Novel hydrogen sulfide releasing compounds

Abstract

The invention relates to novel hydrogen sulfide releasing compounds. Preferably the invention relates to compounds having the general formula I' (I'), as well as it pharmaceutically acceptable salts and solvates and pharmaceutical compositions comprising the compounds of the invention.

Description

[0001]Novel hydrogen sulfide releasing compounds FIELD OF THE INVENTION The invention relates to novel hydrogen sulfidea resling compounds. Said compounds are useful in the treatment of diseases wherein increasing serumo hgyednr sulfide is beneficial, in particular for usne i the treatment of antineutrophil cytoplasmic autiobaondty (ANCA)-associated vasculitides (AAV), including MPO granulomatosis with polyangiitis (Weenger’s granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA; formerlyll cead Churg–Strauss syndrome), microscopic polyangiitis (MPA) and renal limited vasculitis (kidney-limite mdicroscopic polyangiitis or kidney- limited necrotizing crescentic glomerulonephri NtisC,GN). BACKGROUND ART The role of hydrogen sulfide is highly controvelrs inia autoimmune inflammatory diseases. Among the widespread biological functions of hydrogen sul,fide iverse protective functions in inflammatory processes were proposed to this small endogenoudsiat more [Whiteman, M. and P.G. Winyard, Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising. Expert Rev Clin Pharmacol, 20114.(1): p. 13-32].. Interactions with heme proteins may represenety a m kechanism in these processe [sPalinkas, Z., et al. I,nteractions of hydrogen sulfide with myeloperoxidase. Br JPharmacol, 20151.72(6): p. 1516-32].However, H2S may easily turn out to be toxic, also depending c o nditions and concentration.2S Htoxicity is caused by the reaction of2S H with trivalent iron in oxidized cytochrome oxidea,s which inhibits cellular respiration and leads to cellu hlayrpoxia. [Gáll Tamás et al O. verview on hydrogen sulfide-mediated suppression of vascular calcification and hemoglobin / heme-mediated vascular damage in atherosclerosis, Redox Biology, Volume 57, 2022, 102504, ISSN 221331-72.] Thus, this Janus-faced feature o2fS H places a huge burden on the investigator toe ar artiv a correct conclusion, whether 2 HS is beneficial or not in a specific disease anmdp cloex experimentation is required the outcome or result of which could neot p bredicted. O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidxiome) (abbreviated as BGP-15) is a compound covered by an early patent US4187220 and was perodp aoss a new compound useful in the treatment of diabetic angiopathy, a complication of diabetesul rteinsg in the damage of blood vessels below. US6306878 refers to a method for the protection the of mitochondrial genome and / or mitochondrion from damage leading to myopathies and neurodegteivneer daiseases which comprises administering an effective non-toxic dose to a patient susceptibole su tch damage of an amidoximic acid derivative including BGP-15. US6458371 refers to a composition comprising 0.%1-3 o0f a hydroximic acid derivative including BGP-15 as the active ingredient and a carrier thant t ishe i form of a cream, lotion, foam or spray.US6884424 refers to a method for preventing ac ktienricatosis by applying a hydroximic acid derivative including BGP-15 to the affected skin surface. US6451851 refers to a method of treating a pat sieunfftering from a viral infection comprising administering to the patient a pharmaceuticallyec etfivfe amount of a known antivirally active agent together with a hydroximic acid derivative inclugdi BnGP-15. Several patents relate to antitumor activity of B-1G5P in combination with other antitumor agents (see e.g. US6,440,998, US6,656,955, US6,720,337, and,8 U3S86,469. Protective function of BGP-15 in ischemia reperofuns iinjury was first published in the same year., i.e 2000. [Szabados, E et al. Peter Literati-Nagy, Beatrixka Fsa,r Balazs Sumegi, BGP-15, a nicotinicamidoxime derivate protecting heart from ischemepiae r fusion injury through modulation of poly(ADP-ribose) polymerase, Biochemical Pharmacology, Voelu 5m9, Issue 8, 2000, Pages 937-]945,PCT Patent Application WO 00 / 07580 disclosed exmpe nrital data for the antidiabetic effect of BGP-15 in the treatment of type 1 diabetes mellitus a,u atnoimmune disease. Since then, BGP-15 has proved to be a PARP inhr,ib cihtoaperone co-inducer, ROS production reducer, which is able to remodel the organization of chtoelreosl-rich membrane domains. [Pető Á, Kósa D, Fehér P, Ujhelyi Z, Sinka D, Vecsern Myé,s Szilvássy Z, Juhász B, Csanádi Z, Vígh L, et al. Pharmacological Overview of the BGP-15em Chical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome. Molecules. 2020; 25(2):429. https: / / doi.org / 10.3390 / molecules25020]429 Thus its effect is multifold, as illustrated by t fhoellowing publications. It was shown that in diabetes animal models thaPt- B1G5 increases insulin sensitivity[Literáti-Nagy B et al., Metabolic Syndrome and Rte dla Disorders 2014 Vol. 12, No. 2 It has a multifold protective function in severaoln cditions. It improves survival and renal functi aon dprotects cardiac function. [Wachal Z, Szilágyi A, Takács B, Szabó AM, Priksz B Do,mbicz M, Szilvássy J, Juhász B, Szilvássy Z and Varga B (2021) Improved Survival and Retinanl c Ftuion of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment. Front.har Pmacol. 12:650207. doi: 10.3389 / fphar.2021.6502]07 [Kozma M, Bombicz M, Varga B, Priksz D, Gesztelyi T Ra,rjanyi V, Kiss R, Szekeres R, Takacs B, Menes A, et al. Cardioprotective Role of BGP-15 Ag ineing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity. Pharmaceutics. 2022; 14(2):226. https: / / doi.org / 10.3390 / pharmaceutics14020 ]2.26 Apart from diabetes beneficial properties of BGP w-1e5re discovered in acetaminophen-induced liver injury, cisplatin or taxol-induced peripheral nepuarothy and cisplatin related nephrotoxicity. Thete lrat protective effect was accompanied by inhibition ci osfplatin-induced poly-ADP-ribosylation and by the restoration of the disturbed energy metabolism. [Nagy, Gábor et al. BGP-15 inhibits caspase-indeepnetnd programmed cell death in acetaminophen- induced liver injury, Toxicology and Applied Pharcmoalogy, Volume 243, Issue 1, 2010, Pages 96-103, ISSN 0041-008X 17 [Ildiko Racz, Kalman Erzsebet Osz, Laszlo Jaszlits, Sandor Bernath, Balazs Sumegi, Gyorgy Rabloczky, Peteerra Ltiti-Nagy, BGP-15—a novel poly(ADP-ribose) polymerase inhibitor—protects against nephrotoyxi ocift cisplatin without compromising its antitumor activity, Biochemical Pharmacology, Volume 63, Iess 6u, 2002, Pages 1099-1111, ISSN 0006-2952, https: / / doi.org / 10.1016 / S0006-2952(01)0093]5-2. [Bárdos, G et al. BGP-15, a hydroximic acid derivvea,ti protects against cisplatin- or taxol-induced peripheral neuropathy in rats, Toxicology and Aepdpl Pi harmacology, Volume 190, Issue 1, 2003, Pages 9-16, https: / / doi.org / 10.1016 / S0041-008X(03)0015.]5-8 In traumatic brain injury (TBI) it helps the effe ocft chaperones which have a significant advantasgeou effect in this serious impairment of the brain. [Eroglu, Binnur et al., Therapeutic inducers of H thSeP70 / HSP110 protect mice against traumatic brain injury, Journal of Neurochemistry, 2014 Volume1 I3s0s,ue5, Pages 626-6]41 The beneficial effects of BGP-15 on the contrac ftuilnection of regenerating muscles have also been showed. [Nascimento, T.L., Silva, M.T. & Miyabara, E.H. BG1P5- improves contractile function of regenerating soleus muscle J. Muscle Res Cell Motil 39, 25–34 (2018). https: / / doi.org / 10.1007 / s10974-091489-5-y] Most of these effects of BGP-15 were linked to in ithsibition of poly(ADP-ribose) polymerases (PARPs) and interactions with various signaling moleculinescl,uding protein kinase B (Akt) , c-Jun N-terminal kinase (JNK) and extracellular signal-regulateda ksien (ERK). However, the precise molecular mechanism of these [Pető Á, et al., Molecules. 2020, infra]Despite the volatile effects and applications oisf t mholecule, there is no published data indicat tihnagt,BGP-15 interferes with the pathologic functions n oefutrophil granulocytes in MPO-ANCA-associatedvasculitis or any type of vasculitis and no ideas h eamerged that BGP-15 should be combined with aH2S releaser and the prior art is silent about iftesc etf in H2S serum levels or effects thereby. BRIEF DESCRIPTION OF THE INVENTION – GKK895 The invention relates to a compound which is thmeb cionation of an amidoxime compound (in an embodiment a nicotinic-amidoxime compound), prebfelyra BGP-15 analog or a compound having a similar structure as well as a2S H releaser compound. 1. Thus, the invention relates to a compound havoinrmgu fla I or I’ wherein R1is H or a C1-4 alkyl, preferably H, R2is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloalkyl, cycloalleknye or a heterocycle, in a particular embodiment a N and / or O containing heterocycle, in particu ala 6r membered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R3is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H, a 5 to 10 memdb,e prereferably a 6 membered heterocy,c alned C1-4 alkyl, R6, R7, R8, R9and R10, are, independently from each other, selected fHro,m C1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9and R10is H; preferably R8is -OR11wherein R11is C1-4 alkyl, or each of R6, R7, R8, R9and R10is H or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. 2. The H2S donor compound for use according to cla 1im wherein said compound has general formula II.1 or II.1’ R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferablysaturated) cyclic compound, preferably a cycloa,l cky cl loalkylene or a heterocycle, in aparticular embodiment a N and / or O containing hoectyecrle, in particular a 6 membered, Nand / or O containing heterocycle, preferably anh al tipic heterocycle,R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N- containing aromatic heterocycle, preferably pyr,id aynld / or preferably wherein N is in the ortho position, R4 is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H and a 5 to 10 meermedb, preferably a 6 membered heterocycle and C1-4 alkyl wherein in formula (II.1) R6, R8, and R10, is selected from the group consisting of C H1,-4 alkyl, C1-4 alkoxy, halogenide, in particular H and C1-4 alk,oxy whereinin a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. ompound for use according to cla 2im wherein said compound has general formula II. I2I.2 o’r R1is H or a C1-4 alkyl, preferably H, R2is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferablysaturated) cyclic compound, preferably a cycloa,l cky cl loalkylene or a heterocycle, in aparticular embodiment a N and / or O containing hoectyecrle, in particular a 6 membered, Nand / or O containing heterocycle, preferably anh al tipic heterocycle,R3is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N- containing aromatic heterocycle, preferably pyr,id aynld / or preferably wherein N is in the ortho position, R4is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H and a 5 to 10 meermedb, preferably a 6 membered heterocycle and C1-4 alkyl, wherein in formula (II.2) R7, R8, and R9, is selected from the group consisting of C H1,-4 alkyl, C1-4 alkoxy, halogenide, in particular H and C1-4 alko wxhyereinin a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. 4. The compound for use according to cla 3i,m wherein said compound has general formula III I o’ r or X is N or CH, preferably N, R1is H or a C1-4 alkyl, preferably H, R3is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4is H or a C1-4 alkyl, preferably H, R5may be selected from H, a 5 to 10 membered, parbelfyer a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9and R10is H; preferably R8is -OMe or each of6R, R7, R8, R9and R10is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. 5. said compound has general formula IVV o’r I (IV’) or preferably R2 is a 5 to 10 membered, preferably a 6 membereedro hceytcle, in a particular embodiment a N and / or O containing heterocycle, in particular m ae 6mbered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R4 is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H, a 5 to 10 memdb,e prereferably a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9 and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OMe or each of6 R, R7, R8, R9 and R10 is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. Q and U are, independently, selected from N and CH, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. 6. The compound for use according to any of cla 3im tos 5, wherein said compound has formula (V) or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. 7. The compound for use according to any of cla 1im tos 6, for use in the treatment of a disorder. The compound for use according to any of cla 1im tos 6, for use in the treatment of a patient suffering in a disorder. 8. The compound for use according to any of cla 1im tos 7, for use in the treatment of a disorder wherein said disorder is selected from a neoplastic disorder, a proliferative disorder, a neurodegenerative disorder, a neurologic disease an infection, e.g. an infection selected froml v iinrafection, a bacterial infection, a fungal infieocnt, a mycoplasmic infection; a metabolic disease, an oxidative stress disease, preferably a mitocrhiaoln fdunction disease an autoimmune disease, liver injury, neuropathy, traumatic brain injury, nephrotoxicity etc. 9 The compound for use according to any of cla 1im tos 8, for use in the treatment of a disorder wherein said disorder is selected from a condition linked to - inhibition of poly(ADP-ribose) polymerases (PARPs) - its interactions with various signaling molecul seesl,ected from the group consisting of protein kinase B (Akt), c-Jun N-terminal kinase (JNK) anxdtra ecellular signal-regulated kinase (ERK), - its interactions with chaperons or stress-proteins, - a folding-trafficking disease, 10 The compound for use according to any of cla 1im tos 9, for use in the treatment of an autoimmune inflammatory disorder, preferably - inhibiting neutrophil granulocyte activation bnyt ai-MPO antibodies of mammalian subject having AAV (MPO-ANCA associated vasculitis) - inhibiting neutrophil degranulation in the mammianal subject having AAV, - inhibiting neutrophil priming (by translocationf A oNCA antigen MPO) in the mammalian subject having AAV, and / or - preventing kidney damage / protecting the kidne tyhe in mammalian subject having AAV. ANCA vasculitis, preferably MPO-related ANCA vaslictius. Pharmaceutical compositions (medicaments) 11. A pharmaceutical composition comprising the coumnpdo for use according to any of claims 1 to 10, preferably according to any of claims 7 to 10.12. The pharmaceutical composition comprising thep co umnd for use according to clai 1m1,said composition being formulated for systemic andismtriation.13. The pharmaceutical composition comprising thep co umnd for use according to claim 11 or 12,said composition being formulated for oral admirnaitsiotn.14. The pharmaceutical composition comprising thep co umnd for use according to any of claims 11to 13, said composition being formulated in the form opfs cuales and / or tablets.15. The pharmaceutical composition comprising thep co umnd for use according to any of claims 11to 14, wherein said composition is protected from light, moist aurned decay to form2 HS during storage. 16. The pharmaceutical composition comprising2S a H donor compound for use according to cla 1i2m, said composition being formulated for intravenodums ainistration. 17. A pharmaceutical composition comprising2 aS H donor compound for use according to cla 1i6m, said composition being formulated in the form o pfo awder which can be reconstituted in an intravenous injection, or infusion,with an appropriate solution (preferably Ringeru-stiol n… etc.).18. The pharmaceutical composition comprising a coumnpdo for use according to clai 1m6, said composition being formulated as drops, e.g. - eye drops - intranasal drops. 19. The pharmaceutical composition comprising2S a H donor compound for use according to any of claims 1 to 10, preferably according to any ofm clsai 7 to 10, said composition being formulated for topical adimstirnation, preferably in the form of ointment, gel or emuls,ion said topical administration form comprising excniptise to protect the2 HS donor compound moisture and / or decay to form2 HS during storage and optionally from light. 20. The pharmaceutical composition according to afn cyla oims 11 to 19, said composition comprising a light-protective package. 21. The invention also relates to a method of treatm wehnerein said composition or formulation is administered to a mammalian patient having or egnedraend by or showing a tendency to develop, as defined herein, in order to prevent or treat saisidea dse in said patient.In a particular embodiment the invention relates a to reatment method for the treatment of a connditioas defined in any of paragraphs 7 to 10. In a particular embodiment oral administrationp ispl aied. In a particular embodiment diagnostic test is ceadrr oiut, as disclosed herein to identify the pat gieronutp to be treated. 22. In a preferred embodiment before treatment then ptasti are diagnosed with the disorder to be treated. 23. In a preferred embodiment before treatment theen ptasti are diagnosed in any of the disease listed in claims 7 to 10. 24. In a preferred embodiment before treatment the A pAaVtients are diagnosed; 25. In a preferred embodiment before treatment the A pAaVtients are diagnosed; for MPO-ANCA positivity. AAV patients are patients who are considered tow s AhoAV symptoms according to any guidelines asdescribed herein (in a particular embodimethnet ( 2012 revised International Chapel Hill ConsensusConference nomenclature of vasculitides, [Jennette JC, 2012, inf]r,a or any other diagnostic or rating tool, e.g. Birmingham Vasculitis Activity Score (BAVS) and the Vasculitis Damage Index (VDI) or as referred in [ Ball, Gene V., Fessler, Barri J. and Bridges Su.is L,o Eds., Oxford Textbook of Vasculitis, Third edition, Oxford University Press 2014) or kwnno in the art or known at the time given. In this regard the level of diagnosis which suggests thhea pt tatient may have or may develop AAV is suffictien provided that such level advises (or warrant) t sota i)rt treatment, ii) carry out further diagnos sttiecp (e.g. biopsy) and / or iii) detect ANCA. In this regard the methods described or cited ianp Ctehr “Diagnosis of MPO-ANCA associated vasculitis patients” are specifically contemplated or, if aoppprriate”, incorporated herein by reference. The level “advises to” included a case when sympsto frmom at least two organs refer to AAV, or when the protocol in force advises start of treatmen ftu ortrher investigation. In a particular embodiment the mammalian patienst h higaher ANCA titer and multiple affected organ systems (as defined by Houben E et al. 2016, i.nfra) 30. A method for the preparation of a compound acicnogrd to any of claims 1 to 10, preferably claim 10, comprising the step wherein a Lawesson-type reagent according to formula (X r)ea iscted, preferably opened up, with a hydroxy- amidoxime compound of formula (VIII) a O-nucleopehil I under inert atmosphere, wherein R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloalkyl, cycloalleknye or a heterocycle, in a particular embodiment a N and / or O containing heterocycle, in particu ala 6r membered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R6, R7, R8, R9 and R10, are, independently from each other, selected fHro,m C1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OR11 wherein R11 is C1-4 alkyl, or each of R6, R7, R8, R9 and R10 is H. 31. The method according to claim 30 wherein the a Lawesson-type reagent has the formula (XII.1) wherein in formula (XII.1) R6, R8, and R10, is selected from the group consisting of C H1,-4 alkyl, C1- 4 alkoxy, halogenide, in particular H and C1-4 axlyk,o wherein in a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H.32. The method according to clai 3m0 wherein (XII.2) wherein in formula (II.2) R7, R8, and R9, is selected from the group consisting of C H1,-4 alkyl, C1-4 alkoxy, halogenide, in particular H and C1-4 alko wxhyereinin a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H.33. The method according to clai 3m0 whereinthe Lawesson-type reagent is as defined in clai,m or 3 p0referably in claim 31 or 32, and the hydroxy- amidoxime compound is a compound having the streuc otuf general formula (IX), compound of gen foerrmalula (III), or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof, wherein X is N or CH, preferably N, R1 is H or a C1-4 alkyl, preferably H, R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R5 may be selected from H, a 5 to 10 membered, parbelfyer a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9 and R10, (as the case may be) is selected from C1 H-,4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 (as the case may be) is H; preferab8ly is R -OMe or each of6 R, R7, R8, R9 and R10 is H.34. The method according to clai 3m0 whereinthe Lawesson-type reagent is as defined in clai,m or 3 p0referably in claim 31 or 32, and the hydroxy- amidoxime is a the streuc otuf general formula (X), (X) and the resulting compound is a compound of gen foerrmalula (IV), or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof, wherein R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 membereedro hceytcle, in a particular embodiment a N and / or O containing heterocycle, in particular m ae 6mbered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R4 is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H, a 5 to 10 memdb,e prereferably a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9 and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OMe or each of6 R, R7, R8, R9 and R10 is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. Q and U are, independently, selected from N and CH. 35. The method according to clai 3m0, 31, 32, 33 or 34, wherein the reaction is carried out in apolar solvent. 36. The method according to any of claim 30s to 35, wherein the reaction is carried out at a temperature of 0 to 50°C, preferably 10 to 40°Ce,fe prrably 15 to 30 °C, preferably at room temperature, e.g.20 to 25°C. 37. The method according to any of claim 30s to 36, wherein the reaction is carried out at under intert atmoesrep,h preferably under nitrogen atmosphere. 38. The method according to clai 3m0, 31, 32, 33, 34, 3,536 or 37 wherein the Lawesson-type reagent is as defined in clai,m or 3 p0referably in claim 31 or 32, and the hydroxy- amidoxime compound is a compound having the streuc otuf general formula (VIII, IX or X), wherein Lawesson reagent (1) is opened with BGP-15O (2-[)3 (-(1-piperidinyl)-2-hydroxi-1- propyl]nicotinamide-amide-oxime) itself as O-nuocplehile, (V) or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. DEFINITIONSA “subject” as used herein is an individual of an animal sepse,c pireferably a vertebrate, more preferablya mammalian or avian species, in particular a malmiamna species, highly preferably the individual is aprimate, a hominid or a human. “ Apatient” is a subject who is or intended to be under mel d oircaveterinarian care, observation, supervision, diasgisno r treatment. A “treatment” of a subject refers to any process, action, therapy, or the, l wikherein the subject or patient is under aid, in particular medical or vrientaerian aid with the object of improving the sucbt’jse or patient’s condition, either directly or indirelyc.t Improving the subject’s condition may include restoring or maintaining normal function of an onrg oar tissue, preferably at least partly restorinrg o maintaining health (medical or veterinarian treantmt).e Treatment typically refers to the administoranti of an effective amount of a compound or composi dtioenscribed herein. Preferably the administration of the compound is oral administration and res iunlt asn appropriate serum level of2S H in the patient. Particularly preferably treatment includes both micaeld or veterinarian treatment in the early phafse o the disease e.g. in the phase of neutrophil prim inin agn MPO-ANCA positive patient, in particular AAV patient. In a broader sense treatment includes both me odric vaelterinarian treatment in the early phase of the disease including prevention (or prophylaxis) p i.ere.vention of the onset of a disease symptoms or prevention of manifestation of the disease in anO M-APNCA positive patient. In a more limited sense prevention is not covered. A “pharmaceutical composition” of the invention is a composition of matter wh cicohmprises at least one active agent and at least one further subs.ta Pnrecfeerably the compound of the invention is pnretse in an effective amount. Compositions may also coismep frurther biologically active substances useful e.g. in a combination therapy. Furthermore, thep coosmitions may comprise biologically acceptable carriers, formulation agents, excipients etc. wh micahy be known in the art. In a preferred embodim, ent the compound is present in the composition in aonu anmt resulting in an effective serum level o2fS H in a mammalian subject. The term “effective amount” qualifies the amount of a compound required tort e txhee effect of the active agent in a composition. “ Atherapeutically effective amount” is sufficient to relieve the disease condition or prevent one or more of the symptoms ch oarracteristic parameters of a condition, e.g. a disorder or disease. In a particular embodiment the disease is AAV, p tahteient is an AAV patient and the compound of the invention is for use in the treatment of or to pernetv occurrence or manifestation of AAV symptom or exacerbation of the disease condition.A “ H2S donor compound” is a compound, that degrades in response tov ainro ennmental stimulus (forexample water, light, a nucleophile such as a, th thioel action of an enzyme, or other stimuli) toea resle H2S. In particular a H2S donor compound is a compound as defined by P,o Cwhealldwick R. et al [.in: Powell, Chadwick R., Kearsley M. Dillon, and Joh.n M Batson. "A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic aptpiolicnas." Biochemical pharmacology 149 (2018): 110- 123]. In a particular aspect the2S H is released under biological conditions e.g. isnub aject or in a condition providing a model of biological conditiso,n including an in vitro model.A “ slow H2S release”r compound is a H2S donor compound from which2S H is released slower,preferably for a 10 times longer time, more prebfelyra for a 100 times longer time than from a refecreen sulfide compound, preferably from N2Sa under appropriate reference conditions e.g. u inddeenrtical or appropriately comparable conditions. An example th foer measurement of the time period of the release of hydrogen sulfide from N2aS in a cellular environment is indicated by Vitvkiyts et al. on Figure 2 / A [Vitvitsky, Victor, et al. “The mitochondrial NADHo pol is involved in hydrogen sulfide signaling and stimulation of aerobic glycolysis. J”ournal of Biological Chemistry 296 (2021]) or [Lee ZW et al. The slow-releasing hydrogen sulfide donor, GYY4137,ib eixtsh novel anti-cancer effects in vitro and ino v.iv PLoS One.2011;6(6):e21077. doi: 10.1371 / journanle.p.0o02107]7. Other methods of measurement are known in the art.Terms “sulfide” and “H 2S” in particular bioavailable sulfide and2S H are used interchangeably andinclude all protonation isomers (in particula2rS H, HS-, S2-), unless otherwise indicated.A “moiety” is used herein as a part of a molecule which cea dne brived in principle by removing anotherpart, even a hydrogen atom or a group or any h pear et o t f.As used herein, the term “alkyl” alone or in combinations means a straight or bhreadn-cchain (ifappropriate) saturated hydrocarbon group contai pnrinegferably 1 to 15, 1 to 10 or 1 to 8 carbon atso)m(or in particular 1 to 6 or 1 to 4, 1 to 3 or 12 to carbon atom(s) [i.e. “1C-15”, “C 1-10” , “C1-8”, “C 1-6” or inparticular “C1-4”, “C 1-3” or “C1-2” alkyl groups, respectively], such as particula prlryeferably methyl,ethyl, propyl or isopropyl groups.As used herein, the ter “malkoxy” means an alkyl-O- group in which the alkyl grousp as i previouslydescribed. The bond to the rest of the molecul ceo omrplex, i.e. the parent moiety is through the oexnyg (if to a carbon atom, ether oxygen).The term “alkoxy alkyl” means an alkyl group which is substituted by aknox ayl group, i.e. an alkyl—O- group as previously described. The bond tol tkhyel m a oiety is through the oxygen, i.e. it is anh e rtoxygen.As used herein, the term “csarbonyl ”, “ alkyl-carbonyl ”, “ alkenyl-carbonyl” and “alkynyl-carbonyl ”mean a moiety having carbonyl group optionally stiutubtsed with an alkyl group, alkenyl group and alkynyl group, respectively. In a wider sense trhoeu gp can be connected by either the alkyl, alke onryl alkynyl or via the carbonyl group. In a preferremdb eodiment, i.e. narrower sense, the group bonhde to t parent moiety is through the carbon of the carbo gnroylup. In a preferred embodiment the “alkyl— carbonyl”, “alkenyl-carbonyl” and “alkynyl-carbon”y ils alkanoyl, alkenoyl and alkynoyl, respectively. This definition of wider sense and narrower senesreta pins to any analogous groups with a functional group used herein even if not defined separately.As used herein, the term “csarboxyl ”, “ alkyl-carboxyl ”, “ alkenyl- carboxyl” and “alkynyl- carboxyl”are defined to mean a moiety having carboxyl gro putpionally substituted with an alkyl group, alkenyl group and alkynyl group, respectively, wherein bo ton tdhe parent moiety is through the carboxyl gr.oup The group can be connected by either the alkyle,n ayllk or alkynyl or via the carboxyl group (in the latter case being an esther).An “alkenyl” as used herein, alone or in combinations, mea sntrsai aght or branched-chain unsaturatedhydrocarbon group containing at least one carbornb–ocna double bond, said hydrocarbon group containing preferably from 2 to 20, preferably 21 t5o, 2 to 10 or 2 to 8 carbon atoms or 2 to 6, 42, t 2oto 3 or 2 carbon atoms [i.e.2 “-C20”, “C 2-15”, “C 2-10” , “C2-8”, “C 2-6” or “C2-4”,“C 2-3” or “C2” alkyl groups,respectively].An “alkynyl” as used herein is defined analogously to alkenuytal mtis mutandis.A “heterocyclic” ring as used herein is a cyclic moiety that haes, id bes carbon atom(s), atoms of atleast one non-carbon element as member(s) ofn igts(s r)i. A heterocycle may comprise multiple rings, e.g. it may comprise an aromatic heterocycle aunsde,d f to the aromatic heterocycle another ring which may or may not be aromatic; i.e. if it is not arotimca it may form a cyclic substituent of the aromcati heterocycle. In a preferred embodiment, if ther hoeatreyl comprises multiple, in particular two fused rings, both rings are aromatic. Preferably the( rsin)g of the heterocyclic moiety is / are 5 to 6 memebder ring(s).The term “heterocycloalkyl” refers to a “heterocyclic” ring which has a strhatig or branched-chain (ifappropriate) saturated hydrocarbon group and w mhiacyh have an alkyl substituent on the heterocycle, optionally a heteroaryl and / or which is derivabrloem f cycloalkyl group as defined above, wherein at least one of the carbon atoms of the ring is reepdla wcith a heteroatom such as, but not limited to, nitrogen or oxygen.An “aromatic” moiety as used herein can be described as a p claycnlaicr moiety (a ring) wherein thesingle bonds (called σ-bonds) between the ring-forming atoms are formreodm f overlap of hybridized atomic sp2-orbitals in line between the carbone niu,c wlherein a system of delocalize πd-bonds are formed from overlap of atomic p-orbitals of each th oef ring forming atoms above and below the plane of the ring and wherein the number π of electrons, which is provided by the ring-formintgom as, participates in according to molecular orbital trhye,o must be equal to 4n + 2 (Hückel’s rule), inc whhi n = 1, 2, 3, etc., preferably 1 or 2, for a sin rginleg with six π electrons, n = 1. The ring-forming atomstypically provide one or two π electrons to the delocalize πd electron system.The term ”heteroaryl” is defined herein as a group or molecule thata cinosnt an aromatic heterocycle,preferably a moiety that has at least one hetemro,a atos “member”, incorporated within an aromaticg. rin Examples of heteroatoms include nitrogen, oxygedn s aunlfur, preferably nitrogen and oxygen. In an embodiment a heteroaryl may comprise an aromateicro hceycle and, fused to the aromatic heterocycle another ring which may or may not be aromatic; if i. iet. is not aromatic it may form a cyclic subsuteitnt of the aromatic heterocycle. In a preferred emboednitm, if the heteroaryl comprises multiple, in particular two fused rings, both rings are arom.a Mticembers of a heteroaryl relate to the ring-forgmin atoms, either carbon atom(s) or heteroatom(s).The term “aryl” as used herein is a group that contains any c-abrabsoend aromatic ring which ispreferably a mono- or bicyclic group, wherein thicey bclic group preferably comprises two fused rings. In a preferred embodiment the aryl group consisf t csa orbon as ring atoms, i.e. “members” only. In a broader meaning the term aryl also includes opltliyon “aheteroaryl”. Optionally, the term “aryl” is limited to non-heteroaryl which is also includedto in the term aryl and defines a group that conta nins aromatic group that does not contain a heteroatom.An aryl group may be substituted or unsubstitutie.ed. ( optionally substituted). If the aryl group issubstituted it may be substituted with any subesntit ,u and examples of the substituent inclu1d-e4 a Clkyl,C2-4 alkenyl, C1-3 alkyloxy, C1-3 alkanoyl, C1-3 alkylamine, C1-3 alkylamide, halogen, etc.The term “aralkyl” as used herein refers to an aryl alkyl group wh isic lhinked to the parent moleculethrough the alkyl group, which may be further onpatiolly substituted with one or more, preferably oneto three or one to two alkyl substituents. Thuse, a thryl group may be substituted with an alkylsubstituent, preferably each substituent being la nrogter than a C1-4 alkyl.„Aryl” or „heteroaryl” may comprise a monocyclic ring, a condensed r oinrg a, polycyclic ring inwhich a single ring is bounded by a single bonde,fe prrably a monocyclic or bicyclic ring.As used herein, the ter “mfused ring” means that the ring is fused with at least oner o rtihng to form agroup of a compound which comprises two or morges ri wnherein a single bond between two-member atoms of the rings is, together with said two merms,b ceommon in, i.e. shared by the two rings. An example of fused rings is a polycyclic aryl. p Aolycyclic aryl is understood herein as a group that contains multiple rings of a carbon-based groupn agm wohich at least one ring is an aryl and which optionally may also comprise a cycloalkyl and / o hre aterocycloalkyl.A “substituted” moiety comprises a substituent selected fromr tohuep gs and moieties as defined herein;however, a substituent is preferably smaller, s ih.eo.rter, i.e. consists of not more, preferablya letsosmsthan the moiety which is / are substituted therenby th.e I present invention “o,ptionally substituted” , i.e.“unsubstituted or substituted” means that it may su bbestituted with any substituent. In general formulae of the description H atoms t aypreically not shown, however, a skilled person is able to understand said formulae and recognize fu tllh setructure. Terms expressing optionality, like optional emboednimts or variants, are used throughout the specification, among which “particular” relates e tmobodiments or variants of particular interest and “preferred” to those which are preferred for someaes ron.The singular formsa “”, “ an” and “the”, or at leasta “”, “ an”, include plural reference unless the contextclearly dictates otherwise.The term “comprises” or “comprising” or “including” are to be construed here as having a non—exhaustive meaning and allow the addition or inevomlvent of further elements, e.g. features or method steps or members or components to anything whimchp crioses the listed elements. “Comprising” can be substituted by “including” if the practice of a geinv language variant so requires or can be limioted t “consisting essentially of” if other elements than those listed are not eisasle tont reduce the invention to practice orc “onsisting of” in no other elements may be present. BRIEF DESCRIPTION OF THE FIGURES Figure 1. Release of hydrogen sulfide over time b GyYY4137 and GKK895 molecules. Dilutionseries from GYY4137 and GKK895 stock solutions w perre pared, pipetted into a 96-well plate andcovered with lead-acetate impregnated filter pa fopre 5r h, 24 h and 29h. The GKK895 and GYY4137 compounds released hydrogen sulfide gas in a coamblpea mr anner. Figure 2. Measurement of serum sulfide concentratinos of mice treated with GYY4137 or GKK- 895 Mice were treated with 150 µmol / kg GYY4137 or 1 µ1m0ol / kg GKK-895 intraperitoneally. Blood samples were collected from the eye corner atn tdhieca ited time points. The concentrations of hydnroge sulfide were measured with the monobromobimaney a fsrsoam the collected blood serum samples. Treatment with both GYY4137 and GKK-895 resulted si ignnificant elevation of sulfide concentrations in the circulation with GKK-895 causing higher mueraesd sulfide values at 2 and 4 hours after injenc.tio Figure 3. Effect of GYY4137 molecule in ANCA-vasculitis mouse model. Columns indicate the percentage of affected glomeruli in the sulfideo dro tnreated samples compared to their untreateds. p Tahire gray line represents the 0% baseline (same numfb aeffre octed glomeruli in treated and untreated m aicned)the last column indicates the average percentl o thfe al samples.Figure 4. Effect of GKK895 molecule in ANCA-vascultiis mouse model. Mice received isolated splenocytes from MPO-immunized MPO knockout michee. T connected samples indicate the pairs of mice receiving splenocytes from the same MPO KOs me.o Muice that were treated with GKK895 black circles) show diminished levels of affected glomlie croumpared to control samples (black squares). Figure 5. Comparison of GYY4137 and GKK-895 treatmnet in mouse kidney samples Kidney samples from the ANCA vasculitis mouse models w pererepared for histology analysis and evaluated with light spectroscopy. The percentage of affec gtelodmeruli in treated samples were calculatedcompared to their control pairs. Samples that w trer aeted with 150 µmol / kg GYY4137 (labeled withdark gray) and also showed decreased renal symp wtoemres depicted on this figure with an average decrease in affected glomeruli of 64.9 %. Samphlaets w tere treated with 90 µmol / kg GKK-895 (labeled with light gray) showed an average of 56.9 % descere ina affected glomeruli compared to control pairs. Figure 6. Blood sulfide concentration of hydrogenu slfide donor treated mice after 2 hours Mice were treated intraperitoneally with GKK-895 (110o µl / mkg) or GYY4137 (150 µmol / kg). Hydrogen sulfide concentrations were measured from venoouosd b (ldrawn from eye corner) 2h after treatments with the monobromobimane assay.Figure 7. Mass spectrum of GKK-895 Saturated aqueous (0.1% FA) solution of GKK-895s w inafuseddirectly into a Thermo Scientific Q Exactive (HRAM m)ass spectrometer and a Hamilton syringe at a 10 µl / min flow rate using a heated ESI ion sourecte to s positive mode. GKK-895 was successfullyidentified at 481.136 m / z. BGP-15 was also dete acte 2d79.174 m / z.Figure 8. Mass spectrum showing GKK-895 and its deragdation / oxidation products 10 mM GKK- 895 diluted 100x in 0.1 % formic acid / water wasp parreed and was infused directly into a Thermo Scientific Q Exactive (HRAM) mass spectrometer g us ain Hamilton syringe at a 10 µl / min flow rate and a heated ESI ion source set to positive moduelt.ip Mle degradation products were identified, including 2 forms that have already donated thuelifru sr atoms (465.158 m / z and 449.165 m / z) and the oxidized GKK-895 was also detected at 497.13 m / z. DETAILED DESCRIPTION OF THE INVENTION The inventors have arrived at a new concept of cinoamtibon of BGP-15 type compounds with a sulfide donor compound. This novel type of combination upneecxtedly resulted in a more efficient H2S releaser which may be applicable in a broader range of dsiesse.a The exemplary compound, GKK-859 is a novel molec oufle the invention, that was synthetized by linking BGP-15 with the sulfide donor GYY4137 moulelec. GKK-859 While publicly available information on BGP-15 suegsgted that said molecule is non-toxic to mammalian subjects, this could not be foreseenrd reingga the composite molecule. However, GKK-859 proved to be highly effective without observabldee s eiffects in our experiments. Unexpectedly, GKK-895 was found to be a more effective sulfide do mnor lecule, which was shown by the lead-acetateassay (Figure 1). In addition, intraperitonealt tmreeant of mice with GKK-895 in a considerably lowerconcentration unexpectedly resulted in significyan etl evated sulfide levels in mouse blood seracompared to GYY4137 (Figure 2), a slow2S H releaser compound (see US8865684B2 granted to National University of Singapore), the beneficifafel ect of which in ANCA-vasculitis is described ino- cpending international patent filed in parallel with the presentapplication with the Hungarian Intellectual Propyer Otffice as Receiving Office. In the present experiments GYY4137 is used as a reference exam Bpalsee.d on these findings the present inventors have carried out the ANCA-vasculitis mouse modeple erixments using GKK-895 in markedly lower concentration (90 µmol / kg) than GYY4137 (150 µmgo)l. / k Our results suggested that despite the lower dose, GKK-895 was equally effective as GYY4137,c whh ciorrelated well with the measured blood sulfide levels. Our experiments suggest, that tfhfieca ecy of the new molecule correlates with its hydrogen sulfide donor properties, which serves co arsroborating evidence to our hypothesis, that hydrogen sulfide can diminish renal symptoms of AAN-vCasculitis, therefore all hydrogen sulfide donors could be bases for drug development.Thus, said compound increases bioavailab2lSe H level in the serum of a mammalian subject afteradministration of said compound to said subjecet,fe prrably said subject having increase2dS H serum level after a time point of 1 h to 24 h after adimstirnation of said compound, if compared with normal H2S serum level (or the serum level o2fS H without (or before) administration of said comnpdo)u, wherein preferably said increased2S H serum level is at least two times of the normearulm s level. In the present invention the inventors have arri avte tdhe synthesis of GKK895 by the following strgayt.e The present inventors had a few acylation expertism wenith sulfide donor molecules, but they failede th first time (see Scheme 1). However, the BGP-15 su (2rp)risingly found to form a dithiolate derivative more stable to hydroxychloroquine with Lawessoena'sg rent. The Lawesson reagent (1) is opened with BGP-15 (2) itself as O-nucleophile. This reactison kn iown in the literature in with simple alcohoulst b not with such a complex structure. A pure compo (u3n)d was obtained from the reaction mixture. This "GYY-like" compound proved to be relatively stab alned was found to be possibly promising. Scheme 1 Solubility Due to the coupling reaction, GYY4137 loses itsic io cnharacter and BGP-15 its polar character. The product obtained is a double-ion molecule. Theb siolitlyu of the product in water is therefore limit,edand can be slightly improved by shifting the pH th teo alkaline range, up to a concentration of 2,5 / m ml gafter restoration to neutral pH. Structure determination As to structural analysis mass spectrometry wads. use The molecule (molecule ion; m / z=481.13) was ideiendtif by mass spectrometry, and the unreacted ordegradation-derived BGP-15 scaffold (m / z=279.14s) w alaso detected by tandem mass spectrometry.Tandem mass spectrometry (MS / MS) allows the fragtamtieon of proteins and peptides to determinethe amino acid sequence of proteins (top-down aindd l me-down proteomics) and peptides (bottom-upproteomics). Furthermore, tandem mass spectrom alestory allows the identification of post-translatiol na modifications (PTMs) of proteins and peptides.An oxidised product can also be identified at m / 4z9 =7.13, and two products after the loss of on tew orsulphur atoms at m / z = 465.16 and 449.16 (in th peroseducts the two sulphur atoms are replaced by oxygen). (See Figures 7 and 8.) As to the exemplary medical use discovered itl iaste red to the effect of hydrogen sulfide serum lse.vel The prior art results suggest that whil2eS H may influence pathophysiological processes otfro npehuils due to physiological effects significant in inflamatmion, however, discovery of the complex network of effects indicated that the overall effect is unacienrt and unpredictable. Moreover, there is clear evidence that neutropuhniclt fions were not affected by hydrogen sulfide drsono in case of PMA, LPS o Erscherichia coli activation. For example, treatment with the hydrogen sulfidneo dro GYY4137 did not inhibit PMA or LPS induced oxidative burst. In fact, pretreatment of neutrolsph wiith 200 µM GYY4137 before PMA activation increased the production of ROS compared to noant-etdre samples. Treatment with GYY4137 also inhibited apoptosis and promoted cell-viability L inPS induced neutrophils. It was demonstrated that sulfide moderately decreased the formation of RnO LSP iS induced neutrophils, however these effects were measured after 17-18 h incubati [oPne.trushanko, I.Y. e,t al. Influence of the Donor of Hydrogen Sulfide GYY4137 on the Activation of Human Neutroilpsh by E. coli Lipopolysaccharides M. ol Biol 53, 79–86 (2019]) It was also shown by another research group thraiotu vsa sulfide releasing compounds, such as sodium sulfide, diallyl-disulfide, diallyl-trisulfide and cysteine also inhibited neutrophil apoptosis upoMnA P and bacterial activation and promoted oxidativest b.u [Frarahat S. et al. Effect of Hydrogen Sulfide onEssential Functions of Polymorphonuclear Leukoc.y Ttoexsins. 2023; 15(3):198].Rinaldi, L. et al. demonstrated that in the presee onfc NaH2S (1.83 mM) neutrophils were more efficient in killing bacteria than in the absence of sulfid aen,d the sulfide donor also diminished neutrophil apoptosis. [Rinaldi, L., Gobbi, G., Pambianco, M et. al. Hydrogen sulfide prevents apoptosis of human PMN via inhibition of p38 and caspase 3. Lab Invest 86, 391–397 (2006). https: / / doi.org / 10.1038 / labinvest.37003]91 There was no hint in the prior art that sulfide c inahnibit priming, ANCA-induced degranulation and oxidative burst. Rather, the prior art seems tog seustg that hydrogen-sulfide may even increase neutrophil activation by preventing neutrophil atpoospis – a process undesired in an autoimmune disease.Actually, the treatment options of AAV diseases th ien prior art are limited.In a co-pending application the present inventoarvse h demonstrated that treatment with hydrogen sulfide: - inhibited neutrophil granulocyte activation byti a-MnPO antibodies of mammalian subject having AAV (MPO-ANCA associated vasculitis) - inhibited neutrophil degranulation in the mammanal siubject having AAV, - inhibited neutrophil priming (by translocation A ofNCA antigen MPO) in the mammalian subject having AAV, and / or - prevented kidney damage / protecting the kidne tyhe in mammalian subject having AAV. The novel compound of the invention and assumahbely n tovel group of compounds performed better in the experiments set up so far, as illustrated th bey experiments shown herein. GKK895 function as sulfide donor molecule and rseelesa hydrogen sulfide with comparable speed withGYY4137, however, more effectively, i.e. the samevee l of H2S release is achieved by a concentrationof GKK895 significantly lower than GYY4137. (Seeg Fuire 1.) The present inventors have found that, surprisi,n GglKyK895 significantly increased the bioavailable sulfide concentrations in the blood serum of mamiamna slubjects, in particular mice, and this increase of H2S serum level was achieved by a concentration lo thwaenr that of GYY4137, producing the same (or even lower) serum2 HS level. (See Figure 2.) In the presented MPO-ANCA vasculitis animal mod inel, reference experiments it was shown that treatment with hydrogen sulfide releasing compou GnYdY4137 (150 µmol / body weight kg, 3 times / week) significantly diminished ANCA-vascuslit aissociated symptoms in the kidneys. The results with individual aminals are shown on Figure 3. In the same presented MPO-ANCA vasculitis animadl e ml,o the present inventors have shown that treatment with hydrogen sulfide releasing compo GunKdK895 in lower concentration (90 µmol / body weight kg, 3 times / week) significantly diminishedN ACA-vasculitis associated symptoms in the kidneys (Figure 4). Results with each animal pairs which have beenid coernesd in the calculations of reduction of glomei,rul both in case of GYY4137 and GKK895 are collected F oignure 5. The affected glomeruli in the GKK895 treated anism waelre 56.9 (± 17.4) % less than in control anim. alsThis protective effect was about equally efficie wnit h GYY4139 but in a much lower concentration;GYY4139 (150 µmol / kg) also showed decreased reynmapl stoms and resulted in an average decrease in affected glomeruli of 64.9 %. To summarize, novel type hydrogen sulfide donor G-8K9K5 was administered to healthy mice IP and serum concentrations were significantly elevated an 2dh 4h after treatment compared to control and GYY4137 treated samples (Figures 2 and 6). It wlsaos d aemonstrated that GKK-895, at much lower concentrations diminished renal symptoms of ANCAso acsiated vasculitis to the same extent as higher concentrations of GYY4137 in the ANCA mouse modFeiglu (res 3 to 5). Therefore, the compounds of the invention haverp ari ssuing additional advantage over close prior art compounds. Moreover, the compounds of the invention are pualratircly useful in the following conditions. In the treatment of antineutrophil cytoplasmic aunttoibody (ANCA)-associated vasculitis (AAV) in a mammalian patient having AAV of the myeloperoxid-aAsNeCA (MPO-ANCA) serotype, preferably said AAV being a myeloperoxidase (MPO) autoantig peonsitive AAV wherein said subject has an increased MPO-specific ANCA level. The compounds of the invention are slow2S H releaser compound and said compound can beo ursed fpreventing kidney damage and / or protecting thee kyid in the mammalian subject having AAV.In a particular embodiment the disease is sele frcotemd microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) (Wegener’s granulomatosi es)o,sinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome), and renal lim vitaesdculitis. The novel compound may be administered in sevearaysl w. In particular embodiments said compound is - administered orally to said mammalian patienrt, o- administered intraperitoneally to said mamma plian tient, or.- administered intravenously to said mammaliane pnat,ti preferably administered orally to said mammaliatnie pnat. Preparation of compositions or pharmaceutical prraetpioan from the present compounds for use is within the skills of a person skilled in the art. For long time storage it is advantageous if thep co smitions are stored in dry form, e.g. crystalliz oerdlyophilized. Appropriate vehicles are known in the art. A typli vceahicle used is e.g. carboxymethyl-cellulose. Furthermore, several compounds may be sensitiv heyd troolysis which advises towards using a buffer in particular in injectable formulations, however,n ev ine dry formulations avoiding formation of acid oicr basic pH may be advisable. Injectable formulation can be reconstituted bef uosre and therefore only soluble components are to beused. Poor solubility resulting in limited drug loadingan c occur as a problem which has to be solved. Typical excipients may include the following caterigeos and examples: Disintegrants, like crosslinked polymers, polyvipnyyrlrolidone (crospovidone), crosslinked sodium carboxymethyl cellulose (croscarmellose sodium) p,a inrticular the latter. Binders, including for example -saccharides e.g. disaccharides (lactose, sacch);a pros lyesaccharides (e.g. cellulose, starchesetc.), modified polysaccharides such as microclrlyinseta cellulose, cellulose ethers, or derivatized saccharides, e.g. carboxymethyl cellulose etc. b mea uyseful; - sugar alcohols such as xylitol, sorbitol or manln;it no particular mannitol (E421) -protein type binder, like gelatin; (in particulanr l i ght gelatin capsule).Lubricants, like magnesium stearate, or othera stea drerivative (or talc or silica etc.) can be aiepdp.lPolymers having the role of a stabilizer, surfatcta hnickening agent, solubility enhancer, e.g. Ponvied (polyvinylpyrrolidone, PVP) or other synthetic pmolyers, like polyethylene glycol (PEG), preferably Povidone. In the present invention the compounds used aricea tlylyp rather hydrophobic, light sensitive composu.ndThus, when formulating them into pharmaceutical p co smitions these problems should be considereds. It iadvantageous if the compositions are protectedl firgohmt. A preferred formulation is capsule, e.g. light gtienla capsule or hard capsule wherein the activet a igsen protected from light. In an embodiment the pack sahgoeuld protect the azidated compounds from lighotn.- N transparent capsules are preferred for oral adtmraintiiosnAn example is Lonza Capsugel of T2-iOfree light-protected capsules (See [Lonza Preslesa Rse “LonzaExpands its Capsugel® Capsule Offering to Includitaen Tium Dioxide-Free White Hard Gelatin Capsules” May 9, 2022, Basel, Switzerland]). Methods for encapsulation or incorporation intoy pmoelric matrices, including nano- and micro-partsic,le with increased loading are also known and relaotemdp cound is disclosed as a nanoemulsifed formulation and the like are known in the art. EXAMPLES 1) Under nitrogen atmosphere, at room temperature,e Lssaown-reagen1t) ( (3,28 g; 8,12 mmol) was added to 30 ml solution of 4,27 g (15,34 mmol)- O[3-(1-piperidinyl)-2-hydroxi-1-propyl]nicotinamid-eamide- oxime (2) (BGP-15) prepared in freshly distilled dichlorotmhaene, and the mixture was stirred for 12 h and room temperature. White crystals precipitartoemd f the reaction mixture were filtered, washed in 2 x 8 ml dichloromethane, and dried in vacuum. Yie 4ld,8:7 g (10,13 mmol, 66 %), white crystals. M.p.:189 °C.1H NMR(DMSO; 400 MHz) δ = 8.84 (d, J = 1.7 Hz, 1H), 8.62 (dd J, = 4.9, 1.7 Hz, 1H), 8.05 – 7.92 (m, 3H), 7.44 (d Jd, = 8.0, 4.7 Hz, 1H), 6.92 (dd J, = 8.8, 2.6 Hz, 2H), 6.40 (m, 1H), 5.31 – 5.21 (m, 1H), 4.13 (m, 1H), 3.98 (d Jd =, 10.8, 6.5 Hz, 1H), 3.82-3.78 (m, 1H), 3.78 (Hs,), 33.55 – 3.44 (m, 2H),4.41-3.38 (m, 1H), 3.15 – 3.02 (m, 1H),31-1.9.82 (m, 3H), 1.82 – 1.69 (m, 2H), 1.49 – 1.40 (m, 1H);13C NMR (126 MHz, DMSO) δ = 160.97, 150.82, 150.54, 147.45, 136.09, 1341.0362,.12, 132.01, 128.65, 123.82, 113.08, 112.97, 73.46,66,65.97.74, 55.68, 54.99, 53.31, 40.57, 40.48, 40.40, 40.31, 40.24, 40.14, 40.07, 39.98, 39.90, 39.8.16,43,939.48, 23.39, 22.78, 21.46. GKK-895 structure confirmation and purity check by mass spectrometry Method GKK-895 was dissolved in DMSO at 10 mM concentrnati (odiluted to 100 µM in 0.1 % formic acid / water (mass spectrometry grade)) and a seadtu araqtueous (0.1% formic acid, FA) solution was also prepared for mass spectrometry based structurafilrm coantion and purity check. Sample solution were infused directly into a Thermo Scientific Q Exacetiv (HRAM) mass spectrometer using a Hamilton syringe at a 10 µl / min flow rate and a heated EoSnI s iource set to positive mode. GKK-895 was successfully identified at 481.136 m / z. BGP-15 w alasso detected at 279.174 m / z. (Figure 7.)Mass range of 100-800 m / z was set and peaks wrethre r fu investigated using tandem mass spectrometrywith HCD fragmentation. To measure mass spectrum of GKK-895 and its detgiorand / oaxidation products together, in a further experiment 10 mM GKK-895 diluted 100x in 0.1 % foicrm acid / water was prepared and was infused directly into a Thermo Scientific Q Exactive (HRAM m)ass spectrometer using a Hamilton syringe at a 10 µl / min flow rate and a heated ESI ion source to se ptositive mode. Multiple degradation products were identified, including 2 forms that have alryea ddonated their sulfur atoms (465.158 m / z and449.165 m / z) and the oxidized GKK-895 was alsoc dtet de at 497.13 m / z. (Figure 8.)Results Both samples had a base peak at 481.136 m / z conrrdeisnpg to the GKK-895 molecule (M+H = 481.149m / z) as expected. Another molecule with 279.17 w ma / zs also observed that is BGP-15, the precursormolecule and a peak at 157.031 m / z that comes D frMomSO (2M+H). Two small peaks can be identified as products of GKK-895 degradation, one with 4685. a1n5d one with 449.165, where the former haslost one of its sulfur atoms substituted by an oexnyg and the latter that has already released bo ith s ofsulfur atoms substituted by two oxygens. Anotheark p weas also identified at 497.130 that is an oxeidizfrom of GKK-895 having an extra oxygen atom alohneg B t GP-15 backbone based on fragmentationpatterns Measurement of hydrogen sulfide release Filter papers were cut, impregnated with 1% leaedta atce and dried under chemical hood. 5 mg / ml GYY4137 donor molecule was dissolved in DPBS anedn t dhilution series were prepared (5 - 0.03 mg / ml). 6 mg / ml GKK895 was dissolved in 27 mM NaO soHlution. Ph was set to 7.5 with 500 mM sodium-phosphate buffer (pH 7.5) and distilled wr.a Ttehe final concentration of GKK895 was set to 2 mg / ml in 20 mM sodium-phosphate buffer (pH 7.5) a thnedn dilution series were prepared (1 - 0.125 mg / ml).3x200 µl from each solution were pipettnetdo i a 96-well plate and it was covered with thed- lea acetate impregnated paper and icubated in roome treamtupre in the dark for 5h, 24h and 29h. ANCA vasculitis animal model Breeding pairs of Black 6 recombinase-activatinnge g-2e–deficient (Rag2– / –) mice and MPO-deficient (Mpo– / – mice) were purchased from Jackson Laboireasto arnd maintained by the Department of Experimental Pharmacology of the National Instituofte Oncology (ethical decision: PE / EA / 00419- 4 / 2022). Mice that were 10-14 weeks old were usne adll i experiments and different groups were used as presented in the table below (Table 1). Table 1 – Mice groups used in the experiments Control anti-MPO splenocytes Splenocytes PBS 5 19+6 150 µmol / kg GYY4137 5 19 90 µmol / kg GKK-895 - 6 Animal experiments were carried out according tolk’ Fsa published protocol [Xiao, H., et al., Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest, 20021.10(7): p. 955-63]. MPO knockout mice were immunized with mouse MPO based on the following protocol. On d,a 2y010 µl of 20µg murine MPO (mMPO) in totalwith Complete Freud’s Adjuvant were injected to M KPO mice.30-40 µl were injected to the backfootfootpads and 120-160 µl were injected subcutanyeo inus tlhe abdominal region. On day 14, 20 µg mMPO were injected IP with incomplete Freud’s Adajunvt and on day 28 mice were boosted with 20 µg mMPO in DPBS buffer IP.10 days after boostd bl wooas drawn from eye corner and antibody titers were checked by anti-MPO ELISA. If titer were lowic me were boosted again with 20 µg mMPO and titer were checked again 7 days later. If titersre w aeppropriate mice were terminated and splenocytes were isolated. Spleen was removed, gently homoegden iniz RPMI 1640 filtered with 70 µM sterile filter and washed twice with cold RPMI 1640. The remain reindg blood cells were lysed with Red Blood Cell Lysis Buffer according to manufacturer’s instrucntsio. Cells were resuspended in RPMI 1640 in 600 µl. Cells were counted using trypan blue solution, t tohteal cell count varied between 3x71 a0nd 6x107. Splenocytes derived from each MPO deficient mouesree w injected - / - immunodeficient mice intravenously. The pair were treated with 9m0o µl / kg GKK895 and 150 µmol / kg GYY4137 or DPBS 3 times a week for 3 weeks. After 3 weeks m wiecere euthanized with isoflurane, kidney tissue samples were fixed in 10% paraformaldehyde anda preredp for light microscopy analysis. Kidney samples were stained with H&E and periodic acidif Sf scthain. Effect of GYY4137 molecule in ANCA-vasculitis mouse modelRag 2 deficient mice that received splenocytes f crom ntrol or BSA immunized MPO deficient mice didt nodevelop inflammation in their kidneys. Rag 2 deefnicti mice that received splenocytes from MPO immeudniz MPO deficient mice developed symptoms that arer dibeesdc above with great variance. The kidney samplesof 2 different mouse pairs (MPO16,MPO18) showedt t th ea GYY4137 treated samples had elevated levelsof inflammation compared to the untreated samp Olense. individual from 2 different pairs (MPO5, MPO7)have passed away in 24 hours after intravenoucsti ionnje of splenocytes, therefore we have excludetdh bo pairs from the experiment. Semiquantitative comtpivaera analysis of mouse pairs that developed symsptom upon adoptive transfer of splenocytes showed dsimheindi symptoms of renal vasculitis as a result of GYY4137 treatment. Treated mice showed 64,9% lo nwuemrber of affected glomeruli compared to their non treated pairs (excluding MPO3, MPO16 and MPO18g)u (rFei 3). Effect of GKK895 molecule in ANCA-vasculitis mouse model; comparison of GYY4137 and GKK-895 treatment in mouse kidney samples. Mice received isolated splenocytes from MPO-immeudniz MPO knockout mice. The connected samples indicate the pairs of mice receiving spcleytneos from the same MPO KO mouse. Mice that were treated with GKK895 black circles) show dimshineid levels of affected glomeruli compared to control samples (black squares). (Figure 4) To compare GYY4137 and GKK-895 treatment in mouidsene ky, kidney samples from the ANCA vasculitis mouse models were prepared for histo alongaylysis and evaluated with light spectroscopy. The percentage of affected glomeruli in treatedp sleasm were calculated compared to their control pairs. Samples that were treated with 150 µmol / YkgY4 G137 (labeled with dark gray) and also showed decreased renal symptoms were depictedis o fnig tuhre with an average decrease in affected glomeruli of 64.9 %. Samples that were treated w90ith µmol / kg GKK-895 (labeled with light gray) showed an average of 56.9 % decrease in affecotemde grulli compared to control pairs. (Figure 5) Mice that received control splenocytes did not sh reonwal symptoms of ANCA vasculitis. Healthy (Rag2 - / - immunodeficient m)ice and H2S serum level measurement Healthy mice Rag2 - / - immunodeficient mice, seev aeb,o were used for IP administration experiments and held and treated as described above, mutataisn mdius. Blood samples were collected from eye corner ofe m aifcter isoflurane anesthesia and incubated for 30 minutes at room temperature. The coagulated bloamodpl ses were centrifuged at 2000g for 10 minutesthen the sera were collected into fresh tubes μ.l 2 o5f serum samples were mixed with μ 6l6 of a premixedreagent-buffer solution (65 μl 200 mM HEPES pH 8.2 + 1 μl 100 mM MBB in ACN) followed immediately by vigorous vortexing. After exactly 1m0in at 20.0°C the reaction was quenched by the addition of 5 μl 50 % TCA (w / v) and vortexed vigorously. The prpeitcaited proteins were removed bycentrifugation at 3000 g for 5 min and the supearn ta wt as transferred to autosampler vials and hteld a4°C. Calibration samples for quantitation were parep d the same way using a standardized NaHSsolution and diluted further after the derivatiozant.i For the HPLC measurement 3 µl was injected on a Phenomenex Luna C18(2) 250x2mm 3µm column usinragd aie gnt elution profile using water with 0.1% TFA and acetonitrile with 0.1% TFA.The excitationav welength of the fluorescence detector was set at 390 nm and the emission wavelength at 475 nm. Trehpea pration was carried out as before with modified chromatography setup [Ditroi, T., et a Cl.o,mprehensive analysis of how experimental parameters affect H2S measurements by the monobromobimane method. Free Radic Biol Med, 2019. 136: p. 146-158.]. Measurement of serum sulfide concentrations of mice treated with GYY4137 or GKK-895 Measurement of serum sulfide concentrations of m treicaeted with GYY4137 or GKK-895 Mice were treated with 150 µmol / kg GYY4137 or 110 µmol / kg G-K8K95 intraperitoneally. Blood samples were collected from the eye corner after isoflurane athneessia at the indicated time points. All blood samples were incubated at room temperature forin 3u0t mes then centrifuged at 2000 g for 10 minutes. The concentrations of hydrogen sulfide were meads wuriteh the monobromobimane assay from the collected blood serum sampl [e Dsitroi, T., et al., Comprehensive analysis of how experimental parameters affect H2S measurements by the monobromobimane method. Free Radic Biol Med, 2019. 136: p.146-158.]. Treatment with both GYY4137 a GnKdK-895 resulted in significant elevation of sulfide concentrations in the circulation with GK8K9-5 causing higher measured sulfide values at 2 and 4 hours after injection (Figure 2). The incereda eslevation of the sulfide concentration caused by GKK-895 was also significantly higher than the ealteiovn resulted by the administration of GYY4137 (Figure 6).

Claims

CLAIMS 1. A compound having formula (I)wherein R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloalkyl, cycloalleknye or a heterocycle, in a particular embodiment a N and / or O containing heterocycle, in particu ala 6r membered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R5,if any, may be selected from H, a 5 to 10 memb,e prreedferably a 6 membered heterocy,c alned C1- 4 alkyl, R6, R7, R8, R9 and R10, are, independently from each other, selected fHro,m C1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OR11 wherein R11 is C1-4 alkyl, or each of R6, R7, R8, R9 and R10 is H or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

2. The compound for use according to cla 1im wherein said compound has general formula II.1 or (II.1’)R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloa,l cky cl loalkylene or a heterocycle, in aparticular embodiment a N and / or O containing hoectyecrle, in particular a 6 membered, N and / or O containing heterocycle, preferably anh al tipic heterocycle,R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N- containing aromatic heterocycle, preferably pyr,id aynld / or preferably wherein N is in the ortho position, R4 is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H and a 5 to 10 meermedb, preferably a 6 membered heterocycle and C1-4 alkyl wherein in formula (II.1) R6, R8, and R10, is selected from the group consisting of C H1,-4 alkyl, C1-4 alkoxy, halogenide, in particular H and C1-4 alk,oxy wherein in a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

3. The compound for use according to cla 2im wherein said compound has general formula II.2R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloa,l cky cl loalkylene or a heterocycle, in aparticular embodiment a N and / or O containing hoectyecrle, in particular a 6 membered, N and / or O containing heterocycle, preferably anh al tipic heterocycle,R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N- containing aromatic heterocycle, preferably pyr,id aynld / or preferably wherein N is in the ortho position, R4 is H or a C1-4 alkyl, preferably H, wherein in formula (II.2) R7, R8, and R9, is selected from the group consisting of C H1,-4 alkyl, C1-4 alkoxy, halogenide, in particular H and C1-4 alko wxhyerein in a preferred embodiment at least one of and l oera ast two of R6, R8, and R10, and / or at leastone of and or at least two of7, R R8, and R9, is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

4. The for use to cla wherein said compound has general formula III(III) X is N or CH, preferably N, R1 is H or a C1-4 alkyl, preferably H,R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R6, R7, R8, R9 and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OMe or each of6 R, R7, R8, R9 and R10 is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

5. The compound for use according to cla 3i,m wherein said compound has general formula IVR1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 membereedro hceytcle, in a particular embodiment a N and / or O containing heterocycle, in particular m ae 6mbered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R4 is H or a C1-4 alkyl, preferably H, R6, R7, R8, R9 and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OMe or each of6 R, R7, R8, R9 and R10 is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. Q and U are, independently, selected from N and CH, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

6. The compound for use according to any of cla 3im tos 5, wherein said compound has formula (V)(V) or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

7. The compound for use according to any of cla 1im tos 6, for use in the treatment of a disorder.

8. The compound for use according to any of cla 1im tos 7, for use in the treatment of a disorder wherein said disorder is selected from the grounpsi csoting of neoplastic disorders, proliferative disorders, neurodegenerative disorders, neuro dloisgeicases, infections, metabolic diseases, oxidativestress diseases, preferably a mitochondrial func dti soease, autoimmune diseases, neuropathies,traumatic brain injury, nephrotoxicity. 9 The compound for use according to any of cla 1im tos 8, for use in the treatment of a disorder wherein said disorder is selected from a condi ltiinokned to inhibition of poly(ADP-ribose) polymerases (PARPs), the inhibition of the compo wunitdh signaling molecules selected from the group consisting of protein kinase B (Akt), c-Ju-nte Nrminal kinase (JNK) and extracellular signal- regulated kinase (ERK), interaction of the compo wunitdh chaperons or stress-proteins, a folding- trafficking disease.

10. The compound for use according to any of cla 1im tos 9, for use in the treatment of an autoimmune inflammatory disorder, preferably - inhibiting neutrophil granulocyte activation bnyt ai-MPO antibodies of mammalian subject having AAV (MPO-ANCA associated vasculitis) - inhibiting neutrophil degranulation in the mammianal subject having AAV, - inhibiting neutrophil priming (by translocationf A oNCA antigen MPO) in the mammalian subject having AAV, and / or - preventing kidney damage / protecting the kidne tyhe in mammalian subject having AAV. ANCA vasculitis, preferably MPO-related ANCA vaslictius.

11. A pharmaceutical composition comprising the coumnpdo for use according to any of claims 1 to 10, preferably according to any of claims 7 to o 1r0 a, pharmaceutically acceptable salt and / or seolvat and / or complex thereof, and a pharmaceuticallyp atcacbele excipient.

13. The pharmaceutical composition comprising thep co umnd for use according to any of claims 11to 14, wherein said composition is protected froigmht l, moisture and decay to form2S H during storage.

14. The pharmaceutical composition comprising2S a H donor compound for use according to any of claims 11 to 13, said composition being formulated for intraveno audsministration.

15. The pharmaceutical composition comprising2S a H donor compound for use according to to any of claims 11 to 13, said composition being formulated for intraveno audsministration.

16. A method for the preparation of a compound acicnogrd to any of claims 1 to 10, preferably claim 10, comprising the step wherein a Lawesson-type reagent according to formula (X r)ea iscted, preferably opened up, with a hydroxy- amidoxime compound of formula (VIII) a O-nucleopehil5wherein R1 is H or a C1-4 alkyl, preferably H, R2 is a 5 to 10 membered, preferably a 6 memberetudra (stead or unsaturated, preferably saturated) cyclic compound, preferably a cycloalkyl, cycloalleknye or a heterocycle, in a particular embodiment a N and / or O containing heterocycle, in particu ala 6r membered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R6, R7, R8, R9 and R10, are, independently from each other, selected fHro,m C1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 is H; preferably R8 is -OR11 wherein R11 is C1-4 alkyl, or each of R6, R7, R8, R9 and R10 is H.

17. The method according to clai 1m6 whereinthe Lawesson-type reagent is as defined in clai,m an 1d6 the hydroxy-amidoxime compound is a compound having the structure of general formuXla), (Iof gen foerrmalula (III), or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof, wherein X is N or CH, preferably N, R1 is H or a C1-4 alkyl, preferably H, R3 is a 5 to 10 membered, preferably a 6 memberemda atrico heterocycle, preferably a N-containingaromatic heterocycle, preferably pyridyl, and / oerf per ably wherein N is in the ortho position,R4 is H or a C1-4 alkyl, preferably H, R5 may be selected from H, a 5 to 10 membered, parbelfyer a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9 and R10, (as the case may be) is selected from C1 H-,4 alkyl, C1-4 alkoxy, halogenide, wherein at least two of R6, R7, R8, R9 and R10 (as the case may be) is H; preferab8ly is R -OMe or each of6 R, R7, R8, R9 and R10 is H¸ or the Lawesson-type reagent is as defined in clai,m an 1d6 the hydroxy-amidoxime compound is a compound having the structure of general formul)a, (Xand the resulting compound is a compound of gen foerrmalula (IV), or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof, wherein R1is H or a C1-4 alkyl, preferably H, R2is a 5 to 10 membered, preferably a 6 membereedro hceytcle, in a particular embodiment a N and / or O containing heterocycle, in particular m ae 6mbered, N and / or O containing heterocycle, preferably an aliphatic heterocycle, R4is H or a C1-4 alkyl, preferably H, R5, if any, may be selected from H, a 5 to 10 memdb,e prereferably a 6 membered heterocy,c Cle1-4 alkyl R6, R7, R8, R9and R10, is selected from H C,1-4 alkyl, C1-4 alkoxy, halogenide, wherein at least two ofR6, R7, R8, R9 and R10 is H; preferably R8 is -OMe or each of6 R, R7, R8, R9 and R10 is H, or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof. Q and U are, independently, selected from N and CH.

18. The method according to any of claim 16s to 17, wherein the reaction is carried out in apolar solvent, the reaction is carried out at a temperature of 500 t°C, preferably 10 to 40°C, preferably 15 to °C 30, preferably at room temperature, e.g.20 to 25°C and the reaction is carried out at under intert atmoesrep,h preferably under nitrogen atmosphere.

19. The method according to any of claim 16s to 18 wherein Lawesson reagent (1) is opened with BGP-15O (2-[)3 (-(1-piperidinyl)-2-hydroxi-1- propyl]nicotinamide-amide-oxime) itself as O-nuocplehile,or a pharmaceutically acceptable salt and / or seol avnadt / or complex thereof.

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