease (i) mediated by MALT1; or (ii) associated with MALT1 activity; or (iii) characterized by activity (normal or abnormal) of MALT1; or (2) reduce or inhibit the activity of MALT1; or (3) reduce or inhibit the expression of MALT1; or (4) modify the protein levels of MALT1. The term “composition” refers to a product that includes the specified ingredients in therapeutically effective amounts, as well as any product that results, directly, or indirectly, from combinations of the specified ingredients in the specified amounts. Suitable examples of a disease, syndrome, condition, or disorder mediated by MALT1 include, but are not limited to, lymphomas, leukemias, carcinomas, and sarcomas, e.g. non- Hodgkin’s lymphoma (NHL (including B-cell NHL)), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphoma, T-cell lymphoma, Hodgkin’s lymphoma, Burkitt’s lymphoma, multiple myeloma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia, lymphoblastic T cell leukemia, chronic myelogenous leukemia (CML), hairy-cell leukemia, acute lymphoblastic T cell leukemia, plasmacytoma, immunoblastic large cell leukemia, megakaryoblastic leukemia, acute megakaryocytic leukemia, promyelocytic leukemia, erytholeukemia, brain (gliomas), glioblastomas, breast cancer, colorectal / colon cancer, prostate cancer, lung cancer including non-small-cell, gastric cancer, endometrial cancer, melanoma, pancreatic cancer, liver cancer, kidney cancer, squamous cell carcinoma, ovarian cancer, sarcoma, osteosarcoma, thyroid cancer, bladder cancer, head and neck cancer, testicular cancer, Ewing’s sarcoma, rhabdomyosarcoma, medulloblastoma, neuroblastoma, cervical cancer, renal cancer, urothelial cancer, vulval cancer, esophageal cancer, salivary gland cancer, nasopharangeal cancer, buccal cancer, cancer of the mouth, and GIST (gastrointestinal stromal tumor). As used herein, the term "MALT1 inhibitor" refers to an agent that inhibits or reduces at least one condition, symptom, disorder, and / or disease of MALT1. As used herein, unless otherwise noted, the term “affect” or “affected” (when referring to a disease, syndrome, condition or disorder that is affected by the inhibition of MALT1) includes a reduction in the frequency and / or severity of one or more symptoms or manifestations of said disease, syndrome, condition or disorder; and / or includes the prevention of the development of one or more symptoms or manifestations of said disease, syndrome, condition or disorder or the development of the disease, condition, syndrome or disorder. As used herein, the term “treat”, “treating”, or “treatment” of any disease, condition, syndrome or disorder refers, in one embodiment, to ameliorating the disease, condition, syndrome or disorder (i.e. slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In another embodiment, “treat”, “treating”, or “treatment” refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient. In a further embodiment, “treat”, “treating”, or “treatment” refers to modulating the disease, condition, syndrome or disorder either physically (e.g. stabilization of a discernible symptom), physiologically, (e.g. stabilization of a physical parameter), or both. In yet another embodiment, “treat”, “treating”, or “treatment” refers to preventing or delaying the onset or development or progression of the disease, condition, syndrome or disorder. The compounds of the instant invention may be useful in methods for treating or ameliorating a disease, a syndrome, a condition or a disorder that is affected by the inhibition of MALT1. Such methods comprise, consist of and / or consist essentially of administering to a subject, including an animal, a mammal, and a human in need of such treatment, amelioration and / or prevention, a therapeutically effective amount of a compound of Formula (I). One embodiment of the present invention is directed to a method of treating a MALT1- dependent or MALT1-mediated disease or condition in a subject in need thereof, including an animal, a mammal, and a human in need of such treatment, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I). In another embodiment, the MALT1-dependent or MALT1-mediated disease or condition is selected from cancers of hematopoietic origin or solid tumors such as chronic myelogenous leukemia, myeloid leukemia, non-Hodgkin lymphoma, and other B cell lymphomas. In particular, the compounds of Formula (I) may be useful for treating or ameliorating diseases, syndromes, conditions, or disorders such as diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and mucosa-associated lymphoid tissue (MALT) lymphoma. More particularly, the compounds of Formula (I) may be useful for treating or ameliorating diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and mucosa-associated lymphoid tissue (MALT) lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) as herein defined. Further, the compounds of Formula (I) may be useful for treating or ameliorating an immunological disease, syndrome, disorder, or condition selected from the group consisting of rheumatoid arthritis (RA), psoritic arthritis (PsA), psorisis (Pso), ulcerative colitis (UC), Crohn’s disease, systemic lupus erythematosus (SLE), asthma, and chronic obstructive pulmonary disease (COPD). Whenever possible, any embodiment for the compounds of Formula (I) as listed hereinabove or hereinafter, also holds for the compounds of Formula (A). The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl; R2represents halo; n is 0, 1 or 2; R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -NH-(C=O)-R7, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, - NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, - S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of -OR7, -S(=O)2-R7, and -S(=O)2-NR4aR4b; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)-NR4aR4b, -P(=O)-R4cR4d, -O- C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, - Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, and ; or together to form together with the nitrogen atom to which they are attached Het2; Cy1represents C3-6cycloalkyl; or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of -S(=O)2-C1-4alkyl, and -S(=O)2- NR4aR4b; Het1represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het1represents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, -OH, -OR7-S(=O)2-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, - P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, and -C(=O)-NR4aR4b; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three -OH; Het2represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het2represents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of Het6, -S(=O)2-NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)- NR4aR4b, and C1-4alkyl optionally substituted with one, two or three -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with Het4; Het3arepresents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het3arepresents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, and -OH; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, or -C(=O)-C3-6cycloalkyl; Het3brepresents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het3brepresents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, C1-4alkyl, and -OR7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, or -S(=O)2-C1-4alkyl; Het4represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het5represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het6represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); R4aand R4beach independently represent hydrogen, C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl-O- C1-4alkyl; R4cand R4deach independently represent C1-4alkyl or -O-C1-4alkyl; R5represents hydrogen or halo; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl or C3-6cycloalkyl, each optionally substituted with one, two or three halo substituents; p1 and p2 are 2; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2; R1brepresents halo or -C(=O)-NH2; represents phenyl; R3arepresents hydrogen; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; or C3-6cycloalkyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2; R1brepresents F or -C(=O)-NH2; represents phenyl; R3arepresents hydrogen; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; or C3-6cycloalkyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents -CH3or -CH2OH; R7represents C1-4alkyl; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2; R1brepresents F or -C(=O)-NH2; represents phenyl; n is 0; R3arepresents hydrogen; R3brepresents hydrogen; C1-4alkyl; or cyclobutyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents -CH3or -CH2OH; R7represents C1-4alkyl; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2; R1brepresents F; represents phenyl; n is 0; R3arepresents hydrogen; R3brepresents C3-6cycloalkyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents -CH2OH; R7represents C1-4alkyl; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2; R1brepresents F; represents phenyl; n is 0; R3arepresents hydrogen; R3brepresents cyclobutyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents -CH2OH; R7represents C1-4alkyl; and the pharmaceutically acceptable salts thereof. The present invention relates in particular to compounds of Formula (I) as defined herein, and the tautomers and the stereoisomeric forms thereof, wherein R1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl; R2represents halo; n is 0, 1 or 2; R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -NH-(C=O)-R7, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, - NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, - S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of -OR7, -S(=O)2-R7, and -S(=O)2-NR4aR4b; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)-NR4aR4b, -P(=O)-R4cR4d, -O- C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, - Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, and ; or together to form together with the nitrogen atom to which they are attached Het2; Cy1represents C3-6cycloalkyl; or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of -S(=O)2-C1-4alkyl, and -S(=O)2- NR4aR4b; Het1represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het1represents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; provided that the monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl and bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl, are selected from the following heterocyclyls: C-linked azetidinyl, C-linked oxetanyl, C-linked pyrrolidinyl, C-linked tetrayhydrothiophenyl, C-linked tetrahydrofuranyl, C-linked morpholinyl, C-linked 1,4- oxathianyl, C-linked thiazinanyl, C-linked tetrahydropyranyl, C-linked tetrahydrothiopyranyl, C-linked pyrazolidinyl, C-linked isothiazolidinyl, C-linked oxazolidinyl, C-linked piperidinyl, , , total one, two or three substituents each independently selected from the group consisting of oxo, -OH, -OR7-S(=O)2-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, - P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, and -C(=O)-NR4aR4b; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three -OH; Het2represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het2represents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; provided that the monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl and bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl, are selected from the following heterocyclyls: N-linked azetidinyl, N-linked pyrrolidinyl, N-linked morpholinyl, N-linked thiazinanyl, N- linked pyrazolidinyl, N-linked isothiazolidinyl, N-linked oxazolidinyl, N-linked thiomorpholinyl, N-linked piperazinyl, N-linked thiazolidinyl, N-linked azepanyl, N-linked thiadiazepanyl, N-linked piperidinyl, , , total one, two or three substituents each independently selected from the group consisting of -S(=O)2-NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)- NR4aR4b, and C1-4alkyl optionally substituted with one, two or three -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with Het4; Het3arepresents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; provided that the monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl is selected from the following heterocyclyls: N-linked azetidinyl, N-linked pyrrolidinyl, N-linked morpholinyl, N-linked thiazinanyl, N- linked pyrazolidinyl, N-linked isothiazolidinyl, N-linked oxazolidinyl, N-linked thiomorpholinyl, N-linked piperazinyl, N-linked thiazolidinyl, N-linked azepanyl, N-linked thiadiazepanyl, and N-linked piperidinyl; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, and -OH; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, or -C(=O)-C3-6cycloalkyl; Het3brepresents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het3brepresents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; provided that the monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl and bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl, are selected from the following heterocyclyls: C-linked azetidinyl, C-linked oxetanyl, C-linked pyrrolidinyl, C-linked tetrayhydrothiophenyl, C-linked tetrahydrofuranyl, C-linked morpholinyl, C-linked 1,4- oxathianyl, C-linked thiazinanyl, C-linked tetrahydropyranyl, C-linked tetrahydrothiopyranyl, C-linked pyrazolidinyl, C-linked isothiazolidinyl, C-linked oxazolidinyl, C-linked piperidinyl, ; the carbon atoms in said heterocyclyl might be substituted with in substituents each independently selected from the group consisting of oxo, halo, -OH, C1-4alkyl, and -OR7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, or -S(=O)2-C1-4alkyl; Het4represents C-linked oxetanyl; Het5represents C-linked oxetanyl; R4aand R4beach independently represent hydrogen, C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl-O- C1-4alkyl; R4cand R4deach independently represent C1-4alkyl or -O-C1-4alkyl; R5represents hydrogen or halo; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl or C3-6cycloalkyl, each optionally substituted with one, two or three halo substituents; p1 and p2 are 2; and the pharmaceutically acceptable salts thereof. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R2represents fluoro. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein n is 0. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein n is 1. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl. In an embodiment, the present to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl and n is 0. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl, and R6represents methyl. In an embodiment, the present to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl, n is 0, and R6represents methyl. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl, and R6represents -CH2OH. In an embodiment, the present to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein represents phenyl, n is 0, and R6represents -CH2OH. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3brepresents C1-4alkyl; or C3-6cycloalkyl substituted with one -S(=O)2-C1-4alkyl. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3brepresents C1-4alkyl. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3brepresents C3-6cycloalkyl substituted with one -S(=O)2-C1-4alkyl; in particular cyclobutyl substituted with one -S(=O)2-C1-4alkyl; more in particular cyclobutyl substituted with one - S(=O)2-CH3. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein substituent -S(=O)2-C1-4alkyl is limited to -S(=O)2-CH3. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R6represents CH3. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R6represents -CH2OH. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, -CF3, Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, -C(=O)-Het3b, and . In an present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3aand R3bare taken together to form together with the nitrogen atom to which they are attached Het2. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; or C3-6cycloalkyl substituted with one -S(=O)2-R7. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3arepresents hydrogen; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; or C3-6cycloalkyl substituted with one -S(=O)2-R7. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3arepresents hydrogen. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R3arepresents C1-4alkyl. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is trans: . In an (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is cis: . In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is trans: , of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is cis: , and wherein R6represents methyl. In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is trans: , s of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the cyclopropyl moiety in Formula (I) is cis: , In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the substituents on the cyclopropyl moiety in Formula (I) is as indicated below in Formula (I-a): . In an and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein the stereochemistry of the substituents on the cyclopropyl moiety in Formula (I) is as indicated below in Formula (I-b): . In an embodiment, the present invention relates to those compounds of Formula (I) and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein Formula (I) and the stereochemistry of the substituents on the cyclopropyl moiety are as indicated below in Formula (I-a1): . In an and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein Formula (I) and the stereochemistry of the substituents on the cyclopropyl moiety are as indicated below in Formula (I-b1): . In an and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R1bis in para position as indicated below in Formula (I-c): . In an and the pharmaceutically acceptable salts thereof, or any subgroup thereof as mentioned in any of the other embodiments, wherein R1bis in position para. Whenever possible, any embodiment for the compounds of Formula (I) as listed hereinabove, also holds for the compounds of Formula (A). In an embodiment, the present invention relates to a subgroup of Formula (I) as defined in the general reaction schemes. In an embodiment the compound of Formula (I) is selected from the group consisting of any of the exemplified compounds, tautomers and stereoisomeric forms thereof, and the free bases, and the pharmaceutically acceptable salts thereof. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 5, 7, 10, 12, 15, 16, 17, 18, 19, 20, and 23. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 5, 7, 10, 12, 15, 16, 17, 18, 19, 20, and 23; tautomers and stereoisomeric forms thereof, and the pharmaceutically acceptable salts thereof. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 5, 7, 10, 12, 15, 16, 17, 18, 19, 20, and 23; and the pharmaceutically acceptable salts thereof. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, and 321 to 486. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, and 321 to 486; tautomers and stereoisomeric forms thereof, and the pharmaceutically acceptable salts thereof. In an embodiment the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, and 321 to 486; and the pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of Formula (I) is selected from the group consisting of any of the exemplified compounds. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of Formula (I) is selected from the group consisting of any of the exemplified compounds, tautomers and stereoisomeric forms thereof, and the pharmaceutically acceptable salts thereof. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 5, 7, 10, 12, 15, 16, 17, 18, 19, 20, and 23. The present invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) and a pharmaceutically acceptable carrier or excipient, wherein the compound of Formula (I) is selected from the group consisting of compounds 1, 2, 5, 7, 10, 12, 15, 16, 17, 18, 19, 20, and 23; tautomers and stereoisomeric forms thereof, and the pharmaceutically acceptable salts thereof. In an embodiment the compound of Formula (I) is compound 1 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 2 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 5 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 7 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 10 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 12 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 15 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 16 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 17 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 18 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 19 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 20 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 23 or a pharmaceutically acceptable salt thereof. In an embodiment the compound of Formula (I) is compound 1. In an embodiment the compound of Formula (I) is compound 2. In an embodiment the compound of Formula (I) is compound 5. In an embodiment the compound of Formula (I) is compound 7. In an embodiment the compound of Formula (I) is compound 10. In an embodiment the compound of Formula (I) is compound 12. In an embodiment the compound of Formula (I) is compound 15. In an embodiment the compound of Formula (I) is compound 16. In an embodiment the compound of Formula (I) is compound 17. In an embodiment the compound of Formula (I) is compound 18. In an embodiment the compound of Formula (I) is compound 19. In an embodiment the compound of Formula (I) is compound 20. In an embodiment the compound of Formula (I) is compound 23. In an embodiment the compound of Formula (I) is thereof. In an embodiment the compound of Formula (I) is . In an embodiment the compound of Formula (I) is In an embodiment the compound of Formula (I) is . In an embodiment the compound of Formula (I) is acceptable salt thereof. In particular moiety is trans, in particular trans A. In an embodiment the compound of Formula (I) is In an embodiment the compound of Formula (I) is . In an embodiment the compound of Formula (I) is In an embodiment the compound of Formula (I) is In an embodiment the compound of Formula (I) is In an embodiment the compound of Formula (I) is . (I) is . All possible combinations of the above indicated embodiments are considered to be embraced within the scope of the invention. For use in medicine, salts of compounds of Formula (I) refer to non-toxic “pharmaceutically acceptable salts.” Other salts may, however, be useful in the preparation of compounds of Formula (I) or of their pharmaceutically acceptable salt forms thereof. Suitable pharmaceutically acceptable salts of compounds of Formula (I) include acid addition salts that can, for example, be formed by mixing a solution of the compound with a solution of a pharmaceutically acceptable acid such as, hydrochloric acid, sulfuric acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, citric acid, tartaric acid, carbonic acid or phosphoric acid. Furthermore, where the compounds of Formula (I) carry an acidic moiety, suitable pharmaceutically acceptable salts thereof may include alkali metal salts such as, sodium or potassium salts; alkaline earth metal salts such as, calcium or magnesium salts; and salts formed with suitable organic ligands such as, quaternary ammonium salts. Thus, representative pharmaceutically acceptable salts include acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, oleate, pamoate (embonate), palmitate, pantothenate, phosphate / diphosphate, polygalacturonate, salicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate. Representative acids and bases that may be used in the preparation of pharmaceutically acceptable salts include acids including acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor- 10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxy- ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucoronic acid, L-glutamic acid, ^-oxo-glutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1- hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, L-pyroglutamic acid, salicylic acid, 4-amino-salicylic acid, sebaic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid and undecylenic acid; and bases including ammonia, L-arginine, benethamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)-ethanol, ethanolamine, ethylenediamine, N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2-hydroxyethyl)-morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)-pyrrolidine, sodium hydroxide, triethanolamine, tromethamine, and zinc hydroxide. Embodiments of the present invention include prodrugs of compounds of Formula (I). In general, such prodrugs will be functional derivatives of the compounds that are readily convertible in vivo into the required compound. Thus, in the methods of treating or preventing embodiments of the present invention, the term “administering” encompasses the treatment or prevention of the various diseases, conditions, syndromes and disorders described with the compound specifically disclosed or with a compound that may not be specifically disclosed, but which converts to the specified compound in vivo after administration to a patient. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs”, ed. H. Bundgaard, Elsevier, 1985. The pharmaceutically acceptable salts as mentioned hereinabove or hereinafter are meant to comprise the therapeutically active non-toxic acid and base addition salt forms which compounds of Formula (I) and solvates thereof, are able to form. A person of ordinary skill in the art would recognize that the compounds described herein may exist as tautomers and that other tautomeric arrangements of the structures depicted herein are possible. Tautomers are constitutional isomers that readily interconvert. It is understood that all tautomeric forms are encompassed by a structure where one possible tautomeric arrangement of the groups of the compound is described, even if not specifically indicated. Where the compounds according to embodiments of this invention have at least one chiral center, they may accordingly exist as enantiomers. Where the compounds possess two or more chiral centers, they may additionally exist as diastereomers. It is to be understood that all such isomers and mixtures thereof are encompassed within the scope of the present invention. Furthermore, some of the crystalline forms for the compounds may exist as polymorph and as such are intended to be included in the present invention. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be encompassed within the scope of this invention. The skilled artisan will understand that the term compound as used herein, can also include solvated compounds of Formula (I). Where the processes for the preparation of the compounds according to certain embodiments of the invention give rise to mixture of stereoisomers, these isomers may be separated by conventional techniques such as, preparative chromatography. The compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution. The compounds may, for example, be resolved into their component enantiomers by standard techniques such as, the formation of diastereomeric pairs by salt formation with an optically active acid such as, (-)-di-p-toluoyl-d-tartaric acid and / or (+)-di-p-toluoyl-l-tartaric acid followed by fractional crystallization and regeneration of the free base. The compounds may also be resolved by formation of diastereomeric esters or amides, followed by chomatographic separation and removal of the chiral auxiliary. Alternatively, the compounds may be resolved using a chiral HPLC column. It is intended that within the scope of the present invention, any one or more element(s), in particular when mentioned in relation to a compound of Formula (I), shall comprise all isotopes and isotopic mixtures of said element(s), either naturally occurring or synthetically produced, either with natural abundance or in an isotopically enriched form. For example, a reference to hydrogen includes within its scope1H,2H (D), and3H (T). Similarly, references to carbon and oxygen include within their scope respectively12C,13C and14C and16O and18O. The isotopes may be radioactive or non-radioactive. Radiolabelled compounds of formula (I) may comprise one or more isotope(s) selected from the group of3H,11C,18F,122I,123I,125I,131I,75Br,76Br,77Br and82Br. Preferably, the isotope is selected from the group of2H,3H,11C and18F. In particular, deuterated compounds are intended to be included within the scope of the present invention. During any of the processes for preparation of the compounds of the various embodiments of the present invention, it may be necessary and / or desirable to protect sensitive or reactive groups on any of the molecules concerned. This may be achieved by means of conventional protecting groups. The protecting groups may be removed at a convenient subsequent stage using methods known from the art. Even though the compounds of embodiments of the present invention (including their pharmaceutically acceptable salts and pharmaceutically acceptable solvates) can be administered alone, they will generally be administered in admixture with a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient and / or a pharmaceutically acceptable diluent selected with regard to the intended route of administration and standard pharmaceutical or veterinary practice. Thus, particular embodiments of the present invention are directed to pharmaceutical and veterinary compositions comprising compounds of Formula (I) and at least one pharmaceutically acceptable carrier, pharmaceutically acceptable excipient, and / or pharmaceutically acceptable diluent. By way of example, in the pharmaceutical compositions of embodiments of the present invention, the compounds of Formula (I) may be admixed with any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilizing agent(s), and combinations thereof. Solid oral dosage forms such as, tablets or capsules, containing the compounds of the present invention may be administered in at least one dosage form at a time, as appropriate. It is also possible to administer the compounds in sustained release formulations. A therapeutically effective amount of a compound of Formula (I) or a pharmaceutical composition thereof includes a dose range from about 0.1 mg to about 3000 mg, or any particular amount or range therein; although, it is apparent to one skilled in the art that the therapeutically effective amount for a compound of Formula (I) will vary as will the diseases, syndromes, conditions, and disorders being treated. It has been found that the compounds of the present invention inhibit MALT1 activity. In some embodiments, the inhibition of MALT1 by a provided compound may be useful in treating or preventing, in particular treating, the non-limiting list of cancers described herein. The invention relates to compounds of Formula (I) for use as a medicament. The invention relates to compounds of Formula (A) for use as a medicament. The invention relates to compounds of Formula (I) for use in the inhibition of MALT1 activity. The invention relates to compounds of Formula (A) for use in the inhibition of MALT1 activity. The invention relates to compounds of Formula (I) for use in the treatment of diseases mentioned herein. The invention relates to compounds of Formula (A) for use in the treatment of diseases mentioned herein. The invention relates to compounds of Formula (I) for the treatment or prevention, in particular for the treatment, of said diseases. The invention relates to compounds of Formula (A) for the treatment or prevention, in particular for the treatment, of said diseases. The invention relates to compounds of Formula (I) for the treatment or prevention, in particular in the treatment, of MALT1 mediated diseases or conditions. The invention relates to compounds of Formula (A) for the treatment or prevention, in particular in the treatment, of MALT1 mediated diseases or conditions. The invention relates to compounds of Formula (I) for the manufacture of a medicament. The invention relates to compounds of Formula (A) for the manufacture of a medicament. The invention relates to compounds of Formula (I) for the manufacture of a medicament for the inhibition of MALT1. The invention relates to compounds of Formula (A) for the manufacture of a medicament for the inhibition of MALT1. The invention relates to compounds of Formula (I) for the manufacture of a medicament for the treatment or prevention, in particular for the treatment, of any one of the disease conditions mentioned herein. The invention relates to compounds of Formula (A) for the manufacture of a medicament for the treatment or prevention, in particular for the treatment, of any one of the disease conditions mentioned herein. The invention relates to compounds of Formula (I) for the manufacture of a medicament for the treatment of any one of the disease conditions mentioned herein. The invention relates to compounds of Formula (A) for the manufacture of a medicament for the treatment of any one of the disease conditions mentioned herein. The invention relates to compounds of Formula (I) that can be administered to mammals, preferably humans, for the treatment or prevention of any one of the diseases mentioned herein. The invention relates to compounds of Formula (A) that can be administered to mammals, preferably humans, for the treatment or prevention of any one of the diseases mentioned herein. In view of the utility of the compounds of Formula (I), there is provided a method of treating warm-blooded animals, including humans, suffering from or a method of preventing warm- blooded animals, including humans, to suffer from any one of the diseases mentioned herein. In view of the utility of the compounds of Formula (A), there is provided a method of treating warm-blooded animals, including humans, suffering from or a method of preventing warm- blooded animals, including humans, to suffer from any one of the diseases mentioned herein. GENERAL SYNTHETIC METHODS In this section, as in all other sections unless the context indicates otherwise, references to Formula (I) also include all other sub-groups and examples thereof as defined herein. The general preparation of some typical examples of the compounds of Formula (I) is described hereunder and in the specific examples and are generally prepared from starting materials which are either commercially available or prepared by standard synthetic processes commonly used by those skilled in the art of organic chemistry. The following schemes are only meant to represent examples of the invention and are in no way meant to be a limit of the invention. Alternatively, intermediates or compounds of the present invention may also be prepared by analogous reaction protocols as described in the general schemes below and the specific examples, combined with standard synthetic processes commonly used by those skilled in the art. The skilled person will realize that in the reactions described in the Schemes, although this is not always explicitly shown, it may be necessary to protect reactive functional groups (for example hydroxy, amino, or carboxy groups) where these are desired in the final product, to avoid their unwanted participation in the reactions. In general, conventional protecting groups can be used in accordance with standard practice. The protecting groups may be removed at a convenient subsequent stage using methods known from the art. The skilled person will realize that in the reactions described in the Schemes, it may be advisable or necessary to perform the reaction under an inert atmosphere, such as for example under N2-gas atmosphere, for example when NaH, LDA or MeMgBr is used in the reaction. It will be apparent for the skilled person that it may be necessary to cool the reaction mixture before reaction work-up (refers to the series of manipulations required to isolate and purify the product(s) of a chemical reaction such as for example quenching, column chromatography, extraction). The skilled person will realize that heating the reaction mixture under stirring may enhance the reaction outcome. In some reactions microwave heating may be used instead of conventional heating to shorten the overall reaction time. The skilled person will realize that another sequence of the chemical reactions shown in the Schemes below, may also result in the desired compound of Formula (I). The skilled person will realize that intermediates and final compounds shown in the Schemes below may be further functionalized according to methods well-known by the person skilled in the art. The intermediates and compounds described herein can be isolated in free form or as a salt, or a solvate thereof. The intermediates and compounds described herein may be synthesized in the form of mixtures of tautomers and stereoisomeric forms that can be separated from one another following art-known resolution procedures. For abbreviations used in the Schemes below, check the table with abbreviations in the part ‘Examples’. In the preparation of compounds of the present invention, protection of remote functionality (e.g., primary, or secondary amine) of intermediates may be necessary. The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparation methods. Suitable amino-protecting groups (NH-PG) include but are not limited to acetyl, trifluoroacetyl, t-butoxycarbonyl (Boc), benzyl (Bn), benzyloxycarbonyl (CBz) and 9-fluorenylmethyleneoxycarbonyl (Fmoc). Suitable hydroxy-protecting groups include but are not limited to triisopropylsilyl and acetyl. The need for such protection is readily determined by one skilled in the art. In general, compounds of Formula I can be prepared as exemplified below in General Scheme 1, wherein the variables are described as hereabove: General Scheme 1 In general, compounds of Formula I can be prepared as exemplified below in General Scheme 1, wherein the variables are described as hereabove: substitution reaction between an intermediate of Formula (IIb) and a commercially available reagent (III), where X represents a suitable leaving group, such as for instance a halogen, in particular F, Cl, Br. This reaction may be performed in the presence of a suitable base, such as, for example, DIPEA, or Na2CO3. This reaction can be performed in a reaction-inert solvent, such as, for example, acetonitrile, DMF, or EtOH. The reaction is typically performed at a suitable temperature range, such as for instance 40 to 90 °C. It is understood by the persons skilled in the art that an additional deprotection step might be carried out, when R6= C1-4alkyl substituted with a OH, wherein the hydroxy group may be protected with a suitable protecting group. Alternatively, an intermediate of Formula IIb can react with an intermediate of Formula III, where X represents a suitable leaving group, such as for instance a halogen, in particular Cl, Br, I, under coupling reaction conditions, to provide an intermediate of Formula (I). This reaction may be performed in the presence of a suitable base, such as, for example, Cs2CO3, K3PO4 or K2CO3. This reaction can be performed in a reaction-inert solvent, such as, for example, tBuOH, toluene, DMA, or dioxane. The reaction is typically performed in the presence of a catalyst system comprising a suitable catalyst such as tBuXPhos Pd G3, BrettPhos Pd G3, or SPhos Pd G4 and a ligand such as BrettPhos. Preferably, this reaction is carried out under an inert atmosphere, such as nitrogen or argon atmosphere, and in a suitable temperature range, such as for instance room temperature to 60 °C, under conventional heating or microwave irradiation. In general, compounds of Formula (IIb) can be prepared as exemplified below in General Scheme 2, wherein the variables are described as hereabove: General Scheme 2 , halogen, in particular Cl, Br, I, is reacted with the appropriate known phosphonate of Formula (V) according to Horner-Wadsworth-Emmon’s reaction conditions, such as, for instance, triethyl-2-phosphonopropionate or ethyl 2-(diethoxyphosphoryl)-4-methylpentanoate, in the presence of an appropriate base, such as NaH, in a suitable solvent, such THF, at a suitable temperature range, such as for instance 0 °C to 25 °C, to provide an intermediate of Formula (VI). Alternatively, a compound of Formula (VI), in which R6is C1-4alkyl substituted with -OH could be prepared by a person skilled in the art according to described literature procedures (for instance, Pereire, A.A. et al, Eur. J. Org. Chem.2017, 12, 1578-1582). A person skilled in the art will understand that for compounds of Formula (VI), in which R6is C1-4alkyl substituted with -OH, the alcohol moiety might be protected with a suitable protecting group, such as triisopropylsilyl, which was kept throughout the synthetic scheme. Step 2. An intermediate of Formula (VI) is reacted with a suitable reductant, such as for instance, DIBAL-H, in a suitable solvent, such as for instance THF, and a suitable temperature range, such as for instance 0 °C to 25 °C, to provide an intermediate of Formula (VIIa). An intermediate of Formula (VIIa) is protected with a suitable protecting group, such as triisopropylsilyl ether or acetyl, by reaction with a suitable reagent, such as triisopropylsilyl chloride, or acetic anhydride in the presence of a base such as imidazole, pyridine, or triethylamine (TEA) in a suitable solvent, such as for instance DCM, and at a suitable temperature, such as, for instance, 25 °C, to provide an intermediate of Formula (VIIb) where PG= triisopropylsilyl or acetyl. Step 3. An intermediate of Formula (VIIb) is reacted with a suitable difluorocyclopropanation reagent, such as methyl 2,2-difluoro-2-(fluorosulfonyl)acetate, in the presence of additives such as for instance, potassium iodide and trimethylchlorosilane, in a suitable solvent, such bis(2- methoxyethyl)ether, at a suitable temperature, such as, for instance, 120 °C, to provide an intermediate of Formula (VIIIa). Alternatively, an intermediate of Formula (VIIb) is reacted with a suitable difluorocyclopropanation reagent, such as (bromodifluoromethyl)trimethylsilane, in a suitable solvent such as, for instance, toluene, at a suitable temperature, such as, for instance 110 °C, optionally in the presence of a catalyst such as tetrabutylammonium bromide, to provide an intermediate of Formula (VIIIa). An intermediate of Formula (VIIIa) where PG= triisopropylsilyl, is reacted with an appropriate deprotecting reagent / procedure, such as for instance, tetrabutylammonium fluoride, at a suitable temperature range, such as for instance 0 °C to 25 °C, to provide an intermediate of Formula (VIIIb). Step 4. An intermediate of formula (VIIIb) is reacted with a suitable oxidant, such as for instance, (diacetoxyiodo)benzene in the presence of a catalyst, such as for instance TEMPO, and a suitable base, such as NaHCO3, in an appropriate solvent, such as for instance a mixture of water and ACN, and a suitable temperature, such as for instance 25 °C, to provide an intermediate of Formula (IX). Step 5. An intermediate of Formula (IX) is reacted with an appropriate amine R3aR3bNH, wherein the variables are described as hereabove, in the presence of a suitable reagent, such as HATU, and an appropriate base such as for example triethylamine, typically in a solvent such as ACN, at a suitable temperature, such as for example room temperature, to provide an intermediate of Formula (X). Step 6. An intermediate of Formula (X) is coupled in the presence of a metal catalyst such as 4,4’-di-tert-butyl-2,2’-bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) hexafluorophosphate and (2,2’-bipyridine)nickel(II) dibromide, in the presence of additives, such as quinuclidine, with a commercially available reagent of Formula (XI), wherein X=OH, in a suitable solvent such as DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, in a suitable temperature range, such as for instance room temperature, under photoirradiation. It is understood by the persons skilled in the art that prior to the reaction, an intermediate of Formula (XI) requires pre-activation with a reagent such as 5,7-ditert-butyl-3-phenyl-1,3-benzoxazol-3- ium tetrafluoroborate, in the presence of a base, such as pyridine, in a suitable solvent such as TBME, 1,4-dioxane, CPME or CPME / DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, in a suitable temperature range, such as for instance room temperature, for a suitable time-range, such as 10-90 minutes. Step 7. An intermediate of Formula (VI) is reacted with a suitable difluorocyclopropanation reagent, such as (bromodifluoromethyl)trimethylsilane, in a suitable solvent such as, for instance, toluene, at a suitable temperature, such as, for instance 110 °C, optionally in the presence of a catalyst such as tetrabutylammonium bromide, to provide an intermediate of Formula (XII). Step 8. An intermediate of Formula (XII) is reacted under hydrolysis conditions to provide an intermediate of Formula (IX). This reaction can be performed in the presence of a suitable base, such as LiOH, in a suitable solvent system, such as water / THF optionally containing EtOH or MeOH, and at a suitable temperature range, such as room temperature. Alternatively, a compound of Formula (I) can be prepared via a coupling reaction between an intermediate of Formula (XIII) and a commercially available amine of R3aR3bNH, as exemplified below in General Scheme 3. General Scheme 3 In R3aR3bNH, wherein R is hydrogen, and all the other variables are described as hereabove. This reaction is carried out in the presence of a suitable reagent, such as HATU, an appropriate base such as for example TEA, typically in a solvent such as ACN, at a suitable temperature, such as for example room temperature, to provide an intermediate of Formula (I). It is understood by the persons skilled in the art that an additional deprotection step might be carried out, when R6= C1-4alkyl substituted with a OH, wherein the hydroxy is protected with a suitable protecting group. In general, an intermediate of Formula (XIII) can be prepared as exemplified below in General Scheme 4, wherein the variables are described as hereabove. General Scheme 4 such as (XII), wherein X is a leaving group, such as for instance halogen, Cl, Br, I as described in above Scheme 2 and a commercially available reagent of Formula (XI), wherein X is a leaving group, such as for instance a halogen, in particular I, and PG is a suitable amine protecting group, such as Boc or Cbz. The reaction can be performed in the presence of a metal catalyst such as Pd(dppf)Cl2, in the presence of an additive, such as CuI, in a suitable solvent, such as DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, and in a suitable temperature range, such as for instance room temperature to 90 °C. It is understood by the persons skilled in the art that prior to the reaction, reagent of Formula (XI) requires pre-activation in the the presence of a metal, such as zinc, and additives such as for instance, trimethylsilyl chloride and 1,2-dibromoethane, in a suitable solvent, such DMA, at a suitable temperature, such as, for instance, 45 °C. Alternatively, an intermediate of Formula (XII) is coupled with a commercially available reagent of Formula (XI), wherein X is a leaving group such as for instance a halogen, in particular I, and PG a suitable amine protecting group, such as Boc or Cbz. The reaction can be performed in the presence of metals such as zinc and NiI2, in the presence of MgCl2 and dtbbpy, in the presence of a base, such as pyridine, in an appropriate solvent, such as DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, in a suitable temperature range, such as for instance room temperature, for a suitable time-range, such as overnight.. Alternatively, an intermediate of Formula (XII) is coupled with a commercially available reagent of Formula (XI), wherein X=OH, and PG a suitable amine protecting group, such as Boc or Cbz. The reaction can be carried out in the presence of a metal catalyst such as 4,4’-di- tert-butyl-2,2’-bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) hexafluorophosphate and (2,2’- bipyridine)nickel(II) dibromide, in the presence of additives, such as quinuclidine, in a suitable solvent such as DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, in a suitable temperature range, such as for instance room temperature, under photo-irradiation. It is understood by the persons skilled in the art that prior to the reaction, Intermediate of Formula (XI) requires pre-activation with a reagent such as 5,7-ditert-butyl-3-phenyl-1,3-benzoxazol-3- ium tetrafluoroborate, in the presence of a base, such as pyridine, in a suitable solvent such as TBME, 1,4-dioxane, CPME or CPME / DMA, under an inert atmosphere, such as nitrogen or argon atmosphere, in a suitable temperature range, such as for instance room temperature. It is understood by a person skilled in the are that an intermediate of Formula (XIVa) can be submitted to known deprotection reaction conditions, to provide an intermediate of Formula (XIVb). Step 2. Compounds of Formula (XV) can be prepared via a nucleophilic substitution reaction between an intermediate of Formula (XIVb) and a commercially available reagent (III), where X represents a suitable leaving group, such as for instance a halogen, in particular F, Cl, Br. This reaction may be performed in the presence of a suitable base, such as, for example, DIPEA, or Na2CO3. This reaction can be performed in a reaction-inert solvent, such as, for example, acetonitrile, DMF or EtOH. The reaction is typically performed at a suitable temperature range, such as for instance 40 to 90 °C. Alternatively, an intermediate of Formula (XIVb) can react with an intermediate of Formula III, where X represents a suitable leaving group, such as for instance a halogen, in particular Cl, Br, I, under coupling reaction conditions, to provide an intermediate of Formula (XV). This reaction may be performed in the presence of a suitable base, such as, for example, Cs2CO3,K3PO4or K2CO3. This reaction can be performed in a reaction-inert solvent, such as, for example, tBuOH, toluene, DMA or dioxane. The reaction is typically performed in the presence of a catalyst system comprising a suitable catalyst such as tBuXPhos Pd G3, BrettPhos Pd G3, or SPhos Pd G4 and a ligand such as BrettPhos. Preferably, this reaction is carried out under an inert atmosphere, such as nitrogen or argon atmosphere, and in a suitable temperature range, such as for instance room temperature to 60 °C, under conventional heating or microwave irradiation. Step 3. An intermediate of Formula (XV) is reacted with a suitable base, such as LiOH, in a suitable solvent, such as water or a mixture of water and a suitable organic solvent such as dioxane or THF, in a suitable temperature range, such as 0 °C to 40 °C, to provide an intermediate of Formula (XIII). In the preparation of compounds of the present invention, protection of remote functionality (e.g., primary amine or alcohol) of intermediates may be necessary. The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparations methods. Suitable amino-protecting groups include but are not limited to t- butoxycarbonyl (Boc), and acetyl. Suitable alcohol protecting groups include t- butyldimethylsilyl. The need for such protection is readily determined by one skilled in the art. It will be appreciated that where appropriate functional groups exist, compounds of various formulae or any intermediates used in their preparation may be further derivatised by one or more standard synthetic methods employing condensation, substitution, oxidation, reduction, or cleavage reactions. Particular substitution approaches include conventional alkylation, arylation, heteroarylation, acylation, sulfonylation, halogenation, nitration, formylation and coupling procedures. The compounds of Formula (I) may be synthesized in the form of racemic mixtures of enantiomers which can be separated from one another following art-known resolution procedures. The racemic compounds of Formula (I) containing a basic nitrogen atom may be converted into the corresponding diastereomeric salt forms by reaction with a suitable chiral acid. Said diastereomeric salt forms are subsequently separated, for example, by selective or fractional crystallization and the enantiomers are liberated therefrom by alkali. An alternative manner of separating the enantiomeric forms of the compounds of Formula (I) involves liquid chromatography using a chiral stationary phase. Said pure stereochemically isomeric forms may also be derived from the corresponding pure stereochemically isomeric forms of the appropriate starting materials, provided that the reaction occurs stereospecifically. In the preparation of compounds of the present invention, protection of remote functionality (e.g., primary or secondary amine) of intermediates may be necessary. The need for such protection will vary depending on the nature of the remote functionality and the conditions of the preparation methods. Suitable amino-protecting groups (NH-Pg) include acetyl, trifluoroacetyl, t-butoxycarbonyl (Boc), benzyloxycarbonyl (CBz) and 9- fluorenylmethyleneoxycarbonyl (Fmoc). The need for such protection is readily determined by one skilled in the art. EXAMPLES Several methods for preparing the intermediates and Compounds of this invention are illustrated in the following examples. Unless otherwise noted, all starting materials were obtained from commercial suppliers and used without further purification, or alternatively can be synthesized by a skilled person by using well-known methods. Abbreviation Meaning ACN or CH3CN acetonitrile AcOH acetic acid Aq or aq. aqueous Bn Benzyl Boc tert-Butyloxycarbonyl Boc2O Di-tert-butyl dicarbonate Co Compound Co. No. Compound Number CPME Cyclopentyl methyl ether DCM dichloromethane DIBAL-H Diisobutylaluminium hydride DMA N,N-Dimethylacetamide DMF N,N-Dimethylformamide DMF-DMA N,N-Dimethylformamide dimethyl acetal equiv equivalent(s) Et2O ethyl ether Et3N or TEA triethylamine EtOAc ethyl acetate Abbreviation Meaning EtOH ethanol h hour(s) 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxid hexafluorophosphate, N- HATU [(Dimethylamino)-1H-1,2,3-triazolo-[4,5-b]pyridin-1- ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide HCl Hydrochloric acid HPLC high performance liquid chromatography iPrNH2isopropylamine IPA or iPrOH isopropanol K2CO3Potassium carbonate LDA Lithium diisopropylamide LC Liquid chromatography LCMS Liquid chromatography- Mass spectrometry Me methyl MeI methyl iodide MeMgBr Methyl magnesium bromide MeOH methanol MP melting point MgSO4magnesium sulphate MW molecular weight µW microwaves N2nitrogen NaH sodium hydride NaHCO3sodium bicarbonate NH4Cl ammonium chloride NH4HCO3Ammonium bicarbonate Abbreviation Meaning PE Petroleum ether Pd(dppf)Cl2[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)Quant. quantitative rac racemic RP reversed phase Rochelle's salt Potassium sodium tartrate tetrahydrate RT room temperature Rt Retention time RuPhos 2-Dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl [Dicyclohexyl(2′,6′-diisopropoxy-2-biphenylyl)phosphine- RuPhos Pd G4 κP](methanesulfonatato-κO)[2′-(methylamino-κN)-2- biphenylyl-κC2]palladium SFC supercritical fluid chromatography Sat or sat. saturated TEA triethylamine t-BuOH or tBuOH tert-butanol (tert-butyl alcohol) TBAF Tetra-N-butylammonium fluoride TBME Methyl tert-butyl ether TEMPO 2,2,6,6-Tetramethylpiperidine 1-oxyl, 2,2,6,6-Tetramethyl-1- piperidinyloxy, free radical TFA trifluoroacetic acid THF tetrahydrofuran As understood by a person skilled in the art, Compounds synthesized using the protocols as indicated may contain residual solvent or minor impurities. A skilled person will realize that, even where not mentioned explicitly in the experimental protocols below, typically after a column chromatography purification, the desired fractions were collected, and the solvent was evaporated. In case no stereochemistry is indicated, this means it is a mixture of stereoisomers, unless otherwise is indicated or is clear from the context. As understood by a person skilled in the art, compounds synthesized using the protocols as indicated may exist as a solvate e.g. hydrate, and / or contain residual solvent or minor impurities. Compounds or intermediates isolated as a salt form, may be integer stoichiometric i.e. mono- or di-salts, or of intermediate stoichiometry. When an intermediate or compound in the experimental part below is indicated as ‘a HCl salt’ without indication of the number of equivalents of HCl, this means that the number of equivalents of HCl was not determined. Preparation of intermediates For intermediates that were used in a next reaction step as a crude or as a partially purified intermediate, in some cases no mol amounts are mentioned for such intermediate in the next reaction step or alternatively estimated mol amounts or theoretical mol amounts for such intermediate in the next reaction step are indicated in the reaction protocols described below. Intermediate 1 of NaH (60% in mineral oil, 2.59 g, 64.85 mmol) in THF (100 mL) was added triethylphosphonopropionate (13.9 mL, 64.85 mmol) dropwise. The reaction was stirred for 30 minutes, then a solution of 4-bromobenzaldehyde [1122-91-4] (10.0 g, 54.0 mmol) in THF (20 mL) was added dropwise, keeping the internal temperature between 0 °C and 5 °C. The mixture was allowed to warm to RT and stirred for 16 h. The reaction was quenched with a saturated aqueous solution of NH4Cl (60 mL), and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography over silica gel (eluent: heptane / EtOAc up to 90 / 10). The fractions containing compound were combined and concentrated in vacuo to give Intermediate 1 (12.3 g, 84% yield) as a colorless oil. Intermediate 2 of Intermediate 1 (12.3 g, 45.7 mmol) in dry THF (230 mL) under nitrogen, was added DIBAL-H (1M in THF, 115 mL, 115 mmol) dropwise. The mixture was then allowed to slowly warm up to RT and stirred for 1 h. The reaction was cooled down to 0 °C, diluted with EtOAc (100 mL) and quenched with a saturated aqueous solution of Rochelle's salt (250 mL). After stirring for 1 h, the reaction was allowed to warm up to RT, the organic layer was separated, and the aqueous layer was extracted with EtOAc (200 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give Intermediate 2 (9.8 g, 94% yield) as a white solid. Intermediate 3 2 (8.70 g, 38.3 mmol) and imidazole (3.13 g, 46.0 mmol) in DCM (100 mL) pre-cooled to 0 °C, was added triisopropylsilyl chloride (9.0 mL, 42.1 mmol) dropwise. The mixture was allowed to warm up to RT and stirred for 16 h. The mixture was diluted with water (100 mL) and DCM (100 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude was purified by flash column chromatography over silica gel (eluent: heptane / DCM up to 90 / 10) to obtain Intermediate 3 (14 g, 95% yield) as a colorless oil. Intermediate 4 tube charged with Intermediate 3 (1.15 g, 3.0 mmol) and tetrabutylammonium bromide (48.3 mg, 0.15 mmol), was added toluene (6 mL) and (bromodifluoromethyl)trimethylsilane (1.4 mL, 9 mmol). The reaction was stirred at 110 °C for 6 h. Six identical reactions were run in parallel and combined before work-up and purification. The reactions were cooled down to RT, each diluted with water (10-15 mL), EtOAc (20-25 mL), and combined. The organic layer was separated, and the aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was dissolved in anhydrous THF (50 mL), cooled to 0 °C and TBAF (1M in THF, 27 mL, 27 mmol) was added. The reaction was allowed to warm up to RT and stirred for 1 h. Volatiles were removed under reduced pressure and the residue was diluted with water (50 mL) and EtOAc (100 mL). The aqueous layer was separated, and the organic layer was washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography over silica gel (eluent: heptane / EtOAc 70 / 30) to obtain Intermediate 4 (4.6 g, 92% yield) as a yellowish oil. Intermediate 5 4 (3.81 g, 13.75 mmol) in water / MeCN (87 mL / 87 mL), were added TEMPO (1.07 g, 6.87 mmol), (Diacetoxyiodo)benzene (13.29 g, 41.25 mmol) and NaHCO3 (2.89 g, 34.37 mmol). The mixture was stirred for 6 h at RT, the mixture was diluted with water, and aq HCl (1 M) was added until the pH reached approximately 2. EtOAc was added and the organic layer was separated. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over anhydrous MgSO4, filtered, and evaporated. The product was stirred in diisopropyl ether and filtered. The filtrate was evaporated and stirred in heptane to obtain a precipitate that was filtered and dried over anhydrous MgSO4to give Intermediate 5 (3.46 g, 86% yield) as white solid. Intermediate 6 5 (315 mg, 1.08 mmol), N-[(Dimethylamino)-1H-1,2,3-triazolo- [4,5-b]pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide (823 mg, 2.16 mmol) and N,N-Diethylethanamine (0.60 mL, 4.33 mmol) in CH3CN (9 mL), was added methylamine (2 M in THF, 1.35 mL, 2.70 mmol). The mixture was stirred at RT for 1 h, then diluted with EtOAc (30 mL) and water (15 mL). The acqueous layer was separated and extracted with EtOAc (30 mL). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography over silica gel (eluent: heptane / EtOAc up to 50 / 50) to obtain Intermediate 6 (320 mg, 97% yield) as colorless oil. Intermediate 7 1 (118 g, 438.43 mmol), toluene (826 mL) and tetrabutylaminyl bromide [1643-19-2] (4.24 g, 13.15 mmol) was added (bromodifluoromethyl)trimethylsilane [115262-01-6] (1424.76 g, 7014.99 mmol) dropwise over 24 h at 110 °C (with a syringe pump). The resulting mixture was stirred for additional 5 h at 110 °C. The reaction was poured into ice water (1.5 L). The resulting mixture was extracted with PE (3x1 L). The combined organic layers were washed with brine (3x0.5 L), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EtOAc (30:1) to afford Intermediate 7 (92.0 g, 66% yield) as a light-yellow oil. Intermediate 8 and Intermediate 9 Intermediate 7 (100 g, 313.34 mmol) was purified by preparative chiral HPLC (Stationary phase: Chiralpak IG 5x25 cm, 10 μm, Mobile Phase: Hexane / EtOH: 99 / 1). The fractions containing compound were combined and evaporated in vacuo to give Intermediate 8 (23.8 g, 23% yield) as a brown oil and Intermediate 9 (48.7 g, 47% yield) as a brown oil. Intermediate 10 chloride [13154-24-0] (1.7 mL, 0.9 g / mL, 7.94 mmol) was added to a stirred solution of methyl (2E)-3-(4-bromophenyl)-2-(hydroxymethyl)-2-propenoate [1505472-36-5] (1.79 g, 6.6 mmol), DMAP [1122-58-3] (87 mg, 0.71 mmol) and imidazole [288-32-4] (582.6 mg, 8.56 mmol) in dry DCM (35 mL) at room temperature. The reaction was stirred for 24 h, then extra triisopropylsilyl chloride (0.4 mL, 1.87 mmol) and imidazole (111.5 mg, 1.64 mmol) were added and resulting mixture stirred for 24 h more. The crude was diluted with water and DCM, the phases separated and the aqueous layer extracted once with DCM. The combined organic layers were dried over MgSO4, the solids filtered and the solvent evaporated under vacuo. The crude was purified by flash column chromatography over silica gel (eluent: Hexane:EtOAc from 100:0 to 90:10) to give Intermediate 10 (2.0 g, 71% yield) as a colourless oil. Intermediate 11 10 (1.0 g, 2.34 mmol), tetrabutylammonium bromide [1643-19-2] (37.7 mg, 0.17 mmol), dry toluene (2 mL) and TMSCF2Br [115262-01-6] (7.3 mL, 46.8 mmol) was stirred at 110 °C for 72 h, then concentrated under reduced pressure. The crude was purified by flash column chromatography over silic gel (eluent: Hexane:EtOAc from 100:0 to 90:10) to give Intermediate 11 (0.93 g, 33% purity, 27% yield). Intermediate 12 1.8 mL, 3.6 mmol) was added to a stirred solution of Intermediate 11 (570.4 mg; mixture) in THF (3.4 mL). The reaction mixture was stirred at room temperature ovenright, then diluted with aq. HCl 1.0M until pH < 2. EtOAc was added, and the phases separated. The aqueous layer was extracted twice with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to give Intermediate 12as a brown oil, which was used as such in the next step without further purification (assumed quantitative yield). The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 6, starting from Intermediate 12 and the indicated reagents. Resulting Reagent Structure Int. No. trans-3- Intermediate methylsulfonylcyclobutylamine 13 hydrochloride [1408075-97-7] Ammonium chloride [12125-02- Intermediate 9] 14 methylamine (2M in THF) Intermediate [74-89-5] 15 Intermediate 16 10 (140.0 g, 328 mmol) in THF (750 mL) was added DIBAL-H [1191-15-7] (1 M, 983 mL) at -70°C（dry ice / EtOH） dropwise over 30 minutes. The mixture was warmed and stirred at 25 ℃ for 3 hours. The reaction mixture was quenched by addition of a saturated solution of potassium sodium tartrate (100 mL) at -70 °C, and then diluted with water (1000 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3x700 mL). The combined organic layers were washed with brine (800 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash column chromatography over silica gel (Eluent: Petroleum ether:EtOAc from 100:1 to 8:1) to give Intermediate 16 (89.3 g, 68% yield) as a colorless oil. Intermediate 17 16 (89.0 g, 223 mmol) in DCM (450 mL) was added TEA (45.1 g, 446 mmol, 62.0 mL) and acetic anhydride [108-24-7] (34.1 g, 334 mmol, 31.3 mL). The mixture was stirred at 25 °C for 2 hours. The mixture was concentrated to give the crude product. The residue was purified by column chromatography (Mobile phase: Petroleum ether:EtOAc from 100:1 to 8:1) to give Intermediate 17 (78 g, 177 mmol, 79% yield) as a colorless oil. Intermediate 18 17 (17.0 g, 38.5 mmol) in diglyme (20 mL) was added dropwise bis(trimethylsilyl)acetamide [10416-59-8] (783 mg, 3.85 mmol, 951 μL, 0.1 eq) at 170 °C followed by dropwise addition of sodium 2-bromo-2,2-difluoroacetate [84349-27-9] (75.8 g, 385 mmol, 10 eq) in diglyme (240 mL) at 170 °C for 5-8 h. The resulting mixture was stirred at 170 °C for 2 h. The reaction mixture was quenched by addition H2O (500 mL), and the layers were separated. The aqueous phase was extracted with EtOAc (3x200 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography over silic gel (Eluent: Petroleum ether:EtOAc from 100:1 to 10:1) to give Intermediate 18 (30.0 g, 55% yield, 70% purity) as a yellow oil. Intermediate 19 18 (30.0 g, 61.0 mmol), K2CO3(16.8 g, 122 mmol) in MeOH (150 mL) was degassed and purged with nitrogen, and then the mixture was stirred at 25 °C for 1 hour under N2 atmosphere. The reaction mixture was quenched by adding water (10 mL), and then extracted with EtOAc (3x20 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (Eluent: Petroleum ether:EtOAc from 100:1 to 10:1) to give Intermediate 19 (30.0 g, crude) as a colorless oil. Intermediate 20 and Intermediate 21 Intermediate 19 was purified by preparative chiral SFC (Column: DAICEL CHIRALCEL OJ (250mm*50mm, 10um); Mobile phase: [CO2-EtOH (0.1% NH3H2O)]; B%:20%, isocratic elution mode). The fractions containing compound were combined and evaporated in vacuo to give Intermediate 20 (14.6 g, 98% purity) and Intermediate 21 (13.2 g, 98% purity) as yellow oils. Intermediate 22 20 (13.2 g, 29.4 mmol) in DCM (130 mL) was added Dess–Martin periodinane [87413-09-0] (15.0 g, 35.2 mmol, 10.9 mL) at 0 °C and the mixture was stirred at 20 °C for 1 hour under nitrogen atmosphere. The resulting mixture was quenched by addition of a saturated aqueous solution of NaHCO3(50 mL) and a satturated aqueous solution of Na2SO3(50 mL). The phases were separated, and the organic layer was concentrated to give the crude product which was used in the next step without further purification. To a solution of the crude material (12.9 g, 28.8 mmol) and 2-methyl-2-butene [513-35-9] (4.04 g, 57.7 mmol, 6.11 mL) in THF (50 mL) and acetone (50mL) was added a solution of sodium chlorite [7758- 19-2] (3.91 g, 43.3 mmol, 1.5 eq) and NaH2PO4 [7558-80-7] (10.4 g, 86.5 mmol) in water (50 mL) at 0 °C. The mixture was stirred at 20 °C for 1 hr, then quenched by the addition of a saturdated aqueous solution of NaHCO3 (50 mL) and a saturdated aqueous solution of Na2SO3 (50 mL), the phases were separated and the organic layer was concentrated. The residue was purified by flash column chromatography over silica gel (Eluent: Petroleum ether:EtOAc from 100:1 to 10:1) to give Intermediate 20 (10.0 g, 74% yield) as a colorless oil. The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 6, starting from Intermediate 22 and the indicated Reagents. Reagent Resulting Int. No. Structure trans-3- methylsulfonylcyclobutylamine Intermediate 23 hydrochloride [1408075-97-7] methyl-D3-amine hydrochloride Intermediate 24 [7436-22-8] Intermediate 25 flask were added Zn (15.98 g, 244.40 mmol, 3.0 equiv), DMA (350 mL), TMSCl (4.5 mL) and 1,2-dibromoethane (3 mL) at room temperature under nitrogen atmosphere and stirred for 1 h at 80°C. The mixture was allowed to cool down to 45°C. Then to the stirred mixture was added tert-butyl 4-iodopiperidine-1-carboxylate [301673-14-3] (50.70 g, 162.93 mmol, 2.0 equiv) and stirred 1 h at 45°C. Then to the above solution were added Intermediate 7 (26 g, 81.46 mmol, 1.0 equiv), DMA (250 mL), CuI [7681-65-4] (1.55 g, 8.14 mmol, 0.1 equiv) and Pd(dppf)Cl2 [72287-26-4] (2.98 g, 4.07 mmol, 0.05 equiv) under nitrogen atmosphere. The reaction mixture was stirred for overnight at 90°C. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with EtOAc (3x 300 mL). The combined organic layers were washed with brine (3x 300 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (Eluent: PE:EtOAc 10:1). The residue was further purified by reversed-phase flash chromatography (Column, C18 silica gel; mobile phase, MeCN:IPA, 1:1 in water (0.05% NH3.H2O), 70% isocratic gradient) to give Intermediate 25 (10.65 g, 31% yield) as a light-yellow oil. Intermediate 26 by an analogous reaction protocol as Intermediate 12, starting from Intermediate 25 (33.0 g, 77.92 mmol) to provided Intermediate 26 as a white solid (20.11 g, 68% yield). Intermediate 27 and Intermediate 28 Intermediate 26 (20 g, 50.58 mmol) was purified by Prep SFC (Stationary phase: Chiralpak Diacel AD 20 x 250 mm, Mobile phase: CO2, iPrOH + 0.4 iPrNH2). The fractions containing compound were combined and evaporated in vacuo to give Intermediate 27 (9.87 g, 49% yield) and Intermediate 28 (9.93 g, 50% yield). The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 6, starting from Intermediate 27 and the indicated reagent. Reagent Resulting Int. No. Structure Methyl-d3-amine Intermediate 29 hydrochloride [7436-22-8] Intermediate 30 (1.00 g, 3.13 mmol), NiI2 (97.92 mg, 0.31 mmol), dtbbpy (84.10 mg, 0.31 mmol), zinc (0.41 g, 6.27 mmol), MgCl2(0.30 g, 3.13 mmol) was added a colorless solution of tert-butyl 4-bromopiperidine-1-carboxylate [180695-79-8] (1.66 g, 6.27 mmol) in pyridine (0.25 g, 3.13 mmol) and DMA (14 mL) under N2. The resulting mixture was stirred at rt under nitrogen overnight. The reaction solution was diluted with water (5 mL) and the obtained mixture was extracted with EtOAc (3 x 30 mL). The combined organic phases were washed with brine (30 mL), dried with Na2SO4, filtered and concentrated. The obtained solid was submitted to flash column chromatography over silica gel to provide Intermediate 30 as a brown solid (quantitative yield). Intermediate 31 with 5,7-ditert-butyl-3-phenyl-1,3-benzoxazol-3-ium tetrafluoroborate [1207294-92-5] (176.4 mg, 0.572 mmol), tert-butyl 4-hydroxypiperidine-1- carboxylate (125.2 mg, 0.62 mmol) and a magnetic stir bar. TBME (3 mL) was added under nitrogen and resulting suspension was stirred at rt for 5 minutes. Apart, a solution of pyridine (46 µL, 0.572 mmol) in dry TBME (0.5 mL) was prepared and then added dropwise over the course of 2 minutes. The final mixture was stirred rt for 10 min (a white solid precipitated out during this time). Second solution: A 20 mL vial was charged with (4,4'-di-tert-butyl-2,2'- bipyridine)bis[(2-pyridinyl)phenyl]iridium(III) hexafluorophosphate [676525-77-2] (4.6 mg, 0.0051 mmol), (2,2'-bipyridine)nickel(II) dibromide [46389-47-3] (8.2 mg, 0.02 mmol), quinuclidine [100-76-5] (65.5 mg, 0.59 mmol), Intermediate 23 (125 mg, 0.622 mmol) and a magnetic stir bar. Then dry DMA (3.5 mL) was added under nitrogen. The first solution was transferred to a 10 mL syringe under air. Then a syringe disc filter and new needle were installed on the syringe, and the content was injected through the syringe filter into the second solution. The reaction mixture was bubbled with a nitrogen flow (exit via needle) for 5 minutes and the vial was then sealed with parafilm. The reaction was then stirred in a PennOC Integrated Photoreactor for 16 hours (irradiated under 450 nm LED modules at 100% light intensity with maxed fan speed). The reaction was diluted with water (20 mL) and EtOAc (30 mL). The layers were separated, and the organic layer was washed with brine (4 x 10 mL). The combined aqueous layers were extracted with EtOAc (20 mL). The combined organic layers were then dried over MgSO4, filtered, and concentrated under vacuo. The crude material was purified by flash column chromatography over silica gel (Eluent: heptane / EtOAc from 100:0 to 40:60) to obtain Intermediate 31 (220 mg, 94% yield) as a colorless paste. The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 31, starting from the indicated Intermediates and tert-butyl 4-hydroxypiperidine- 1-carboxylate [109384-19-2]. Reagent Resulting Int. No. Structure Intermediate 6 Intermediate 32 Intermediate 13 Intermediate 33 Intermediate 14 Intermediate 34 Intermediate 15 Intermediate 35 Intermediate 24 Intermediate 36 Intermediate 37 mL, 244.2 mmol) was added to a solution of Intermediate 25 (10.3 g, 24.4 mmol) in 1,4-dioxane (40 mL). The reacton was stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure. The residue was then suspended in diisopropyl ether and the solvents were evaporated (2x) to obtain a white solid. The crude product was used as such in the following step. The following intermediates were synthesized by analogous reaction protocol as described for Intermediate 37, starting from the indicated Intermediates. Reagent Resulting Int. No. Structure Intermediate 27 Intermediate 38 Intermediate 29 Intermediate 39 Intermediate 30 Intermediate 40 Intermediate 31 Intermediate 41 Reagent Resulting Int. No. Structure Intermediate 32 Intermediate 42 Intermediate 33 Intermediate 43 Intermediate 34 Intermediate 44 Intermediate 35 Intermediate 45 Intermediate 36 Intermediate 46 Intermediate 47 prevous step, assumed 0.315 mmol), 2-chloro-5- mg, 0.347 mmol) and DIPEA (217 µL, 1.26 mmol) in CH3CN (2.5 mL) was stirred at 70 °C for 3 h. The reaction was concentrated under reduced pressure. The crude was purified by flash column chromatography over silica gel (24 g, gradient: from heptane 100% up to hept / EtOAc 2 / 8) to obtain Intermediate 47 (98.0 mg, 53% yield) as a yellow solid. The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 47, starting from the indicated Intermediates and 2-chloro-5-fluoro-3- nitropyridine [136888-21-6]. Intermediate No. Resulting Int. No. Structure Intermediate 37 Intermediate 48 Intermediate 38 Intermediate 49 Intermediate 39 Intermediate 50 Intermediate 42 / Intermediate 51 Intermediate 44 / Intermediate 52 Intermediate 45 Intermediate 53 Intermediate 46 Intermediate 54 The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 47, starting from the indicated Intermediates and 6-chloro-5-nitro-pyridine-2- carboxamide [1224637-03-9]. Intermediate No. Resulting Int. No. Structure Intermediate 40 Intermediate 55 Intermediate No. Resulting Int. No. Structure Intermediate 43 Intermediate 56 Intermediate 46 Intermediate 57 The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 12 the indicated reagents. Starting Int. No. Resulting Int. No. Structure Intermediate 48 Intermediate 58 Intermediate 55 Intermediate 59 Intermediate 60 reaction protocol as Intermediate 6, starting from mmol), and trans-3-methylsulfonylcyclobutylamine hydrochloride [1408075-97-7] (103.6 mg, 0.56 mmol) to provide Intermediate 60 (0.21 g, quantitative yield) as yellow oil. Intermediate 61 an analogous reaction protocol as Intermediate 6, starting from Intermediate 58 (156.0 mg, 0.36 mmol) and ammonia (0.5 M in dioxane) [7664-41-7] (2.24 ml, 0.90 mmol) to provide Intermediate 61 (140.0 mg, 90% yield) as yellow oil. The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 6, starting from Intermediate 59 and the indicated Reagent. Resulting Int. Reagent Structure No. Trans-3- methylsulfonylcyclobutyl- Intermediate amine hydrochloride 62 [1408075-97-7] Methyl-D3-amine Intermediate hydrochloride [7436-22-8] 63 Ammonium chloride Intermediate [12125-02-9] 64 Methylamine Intermediate hydrochloride 65 [593-51-1] Intermediate 66 Intermediate 66 was prepared by an analogous reaction protocol as Intermediate 47, starting from Intermediate 37 (2.0 g, 5.56 mmol) and 3-chloro-2-fluoropyridine [1480-64-4] (2.19 g, 16.67 mmol) to provide Intermediate 66 (1.88 mg, 78% yield) as a white solid. Intermediate 67 g, 119.89 mmol) in 1,4-dioxane (930 mL) was treated with 17-9] (41.25 g, 239.78 mmol) and Cs2CO3 (117.19 g, 359.67 mmol) under nitrogen atmosphere followed by the addition of Ruphos Pd G4 (12.23 g, 14.38 mmol) at room temperature. The resulting mixture was stirred for additional 48 h at 120°C. The resulting mixture was filtered, the filter cake was washed with dioxane (2x100 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with petroleum ether / ethyl acetate (10 / 1) to afford Intermediate 67 (22.1 g, 42% yield) as a light-yellow oil. Intermediate 68 10.2 mmol), tetrahydroxydiboron (2.93 g, 32.7 mmol), in DMF (107 mL) was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc (50 mL) and brine (50 mL). After the separation of phases, the aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (3 x 100 mL), dried over Na2SO4, filtered, and concentrated. The residue was submitted to reversed phase column eluting with CH3CN (5~95%) and H2O (0.05% TFA) yielding Intermediate 68 (3.1 g, 63% yield) as a yellow solid. The following Intermediates were synthesized by analogous reaction protocol as described for Intermediate 12, from the indicated Intermediates. Starting Int. No. Resulting Int. No. Structure Intermediate 66 Intermediate 69 Intermediate 67 Intermediate 70 Intermediate 68 Intermediate 71 Intermediate 72 and Intermediate 73 Intermediate 70 (15.0 g, 38.82 mmol) was purified by Prep SFC (Stationary phase: Chiralpak Diacel AD 20 x 250 mm, Mobile phase: CO2, iPrOH + 0.4 iPrNH2). The fractions containing compound were combined and evaporated in vacuo to give Intermediate 72 (5.98 g, 40% yield) and Intermediate 73 (6.37 g, 42% yield). Intermediate 74 Intermediate 74 was prepared by an analogous reaction protocol as Intermediate 47, starting from Intermediate 38 (1.86 g, 5.61 mmol) and 2-chloro-3-nitro-pyridine [5470-18-8] (2.00 g, 12.60 mmol) to provide Intermediate 74 (1.80 g, 77% yield) as a white powder. Intermediate 75 g, 12.9 mmol) was added at once to a stirring solution of and 4,4'-bipyridine (40.4 mg, 0.260 mmol) in dry DMF (50 mL). The reaction was stirred at rt for 90 min. The reaction was diluted with water (50 mL) and EtOAc (100 mL). The aqueous layer was separated and the organic one was washed with brine (3 x 30 mL). The organic layer was then dried over MgSO4, filtered, concentrated under reduced pressure and purified by preparative HPLC (Stationary phase: RP XBridge Prep C18 OBD- 10µm, 50x150mm, Mobile phase: 0.25% NH4HCO3 solution in water, CH3CN) yielding Intermediate 75 (0.98 g, 59% yield) as a white powder. Compound 1 mg, 0.36 mmol) in DMF (3 mL) was added 4,4'-Dipyridyl , acid [13675-18-8] (111.949 mg, 1.249 mmol). The resulting mixture was stirred at room temperature for 3 min. The reaction was quenched with water (50 mL). The layers were separated, and the aqueous phase was extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (Column: XBridge Shield RP OBD C18 Column, 30*150 mm, 5µm; Mobile Phase A: Water (10mmol / L NH4HCO3), Mobile Phase B: CH3CN to afford Compound 1 as a white solid (35.2 mg, 22% yield). The following Compounds were synthesized by analogous reaction protocol as described for Compound 1, starting from the indicated Intermediates. Reagent Resulting Cpd. Comment Intermediate 50 (144.9 mg, 61% yield) Compound 2 Intermediate A purification was performed on 51 Compound 3 via Prep SFC (Stationary phase: Chiralcel Diacel OD 20 x 250 mm, Mobile phase: CO2, EtOH + 0.4 Compound 3 iPrNH2) yielding Compound 4 (22.0 mg, 21% yield) and Compound 5 (19.5 mg, 19% yield) as off-white solids. Compound 4 Compound 5 Intermediate A purification was performed on 52 Compound 6 via Prep SFC (Stationary phase: Chiralcel Diacel AD 20 x 250 mm, Mobile phase: CO2, EtOH + 0.4 Compound 6 iPrNH2) yielding Compound 7 (6.0 mg, 21% yield) and Compound 8 (6.0 mg, 21% yield) as white solids. Compound 7 Compound 8 Reagent Resulting Cpd. Comment Intermediate A purification was performed on 53 Compound 9 via Prep SFC (Stationary phase: Chiralcel Diacel IH 20 x 250 mm, Mobile phase: CO2, EtOH + 0.4 Compound 9 iPrNH2) yielding Compound 10(14.0 mg, 25% yield) and Compound 11 ( 14.0 mg, 25% yield) as white solids. Compound 10 Compound 11 Intermediate 60 (79.2 mg, 72% yield) Compound 12

[0002] Reagent Resulting Cpd. Comment Intermediate A purification was performed on 61 Compound 13 via Prep SFC (Stationary phase: Chiralcel Diacel IG 20 x 250 mm, Mobile phase: CO2, Compound 13 EtOH + 0.4 iPrNH2) yielding Compound 14 (21.5 mg, 16% yield) and Compound 15 (22.5 mg, 17% yield) as white solids. Compound 14 Compound 15 Intermediate 62 (50.0 mg, 34% yield) Compound 16 Intermediate 64 (28.9 mg, 25% yield) Compound 17 Intermediate 65 (8.5 mg, 25% yield) Compound 18 Compound 19 A mixture of Intermediate 47 (265 mg, 85% pure, 0.387 mmol) and iron [7439-89-6] (216 mg, 3.87 mmol) in acetic acid (7.0 mL) was stirred at 60 °C for 1 h. The reaction was cooled down to rt, diluted with EtOAc and filtered over dicalite. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (Mobile phase: DCM:MeOH from 100:0 to 96:4) and further purified by preparative HPLC (Stationary phase: RP XBridge Prep C18 OBD-10µm, 50x150mm, Mobile phase: 0.25% NH4HCO3 solution in water, CH3CN) yielding Compound 19 (132 mg, 61% yield) as a white solid. The following Intermediates were synthesized by analogous reaction protocol as described for Compound 19, starting from the indicated Intermediates. Reagent Resulting Cpd. Structure Intermediate (16.0 mg, 74% yield) 54 Compound 20 A purification was Compound 21 performed on Compound 21 via Prep SFC (Stationary phase: Chiralcel Diacel OJ 20 x 250 mm, Mobile phase: Intermediate CO2, EtOH + 0.4 iPrNH2) 56 yielding Compound 22 (5.0 mg, 13% yield) and Compound 22 Compound 23 (6.0 mg, 13% yield). Compound 23 Reagent Resulting Cpd. Structure Intermediate (27.0 mg, 82% yield) 57 Compound 24 The following Compounds were synthesized by a reaction protocol as described below: A stock solution of Intermediate 69 (30.51 mg, 0.075 mmol) in CH3CN (0.4 mL) was added to the preweighed reagent indicated in table (0.225 mmol), followed by a stock solution of HATU (57 mg, 0.15 mmol) in CH3CN (0.4 mL) and TEA (42 µL, 0.3 mmol). The reaction was stirred at rt for 16 h. Afterwards, the solvent was removed under reduced pressure. The crude mixture was dissolved in 2 mL DCM / EtOAc (2 / 1) and washed with 1 mL 1M citric acid. The solvent was removed under reduced pressure and the crude mixtures were redissolved in 3 mL MeOH / CH3CN (2 / 1), filtered, and submitted for purification. Purification was performed via Prep HPLC (Stationary phase: RP XBridge Prep C18 OBD-10µm, 30x150mm, Mobile phase: 0.25% NH4HCO3solution in water, CH3CN, or MeOH). In case repurification an orthogonal Prep SFC was used: SFC (Stationary phase: Torus Diol 30 x 150 mm, Mobile phase: CO2, MeOH + 20mM NH4OH). Reagent Resulting Cpd. No. Structure 1-[4-(tert- Compound 25 butoxy)phenyl]methan amine [84697-13-2] 1-(2- Compound 26 methanesulfonylethyl) piperidin-4-amine [920111-82-6]

[0003] Reagent Resulting Cpd. No. Structure 1-[4-(2,2,2- Compound 27 trifluoroethoxy)phenyl ]ethan-1-amine [942938-39-8] (2R)-1-(2,2-dimethyl- Compound 28 3,4-dihydro-2H-1- benzopyran-6- yl)propan-2-amine hydrochloride [2309431-68-1] 1-(4-ethoxy-3- Compound 29 methylphenyl)methan amine [1184137-77-6] (2R)-1-fluoro-3- Compound 30 methoxypropan-2- amine hydrochloride [2361610-41-3]

[0004] Reagent Resulting Cpd. No. Structure 1-{2,3- Compound 31 diazabicyclo[2.2.2]oct -2-en-1- yl}methanamine [396715-58-5] 3,3,4,4- Compound 32 tetrafluorobutan-1- amine hydrochloride [2309453-93-6] 2,2-difluoro-1- Compound 33 (pyridin-2-yl)ethan-1- amine dihydrochloride [2377035-91-9] 3-[4-(pyridin-4- Compound 34 yl)piperazin-1- yl]propan-1-amine [942613-54-9] (3-amino-1- Compound 35 phenylpropyl)- dimethylamine dihydrobromide [1258650-48-4] Reagent Resulting Cpd. No. Structure 1-[4- Compound 36 (trifluoromethyl)phen yl]propan-2-amine hydrochloride [882- 00-8] 1-[cis-5-tert- Compound 37 butyloxolan-2- yl]methanamine hydrochloride [2307777-78-0] 1-{4-[3- Compound 38 (dimethylamino)- propoxy]phenyl}- methanamine [91637- 76-2] 4-(1- Compound 39 aminocyclopropyl)- 1lambda6-thiane-1,1- dione hydrochloride [2241128-99-2] (2R)-4,4,4-trifluoro-2- Compound 40 methylbutan-1-amine hydrochloride [136564-83-5] Reagent Resulting Cpd. No. Structure 2,2- Compound 41 difluorobicyclo[4.1.0] heptan-7-amine hydrochloride [2361645-08-9] 3-[4- Compound 42 (difluoromethoxy)- phenyl]cyclobutan-1- amine hydrochloride [1311314-39-2] 1-(4- Compound 43 methanesulfonylcyclo hexyl)methanamine hydrochloride [2126162-56-7] 1-(7-bromo-1,3- Compound 44 dioxaindan-5- yl)methanamine [1094225-67-8] 4- Compound 45 methoxybicyclo[2.2.1] heptan-1-amine hydrochloride [2260933-13-7] Reagent Resulting Cpd. No. Structure 2-[4-(prop-2-yn-1- Compound 46 yloxy)phenyl]ethan-1- amine hydrochloride [1221725-46-7] 1-(5-methanesulfonyl- Compound 47 Cl F pyridin-2- F N O yl)methanamine N O S trans O hydrochloride HN N [848141-14-0] 1-{8-methyl-1- Compound 48 oxaspiro[4.5]decan-2- yl}methanamine hydrochloride [2230799-51-4] (3-aminobutyl)- Compound 49 dimethylamine [13022-87-2] 1-methyl-8-oxa-1- Compound 50 azaspiro[4.5]decan-3- amine [2248291-75-8]

[0005] Reagent Resulting Cpd. No. Structure 1-{1-[2- Compound 51 (dimethylamino)ethyl] piperidin-4- yl}methanamine [1019381-31-7] 1-[(4- Compound 52 fluorophenyl)methyl]p iperidin-4-amine [92539-14-5] 1-[5-(difluoromethyl)- Compound 53 1H-pyrazol-4- yl]methanamine; trifluoroacetic acid 1-(4H-1,2,4-triazol-3- Compound 54 yl)methanamine dihydrochloride [859791-21-2] 1-[4-(trifluoromethyl)- Compound 55 bicyclo[2.2.1]heptan- 1-yl]methanamine hydrochloride [2361635-16-5] [(2R)-2-amino-2- Compound 56 phenylethyl]dimethyla mine [174636-94-3] Reagent Resulting Cpd. No. Structure 1-[4- Compound 57 (difluoromethoxy)-2- fluorophenyl]methana mine [1261440-05-4] 1-(1,2,2- Compound 58 trimethylcyclopropyl) methanamine hydrochloride [2089255-87-6] 3-(2- Compound 59 methylpropyl)bicyclo- [1.1.1]pentan-1-amine hydrochloride [2703775-04-4] 1-[3,3-difluoro-1- Compound 60 (methanesulfonylmeth yl)cyclobutyl]methana mine hydrochloride [2694728-01-1] trans-2- Compound 61 aminocyclobutane-1- sulfonamide hydrochloride [2624109-62-0]

[0006] Reagent Resulting Cpd. No. Structure 5-bromo-2,3-dihydro- Compound 62 1H-inden-2-amine hydrobromide [321352-52-7] trans-3-amino-4- Compound 63 hydroxy-1lambda6- thiolane-1,1-dione [20688-37-3] 1-[1-(4- Compound 64 bromophenyl)cyclopr opyl]methanamine [771583-34-7] (4- Compound 65 aminobutyl)(methyl)( propan-2-yl)amine [947263-52-7] 1-(2,2-difluoro-3,3- Compound 66 dimethylcyclopropyl) methanamine hydrochloride [1955514-92-7] 1-[1-methyl-3- Compound 67 (trifluoromethyl)cyclo butyl]methanamine hydrochloride [2503208-13-5] Reagent Resulting Cpd. No. Structure 2-(4- Compound 68 cyclopropylphenyl)-2- methylpropan-1- amine hydrochloride [2613382-28-6] N1,N1- Compound 69 dimethylspiro[3.3]hep tane-1,3-diamine dihydrochloride [1989671-57-9] 1-[trans-2- Compound 70 (difluoromethyl)cyclo butyl]methanamine hydrochloride [2490344-64-2] 1,2- Compound 71 dimethylcyclopropan- 1-amine hydrochloride [1987865-95-1] 4-methyl-4- Compound 72 (pyrrolidin-1- yl)cyclohexan-1- amine [2092357-20-3]

[0007] Reagent Resulting Cpd. No. Structure 1-cyclopropyl-1-(6- Compound 73 methoxypyridin-3- yl)methanamine [1270387-42-2] 1-{4- Compound 74 methanesulfonyl-2- oxabicyclo[2.1.1]hexa n-1-yl}methanamine hydrochloride [2751621-40-4] 1-[3- Compound 75 (difluoromethyl)bicycl o[1.1.1]pentan-1- yl]methanamine hydrochloride [2639437-56-0] 1-(3,3,3- Compound 76 trifluoropropyl)cyclop ropan-1-amine hydrochloride [2243505-37-3] 3,3-difluoro-1- Compound 77 (methanesulfonylmeth yl)cyclobutan-1-amine hydrochloride [2742657-08-3] Reagent Resulting Cpd. No. Structure 1-[1-(trifluoromethyl)- Compound 78 1H-pyrazol-3- yl]methanamine hydrochloride [2639448-02-3] cis-3-amino-1- Compound 79 ethylcyclobutan-1-ol hydrochloride [2680528-05-4] 2- Compound 80 methanesulfonylpropa n-1-amine hydrochloride [2031260-87-2] trans-5- Compound 81 (aminomethyl)-1,4- dioxan-2-yl]methanol hydrochloride [2624109-63-1] 1-methanesulfonyl-3- Compound 82 methylazetidin-3- amine hydrochloride [1989671-37-5] 1-(1,5,5- Compound 83 trimethylpyrrolidin-3- yl)methanamine [1557338-17-6] Reagent Resulting Cpd. No. Structure trans-2-(1H-imidazol- Compound 84 4-yl)cyclopropan-1- amine dihydrochloride [223571-77-5] trans-N2,N2- Compound 85 dimethyl-1,2,3,4- tetrahydronaphthalene -1,2-diamine [2763584-99-0] cis-3- Compound 86 (trifluoromethyl)cyclo pentan-1-amine hydrochloride [2095396-41-9] 1-(4-bromo-1-methyl- Compound 87 1H-pyrrol-2- yl)methanamine hydrochloride [2344680-56-2] (1S)-2,2-difluoro-1- Compound 88 (oxan-4-yl)ethan-1- amine hydrochloride [2550997-37-8] trans-N1,N1,1- Compound 89 trimethylcyclopentane -1,2-diamine dihydrochloride [2763584-12-7] Reagent Resulting Cpd. No. Structure cis-3-amino-2-methyl- Compound 90 1lambda6-thiolane- 1,1-dione hydrochloride [2044706-25-2] 2-[1-(propan-2- Compound 91 yl)piperidin-4- yl]ethan-1-amine [132740-59-1] 1-[3-(difluoromethyl)- Compound 92 1- methoxycyclobutyl]m ethanamine hydrochloride [2551119-00-5] trans-2,2- Compound 93 difluorobicyclo[3.1.0] hexan-1-amine hydrochloride [2763583-95-3] 1-[1-(propan-2-yl)- Compound 94 1H-pyrazol-4- yl]methanamine dihydrochloride [2567504-61-2] cis-2-ethoxy-2- Compound 95 methylcyclopropan-1- amine hydrochloride [1429305-42-9] Reagent Resulting Cpd. No. Structure 1-(2- Compound 96 phenylethyl)cycloprop an-1-amine hydrochloride [2060063-29-6] 1-(3-bromo-4- Compound 97 methoxyphenyl)ethan- 1-amine hydrochloride [1171612-59-1] 3-(4-methyl-1H- Compound 98 pyrazol-1-yl)butan-2- amine [1248214-35-8] 4-amino-2,2- Compound 99 dimethyl-1lambda6- thiolane-1,1-dione hydrochloride [2680540-30-9] (2- Compound 100 aminoethyl)pentafluor o-lambda6-sulfane hydrochloride [2470437-67-1] Reagent Resulting Cpd. No. Structure 1-[2- Compound 101 (difluoromethoxy)pyri din-4-yl]methanamine [943894-77-7] 3- Compound 102 methoxycyclopentan- 1-amine [1393527-89- 3] 1-[1-(3,5- Compound 103 dimethoxyphenyl)cycl opropyl]methanamine [1503721-53-6] 5H,6H,7H,8H- Compound 104 imidazo[1,5- a]pyridin-6-amine dihydrochloride [1909312-62-4] 1-{[4- Compound 105 (trifluoromethyl)phen yl]methyl}cyclopropa n-1-amine hydrochloride [29813- 02-3] Reagent Resulting Cpd. No. Structure 2-(5-bromopyridin-2- Compound 106 yl)-2-methylpropan-1- amine dihydrochloride [2460751-11-3] 1-(4-aminopiperidin- Compound 107 1-yl)-2-methylpropan- 1-one hydrochloride [1158391-26-4] 2,2- Compound 108 dimethoxycyclobutan- 1-amine [2059967-05- 2] 4-amino-6-fluoro-3,4- Compound 109 dihydro-2H- 1lambda6- benzothiopyran-1,1- dione hydrochloride [1191908-73-2] (3R)-2-methylpentan- Compound 110 3-amine hydrochloride [196929-99-4] 1-(6-chloropyridin-3- Compound 111 yl)ethan-1-amine [132219-51-3] Reagent Resulting Cpd. No. Structure 1-(1- Compound 112 methoxycyclobutyl)et han-1-amine [1595919-41-7] 1-{8-methyl-1- Compound 113 oxaspiro[4.5]decan-2- yl}methanamine hydrochloride [2230799-51-4] 1-[1-methyl-3- Compound 114 (trifluoromethyl)cyclo butyl]methanamine hydrochloride [2503208-13-5] 3- Compound 115 methoxycyclopentan- 1-amine [1393527-89- 3] 2- Compound 116 methanesulfonylethan -1-amine hydrochloride [104458-24-4] 3-(2,2,2- Compound 117 trifluoroethyl)cyclobut an-1-amine hydrochloride [2247102-11-8] Reagent Resulting Cpd. No. Structure 3-(2- Compound 118 methanesulfonylethyl) cyclobutan-1-amine hydrochloride [2460754-98-5] 2-methyl-2- Compound 119 azaspiro[3.3]heptan-6- amine dihydrochloride [2306276-66-2] 1-(1- Compound 120 methanesulfonylcyclo propyl)methanamine hydrochloride [1628734-96-2] trans-2-(1-methyl-1H- Compound 121 imidazol-5- yl)cyclopropan-1- amine dihydrochloride [2307731-69-5] (2S)-2-amino-1-[3- Compound 122 (dimethylamino)pyrro lidin-1-yl]-4- methylpentan-1-one dihydrochloride [1807938-67-5] Reagent Resulting Cpd. No. Structure 1-(2,2-difluoro-1,3- Compound 123 dioxaindan-5- yl)methanamine [135132-35-3] cis-3-(1,2-oxazol-3- Compound 124 yl)cyclobutan-1-amine hydrochloride [2416235-11-3] 1-(4- Compound 125 methoxyphenyl)pyrrol idin-3-amine [1083424-44-5] 1-(1-tert- Compound 126 butylpyrrolidin-3- yl)methanamine [1017474-41-7] 1-(1- Compound 127 fluorocyclobutyl)meth anamine hydrochloride [1462885-81-9] 2,2-difluoro-3- Compound 128 methylbutan-1-amine hydrochloride [1779919-89-9] Reagent Resulting Cpd. No. Structure 1-(4-bromo-2- Compound 129 methoxyphenyl)metha namine hydrochloride [2230802-60-3] 1-[4- Compound 130 (ethanesulfonyl)pheny l]methanamine hydrochloride [98959- 89-8] 3-(difluoromethyl)- Compound 131 cyclobutan-1-amine hydrochloride [1803586-55-1] 3-fluoro-3- Compound 132 methylcyclobutan-1- amine hydrochloride [1638768-85-0] trans-2-(4- Compound 133 bromophenyl)cyclopr opan-1-amine hydrochloride [1228092-84-9] Reagent Resulting Cpd. No. Structure 5H,6H,7H- Compound 134 pyrrolo[1,2- c]imidazol-7-amine dihydrochloride [1864073-39-1] 2-chloro-5H,6H,7H- Compound 135 cyclopenta[b]pyridin- 7-amine hydrochloride [2375195-32-5] 1-(2-chloro-1,3- Compound 136 thiazol-5- yl)methanamine hydrochloride [153471-67-1] N1,N1- Compound 137 dimethylbicyclo- [1.1.1]pentane-1,3- diamine dihydrochloride [2387602-38-0] 1-(propan-2- Compound 138 yl)cyclopropan-1- amine hydrochloride [1215107-56-4] 1-(2-aminoethyl)- Compound 139 N,N- dimethylpiperidin-3- amine [1353963-42-4] Reagent Resulting Cpd. No. Structure 4-amino-1-(4- Compound 140 fluorophenyl)- cyclohexan-1-ol [1539993-45-7] trans-2- Compound 141 ethylcyclopropan-1- amine hydrochloride [1807938-31-3] 1-(1-methyl-1H- Compound 142 pyrrol-3-yl)ethan-1- amine [279226-15-2] 1-{6,6- Compound 143 difluorospiro[2.5]- octan-1- yl}methanamine [2025402-94-0] 1-(1-methyl-1H- Compound 144 imidazol-5-yl)ethan-1- amine [1509765-41-6] 3,3- Compound 145 difluorocyclopentan- 1-amine hydrochloride [939398-48-8] Reagent Resulting Cpd. No. Structure [2-(2- Compound 146 Cl F F aminoethoxy)ethyl]- N O dimethylamine N trans [85322-63-0] N NH O 2-(trifluoromethoxy)- Compound 147 ethan-1-amine hydrochloride [886050-51-7] 6-ethoxy-3,4-dihydro- Compound 148 2H-1-benzopyran-4- amine [927970-57-8] (2S)-2-aminopropane- Compound 149 1-sulfonamide hydrochloride [1140948-90-8] (3-amino-2,2- Compound 150 dimethylpropyl)dimet hylamine [53369-71- 4] 3-amino-3- Compound 151 methylbutan-2-ol [13325-14-9] Reagent Resulting Cpd. No. Structure 1-(5-fluoropyridin-2- Compound 152 yl)methanamine [561297-96-9] trans-2-(4- Compound 153 fluorophenyl)-1- methylpyrrolidin-3- amine [2219376-30-2] 4,4,4-trifluoro-2- Compound 154 methylbutan-2-amine hydrochloride [93339- 72-1] 1-(3-amino-3- Compound 155 methylazetidin-1- yl)ethan-1-one [1480257-74-6] 2-ethoxycyclopropan- Compound 156 1-amine hydrochloride [1461713-33-6] 2-methyloxan-4- Compound 157 amine [89584-06-5] Reagent Resulting Cpd. No. Structure 1-(3-fluoro-5- Compound 158 methoxyphenyl)metha namine [914465-85-3] 1-[4-(4- Compound 159 methylpiperazin-1- yl)phenyl]methanamin e [216144-45-5] N1,N1- Compound 160 dimethylcyclohexane- 1,3-diamine [885280- 64-8] 6-methoxy-2,3- Compound 161 dihydro-1H-inden-1- amine hydrochloride [103028-80-4] 1-(1H-1,2,3,4- Compound 162 tetrazol-5- yl)cyclopropan-1- amine hydrochloride [521286-65-7] 3-methyl-4,5,6,7- Compound 163 tetrahydro-2H- indazol-6-amine [1493995-94-0] Reagent Resulting Cpd. No. Structure 1-(1,3- Compound 164 dimethylpiperidin-3- yl)methanamine dihydrochloride [1461714-55-5] 1-methyl-4- Compound 165 phenylpiperidin-4- amine [100316-65-2] 1,1,1-trifluoro-4,4- Compound 166 dimethylpentan-3- amine [1248988-57-9] 1-(1,3-oxazol-4- Compound 167 yl)ethan-1-amine hydrochloride [2305252-95-1] 4- Compound 168 methanesulfonylbutan -2-amine [1247371- 90-9] 1-(2-bromo-5- Compound 169 chlorophenyl)- methanamine [942400-60-4] Reagent Resulting Cpd. No. Structure 7-amino-2lambda6- Compound 170 thiaspiro[3.5]nonane- 2,2-dione hydrochloride [2138134-58-2] 2-{[4- Compound 171 (trifluoromethyl)phen yl]methyl}cyclopropa n-1-amine hydrochloride [1394042-04-6] 4-(aminomethyl)-1- Compound 172 (propan-2- yl)piperidin-4-ol [132740-55-7] 2-(1H-1,2,3,4- Compound 173 tetrazol-5-yl)propan- 1-amine hydrochloride [1461705-04-3] 3- Compound 174 aminobicyclo[1.1.1]pe ntane-1-sulfonamide hydrochloride [2228748-18-1]

[0008] Reagent Resulting Cpd. No. Structure 3-(1-aminoethyl)- Compound 175 1lambda6-thietane- 1,1-dione hydrochloride [2138083-60-8] 1-(5-bromo-2,3- Compound 176 dihydro-1-benzofuran- 7-yl)methanamine hydrochloride [1461704-70-0] 1-(2,2- Compound 177 difluoroethyl)cyclopro pan-1-amine hydrochloride [2416235-60-2] 1-(5-methyl-1,3,4- Compound 178 oxadiazol-2-yl)ethan- 1-amine hydrochloride [1384662-01-4] cis-2-(4- Compound 179 methoxyphenyl)cyclo butan-1-amine hydrochloride [2209078-70-4]

[0009] Reagent Resulting Cpd. No. Structure 2-(4-fluorophenyl)-2- Compound 180 methylcyclopropan-1- amine hydrochloride [1803605-97-1] N1,N1- Compound 181 dimethylcyclohexane- 1,3-diamine [885280- 64-8] trans-2-ethyloxolan-3- Compound 182 amine [2307770-28-9] 3-(4- Compound 183 chlorophenyl)cyclope ntan-1-amine hydrochloride [100129-34-8] Reagent Resulting Cpd. No. Structure 1-(propan-2- Compound 184 yl)pyrrolidin-3-amine dihydrochloride [19985-09-2] 1- Compound 185 methanesulfonylpyrrol idin-3-amine hydrochloride [1190044-27-9] (3S)-3-fluorobutan-1- Compound 186 amine hydrochloride [2408936-88-7] (2S)-1,1-difluoro-3- Compound 187 methylbutan-2-amine hydrochloride [869334-34-9] 3- Compound 188 methanesulfonylcyclo hexan-1-amine hydrochloride [1334147-71-5] 1-(4,5-dimethyl-4H- Compound 189 1,2,4-triazol-3- yl)piperazine dihydroiodide [1909314-04-0] Reagent Resulting Cpd. No. Structure 4-amino-2lambda6- Compound 190 thiabicyclo[2.1.1]hexa ne-2,2-dione hydrochloride [2408972-49-4] N-methyl-1-(pyridin- Compound 191 4-yl)pyrrolidin-3- amine [1365236-92-5] (1R)-1-[3-fluoro-4-(2- Compound 192 fluoroethoxy)phenyl]e than-1-amine hydrochloride [2411178-17-9] dimethyl[3- Compound 193 (morpholin-2- yl)propyl]amine [1779649-03-4] imino(methyl)(pyrroli Compound 194 din-3-yl)-lambda6- sulfanone [2680904- 44-1] Reagent Resulting Cpd. No. Structure cis-hexahydro-2H- Compound 195 1lambda6-thieno[2,3- c]pyrrole-1,1-dione hydrochloride [1320326-61-1] cis-4-(5-methyl-1H- Compound 196 1,2,4-triazol-3- yl)oxolan-3-amine hydrochloride [2408937-51-7] 3- Compound 197 difluoromethanesulfon ylazetidine hydrochloride [2445791-16-0] 1-{8,8- Compound 198 difluorodispiro[2.0.3^ {4}.1^{3}]octan-6- yl}methanamine [2413898-02-7] 3- Compound 199 methanesulfonylbutan -2-amine hydrochloride [1334148-36-5] Reagent Resulting Cpd. No. Structure trans- Compound 200 decahydropyrido[4,3- d]pyrimidin-2-one hydrochloride [2460739-50-6] trans-3-fluoro-1- Compound 201 phenylcyclobutyl]met hanamine 9-methyl-2,9- Compound 202 diazaspiro[5.5]undeca ne [1211582-98-7] 2,2-difluoro-2-(4- Compound 203 fluorophenyl)ethan-1- amine [454483-93-3] 2-(4- Compound 204 bromophenyl)ethan-1- amine [73918-56-6] 2-(3,3- Compound 205 difluorocyclobutyl)aze tidine hydrochloride [2344686-04-8] Reagent Resulting Cpd. No. Structure 1,2-dimethyl- Compound 206 1H,4H,5H,6H,7H- imidazo[4,5- c]pyridine dihydrochloride [87673-91-4] 3- Compound 207 fluorobicyclo[3.1.0]he xan-2-amine hydrochloride [2408963-81-3] 1-[5-(1,1- Compound 208 Cl F F F difluoroethyl)-1,2- N F N trans O oxazol-3- HN O yl]methanamine N hydrochloride [2413904-40-0] 1-[5-(1,1- Compound 209 difluoroethyl)-1,2- oxazol-3- yl]methanamine hydrochloride [1187927-75-8] 4-(azetidin-3-yl)-4H- Compound 210 1,2,4-triazole dihydrochloride [2375262-06-7]

[0010] Reagent Resulting Cpd. No. Structure N-(piperidin-4- Compound 211 yl)methanesulfonamid e hydrochloride [68996-26-9] [(1-methyl-1H- Compound 212 imidazol-5- yl)methyl](propan-2- yl)amine [1479373- 54-0] (1R)-1-(2,5- Compound 213 difluorophenyl)ethan- 1-amine hydrochloride [1391449-47-0] 3-amino-1- Compound 214 (trifluoromethyl)cyclo pentan-1-ol hydrochloride [1333658-57-3] cis-3-fluoro-4- Compound 215 methoxypiperidine hydrochloride [1147110-70-0]

[0011] Reagent Resulting Cpd. No. Structure 1-imino-2,2-dimethyl- Compound 216 Cl F F 1lambda6- N hiomorpholin-1-one tr O t N ans dihydrochloride N [2411252-57-6] S or R S ONH3- Compound 217 fluorobicyclo[3.1.0]he xan-2-amine hydrochloride [2408963-81-3] 1-imino-2,2-dimethyl- Compound 218 1lambda6- thiomorpholin-1-one dihydrochloride [2411252-57-6] 2-(methylamino)-N- Compound 219 (pyridin-4- yl)acetamide dihydrochloride [109707-42-8] cis-hexahydro-2H- Compound 220 1lambda6-thieno[2,3- c]pyrrole-1,1-dione hydrochloride [1320326-61-1] 7-oxa-2,5- Compound 221 diazaspiro[3.5]nonan- 6-one hydrochloride [1955505-70-0] Reagent Resulting Cpd. No. Structure {[(2S,4S)-4- Compound 222 methoxypyrrolidin-2- yl]methyl}dimethyla mine [1932138-97-0] The following Compounds were synthesized by a reaction protocol as described below: A stock solution of Intermediate 72 (21.5 mg, 0.05 mmol) in CH3CN (0.5 mL) was added to a preweighed amine (0.1 mmol), followed by 1-propanephosphonic anhydride in DMF (50% Wt) (60 μL, 0.1 mmol) and DIPEA (26 µL, 0.15 mmol). The reaction was stirred at rt for 16 h. Afterwards the solvent was removed under reduced pressure. The crude mixture was dissolved in 2 mL DCM / EtOAc (2 / 1) and washed with 1 mL 1M citric acid. The solvent was removed under reduced pressure and the crude mixtures were redissolved in 3 mL MeOH / CH3CN (2 / 1), filtered, and submitted for purification. A purification was performed via Prep HPLC (Stationary phase: RP XBridge Prep C18 OBD-10µm, 30x150mm, Mobile phase: 0.25% NH4HCO3 solution in water, CH3CN or MeOH). In case repurification an orthogonal Prep SFC was used: SFC (Stationary phase: Torus Diol 30 x 150 mm, Mobile phase: CO2, MeOH + 20mM NH4OH) Reagent Resulting Cpd. Structure No. 1-acetyl-3- Compound 223 aminopyrrolidine [833483-45-7] trans-3-Methylsulfonyl- Compound 224 cyclobutylamine [1363381-54-7] Methylamine [74-89-5] Compound 225 Reagent Resulting Cpd. Structure No. 3-Aminobicyclo[1.1.1]- Compound 226 pentane-1-sulfonamide hydrochloride [2228748- 18-1] (2S)-2-Aminopropane-1- Compound 227 sulfonamide hydrochloride [1140948-90-8] trans-4- Compound 228 F F aminotetrahydrothiophene- N H N N O 3-ol 1,1-dioxide [20688-trans A SOOHO 37-3]transCompound 228 Compound 229 Compound 229 Compound 230 Compound 230 A purification was performed on Compound 228 via Prep SFC (Stationary phase: Chiralcel Diacel IG 20 x 250 mm, Mobile phase: CO2, EtOH + 0.4 iPrNH2) yielding Compound 229 (16 mg, 12% yield) and Compound 230 (14 mg, 10% yield) as white solids. Reagent Resulting Cpd. Structure No. 2-aminoethylmetylsulfone Compound 231 hydrochloride [104458-24- 4] cis-3-(1,2-oxazol-3- Compound 232 yl)cyclobutan-1-amine hydrochloride [2416235- 11-3] cis-3-amino-1- Compound 233 methylcyclobutan-1-ol hydrochloride [1523606- 23-6] cis-4-aminocyclohexan-1- Compound 234 ol hydrochloride [56239- 26-0] trans-2- Compound 235 methanesulfonylcyclobuta n-1-amine hydrochloride [2624108-62-7] trans-2-aminocyclobutan- Compound 236 1-ol hydrochloride [1609406-69-0] Reagent Resulting Cpd. Structure No. cis-3- Compound 237 (aminomethyl)cyclobutan- 1-ol [917827-91-9] tetrahydro-2H-pyran-3- Compound 238 amine hydrochloride [675112-58-0] tetrahydro-2H-pyran-3- Compound 239 amine hydrochloride [675112-58-0] 1-(3-amino-3- Compound 240 methylazetidin-1-yl)ethan- 1-one [1480257-74-6] trans-3-(1H-imidazol-1- Compound 241 yl)cyclobutan-1-amine dihydrochloride [2287332- 13-0] (3R,4S)-4-aminooxolan-3- Compound 242 ol hydrochloride [190792- 71-3] Reagent Resulting Cpd. Structure No. trans-3- Compound 243 methanesulfonylcyclobuta n-1-amine hydrochloride [1408075-97-7] (2S)-1-aminopropan-2-ol Compound 244 [2799-17-9] (1R,3S)-3- Compound 245 aminocyclohexan-1-ol hydrochloride [1849594- 88-2] cis-2-aminocyclobutan-1- Compound 246 ol hydrochloride [2070860-49-8] trans-4-aminooxan-3-ol Compound 247 hydrochloride [215941-06- 3] 4-amino-2lambda6- Compound 248 thiabicyclo[2.1.1]hexane- 2,2-dione hydrochloride [2408972-49-4] Reagent Resulting Cpd. Structure No. 1-(3-aminoazetidin-1- Compound 249 yl)ethan-1-one; trifluoroacetic acid [1449278-64-1] -(1-methyl-1H-pyrazol-3- Compound 250 yl)pyrrolidin-3-amine [1315365-78-6] cis-4-aminooxolan-3-ol Compound 251 [535936-61-9] (1S,3R)-3- Compound 252 aminocyclohexan-1-ol hydrochloride [2331211- 57-3] -amino-1lambda6-thiane- Compound 253 1,1-dione hydrochloride [76943-07-2] cis-3-aminocyclobutan-1- Compound 254 ol hydrochloride [1219019-22-3] Reagent Resulting Cpd. Structure No. 2- Compound 255 (cyclopropanesulfonyl)eth an-1-amine hydrochloride [1909347-74-5] 3-(aminomethyl)- Compound 256 1lambda6-thiolane-1,1- dione hydrochloride [3193-51-9] trans-3- Compound 257 (methanesulfonylmethyl)c yclobutan-1-amine hydrochloride [2361595- 50-6] 2-amino-N- Compound 258 [dimethyl(oxo)-lambda6- sulfanylidene]acetamide hydrochloride [1955520- 93-0] 1-(1- Compound 259 F F methanesulfonylcycloprop N yl)methanamineN Otrans A O NH hydrochloride [1628734- S 96-2] O 2- Compound 260 difluoromethanesulfonylet han-1-amine hydrochloride [2460755- 48-8] Reagent Resulting Cpd. Structure No. 3-amino-1lambda6- Compound 261 thiolane-1,1-dione hydrochloride [51642-03- 6] 3-amino-1lambda6- Compound 262 thietane-1,1-dione hydrochloride [1422344- 24-8] 4-amino-1lambda6-thiane- Compound 263 1,1-dione hydrochloride [116529-31-8] 2-(aminomethyl)- Compound 264 1lambda6-thietane-1,1- dione hydrochloride [1699087-66-5] 1-(5-methyl-4H-1,2,4- Compound 265 triazol-3-yl)cyclopropan- 1-amine hydrochloride [2361644-61-1] [(2- Compound 266 aminoethyl)imino]dimethy l-lambda6-sulfanone hydrochloride [1621962- 48-8] Reagent Resulting Cpd. Structure No. 2-[trans-4- Compound 267 aminocyclohexyl]- 1lambda6,2-thiazolidine- 1,1-dione [1092493-87-2] cis-3- Compound 268 (methanesulfonylmethyl)c yclobutan-1-amine hydrochloride [2361595- 87-9] cis-2-(aminomethyl)oxan- Compound 269 4-ol [2219375-11-6] oxan-4-amine Compound 270 hydrochloride [33024-60- 1] 1-(1H-1,2,3,4-tetrazol-5- Compound 271 yl)cyclobutan-1-amine hydrochloride [2089254- 98-6] cis-3-aminocyclopentan-1- Compound 272 ol hydrochloride [1284248-73-2] Reagent Resulting Cpd. Structure No. 5H,6H,7H,8H- Compound 273 imidazo[1,5-a]pyridin-6- amine dihydrochloride [1909312-62-4] 1-(4-aminopiperidin-1- Compound 274 yl)ethan-1-one [160357- 94-8] 1-[cis-3-(1H-imidazol-1- Compound 275 yl)cyclobutyl]methanamin e dihydrochloride [2408962-83-2] 1-(oxetan-3-yl)azetidin-3- Compound 276 amine; bis(trifluoroacetic acid) [2375273-82-6] 3- Compound 277 methanesulfonylcyclopent an-1-amine hydrochloride [2138539-43-0] Reagent Resulting Cpd. Structure No. 1-(1H-imidazol-4- Compound 278 yl)methanamine dihydrochloride [13400- 46-9] cis-4- Compound 279 methanesulfonylcyclohexa n-1-amine hydrochloride [2230789-74-7] trans-3-aminooxan-4-ol Compound 280 hydrochloride [1630906- 89-6] (3S,4R)-4-aminooxolan-3- Compound 281 ol hydrochloride [1955473-62-7] 1-[1- Compound 282 F F (dimethylphosphoryl)cyclo N O propyl]methanamineNtrans A NH hydrochloride [2460757- P 39-3] O 1-(1-methyl-1H-pyrazol-4- Compound 283 yl)pyrrolidin-3-amine [1153295-09-0]

[0012] Reagent Resulting Cpd. Structure No. (2R)-1-aminopropan-2-ol Compound 284 [2799-16-8] 1-[(3R)-3- Compound 285 aminopyrrolidin-1- yl]ethan-1-one hydrochloride [1286208- 55-6] trans-4-aminocyclohexan- Compound 286 -ol hydrochloride [50910- 54-8] (1R,3S)-3- Compound 287 aminocyclopentan-1-ol hydrochloride [1279032- 31-3] trans-2-(1-methyl-1h- Compound 288 imidazol-5- yl)cyclopropan-1-amine dihydrochlor+ide [2307731-69-5] 1-amino-3,3- Compound 289 difluorocyclobutane-1- methanol hcl [1523618- 37-2] Reagent Resulting Cpd. Structure No. 3-amino-3-(2- Compound 290 hydroxyethyl)-1lambda6- thietane-1,1-dione hydrochloride [2243514- 92-1] trans-3-aminocyclopentan- Compound 291 1-ol hydrochloride, trans [124555-33-5] The following Compounds were synthesized by a reaction protocol as described below: A stock solution of Intermediate 75(39 mg, 0.1 mmol) in CH3CN (1.0 mL) was added to a preweighed Reagent indicated in table below (0.2 mmol), followed by 1-propanephosphonic anhydride in DMF (50% Wt) (120 μL, 0.2 mmol) and DIPEA (104 µL, 0.3 mmol). The reaction was stirred at rt for 16 h. Afterwards the solvent was removed under reduced pressure. The crude mixture was dissolved in 2 mL DCM / EtOAc (2 / 1) and washed with 1 mL 1M citric acid. The solvent was removed under reduced pressure and the crude mixtures were redissolved in 3 mL MeOH / CH3CN (2 / 1), filtered and submitted for purification. A purification was performed via Prep HPLC (Stationary phase: RP XBridge Prep C18 OBD-10µm, 30x150mm, Mobile phase: 0.25% NH4HCO3 solution in water, CH3CN or MeOH). In case repurification an orthogonal Prep SFC was used: SFC (Stationary phase: Torus Diol 30 x 150 mm, Mobile phase: CO2, MeOH + 20mM NH4OH). Reagent Resulting Structure Cpd. No. 3-Aminobicyclo[1.1.1]pentane-1- Compound sulfonamide hydrochloride 292 [2228748-18-1] Reagent Resulting Structure Cpd. No. (2S)-2-Aminopropane-1- Compound sulfonamide hydrochloride 293 [1140948-90-8] trans-4- Compound aminotetrahydrothiophene-3-ol 294 1,1-dioxide [20688-37-3] Compound 294 Compound 295 Compound 295 Compound 296 Compound 296 A purification was performed on Compound 294 via Prep SFC (Stationary phase: Chiralcel Diacel IG 20 x 250 mm, Mobile phase: CO2, EtOH + 0.4 iPrNH2) yielding Compound 295(23 mg, 17% yield) and Compound 296 (18 mg, 13% yield) as white solids. 2-aminoethylmetylsulfone Compound hydrochloride [104458-24-4] 297 Reagent Resulting Structure Cpd. No. cis-3-(1,2-oxazol-3- Compound yl)cyclobutan-1-amine 298 hydrochloride [2416235-11-3] 5-oxaspiro[2.4]heptan-1-amine Compound hydrochloride [2503208-63-5] 299 4-amino-2-methyl-1lambda6,2- Compound thiazinane-1,1-dione 300 hydrochloride [2758001-73-7] -(3-aminooxolan-3-yl)propan-2- Compound ol hydrochloride [2375262-50-1] 301 trans-2-(1-methyl-1H-pyrazol-4- Compound yl)cyclopropan-1-amine 302 dihydrochloride [1899946-29-2]

[0013] Reagent Resulting Structure Cpd. No. (1R,5S,7s)-7-amino-3lambda6- Compound thiabicyclo[3.3.1]nonane-3,3- 303 dione hydrochloride [2503155-15- 3] 2-(3-methyl-1,2-oxazol-5- Compound yl)propan-2-amine hydrochloride 304 [2445792-11-8] 3-oxabicyclo[3.1.1]heptan-1- Compound amine hydrochloride [2580199- 305 45-5] 2-(2-aminoethyl)-1lambda6,2- Compound thiazolidine-1,1-dione 306 hydrochloride [1190044-24-6] trans-4-methanesulfonyloxolan-3- Compound amine hydrochloride [2460739- 307 95-9]

[0014] Reagent Resulting Structure Cpd. No. 4-aminobicyclo[2.2.2]octan-1-ol Compound hydrochloride [1403864-74-3] 308 2-(2-methyl-1H-imidazol-1- Compound yl)ethan-1-amine [113741-01-8] 309 7-oxaspiro[3.5]nonan-2-amine Compound hydrochloride [1632228-23-9] 310 1RS,2RS,4SR,6SR)-6- Compound aminobicyclo[2.2.1]heptan-2-ol 311 hydrochloride [2408937-20-0] -(1,3-oxazol-4-yl)ethan-1-amine; Compound trifluoroacetic acid [2411246-11- 312 0] 1-{4-methanesulfonyl-2- Compound oxabicyclo[2.1.1]hexan-1- 313 yl}methanamine hydrochloride [2751621-40-4] Reagent Resulting Structure Cpd. No. 1-amino-N,N- Compound dimethylcyclopropane-1- 314 carboxamide hydrochloride [2155855-69-7] 2-methoxyethan-1-amine [109- Compound 85-3] 315 ,7-dioxaspiro[4.4]nonan-3-amine Compound hydrochloride [2416236-11-6] 316 1-[1-(oxan-4- Compound yl)cyclopropyl]methanamine 317 [1492419-35-8] hexahydro-1H- Compound cyclopenta[c]furan-5-amine 318 [1361415-15-7] -(2-methoxyethyl)pyrrolidin-3- Compound amine [1096335-57-7] 319 The following Compounds were synthesized by a reaction protocol as described below: A stock solution of Intermediate 71 (21 mg, 0.05 mmol) in CH3CN (0.5 mL) was added to the pre-weighed reagent indicated in the table below (0.2 mmol), followed by 1-propanephosphonic anhydride in DMF (50% Wt) (60 μL, 0.1 mmol) and DIPEA (52 µL, 0.15 mmol). The reaction was stirred at rt for 16 h. Afterwards the solvent was removed under reduced pressure. The crude mixture was dissolved in 2 mL DCM / EtOAc (2 / 1) and washed with 1 mL 1M citric acid. The solvent was removed under reduced pressure and the crude mixtures were redissolved in 3 mL MeOH / CH3CN (2 / 1), filtered and submitted for purification. A purification was performed via Prep HPLC (Stationary phase: RP Xbridge Prep C18 OBD-10µm, 30x150mm, Mobile phase: 0.25% NH4HCO3 solution in water, CH3CN or MeOH). In case repurification an orthogonal Prep SFC was used: SFC (Stationary phase: Torus Diol 30 x 150 mm, Mobile phase: CO2, MeOH + 20mM NH4OH) Reagent Resulting Cpd. Structure No. 1-(1-methyl-1H-1,2,3- Compound 320 triazol-4-yl)ethan-1-amine [1515908-30-1] 1-(2-methoxy-6- Compound 321 methylpyrimidin-4- yl)methanamine [1520626-70-3] (2S)-2-methoxypropan-1- Compound 322 amine hydrochloride [907544-43-8] 6-amino-2lambda6- Compound 323 thiaspiro[3.3]heptane-2,2- dione hydrochloride [2137836-62-3] Reagent Resulting Cpd. Structure No. 1-[(2-aminoethyl)imino]- Compound 324 1lambda6-thiolan-1-one; oxalic acid [1955499-23- 6] 4,5,6,7-tetrahydro-1H- Compound 325 1,2,3-benzotriazol-5-amine hydrochloride [2247102- 48-1] 3-(aminomethyl)-N,N- Compound 326 dimethylazetidine-1- carboxamide dihydrochloride [2648957- 24-6] (5R)-5-(aminomethyl)-3- Compound 327 methyl-1,3-oxazolidin-2- one hydrochloride [2031242-17-6]

[0015] Reagent Resulting Cpd. Structure No. trans-2- Compound 328 methanesulfonylcyclopent an-1-amine [2445750-12- 7] trans-2-(1-methyl-1H- Compound 329 pyrazol-4-yl)cyclopropan- 1-amine dihydrochloride [1899946-29-2] 3-(1H-1,2,3-triazol-1- Compound 330 yl)cyclobutan-1-amine dihydrochloride [2408975- 49-3] 1-(aminomethyl)-N,N- Compound 331 dimethylcyclobutane-1- carboxamide hydrobromide [1803600- 46-5] 5H,6H,7H-pyrazolo[3,2- Compound 332 b][1,3]oxazin-6-amine dihydrochloride [2758001- 71-5]

[0016] Reagent Resulting Cpd. Structure No. 1-(1-cyclobutyl-1H-1,2,3- Compound 333 triazol-4-yl)methanamine dihydrochloride [1909312- 25-9] 1-{3-methyl- Compound 334 5H,6H,7H,8H- [1,2,4]triazolo[4,3- a]pyridin-6- yl}methanamine [1315368-27-4] trans-2-amino-5-oxa-7- Compound 335 azaspiro[3.4]octan-6-one hydrochloride [2305253- 28-3] methyl 4-aminopiperidine- Compound 336 1-carboxylate hydrochloride [1187160- 88-8] trans-4-amino-2,2- Compound 337 dimethyloxolan-3-ol hydrochloride [2743608- 15-1] Reagent Resulting Cpd. Structure No. 5H,6H,7H,8H- Compound 338 [1,2,3,4]tetrazolo[1,5- a]pyridin-7-amine hydrochloride [2375260- 34-5] 3-methoxycyclopentan-1- Compound 339 amine [1393527-89-3] 4,4-difluorooxolan-3- Compound 340 amine hydrochloride [2408969-70-8] 1-(pyridazin-4-yl)ethan-1- Compound 341 amine [1008498-13-2] 1-[trans-2-(1-methyl-1H- Compound 342 pyrazol-5- yl)cyclopropyl]methanami ne dihydrochloride [1899946-40-7] 2-methyl-5,6,7,8- Compound 343 tetrahydroquinazolin-6- amine [929973-41-1] Reagent Resulting Cpd. Structure No. 1-amino-N- Compound 344 methylcyclopropane-1- carboxamide hydrochloride [2193058- 19-2] 4-amino-3,3-difluoro-2- Compound 345 methylbutan-2-ol hydrochloride [2089649- 04-5] (2R)-2-methoxypropan-1- Compound 346 amine hydrochloride [907545-98-6] 2-(5-fluoropyrimidin-2- Compound 347 yl)ethan-1-amine dihydrochloride [2225136- 69-4] 2-methyl-5H,6H,7H,8H- Compound 348 imidazo[1,2-a]pyridin-6- amine [1099621-16-5]

[0017] Reagent Resulting Cpd. Structure No. trans-4-(5-methyl-1H- Compound 349 1,2,4-triazol-3- yl)cyclohexan-1-amine dihydrochloride [2287274- 86-4] 1-{5H,6H,8H- Compound 350 imidazo[2,1-c][1,4]oxazin- 3-yl}methanamine hydrochloride [2137845- 30-6] (2R)-2-amino-2-(pyridin- Compound 351 2-yl)ethan-1-ol dihydrochloride [2097958- 04-6] trans-2-amino-4,4- Compound 352 difluorocyclopentan-1-ol [1902951-20-5] 1-[3- Compound 353 (aminomethyl)pyrrolidin- 1-yl]ethan-1-one dihydrochloride [1803596- 63-5] Reagent Resulting Cpd. Structure No. 3-(2-aminoethyl)-1,3- Compound 354 oxazolidin-2-one hydrochloride [1262773- 49-8] 2-(2-aminoethyl)- Compound 355 1lambda6,2-thiazolidine- 1,1-dione hydrochloride [1190044-24-6] 3-(aminomethyl)-5- Compound 356 methyl-4H,5H,6H,7H- pyrazolo[1,5-a]pyrazin-4- one [2309457-51-8] 4H,5H,6H,7H- Compound 357 pyrazolo[1,5-a]pyridin-4- amine [1547114-20-4] (2- Compound 358 aminoethyl)(methyl)(meth ylimino)-lambda6- sulfanone; oxalic acid [1955558-24-3] Reagent Resulting Cpd. Structure No. 1-methyl-4,5,6,7- Compound 359 tetrahydro-1H-1,2,3- benzotriazol-5-amine [1781899-23-7] 3-(aminomethyl)-2,3- Compound 360 dimethyl-1lambda6,2- thiazolidine-1,1-dione; trifluoroacetic acid [2248288-71-1] (3R)-3-amino-2- Compound 361 methylbutan-2-ol hydrochloride [157769-82- 9] 1-{2- Compound 362 oxabicyclo[2.1.1]hexan-1- yl}methanamine hydrochloride [2413903- 70-3] Reagent Resulting Cpd. Structure No. 1-(3-aminooxetan-3-yl)- Compound 363 2,2,2-trifluoroethan-1-ol [2445790-76-9] 1-(1-cyclopropyl-1H- Compound 364 NH2pyrazol-4-yl)methanamine ONN[1784308-56-0] F NH2(R) F (S) O NH NN3-methyl-5H,6H,7H- Compound 365 cyclopenta[c]pyridin-7- amine hydrochloride [1398503-97-3]

[0018] Reagent Resulting Cpd. Structure No. 2-methyl-4,5,6,7- Compound 366 tetrahydro-1H-1,3- benzodiazol-7-amine dihydrochloride [2411270- 20-5] 3-amino-1- Compound 367 methylpyrrolidin-2-one [119329-48-5] 3-aminooxolane-3- Compound 368 carboxamide hydrochloride [1427380- 19-5] (2S)-2-amino-2-(pyridin-2- Compound 369 yl)ethan-1-ol dihydrochloride [1269652- 00-7]

[0019] Reagent Resulting Cpd. Structure No. 1-methanesulfonyl-3- Compound 370 methylazetidin-3-amine hydrochloride [1989671- 37-5] (2S)-1-amino-N- Compound 372 methylpropane-2- sulfonamide hydrochloride [2751603-25-3] (2R)-2-aminopropane-1- Compound 372 sulfonamide hydrochloride [2219353-60-1] [(1- Compound 373 aminocyclobutyl)methyl](i mino)methyl-lambda6- sulfanone dihydrochloride [2758002-17-2] 3-amino-3-methyl- Compound 374 1lambda6-thietane-1,1- dione hydrochloride [2225141-46-6] Reagent Resulting Cpd. Structure No. 1- Compound 375 (aminomethyl)cyclopropan e-1-sulfonamide hydrochloride [2094590- 67-5] 1-(2,5-dimethyl-1H- Compound 376 imidazol-4- yl)methanamine dihydrochloride [2137970- 46-6] (3-aminooxolan-3- Compound 377 yl)methanol [1132878-81- 9] trans-2-aminocyclobutane- Compound 378 1-sulfonamide hydrochloride [2624109- 62-0]

[0020] Reagent Resulting Cpd. Structure No. 4-(aminomethyl)-4- Compound 379 (hydroxymethyl)- lambda6-thiane-1,1-dione hydrochloride [2418730- 61-5] (2R)-1-(1-methyl-1H- Compound 380 pyrazol-5-yl)propan-2- amine dihydrochloride [2375248-30-7] (2R)-1- Compound 381 methanesulfonylpropan-2- amine hydrochloride [1350713-62-0] 2-amino-2-(oxolan-3- Compound 382 yl)ethan-1-ol hydrochloride [1384429- 43-9]

[0021] Reagent Resulting Cpd. Structure No. 3-amino-1lambda6- Compound 383 thiolane-1,1-dione hydrochloride [51642-03- 6] trans-2-(1-methyl-1H- Compound 384 imidazol-2-yl)oxolan-3- amine dihydrochloride [2059909-26-9] 1-(3-aminopyrrolidin-1- Compound 385 yl)propan-1-one [833483- 46-8] 2-amino-2-methyl-1- Compound 386 (pyrrolidin-1-yl)propan-1- one hydrochloride [1220031-32-2] 3-amino-1lambda6- Compound 387 thietane-1,1-dione hydrochloride [1422344- 24-8] Reagent Resulting Cpd. Structure No. (3-aminooxan-3- Compound 388 yl)methanol [1343680-15- 8] trans-2- Compound 389 methanesulfonylcyclobuta n-1-amine hydrochloride [2624108-62-7] 1- Compound 390 methanesulfonylazetidin- 3-amine hydrochloride [1956306-51-6] 2-amino-2-(4-methyl-4H- Compound 391 1,2,4-triazol-3-yl)ethan-1- ol dihydrochloride [1989671-86-4]

[0022] Reagent Resulting Cpd. Structure No. 1- Compound 392 NH2O methanesulfonylpiperidin-NHN2N 4-amine hydrochloride [651057-01-1] (R) F F (S) O HN N S O O 2-{5H,6H,8H- Compound 393 [1,2,4]triazolo[3,4- c][1,4]oxazin-3-yl}ethan- 1-amine dihydrochloride [2580241-76-3] 1-(3-amino-3- Compound 394 methylazetidin-1-yl)-2- methoxyethan-1-one [1487332-80-8] 1-amino-3-(1H-1,2,3- Compound 395 triazol-1-yl)propan-2-ol [477575-14-7]

[0023] Reagent Resulting Cpd. Structure No. (4-aminooxan-4- Compound 396 yl)methanol [720706-20- 7] 3-methanesulfonylpropan- Compound 397 1-amine hydrochloride [157825-88-2] 4-amino-1-methyl- Compound 398 1lambda5-phosphinan-1- one [2375269-75-1] 1-{5H,6H,8H,9H- Compound 399 [1,2,4]triazolo[4,3- d][1,4]oxazepin-3- yl}methanamine dihydrochloride [2241141- 68-2] 2-(4-aminopiperidin-1- Compound 400 yl)ethan-1-ol [89850-72-6]

[0024] Reagent Resulting Cpd. Structure No. cis-4- Compound 401 methanesulfonylcyclohexa n-1-amine hydrochloride [2230789-74-7] 2,5-dioxaspiro[3.4]octan- Compound 402 7-amine [2103779-12-8] [5-(aminomethyl)-4H- Compound 403 1,2,4-triazol-3-yl]methanol hydrochloride [2031259- 31-9] cis-3- Compound 404 (methanesulfonylmethyl)c yclobutan-1-amine hydrochloride [2361595- 87-9]

[0025] Reagent Resulting Cpd. Structure No. 2-amino-N,N- Compound 405 dimethylacetamide hydrochloride [72287-77- 5] 2-aminoethane-1- Compound 406 sulfonamide hydrochloride [89756-60-5] 3-amino-1- Compound 407 methylpiperidine-2,6- dione hydrochloride [1909304-98-8] 3- Compound 408 methanesulfonylcyclopent an-1-amine hydrochloride [2138539-43-0]

[0026] Reagent Resulting Cpd. Structure No. (2S)-2-aminopropane-1- Compound 409 sulfonamide hydrochloride [1140948-90-8] imino(methyl)[(1s,3s)-3- Compound 410 aminocyclobutyl]- lambda6-sulfanone dihydrochloride [2751608- 20-3] (3- Compound 411 aminocyclobutyl)methanes ulfonamide hydrochloride [2413899-21-3] 4-(2-aminoethyl)- Compound 412 1lambda6-thiomorpholine- 1,1-dione dihydrochloride [625106-56-1] 3-(aminomethyl)-3- Compound 413FFmethyl-1lambda6-thietane- NH (S) 2 O (R)1,1-dione hydrochloride N NH [2219373-86-9] N O S NH2O O Reagent Resulting Cpd. Structure No. (2S)-2-amino-N,N- Compound 414 dimethylpropanamide hydrochloride [125218-79- 3] 3,3-difluoro-1- Compound 415 (methanesulfonylmethyl)c yclobutan-1-amine hydrochloride [2742657- 08-3] 1-(3-amino-3- Compound 416 methylazetidin-1-yl)ethan- 1-one [1480257-74-6] (2R)-2-amino-N,N- Compound 417 dimethylpropanamide hydrochloride [1384435- 39-5]

[0027] Reagent Resulting Cpd. Structure No. (2S)-1- Compound 418 methanesulfonylpropan-2- amine hydrochloride [2694056-63-6] 4-aminooxan-3-ol Compound 419 hydrochloride [2059931- 96-1] trans-3- Compound 420 (methanesulfonylmethyl)c yclobutan-1-amine hydrochloride [2361595- 50-6] 1-(3-aminopyrrolidin-1- Compound 421 yl)ethan-1-one hydrochloride [1394041- 16-7]

[0028] Reagent Resulting Cpd. Structure No. 1-(1- Compound 422 methanesulfonylcycloprop yl)methanamine hydrochloride [1628734- 96-2] 1-(3-methyl-1H-1,2,4- Compound 423 triazol-5-yl)methanamine hydrochloride [1220039- 82-6] 1- Compound 424 NH2(dimethylphosphoryl)meth ONNanamine hydrochloride NH2[1429201-51-3] (R) F F (S) O NH O P 1-{5H,6H,8H- Compound 425 imidazo[2,1-c][1,4]oxazin- 2-yl}methanamine dihydrochloride [2408971- 29-7] Reagent Resulting Cpd. Structure No. 2-methyl-5H,6H,7H,8H- Compound 426 [1,2,4]triazolo[1,5- a]pyridin-6-amine [1251925-31-1] 3-(aminomethyl)- Compound 427 1lambda6-thietane-1,1- dione hydrochloride [1909318-80-4] cis-3- Compound 428 methanesulfonylcyclobuta n-1-amine hydrochloride [1408074-56-5] 3-(aminomethyl)- Compound 429 lambda6-thiane-1,1-dione hydrochloride [1780271- 77-3]

[0029] Reagent Resulting Cpd. Structure No. 2-(aminomethyl)- Compound 430 1lambda6-thietane-1,1- dione hydrochloride [1699087-66-5] 1-[trans-3- Compound 431 methanesulfonylcyclobutyl ]methanamine hydrochloride [2411279- 71-3] cis-4- Compound 432 (aminomethyl)oxolan-3-ol hydrochloride [2094653- 70-8] 3-(aminomethyl)-1- Compound 433 methanesulfonylpyrrolidin -3-ol hydrochloride [2445792-32-3]

[0030] Reagent Resulting Cpd. Structure No. 5H,6H,7H,8H- Compound 434 [1,2,3,4]tetrazolo[1,5- a]pyridin-6-amine hydrochloride [2375267- 44-8] cis-3- Compound 435 methanesulfonylcyclobutyl ]methanamine hydrochloride [2413878- 52-9] 2-(3-aminooxetan-3- Compound 436 yl)ethan-1-ol hydrochloride [2138271- 93-7] 1-(4-amino-octahydro-1H- Compound 437 isoindol-2-yl)ethan-1-one [1565012-36-3]

[0031] Reagent Resulting Cpd. Structure No. 3-amino-1-(4- Compound 438 hydroxypiperidin-1- yl)propan-1-one hydrochloride [1220038- 99-2] trans-4-(4-aminopiperidin- Compound 439 1-yl)oxolan-3-ol [2165941-16-0] 3-(aminomethyl)-3- Compound 440 hydroxy-1lambda6- thiolane-1,1-dione hydrochloride [1864052- 26-5] 2-(2- Compound 441 methanesulfonylethoxy)et han-1-amine hydrochloride [947664-66- 6] 3-methyl-5H,6H,7H,8H- Compound 442 imidazo[1,5-a]pyridin-6- amine dihydrochloride [2758004-48-5] Reagent Resulting Cpd. Structure No. 2-(5-methyl-2H-1,2,3- Compound 443 triazol-4-yl)ethan-1-amine dihydrochloride [1971124- 48-7] 2-(aminomethyl)- Compound 444 1lambda6-thiane-1,1-dione hydrochloride [1461707- 48-1] trans-4-methoxy-1- Compound 445 methylpyrrolidin-3-amine [1212103-66-6] 1-[2- Compound 446 (aminomethyl)pyrrolidin- 1-yl]ethan-1-one dihydrochloride [2694744- 51-7] (1S)-1-(1H-1,2,3-triazol-4- Compound 447 yl)ethan-1-amine hydrochloride [2241107- 68-4]

[0032] Reagent Resulting Cpd. Structure No. (3R)-3-aminopyrrolidine- Compound 448 1-sulfonamide hydrochloride [2639391- 39-0] (1S)-1-[5-(aminomethyl)- Compound 449 1H-1,2,4-triazol-3- yl]ethan-1-ol hydrochloride [2253619- 67-7] 4-amino-2lambda6- Compound 450 thiabicyclo[2.1.1]hexane- 2,2-dione hydrochloride [2408972-49-4] cis-hexahydrofuro[2,3- Compound 451 c]furan-2-yl]methanamine [2137434-38-7]

[0033] Reagent Resulting Cpd. Structure No. 3-(aminomethyl)oxetan-3- Compound 452 ol [1305208-47-2] 1-(1- Compound 453 methanesulfonylpiperidin- 4-yl)methanamine hydrochloride [851308-25- 3] 3-(1-aminoethyl)- Compound 454 1lambda6-thietane-1,1- dione hydrochloride [2138083-60-8]

[0034] Reagent Resulting Cpd. Structure No. 2-(3-methyl-1H-pyrazol-5- Compound 455 yl)ethan-1-amine dihydrochloride [1107501- 74-5] 4-(aminomethyl)-4- Compound 456 hydroxy-1lambda6-thiane- 1,1-dione hydrochloride [1190044-30-4] 1-(1-methyl-1H-1,2,3,4- Compound 457 tetrazol-5-yl)methanamine hydrochloride [55446-85- 0] 5-[(1S)-1-aminoethyl]-2,3- Compound 458 dihydro-1,3,4-oxadiazol-2- one hydrochloride [2550997-83-4]

[0035] Reagent Resulting Cpd. Structure No. 5-[(1R)-1-aminoethyl]-2,3- Compound 459 dihydro-1,3,4-oxadiazol-2- one hydrochloride [1046079-44-0] [3-(aminomethyl)oxetan- Compound 460 NH2O 3-yl]methanol [45513-32-NH NN4]2(R) F F (S) O N O H OH 1- Compound 461 methanesulfonylpyrrolidin -3-amine hydrochloride [1190044-27-9] 3-(aminomethyl)-3- Compound 462 hydroxy-1lambda6- thietane-1,1-dione hydrochloride [2551119- 19-6]

[0036] Reagent Resulting Cpd. Structure No. 3-(aminomethyl)-3- Compound 463 hydroxy-1lambda6-thiane- 1,1-dione hydrochloride [2624119-20-4] cis-3-(5-methyl-1,3,4- Compound 464 oxadiazol-2-yl)cyclobutan- 1-amine hydrochloride [2241107-53-7] trans-3-(5-methyl-1,3,4- Compound 465 oxadiazol-2-yl)cyclobutan- 1-amine hydrochloride [2243501-57-5] 5H,6H,7H,8H- Compound 466 [1,2,4]triazolo[1,5- a]pyridin-7-amine dihydrochloride [2375268- 03-2] Reagent Resulting Cpd. Structure No. 1-{4-methanesulfonyl-2- Compound 467 oxabicyclo[2.1.1]hexan-1- yl}methanamine hydrochloride [2751621- 40-4] 4-aminopiperidine-1- Compound 468 sulfonamide hydrochloride [1820640-75-2] 2-methyl-5H,6H,7H,8H- Compound 469 [1,2,4]triazolo[1,5- a]pyridin-8-amine [1376387-23-3] 4-(aminomethyl)- Compound 470 1lambda6-thiane-1,1-dione hydrochloride [1107645- 98-6]

[0037] Reagent Resulting Cpd. Structure No. 3-(2-aminoethyl)- Compound 471 1lambda6-thietane-1,1- dione hydrochloride [1803581-09-0] 2-[1- Compound 472 (methanesulfonylmethyl)c yclopropyl]ethan-1-amine hydrochloride [1955531- 16-4] 1-(1- Compound 473 methanesulfonylpiperidin- 2-yl)methanamine hydrochloride [1091613- 74-9] 1-(4-methyl-1H-imidazol- Compound 474 2-yl)methanamine dihydrochloride [855250- 27-0]

[0038] Reagent Resulting Cpd. Structure No. 3-(aminomethyl)-1- Compound 475 (trifluoromethyl)cyclobuta n-1-ol hydrochloride [2408968-79-4] 3-(aminomethyl)- Compound 476 1lambda6-thiolane-1,1- dione hydrochloride [3193-51-9] 1-(2,5-dimethyl-2H-1,2,3- Compound 477 triazol-4-yl)methanamine hydrochloride [2680529- 41-1] 1-(1- Compound 478 methanesulfonylazetidin- 3-yl)methanamine [1353897-67-2] Reagent Resulting Cpd. Structure No. cis-1-(aminomethyl)-4- Compound 479 methanesulfonylcyclohexa n-1-ol hydrochloride (2R)-3-amino-1,1,1- Compound 480 trifluoropropan-2-ol hydrochloride [1305712- 58-6] (1R)-1-[5-(aminomethyl)- Compound 481 1H-1,2,4-triazol-3- yl]ethan-1-ol hydrochloride [2253619- 49-5] (2S)-3-amino-1,1,1- Compound 482 trifluoropropan-2-ol hydrochloride [1308646- 85-6]

[0039] Reagent Resulting Cpd. Structure No. 2-amino-2-(1-methyl-1H- Compound 483 pyrazol-5-yl)ethan-1-ol [1523376-59-1] 1-(1-methyl-1H-1,2,3,4- Compound 484 NH2tetrazol-5-yl)ethan-1- O N N amine [1267600-33-8] NH2(R) F F (S) O NH N N N N oxetan-3-amine [21635- Compound 485 88-1] 1-[3- Compound 486 (aminomethyl)azetidin-1- yl]ethan-1-one [1493605- 67-6]

[0040] Table: LCMS results. Rt means retention time, in minutes (min.); [M+H]+means the protonated mass of the compound; method refers to the method used for LCMS analysis of compounds; No. means number. Rt means retention time (in minutes). Compound No. LCMS results 1 confirms the MW, Rt: 0.75, [M+H]+: 447.3, Method: 5 2 confirms the MW, Rt: 1.91, [M+H]+: 422.3, Method: 1 3 confirms the MW, Rt: 1.04, [M+H]+: 419.3, Method: 3 4 confirms the MW, Rt: 1.93, [M+H]+: 419.4, Method: 2 5 confirms the MW, Rt: 1.93, [M+H]+: 419.4, Method: 2 6 confirms the MW, Rt: 1.71, [M+H]+: 421.4, Method: 1 7 confirms the MW, Rt: 1.70, [M+H]+: 421.2, Method: 1 8 confirms the MW, Rt: 1.70, [M+H]+: 421.2, Method: 1 9 confirms the MW, Rt: 1.68, [M+H]+: 435.3, Method: 1 10 confirms the MW, Rt: 1.76, [M+H]+: 435.4, Method: 2 11 confirms the MW, Rt: 1.76, [M+H]+: 435.4, Method: 2 12 confirms the MW, Rt: 1.02, [M+H]+: 537.3, Method: 3 13 confirms the MW, Rt: 1.85, [M+H]+: 405.4, Method: 1 14 confirms the MW, Rt: 1.84, [M+H]+: 405.6, Method: 1 15 confirms the MW, Rt: 1.84, [M+H]+: 405.6, Method: 1 16 confirms the MW, Rt: 1.08, [M+H]+: 562.3, Method: 4 17 confirms the MW, Rt: 0.72, [M+H]+: 430.2, Method: 5 18 confirms the MW, Rt: 0.74, [M+H]+: 444.2, Method: 5 19 confirms the MW, Rt: 1.76, [M+H]+: 553.5, Method: 1 20 confirms the MW, Rt: 1.72, [M+H]+: 438.5, Method: 1 21 confirms the MW, Rt: 1.55, [M+H]+: 578.3, Method: 1 22 confirms the MW, Rt: 1.42, [M+H]+: 578.5, Method: 2 23 confirms the MW, Rt: 1.55, [M+H]+: 578.3, Method: 1 24 confirms the MW, Rt: 1.39, [M+H]+: 463.5, Method: 1 25 confirms the MW, Rt: 1.46, [M+H]+: 568.4, Method: 6 26 confirms the MW, Rt: 1.21, [M+H]+: 595.4, Method: 6 27 confirms the MW, Rt: 1.43, [M+H]+: 608.4, Method: 6 28 confirms the MW, Rt: 1.52, [M+H]+: 608.5, Method: 6 29 confirms the MW, Rt: 1.46, [M+H]+: 554.4, Method: 6 30 confirms the MW, Rt: 1.31, [M+H]+: 496.4, Method: 6 31 confirms the MW, Rt: 1.28, [M+H]+: 528.4, Method: 6 32 confirms the MW, Rt: 1.35, [M+H]+: 534.4, Method: 6 33 confirms the MW, Rt: 1.37, [M+H]+: 547.4, Method: 6 Compound No. LCMS results 34 confirms the MW, Rt: 1.19, [M+H]+: 609.5, Method: 6 35 confirms the MW, Rt: 1.37, [M+H]+: 567.4, Method: 6 36 confirms the MW, Rt: 1.48, [M+H]+: 592.4, Method: 6 37 confirms the MW, Rt: 1.51, [M+H]+: 546.4, Method: 6 38 confirms the MW, Rt: 1.25, [M+H]+: 597.5, Method: 6 39 confirms the MW, Rt: 1.23, [M+H]+: 578.4, Method: 6 40 confirms the MW, Rt: 1.40, [M+H]+: 530.4, Method: 6 41 confirms the MW, Rt: 1.38, [M+H]+: 536.4, Method: 6 42 confirms the MW, Rt: 1.43, [M+H]+: 602.4, Method: 6 43 confirms the MW, Rt: 1.25, [M+H]+: 580.4, Method: 6 44 confirms the MW, Rt: 1.40, [M+H]+: 618.3, Method: 6 45 confirms the MW, Rt: 1.36, [M+H]+: 530.5, Method: 7 46 confirms the MW, Rt: 1.36, [M+H]+: 564.5, Method: 7 47 confirms the MW, Rt: 1.20, [M+H]+: 575.5, Method: 7 48 confirms the MW, Rt: 1.54, [M+H]+: 572.3, Method: 6 49 confirms the MW, Rt: 1.14, [M+H]+: 505.6, Method: 7 50 confirms the MW, Rt: 1.23, [M+H]+: 559.6, Method: 7 51 confirms the MW, Rt: 1.20, [M+H]+: 574.4, Method: 6 52 confirms the MW, Rt: 1.41, [M+H]+: 597.6, Method: 7 53 confirms the MW, Rt: 1.22, [M+H]+: 536.5, Method: 7 54 confirms the MW, Rt: 1.10, [M+H]+: 487.5, Method: 7 55 confirms the MW, Rt: 1.46, [M+H]+: 582.6, Method: 7 56 confirms the MW, Rt: 1.39, [M+H]+: 553.6, Method: 7 57 confirms the MW, Rt: 1.40, [M+H]+: 580.3, Method: 6 58 confirms the MW, Rt: 1.47, [M+H]+: 502.5, Method: 7 59 confirms the MW, Rt: 1.53, [M+H]+: 528.6, Method: 7 60 confirms the MW, Rt: 1.28, [M+H]+: 602.5, Method: 7 61 confirms the MW, Rt: 1.20, [M+H]+: 539.3, Method: 6 62 confirms the MW, Rt: 1.47, [M+H]+: 600.5, Method: 7 63 confirms the MW, Rt: 1.15, [M+H]+: 540.5, Method: 7 64 confirms the MW, Rt: 1.50, [M+H]+: 614.5, Method: 7 65 confirms the MW, Rt: 1.14, [M+H]+: 533.6, Method: 7 66 confirms the MW, Rt: 1.40, [M+H]+: 524.5, Method: 7 67 confirms the MW, Rt: 1.42, [M+H]+: 556.6, Method: 7 68 confirms the MW, Rt: 1.53, [M+H]+: 578.6, Method: 7 69 confirms the MW, Rt: 1.36, [M+H]+: 543.3, Method: 6 70 confirms the MW, Rt: 1.36, [M+H]+: 524.5, Method: 7 71 confirms the MW, Rt: 1.37, [M+H]+: 474.5, Method: 7 Compound No. LCMS results 72 confirms the MW, Rt: 1.20, [M+H]+: 571.7, Method: 7 73 confirms the MW, Rt: 1.37, [M+H]+: 567.6, Method: 7 74 confirms the MW, Rt: 1.21, [M+H]+: 580.3, Method: 6 75 confirms the MW, Rt: 1.36, [M+H]+: 536.5, Method: 7 76 confirms the MW, Rt: 1.39, [M+H]+: 542.5, Method: 7 77 confirms the MW, Rt: 1.28, [M+H]+: 588.5, Method: 7 78 confirms the MW, Rt: 1.34, [M+H]+: 554.5, Method: 7 79 confirms the MW, Rt: 1.24, [M+H]+: 504.5, Method: 7 80 confirms the MW, Rt: 1.20, [M+H]+: 526.5, Method: 7 81 confirms the MW, Rt: 1.15, [M+H]+: 536.6, Method: 7 82 confirms the MW, Rt: 1.24, [M+H]+: 553.5, Method: 7 83 confirms the MW, Rt: 1.14, [M+H]+: 531.6, Method: 7 84 confirms the MW, Rt: 1.15, [M+H]+: 512.5, Method: 7 85 confirms the MW, Rt: 1.40, [M+H]+: 579.6, 55% and Rt: 1.41, [M+H]+: 579.6, 45%, Method: 7 86 confirms the MW, Rt: 1.40, [M+H]+: 542.5, Method: 7 87 confirms the MW, Rt: 1.39, [M+H]+: 577.5, Method: 7 88 confirms the MW, Rt: 1.30, [M+H]+: 554.6, Method: 7 89 confirms the MW, Rt: 1.17, [M+H]+: 531.6, Method: 7 90 confirms the MW, Rt: 1.23, [M+H]+: 538.5, Method: 7 91 confirms the MW, Rt: 1.20, [M+H]+: 559.4, Method: 6 92 confirms the MW, Rt: 1.34, [M+H]+: 554.5, Method: 7 93 confirms the MW, Rt: 1.33, [M+H]+: 522.5, Method: 7 94 confirms the MW, Rt: 1.27, [M+H]+: 528.5, Method: 7 95 confirms the MW, Rt: 1.38, [M+H]+: 504.5, Method: 7 96 confirms the MW, Rt: 1.45, [M+H]+: 550.6, Method: 7 97 confirms the MW, Rt: 1.42, [M+H]+: 618.5, Method: 7 98 confirms the MW, Rt: 1.36, [M+H]+: 542.6, Method: 7 99 confirms the MW, Rt: 1.26, [M+H]+: 552.5, Method: 7 100 confirms the MW, Rt: 1.37, [M+H]+: 560.5, Method: 7 101 confirms the MW, Rt: 1.34, [M+H]+: 563.5, Method: 7 102 confirms the MW, Rt: 1.30, [M+H]+: 504.5, Method: 7 103 confirms the MW, Rt: 1.41, [M+H]+: 596.6, Method: 7 104 confirms the MW, Rt: 1.20, [M+H]+: 526.5, Method: 7 105 confirms the MW, Rt: 1.47, [M+H]+: 604.6, Method: 7 106 confirms the MW, Rt: 1.49, [M+H]+: 617.5, Method: 7 107 confirms the MW, Rt: 1.27, [M+H]+: 559.6, Method: 7 108 confirms the MW, Rt: 1.37, [M+H]+: 520.5, Method: 7 Compound No. LCMS results 109 confirms the MW, Rt: 1.30, [M+H]+: 604.5, Method: 7 110 confirms the MW, Rt: 1.44, [M+H]+: 490.5, Method: 7 111 confirms the MW, Rt: 1.34, [M+H]+: 545.5, Method: 7 112 confirms the MW, Rt: 1.42, [M+H]+: 518.6, Method: 7 113 confirms the MW, Rt: 1.56, [M+H]+: 572.6, Method: 7 114 confirms the MW, Rt: 1.46, [M+H]+: 556.3, Method: 6 115 confirms the MW, Rt: 1.37, [M+H]+: 504.3, Method: 6 116 confirms the MW, Rt: 1.17, [M+H]+: 512.5, Method: 7 117 confirms the MW, Rt: 1.39, [M+H]+: 542.5, Method: 7 118 confirms the MW, Rt: 1.25, [M+H]+: 566.3, Method: 6 119 confirms the MW, Rt: 1.16, [M+H]+: 515.3, Method: 6 120 confirms the MW, Rt: 1.26, [M+H]+: 538.3, Method: 6 121 confirms the MW, Rt: 1.22, [M+H]+: 526.3, Method: 6 122 confirms the MW, Rt: 1.35, [M+H]+: 616.5, Method: 6 123 confirms the MW, Rt: 1.44, [M+H]+: 576.3, Method: 6 124 confirms the MW, Rt: 1.31, [M+H]+: 527.3, Method: 6 125 confirms the MW, Rt: 1.43, [M+H]+: 581.3, Method: 6 126 confirms the MW, Rt: 1.20, [M+H]+: 545.4, Method: 6 127 confirms the MW, Rt: 1.38, [M+H]+: 492.4, Method: 6 128 confirms the MW, Rt: 1.41, [M+H]+: 512.3, Method: 6 129 confirms the MW, Rt: 1.46, [M+H]+: 604.2, Method: 6 130 confirms the MW, Rt: 1.29, [M+H]+: 588.3, Method: 6 131 confirms the MW, Rt: 1.35, [M+H]+: 510.3, Method: 6 132 confirms the MW, Rt: 1.36, [M+H]+: 492.4, Method: 6 133 confirms the MW, Rt: 1.48, [M+H]+: 600.3, Method: 6 134 confirms the MW, Rt: 1.19, [M+H]+: 512.4, Method: 6 135 confirms the MW, Rt: 1.38, [M+H]+: 557.3, Method: 6 136 confirms the MW, Rt: 1.37, [M+H]+: 537.3, Method: 6 137 confirms the MW, Rt: 1.31, [M+H]+: 515.4, Method: 6 138 confirms the MW, Rt: 1.43, [M+H]+: 488.4, Method: 6 139 confirms the MW, Rt: 1.18, [M+H]+: 560.4, Method: 6 140 confirms the MW, Rt: 1.37, [M+H]+: 598.4, Method: 6 141 confirms the MW, Rt: 1.40, [M+H]+: 474.4, Method: 6 142 confirms the MW, Rt: 1.37, [M+H]+: 513.3, Method: 6 143 confirms the MW, Rt: 1.43, [M+H]+: 564.4, Method: 6 144 confirms the MW, Rt: 1.22, [M+H]+: 514.4, Method: 6 145 confirms the MW, Rt: 1.36, [M+H]+: 510.3, Method: 6 146 confirms the MW, Rt: 1.14, [M+H]+: 521.4, Method: 6 Compound No. LCMS results 147 confirms the MW, Rt: 1.37, [M+H]+: 518.3, Method: 6 148 confirms the MW, Rt: 1.44, [M+H]+: 582.4, Method: 6 149 confirms the MW, Rt: 1.20, [M+H]+: 527.3, Method: 6 150 confirms the MW, Rt: 1.42, [M+H]+: 519.4, Method: 6 151 confirms the MW, Rt: 1.32, [M+H]+: 492.4, Method: 6 152 confirms the MW, Rt: 1.31, [M+H]+: 515.3, Method: 6 153 confirms the MW, Rt: 1.41, [M+H]+: 583.4, Method: 6 154 confirms the MW, Rt: 1.45, [M+H]+: 530.3, Method: 6 155 confirms the MW, Rt: 1.21, [M+H]+: 517.3, Method: 6 confirms t+156 he MW, Rt: 1.33, [M+H] : 490.3, 23% and Rt: 1.35, [M+H]+: 490.3, 76%, Method: 6 157 confirms the MW, Rt: 1.33, [M+H]+: 504.4, Method: 6 158 confirms the MW, Rt: 1.39, [M+H]+: 544.3, Method: 6 159 confirms the MW, Rt: 1.31, [M+H]+: 594.4, Method: 6 160 confirms the MW, Rt: 1.21, [M+H]+: 531.3, Method: 6 161 confirms the MW, Rt: 1.43, [M+H]+: 552.3, Method: 6 162 confirms the MW, Rt: 0.98, [M+H]+: 514.3, Method: 6 163 confirms the MW, Rt: 1.26, [M+H]+: 540.4, Method: 6 164 confirms the MW, Rt: 1.24, [M+H]+: 531.4, Method: 6 165 confirms the MW, Rt: 1.32, [M+H]+: 579.4, Method: 6 166 confirms the MW, Rt: 1.45, [M+H]+: 558.3, Method: 6 167 confirms the MW, Rt: 1.28, [M+H]+: 501.3, Method: 6 168 confirms the MW, Rt: 1.22, [M+H]+: 540.3, Method: 6 169 confirms the MW, Rt: 1.49, [M+H]+: 608.2, Method: 6 170 confirms the MW, Rt: 1.27, [M+H]+: 578.4, Method: 6 171 confirms the MW, Rt: 1.48, [M+H]+: 604.4, Method: 6 172 confirms the MW, Rt: 1.14, [M+H]+: 561.3, Method: 6 173 confirms the MW, Rt: 0.98, [M+H]+: 516.3, Method: 6 174 confirms the MW, Rt: 1.20, [M+H]+: 551.2, Method: 6 175 confirms the MW, Rt: 1.24, [M+H]+: 538.3, Method: 6 176 confirms the MW, Rt: 1.45, [M+H]+: 618.3, Method: 6 177 confirms the MW, Rt: 1.36, [M+H]+: 510.3, Method: 6 178 confirms the MW, Rt: 1.24, [M+H]+: 516.3, Method: 6 179 confirms the MW, Rt: 1.43, [M+H]+: 566.4, 53% and Rt: 1.44, [M+H]+: 566.4, 46%, Method: 6 180 confirms the MW, Rt: 1.48, [M+H]+: 554.3, Method: 6 181 confirms the MW, Rt: 1.21, [M+H]+: 531.4, Method: 6 182 confirms the MW, Rt: 1.35, [M+H]+: 504.4, Method: 6 183 confirms the MW, Rt: 1.52, [M+H]+: 584.3, Method: 6 Compound No. LCMS results 184 confirms the MW, Rt: 1.23 [M+H]+: 517.4, Method: 6 185 confirms the MW, Rt: 1.24, [M+H]+: 553.3, Method: 6 186 confirms the MW, Rt: 1.33, [M+H]+: 480.3, Method: 6 187 confirms the MW, Rt: 1.41, [M+H]+: 512.3, Method: 6 188 confirms the MW, Rt: 1.26, [M+H]+: 566.4, Method: 6 189 confirms the MW, Rt: 1.18, [M+H]+: 570.4, Method: 6 190 confirms the MW, Rt: 1.25, [M+H]+: 536.3, Method: 6 191 confirms the MW, Rt: 1.24, [M+H]+: 566.4, Method: 6 192 confirms the MW, Rt: 1.38, [M+H]+: 590.4, Method: 6 193 confirms the MW, Rt: 1.19, [M+H]+: 561.4, Method: 6 194 confirms the MW, Rt: 1.13, [M+H]+: 537.3, Method: 6 195 confirms the MW, Rt: 1.23, [M+H]+: 550.3, Method: 6 196 confirms the MW, Rt: 1.14, [M+H]+: 557.4, Method: 6 197 confirms the MW, Rt: 1.30, [M+H]+: 560.3, Method: 6 198 confirms the MW, Rt: 1.45, [M+H]+: 562.4, Method: 6 199 confirms the MW, Rt: 1.25, [M+H]+: 540.3, Method: 6 200 confirms the MW, Rt: 1.14, [M+H]+: 544.4, Method: 6 201 confirms the MW, Rt: 1.46, [M+H]+: 568.4, Method: 6 202 confirms the MW, Rt: 1.27, [M+H]+: 557.4, Method: 6 203 confirms the MW, Rt: 1.41, [M+H]+: 564.3, Method: 6 204 confirms the MW, Rt: 1.46, [M+H]+: 588.3, Method: 6 205 confirms the MW, Rt: 1.44, [M+H]+: 536.3, Method: 6 206 confirms the MW, Rt: 1.25, [M+H]+: 540.4, Method: 6 207 confirms the MW, Rt: 1.37, [M+H]+: 504.3, Method: 6 208 confirms the MW, Rt: 1.36, [M+H]+: 551.3, Method: 6 209 confirms the MW, Rt: 1.46, [M+H]+: 602.3, Method: 6 210 confirms the MW, Rt: 1.12, [M+H]+: 513.3, Method: 6 211 confirms the MW, Rt: 1.23, [M+H]+: 567.4, Method: 6 212 confirms the MW, Rt: 1.30, [M+H]+: 542.4, Method: 6 213 confirms the MW, Rt: 1.42, [M+H]+: 546.3, Method: 6 214 confirms the MW, Rt: 1.32, [M+H]+: 558.3, Method: 6 215 confirms the MW, Rt: 1.33, [M+H]+: 522.4, Method: 6 216 confirms the MW, Rt: 1.22, [M+H]+: 551.3, Method: 6 217 confirms the MW, Rt: 1.40, [M+H]+: 504.3, Method: 6 218 confirms the MW, Rt: 1.32, [M+H]+: 551.3, Method: 6 219 confirms the MW, Rt: 1.23, [M+H]+: 554.4, Method: 6 220 confirms the MW, Rt: 1.22, [M+H]+: 550.3, Method: 6 221 confirms the MW, Rt: 1.16, [M+H]+: 531.3, Method: 6 Compound No. LCMS results 222 confirms the MW, Rt: 1.32, [M+H]+: 547.4, Method: 6 223 confirms the MW, Rt: 1.10, [M+H]+: 497.6, Method: 7 224 confirms the MW, Rt: 1.13, [M+H]+: 518.5, Method: 7 225 confirms the MW, Rt: 1.19, [M+H]+: 400.2, Method: 8 226 confirms the MW, Rt: 2.01, [M+H]+: 531.7, Method: 1 227 confirms the MW, Rt: 2.04, [M+H]+: 507.4, Method: 1 228 confirms the MW, Rt: 2.02, [M+H]+: 520.3, Method: 1 229 confirms the MW, Rt: 1.98, [M+H]+: 520.3, Method: 1 230 confirms the MW, Rt: 1.98, [M+H]+: 520.3, Method: 1 231 confirms the MW, Rt: 2.05, [M+H]+: 492.4, Method: 1 232 confirms the MW, Rt: 2.22, [M+H]+: 507.3, Method: 1 233 confirms the MW, Rt: 1.15, [M+H]+: 470.5, Method: 6 234 confirms the MW, Rt: 1.16, [M+H]+: 484.5, Method: 6 235 confirms the MW, Rt: 1.16, [M+H]+:518.4, Method: 6 236 confirms the MW, Rt: 1.14, [M+H]+: 456.4, Method: 6 237 confirms the MW, Rt: 1.13, [M+H]+: 470.4, Method: 6 238 confirms the MW, Rt: 1.24, [M+H]+: 470.4, Method: 6 239 confirms the MW, Rt: 1.15, [M+H]+: 470.4, Method: 6 240 confirms the MW, Rt: 1.14, [M+H]+: 497.5, Method: 6 241 confirms the MW, Rt: 1.15, [M+H]+: 506.4, Method: 6 242 confirms the MW, Rt: 1.10, [M+H]+: 472.4, Method: 6 243 confirms the MW, Rt: 1.14, [M+H]+: 518.4, Method: 6 244 confirms the MW, Rt: 1.13, [M+H]+: 444.4, Method: 6 245 confirms the MW, Rt: 1.18, [M+H]+: 484.5, Method: 6 246 confirms the MW, Rt: 1.17, [M+H]+: 456.4, Method: 6 247 confirms the MW, Rt: 1.11, [M+H]+: 486.4, Method: 6 248 confirms the MW, Rt: 1.18, [M+H]+: 516.4, Method: 6 249 confirms the MW, Rt: 1.10, [M+H]+: 483.4, Method: 6 250 confirms the MW, Rt: 1.21, [M+H]+: 535.5, Method: 6 251 confirms the MW, Rt: 1.11, [M+H]+: 472.4, Method: 6 252 confirms the MW, Rt: 1.18, [M+H]+: 484.5, Method: 6 253 confirms the MW, Rt: 1.17, [M+H]+: 518.4, Method: 6 254 confirms the MW, Rt: 1.12, [M+H]+: 456.4, Method: 6 255 confirms the MW, Rt: 1.18, [M+H]+: 518.4, Method: 6 256 confirms the MW, Rt: 1.14, [M+H]+: 518.4, Method: 6 257 confirms the MW, Rt: 1.15, [M+H]+: 532.4, Method: 6 258 confirms the MW, Rt: 1.09, [M+H]+: 519.4, Method: 6 259 confirms the MW, Rt: 1.19, [M+H]+: 518.4, Method: 6 Compound No. LCMS results 260 confirms the MW, Rt: 1.22, [M+H]+: 528.3, Method: 6 261 confirms the MW, Rt: 1.15, [M+H]+: 504.4, Method: 6 262 confirms the MW, Rt: 1.16, [M+H]+: 490.4, Method: 6 263 confirms the MW, Rt: 1.15, [M+H]+: 518.4, Method: 6 264 confirms the MW, Rt: 1.16, [M+H]+: 504.4, Method: 6 265 confirms the MW, Rt: 1.09, [M+H]+: 507.5, Method: 6 266 confirms the MW, Rt: 1.06, [M+H]+: 505.4, Method: 6 267 confirms the MW, Rt: 1.21, [M+H]+: 587.5, Method: 6 268 confirms the MW, Rt: 1.15, [M+H]+: 532.4, Method: 6 269 confirms the MW, Rt: 1.11, [M+H]+: 500.5, Method: 6 270 confirms the MW, Rt: 1.21, [M+H]+: 470.4, Method: 6 271 confirms the MW, Rt: 0.94, [M+H]+: 508.5, Method: 6 272 confirms the MW, Rt: 1.15, [M+H]+: 470.4, Method: 6 273 confirms the MW, Rt: 1.16, [M+H]+: 506.5, Method: 6 274 confirms the MW, Rt: 1.14, [M+H]+: 511.5, Method: 6 275 confirms the MW, Rt: 1.16, [M+H]+: 520.5, Method: 6 276 confirms the MW, Rt: 1.11, [M+H]+: 497.5, Method: 6 277 confirms the MW, Rt: 1.17, [M+H]+: 532.4, Method: 6 278 confirms the MW, Rt: 1.07, [M+H]+: 466.4, Method: 6 279 confirms the MW, Rt: 1.17, [M+H]+: 546.4, Method: 6 280 confirms the MW, Rt: 1.11, [M+H]+: 486.5, Method: 6 281 confirms the MW, Rt: 1.10, [M+H]+: 472.4, Method: 6 282 confirms the MW, Rt: 1.08, [M+H]+: 516.4, Method: 6 283 confirms the MW, Rt: 1.19, [M+H]+: 535.5, Method: 6 284 confirms the MW, Rt: 1.12, [M+H]+: 444.4, Method: 6 285 confirms the MW, Rt: 1.11, [M+H]+: 497.4, Method: 6 286 confirms the MW, Rt: 1.16, [M+H]+: 484.5, Method: 6 287 confirms the MW, Rt: 1.13, [M+H]+: 470.4, Method: 6 288 confirms the MW, Rt: 1.13, [M+H]+: 506.6, Method: 6 289 confirms the MW, Rt: 1.20, [M+H]+: 506.5, Method: 6 290 confirms the MW, Rt: 1.11, [M+H]+: 534.6, Method: 6 291 confirms the MW, Rt: 1.12, [M+H]+: 470.5, Method: 6 292 confirms the MW, Rt: 1.71, [M+H]+: 532.6, Method: 1 293 confirms the MW, Rt: 1.80, [M+H]+: 508.5, Method: 1 294 confirms the MW, Rt: 1.68, [M+H]+: 521.3, Method: 1 295 confirms the MW, Rt: 1.68, [M+H]+: 521.3, Method: 1 296 confirms the MW, Rt: 1.67, [M+H]+: 521.3, Method: 1 297 confirms the MW, Rt: 1.71, [M+H]+: 493.3, Method: 1 Compound No. LCMS results 298 confirms the MW, Rt: 1.10, [M+H]+: 508.3, Method: 1 299 confirms the MW, Rt: 1.07, [M+H]+: 483.5, Method: 6 300 confirms the MW, Rt: 1.06, [M+H]+: 434.4, Method: 6 301 confirms the MW, Rt: 1.08, [M+H]+: 515.5, Method: 6 302 confirms the MW, Rt: 1.07, [M+H]+: 507.5, Method: 6 303 confirms the MW, Rt: 1.05, [M+H]+: 559.4, Method: 6 304 confirms the MW, Rt: 1.17, [M+H]+: 510.5, Method: 6 305 confirms the MW, Rt: 1.12, [M+H]+: 483.4, Method: 6 306 confirms the MW, Rt: 1.02, [M+H]+: 534.4, Method: 6 307 confirms the MW, Rt: 1.01, [M+H]+: 535.4, Method: 6 308 confirms the MW, Rt: 1.07, [M+H]+: 511.5, Method: 6 309 confirms the MW, Rt: 0.96, [M+H]+: 495.5, Method: 6 310 confirms the MW, Rt: 1.14, [M+H]+: 511.5, Method: 6 311 confirms the MW, Rt: 1.13, [M+H]+: 497.5, Method: 6 312 confirms the MW, Rt: 1.04, [M+H]+: 482.4, Method: 6 313 confirms the MW, Rt: 1.00, [M+H]+: 561.4, Method: 6 314 confirms the MW, Rt: 1.00, [M+H]+: 498.5, Method: 6 315 confirms the MW, Rt: 1.05, [M+H]+: 445.4, Method: 6 316 confirms the MW, Rt: 1.04, [M+H]+: 513.5, Method: 6 317 confirms the MW, Rt: 1.18, [M+H]+: 525.5, Method: 6 318 confirms the MW, Rt: 1.07, [M+H]+: 497.5, Method: 6 319 confirms the MW, Rt: 1.02, [M+H]+: 514.5, Method: 6 320 confirms the MW, Rt: 0.84, [M+H]+: 539.5, 42% and Rt: 0.85, [M+H]+: 539.5, 58%, Method: 7 321 confirms the MW, Rt: 0.94, [M+H]+: 566.5, Method: 1 322 confirms the MW, Rt: 0.93, [M+H]+: 502.5, Method: 1 323 confirms the MW, Rt: 0.87, [M+H]+: 574.5, Method: 1 324 confirms the MW, Rt: 0.82, [M+H]+: 575.5, Method: 1 confirms the MW, Rt: 0.83, [M+H+325 ] : 551.5, 44% and Rt: 0.84, [M+H]+: 551.5, 56%, Method: 1 326 confirms the MW, Rt: 0.78, [M+H]+: 570.6, Method: 1 327 confirms the MW, Rt: 0.83, [M+H]+: 543.5, Method: 1 confirms the MW, Rt: 0.89, [M+H+328 ] : 576.5, 32% and Rt: 0.90, [M+H]+: 576.5, 68%, Method: 1 329 confirms the MW, Rt: 0.91, [M+H]+: 550.2, Method: 1 330 confirms the MW, Rt: 0.85, [M+H]+: 551.5, Method: 1 331 confirms the MW, Rt: 0.93, [M+H]+: 569.6, Method: 1 confirms t+332 he MW, Rt: 0.89, [M+H] : 552.5, 49% and Rt: 0.90, [M+H]+: 551.2, 49%, Method: 1 333 confirms the MW, Rt: 0.92, [M+H]+: 565.5, Method: 1 Compound No. LCMS results 334 confirms the MW, Rt: 0.80, [M+H]+: 579.6, Method: 1 335 confirms the MW, Rt: 0.83, [M+H]+: 555.6, Method: 1 336 confirms the MW, Rt: 0.94, [M+H]+: 571.5, Method: 1 337 confirms the MW, Rt: 0.86, [M+H]+: 544.6, Method: 1 confirms the MW, Rt+338 : 0.84, [M+H] : 552.5, 43% and Rt: 0.85, [M+H]+: 552.5, 57%, Method: 1 339 confirms the MW, Rt: 0.96, [M+H]+: 528.6, Method: 1 340 confirms the MW, Rt: 0.95, [M+H]+: 536.5, Method: 1 341 confirms the MW, Rt: 0.83, [M+H]+: 536.2, Method: 1 342 confirms the MW, Rt: 0.92, [M+H]+: 564.6, Method: 1 343 confirms the MW, Rt: 0.88, [M+H]+: 576.6, Method: 1 344 confirms the MW, Rt: 0.83, [M+H]+: 527.6, Method: 1 345 confirms the MW, Rt: 0.92, [M+H]+: 552.6, Method: 1 346 confirms the MW, Rt: 0.93, [M+H]+: 502.6, Method: 1 347 confirms the MW, Rt: 0.91, [M+H]+: 554.5, Method: 1 confirms the MW, Rt: 0.84, [M+H]+348 : 564.6, 43% and Rt: 0.85, [M+H]+: 564.6, 55%, Method: 1 349 confirms the MW, Rt: 0.83, [M+H]+: 593.6, Method: 1 350 confirms the MW, Rt: 0.82, [M+H]+: 566.5, Method: 1 351 confirms the MW, Rt: 0.85, [M+H]+: 551.6, Method: 1 352 confirms the MW, Rt: 0.90, [M+H]+: 550.5, 39% and Rt: 0.92, [M+H]+: 550.5, 59%, Method: 1 353 confirms the MW, Rt: 0.83, [M+H]+: 555.6, Method: 1 354 confirms the MW, Rt: 0.82, [M+H]+: 543.5, Method: 1 355 confirms the MW, Rt: 0.85, [M+H]+: 577.5, Method: 1 356 confirms the MW, Rt: 0.86, [M+H]+: 593.6, Method: 1 357 confirms the MW, Rt: 0.91, [M+H]+: 550.6, Method: 1 358 confirms the MW, Rt: 0.80, [M+H]+: 549.6, Method: 1 confirms the MW, Rt: 0+359 .84, [M+H] : 565.6, 49% and Rt: 0.86, [M+H]+: 565.6, 50%, Method: 1 360 confirms the MW, Rt: 0.88, [M+H]+: 591.5, Method: 1 361 confirms the MW, Rt: 0.90, [M+H]+: 516.6, Method: 1 362 confirms the MW, Rt: 0.93, [M+H]+: 526.6, Method: 1 363 confirms the MW, Rt: 0.91, [M+H]+: 584.6, Method: 1 364 confirms the MW, Rt: 0.91, [M+H]+: 550.6, Method: 1 confirms the MW, Rt: 0+365 .95, [M+H] : 561.6, 39% and Rt: 0.97, [M+H]+: 561.6, 61%, Method: 1 366 confirms the MW, Rt: 0.84, [M+H]+: 564.6, Method: 1 367 confirms the MW, Rt: 0.83, [M+H]+: 527.6, Method: 1 368 confirms the MW, Rt: 0.78, [M+H]+: 543.6, Method: 1 Compound No. LCMS results 369 confirms the MW, Rt: 0.86, [M+H]+: 551.5, Method: 1 370 confirms the MW, Rt: 0.90, [M+H]+: 577.5, Method: 1 371 confirms the MW, Rt: 0.87, [M+H]+: 565.5, Method: 1 372 confirms the MW, Rt: 0.83, [M+H]+: 551.5, Method: 1 373 confirms the MW, Rt: 0.85, [M+H]+: 575.6, Method: 1 374 confirms the MW, Rt: 0.89, [M+H]+: 548.5, Method: 1 375 confirms the MW, Rt: 0.84, [M+H]+: 563.5, Method: 1 376 confirms the MW, Rt: 0.80, [M+H]+: 538.6, Method: 1 377 confirms the MW, Rt: 0.83, [M+H]+: 530.6, Method: 1 confi+378 rms the MW, Rt: 0.83, [M+H] : 563.5, 41% and Rt: 0.84, [M+H]+: 563.5, 59%, Method: 1 379 confirms the MW, Rt: 0.82, [M+H]+: 606.6, Method: 1 380 confirms the MW, Rt: 0.92, [M+H]+: 552.2, Method: 1 381 confirms the MW, Rt: 0.85, [M+H]+: 550.5, Method: 1 382 confirms the MW, Rt: 0.81, [M+H]+: 544.6, Method: 1 383 confirms the MW, Rt: 0.85, [M+H]+: 548.5, Method: 1 384 confirms the MW, Rt: 0.86, [M+H]+: 580.6, Method: 1 385 confirms the MW, Rt: 0.86, [M+H]+: 555.6, Method: 1 386 confirms the MW, Rt: 0.91, [M+H]+: 569.6, Method: 1 387 confirms the MW, Rt: 0.85, [M+H]+: 534.5, Method: 1 confirms the M+388 W, Rt: 0.88, [M+H] : 544.5, 53% and Rt: 0.89, [M+H]+: 544.5, 47%, Method: 1 confirms the MW, Rt:+389 0.86, [M+H] : 562.5, 27% and Rt: 0.87, [M+H]+: 562.5, 73%, Method: 1 390 confirms the MW, Rt: 0.86, [M+H]+: 563.5, Method: 1 391 confirms the MW, Rt: 0.74, [M+H]+: 555.5, Method: 1 392 confirms the MW, Rt: 0.89, [M+H]+: 591.5, Method: 1 393 confirms the MW, Rt: 0.78, [M+H]+: 581.6, Method: 1 394 confirms the MW, Rt: 0.85, [M+H]+: 571.6, Method: 1 395 confirms the MW, Rt: 0.79, [M+H]+: 555.5, Method: 1 396 confirms the MW, Rt: 0.85, [M+H]+: 544.2, Method: 1 397 confirms the MW, Rt: 0.82, [M+H]+: 550.5, Method: 1 398 confirms the MW, Rt: 0.77, [M+H]+: 560.5, Method: 1 399 confirms the MW, Rt: 0.79, [M+H]+: 581.6, Method: 1 400 confirms the MW, Rt: 0.76, [M+H]+: 557.6, Method: 1 401 confirms the MW, Rt: 0.87, [M+H]+: 590.6, Method: 1 402 confirms the MW, Rt: 0.81, [M+H]+: 542.5, Method: 1 403 confirms the MW, Rt: 0.73, [M+H]+: 541.5, Method: 1 404 confirms the MW, Rt: 0.85, [M+H]+: 576.5, Method: 1 Compound No. LCMS results 405 confirms the MW, Rt: 0.84, [M+H]+: 515.5, Method: 1 406 confirms the MW, Rt: 0.79, [M+H]+: 537.5, Method: 1 407 confirms the MW, Rt: 0.88, [M+H]+: 555.6, Method: 1 confirms the MW, Rt: 0.85, [M+H]+: 576.5, 8%, Rt: 408 0.86, [M+H]+: 576.5, 41%, and Rt: 0.87, [M+H]+: 576.5, 51%, Method: 1 409 confirms the MW, Rt: 0.82, [M+H]+: 551.5, Method: 1 410 confirms the MW, Rt: 0.77, [M+H]+: 561.5, Method: 1 411 confirms the MW, Rt: 0.82, [M+H]+: 577.5, Method: 1 412 confirms the MW, Rt: 0.83, [M+H]+: 591.5, Method: 1 413 confirms the MW, Rt: 0.88, [M+H]+: 562.5, Method: 1 414 confirms the MW, Rt: 0.88, [M+H]+: 529.6, Method: 1 415 confirms the MW, Rt: 0.95, [M+H]+: 612.5, Method: 1 416 confirms the MW, Rt: 0.84, [M+H]+: 541.6, Method: 1 417 confirms the MW, Rt: 0.88, [M+H]+: 529.5, Method: 1 418 confirms the MW, Rt: 0.86, [M+H]+: 550.5, Method: 1 confirms the MW, Rt: 0.81, [M+H+419 ] : 530.5, 43% and Rt: 0.82, [M+H]+: 530.5, 54%, Method: 1 420 confirms the MW, Rt: 0.85, [M+H]+: 576.5, Method: 1 421 confirms the MW, Rt: 0.82, [M+H]+: 541.5, Method: 1 422 confirms the MW, Rt: 0.89, [M+H]+: 562.5, Method: 1 423 confirms the MW, Rt: 0.77, [M+H]+: 525.5, Method: 1 424 confirms the MW, Rt: 0.76, [M+H]+: 520.5, Method: 1 425 confirms the MW, Rt: 0.82, [M+H]+: 566.5, Method: 1 426 confirms the MW, Rt: 0.83, [M+H]+: 565.6, Method: 1 427 confirms the MW, Rt: 0.85, [M+H]+: 548.5, Method: 1 428 confirms the MW, Rt: 0.84, [M+H]+: 562.5, Method: 1 429 confirms the MW, Rt: 0.85, [M+H]+: 576.5, Method: 1 430 confirms the MW, Rt: 0.85, [M+H]+: 548.5, Method: 1 431 confirms the MW, Rt: 0.85, [M+H]+: 576.5, Method: 1 432 confirms the MW, Rt: 0.81, [M+H]+: 530.5, Method: 1 433 confirms the MW, Rt: 0.82, [M+H]+: 607.6, Method: 1 434 confirms the MW, Rt: 0.85, [M+H]+: 552.6, Method: 1 435 confirms the MW, Rt: 0.84, [M+H]+: 576.5, Method: 1 436 confirms the MW, Rt: 0.80, [M+H]+: 530.5, Method: 1 confirms the MW, Rt: 0.90, [M+H]+: 595.6, 32%, Rt: 437 0.91, [M+H]+: 595.6, 37%, and Rt: 0.93, [M+H]+: 595.6, 30%, Method: 1 438 confirms the MW, Rt: 0.79, [M+H]+: 585.6, Method: 1 439 confirms the MW, Rt: 0.85, [M+H]+: 599.3, Method: 1 Compound No. LCMS results 440 confirms the MW, Rt: 0.80, [M+H]+: 578.5, Method: 1 441 confirms the MW, Rt: 0.83, [M+H]+: 580.5, Method: 1 confirms the MW, Rt: 0.83,+442 [M+H] : 564.5, 43% and Rt: 0.84, [M+H]+: 564.5, 57%, Method: 1 443 confirms the MW, Rt: 0.83, [M+H]+: 539.5, Method: 1 444 confirms the MW, Rt: 0.89, [M+H]+: 576.5, Method: 1 445 confirms the MW, Rt: 0.86, [M+H]+: 543.5, Method: 1 446 confirms the MW, Rt: 0.88, [M+H]+: 555.6, Method: 1 confirms the+447 MW, Rt: 0.81, [M+H] : 525.6, 27% and Rt: 0.82, [M+H]+: 525.6, 71%, Method: 1 448 confirms the MW, Rt: 0.82, [M+H]+: 578.5, Method: 1 449 confirms the MW, Rt: 0.75, [M+H]+: 555.6, Method: 1 450 confirms the MW, Rt: 0.87, [M+H]+: 560.5, Method: 1 confirms the MW, Rt:+451 0.88, [M+H] : 556.5, 72% and Rt: 0.89, [M+H]+: 556.5, 28%, Method: 1 452 confirms the MW, Rt: 0.80, [M+H]+: 516.5, Method: 1 453 confirms the MW, Rt: 0.90, [M+H]+: 605.6, Method: 1 confirms the MW, R+454 t: 0.87, [M+H] : 562.5, 41% and Rt: 0.88, [M+H]+: 562.5, 59%, Method: 1 455 confirms the MW, Rt: 0.87, [M+H]+: 538.6, Method: 1 456 confirms the MW, Rt: 0.80, [M+H]+: 592.5, Method: 1 457 confirms the MW, Rt: 0.84, [M+H]+: 526.5, Method: 1 458 confirms the MW, Rt: 0.85, [M+H]+: 542.5, Method: 1 459 confirms the MW, Rt: 0.83, [M+H]+: 542.5, Method: 1 460 confirms the MW, Rt: 0.80, [M+H]+: 530.6, Method: 1 461 confirms the MW, Rt: 0.87, [M+H]+: 577.5, Method: 1 462 confirms the MW, Rt: 0.83, [M+H]+: 564.5, Method: 1 463 confirms the MW, Rt: 0.81, [M+H]+: 592.5, Method: 1 464 confirms the MW, Rt: 0.88, [M+H]+: 566.6, Method: 1 465 confirms the MW, Rt: 0.88, [M+H]+: 566.6, Method: 1 66 confirms the MW+4 , Rt: 0.81, [M+H] : 551.6, 47% and Rt: 0.82, [M+H]+: 551.6, 53%, Method: 1 467 confirms the MW, Rt: 0.84, [M+H]+: 604.6, Method: 1 468 confirms the MW, Rt: 0.84, [M+H]+: 592.6, Method: 1 469 confirms the MW, Rt: 0.84, [M+H]+: 565.6, 41% and Rt: 0.85, [M+H]+: 565.6, 58%, Method: 1 470 confirms the MW, Rt: 0.84, [M+H]+: 576.6, Method: 1 471 confirms the MW, Rt: 0.85, [M+H]+: 562.5, Method: 1 472 confirms the MW, Rt: 0.89, [M+H]+: 590.6, Method: 1 473 confirms the MW, Rt: 0.94, [M+H]+: 605.6, Method: 1 Compound No. LCMS results 474 confirms the MW, Rt: 0.83, [M+H]+: 524.6, Method: 1 475 confirms the MW, Rt: 0.94, [M+H]+: 582.5, Method: 1 476 confirms the MW, Rt: 0.84, [M+H]+: 562.5, Method: 1 477 confirms the MW, Rt: 0.90, [M+H]+: 539.6, Method: 1 478 confirms the MW, Rt: 0.86, [M+H]+: 577.5, Method: 1 479 confirms the MW, Rt: 0.81, [M+H]+: 620.6, Method: 1 480 confirms the MW, Rt: 0.92, [M+H]+: 542.5, Method: 1 481 confirms the MW, Rt: 0.75, [M+H]+: 555.6, Method: 1 482 confirms the MW, Rt: 0.92, [M+H]+: 542.5, Method: 1 483 confirms the MW, Rt: 0.80, [M+H]+: 554.6, Method: 1 484 confirms the MW, Rt: 0.88, [M+H]+: 540.6, Method: 1 485 confirms the MW, Rt: 0.84, [M+H]+: 486.6, Method: 1 486 confirms the MW, Rt: 0.80, [M+H]+: 541.6, Method: 1 Table: Analytical SFC data – Rtmeans retention time (in minutes), method refers to the method used for (SFC)MS analysis of enantiomerically pure compounds. No. means number. Compound No. SFC Method Rt UV Area (%) 4 5 4.22 100 5 5 4.44 99 7 4 4.78 100 8 4 5.20 100 10 1 3.87 100 11 1 4.52 100 14 6 5.29 100 15 6 6.13 100 19 3 4.90 100 20 1 3.91 100 22 2 5.26 100 23 2 5.89 100 229 1 4.14 100 230 1 4.56 98 295 1 5.18 98 296 1 5.70 100 Analytical Analysis The high performance liquid chromatography (HPLC) measurement was performed using a LC pump, a diode-array (DAD) or a UV detector and a column as specified in the respective methods. If necessary, additional detectors were included (see table of methods below). Flow from the column was brought to the Mass Spectrometer (MS) which was configured with an atmospheric pressure ion source. It is within the knowledge of the skilled person to set the tune parameters (e.g., scanning range, dwell time…) to obtain ions allowing the identification of the compound’s nominal monoisotopic molecular weight (MW). Data acquisition was performed with appropriate software. Compounds are described by their experimental retention times (Rt) and ions. If not specified differently in the table of data, the reported molecular ion corresponds to the [M+H]+(protonated molecule) and / or [M-H]- (deprotonated molecule). In case the compound was not directly ionizable the type of adduct is specified (i.e. [M+NH4]+, [M+HCOO]-, etc…). For molecules with multiple isotopic patterns (Br, Cl), the reported value is the one obtained for the lowest isotope mass. All results were obtained with experimental uncertainties that are commonly associated with the method used. Hereinafter, “SQD” means Single Quadrupole Detector, “MSD” Mass Selective Detector, “RT” room temperature, “BEH” bridged ethylsiloxane / silica hybrid, “DAD” Diode Array Detector, “HSS” High Strength silica. LCMS Method Codes (Flow expressed in mL / min, column temperature (T) in °C, Run time in minutes) Flow Method ------- Run Instrument column mobile phase gradient Code --- time Col T From 100% Waters: Waters: A: 10mM A to Acquity®BEH NH4HCO35% A in 2.10 0.6 1 UPLC®- (1.7µm, in 95% H2O + 5% min, and 2.1*10 CH3CN to 0 ------- 3.5 DAD % A in D 0mm) B: CH3CN 0. 55 SQ 9min, to 5% A in 0.5min Flow Method ------- Run Instrument column mobile phase gradient Code --- time Col T From 100% Waters: Waters: A: 10mM A to 2 Acquity®BEH CH 5% A in 3COONH4 0.6 UPLC®- (1.7µm, in 95% H2O + 5% 2.10min, ------- 3.5 DAD and 2.1*10 CH3CN to 0% A in 0 55 SQD 0mm) B: CH .9min, 3CN to 5% A in 0.5min Waters: Waters: A: 10mM From 95% 3 Acquity®BEH CH3COONH4 A to 5% A 0.8 UPLC®- (1.7µm, in 95% H2O + 5% in ------- 2 DAD and 2.1*10 CH3CN 1.3min,held 55 SQD 0mm) B: CH3CN for 0.7 min From 70% A to 30% A 4 Shimadzu Shim‐ A: Water / 5mM in 1.7 min, 1.2 LCMS‐2020 Pack NH4HCO3 to 5% A in --- 3.0 C18 B: Acetonitrile 0.5 min, to 40 5% A in 0.5 min HALO C18 A:Water / 0.05%TF From 95% 5 Shimadzu (2.0 A A to 0% A 1.5 LCMS‐2020 um, 3.0 B:Acetonitrile / 0.05 in 1.2 min, --- 2.0 x 30 %TFA to 0% A in 40 mm) 0.5 min Waters: Waters: A: 0.1% NH HC From 100% Acquity®BEH4O3in 95% H A to 5% A 0.8 6 UPLC®- (1.7µm,2O + 5% CH CN in 1.3 min, ------- 2.0 DAD and 2.1*503B: CH hold for 0.7 55 SQD mm)3CN min Waters: Waters: A: 10mM From 100% Acquity®BEH CH3COONH4 A to 5% A 0.8 7 UPLC®- (1.7µm, in 95% H2O + 5% in 1.3min, ------- 2.0 DAD and 2.1*50 CH3CN hold for 0.7 55 SQD mm) B: CH3CN min Flow Method ------- Run Instrument column mobile phase gradient Code --- time Col T From 100% Waters: Waters: A: 0.1% NH4HCO3A to ® 0.8 8 Acquity CSH in 95% H2O + 5% 5% A in 1.3 UPLC®- (1.7µm, ------- 2.0 CH3CN min, DAD and 2.1*50 55 SQD mm) B: CH3CN hold 0.7 min SFC-MS methods: The SFC measurement was performed using an Analytical Supercritical fluid chromatography (SFC) system composed by a binary pump for delivering carbon dioxide (CO2) and modifier, an autosampler, a column oven, a diode array detector equipped with a high-pressure flow cell standing up to 400 bars. If configured with a Mass Spectrometer (MS) the flow from the column was brought to the (MS). It is within the knowledge of the skilled person to set the tune parameters (e.g., scanning range, dwell time…) to obtain ions allowing the identification of the compound’s nominal monoisotopic molecular weight (MW). Data acquisition was performed with appropriate software. Analytical SFC-MS Methods (Flow expressed in mL / min, column temperature (Col T) in °C, Run time in minutes, Backpressure (BPR) in bars. “iPrNH2” means isopropylamine, “iPrOH” means 2-propanol, “EtOH” means ethanol, “min” mean minutes. SFC methods:

[0041] Run Flow SFC time Column mobile phase gradient ------- Method ------- Col T BPR A:CO 1 Daicel Chiralpak®210%-50% B 2.5 9.5 B: EtOH IH3 column (3.0 in 6 min, ------- ------- +0.2% μm, 150 x 4.6 mm) hold 3.5 min 40 130 iPrNH2 ® A:CO2 2 Daicel Chiralpak 10%-50% B 2.5 9.5 B: OJ3 column (3.0 in 6 min, ------- ------- EtOH+0.2% μm, 150 x 4.6 mm) hold 3.5 min 40 130 iPrNH2A:CO2 10%-5 Daicel Chiral®0% B B: 2.5 9.5 3 pak in 6 min, ------- ------- OD3 column (3.0 MeOH+0.2% hold 3.5 min 40 130 μm, 150 x 4.6 mm) iPrNH2 A: Da®CO2 2.5 9.5 4 icel Chiralpak 10%-50% B B: AD3 column (3.0 in 6 min, ------- ------- EtOH+0.2% 40 130 μm, 150 x 4.6 mm) hold 3.5 min iPrNH2A:CO2 Daicel C®10%-50% B B: 2.5 9.5 5 hiralpak in 6 min, OD3 column (3.0 EtOH+0.2% ------- ------- hold 3.5 min 6 mm) iPr 40 130 μm, 150 x 4. NH2 A: CO2Daicel Chi®10%-50% B B: 2.5 9.5 6 ralpak in 6 min, IG3 column (3.0 EtOH+0.2% ------- ------- hold 3.5 min m, 150 x 4.6 mm) i 40 130 μ PrNH2 NMR1H NMR spectra were recorded on Bruker Avance III 400MHz and Avance NEO 400MHz spectrometers. CHLOROFORM-d was used as solvent, unless otherwise mentioned. The chemical shifts are expressed in ppm relative to tetramethylsilane. Compound No 11H NMR (DMSO-d6, 400 MHz): δ (ppm) 8.13 (s, 1H), 7.46 - 7.54 (m, 2H), 7.28 - 7.37 (m, 2H), 7.14 - 7.26 (m, 3H), 6.96 - 7.05 (m, 1H), 5.43 (s, 2H), 3.46 - 3.63 (m, 3H), 2.62 - 2.85 (m, 3H), 1.80 - 2.01 (m, 4H), 1.07 - 1.19 (m, 3H). 21H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.63 (d, J = 2.7 Hz, 1H), 7.18-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 5.85 (s, 1H), 4.03 (s, 2H), 3.62 (dd, J = 15.8, 2.9 Hz, 1H), 3.37 (br d, J = 12.0 Hz, 2H), 2.87 (td, J = 12.2, 2.3 Hz, 2H), 2.68 (tt, J = 12.0, 3.8 Hz, 1H), 1.92-2.01 (m, 2H), 1.76-1.91 (m, 2H), 1.12-1.23 (m, 3H) 31H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.20-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 5.85 (br s, 1H), 4.03 (br s, 2H), 3.62 (dd, J = 15.8, 2.8 Hz, 1H), 3.37 (br d, J = 12.2 Hz, 2H), 2.92 (d, J = 4.8 Hz, 3H), 2.83-2.91 (m, 2H), 2.68 (tt, J = 12.0, 3.7 Hz, 1H), 1.93-2.03 (m, 2H), 1.78-1.91 (m, 2H), 1.18 (t, J = 2.2 Hz, 3H) 19F NMR (CHLOROFORM-d, 376 MHz): δ (ppm) -129.05 (br dd, J = 154.2, 15.8 Hz, 1F), -134.26 (d, J = 9.3 Hz, 1F), -140.09 (br d, J = 154.3 Hz, 1F) 41H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.20-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 5.82 (br s, 1H), 4.02 (br s, 2H), 3.61 (dd, J = 15.7, 2.8 Hz, 1H), 3.37 (br d, J = 12.2 Hz, 2H), 2.92 (d, J = 4.8 Hz, 3H), 2.82-2.91 (m, 2H), 2.68 (tt, J = 12.0, 3.8 Hz, 1H), 1.92-2.04 (m, 2H), 1.77-1.91 (m, 2H), 1.18 (t, J = 2.0 Hz, 3H) 51H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.7 Hz, 1H), 7.20-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 5.82 (br s, 1H), 4.02 (s, 2H), 3.61 (dd, J = 15.8, 2.9 Hz, 1H), 3.37 (br d, J = 12.3 Hz, 2H), 2.92 (d, J = 4.8 Hz, 3H), 2.88 (td, J = 12.3, 2.2 Hz, 2H), 2.68 (tt, J = 12.0, 3.8 Hz, 1H), 1.93- 2.02 (m, 2H), 1.78-1.91 (m, 2H), 1.18 (t, J = 2.2 Hz, 3H) 71H NMR (DMSO-d6, 400 MHz): δ (ppm) 7.57 (s, 2H), 7.48 (d, J = 2.8 Hz, 1H), 7.22-7.35 (m, 4H), 6.82 (dd, J = 10.5, 2.8 Hz, 1H), 5.30 (t, J = 4.0 Hz, 1H), 5.22 (s, 2H), 3.64 (br d, J = 15.3 Hz, 1H), 3.47-3.61 (m, 2H), 3.31 - 3.37 (m, 2 H), 2.59-2.78 (m, 3H), 1.78-1.97 (m, 4H) 19F NMR (DMSO-d6, 376 MHz): δ (ppm) -127.57 (br dd, J = 153.5, 14.7 Hz, 1F), -135.53 (d, J = 10.4 Hz, 1F), -139.93 (br d, J = 152.6 Hz, 1F) 81H NMR (DMSO-d6, 400 MHz): δ (ppm) 7.56 (s, 2H), 7.47 (d, J = 2.7 Hz, 1H), 7.23-7.32 (m, 4H), 6.81 (dd, J = 10.5, 2.8 Hz, 1H), 5.30 (t, J = 3.8 Hz, 1H), 5.21 (s, 2H), 3.64 (br d, J = 15.5 Hz, 1H), 3.48-3.61 (m, 2H), 3.31 - 3.37 (m, 2 H), 2.59-2.77 (m, 3H), 1.76-1.98 (m, 4H) 19F NMR (DMSO-d6, 376 MHz): δ (ppm) -127.57 (br dd, J = 153.5, 14.7 Hz, 1F), -135.53 (d, J = 10.4 Hz, 1F), -139.93 (br d, J = 154.3 Hz, 1F) Compound No 101H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.20-7.26 (m, 5H), 6.73 (dd, J = 9.4, 2.7 Hz, 1H), 4.03 (s, 2H), 3.93 (br dd, J = 14.6, 3.2 Hz, 2H), 3.51 (br d, J = 12.6 Hz, 1H), 3.38 (br d, J = 12.0 Hz, 2H), 2.94 (d, J = 4.8 Hz, 3H), 2.88 (td, J = 12.3, 2.4 Hz, 2H), 2.68 (tt, J = 12.0, 3.8 Hz, 1H), 2.12 (s, 1H), 1.93-2.02 (m, 2H), 1.77-1.90 (m, 2H) 111H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.63 (d, J = 2.6 Hz, 1H), 7.18-7.25 (m, 5H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 4.02 (s, 2H), 3.88-3.97 (m, 2H), 3.50 (br d, J = 12.6 Hz, 1H), 3.37 (br d, J = 12.0 Hz, 2H), 2.93 (d, J = 4.8 Hz, 3H), 2.87 (td, J = 12.2, 2.4 Hz, 2H), 2.67 (tt, J = 12.0, 3.7 Hz, 1H), 2.07- 2.15 (m, 1H), 1.92-2.01 (m, 2H), 1.77-1.89 (m, 2H) 121H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.17-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.7 Hz, 1H), 6.09 (br d, J = 6.4 Hz, 1H), 4.53 (sxt, J = 7.6 Hz, 1H), 4.03 (s, 2H), 3.79 (tt, J = 9.6, 4.6 Hz, 1H), 3.59 (dd, J = 15.9, 2.8 Hz, 1H), 3.37 (br d, J = 11.9 Hz, 2H), 2.91-3.00 (m, 2H), 2.86- 2.91 (m, 2H), 2.82-2.86 (m, 3H), 2.64-2.72 (m, 2H), 2.58-2.64 (m, 1H), 1.93- 2.04 (m, 2H), 1.76-1.91 (m, 2H), 1.18 (s, 3H) 131H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.20-7.26 (m, 4H), 6.72 (dd, J = 9.4, 2.8 Hz, 1H), 5.78 (br s, 1H), 5.56 (br s, 1H), 4.02 (br s, 2H), 3.61 (dd, J = 15.7, 3.0 Hz, 1H), 3.37 (br d, J = 12.3 Hz, 2H), 2.88 (td, J = 12.3, 2.1 Hz, 2H), 2.69 (tt, J = 12.0, 3.8 Hz, 1H), 1.93-2.04 (m, 2H), 1.75-1.91 (m, 2H), 1.21 (t, J = 2.2 Hz, 3H) 19F NMR (CHLOROFORM-d, 377 MHz): δ (ppm) -129.39--128.77 (m, 1F), -134.25 (d, J = 9.0 Hz, 1F), -139.98 (br d, J = 154.6 Hz, 1F) 141H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.19-7.28 (m, 4H), 6.72 (dd, J = 9.5, 2.6 Hz, 1H), 5.78 (br s, 1H), 5.59 (br s, 1H), 4.02 (s, 2H), 3.61 (dd, J = 15.8, 2.9 Hz, 1H), 3.38 (br d, J = 12.3 Hz, 2H), 2.88 (td, J = 12.3, 2.1 Hz, 2H), 2.69 (tt, J = 12.0, 3.7 Hz, 1H), 1.93-2.04 (m, 2H), 1.77-1.91 (m, 2H), 1.21 (t, J = 2.2 Hz, 3H) 151H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.64 (d, J = 2.6 Hz, 1H), 7.20-7.28 (m, 4H), 6.72 (dd, J = 9.5, 2.6 Hz, 1H), 5.78 (br s, 1H), 5.57 (br s, 1H), 4.02 (s, 2H), 3.61 (dd, J = 15.7, 3.0 Hz, 1H), 3.37 (br d, J = 12.3 Hz, 2H), 2.88 (td, J = 12.3, 2.3 Hz, 2H), 2.69 (tt, J = 12.0, 3.7 Hz, 1H), 1.92-2.04 (m, 2H), 1.77-1.91 (m, 2H), 1.21 (t, J = 2.2 Hz, 3H) 161H NMR (DMSO-d6, 300 MHz): δ (ppm) 8.52 (m, 1H), 7.50 (m, 2H), 7.32 (m, 2H), 7.15 – 7.26 (m, 3H), 7.00 (m, 1H), 5.43 (s, 2H), 4.44 (m, 1H), 3.83 (m, 1H), 3.53 (m, 3H), 2.96 (s, 3H), 2.58 – 2.85 (m, 5H), 2.45 (m, 2H), 1.91 (m, 4H), 1.15 (s, 3H). 171H NMR (DMSO-d6, 400 MHz): δ (ppm) 7.71 (s, 1H), 7.46 - 7.55 (m, 3H), 7.28 - 7.37 (m, 2H), 7.17 - 7.24 (m, 3H), 6.96 - 7.06 (m, 1H), 5.44 (s, 2H), 3.45 - 3.61 (m, 3H), 2.62 - 2.85 (m, 3H), 1.79 - 2.00 (m, 4H), 1.07 - 1.18 (m, 3H). 181H NMR (DMSO-d6, 400 MHz): δ (ppm) 8.15 (m, 1H), 7.50 (m, 2H), 7.29 – 7.35 (m, 2H), 7.15 – 7.24 (m, 3H), 7.00 (m, 1H), 5.43 (s, 2H), 3.50 – 3.62 (m, 2H), 3.49 (s, 1H), 2.73 – 2.84 (m, 2H), 2.69 (m, 4H), 1.82 – 1.98 (m, 4H), 1.12 (m, 3H) 191H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.63 (d, J = 2.6 Hz, 1H), 7.62 (br d, J = 6.4 Hz, 1H), 7.16-7.25 (m, 4H), 6.72 (dd, J = 9.5, 2.6 Hz, 1H), Compound No 4.49-4.63 (m, 1H), 4.02 (s, 2H), 3.86-3.97 (m, 2H), 3.73-3.84 (m, 1H), 3.45- 3.55 (m, 1H), 3.37 (br d, J = 12.1 Hz, 2H), 2.92-3.01 (m, 2H), 2.81-2.91 (m, 5H), 2.55-2.72 (m, 3H), 2.13 (dd, J = 7.8, 4.3 Hz, 1H), 1.90-2.00 (m, 2H), 1.76-1.89 (m, 2H) 19F NMR (377 MHz, DMSO-d6) δ ppm -139.97 (d, J=154.3 Hz), -135.53 (d, J=10.4 Hz), -127.02 (dd, J=154.2, 15.3 Hz). 201H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.63 (d, J = 2.6 Hz, 1H), 7.16-7.25 (m, 5H), 6.72 (dd, J = 9.5, 2.6 Hz, 1H), 4.02 (s, 2H), 3.87-3.97 (m, 2H), 3.50 (br dd, J = 12.7, 1.4 Hz, 1H), 3.37 (br d, J = 12.3 Hz, 2H), 2.87 (td, J = 12.2, 2.0 Hz, 2H), 2.67 (tt, J = 12.0, 3.7 Hz, 1H), 2.12 (dd, J = 7.9, 4.2 Hz, 1H), 1.92-2.01 (m, 2H), 1.76-1.90 (m, 2H) 19F NMR (CHLOROFORM-d, 377 MHz): δ (ppm) -128.51 (ddd, J = 157.4, 14.8, 4.5 Hz, 1F), -134.19 (d, J = 9.0 Hz, 1F), -141.12 (br d, J = 157.6 Hz, 1F) 221H NMR (METHANOL-d4, 400 MHz): δ (ppm) 7.64 (d, J = 8.0 Hz, 1H), 7.27- 7.37 (m, 4H), 7.07 (d, J = 8.0 Hz, 1H), 4.58-4.69 (m, 1H), 3.84-3.96 (m, 1H), 3.71-3.79 (m, 1H), 3.69 (br d, J = 14.8 Hz, 1H), 3.59 (br d, J = 12.2 Hz, 3H), 2.95 (s, 3H), 2.84-2.94 (m, 4H), 2.70-2.81 (m, 1H), 2.53-2.68 (m, 2H), 1.92- 2.03 (m, 4H) 19F NMR (METHANOL-d4, 376 MHz): δ (ppm) -129.68 (dd, J=157.8, 15.6 Hz), -142.80 (br d, J = 157.8 Hz, 1F) 231H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.79 (d, J = 7.9 Hz, 1H), 7.61 (br d, J = 6.4 Hz, 1H), 7.56 (br d, J = 3.5 Hz, 1H), 7.20-7.25 (m, 4H), 7.01 (d, J = 7.9 Hz, 1H), 5.33 (br d, J = 2.4 Hz, 1H), 4.50-4.63 (m, 1H), 4.15 (s, 2H), 3.87-3.99 (m, 2H), 3.74-3.84 (m, 1H), 3.46-3.60 (m, 3H), 2.82-3.01 (m, 7H), 2.71 (tt, J = 11.9, 3.7 Hz, 1H), 2.55-2.66 (m, 2H), 2.12 (dd, J = 7.7, 4.0 Hz, 1H), 1.94-2.04 (m, 2H), 1.78-1.93 (m, 2H) 19F NMR (CHLOROFORM-d, 377 MHz): δ (ppm) -128.91 (ddd, J = 156.6, 15.1, 4.0 Hz, 1F), -141.14 (br d, J = 156.6 Hz, 1F) 241H NMR (CHLOROFORM-d, 400 MHz): δ (ppm) 7.78 (d, J = 8.1 Hz, 1H), 7.57 (br s, 1H), 7.18-7.25 (m, 5H), 7.01 (d, J = 7.9 Hz, 1H), 5.45 (br d, J = 2.4 Hz, 1H), 4.16 (br s, 2H), 3.86-3.99 (m, 2H), 3.49-3.58 (m, 3H), 2.89 (td, J = 12.1, 1.5 Hz, 2H), 2.70 (tt, J = 12.0, 3.9 Hz, 1H), 2.14 (br d, J = 2.0 Hz, 1H), 1.93-2.04 (m, 2H), 1.78-1.93 (m, 2H) 19F NMR (CHLOROFORM-d, 377 MHz): δ (ppm) -128.50 (ddd, J = 157.4, 14.8, 4.5 Hz, 1F), -141.12 (br d, J = 157.6 Hz, 1F) Pharmacological Analysis Biological Examples In vitro assays include assays that determine cell morphology, protein expression, and / or the cytotoxicity, enzyme inhibitory activity, and / or the subsequent functional consequences of treatment of cells with compounds of the invention. Alternate or additional in vitro assays may be used to quantitate the ability of the inhibitor to bind to protein or nucleic acid molecules within the cell. Inhibitor binding may be measured by radiolabelling the inhibitor prior to binding, isolating the inhibitor / target molecule complex and determining the amount of radiolabel bound. Alternatively, or additionally, inhibitor binding may be determined by running a competition experiment where new inhibitors are incubated with purified proteins or nucleic acids bound to known radioligands. Detailed conditions of exemplary systems for assaying a compound of Formula (I) of the present invention as MALT1 inhibitors are set forth in the Biological Examples below. Such assays are exemplary and not intended to limit the scope of the invention. The skilled practitioner can appreciate that modifications can be made to conventional assays to develop equivalent or other assays that can be employed to comparably assess activity or otherwise characterize compounds and / or compositions as described herein. In Vitro Assays Biological Example 1 MALT1 Biochemical Protease Assay MALT1 protease activity was assessed in an in vitro assay using a tetrapeptide as substrate and full-length MALT1 protein (Strep-MALT1(1-824)-His) purified from baculovirus-infected insect cells. The tetrapeptide LRSR is coupled to AMC (7-amino-4-methylcoumarin) and provides a quenched, fluorescent substrate for the MALT1 protease (SM Biochemicals). Cleavage of AMC from the Arginine residue results in an increase in coumarin fluorescence measured at 460 nm (excitation 355 nm). The final assay buffer consisted of 10 nM FL MALT1 protein, 200 µM Ac-LRSR-AMC, 50 mM Tris pH 7.5, 0.6 M Citrate, 1 mM dithiothreitol (DTT), 1 mM ethylenediaminetetraacetic acid (EDTA), 0.05% bovine serum albumin (BSA) and 1.5% dimethyl sulfoxide (DMSO). Test compounds were spotted at 50 nL in 100% DMSO per well of a black 384-Proxiplate (Perkin Elmer). Test compound concentrations ranged from 30 µM to 0.5 nM using 11 dilution steps (1:3). Background signal was measured from control wells containing assay buffer without enzyme which functions as low control (LC). High control (HC) values were generated using the reaction with enzyme but no compound treatment. Compounds were pre-incubated with MALT1 enzyme for 50 minutes at RT. Substrate was added subsequently, and fluorescence was measured in Labsystems fluoroskan at excitation 355 nm and emission 460 nm to determine time 0. The reaction was subsequently incubated for 4 h at RT and fluorescence was measured. For IC50 calculations, timepoint 0 was subtracted from the 4 h timepoint to correct for any potential autofluorescence of the compounds. The enzyme reaction was linear during the 4 h incubation period. Characterization of the substrate Ac-LRSR-AMC determined the Michaelis constant KM at 200 µM. IC50values were calculated using the following formula (Z prime should be >0.5): LC = Median of the low control values = Low control: Reaction without enzyme HC = Median of the High control values = High Control: Reaction with enzyme %Effect = 100-[((sample-LC) / (HC-LC)) x 100] %Control = (sample / HC) x 100 %Controlmin = ((sample-LC) / (HC-LC)) x 100 A best-fit curve was fitted by a minimum sum of squares method to the plot of %Controlmin vs. compound concentration. From this an IC50 value (inhibitory concentration causing 50 % inhibition) can be obtained. An estimate of the slope of the plot in terms of the Hill coefficient was also obtained. IC50Calculation: yi= LB + UB – LB 1(h*(pCONCi-pIC50)) y = estimated response UB = upper bound LB = lower bound h = Hill slope of curve CONC = concentration Used in “Lexis Dose Response Curve Fitting” Version 1.0. Resultant data are shown in Table 2 (Cpd No. means Compound Number). MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 1 0.0075 35 0.14 2 0.0088 36 >2.10 3 0.0082 37 1.17 4 0.90 38 0.10 5 0.0042 39 0.33 7 0.0027 40 0.57 8 0.57 41 0.23 10 0.0034 42 >2.04 11 3.65 43 0.15 12 0.0057 44 >1.86 13 0.012 45 0.16 14 4.76 46 0.40 15 0.0069 47 0.11 16 0.021 48 >1.96 17 0.0086 49 0.11 18 0.0090 50 0.084 19 0.0040 51 0.1127 20 0.0058 52 0.15 22 3.59 53 0.20 23 0.014 54 0.073 24 0.0069 55 >5.02 25 >1.27 56 0.51 26 0.058 57 0.92 27 >2.22 58 0.51 28 >2.75 59 >0.83 29 >0.61 60 0.30 30 0.20 61 0.059 31 0.25 62 >1.23 32 0.24 63 0.05 33 1.24 64 0.60 34 0.056 65 0.056 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 66 0.45 100 0.30 67 1.62 101 0.42 68 >1.97 102 0.066 69 0.16 103 0.62 70 0.26 104 0.10 71 0.20 105 >4.26 72 0.049 106 >1.30 73 >0.80 107 0.10 74 0.11 108 0.37 75 0.66 109 0.81 76 0.63 110 >1.60 77 0.43 111 0.40 78 0.27 112 0.98 79 0.081 113 >0.82 80 0.081 114 1.31 81 0.11 115 0.16 82 0.15 116 0.045 83 0.062 117 0.28 84 0.061 118 0.068 85 1.41 119 0.052 86 0.26 120 0.086 87 0.62 121 0.12 88 0.46 122 2.20 89 0.17 123 1.54 90 0.20 124 0.070 91 0.063 125 0.55 92 0.45 126 0.13 93 0.18 127 0.26 94 0.23 128 0.31 95 1.56 129 >1.79 96 >1.48 130 0.20 97 >1.69 131 0.089 98 0.58 132 0.088 99 0.085 133 >1.11 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 134 0.083 168 0.096 135 0.42 169 1.44 136 0.17 170 0.086 137 0.063 171 0.28 138 0.36 172 0.046 139 0.057 173 0.088 140 0.35 174 0.031 141 0.12 175 0.11 142 0.56 176 >1.63 143 0.62 177 0.28 144 0.99 178 0.099 145 0.12 179 0.72 146 0.035 180 1.16 147 0.31 181 0.051 148 >1.98 182 0.14 149 0.036 183 0.19 150 0.088 184 0.047 151 0.42 185 0.050 152 0.18 186 0.19 153 0.49 187 0.57 154 0.84 188 0.11 155 0.096 189 0.76 156 0.15 190 0.077 157 0.11 191 0.57 158 0.90 192 >1.047 159 0.12 193 1.22 160 0.066 194 0.32 161 >0.70 195 >1.44 162 0.47 196 0.22 163 0.17 197 0.47 164 2.18 198 2.44 165 0.87 199 0.31 166 >2.29 200 0.59 167 0.14 201 >1.21 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 202 >1.86 237 0.017 203 0.43 238 0.022 204 >0.63 239 0.018 205 >1.89 240 0.016 206 1.39 241 0.027 207 0.12 242 0.016 208 0.83 243 0.030 209 0.67 244 0.029 210 0.13 245 0.046 211 0.23 246 0.030 212 2.23 247 0.063 213 >1.20 248 2.13 214 0.16 249 0.013 215 0.66 250 0.061 216 1.02 251 0.028 217 0.21 252 0.045 218 1.25 253 0.027 219 1.13 254 0.018 220 0.44 255 0.037 221 0.083 256 0.029 222 2.05 257 0.020 223 0.016 258 0.046 224 0.020 259 0.036 225 0.015 260 0.041 226 0.023 261 0.018 227 0.014 262 0.027 229 0.044 263 0.023 230 0.016 264 0.090 231 0.020 265 0.022 232 0.033 266 0.11 233 0.036 267 0.032 234 2.15 268 0.024 235 0.036 269 0.047 236 0.014 270 0.018 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 271 0.40 306 0.014 272 0.023 307 0.013 273 0.051 308 0.032 274 0.026 309 0.013 275 0.064 310 0.020 276 0.026 311 0.064 277 0.029 312 0.011 278 0.043 313 0.020 279 0.056 314 0.031 280 0.36 315 0.011 281 0.015 316 0.0088 282 0.051 317 0.035 283 0.041 318 0.0089 284 0.022 319 0.020 285 0.024 320 0.023 286 0.019 321 0.053 287 0.023 322 0.010 288 0.033 323 0.011 289 0.058 324 0.026 290 0.016 325 0.019 291 0.014 326 0.018 292 0.013 327 0.021 293 0.012 328 0.015 295 0.019 329 0.023 296 0.0078 330 0.0066 297 0.013 331 0.056 298 0.012 332 0.026 299 0.014 333 0.058 300 0.012 334 0.021 301 0.10 335 0.021 302 0.015 336 0.029 303 0.013 337 0.014 304 0.027 338 0.011 305 0.012 339 0.016 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 340 0.011 374 0.011 341 0.018 375 0.015 342 0.019 376 0.031 343 0.031 377 0.016 344 0.020 378 0.013 345 0.015 379 0.017 346 0.018 380 0.024 347 0.014 381 0.014 348 0.026 382 0.028 349 0.048 383 0.0088 350 0.029 384 0.036 351 0.037 385 0.022 352 0.0093 386 0.044 353 0.017 387 0.0079 354 0.011 388 0.050 355 0.019 389 0.016 356 0.024 390 0.0055 357 0.030 391 0.047 358 0.019 392 0.020 359 0.022 393 0.024 360 0.025 394 0.037 361 0.025 395 0.014 362 0.020 396 0.033 363 0.037 397 0.017 364 0.027 398 0.031 365 0.041 399 0.041 366 0.041 400 0.051 367 0.022 401 0.031 368 0.021 402 0.019 369 0.047 403 0.015 370 0.015 404 0.012 371 0.011 405 0.026 372 0.018 406 0.010 373 0.044 407 0.038 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 408 0.015 442 0.025 409 0.011 443 0.020 410 0.025 444 0.034 411 0.012 445 0.021 412 0.013 446 0.039 413 0.015 447 0.014 414 0.039 448 0.0088 415 0.044 449 0.025 416 0.026 450 0.010 417 0.047 451 0.019 418 0.022 452 0.0099 419 0.030 453 0.040 420 0.020 454 0.021 421 0.020 455 0.016 422 0.016 456 0.016 423 0.016 457 0.018 424 0.020 458 0.023 425 0.040 459 0.028 426 0.014 460 0.012 427 0.0098 461 0.0097 428 0.020 462 0.020 429 0.027 463 0.029 430 0.021 464 0.014 431 0.021 465 0.025 432 0.017 466 0.021 433 0.023 467 0.027 434 0.011 468 0.017 435 0.022 469 0.048 436 0.011 470 0.018 437 0.056 471 0.011 438 0.023 472 0.027 439 0.043 473 0.040 440 0.017 474 0.032 441 0.017 475 0.021 MALT1_Biochemical MALT1_Biochemical Cpd Cpd activity (Ac-LRSR- activity (Ac-LRSR- No. No. AMC) IC50 (^M) AMC) IC50 (^M) 476 0.010 482 0.0092 477 0.012 483 0.028 478 0.016 484 0.023 479 0.025 485 0.0064 480 0.0081 486 0.017 481 0.031 Biological Example 2 GloSensor reporter MALT1-mediated cleavage In Jurkat Cells MALT1 GloSensorTMis a split luciferase reporter, which utilizes a genetically modified form of firefly luciferase (CP UltraGlo) split into 2 distinct domains by insertion of a RelB MALT1 cleavage site sequence PRLVSRGA. MALT1-induced cleavage allows for a conformational change that reestablishes a functional luciferase protein resulting in luminescence, and hence luciferase activity would be a surrogate of endogenous MALT1 protease activity. Jurkat MALT1 GloSensorTMwere generated by electroporation and selected and maintained in the presence of 0.5 mg / mL Geneticin. MALT1 protease is basally inactive in Jurkat cells and can be activated by treatment with PMA / Ionomycin. Small molecule MALT1 inhibitors added prior to PMA / Ionomycin addition prevent MALT1 protease activation and, therefore, the cleavage of the MALT1 GloSensor split luciferase reporter in a dose-dependent manner. Jurkat MALT1 GloSensorTMcells were maintained in complete RPMI 1640 media containing 10% fetal bovine serum, 10mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 100 units / mL of penicillin, 100 µg / mL of streptomycin and 0.5 mg / mL Geneticin. Prior to the assay, compounds were made 2.5-fold serial dilutions in DMSO. 100 nL of of test compounds were spotted per well of 384-well plates (Perkin Elmer, catalogue number 6007688). Jurkat cells were harvested by centrifuge at 1200 RPM for 5 min and suspended in fresh complete RPMI 1640 media with 2% GloSensor™ cAMP Reagent and preincubated for 45-60 minutes at 37 °C in a 5% CO2 incubator. A volume of 50 uL of preincubated Jurkat MALT1 GloSensorTMcells (1 x 105cells) were seeded in each well of 384-well plate. Next, a volume 2 µL of diluted PMA / Ionomycin (2.5 ^g / mL / 25 µM respectively, Sigma, catalogue number P1585 and 407953) in DMSO were added to each well. After incubation at 37 °C in 5% CO2incubator for 4 h, luminescence was measured on the Envision (Perkin Elmer) at 37 °C. IC50values were calculated using SmartFit in GeneData Screener^: x = concentration y = activity S0= activity at bottom plateau of curve Sinf= activity at top plateau of curve S50 = inflection point, halfway between S0 and Sinf h = Hill slope of curve Resultant data are shown in Table 3. Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 1 0.020 23 0.019 42 0.35 2 0.0030 24 0.030 43 0.052 3 0.0073 25 >0.47 44 0.66 4 0.37 26 0.041 45 0.095 5 0.0042 27 >0.44 46 0.33 7 0.0027 28 >0.56 47 0.038 8 0.35 29 >0.68 48 >0.55 10 0.0033 30 0.096 49 0.067 11 0.43 31 0.073 50 0.069 12 0.0043 32 0.064 51 0.15 13 0.0077 33 0.32 52 0.043 14 >0.29 34 0.072 53 0.12 15 0.0041 35 0.088 54 0.052 16 0.014 36 >0.97 55 >1.08 17 0.017 37 0.44 56 0.26 18 0.027 38 0.13 57 0.49 19 0.0023 39 0.086 58 0.25 20 0.0053 40 0.20 59 >0.39 22 >2.00 41 0.095 60 0.092 Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 61 0.030 95 0.41 130 0.11 62 >0.87 96 >0.59 131 0.029 63 0.030 97 >0.76 132 0.027 64 >0.39 98 0.15 134 0.057 65 0.051 99 0.036 135 0.18 66 0.18 100 0.16 136 0.13 67 0.40 101 0.27 137 0.030 68 >1.18 102 0.032 138 0.27 69 0.11 103 >0.61 139 0.049 70 0.098 104 0.043 140 0.15 71 0.17 105 >0.43 141 0.057 72 0.087 107 0.046 142 0.14 73 0.42 108 0.11 143 0.34 74 0.055 109 0.14 145 0.043 75 0.16 110 0.21 146 0.035 76 0.48 111 0.097 147 0.14 77 0.22 112 0.30 149 0.016 78 0.13 113 >0.27 150 0.077 79 0.024 115 0.088 151 0.10 80 0.031 116 0.027 152 0.087 81 0.025 117 0.12 153 0.21 82 0.045 118 0.022 154 0.32 83 0.090 119 0.051 155 0.031 84 0.027 120 0.049 156 0.12 85 >0.34 121 0.055 157 0.058 86 0.14 122 >0.64 158 0.42 88 0.12 123 0.85 159 0.12 89 0.19 124 0.053 160 0.032 90 0.026 125 0.23 161 0.47 91 0.048 126 0.072 162 0.21 92 0.16 127 0.11 163 0.063 93 0.078 128 0.15 164 0.50 94 0.10 129 >0.73 165 >0.50 Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 166 >0.52 199 0.057 233 0.017 167 0.064 200 0.094 234 0.025 168 0.044 201 0.50 235 0.017 169 >0.53 202 >0.50 236 0.011 170 0.036 203 0.40 237 0.020 171 >0.47 204 0.60 238 0.024 172 0.10 205 >0.026 239 0.015 173 0.20 206 0.21 240 0.018 174 0.019 207 0.064 241 0.016 175 0.036 208 0.30 242 0.014 176 >0.48 209 >0.39 243 0.019 177 0.15 210 0.047 244 0.016 178 0.047 211 0.051 245 0.017 179 0.29 212 >0.61 246 0.032 180 >0.52 213 >0.41 247 0.019 181 0.040 214 0.071 248 0.026 182 0.089 215 0.14 249 0.011 183 >0.38 216 0.17 250 0.035 184 0.041 217 0.11 251 0.021 185 0.020 218 0.085 252 0.028 186 0.086 219 0.27 253 0.012 187 0.13 220 0.069 254 0.013 188 0.032 221 0.043 255 0.019 189 0.11 222 0.96 256 0.020 190 0.029 223 0.013 257 0.010 191 0.13 224 0.017 258 0.034 192 0.47 225 0.064 259 0.038 193 0.40 226 0.014 260 0.015 194 0.034 227 0.013 261 0.011 195 0.20 229 0.033 262 0.016 196 0.083 230 0.022 263 0.024 197 0.085 231 0.013 264 0.022 198 0.74 232 0.027 265 0.021 Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 266 0.13 300 0.018 333 0.042 267 0.017 301 0.056 334 0.16 268 0.016 302 0.011 335 0.017 269 0.012 303 0.013 336 0.024 270 0.019 304 0.038 337 0.012 271 0.099 305 0.012 338 0.027 272 0.013 306 0.022 339 0.017 273 0.034 307 0.012 340 0.010 274 0.017 308 0.033 341 0.027 275 0.047 309 0.014 342 0.015 276 0.020 310 0.011 343 0.017 277 0.018 311 0.040 344 0.047 278 0.031 312 0.013 345 0.027 279 0.037 313 0.020 346 0.020 280 0.013 314 0.032 347 0.024 281 0.009 315 0.016 348 0.036 282 0.064 316 0.0094 349 0.016 283 0.020 317 0.044 350 0.024 284 0.024 318 0.010 351 0.034 285 0.012 319 0.021 352 0.0091 286 0.021 320 0.026 353 0.028 287 0.018 321 0.045 354 0.019 288 0.028 322 0.018 355 0.030 289 0.047 323 0.010 356 0.026 290 0.015 324 0.041 357 0.020 291 0.012 325 0.016 358 0.031 292 0.0081 326 0.087 359 0.023 293 0.016 327 0.033 360 0.034 295 0.033 328 0.031 361 0.040 296 0.011 329 0.012 362 0.025 297 0.012 330 0.010 363 0.073 298 0.012 331 0.076 364 0.019 299 0.023 332 0.016 365 0.024 Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 366 0.035 399 >0.059 432 0.011 367 0.048 400 0.031 433 0.041 368 0.056 401 0.038 434 0.017 369 0.060 402 0.036 435 0.034 370 0.018 403 0.093 436 0.021 371 0.021 404 0.021 437 0.069 372 0.040 405 0.045 438 0.042 373 0.077 406 0.025 439 0.036 374 0.016 407 0.046 440 0.041 375 0.020 408 0.014 441 0.022 376 0.022 409 0.030 442 0.022 377 0.022 410 0.037 443 0.021 378 0.022 411 0.010 444 0.027 379 0.063 412 0.021 445 0.028 380 0.032 413 0.020 446 0.032 381 0.024 414 0.043 447 0.086 382 0.046 415 0.052 448 0.010 383 0.012 416 0.025 449 0.068 384 0.038 417 0.095 450 0.012 385 0.025 418 0.044 451 0.031 386 0.038 419 0.068 452 0.024 387 0.009 420 0.017 453 0.023 388 0.053 421 0.032 454 0.029 389 0.023 422 0.019 455 0.018 390 0.0038 423 0.029 456 0.038 391 0.30 424 0.101 457 0.028 392 0.020 425 0.036 458 0.11 393 0.053 426 0.021 459 0.048 394 0.038 427 0.019 460 0.023 395 0.038 428 0.019 461 0.011 396 0.043 429 0.034 462 0.040 397 0.026 430 0.035 463 0.045 398 0.11 431 0.026 464 0.012 Jurkat Jurkat Jurkat Cpd MALT1 Cpd MALT1 Cpd MALT1 No. GloSensor^ No. GloSensor^ No. GloSensor^ IC50 (^M) IC50 (^M) IC50 (^M) 465 0.016 473 0.038 481 0.065 466 0.023 474 0.025 482 0.011 467 0.032 475 0.017 483 0.051 468 0.022 476 0.031 484 0.052 469 0.064 477 0.022 485 0.0080 470 0.022 478 0.016 486 0.030 471 0.019 479 0.054 472 0.026 480 0.010 Biological Example 3 Human IL-6 / IL-10 Mesoscale Assay OCI-Ly3 cells were propagated in RPMI-1640 (Sigma Aldrich) supplemented with 10% fetal bovine serum (HyClone), 2 mM L-glutamine (Sigma Aldrich) and 1% PenStrep (Sigma Aldrich). Cell passage number should not exceed 30. Cells should be kept between 0.5 – 1.5 million cells per mL during culturing. For the Mesoscale assay, 100,000 OCI-Ly3 cells were seeded per well into black-colored 96- well plates with clear bottom (Corning®#3904) and test compounds were added in 9 dilution steps (1:2) ranging from 15 µM to 58.6 nM (final DMSO concentration 0.3%). DMSO control wells were used to determine the maximum signal (High Control (HC)). Treatment with reference compounds at an appropriate dose served as positive control for MALT1 inhibition and was used to determine the maximum inhibition (Low Control (LC)). Compounds and cells were incubated for 24 h at 37 °C and 5% CO2 (assay volume is 150 µL). After 24 h of incubation 50 µL of the supernatant was transferred to an MSD plate (V-Plex Proinflammation Panel 1 (human) kit, Mesoscale (MSD)) and incubated for 2 h with vigorous shaking (600 rpm) at room temperature. Following incubation, plates were washed 3x with phosphate-buffered saline (PBS) + 0.05% Tween-20 and 25 µL detection antibody solution (IL-6 & IL-10 antibodies in diluent 3 (MSD)) was added per well followed by 2 h of incubation with vigorous shaking (600 rpm) at room temperature. After 3x washes with PBS + 0.05% Tween-20, plates were incubated with 150 µL 2x Read Buffer T and read on SECTOR imager. Resultant data are shown in Table 4. Human IL6 Mesoscale Human IL10 Mesoscale assay Cpd No. assay (OCI-Ly3) (OCI-Ly3) IC50 (µM) IC50 (µM) 1 0.21 0.16 2 0.028 0.0068 3 0.040 0.020 5 0.013 0.0065 7 0.013 0.0072 10 0.016 0.0049 12 0.012 0.0051 15 0.028 0.013 16 0.048 0.028 17 0.16 0.058 18 0.17 0.12 19 0.011 0.0058 20 0.019 0.011 23 0.10 0.058 26 0.26 0.11 47 0.65 0.28 50 0.32 0.13 61 0.13 0.072 63 0.16 0.11 65 0.87 0.49 74 0.44 0.19 79 0.26 0.085 81 0.045 0.035 84 0.51 0.18 90 0.25 0.34 102 - 0.10 116 0.17 0.068 118 - 0.098 119 0.36 0.091 124 0.25 0.13 132 0.28 0.21 137 0.35 0.15 146 0.32 0.093 149 0.17 0.040 Human IL6 Mesoscale Human IL10 Mesoscale assay Cpd No. assay (OCI-Ly3) (OCI-Ly3) IC50 (µM) IC50 (µM) 155 0.46 0.15 160 0.74 0.30 170 0.22 0.12 174 0.098 0.054 184 0.29 0.13 185 0.12 0.062 190 0.18 0.098 224 0.074 0.033 225 0.14 0.023 226 0.034 0.015 227 0.054 0.012 230 0.076 0.021 237 0.12 0.029 239 0.049 0.019 240 0.095 0.018 241 0.11 0.026 242 0.16 0.030 249 0.035 0.012 257 0.049 0.013 263 0.15 0.028 268 0.12 0.044 270 0.28 0.043 281 0.047 0.016 284 0.12 0.030 285 0.058 0.014 292 0.020 0.008 293 0.051 0.025 295 0.059 0.021 296 0.035 0.013 297 0.091 0.047 303 0.045 0.015 306 0.062 0.025 309 0.062 0.031 312 0.050 0.026 Human IL6 Mesoscale Human IL10 Mesoscale assay Cpd No. assay (OCI-Ly3) (OCI-Ly3) IC50 (µM) IC50 (µM) 315 0.055 0.020 352 0.068 0.024 378 >0.047 0.050 390 0.056 0.020 485 0.12 0.034 Biological Example 4 Proliferation Assays OCI-Ly3 cells were propagated in RPMI-1640 with Glutamax (ThermoFisher) supplemented with 10% heat inactivated fetal bovine serum (ThermoFisher). Cells should be kept between 0.2 – 1.5 million cells per mL and passed every 3-4 days during culturing. OCI- Ly7 cells were propagated in IMDM (ThermoFisher) supplemented with 10% fetal bovine serum (HyClone), 2 mM L-glutamine (Sigma Aldrich) and 50 µg / mL Gentamycin. Cells should be kept between 0.15 – 3 million cells per mL and passed every 3-4 days during culturing. Cell passage numbers should not exceed 20. To assess anti-proliferative effects, 450 nL of test compounds were spotted per well of U-bottom 96-well plates (Corning®, #3975). 500 OCI-Ly3 or OCI-Ly7 cells were seeded in 150 µL media per well and incubated for 8 days at 37 °C and 5% CO2. Cell plating numbers were chosen based on growth curves to ensure linear cell growth. After 8 days of incubation, 100 µL of the plated cells were resuspended up and down by pipette and transferred to a flat bottom black plate (Corning®, #3904). 50 µL CellTiterGLO reagent (Promega) were added to each well and luminescence was measured on Envision (Perkin Elmer) after 10 minutes shaking at 300 rpm followed by 10 minutes of incubation at room temperature in the dark. IC50 values were calculated using SmartFit in GeneData Screener^: x = concentration y = activity S0 = activity at bottom plateau of curve Sinf = activity at top plateau of curve S50 = inflection point, halfway between S0 and Sinf h = Hill slope of curve Resultant data are shown in Table 5: Anti-proliferation: OCI-Ly3 Anti-proliferation: OCI-Ly7 Cpd No. IC50 (^M) IC50 ^^M) 1 0.70 - 2 0.23 - 3 0.25 - 4>13.435 0.24 12.1 7 0.12 - 10 0.12 - 12 0.065 - 15 0.16 >6.47 16 0.19 - 17 0.60 - 18 0.62 - 19 0.06 - 20 0.15 - 23 0.34 - 24 0.49 - 26 0.60 - 34 0.027 - 47 0.55 - 50 0.65 - 61 0.028 4.34 63 0.33 - 65 0.15 0.41 74 2.25 - 79 0.079 1.32 81 0.29 - 84 0.93 - 90 0.12 1.12 102 0.48 - 116 0.14 4.55 118 0.41 - 119 0.29 - 124 0.64 - 132 0.22 - 137 0.59 - 146 0.035 0.51 149 0.33 7.51 155 1.76 - 160 0.79 - 170 0.27 1.50 Cpd No. Anti-proliferation: OCI-Ly3 Anti-proliferation: OCI-Ly7 IC50 (^M) IC50 ^^M) 174 0.43 - 184 0.64 - 185 0.62 - 190 0.38 - 223 1.04 - 224 0.87 - 225 0.29 - 226 0.31 - 227 0.34 - 230 1.28 - 231 0.83 - 233 0.33 - 236 1.00 - 237 0.55 - 238 0.26 - 239 0.62 - 240 0.77 - 241 0.29 - 242 0.59 - 243 1.22 - 244 0.44 - 249 0.32 - 253 0.55 - 254 0.39 - 257 0.46 - 260 0.32 - 261 0.25 - 263 1.92 - 267 0.85 - 268 0.32 - 270 0.52 - 272 0.38 - 274 0.55 - 276 0.22 - 279 1.20 - 281 0.33 - 283 0.27 - 284 0.51 - 285 0.95 - 286 0.59 - 287 0.75 - 288 0.67 - 290 0.28 - 291 0.21 - 292 0.14 - 293 0.35 - Cpd No. Anti-proliferation: OCI-Ly3 Anti-proliferation: OCI-Ly7 IC50 (^M) IC50 ^^M) 295 0.50 - 296 0.40 - 297 0.16 - 298 0.34 - 299 0.60 - 300 0.63 - 302 0.21 - 303 0.64 - 305 0.22 - 306 0.53 - 307 0.53 - 308 1.31 - 309 0.45 - 310 0.29 - 312 0.30 - 313 0.59 - 315 0.36 - 316 0.23 - 317 0.55 - 318 0.20 - 319 1.59 - 320 0.31 - 323 0.21 - 325 0.54 - 329 0.49 - 330 0.39 - 332 0.91 - 337 0.39 - 340 0.31 - 342 0.57 - 349 0.60 - 352 0.20 - 374 0.50 - 377 1.09 - 378 0.21 - 381 0.27 - 383 0.51 - 387 0.24 - 389 0.22 - 390 0.13 - 408 0.46 - 411 0.44 - 412 0.71 - 418 0.23 - 420 0.26 - Cpd No. Anti-proliferation: OCI-Ly3 Anti-proliferation: OCI-Ly7 IC50 (^M) IC50 ^^M) 432 0.45 - 440 0.38 - 448 0.42 - 450 0.40 - 457 0.21 - 461 0.47 - 464 0.32 - 465 0.49 - 478 0.65 - 480 0.28 - 482 0.43 - 485 0.34 -

Claims

1. CLAIMS 1. A compound of Formula (I)or a tautomer or a stereoisomeric form thereof, wherein R1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl;R2represents halo; n is 0, 1 or 2; R3arepresents hydrogen or C1-4alkyl; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted withone, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, -CF3, Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, -C(=O)-Het3b, and ; ortogether to form together with the nitrogen atom to which they are attached Het2; Cy1represents C3-6cycloalkyl; or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of halo, -OH, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; Het1represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het1represents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7-S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b,-C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het2represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het2represents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, cyano, -OH, -OR7, Het6, -S(=O)2-R7, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, -S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, Het4and -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, Het4, or -C(=O)-C3-6cycloalkyl; Het3arepresents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het3arepresents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b,-C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het3brepresents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het3brepresents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, C1-4alkyl, -OR7, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -NR4aR4b, -S(=O)(=NH)-C1-4alkyl, -N=S(=O)-(C1-4alkyl)2, -NH-(C=O)-C1-4alkyl, -NH-(C=O)-C3-6cycloalkyl, -C(=O)-NR4aR4b, and -NH-S(=O)2-R7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-NR4aR4b, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three substituents each independently selected from the group consisting of -OH and halo; Het4represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het5represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het6represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); R4aand R4beach independently represent hydrogen, C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl-O-C1-4alkyl; R4cand R4deach independently represent C1-4alkyl or -O-C1-4alkyl; R5represents hydrogen or halo;R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl or C3-6cycloalkyl, each optionally substituted with one, two or three halo substituents; p1 and p2 each independently are 1, 2 or 3; or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; adamantyl; C6-10carbobicyclic; Het1; C3-6cycloalkyl substituted with one, two, three or four substituents each independently selected from the group consisting of oxo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -NH-(C=O)-R7, -S(=O)(=NH)-NR4aR4b, -P(=O)-R4cR4d, - NH-S(=O)2-R7, Het3a, Het3b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, halo, - S(=O)(=NH)-C1-4alkyl, -C(=O)-NR4aR4b, -S(=O)2-NR4aR4b, and -S(=O)2-C1-4alkyl; C6-10carbobicyclic substituted with one, two, three or four substituents each independently selected from the group consisting of -OR7, -S(=O)2-R7, and -S(=O)2-NR4aR4b; or C1-4alkyl substituted with one, two, three or four substituents each independently selected from the group consisting of cyano, halo, -OH, -OR7, -S(=O)2-R7, -S(=O)2-NR4aR4b, - NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)-NR4aR4b, -P(=O)-R4cR4d, -O- C1-4alkyl-C(=O)-NR4aR4b, -S(=O)(=NH)-C1-4alkyl-O-R7, -NH-S(=O)2-R7, - Cy1, Het3a, Het3b, -O-Het3b, -C(=O)-Het3a, and ; ortogether to form together with the nitrogen atom to which they are attached Het2; Cy1represents C3-6cycloalkyl; or C3-6cycloalkyl substituted with one, two or three substituents each independently selected from the group consisting of -S(=O)2-C1-4alkyl, and -S(=O)2- NR4aR4b; Het1represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het1represents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N;wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, -OH, -OR7-S(=O)2-R7, -C(=O)-NR4aR4b, -S(=O)(=NH)-NR4aR4b, - P(=O)-R4cR4d, -O-C1-4alkyl-C(=O)-NR4aR4b, and C1-4alkyl optionally substituted with one, two or three substituents each independently selected from the group consisting of -OH, and -C(=O)-NR4aR4b; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, -C(=O)-C3-6cycloalkyl, or C1-4alkyl substituted with one, two or three -OH; Het2represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het2represents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of Het6, -S(=O)2-NR4aR4b, -S(=O)(=NH)-R7, -N=S(=O)-(C1-4alkyl)2, -C(=O)- NR4aR4b, and C1-4alkyl optionally substituted with one, two or three -S(=O)2-C1-4alkyl; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with Het4; Het3arepresents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; or Het3arepresents a bicyclic N-linked 6- to 11-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, and -OH; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, -C(=O)-C1-4alkyl, -S(=O)2-C1-4alkyl, -S(=O)2-NR4aR4b, or -C(=O)-C3-6cycloalkyl;Het3brepresents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; or Het3brepresents a bicyclic C-linked 6- to 11-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the carbon atoms in said heterocyclyl might be substituted with in total one, two or three substituents each independently selected from the group consisting of oxo, halo, -OH, C1-4alkyl, and -OR7; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); wherein one or more of the N-atoms in said heterocyclyl might be substituted with C1-4alkyl, Het5, or -S(=O)2-C1-4alkyl; Het4represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het5represents a monocyclic C-linked 4- to 7-membered fully saturated heterocyclyl containing one, two or three heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); Het6represents a monocyclic N-linked 4- to 7-membered fully saturated heterocyclyl containing one N-atom and optionally one or two heteroatoms each independently selected from O, S, and N; wherein one or more of the S-atoms in said heterocyclyl might be substituted to form S(=O), S(=O)2, or S(=O)(=NH); R4aand R4beach independently represent hydrogen, C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl-O- C1-4alkyl; p1 and p2 are 2.

3. The compound according to claim 1 or 2 wherein R1arepresents -NH2; R1brepresents halo or -C(=O)-NH2; represents phenyl;n is 0; R3arepresents hydrogen; R3brepresents hydrogen; C1-4alkyl; C3-6cycloalkyl; or C3-6cycloalkyl substituted with one -S(=O)2-R7; R5represents hydrogen; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; R7represents C1-4alkyl.

4. The compound according to any one of the preceding claims wherein n is 0.

5. The compound according to any one of the preceding claims wherein represents phenyl, and R6represents methyl.

6. The compound according to any one of the preceding claims wherein represents phenyl, and R6represents -CH2OH.

7. The compound according to any one of the preceding claims wherein R3arepresents hydrogen.

8. A pharmaceutical composition comprising a compound as claimed in any one of claims 1 to 7 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.

9. A compound as claimed in any one of claims 1 to 7 or a pharmaceutical composition as claimed in claim 8 for use as a medicament.

10. A compound as claimed in any one of claims 1 to 7 or a pharmaceutical compositionas claimed in claim 8 for use in the treatment or prevention of cancer.

11. A compound as claimed in any one of claims 1 to 7 or a pharmaceutical composition as claimed in claim 18 for use for use in the treatment or prevention of a disease, syndrome, condition, or disorder, wherein said disease, syndrome, condition, or disorder is affected by the inhibition of MALT1.

12. A method of treating a disease, syndrome, condition, or disorder, wherein said disease, syndrome, condition, or disorder is affected by the inhibition of MALT1, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as claimed in any one of claims 1 to 7 or a pharmaceutical composition as claimed in claim 8.

13. A Compound of Formula (A) orR1arepresents -NH2, methyl or halo; R1brepresents hydrogen, halo or -C(=O)-NH2; represents phenyl or pyridyl;R2represents halo; n is 0, 1 or 2; R5represents hydrogen or halo; R6represents C1-4alkyl; or C1-4alkyl substituted with one -OH; or a pharmaceutically acceptable salt thereof.

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