5,5-condensed arylene or heteroarylene hepatitis c virus inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to 5,5-condensed heteroarylene compounds IIIB, where U2, V1, V2 and W1 are selected from O, N, NH, S or CR3a; U1, W2, X1 and X2 represent C or N; R1 and R2 represents hydrogen, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a or -C(O)OR1a; R3a represents hydrogen or R3; R3 represents halogen or -C(O)OR1a; L1 and L2 are such as given in invention formula, each Z1 and Z2 represents bond or -O-; each Rla, R1b and R1c represents hydrogen, C1-6 alkyl or C6-14 aryl; or Rlb and Rlc together with N atom, which they are bound to, form 5-6-membered heterocyclyl; q, r, s, t and u equal 1. Invention also relates to pharmaceutical compositions, containing 5,5-condensed heteroarylene compounds, and methods of treating or preventing HCV infection.

EFFECT: 5,5-condensed heteroarylene derivatives, possessing inhibiting activity with respect to hepatitis C virus.

43 cl, 42 ex

 

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority on provisional application for U.S. patent No. 61/288207, filed December 18, 2009; and 61/371634, filed August 6, 2010; the contents of which are incorporated herein by reference in its entirety.

The technical field to which the invention relates

The present invention relates to 5,5-condensed heteroarenes compounds - inhibitors of hepatitis C virus, pharmaceutical compositions containing these compounds, and methods for their preparation. Also the proposed methods of their use for the treatment of HCV infection in the host in need of such treatment.

The LEVEL of TECHNOLOGY

It is known that hepatitis C virus (HCV) is the cause of at least 80% of cases of posttransfusion hepatitis and a large number of cases of acute sporadic hepatitis (Kuo et al., Science 1989, 244, 362-364; Thomas, Curr. Top. Microbiol. Immunol. 2000, 25-41). Preliminary data also shows that HCV is the cause of "idiopathic" chronic hepatitis, "cryptogenic" cirrhosis, and probably hepatocellular carcinoma unrelated to other hepatitis viruses such as hepatitis B virus (Di Besceglie et al., Scientific American, 1999, October, 80-85; Boyer et al., J. Hepatol. 2000, 32, 98-112).

HCV is a virus with the envelope containing the genome with positive�iloveu single-stranded RNA approximately from 9.4 T. D. (Kato et al., Proc. Natl. Acad. Sci. USA 1990, 87, 9524-9528; Kato, Acta Medica Okayama, 2001, 55, 133-159). The viral genome consists of 5'-netransliruemoi region (UTR), a long open reading frame that encodes a polyprotein precursor of approximately 3011 amino acids, and a short 3'-UTR. 5'-UTR is the most preserved part of the HCV genome and are important for the initiation and regulation of translation of the polyprotein. Translation of the HCV genome is initiated by cap-independent mechanism known as internal ribosome entry. This mechanism involves the binding of ribosomes to the RNA sequence, known as the sign-in site internal ribosome (IRES). Recently it was found that the structure of the pseudonode RNA is an essential structural element of the HCV IRES. Viral structural proteins include nucleocapsids from crustal protein (C) and two membrane glycoprotein, E1 and E2. HCV also encodes two proteases, zinc-dependent the metalloproteinases encoded by the region of the NS2-NS3, and semipretioase encoded in the NS3 region. These proteinase required for cleavage of specific regions of the polyprotein precursor with the formation of the Mature peptides. The carboxyl half of nonstructural protein 5, NS5B, contains RNA-dependent RNA polymerase. The function of the remaining nonstructural proteins, NS4A and NS4B, and NS5A function (aminobenzene half of nonstructural protein 5) remain unknown.

In on�this time in the most effective HCV therapy use a combination of alpha interferon and ribavirin, that gives a long lasting effect in approximately 40% of patients (Poynard et al., Lancet 1998, 352, 1426-1432). The results of recent clinical trials demonstrate that pegylated alpha-interferon is more effective than unmodified alpha-interferon as monotherapy. However, even with experimental therapeutic regimens, including the combination of pegylated alpha interferon and ribavirin, a substantial portion of patients do not have a prolonged decrease in viral load (Manns et al., Lancet 2001, 358, 958-965; Fried et al., N. Engl. J. Med. 2002, 347, 975-982; Hadziyannis et al., Ann. Intern. Med. 2004, 140, 346-355). Thus, there is a clear and unmet need to develop effective therapies for HCV infection.

Summary of the INVENTION

The present invention relates to the compound of the formula I:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

s, t, A, and E is an (i), (ii) or (iii):

(i) s is 1 or 2; t is 1; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C2-6 akinyan-C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed Allen, C2-6 akinyan-5,6 -�and 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) s is 1 or 2; t is 0; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan-R3a, C3-7 cycloalkyl-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

(iii) s is 0; t is 1; A is 5,5-condensed heteroaryl-R3a; E is a C2-6 akinyan, C3-7 cycloalkyl, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

each R1 and R2 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S()NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 that are attached to the same ring, together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

each L1 and L2 independently represents (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C6-14 Allen-heteroaryl, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-; provided that Allen and Allenova group, C6-14 Allen-heteroaryl not represent a 5,6 - or 6,6-condensed Allen, and heteroaryl and heteroarenes group in C6-14 Allen-heteroaryl, heteroaryl-C1-6-alkylene, heteroaryl-C2-6-alkeline and heteroaryl-C2-6-alkylamine not represent a 5,6 - or 6,6-condensed heteroaryl;

each Z1 and Z2 is independently a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d-NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

each n and p independently represents an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

each q and r independently represents an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

The present invention also relates to a compound of the formula I:

or its individual Enan�imeru, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

s, t, A, and E is an (i), (ii) or (iii):

(i) s is 1; t is 1; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) s is 1; t is 0; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

(iii) s is 0; t is 1; A is 5,5-condensed heteroaryl-R3a; E is a C2-6 akinyan, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

R1 and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a R�ulation independently a hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z1 and Z2 are, each independently, a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

n and p are, each independently, an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

q and r are, each independently, an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc-NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one embodiment, the implementation of one two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

The present invention relates to the compound of formula IA:

or its enantiomer, a racemic mixture, a mixture of dieste�of pomerov or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

A represents the 5,5-condensed arisen or 5,5-condensed heteroaryl;

t and E represent (i) or (ii):

(i) t is 1; and E represents a C2-6 akinyan, C6-14 Allen, C2-6 akinyan-C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed Allen, C2-6 akinyan-5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) t is 0; and E represents C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

R1, R1A and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(ONR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C6-14 Allen-heteroaryl, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z2 is a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they prise�United, form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

p is an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

r is an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three �or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

The present invention relates to the compound of formula IA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

A represents the 5,5-condensed arisen or 5,5-condensed heteroaryl;

t and E represent (i) or (ii):

(i) t is 1; and E represents a C2-6 akinyan, C6-14 aralen or heteroaryl; ol� condition, that E represents a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) t is 0; and E represents C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

R1, R1A and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3 - cycloalkyl, C6-14 Allen, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z2 is a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

p is an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

r is an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl�, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, Goethe�auril and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

The present invention relates to the compound of formula IB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

U1, U2, V1, V2, W1 and W2 are each independently C, N, O, S, CR3a, or NR3a;

X1 and X2 are, each independently, C or N;

each R1 and R2 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycleall�l, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 that are attached to the same ring, together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; and broken line (in each group indicates the point of attachment through which the group is associated withor; and where T3 is a bond, C, N, O, S, CR3a, or NR3a; U3, V3, W3, and X3 are each independently C, N, O, S, CR3a, or NR3a; and Y3 represents C or N;

each Z1 and Z2 is independently a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c-C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

each n and p independently represents an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7;

each q and r independently represents an integer equal to 1, 2, 3 or 4;

s and t represent each independently an integer of 0, 1 or 2; and

u is an integer equal to 1 or 2;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, cycloalkyl, aryl, aralkyl, heteroaryl and heterocyclyl optionally substituted by one or more substituents Q, where each Q is independently selected from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one embodiment osuwestvlenieaj.in, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are joined�report contains, form heterocyclyl.

The present invention provides pharmaceutical compositions containing a compound described herein, e.g. a compound of formula I, IA or IB, including a single enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; in combination with one or more pharmaceutically acceptable inert excipients or carriers.

In addition, the present invention provides a method of treating or preventing HCV infection, which comprises administering to the subject a therapeutically effective amount of a compound described herein, e.g. compounds of formula I, IA or IB, including a single enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug.

Additionally, the present invention provides a method for the treatment, prevention or attenuation of one or more symptoms of a liver disease or disorder associated with an HCV infection, comprising administering to the subject a therapeutically effective amount of a compound described herein, e.g. compounds of formula I, IA or IB, including a single enantiomer, a racemic mixture, smalldatetime or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug.

The present invention provides a method for inhibiting replication of a virus in the "host" organism, which includes the introduction in the "host" organism a therapeutically effective amount of a compound described herein, e.g. compounds of formula I, IA or IB, including a single enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug.

Detailed description of the invention

To facilitate understanding of the description below are definitions of some terms.

Generally, as used herein, the terminology and methodology of laboratory research in the field of organic chemistry, medicinal chemistry, and pharmacology described herein are well known and are widely used in the field. If not defined otherwise, all technical and scientific terms used herein generally have the same values, which are usually used by experts in the field, belongs to this description.

The term “subject” refers to an animal, including, but not limited to, a Primate (e.g., human), cow, pig, sheep, goat, horse, dog, cat, rabbit, CRISIL mouse. The terms “subject” and “patient” are used interchangeably herein in reference, for example, in one of the embodiments to person.

The term “host” refers to a unicellular or multicellular organism in which the virus can replicate, including, but not limited to, a cell, cell line and animal, such as man.

The terms “treat”, “treating” and “treatment” refer to reduction or elimination of the disorder, disease or condition, or one or more symptoms associated with the disorder, disease or condition; or reduction or elimination of the causes(s) of the disorder, disease or condition.

The terms “prevent”, “prevention” and “prevention” refers to a method of deter and/or prevent a disorder, disease or condition, and/or its accompanying symptoms; prevent the acquisition by the subject of the disorder, disease or condition; or reducing the risk of acquiring subject of a disorder, disease or condition.

The term “therapeutically effective amount” means an amount of compound that when administered is effective to prevent the development or attenuate, to some extent, of one or more symptoms of the disorder, Zabol�tion or condition exposed to treatment. The term “therapeutically effective amount” also refers to the amount of compound which is sufficient to cause the biological or medical response of a biological molecule (e.g., protein, enzyme, RNA or DNA), cell, tissue, system, animal or human that is necessary for the researcher, veterinarian, medical doctor or Clinician.

The term “IC50” or “EC50” refers to the amount, concentration or dose of a compound required for 50% inhibition of the maximum response in the study that determines this response.

The term “CC50” refers to the amount, concentration or dose of a compound that causes 50% reduction in survival of the host. In specific embodiments, CC50 compound is an amount, concentration or dose of a compound required to reduce cell survival by 50% compared with cells treated with the compound.

The term “pharmaceutically acceptable carrier,” “pharmaceutically acceptable excipient,” “physiologically acceptable carrier” or “physiologically acceptable excipient” refers to a pharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler, diluent, solvent or encapsulating ve�the society. In one embodiment, the implementation of each component is “pharmaceutically acceptable” in the sense that it is compatible with other ingredients of the pharmaceutical compositions and are suitable for use in contact with tissue or organ of humans and animals without causing excessive toxicity, irritation, allergic response, immunogenicity, or other problems or complications, appropriate reasonable ratio favourable effect/risk. Cm. Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, PA, 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, FL, 2009.

The term “about” or “approximately” means an acceptable deviation from a specific value defined by an ordinary person skilled in the art, which depends, in part, on the method of measurement or determination of value. In specific embodiments, the term “about” or “approximately” means a deviation within 1, 2, 3, or 4 standard deviations. In specific embodiments, the term “about” or “approximately” means deviation within 50%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0,5% or 0.05% of a given value or range.

The terms “active ingred�UNT” and “active substance” refer to the mix, which is administered alone or in combination with one or more pharmaceutically acceptable inert excipients to a subject to treat, prevent or ameliorate one or more symptoms of a condition, disorder or disease. As used herein, “active ingredient” and “active substance” may be an optically active isomer or isotopic variant of a compound described herein.

The terms “medicament”, “therapeutic agent” and “chemotherapeutic agent” refer to a compound or pharmaceutical composition that is administered to a subject to treat, prevent or ameliorate one or more symptoms of a condition, disorder or disease.

The term “alkyl” denotes a linear or branched saturated monovalent hydrocarbon radical, where alkyl may optionally be substituted by one or more substituents Q as described herein. For example, C1-6 alkyl refers to a linear saturated monovalent hydrocarbon radical containing from 1 to 6 carbon atoms, or branched saturated monovalent hydrocarbon radical containing from 3 to 6 carbon atoms. In specific embodiments, alkyl is a linear saturated Mont�valent hydrocarbon radical, which contains from 1 to 20 (C1-20), from 1 to 15 (C1-15), from 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated monovalent hydrocarbon radical containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 alkyl groups are also referred to as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including all isomeric forms), n-propyl, isopropyl, butyl (including all isomeric forms), n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl (including all isomeric forms), and hexyl (including all isomeric forms).

The term “alkylene” refers to linear or branched saturated divalent hydrocarbon radical, where alkylene may optionally be substituted by one or more substituents Q as described herein. For example, C1-6 alkylene refers to a linear saturated divalent hydrocarbon radical containing from 1 to 6 carbon atoms, or branched saturated divalent hydrocarbon radical containing from 3 to 6 carbon atoms. In specific embodiments, alkylene is a linear saturated divalent hydrocarbon radical that contains from 1 to 20 (C1-20), from 1 to 15 (C1-15), from 1 to 0 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated divalent hydrocarbon radical containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 alkylene groups are also referred to as “low alkylen.” Examples alkilinity groups include, but are not limited to, methylene, ethylene, propylene (including all isomeric forms), n-propylene, isopropylene, butylene (including all isomeric forms), n-butylene, isobutylene, tert-butylene, pentile (including all isomeric forms), and exile (including all isomeric forms).

The term “heteroalkyl” denotes a linear or branched saturated divalent hydrocarbon radical that contains one or more heteroatoms, each independently selected from O, S and N, in the carbon chain. For example, C1-6 heteroalkyl denotes a linear saturated divalent hydrocarbon radical containing from 1 to 6 carbon atoms, or branched saturated divalent hydrocarbon radical containing from 3-6 carbon atoms. In specific embodiments, heteroalkyl is a linear saturated divalent hydrocarbon radical that contains from 1 to 20 (C1-20), from 1 to 15 (C1-15), from 1 to 10 (C1-10), or 1 to 6 (C1-6) carbon atoms, or branched saturated dvwhv�turbulent hydrocarbon radical, containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. As used herein, linear C1-6 and branched C3-6 heteroarenes groups are also referred to as “low heteroalkyl.” Examples heteroarenes groups include, but are not limited to, -CH2O-, -CH2OCH2-, -CH2CH2O-, -CH2NH-, -CH2NHCH2-, -CH2CH2NH-, -CH2S-, -CH2SCH2 -, and-CH2CH2S-. In specific embodiments, heteroalkyl may also be optionally substituted by one or more substituents Q as described herein.

The term “alkenyl” denotes a linear or branched monovalent hydrocarbon radical, which contains one or more, in one of embodiments one to five, in another embodiment, one implementation, the carbon-carbon double(s) relationship(s). The alkenyl may be optionally substituted by one or more substituents Q as described herein. The term “alkenyl” embraces radicals having a “CIS” or “TRANS” configuration or a mixture thereof, or alternatively, “Z” or “E” configuration or a mixture thereof, that is taken into account by the person skilled in the art. For example, C2-6 alkenyl refers to a linear unsaturated monovalent hydrocarbon radical containing from 2 to 6 carbon atoms, or a branched unsaturated monovalent hydrocarbon radical, �aderrasi from 3 to 6 carbon atoms. In specific embodiments, the alkenyl is a linear monovalent hydrocarbon radical containing from 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10) or 2 to 6 (C2-6) carbon atoms, or a branched monovalent hydrocarbon radical containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, propene-1-yl, propene-2-yl, allyl, butenyl and 4-methylbutanal.

The term “albaniles” denotes a linear or branched divalent hydrocarbon radical, which contains one or more, in one of embodiments one to five, in another embodiment, one implementation, the carbon-carbon double(s) relationship(s). Albaniles may be optionally substituted by one or more substituents Q as described herein. The term “albaniles” embraces radicals having a “CIS” or “TRANS” configuration or a mixture thereof, or alternatively, “Z” or “E” configuration or a mixture thereof, that is taken into account by the person skilled in the art. For example, C2-6 albaniles refers to a linear unsaturated divalent hydrocarbon radical containing from 2 to 6 carbon atoms, or a branched unsaturated divalent hydrocarbon radical containing from 3 to 6 carbon atoms. In con�specific embodiments, albaniles is a linear divalent hydrocarbon radical, containing from 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10) or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. Examples alkenylamine groups include, but are not limited to, ethenylene, allele, propylen, butylen and 4-methylbutane.

The term “heteroalkyl” denotes a linear or branched divalent hydrocarbon radical, which contains one or more, in one of embodiments one to five, in another embodiment, one implementation, the carbon-carbon double(s) relationship(s), and which contains one or more heteroatoms, each independently selected from O, S and N, in the carbon chain. Heteroalkyl may be optionally substituted by one or more substituents Q as described herein. The term “heteroalkyl” embraces radicals having a “CIS” or “TRANS” configuration or a mixture thereof, or alternatively, “Z” or “E” configuration or a mixture thereof, that is taken into account by the person skilled in the art. For example, C2-6 heteroalkyl refers to a linear unsaturated divalent hydrocarbon radical containing from 2 to 6 carbon atoms, or a branched unsaturated divalent hydrocarbon radical, containing�th from 3 to 6 carbon atoms. In specific embodiments, heteroalkyl is a linear divalent hydrocarbon radical containing from 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10) or 2 to 6 (C2-6) carbon atoms, or a branched divalent hydrocarbon radical containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. Examples heterogeniety groups include, but are not limited to, -CH=CHO-, -CH=CHOCH2-, -CH=CHCH2O-, -CH=CHS-, -CH=CHSCH2-, -CH=CHCH2S - or-CH=CHCH2NH-.

The term “alkynyl” denotes a linear or branched monovalent hydrocarbon radical, which contains one or more, in one of embodiments one to five, in another embodiment, one implementation, the carbon-carbon triple(s) relationship(s). Alkynyl may be optionally substituted by one or more substituents Q as described herein. For example, C2-6 alkynyl refers to a linear unsaturated monovalent hydrocarbon radical containing from 2 to 6 carbon atoms, or a branched unsaturated monovalent hydrocarbon radical containing from 3 to 6 carbon atoms. In specific embodiments, alkynyl is a linear monovalent hydrocarbon radical containing from 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10) or 2 to 6 (C2-6) carbon atoms, or branched monova�entry hydrocarbon radical, containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. Examples etkinlik groups include, but are not limited to, ethinyl (-C≡CH), PROPYNYL (including all isomeric forms, e.g., 1-PROPYNYL (-C≡CCH3) and propargyl (-CH2C≡CH), butynyl (including all isomeric forms, e.g., 1-Butin-1-yl and 2-butyn-1-yl), pentenyl (including all isomeric forms, e.g., 1-Pentin-1-yl and 1-methyl-2-Butin-1-yl) and hexenyl (including all isomeric forms, e.g., 1-hexyn-1-yl).

The term “akinyan” denotes a linear or branched divalent hydrocarbon radical, which contains one or more, in one of embodiments one to five, in another embodiment, one implementation, the carbon-carbon triple(s) relationship(s). Akinyan may be optionally substituted by one or more substituents Q as described herein. For example, C2-6 akinyan refers to a linear unsaturated divalent hydrocarbon radical containing from 2 to 6 carbon atoms, or a branched unsaturated divalent hydrocarbon radical containing from 3 to 6 carbon atoms. In specific embodiments, akinyan is a linear divalent hydrocarbon radical containing from 2 to 20 (C2-20), 2 to 15 (C2-15), 2 to 10 (C2-10) or 2 to 6 (C2-6) carbon atoms, or branched of dvwhv�turbulent hydrocarbon radical, containing from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or 3 to 6 (C3-6) carbon atoms. Examples elchininova groups include, but are not limited to, echinilin, propylen (including all isomeric forms, e.g., 1-propylen and propargyl), Butyrin (including all isomeric forms, e.g., 1-Butin-1-yl and 2-butyn-1-ilen), pentikinen (including all isomeric forms, e.g., 1-Pentin-1-yl and 1-methyl-2-butyn-1-ilen), and hexenlied (including all isomeric forms, e.g., 1-hexyn-1-yl).

The term “cycloalkyl” refers to a cyclic monovalent hydrocarbon radical, which may be optionally substituted by one or more substituents Q as described herein. In one embodiment, the implementation cycloalkyl groups can be saturated or unsaturated but non-aromatic, and/or United by bridging connection and/or not connected by bridging connection and/or condensed bicyclic group. In specific embodiments, cycloalkyl contains from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or from 3 to 7 (C3-7) carbon atoms. Examples cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decaline and and�amantel.

The term “cycloalkyl” refers to divalent cyclic hydrocarbon radical, which may be optionally substituted by one or more substituents Q as described herein. In one embodiment, the implementation cycloalkyl groups can be saturated or unsaturated but non-aromatic, and/or United by bridging connection and/or not connected by bridging connection and/or condensed bicyclic group. In specific embodiments, cycloalkyl contains from 3 to 20 (C3-20), 3 to 15 (C3-15), 3 to 10 (C3-10) or from 3 to 7 (C3-7) carbon atoms. Examples cycloalkenes groups include, but are not limited to, cyclopropyl (e.g., 1,1-cyclopropyl and 1,2-cyclopropyl), cyclobutyl (e.g., 1,1-cyclobutyl, 1,2-cyclobutyl or 1,3-CYCLOBUTANE), cyclopentene (e.g., 1,1-cyclopentyl, 1,2-cyclopentyl or 1,3-cyclopentane), cyclohexene (e.g., 1,1-cyclohexyl, 1,2-cyclohexyl, 1,3-cyclohexyl or 1,4-cyclohexyl), Cycloheptane (e.g., 1,1-Cycloheptane, 1,2-cycloheptadiene, 1,3-cycloheptadiene or 1,4-Cycloheptane), declinein and Adamantine.

The term “aryl” refers to a monovalent monocyclic aromatic group and/or monovalent polycyclic aromatic group that contains at least one aromatic �paradnoe ring. In specific embodiments, the aryl contains from 6 to 20 (C6-20), from 6 to 15 (C6-15) or from 6 to 10 (C6-10) ring atoms. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, fluorenyl, azulene, antril, tenantry, pyrenyl, biphenyl and terphenyl. Aryl also refers to bicyclic or tricyclic carbon rings, where one of the rings is aromatic, and others may be saturated, partially unsaturated or aromatic, for example, dihydronaphtho, indenyl, indanyl or tetrahydronaphthyl (tetralinyl). In particular embodiments, aryl may be optionally substituted by one or more substituents Q as described herein.

The term “Allen” refers to a divalent monocyclic aromatic group and/or a divalent polycyclic aromatic group that contains at least one aromatic carbon ring. In specific embodiments, Allen contains from 6 to 20 (C6-20), from 6 to 15 (C6-15) or from 6 to 10 (C6-10) ring atoms. Examples arenovich groups include, but are not limited to, phenylene, naftilan, fluorenyl, azulene, entrylen, phenanthrolin, phrenilin, biphenylene and terminalen. Allen also refers to bicyclic or tricyclic carbon ring, where one of the rings is aromatic and the other mo�ut to be rich, partially unsaturated or aromatic, for example, dihydronaphthalene, indirilen, indirilen or tetrahydronaphtalene (tetralinyl). In specific embodiments, Allen may be optionally substituted by one or more substituents Q as described herein.

The term “aralkyl” or “arylalkyl” refers to a monovalent alkyl group substituted by one or more aryl groups. In specific embodiments, aralkyl contains from 7 to 30 (C7-30), from 7 to 20 (C7-20) or from 7 to 16 (C7-16) carbon atoms. Examples kalkilya groups include, but are not limited to, benzyl, 2-phenylethyl and 3-phenylpropyl. In specific embodiments, aralkyl optionally substituted by one or more substituents Q as described herein.

The term “heteroaryl” refers to a monovalent monocyclic aromatic group or monovalent polycyclic aromatic group that contains at least one aromatic ring, where at least one aromatic ring contains one or more heteroatoms independently selected from O, S and N, in the ring. Heteroaryl group linked to UTStarcom of the molecule via an aromatic ring. Each ring heteroaryl group can contain one or two O atom, S atom and/or one �about four N atoms, provided that the total number of heteroatoms in each ring is equal to four or less and each ring contains at least one carbon atom. In specific embodiments, heteroaryl contains from 5 to 20, 5 to 15 or from 5 to 10 ring atoms. Examples of monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolin, isoxazolyl, oxadiazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, triazinyl and triazolyl. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzisoxazoles, benzopyranyl, benzothiazolyl, benzotriazolyl, benzothiazyl, benzotriazolyl, benzoxazolyl, properity, imidazopyridines, imidazothiazoles, indolizine, indole, indazole, isobenzofuranyl, isobenzofuranyl, isoindolyl, ethenolysis, isothiazolin, naphthyridines, oxazolopyridine, phthalazine, pteridine, purinol, iridoviridae, pyrrolopyridine, chinoline, chinoxalin, chinazoline, thiadiazolidine and cyanopyridyl. Examples of tricyclic heteroaryl groups include, but are not limited to, acridine, benzoindole, carbazolyl, dibenzofuran, pyrimidinyl, phenanthrolines, phenanthridines, phenarsazine, phenazines, �fenotiazinas, phenoxazines and xantinol. In specific embodiments, heteroaryl may also be optionally substituted by one or more substituents Q as described herein.

The term “heteroaryl” refers to a divalent monocyclic aromatic group or a divalent polycyclic aromatic group that contains at least one aromatic ring, where at least one aromatic ring contains one or more heteroatoms independently selected from O, S and N, in the ring. Each ring heteroarenes group may contain one or two O atom, S atom and/or one to four N atoms, provided that the total number of heteroatoms in each ring is equal to four or less and each ring contains at least one carbon atom. In specific embodiments, heteroaryl contains from 5 to 20, 5 to 15 or from 5 to 10 ring atoms. Examples of monocyclic heteroarylboronic groups include, but are not limited to, TuranAlem, imidazoline, isothiazoline, isoxazoline, oxadiazolyl, oxadiazolyl, oxazolyl, personalen, pyrazoline, pyridazinyl, peridinin, pyrimidinyl, pyrrolidin, thiadiazolyl, thiazoline, Tianjin, tetrazolyl, triazinyl and triazolyl. Examples of bicyclic heteroarylboronic GRU�include p, but not limited to, benzofuranyl, benzimidazolyl, benzisoxazole, benzopyranyl, benzothiadiazine, benzothiazolyl, benzothiazole, benzotriazole, benzoxazole, Phenoperidine, imidazopyridine, imidazothiazole, indolizinyl, indoline, indazole, isobenzofuranyl, isobenzofuran, isoindole, izohinolinove, isothiazoline, naphthyridine, oxazolopyridine, phthalazine, pteridine, phrenilin, pyridopyrimidines, pyrrolopyridine, chinoline, chinoxalin, chinazoline, thiadiazolidine and thienopyridines. Examples of tricyclic heteroarylboronic groups include, but are not limited to, acridine, benzoindole, carbazolyl, dibenzofurane, pyrimidinyl, phenanthroline, phenanthridine, phenarsazine, phenazine, phenothiazinyl, phenoxazine and xantener. In specific embodiments, heteroaryl may also be optionally substituted by one or more substituents Q as described herein.

The term “heterocyclyl” or “heterocyclic” refers to a monovalent monocyclic non-aromatic ring system or a monovalent polycyclic ring system that contains at least one non-aromatic ring, where one or more non-aromatic ring atom�to represent heteroatoms, independently selected from O, S and N; and the remaining ring atoms are carbon atoms. In specific embodiments, heterocyclyl or heterocyclic group contains from 3 to 20, 3 to 15, 3 to 10, 3 to 8, from 4 to 7 or from 5 to 6 ring atoms. Heterocyclyl group linked to the remainder of the molecule via a non-aromatic ring. In specific embodiments, heterocyclyl represents a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may be condensed or linked by bridging connection and in which the nitrogen atoms or sulfur may be optionally oxidized, the nitrogen atoms can be optionally quaternization, and some rings may be partially or fully saturated or aromatic. Heterocyclyl can be attached to the main structure at any heteroatom or carbon atom that results in the formation of stable compounds. Examples of such heterocyclic groups include, but are not limited to, azepines, benzodioxane, benzodioxole, benzofuranyl, benzopyranyl, benzopyranyl, besttravelforyou, betterregulation, benzothiophenes, benzoxazines, β-carbolines, bromanil, chromones, cinnoline, coumarinyl, decahydroquinoline, dihydromethysticin, dihydroergotoxine, di�hydrofoil, dihydroisoquinolyl, dihydropyran, dihydropyrazolo, dihydropyrazine, dihydropyridines, dihydropyrimidines, dihydropyrrole, DIOXOLANYL, 1,4-dithienyl, furanones, imidazolidinyl ureido, imidazolyl, indolinyl, isobenzofuranyl, isobenzofuranyl, isopropanol, isocoumarins, isoindoline, isothiazoline, isoxazolidine, morpholine, octahedrally, activitiesunder, oxazolidinones, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidinyl, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, hinokitiol, tetrahydrofuryl, tetrahydroisoquinoline, tetrahydropyranyl, tetrahydrofuranyl, thiomorpholine, thiazolidine, tetrahydroquinolines and 1,3,5-tritional. In specific embodiments, the heterocyclic group may also be optionally substituted by one or more substituents Q as described herein.

The term “heterocyclyl” refers to a divalent monocyclic non-aromatic ring system or a divalent polycyclic ring system that contains at least one non-aromatic ring, where one or more non-aromatic ring atoms are heteroatoms independently selected from O, S and N; and the remaining ring atoms are carbon atoms. In specific embodiments, the OS�span geterotsiklicheskie group contains from 3 to 20, from 3 to 15, 3 to 10, 3 to 8, from 4 to 7 or from 5 to 6 ring atoms. In specific embodiments, heterocyclyl represents a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which may be condensed or linked by bridging connection and in which the nitrogen atoms or sulfur may be optionally oxidized, the nitrogen atoms can be optionally quaternization and some rings may be partially or fully saturated or aromatic. Heterocyclyl can be attached to the main structure at any heteroatom or carbon atom that results in the formation of stable compounds. Examples of such geterotsiklicheskikh groups include, but are not limited to, azepines, benzodioxane, benzodioxole, benzofuranyl, benzopyranyl, benzopyranyl, besttravelforyou, benzocycloheptene, benzothiophene, benzoxazine, β-carbolines, romanien, chromosomen, cinnoline, coumarinyl, decahydroquinoline, dihydromethysticin, dihydroergotoxine, dihydrofuran, dihydroisoquinoline, dihydropyrrole, dihydropyrazolo, dihydropyrazine, dihydropyridine, dihydropyrimidine, dihydropyrrole, DIOXOLANYL, 1,4-titanyen, furanone, imidazolidinyl, imidazolyl�n, indolinyl, isobenzofurandione, isobenzofurandione, isopropanole, isocoumarins, isoindoline, isothiazoline, isoxazolidine, morpholine, octagenarian, octahydrophenanthrene, oxazolidinone, oxazolidinone, oxiranyl, piperazinyl, piperidinyl, 4-piperidinyl, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, hinkleyville, tetrahydrofuran, tetrahydrothiopyran, tetrahydropyranyl, tetrahydrothieno, thiomorpholine, thiazolidine, tetrahydroquinoline and 1,3,5-tretinoin. In specific embodiments, the heterocyclic group may also be optionally substituted by one or more substituents Q as described herein.

The term “halogen”, “halide” or “halogen” refers to fluorine, chlorine, bromine and/or iodine.

The term “optionally substituted” indicates that a group or substituent, such as alkyl, alkylen, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl or geterotsiklicheskie group may be substituted by one or more substituents Q, each independently selected from, for example, (a) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, GE�of eroarea and heterocyclyl, each further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (b) oxo (=O), halogen, cyano (-CN), nitro (-NO2), -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one embodiment, the implementation of one two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached, form heteroaryl or heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa. As used herein, all groups that can be substituted are “optionally substituted”, unless otherwise indicated.

In one embodiment, the implementation of each Qa is independently selected from the group consisting of (a) oxo, cyano, halogen and nitro; and (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re,- OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORh, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached, form heteroaryl or heterocyclyl.

In specific embodiments, the phrase “optically active” and ”enantiomerically active” refers to a group of molecules that have an enantiomeric excess of no less than about 50%, less than about 70%, less than about 80%, less than about 90%, less than about 91%, no less than about 92%, no less than about 93%, no less than about 94%, no less than about 95%, no less than about 96%, no less than about 97%, no less than about 98%, no less than about 99%, no less than about 99.5%, or no less than about 99.8 per cent. In specific embodiments, the compound contains about 95%, or more of one enantiomer and about 5% or less of the other enantiomer of the total weight of the racemate.

In describing an optically active compound the prefixes R and S are used to denote the absolute configuration of the molecule about its chiral(s) centre(s). The plus sign (+) and (-) are used to denote optical VR�communication connection, that is, the direction in which rotates the plane of polarized light in optically active compounds. The prefix (-) indicates that the compound is levorotatory, that is, the compound rotates the plane of polarized light to the left or counterclockwise. The prefix (+) indicates that the compound is dextrorotatory, that is, the compound rotates the plane of polarized light to the right or clockwise. However, the sign of the optical rotation (+) and (-) is not associated with the designation of the absolute configuration of the molecule, R and S.

The term “isotopic variant” refers to a compound that contains unnatural isotope at one or more atoms forming such compounds. In specific embodiments, an “isotopic variant” of a compound contains unnatural content of one or more isotopes, including, but not limited to: hydrogen (1H), deuterium (2H), tritium (3H), carbon-11 (11C), carbon-12 (12C), carbon-13 (13C), carbon-14 (14C), nitrogen-13 (13N), nitrogen-14 (14N), nitrogen-15 (15N), oxygen-14 (14O), oxygen-15 (15O), oxygen-16 (16O), oxygen-17 (17O), oxygen-18 (18O), fluorine-17 (17F), fluorine-18 (18F), phosphorus-31 (31P), phosphorus-32 (32P), phosphorus-33 (33P), sulfur-32 (32S), sulfur-33 (33S), sulfur-34 (34S), sulfur-35 (35S), sulfur-36 (36S), chlorine-35 (35Cl), chlorine-36 (36Cl), chlorine-37 (37Cl), bromine-79 (79Br), bromine-81 (81Br), iodine-123 (123I), iodine-125 (125I), iodine-127 (127I), iodine-129 (129I) and iodine-131 (131I). In particular embodiments, “isotopes�Phnom variant” connection is in a stable form, that is, non-radioactive. In specific embodiments, an “isotopic variant” of a compound contains unnatural amount of one or more isotopes, including, but not limited to, hydrogen (1H), deuterium (2H), carbon-12 (12C), carbon-13 (13C), nitrogen-14 (14N), nitrogen-15 (15N), oxygen-16 (16O), oxygen-17 (17O), oxygen-18 (18O), fluorine-17 (17F), phosphorous-31 (31P), sulfur-32 (32S), sulfur-33 (33S), sulfur-34 (34S), sulfur-36 (36S), chlorine-35 (35Cl), chlorine-37 (37Cl), bromine-79 (79Br), bromine-81 (81Br) and iodine-127 (127I). In specific embodiments, an “isotopic variant” of a compound is unstable, i.e. radioactive. In specific embodiments, an “isotopic variant” of a compound contains unnatural amount of one or more isotopes, including, but not limited to tritium (3H), carbon-11 (11C), carbon-14 (14C), nitrogen-13 (13N), oxygen-14 (14O), oxygen-15 (15O), fluorine-18 (18F), phosphorus-32 (32P), phosphorus-33 (33P), sulfur-35 (35S), chlorine-36 (36Cl), iodine-123 (123I), iodine-125 (125I), iodine-129 (129I) and iodine-131 (131I). Be aware that in the compound provided herein, any hydrogen can be, for example, 2H, or any carbon can be, for example, 13C, or any nitrogen can be, for example, 15N, and any oxygen can be 18O, in the case where it is possible, depending on the judgment of a specialist in this field. In specific embodiments, the implementation�“isotopic variant” of a compound contains unnatural amount of deuterium.

The term “solvate” refers to a complex or aggregate formed by one or more molecules of the solution, for example, compounds provided herein and one or more molecules of solvent that is present in stoichiometric or non-stoichiometric amounts. Suitable solvents include, but are not limited to, water, methanol, ethanol, n-propanol, isopropanol and acetic acid. In specific embodiments, the solvent is pharmaceutically acceptable. In one embodiment, the implementation of the complex or unit is in crystalline form. In another embodiment, the implementation of the complex or unit is in a noncrystalline form. In the case where the solvent is water, the solvate is a hydrate. Examples of hydrates include, but are not limited to, the gemigidrata, monohydrate, dihydrate, trihydrate, tetrahydrate, and pentahydrate.

The phrase “individual enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug” has the same meaning as the phrase “a single enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant of a compound described herein; or a pharmaceutically acceptable salt, solvate or proscar�tvo connections, described herein, or a single enantiomer, a racemic mixture, a mixture of diastereomers, or isotopic variant of the compound described in this document.

Connection

HCV contains a genome consisting of single-stranded RNA of positive polarity with a length of about 9,6 i.e., encoding a large polyprotein length of about 3010 amino acids. Then this primary polyprotein processores with the formation of several structural proteins, including protein from crustal, C, and shell glycoproteins E1 and E2; and non-structural proteins, including NS2, NS3, NS4A, NS4B, NS5A and NS5B, with the help of signal peptides master and two viral proteases, NS2-3 and NS3. Non-structural protein 5A (NS5A) is a multifunctional protein required for replication of HCV. Because of its vital role in viral replication, HCV NS5A protein is actively pursued as drug targets for the development of anti-HCV therapy.

In one of the embodiments of the present invention relates to the compound of the formula I:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

s, t, A, and E is an (i), (ii) or (iii):

(i) s is 1 or 2; t is 1; A is 5,5-condensed hetero�Allen; and E represents C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C2-6 akinyan-C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed Allen, C2-6 akinyan-5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) s is 1 or 2; t is 0; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan-R3a, C3-7 cycloalkyl-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6-or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

(iii) s is 0; t is 1; A is 5,5-condensed heteroaryl-R3a; E is a C2-6 akinyan, C3-7 cycloalkyl, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

each R1 and R2 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, 2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 that are attached to the same ring, together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 albaniles or C2-6 heteroalkyl;

each L1 and L2 independently represents (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C6-14 Allen-heteroaryl, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-; provided that Allen and Allenova group in C6-14 Allen-heteroarenes not represent a 5,6 - or 6,6-condensed Allen, and heteroaryl and heteroarenes group in C6-14 Allen-heteroaryl, heteroaryl-C1-6-alkylene, heteroaryl-C2-6-alkeline and heteroaryl-C2-6-alkylamine not represent a 5,6 - or 6,6-condensed heteroaryl;

each Z1 and Z2 is independently a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 represents�Oh independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

each n and p independently represents an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

each q and r independently represents an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each additional�Uo optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; Il� (iii) Rf and Rg together with the N atom, to which they are attached to form heterocyclyl.

In another embodiment of the present invention relates to the compound of the formula I:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

s, t, A, and E is an (i), (ii) or (iii):

(i) s is 1; t is 1; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) s is 1; t is 0; A is 5,5-condensed heteroaryl; and E represents a C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

(iii) s is 0; t is 1; A is 5,5-condensed heteroaryl-R3a; E is a C2-6 akinyan, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

R1 and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycleall�l, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z1 and Z2 are, each independently, a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkene�l, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

n and p are, each independently, an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

q and r are, each independently, an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each further optionally Zam�puppy one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf Rg together with the N atom, to which they are attached to form heterocyclyl.

In one of the embodiments of Allen and Allenova group, C6-14 Allen-heteroaryl in L1 or L2 in formula I does not represent a 5,6 - or 6,6-condensed Allen, and heteroaryl and heteroarenes group, C6-14 Allen-heteroaryl, heteroaryl-C1-6 alkylene, heteroaryl-C2-6 Alcanena and heteroaryl-C2-6 albinyana in L1 or L2 in formula I does not represent a 5,6 - or 6,6-condensed heteroaryl.

In yet another embodiment of the present invention relates to the compound of formula II:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

R1, R2, R3, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s and t each, are as defined herein;

U1, U2, V1, V2, W1 and W2 are each independently C, N, O, S, CR3a, or NR3a, where R3a is as defined herein;

X1 and X2 are, each independently, C or N; and

m represents an integer of 0, 1, 2, 3 or 4;

where communication between U1 and V1, U1, X1, V1 and W1, W1 and X2, U2 and V2, U2, X1, V2, and W2, W2 and X2 and X1 and X2 are, each, single or double bond.

In yet another embodiment of the present invention relates � the compound of formula III:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein; and each R1e independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each of which is optionally substituted by one or more substituents Q; or (c) -C(O)R1b, -C(O)OR1b, or-C(O)NR1bR1d, where R1b and R1d each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, III, IIIa, IIIb or IIIc, in one of the embodiments, U1 and X2 are N, U2 is a S, W1 and W2 are CH, and V1, V2, and X1 are C; in another embodiment of the U1 represents S, U2 and X2 are N, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 and X2 are N, U2 is O, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 is O, U2 and X2 are N, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 represents S, U2 and W1 are CH, W2 is a NR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 is a NR3a, U2 and W1 are CH, W2 is an S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 is a NR3a, U2 is a combintion of�th S, W1 represents CH and W2 represents N, and V1, V2, X1, and X2 are C; in another embodiment of the U1 represents S, U2 is NR3a a, W1 represents N, and W2 represents CH, and V1, V2, X1, and X2 are C; each R3a is as defined herein.

In formula II, III, IIIa, IIIb or IIIc, in one of the embodiments of U1 and X2 are N, U2 is a S, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a NR3a;in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1, and X2 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2, and X2 are C, and W1 represents S; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IV:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or a pharmaceuti�ski acceptable salt, the solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IVa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IVb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IVc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, IV, IVa, IVb or IVc, in one of the embodiments, U1, W2, X1, and X2 are C, U2 and W1 are�Oh S, and V1 and V2 are CH; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are CH, and V1 and V2 are N; in yet another embodiment of the U1, X1, and X2 are C, U2, V1 and V2 are CH, W1 is a S, and W2 represents N; in another embodiment of the U1 represents N, U2 is a S, V1, V2, and W1 are CH, W2, X1 and X2 represent a C.

In formula II, IV, IVa, IVb or IVc, in one of embodiments U1, X1, and X2 are C, V1, V2, U2 are each independently CR3a, W1 represents S, and W2 represents N; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are S, and V1 and V2 are each independently CR3a; in yet another embodiment of the U1, W2, X1 and X2 represent C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents S; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents O; in another embodiment of the U1, W2, X1, and X2 are C, U2 is a S, V1 and V2 are each independently CR3a, and W1 is NR3a a; in yet another embodiment of the U1 and X1 are C, U2, V1 V2 represent each independently CR3a, W1, W2 and X2 are N; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 and W2 are each independently CR3a, V1 and V2 are N; in another embodiment of the U1 represents N, U2 is a S, V1, V2 and W1 are each independently CR3a, W2, X1, and X2 are C; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of the formula V:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula Va:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula Vb:

�whether its isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula Vc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, V, Va, Vb or Vc, in one of embodiments U1 represents S, U2, V2, and W1 are CH, and V1, X1, and X2 are C, and W2 represents N; in another embodiment of the U1 and V2 are CH, U2 and W1 are S, and V1, W2, X1 and X2 represent a C.

In formula II, V, Va, Vb or Vc, in one of the embodiments, U1 and V2 are each independently CR3a, U2 and W1 are S, and V1, W2, X1, and X2 are C; in another embodiment of the U1 and V2 are each independently CR3a, U2 is a S, V1, W2, X1, and X2 are C, and W1 represents NR3a; in yet another embodiment of the U1 and X2 are N, U2 represents S, V1, W2, and X1 are C, and V2 and W1 are each independent�isimo, CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VI:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula VIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, VI, VIa, VIb or VIc, in one of the embodiments of U1, V1 and W2 are CH, U2 represents S, V2, X1, and X2 are C, and W1 represents N; in another embodiment of the U1 and W2 are S, U2 and V1 represent CH, and V2, W1, X1 and X2 represent a C.

In formula II, VI, VIa, VIb or VIc, in one of the embodiments, U1 and W2 are S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; in another embodiment of the U1 represents S, U2 and X2 are N, V1 and W2 are each independently CR3a, and V2, W1, and X1 are C; in yet another embodiment of the U1 represents S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; and W2 represents NR3a; where each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VII:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or �th pharmaceutically acceptable salt, the solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula VIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, VII, VIIa, VIIb or VIIc, in one of the embodiments, U1 and X2 are N, U2 is V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1 and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 �predstavlyaet a C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1, and X2 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2, and X2 are C, and W1 represents S; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIII:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula VIIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate Il� the prodrug; where R1, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of the formula VIIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, m, n, p, q, r, s and t each, are as defined herein.

In formula II, VIII, VIIIa, VIIIb or VIIIc, in one of the embodiments, U1 and X2 are N, U2 is a S, V1, W1 and X1 are C, and V2 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, W1 and X1 are C, and V2 and W2 are each independently CR3a, where each R3a is as defined herein.

In yet another embodiment of the present invention Rel�among the compound of the formula IX:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein;

T3 is a bond, C, N, O, S, CR3a, or NR3a, where R3a is as defined herein;

U3, V3, W3, and X3 are each independently C, N, O, S, CR3a, or NR3a, where R3a is as defined herein; and

Y3 represents C or N.

In yet another embodiment of the present invention relates to the compound of the formula X:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula Xa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p,q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula Xb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula Xc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, X, Xa, Xb or Xc, in one of the embodiments of U1 and X2 are N, U2 is a S, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another one�m embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 represents NR3a; in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1 and X2 are C, and W1 and W2 represent �Wallpaper, each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2, and X2 are C, and W1 represents S; each R3a is as defined herein.

In formula IX, X, Xa, Xb or Xc, in one of the embodiments, T3, U3, W3, and X3 are each independently CR3a, V3 and Y3 are C; in another embodiment of the T3 is a bond; in yet another embodiment of the T3 is a bond, U3 is a NR3a, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3, W3, and X3 represent, each independently CR3a, V3 represents C, and Y3 are N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is a CR3a, and X3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W1 represents N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3 is represented by N, V3 and Y3 are C, W3 is a NR3a, and X3 represents CR3a; each R3a is as defined herein;

In yet another embodiment of the present invention relates to the compound of formula XI:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of the formula XIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIc:

or an isotopic variant; or agopermalink acceptable salt, the solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, XI, XIa, XIb, or XIc, in one of the embodiments, U1, X1, and X2 are C, V1, V2, U2 are each independently CR3a, W1 represents S, and W2 represents N; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are S, and V1 and V2 are each independently CR3a; in yet another embodiment of the U1, W2, X1 and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents S; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents O; in another embodiment of the U1, W2, X1, and X2 are C, U2 is a S, V1 and V2 are each independently CR3a, and W1 represents NR3a; in yet another embodiment of the U1 and X1 are C, U2, V1 and V2 are each independently CR3a, W1, W2 and X2 are N; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 and W2 are each independently CR3a, V1 and V2 are N; in another embodiment of the U1 is a fun� N, U2 represents S, V1, V2 and W1 are each independently CR3a, W2, X1, and X2 are C; each R3a is as defined herein.

In formula IX, XI, XIa, XIb, or XIc, in one of the embodiments, T3, U3, W3, and X3 are each independently CR3a, V3 and Y3 are C; in another embodiment of the T3 is a bond; in yet another embodiment of the T3 is a bond, U3 is a NR3a, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3, W3, and X3 represent, each independently CR3a, V3 represents C, and Y3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is a CR3a, and X3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3 is represented by N, V3 and Y3 are C, W3 is a NR3a, and X3 represents CR3a; each R3a is as defined herein.

In yet another variant implementation of the present Fig�the notification relates to a compound of formula XII:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula XIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, XII, XIIa, XIIb or XIIc, in one of the embodiments, U1 and V2 are each independently CR3a, U2 and W1 are S, and V1, W2, X1, and X2 are C; in another embodiment of the U1 and V2 are each independently CR3a, U2 is a S, V1, W2, X1, and X2 are C, and W1 represents NR3a; in yet another embodiment of the U1 and X2 are N, U2 represents S, V1, W2, and X1 are C, and V2 and W1 are each independently CR3a; each R3a is as defined herein.

In formula IX, XII, XIIa, XIIb or XIIc, in one of the embodiments, T3, U3, W3, and X3 are each independently CR3a, V3 and Y3 are C; in another embodiment of the T3 is a bond; in yet another embodiment of the T3 is a bond, U3 is a NR3a, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3, W3, and X3 represent, each independently CR3a, V3 represents C, and Y3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 pre�is CR3a, and X3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3 is represented by N, V3 and Y3 are C, W3 is a NR3a, and X3 represents CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIII:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula XIIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, XIII, XIIIa, XIIIb or XIIIc, in one of the embodiments, U1 and W2 are S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; in another embodiment of the U1 represents S, U2 and X2 are N, V1 and W2 are each independently CR3a, and V2, W1, and X1 are C; in yet another embodiment of the U1 represents S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; and W2 represents NR3a; where each R3a is as defined herein.

In formula IX, XIII, XIIIa, XIIIb or XIIIc, in one of the embodiments, T3, U3, W3, and X3 are each independently CR3a, V3 and Y3 are C; in �other embodiment of the T3 is a bond; in yet another embodiment of the T3 is a bond, U3 is a NR3a, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3, W3, and X3 are each independently CR3a, V3 represents C, and Y3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is a CR3a, and X3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3 is represented by N, V3 and Y3 are C, W3 is a NR3a, and X3 represents CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIV:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of the formula XIVa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIVb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIVc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, XIV, XIVa, XIVb or XIVc, in one of the embodiments, U1 and X2 are N, U2 is a S, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 before�provide a S U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 represent each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1, and X2 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2 and X2 are C, and W1 represents S; each R3a is as defined herein.

In formula IX, XIV, XIVa, XIVb or XIVc, in one of the embodiments, T3, U3, V3 and X3 are each independently CR3a, W3 and Y3 are C; in another embodiment of the T3 is a bond; where each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XV:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to �the connection formula XVa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of the formula part no xvb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula IX, XV, XVa, part no xvb or XVc, in one of the embodiments, U1 and X2 are N, U2 is a S, V1, W1 and X1 are C, and V2 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, W1 and X1 are C, and V2 and W2 represent, ka�everyone regardless CR3a, where each R3a is as defined herein.

In formula IX, XV, XVa, part no xvb or XVc, in one of the embodiments, T3, U3, W3, and X3 are each independently CR3a, V3 and Y3 are C; in another embodiment of the T3 is a bond; in yet another embodiment of the T3 is a bond, U3 is a NR3a, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3, W3, and X3 represent, each independently CR3a, V3 represents C, and Y3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is a CR3a, and X3 represents N; in yet another embodiment of the T3 is a bond, U3 is a S, V3 and Y3 are C, W3 is represented by N, and X3 is a CR3a; in yet another embodiment of the T3 is a bond, U3 is represented by N, V3 and Y3 are C, W3 is a NR3a, and X3 represents CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVI:

or its individual EN�Timaru, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVII:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula XVIIa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XVIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each are �akimi, as defined in this document.

In yet another embodiment of the present invention relates to the compound of formula XVIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula II, XVI, XVII, XVIIa, XVIIb or XVIIc, in one of the embodiments, U1 and X2 are N, U2 is a S, W1 and W2 are CH, and V1, V2, and X1 are C; in another embodiment of the U1 represents S, U2 and X2 are N, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 and X2 are N, U2 is O, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 is O, U2 and X2 are N, W1 and W2 are CH, and V1, V2, and X1 are C; in yet another embodiment of the U1 represents S, U2 and W1 are CH, W2 is a NR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 is a NR3a, U2 and W1 are CH, W2 is an S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 �predstavljaet a NR3a, U2 represents S, W1 represents CH and W2 represents N, and V1, V2, X1, and X2 are C; in another embodiment of the U1 represents S, U2 is NR3a a, W1 represents N, and W2 represents CH, and V1, V2, X1, and X2 are C; each R3a is as defined herein.

In formula II, XVI, XVII, XVIIa, XVIIb or XVIIc, in one of the embodiments, U1 and X2 are N, U2 is a S, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1 and X2 are C, W1 is a CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1, and X2 represent the FDS�With th, W1 represents NR3a; in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1 and X2 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2, and X2 are C, and W1 represents S; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVIII:

or its enantiomer, RA�epicheskoi mixture, mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVIIIa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XVIIIb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XVIIIc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined�Elena in this document.

In formula II, XVI, XVIII, XVIIIa, XVIIIb or XVIIIc, in one of the embodiments, U1, W2, X1, and X2 are C, U2 and W1 are S, and V1 and V2 are CH; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are CH, and V1 and V2 are N; in yet another embodiment of the U1, X1, and X2 are C, U2, V1 and V2 are CH, W1 represents S, and W2 represents N; in another embodiment of the U1 represents N, U2 is a S, V1, V2, and W1 are CH, W2, X1 and X2 represent a C.

In formula II, XVI, XVIII, XVIIIa, XVIIIb or XVIIIc, in one of the embodiments, U1, X1, and X2 are C, V1, V2, U2 are each independently CR3a, W1 represents S, and W2 represents N; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are S, and V1 and V2 are each independently CR3a; in yet another embodiment of the U1, W2, X1 and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents S; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents O; in another embodiment of the U1, W2, X1, and X2 are C, U2 is V1 and V2 are each independently CR3a, and W1 is a NR3a; in yet another embodiment of the U1 and X1 are C, U2, V1 and V2 are each independently CR3a, W1, W2 and X2 are N; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 and W2 are each independently CR3a, V1 and V2 are N; in another embodiment of the U1 represents N, U2 is a S V1, V2 and W1 are each independently CR3a, W2, X1, and X2 are C; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIX:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIXa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIXb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIXc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula II, XVI, XIX, XIXa, XIXb, or XIXc, in one of the embodiments, U1 is a S, U2, V2, and W1 are CH, and V1, X1, and X2 are C, and W2 represents N; in another embodiment of the U1 and V2 are CH, U2 and W1 are S, and V1, W2, X1 and X2 represent a C.

In formula II, XVI, XIX, XIXa, XIXb, or XIXc, in one of the embodiments, U1 and V2 are each independently CR3a, U2 and W1 are S, and V1, W2, X1, and X2 are C; in another embodiment of the U1 and V2 represent�t a, each independently CR3a, U2 is a S, V1, W2, X1, and X2 are C, and W1 represents NR3a; in yet another embodiment of the U1 and X2 are N, U2 is a S, V1, W2, and X1 are C, and V2 and W1 are each independently CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XX:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula XXa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XXb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prohle�arctwo; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XXc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In formula II, XVI, XX, XXa, XXb or XXc, in one of the embodiments, U1, V1 and W2 are CH, U2 represents S, V2, X1, and X2 are C, and W1 represents N; in another embodiment of the U1 and W2 are S, U2 and V1 represent CH, and V2, W1, X1 and X2 represent a C.

In formula II, XVI, XX, XXa, XXb or XXc, in one of the embodiments, U1 and W2 are S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; in another embodiment of the U1 represents S, U2 and X2 are N, V1 and W2 are each independently CR3a, and V2, W1, and X1 are C; in yet another embodiment of the U1 represents S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; and W2 represents NR3a; where each R3a is as defined in this �the document.

In another embodiment, the implementation of each bivalent groupindependently selected from the group consisting of:

wherein each bivalent group is optionally substituted with one, two, three or four R3 groups.

In yet another embodiment of the present invention relates to the compound of formula XXI:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R3, A and m, each, are as defined herein; each R2a independently represents (i) hydrogen; or (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each of which is optionally substituted by one or more, in one embodiment, the implementation of one two, or three substituents Q.

In yet another embodiment of the present invention relates to the compound of formula XXII:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R2a, R3, A and m, each, are as defined herein.

In one embodiment, the implementation of A in the formula XXI or XXII is selected from:

where each dohale�community group optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In another embodiment, the implementation of A in the formula XXI or XXII is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In yet another embodiment of the A in the formula XXI or XXII is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In another embodiment, the implementation in A form�e XXI or XXII is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In yet another embodiment of the present invention relates to the compound of formula XXIII:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R2a defined herein; and A is selected from the group consisting of:

wherein each bivalent group is optionally substituted by one to four R3 groups.

In one of the embodiments of the present invention relates to the compound of formula IA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

A represents the 5,5-condensed ar�flax or 5,5-condensed heteroaryl;

t and E represent (i) or (ii):

(i) t is 1; and E represents a C2-6 akinyan, C6-14 Allen, C2-6 akinyan-C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed Allen, C2-6 akinyan-5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) t is 0; and E represents C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

R1, R1A and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together � education connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, C6-14 Allen-heteroaryl, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a-, -C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z2 is a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

p is an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

r pre�is an integer, 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q is independently selected from (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one embodiment, the implementation of one, �two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) oxo, cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

In another embodiment of the present invention relates to the compound of formula IA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

A represents the 5,5-condensed arisen or 5,5-condensed heteroaryl;

t and E represent (i) or (ii):

(i) t is 1; and E represents a C2-6 akinyan, C6-14 aralen or heteroaryl; provided that E does not represent a 5,6 - or 6,6-condensed arisen or 5,6 - or 6,6-condensed heteroaryl;

(ii) t is 0; and E ameri� a C2-6 akinyan-R3a, C6-14 Allen-R3a or heteroaryl-R3a, with the proviso that E is not a 5,6 - or 6,6-condensed Allen-R3a, or 5,6 - or 6,6-condensed heteroaryl-R3a;

R1, R1A and R2 are each independently (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 are linked together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 are each independently, (a) communication; (b) C1-6 alkylene, C2-6 albaniles, C2-6 akinyan, C3-7 cycloalkyl, C6-14 Allen, heteroaryl, heteroaryl-C1-6 alkylen, heteroaryl-C2-6 albaniles, heteroaryl-C2-6 akinyan or heterocyclyl; or (c) -C(O)-, -C(O)O-, -C(O)NR1a - C(=NR1a)NR1c-, -O-, -OC(O)O-, -OC(O)NR1a-, -OC(=NR1a)NR1c-, -OP(O)(OR1a)-, -NR1a-, -NR1aC(O)NR1c-, -NR1aC(=NR1b)NR1c-, -NR1aS(O)NR1c-, -NR1aS(O)2NR1c-, -S-, -S(O)-, -S(O)2-, -S(O)NR1a -, or-S(O)2NR1a-;

Z2 is a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

p is an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7; and

r is an integer equal to 1, 2, 3 or 4;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, akinyan, cycloalkyl, cycloalkyl, aryl, Allen, aralkyl, heteroaryl, heteroaryl, heterocyclyl and heterocyclyl in R1, R2, R3, R5, R6, R7, R1a, R1b, R1c, R1d, A, E, L1, or L2 is optionally substituted by one or more substituents Q, where each Q independently �Imran from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) -C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom, to which they are attached to form heterocyclyl.

In yet another embodiment of the present invention relates to the compound of formula IIA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIIA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IIIAa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate� or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IIIAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIIAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IVA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IVa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IVAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IVAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as �predelino in this document.

In one of the embodiments of the present invention relates to the compound of formula VAa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, Solvay�at or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula VIAa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIIA:

or its enantiomer, R�chimicheskoy mixture, mixture of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIIIA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula VIIIAa:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIIIAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined in�this document.

In yet another embodiment of the present invention relates to the compound of formula VIIIAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IXA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IXAa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IXAb:

or �stopnow embodiment; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IXAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XAa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, that are�them as defined in this document.

In another embodiment of the present invention relates to the compound of formula XAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of the formula XIA:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula XIAa:

or an isotopic variant; or �farmacevtichesky acceptable salt, the solvate or prodrug; where R1, R1A, R2, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula XIAb:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula XIAc:

or an isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R1A, R3, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z2, p, r and t, each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug;

where:

U1, U2, V1, V2, W1 and W2 are each independently C, N, O, S, CR3a, or NR3a;

X1 and X2 are, each independently, C or N;

each R1 and R2 is netavis�mo (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)R1b)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1a, -C(O)CH(N(R1c)C(O)NR1bR1d)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R3a independently represents hydrogen or R3;

each R3, R5 and R6 represents independently (a) cyano, halo or nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -service release 1A, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c; or

two R5 or two R6 that are attached to the same ring, together with the formation of the connection, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 Alcanena or C2-6 heterouncinata;

L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; (in each group indicates the point of attachment through which the group is associated withand�and ; and where T3 is a bond, C, N, O, S, CR3a, or NR3a; U3, V3, W3, and X3 are each independently C, N, O, S, CR3a, or NR3a; and Y3 represents C or N;

each Z1 and Z2 is independently a bond, -O-, -S-, -S(O)-, -S(O2)- or-N(R7)-;

each R7 independently represents (a) hydrogen; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (c) -C(O)R1a, -C(O)OR1a, -C(O)NR1bR1c, -C(NR1a)NR1bR1c, -OR1a, -OC(O)R1a, -OC(O)OR1a, -OC(O)NR1bR1c, -OC(=NR1a)NR1bR1c, -OS(O)R1a, -OS(O)2R1a, -OS(O)NR1bR1c, -OS(O)2NR1bR1c, -NR1bR1c, -NR1aC(O)R1d, -NR1aC(O)OR1d, -NR1aC(O)NR1bR1c, -NR1aC(=NR1d)NR1bR1c, -NR1aS(O)R1d, -NR1aS(O)2R1d, -NR1aS(O)NR1bR1c, -NR1aS(O)2NR1bR1c, -P(O)(OR1a)R1d, -CH2P(O)(OR1a)R1d, -S(O)R1a, -S(O)2R1a, -S(O)NR1bR1c, or-S(O)2NR1bR1c;

each R1a, R1b, R1c and R1d independently represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl; or R1b and R1c together with the N atom to which they are attached to form heterocyclyl;

each n and p independently represents an integer equal to 0, 1, 2, 3, 4, 5, 6 or 7;

each q and r independently represents an integer equal to 1, 2, 3 or 4;

s and t represent each independently an integer of 0, 1 or 2; and

u is an integer equal to 1 or 2;

where each alkyl, alkylene, heteroalkyl, alkenyl, albaniles, heteroalkyl, alkenyl, cycle�alkyl, aryl, aralkyl, heteroaryl and heterocyclyl optionally substituted by one or more substituents Q, where each Q is independently selected from (a) cyano, halogen and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl, each of which is further optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; and (c) -C(O)Ra, -C(O)ORa, -C(O)NRbRc, -C(NRa)NRbRc, -ORa, -OC(O)Ra, -OC(O)ORa, -OC(O)NRbRc, -OC(=NRa)NRbRc, -OS(O)Ra, -OS(O)2Ra, -OS(O)NRbRc, -OS(O)2NRbRc, -NRbRc, -NRaC(O)Rd, -NRaC(O)ORd, -NRaC(O)NRbRc, -NRaC(=NRd)NRbRc, -NRaS(O)Rd, -NRaS(O)2Rd, -NRaS(O)NRbRc, -NRaS(O)2NRbRc, -SRa, -S(O)Ra, -S(O)2Ra, -S(O)NRbRc, and-S(O)2NRbRc, where each of Ra, Rb, Rc and Rd independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl, each optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa; or (iii) Rb and Rc together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more, in one of embodiments one, two, three or four substituents Qa;

where each Qa is independently selected from the group consisting of (a) cyano, halo and nitro; (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl and heterocyclyl; and (c) C(O)Re, -C(O)ORe, -C(O)NRfRg, -C(NRe)NRfRg, -ORe, -OC(O)Re, -OC(O)ORe, -OC(O)NRfRg, -OC(=NRe)NRfRg, -OS(O)Re, -OS(O)2Re, -OS(O)NRfRg, -OS(O)2NRfRg, and-NRfRg, -NReC(O)Rh, -NReC(O)ORf, -NReC(O)NRfRg, -NReC(=NRh)NRfRg, -NReS(O)Rh, -NReS(O)2Rh, -NReS(O)NRfRg, -NReS(O)2NRfRg, -SRe, -S(O)Re, -S(O)2Re, -S(O)NRfRg, and-S(O)2NRfRg; where each Re, Rf, Rg and Rh independently represents (i) hydrogen; (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl or heterocyclyl; or (iii) Rf and Rg together with the N atom to which they are attached to form heterocyclyl.

In specific embodiments, L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; (in each group indicates the point of attachment through which the group is associated withor; where each R3 is as defined herein.

In specific embodiments, L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; � ( in each group indicates the point of attachment through which the group is associated withor; where each R3 is as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable �Oli, the solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IIB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and V1 and V2 represent, each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula IIBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IIBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or n�lekarstwo; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In formula IB, IIB, IIBa, or IIBb IIBc, in one of the embodiments, U1 and X2 are N, U2 is a S, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 and X2 are N, U2 is O, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is O, U2 and X2 are N, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 is a NR3a, U2 is a S, V1, V2, X1 � X2 represent C, W1 represents CR3a, and W2 represents N; in yet another embodiment of the U1 and W2 are each independently CR3a, U2 is a S, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 represents S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C, W2 represents NR3a; in yet another embodiment of the U1 and W2 are each independently, CR3a, U2 is O, V1, V2, X1, and X2 are C, W1 is a NR3a; in yet another embodiment of the U1 and W2 are N, U2 and W1 are S, and V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and W2 are S, U2 and W1 are each independently CR3a, V1, V2, X1, and X2 are C; in yet another embodiment of the U1 and X2 are N, U2 is a NR3a, V1, V2, and X1 are C, and W1 and W2 are each independently CR3a; in yet another embodiment of the U1 represents S, U2 is a NR3a, V1, V2, X1, and X2 are C, and W1 and W2 are each independently CR3a; in another embodiment of the U1, W2, and X1 are N, U2 is a CR3a, V1, V2, and X2 are C, and W1 represents S; where each R3a is as defined in the present�hydrology and hydrogeology.

In yet another embodiment of the present invention relates to the compound of formula IIIB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U2, V1, V2, W1, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and U1 and W2 are each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula IIIBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IIIBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another�nom embodiment of the present invention relates to the compound of formula IIIBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIIBd:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In IB, IIIB, IIIBa, IIIBb, IIIBc or IIIBd, in one of embodiments U1, X1, and X2 are C, V1, V2, U2 are each independently CR3a, W1 represents S, and W2 represents N; in another embodiment of the U1, W2, X1, and X2 are C, U2 and W1 are S, and V1 and V2 are each independently CR3a; in yet another embodiment of the U1, W2, X1 and X2 are C, U2 is a NR3a, V1 and V2 are each independently CR3a, and W1 represents S; in yet another embodiment of the U1, W2, X1, and X2 are C, U2 R�ulation of a NR3a, V1 and V2 are each independently CR3a, and W1 represents O; in another embodiment of the U1, W2, X1, and X2 are C, U2 is a S, V1 and V2 are each independently CR3a, and W1 is a NR3a; in yet another embodiment of the U1 and X1 are C, U2, V1 and V2 are each independently CR3a, W1, W2 and X2 are N; in yet another embodiment of the U1, W2, X1 and X2 are C, U2 and W2 are each independently CR3a, V1 and V2 are N; in another embodiment of the U1 represents N, U2 is a S, V1, V2 and W1 are each independently CR3a, W2, X1, and X2 are C; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IVB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V2, W1, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and V1 and W2 are each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula IVBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IVBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IVBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In formula IB, IVB, IVBa, IVBb or IVBc, in one of the embodiments, U1 and V2 are each independently CR3a, U2 and W1 are S, and V1, W2, X1, and X2 are C; in another VA�iante implementation of U1 and V2 represent each independently CR3a, U2 is a S, V1, W2, X1, and X2 are C, and W1 represents NR3a; in yet another embodiment of the U1 and X2 are N, U2 is a S, V1, W2, and X1 are C, and V2 and W1 are each independently CR3a; each R3a is as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and V2 and W1 are each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula VBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In formula IB, VB, VBa, VBb, or VBc, in one of the embodiments, U1 and W2 are S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; in another embodiment of the U1 represents S, U2 and X2 are N, V1 and W2 are each independently CR3a, and V2, W1, and X1 are C; in yet another embodiment of the U1 represents S, U2 and V1 are each independently CR3a, and V2, W1, X1, and X2 are C; and W2 represents NR3a; where each R3a is as defined herein.

In another embodiment, the implementation of n�worthwhile the invention relates to the compound of formula VIB:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V2, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and V1 and W1 are each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula VIBa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula VIBb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula VIBc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein. In formula IB, VIB, VIBa, VIBb or VIBc, in one of the embodiments of U1 and X2 are N, U2 is a S, V1, W1 and X1 are C, and V2 and W2 are each independently CR3a; in another embodiment of the U1 represents S, U2 and X2 are N, V1, W1 and X1 are C, and V2 and W2 are each independently CR3a, where each R3a is as defined herein.

In another embodiment of the present invention relates to the compound of formula AA:

where R1, R2, R5, R6, L1, L2, U2, V1, V2, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein; and U1 and W1 are each independently, C or N.

In one of the embodiments of the present invention relates to the compound of formula AAa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of the formula AAb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, X1, X2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula AAc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, U1, U2, V1, V2, W1, W2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IC:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined in �esteem document.

In one of the embodiments of the present invention relates to the compound of formula ICa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula ICb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula ICc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula ICd:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, L2, Z1, Z2, n, p, q, r, s, t and u, each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IIC:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In one of the embodiments of the present invention relates to the compound of formula IICa:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1, R2, R5, R6, L1, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In another embodiment of the present invention relates to the compound of formula IICb:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or pharmaceutical�wtiches acceptable salt, the solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IICc:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

In yet another embodiment of the present invention relates to the compound of formula IICd:

or its enantiomer, racemic mixtures, mixtures of diastereomers, or isotopic variant; or its pharmaceutically acceptable salt, solvate or prodrug; where R1a, R1c, R1e, R5, R6, L1, Z1, Z2, n, p, q, r, s and t each, are as defined herein.

Groups R1, R1A, R1a, R1b, R1c, R1e, R2, R3, R3a, R5, R6, L1, L2, T3, U1, U2, U3, V1, V2, V3, W1, W2, W3, X1, X2, X3, Y3, Z1, Z2, m, n, p, q, r, s and t in the formula described herein, including formula I-XXIII, IIIa-VIIIa, Xa-XVa, XVIIa-XXa, IIIb-VIIIb, Xb-part no xvb, XVIIb-XXb, IIIc-VIIIc, Xc-XVc, XVIIc-XXc, IA-XIA, IIIAa-VIAa, VIIIAa-XIAa, IIIAb-VIAb, VIIIAb-XIAb, IIIAc-VIAc, VIIIAc-XIAc, IB-VIB, IBa-VIBa, IBb-VIBb, IBc-VIBc, IIIBd, ICa-ICd, IIC-IICd and AA, AAa, AAb and AAc are defined later in this document. All combinations of their embodiments, predust�applied in this document for these groups is included in the scope of the present description.

In specific embodiments, R1 represents hydrogen. In specific embodiments, R1 is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1 is heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1 represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R1 represents-C(O)CH(NR1bR1c)R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R1 represents-C(O)CH[N(C(O)R1b)R1c]R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R1 represents-C(O)CH[N(C(O)OR1b)R1c]R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R1 represents-C(O)CH[N(C(O)NR1bR1d)R1c]R1a, where R1a, R1b, R1c and R1d each, are as defined herein. In specific embodiments, R1 represents-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R1 represents-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R1 is a-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R1 represents-P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R1 is a-CH2P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In concretisering implementation R1 represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R1 represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, R1 represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R1 represents-S(O)2NR1bR1c, where R1b and R1c, each, are as defined herein.

In specific embodiments, R1A represents hydrogen. In specific embodiments, R1A represents a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents a C7-15 aralkyl, neobyazatelnostyu one or more substituents Q. In specific embodiments, R1A represents heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1A represents heterocyclyl. In specific embodiments, R1A represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R1A represents-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R1A represents-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R1A represents-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R1A represents-P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R1A represents-CH2P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R1A represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R1A represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, �of sushestvennee R1A represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R1A represents-S(O)2NR1bR1c, where R1b and R1c, each, are as defined herein.

In specific embodiments, R2 represents hydrogen. In specific embodiments, R2 is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R2 is heterocy�Lil, optionally substituted by one or more substituents Q.

In specific embodiments, R2 is a-C(O)R1a, where R1a is as defined herein. In specific embodiments, R2 is a-C(O)CH(NR1bR1c)R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R2 is a-C(O)CH[N(C(O)R1b)R1c]R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R2 is a-C(O)CH[N(C(O)OR1b)R1c]R1a, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R2 is a-C(O)CH[N(C(O)NR1bR1d)R1c]R1a, where R1a, R1b, R1c and R1d each, are as defined herein. In specific embodiments, R2 is a-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R2 is a-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R2 is a-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R2 represents-P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R2 is a-CH2P(O)(OR1a)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R2 represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R2 represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, R2 represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R2 represents-S(O)2NR1bR1c, where R1b and R1c, each, are as defined herein.

In specific embodiments, R1 and R2, each independently selected from 2(R)-(dimethylamino)propionyl, 2-(methoxycarbonylamino)propionyl, 2(R)-(methoxy-carbylamine)propionyl, 2-(ethoxycarbonyl)propionyl, 2(R)-(methoxycarbonyl-amino)-3-methoxy-propionyl, 2(R)-(methoxycarbonylamino)-3-aminocarbonyl-propionyl, 2-(methoxycarbonylamino)-2-methylpropionyl, 2(R)-(methoxycarbonylamino)-3(R)-hydroxy-butanoyl, 2(R)-(methoxycarbonylamino)-3(S)-hydroxybutanal, 2(R)-(methoxycarbonyl-amino)-3-methylbutanoyl, 2(S)-(methoxycarbonylamino)-3-methylbutanoyl, 2(R)-(ethoxycarbonyl-amino)-3-methylbutanoyl, 2(S)-(ethoxycarbonyl)-3-methylbutanoyl, 2(R)-isoproterenol-amino)-3-methylbutanoyl, 2(S)-(isopropoxycarbonyl)-3-methylbutanoyl, 2(R)-(tert-butoxycarbonylamino)-3-methylbutanoyl, 2(S)-(tert-butoxycarbonylamino)-3-methylbutanoyl, 2(R)-(methoxycarbonylamino)-3-hydroxy-3-methylbutanoyl, 2-(methoxycarbonylamino)-2-cyclopropyl-acetyl, 2-(methoxycarbonylamino)pentanoyl, 2-(methoxycarbonylamino)pent-4-Enola, 1-(methoxycarbonylamino)cyclopropanecarbonyl, 1-(methoxycarbonylamino)cyclobutanecarbonyl, 1-(methoxycarbonylamino)cyclopentyl-carbonyl, 2(R)-(methoxycarbonylamino)-2-phenylacetyl, 2(R)-(ethoxycarbonylethyl)-2-phenylacetyl, 2(R)-(isopropoxycarbonyl)-2-phenylacetyl, 2(R)-(tert-butoxycarbonylamino)-2-phenylacetyl, 2(S)-(tert-butoxycarbonylamino)-2-phenylacetyl, 2(R)-(methoxycarbonyl-amino)-2-(2-chlorophenyl)acetyl, 2(R)-(dimethylamino)-2-phenylacetyl, 2-(dimethylamino)-2-(4-nitrophenyl)acetyl, 2-(dimethylamino)-2-(2-fluorophenyl)acetyl, 2(R)-(dimethylamino)-2-(2-fluorophenyl)acetyl, 2(S)-(dimethylamino)-2-(2-fluorophenyl)acetyl, 2-(dimethyl-amino)-2-(3-fluorophenyl)acetyl, 2-(dimethylamino)-2-(2-chlorophenyl)acetyl, 2(R)-(dimethylamino)-2-(2-chlorophenyl)acetyl, 2-(dimethylamino)-2-(3-chlorophenyl)acetyl, 2-(dimethylamino)-2-(4-chlorophenyl)acetyl, 2-(dimethylamino)-2-(2-trifluoromethyl-phenyl)acetyl, 2-(dimethyl-amino)-2-(3-triptoreline)acetyl, 2-(dimethylamino)-2-(Thien-2-yl)acetyl, 2-(dimethylamino)-2-(Thien-3-yl)acetyl, 2-(dimethylamino)-2-(2-thiazole-4-yl)ACO�silt, 2-(dimethylamino)-2-(benzothieno-3-yl)acetyl, 2-(dimethylamino)-2-(2-methyl-benzothiazol-5-yl)acetyl, 2-(dimethylamino)-2-(benzisoxazol-3-yl)acetyl, 2-(dimethylamino)-2-(quinolin-3-yl)acetyl, 2(R)-(diethylamino)-2-phenylacetyl, 2(R)-(methylethylamine)-2-phenylacetyl, 2-(dimethylamino)-2-naphthas-1-lacetera, 2(R)-(pyrrolidin-1-yl)-2-phenylacetyl, 2-(3(S)-ftorpirimidinu-1-yl)-2-phenylacetyl, 2(R)-(morpholine-4-yl)-2-phenylacetyl, 2(R)-(piperidine-1-yl)-2-phenylacetyl, 2(R)-(piperidine-1-yl)-2-(2-fluorophenyl)acetyl, 2-(4-hydroxy-piperidine-1-yl)-2-phenylacetyl, 2-(4-phenylpiperazin-1-yl)-2-phenylacetyl, 2(R)-(4-hydroxy-4-demerol-1-yl)-2-phenylacetyl, 2(R)-(4-hydroxy-4-phenylpiperidine-1-yl)-2-phenylacetyl, 2-(3-oxopiperidin-1-yl)-2-phenylacetyl, 2-(4-methylpiperazin-1-yl)-2-phenylacetyl, 2-(dimethylamino)-2-(pyridin-2-yl)acetyl, 2-(dimethylamino)-2-(pyridin-3-yl)acetyl, 2-(dimethylamino)-2-(pyridin-4-yl)acetyl, 2-(dimethylamino)-2-(6-chloropyridin-3-yl)acetyl, 2-(2-dimethylaminomethyl)phenylacetyl, 2-(2-pyrrolin-1-ylmethyl)phenylacetyl, 2-(2-piperidine-1-ylmethyl)phenylacetyl, 2-(2-morpholine-4-ylmethyl)phenylacetyl, 2-(2-(4-methylpiperazin-1-ylmethyl)phenylacetyl, 1 methylpyrrolidine-2(R)carbonyl, 1-methyl-4(R)-fluoro-pyrrolidin-2(R)carbonyl, 2-(R)-(methylaminoquinoline)-2-phenylacetyl, 2-(R)-(ethylenediamino)-2-phenylacetyl, 2(R)-(cyclopentanecarbonyl)-2-phenylacetyl, 2(R)-(dimethylaminocarbonylmethyl)-2-phenylace�La, (N,N-benzylmethyl-amino)acetyl, and 2-(N,N-benzylmethylamine)-3-methylbutanoyl. Other examples of R1 and R2 is, for example, in the publication of the patent application U.S. No. 2009/0202478 and 2009/0202483; and in international patent application no WO 2008/144380 and in WO 2009/102694, a description of each of which are incorporated herein fully by reference.

In specific embodiments, R1a represents hydrogen. In specific embodiments, R1a represents a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a represents a C1-6 alkyl, optionally substituted by one or more substituents, where each Deputy independently selected from hydroxyl, merkapto, methylthio, amino, carboxy, carbamoyl, guanidino, phenyl, hydroxyphenyl, imidazolyl or indolyl. In specific embodiments, R1a represents a C1-6 alkyl, optionally substituted by one or more substituents, each independently selected from hydroxyl, merkapto, methylthio, amino, carboxy, carbamoyl, guanidino, phenyl, hydroxyphenyl, imidazolyl or indolyl. In specific embodiments, R1a is methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents Q. In particular embodiments, osushestvlenie� R1a is methyl, ethyl, propyl or butyl, each optionally substituted by one or more substituents, where each Deputy independently selected from hydroxyl, merkapto, methylthio, amino, carboxy, carbamoyl, guanidino, phenyl, hydroxyphenyl, imidazolyl or indolyl. In specific embodiments, R1a is methyl, isopropyl, 2-methylpropyl", 1-methylpropyl", 2-methylthioethyl, benzyl, 3-indolylmethane, gidroximetil, 1-hydroxyethyl, mercaptomethyl, 4-hydroxybenzyl, carbamoylmethyl, 2-carbamoylethyl, carboxymethyl, 2-carboxyethyl, 4-aminobutyl, 3-guanidinopropionic or 4-imidazolidinyl.

In specific embodiments, R1a represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a represents a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a represents a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R1a is a phenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a before�provide a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1a is a benzyl or hydroxybenzyl. In specific embodiments, R1a is a benzyl or 4-hydroxybenzyl. In specific embodiments, R1a represents heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1a represents heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1b represents hydrogen. In specific embodiments, R1b is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1b represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1b represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1b is a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1b is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, osushestvlenie� R1b represents a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1b is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1b is heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1c represents hydrogen. In specific embodiments, R1c represents a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1c is methyl. In specific embodiments, R1c represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1c represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1c represents a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1c represents a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R1c represents a C7-15 aralkyl, optionally substituted by one or more substituents Q. In the nodules�tions embodiments, R1c represents heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1c is heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1a and R1c together with the C and N atoms to which they are attached to form heterocyclyl, in one of the embodiments of pyrrolidinyl, in another embodiment of the 2-pyrrolidinyl, each optionally substituted by one or more substituents Q.

In specific embodiments, R1b and R1c together with the N atom to which they are attached to form heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1d represents hydrogen. In specific embodiments, R1d is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1d is methyl. In specific embodiments, R1d represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1d represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1d represents a C3-7 cycloalkyl, neobythites�but substituted by one or more substituents Q. In specific embodiments, R1d is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R1d represents a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1d is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1d is heterocyclyl, optionally substituted by one or more substituents Q.

In specific embodiments, R1e is a hydrogen. In specific embodiments, R1e is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e represents a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e represents a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e represents a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e represents a C6-14 aryl, optionally substituted by one or more substituents Q. In con�specific embodiments, R1e represents a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R1e is heterocyclyl, each optionally substituted by one or more substituents Q. In particular embodiments, R1e represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R1e represents-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R1e represents-C(O)O-C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R1e represents a methoxycarbonyl or butoxycarbonyl. In specific embodiments, R1e is ethoxycarbonyl or propoxycarbonyl. In specific embodiments, R1e is isopropoxycarbonyl. In specific embodiments, R1e is isobutoxide. In specific embodiments, R1e represents a tert-butoxycarbonyl. In specific embodiments, R1e represents-C(O)NR1bR1d, where R1b and R1d each, are as defined in this Doc�the COP.

In specific embodiments, R3a represents hydrogen. In specific embodiments, R3a represents R3, which is the same as defined herein. In specific embodiments, R3a represents hydrogen, chlorine, fluorine, nitro, amino, methyl, trifluoromethyl, phenyl or methoxy.

In specific embodiments, R3 is an oxo. In specific embodiments, R3 is a cyano. In specific embodiments, R3 is a halogen. In specific embodiments, R3 is a nitro. In specific embodiments, R3 is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is methyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In specific embodiments, the implementation�Oia R3 represents cyclohexyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 represents a cyclohexyl. In specific embodiments, R3 is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R3 is heterocyclyl, optionally substituted by one or more substituents Q. In particular embodiments, R3 represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R3 represents-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R3 represents-C(O)OCH3. In specific embodiments, R3 represents-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 represents-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, the OS�span R3 represents-OR1a, where R1a is as defined herein. In specific embodiments, R3 represents-OH. In specific embodiments, R3 represents-OC(O)R1a, where R1a is as defined herein. In specific embodiments, R3 represents-OC(O)OR1a, where R1a is as defined herein. In specific embodiments, R3 represents-OC(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 represents-OC(=NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R3 represents-OS(O)R1a, where R1a is as defined herein. In specific embodiments, R3 represents-OS(O)2R1a, where R1a is as defined herein. In specific embodiments, R3 represents-OS(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 represents-OS(O)2NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 represents-NR1bR1c, where R1b and R1c, each, are as defined � this document. In specific embodiments, R3 represents-NR1aC(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R3 represents-NR1aC(O)OR1d, where R1a and R1d each, are as defined herein. In specific embodiments, R3 represents-NR1aC(O)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R3 represents-NR1aC(=NR1d)NR1bR1c, where R1a, R1b, R1c and R1d each, are as defined herein. In specific embodiments, R3 represents-NR1aS(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R3 represents-NR1aS(O)2R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R3 represents-NR1aS(O)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R3 represents-NR1aS(O)2NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R3 represents-service release 1A, where R1a is as defined herein. In specific embodiments, 3 represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R3 represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, R3 represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 represents-S(O)2NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R3 is a chlorine, fluorine, nitro, amino, methyl, trifluoromethyl, phenyl or methoxy.

In specific embodiments, R5 is a cyano. In specific embodiments, R5 is a halogen. In specific embodiments, R5 is a nitro. In specific embodiments, R5 is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is a C3-7 cycloalkyl, optionally substituted with one, and�and several substituents Q. In specific embodiments, R5 is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is a C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R5 is heterocyclyl, optionally substituted by one or more substituents Q. In particular embodiments, R5 represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R5 is a-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R5 is a-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 is a-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R5 represents-OR1a, where R1a is as defined herein. In specific embodiments, R5 represents-OC(O)R1a, where R1a is as defined in N.� - alone document. In specific embodiments, R5 represents-OC(O)OR1a, where R1a is as defined herein. In specific embodiments, R5 represents-OC(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 represents-OC(=NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R5 represents-OS(O)R1a, where R1a is as defined herein. In specific embodiments, R5 represents-OS(O)2R1a, where R1a is as defined herein. In specific embodiments, R5 represents-OS(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 represents-OS(O)2NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 is a-NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 is a-NR1aC(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R5 is a-NR1aC(O)OR1d, where R1a and R1d, every,are, as defined in the present document. In specific embodiments, R5 is a-NR1aC(O)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R5 is a-NR1aC(=NR1d)NR1bR1c, where R1a, R1b, R1c and R1d each, are as defined herein. In specific embodiments, R5 is a-NR1aS(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R5 is a-NR1aS(O)2R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R5 is a-NR1aS(O)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R5 is a-NR1aS(O)2NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R5 represents a-service release 1A, where R1a is as defined herein. In specific embodiments, R5 represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R5 represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, p�effect to R5 represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R5 represents-S(O)2NR1bR1c, where R1b and R1c, each, are as defined herein.

In specific embodiments, two R5 are linked together with the formation of the connection. In specific embodiments, two R5 are linked together with the formation of-O-. In specific embodiments, two R5 are linked together with the formation of-NR7-, where R7 is as defined herein. In specific embodiments, two R5 are linked together with the formation of-S-. In specific embodiments, two R5 are linked together with the formation of the C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, two R5 are linked together with the formation of methylene, ethylene, or propylene, each optionally substituted by one or more substituents Q. In particular embodiments, two R5 are linked together with the formation of the C1-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, two R5 are linked together with the formation of C2-6 Alcanena, optionally substituted by one or more substituents Q. In particular embodiments, two R5 are linked together with the formation of 2-6 heterouncinata, optionally substituted by one or more substituents Q. In particular embodiments, two R5 are linked together with the formation of a condensed ring. In specific embodiments, two R5 are linked together with the formation of the United bridge connection ring. In specific embodiments, two R5 are linked together with the formation of the Spiro-ring.

In specific embodiments, R6 represents cyano. In specific embodiments, R6 is a halogen. In specific embodiments, R6 is a nitro. In specific embodiments, R6 is a C1-6 alkyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 is a C2-6 alkenyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 is a C2-6 alkynyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 represents a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 is a C6-14 aryl, optionally substituted by one or more substituents Q. In particular embodiments, R6 represents�Oh C7-15 aralkyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 represents heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, R6 represents heterocyclyl, optionally substituted by one or more substituents Q. In particular embodiments, R6 represents-C(O)R1a, where R1a is as defined herein. In specific embodiments, R6 represents-C(O)OR1a, where R1a is as defined herein. In specific embodiments, R6 represents-C(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-C(NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R6 represents-OR1a, where R1a is as defined herein. In specific embodiments, R6 represents-OC(O)R1a, where R1a is as defined herein. In specific embodiments, R6 represents-OC(O)OR1a, where R1a is as defined herein. In specific embodiments, R6 represents OC(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-OC(=NR1a)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R6 represents-OS(O)R1a, where R1a is as defined herein. In specific embodiments, R6 represents-OS(O)2R1a, where R1a is as defined herein. In specific embodiments, R6 represents-OS(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-OS(O)2NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-NR1aC(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R6 represents-NR1aC(O)OR1d, where R1a and R1d each, are as defined herein. In specific embodiments, R6 represents-NR1aC(O)NR1bR1c, where R1a, R1b and R1c each, are as defined in this Doc�cops. In specific embodiments, R6 represents-NR1aC(=NR1d)NR1bR1c, where R1a, R1b, R1c and R1d each, are as defined herein. In specific embodiments, R6 represents-NR1aS(O)R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R6 represents-NR1aS(O)2R1d, where R1a and R1d each, are as defined herein. In specific embodiments, R6 represents-NR1aS(O)NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R6 represents-NR1aS(O)2NR1bR1c, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, R6 represents-service release 1A, where R1a is as defined herein. In specific embodiments, R6 represents-S(O)R1a, where R1a is as defined herein. In specific embodiments, R6 represents-S(O)2R1a, where R1a is as defined herein. In specific embodiments, R6 represents-S(O)NR1bR1c, where R1b and R1c, each, are as defined herein. In specific embodiments, R6 represents-S(O)2NR1bR1c where R1b � R1c, each, are as defined herein.

In specific embodiments, two R6 are linked together with the formation of the connection. In specific embodiments, two R6 are linked together with the formation of-O-. In specific embodiments, two R6 are linked together with the formation of-NR7-, where R7 is as defined herein. In specific embodiments, two R6 are linked together with the formation of-S-. In specific embodiments, two R6 are linked together with the formation of the C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, two R6 are linked together with the formation of methylene, ethylene, or propylene, each optionally substituted by one or more substituents Q. In particular embodiments, two R6 are linked together with the formation of the C1-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, two R6 are linked together with the formation of C2-6 Alcanena, optionally substituted by one or more substituents Q. In particular embodiments, two R6 are linked together with the formation of C2-6 heterouncinata, optionally substituted by one or more substituents Q. In particular embodiments, two R6 are linked together with clicks�use of the condensed ring. In specific embodiments, two R6 are linked together with the formation of the United bridge connection ring. In specific embodiments, two R6 are linked together with the formation of the Spiro-ring.

In particular embodiments, A represents the 5,5-condensed heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In particular embodiments, A represents A thieno[3,2-b]tienlen, imidazo[3,4-c]pyrroline, 4H-thieno[3,2-b]pyrrolidin, 6H-thieno[2,3-b]pyrrolidin, imidazo[2,1-b]oxazoline, imidazo[2,1-b]thiazoline or 4H-imidazo[3,2-d]thiazoline, each optionally substituted by one or more substituents R3, where R3 is as defined herein. In particular embodiments, A represents A thieno[3,2-b]Thien-2,6-yl, thieno[3,2-b]Thien-3,6-yl, imidazo[3,4-c]pyrrol-1,4-yl, 4H-thieno[3,2-b]pyrrol-2,5-yl, 6H-thieno[2,3-b]pyrrole-3,6-ilen, imidazo[2,1-b]oxazol-2,6-ilen, imidazo[2,1-b]the thiazole-2,6-yl or 4H-imidazo[3,2-d]thiazole-2,5-yl, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In particular embodiments, A represents the 3H-pyrrolizine, 4H-furo[3,2-b]pyrrolidin, furo[3,2-b]TuranAlem, 1,4-dihydropyrrol�[3,2-b]pyrrolidin, 5H-imidazo[1,2-c]imidazolyl, 4H-furo[3,2-b]pyrrolidin, 6H-imidazo[1,2-b]pyrazoline, 5H-imidazo[1,2-a]imidazolyl, thieno[3,2-b]TuranAlem, 1H-furo[3,2-c]pyrazoline, 1H-thieno[3,2-c]pyrazoline, 1,4-dihydropyrrolo[3,2-c]pyrazoline, 1H-imidazo[1,2-a]imidazolyl, pyrazolo[5,1-b]oxazoline, pyrazolo[5,1-b]thiazoline, 5H-imidazo[1,2-b]pyrazoline, imidazo[1,2-b]isoxazolyl, imidazo[1,2-b]isothiazoline, imidazo[1,5-b]isoxazolyl, imidazo[1,5-b]isothiazoline, imidazo[5,1-b]oxazoline, imidazo[5,1-b]thiazoline, 1H-imidazo[1,5-a]imidazolyl, 6H-imidazo[3,2-d]isoxazoline, 6H-imidazo[3,2-d]isothiazoline, imidazo[2,1-b][1,3,4]oxadiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-imidazo[1,2-b][1,2,4]triazolyl, 3H-furo[2,3-d]imidazoline, 3H-thieno[2,3-d]imidazoline, 3,4-dihydropyrrolo[2,3-d]imidazoline, furo[3,2-d]thiazoline, thieno[3,2-d]thiazoline, 4H-imidazo[3,2-d]thiazoline, 4H-pyrazolo[3,4-d]isoxazoline, 4H-pyrazolo[3,4-d]isothiazoline, 1,4-dihydropyrazolo[4,3-c]pyrazoline, isoxazole[5,4-d]isoxazoline, isothiazole[5,4-d]isothiazoline, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-imidazo[1,5-a]imidazolyl, imidazo[2,1-b]oxazoline, imidazo[2,1-b]thiazoline, 1H-imidazo[1,2-a]imidazolyl, 1H-imidazo[1,2-a]imidazolyl, thieno[3,2-b]TuranAlem or thiazolo[5,4-d]thiazoline, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, about�of westlane A represents imidazo[2,1-b]thiazole-5,6-yl, 3H-pyrrolizine-1,5-yl, 3H-pyrrolizine-2,6-yl, 4H-furo[3,2-b]pyrrol-2,5-yl, 4H-furo[3,2-b]pyrrole-3,6-yl, furo[3,2-b]furan-2,5-yl, furo[3,2-b]furan-3,6-ilen, 1,4-dihydropyrrolo[3,2-b]pyrrol-2,5-yl, 1,4-dihydropyrrolo[3,2-b]pyrrole-3,6-yl, 5H-imidazo[1,2-c]imidazole-3,7-yl, 4H-furo[3,2-b]pyrrol-2,4-yl, 4H-furo[3,2-b]pyrrol-2,5-yl, 4H-furo[3,2-b]pyrrol-3,4-yl, 4H-furo[3,2-b]pyrrole-3,6-yl, 6H-imidazo[1,2-b]pyrazole-2,5-yl, 5H-imidazo[1,2-a]imidazole-2,6-ilen, 5H-imidazo[1,2-a]imidazole-3,7-yl, thieno[3,2-b]furan-2,5-yl, thieno[3,2-b]furan-3,6-yl, 1H-furo[3,2-c]pyrazol-3,6-yl, 1H-thieno[3,2-c]pyrazol-3,6-ilen, 1,4-dihydropyrrolo[3,2-c]pyrazol-3,6-yl, 1H-imidazo[1,2-a]imidazole-2,6-ilen, pyrazolo[5,1-b]oxazol-2,6-ilen, pyrazolo[5,1-b]oxazol-3,7-ilen, pyrazolo[5,1-b]thiazole-2,6-ilen, pyrazolo[5,1-b]thiazole-3,7-yl, 5H-imidazo[1,2-b]pyrazole-2,6-yl, 5H-imidazo[1,2-b]pyrazol-3,7-ilen, imidazo[1,2-b]isoxazol-2,6-ilen, imidazo[1,2-b]isoxazol-3,7-ilen, imidazo[1,2-b]isothiazol-2,6-ilen, imidazo[1,2-b]isothiazol-3,7-ilen, imidazo[1,5-b]isoxazol-3,7-ilen, imidazo[1,5-b]isothiazol-3,6-ilen, imidazo[5,1-b]oxazol-3,7-ilen, imidazo[5,1-b]thiazole-3,7-yl, 1H-imidazo[1,5-a]imidazole-3,7-yl, 6H-imidazo[3,2-d]izocsazol-3,6-yl, 6H-imidazo[3,2-d]isothiazol-3,6-yl, imidazo[2,1-b][1,3,4]oxidiazol-2,6-yl, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl, 1H-imidazo[1,2-b][1,2,4]triazole-1,5-yl, 1H-imidazo[1,2-b][1,2,4]triazole-2,6-yl, 3H-furo[2,3-d]imidazole-2,5-yl, 3H-furo[2,3-d]imidazole-3,6-yl, 3H-thieno[2,3-d]imidazole-2,5-yl, 3H-thieno[2,3-d]them�Azol-3,6-yl, 3,4-dihydropyrrolo[2,3-d]imidazole-2,5-yl, 3,4-dihydropyrrolo[2,3-d]imidazole-3,6-yl, furo[3,2-d]thiazole-2,5-yl, thieno[3,2-d]thiazole-2,5-yl, 4H-imidazo[3,2-d]thiazole-2,5-yl, 4H-pyrazolo[3,4-d]izocsazol-3,6-yl, 4H-pyrazolo[3,4-d]isothiazol-3,6-yl, 1,4-dihydropyrazolo[4,3-c]pyrazole-1,4-ilen, 1,4-dihydropyrazolo[4,3-c]pyrazol-3,6-ilen, isoxazole[5,4-d]izocsazol-3,6-ilen, isothiazole[5,4-d]isothiazol-3,6-ilen, imidazo[2,1-b][1,3,4]thiadiazole-2,5-yl, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl, 6H-imidazo[3,2-d]izocsazol-3,6-yl, 1H-imidazo[1,5-a]imidazole-1,5-yl, imidazo[2,1-b]oxazol-2,5-yl, imidazo[2,1-b]thiazole-2,5-yl, 1H-imidazo[1,2-a]imidazole-2,5-yl, 1H-imidazo[1,2-a]imidazole-1,5-yl, thieno[3,2-b]furan-3,6-yl or thiazolo[5,4-d]thiazole-2,5-yl, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, A is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 independently represents chlorine, fluorine, nitro, amino, methyl, trifluoromethyl, phenyl or methoxy.

In specific embodiments, or A divalent group selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In specific embodiments, or A divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In specific embodiments, or A divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In particular in�the options of implementation, each R3 represents, independently oxo, chlorine, fluorine, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In specific embodiments, or A divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, amino, methyl, trifluoromethyl, cyclohexyl, phenyl or methoxy.

In particular embodiments, A represents the 5,5-condensed heteroaryl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In particular embodiments, A represents A thieno[3,2-b]Tianjin-R3a, imidazo[3,4-c]pyrrolidin-R3a, 4H-thieno[3,2-b]pyrrolidin-R3a, 6H-thieno[2,3-b]pyrrolidin-R3a, imidazo[2,1-b]oxazoline-R3a, imidazo[2,1-b]thiazoline-R3a or 4H-imidazo[3,2-d]thiazolidin-R3a, each optionally substituted by one or more substituents R3, where R3a and R3, each, are as defined herein. In particular embodiments, A represents A thieno[3,2-b]thienyl, imidazo[3,4-c]pyrrolyl, tieno[3,2-b]pyrrolyl, 6H-thieno[2,3-b]pyrrolyl, imidazo[2,1-b]oxazolyl, imidazo[2,1-b]thiazolyl or 4H-imidazo[3,2-d]thiazolyl, each optionally substituted by one or more substituents R3, where R3 is as defined herein. In particular embodiments, A represents a thieno[3,2-b]Thien-3,6-yl-R3a, imidazo[3,4-c]pyrrol-1,4-ilen-R3a, 4H-thieno[3,2-b]pyrrol-2,5-yl-R3a, 6H-thieno[2,3-b]pyrrole-3,6-yl-R3a, imidazo[2,1-b]oxazol-2,6-yl-R3a, imidazo[2,1-b]the thiazole-2,6-yl-R3a or 4H-imidazo[3,2-d]thiazole-2,5-yl-R3a, each optionally substituted by one or more substituents R3, where R3a and R3, each, are as defined herein.

In particular embodiments, a represents the 3H-pyrrolizine-R3a, 4H-furo[3,2-b]pyrrolidin-R3a, furo[3,2-b]TuranAlem-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrolidin-R3a, 5H-imidazo[1,2-c]imidazolium-R3a, 4H-furo[3,2-b]pyrrolidin-R3a, 6H-imidazo[1,2-b]pyrazoline-R3a, 5H-imidazo[1,2-a]imidazolidin-R3a, thieno[3,2-b]TuranAlem-R3a, 1H-furo[3,2-c]pyrazoline-R3a, 1H-thieno[3,2-c]pyrazoline-R3a, 1,4-dihydropyrrolo[3,2-c]pyrazoline-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, pyrazolo[5,1-b]oxazoline-R3a, pyrazolo[5,1-b]thiazoline-R3a, 5H-imidazo[1,2-b]pyrazoline-R3a, imidazo[1,2-b]isoxazolin-R3a, imidazo[1,2-b]isothiazoline-R3a, imidazo[1,5-b]isoxazolin-R3a, imidazo[1,5-b]isothiazoline-R3a, imidazo[5,1-b]oxazoline-R3a, imidazo[5,1-b]thiazoline-R3a, 1H-imidazo[1,5-a]imidazole�Yong-R3a, 6H-imidazo[3,2-d]isoxazolin-R3a, 6H-imidazo[3,2-d]isothiazoline-R3a, imidazo[2,1-b][1,3,4]oxadiazolyl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-R3a, 1H-imidazo[1,2-b][1,2,4]triazolium-R3a, 3H-furo[2,3-d]imidazolidin-R3a, 3H-thieno[2,3-d]imidazolidin-R3a, 3,4-dihydropyrrolo[2,3-d]imidazolidin-R3a, furo[3,2-d]thiazolidin-R3a, thieno[3,2-d]thiazolidin-R3a, 4H-imidazo[3,2-d]thiazolidin-R3a, 4H-pyrazolo[3,4-d]isoxazolin-R3a, 4H-pyrazolo[3,4-d]isothiazoline-R3a, 1,4-dihydropyrazolo[4,3-c]pyrazoline-R3a, isoxazole[5,4-d]isoxazolin-R3a, isothiazole[5,4-d]isothiazoline-R3a, imidazo[2,1-b][1,3,4]thiadiazole-R3a, 1H-imidazo[1,5-a]imidazolidin-R3a, imidazo[2,1-b]oxazoline-R3a, imidazo[2,1-b]thiazoline-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, thieno[3,2-b]TuranAlem-R3a or thiazolo[5,4-d]thiazolidin-R3a, each optionally substituted by one or more substituents R3, where R3 is as as defined in this document.

In particular embodiments, A represents imidazo[2,1-b]thiazole-5,6-yl-R3a, 3H-pyrrolizine-1,5-yl-R3a, 3H-pyrrolizine-2,6-yl-R3a, 4H-furo[3,2-b]pyrrol-2,5-yl-R3a, 4H-furo[3,2-b]pyrrole-3,6-yl-R3a, furo[3,2-b]furan-2,5-yl-R3a, furo[3,2-b]furan-3,6-yl-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrol-2,5-yl-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrole-3,6-yl-R3a, 5H-imidazo[1,2-c]imidazole-3,7-yl-R3a, 4H-furo[3,2-b]pyrrol-2,4-yl-R3a, 4H-furo[3,2-b]pyrrol-2,5-yl-R3a, 4H-furo[3,2-b]the pyrrole-3,4-yl-R3a, 4H-furo[3,2-b]pyrrole-3,6-yl-R3a, 6H-imidazo[1,2-a]pyrazole-2,5-yl-R3a, 5H-imidazo[1,2-a]imidazole-2,6-yl-R3a, 5H-imidazo[1,2-a]imidazole-3,7-yl-R3a, thieno[3,2-b]furan-2,5-yl-R3a, thieno[3,2-b]furan-3,6-yl-R3a, 1H-furo[3,2-c]pyrazol-3,6-yl-R3a, 1H-thieno[3,2-c]pyrazol-3,6-yl-R3a, 1,4-dihydropyrrolo[3,2-c]pyrazol-3,6-yl-R3a, 1H-imidazo[1,2-a]imidazole-2,6-yl-R3a, pyrazolo[5,1-b]oxazol-2,6-yl-R3a, pyrazolo[5,1-b]oxazol-3,7-yl-R3a, pyrazolo[5,1-b]thiazole-2,6-yl-R3a, pyrazolo[5,1-b]thiazole-3,7-yl-R3a, 5H-imidazo[1,2-b]pyrazole-2,6-yl-R3a, 5H-imidazo[1,2-b]pyrazol-3,7-yl-R3a, imidazo[1,2-b]isoxazol-2,6-yl-R3a, imidazo[1,2-b]isoxazol-3,7-yl-R3a, imidazo[1,2-b]isothiazol-2,6-yl-R3a, imidazo[1,2-b]isothiazol-3,7-yl-R3a, imidazo[1,5-b]isoxazol-3,7-yl-R3a, imidazo[1,5-b]isothiazol-3,6-yl-R3a, imidazo[5,1-b]oxazol-3,7-yl-R3a, imidazo[5,1-b]thiazole-3,7-yl-R3a, 1H-imidazo[1,5-a]imidazole-3,7-yl-R3a, 6H-imidazo[3,2-d]izocsazol-3,6-yl-R3a, 6H-imidazo[3,2-d]isothiazol-3,6-yl-R3a, imidazo[2,1-b][1,3,4]oxidiazol-2,6-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl-R3a, 1H-imidazo[1,2-b][1,2,4]triazole-1,5-yl-R3a, 1H-imidazo[1,2-b][1,2,4]triazole-2,6-yl-R3a, 3H-furo[2,3-d]imidazole-2,5-yl-R3a, 3H-furo[2,3-d]imidazole-3,6-yl-R3a, 3H-thieno[2,3-d]imidazole-2,5-yl-R3a, 3H-thieno[2,3-d]imidazole-3,6-yl-R3a, 3,4-dihydropyrrolo[2,3-d]imidazole-2,5-yl-R3a, 3,4-dihydropyrrolo[2,3-d]imidazole-3,6-yl-R3a, furo[3,2-d]thiazole-2,5-yl-R3a, thieno[3,2-d]thiazole-2,5-yl-R3a, 4H-imidazo[3,2-d]thiazole-2,5-yl-R3a, 4H-pyrazolo[3,4-d]izocsazol-3,6-yl-R3a, 4H-pyrazolo[3,4-d]isothiazol-3,6-yl-R3a, 1,4-dihydropyrazolo[4,3-c]pyrazole-1,4-ilen-R3a, 1,4-Digi�reperusal[4,3-c]pyrazol-3,6-yl-R3a, isoxazole[5,4-d]izocsazol-3,6-yl-R3a, isothiazole[5,4-d]isothiazol-3,6-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,5-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl-R3a, 6H-imidazo[3,2-d]izocsazol-3,6-yl-R3a, 1H-imidazo[1,5-a]imidazole-1,5-yl-R3a, imidazo[2,1-b]oxazol-2,5-yl-R3a, imidazo[2,1-b]thiazole-2,5-yl-R3a, 1H-imidazo[1,2-a]imidazole-2,5-yl-R3a, 1H-imidazo[1,2-a]imidazole-1,5-yl-R3a, thieno[3,2-b]furan-3,6-yl-R3a or thiazolo[5,4-d]thiazole-2,5-yl-R3a, each optionally substituted by one or more substituents R3, where R3 is as as defined in this document.

In specific embodiments, E is C2-6 akinyan, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin. In specific embodiments, E is a C3-7 cycloalkyl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is cyclohexyl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a C6-14 Allen, optionally substituted by one or more of the Deputy�the sinks R3, where R3 is as defined herein. In specific embodiments, E is a monocyclic, Allen, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a phenylene optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a bicyclic, Allen, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is C2-6 akinyan-C6-14 Allen, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin-C6-14 Allen, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin-phenylene, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, is�the implementation of E represents echinilin-1,4-phenylene, optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, E is heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a monocyclic, heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a 5-membered, heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is TuranAlem, isothiazoline, isoxazoline, imidazoline, Tianjin or thiazoline, each optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E represents thiazol-2,5-yl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a 6-membered, heteroaryl, niobate�till then substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a bicyclic, heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a 5,5-condensed heteroaryl, optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a thieno[3,2-b]tienlen, imidazo[3,4-c]pyrroline, 4H-thieno[3,2-b]pyrrolidin, 6H-thieno[2,3-b]pyrrolidin, imidazo[2,1-b]oxazoline, imidazo[2,1-b]thiazoline or 4H-imidazo[3,2-d]thiazoline, each optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a thieno[3,2-b]Thien-2,6-yl, thieno[3,2-b]Thien-3,6-yl, imidazo[3,4-c]pyrrol-1,4-yl, 4H-thieno[3,2-b]pyrrol-2,5-yl, 6H-thieno[2,3-b]pyrrole-3,6-ilen, imidazo[2,1-b]oxazol-2,6-ilen, imidazo[2,1-b]the thiazole-2,6-yl or 4H-imidazo[3,2-d]thiazole-2,5-yl, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, E has the pleasure to present a 3H-pyrroles�nilen, 4H-furo[3,2-b]pyrrolidin, furo[3,2-b]TuranAlem, 1,4-dihydropyrrolo[3,2-b]pyrrolidin, 5H-imidazo[1,2-c]imidazolyl, 4H-furo[3,2-b]pyrrolidin, 6H-imidazo[1,2-b]pyrazoline, 5H-imidazo[1,2-a]imidazolyl, thieno[3,2-b]TuranAlem, 1H-furo[3,2-c]pyrazoline, 1H-thieno[3,2-c]pyrazoline, 1,4-dihydropyrrolo[3,2-c]pyrazoline, 1H-imidazo[1,2-a]imidazolyl, pyrazolo[5,1-b]oxazoline, pyrazolo[5,1-b]thiazoline, 5H-imidazo[1,2-b]pyrazoline, imidazo[1,2-b]isoxazolyl, imidazo[1,2-b]isothiazoline, imidazo[1,5-b]isoxazolyl, imidazo[1,5-b]isothiazoline, imidazo[5,1-b]oxazoline, imidazo[5,1-b]thiazoline, 1H-imidazo[1,5-a]imidazolyl, 6H-imidazo[3,2-d]isoxazoline, 6H-imidazo[3,2-d]isothiazoline, imidazo[2,1-b][1,3,4]oxadiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-imidazo[1,2-b][1,2,4]triazolyl, 3H-furo[2,3-d]imidazoline, 3H-thieno[2,3-d]imidazoline, 3,4-dihydropyrrolo[2,3-d]imidazoline, furo[3,2-d]thiazoline, thieno[3,2-d]thiazoline, 4H-imidazo[3,2-d]thiazoline, 4H-pyrazolo[3,4-d]isoxazoline, 4H-pyrazolo[3,4-d]isothiazoline, 1,4-dihydropyrazolo[4,3-c]pyrazoline, isoxazole[5,4-d]isoxazoline, isothiazole[5,4-d]isothiazoline, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-imidazo[1,5-a]imidazolyl, imidazo[2,1-b]oxazoline, imidazo[2,1-b]thiazoline, 1H-imidazo[1,2-a]imidazolyl, 1H-imidazo[1,2-a]imidazolyl, thieno[3,2-b]TuranAlem or thiazolo[5,4-d]thiazoline, each optionally substituted by one or more substituents R3, where R3 assetdetail, as defined in this document.

In specific embodiments, E is imidazo[2,1-b]thiazole-5,6-yl, 3H-pyrrolizine-1,5-yl, 3H-pyrrolizine-2,6-yl, 4H-furo[3,2-b]pyrrol-2,5-yl, 4H-furo[3,2-b]pyrrole-3,6-yl, furo[3,2-b]furan-2,5-yl, furo[3,2-b]furan-3,6-ilen, 1,4-dihydropyrrolo[3,2-b]pyrrol-2,5-yl, 1,4-dihydropyrrolo[3,2-b]pyrrole-3,6-yl, 5H-imidazo[1,2-c]imidazole-3,7-yl, 4H-furo[3,2-b]pyrrol-2,4-yl, 4H-furo[3,2-b]pyrrol-2,5-yl, 4H-furo[3,2-b]pyrrol-3,4-yl, 4H-furo[3,2-b]pyrrole-3,6-yl, 6H-imidazo[1,2-b]pyrazol-2,5-yl, 5H-imidazo[1,2-a]imidazole-2,6-yl, 5H-imidazo[1,2-a]imidazole-3,7-yl, thieno[3,2-b]furan-2,5-yl, thieno[3,2-b]furan-3,6-yl, 1H-furo[3,2-c]pyrazol-3,6-yl, 1H-thieno[3,2-c]pyrazol-3,6-ilen, 1,4-dihydropyrrolo[3,2-c]pyrazol-3,6-yl, 1H-imidazo[1,2-a]imidazole-2,6-ilen, pyrazolo[5,1-b]oxazol-2,6-ilen, pyrazolo[5,1-b]oxazol-3,7-ilen, pyrazolo[5,1-b]thiazole-2,6-ilen, pyrazolo[5,1-b]thiazole-3,7-yl, 5H-imidazo[1,2-b]pyrazole-2,6-yl, 5H-imidazo[1,2-b]pyrazol-3,7-ilen, imidazo[1,2-b]izocsazol-2,6-ilen, imidazo[1,2-b]isoxazol-3,7-ilen, imidazo[1,2-b]isothiazol-2,6-ilen, imidazo[1,2-b]isothiazol-3,7-ilen, imidazo[1,5-b]isoxazol-3,7-ilen, imidazo[1,5-b]isothiazol-3,6-ilen, imidazo[5,1-b]oxazol-3,7-ilen, imidazo[5,1-b]thiazole-3,7-yl, 1H-imidazo[1,5-a]imidazole-3,7-yl, 6H-imidazo[3,2-d]izocsazol-3,6-yl, 6H-imidazo[3,2-d]isothiazol-3,6-yl, imidazo[2,1-b][1,3,4]oxidiazol-2,6-yl, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl, 1H-imidazo[1,2-b][1,2,4]triazole-1,5-yl, Nerola[1,2-b][1,2,4]triazole-2,6-ilen, 3H-furo[2,3-d]imidazole-2,5-yl, 3H-furo[2,3-d]imidazole-3,6-yl, 3H-thieno[2,3-d]imidazole-2,5-yl, 3H-thieno[2,3-d]imidazole-3,6-yl, 3,4-dihydropyrrolo[2,3-d]imidazole-2,5-yl, 3,4-dihydropyrrolo[2,3-d]imidazole-3,6-yl, furo[3,2-d]thiazole-2,5-yl, thieno[3,2-d]thiazole-2,5-yl, 4H-imidazo[3,2-d]thiazole-2,5-yl, 4H-pyrazolo[3,4-d]izocsazol-3,6-yl, 4H-pyrazolo[3,4-d]isothiazol-3,6-ilen, 1,4-dihydropyrazolo[4,3-c]pyrazole-1,4-ilen, 1,4-dihydropyrazolo[4,3-c]pyrazol-3,6-ilen, isoxazole[5,4-d]izocsazol-3,6-ilen, isothiazole[5,4-d]isothiazol-3,6-ilen, imidazo[2,1-b][1,3,4]thiadiazole-2,5-yl, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl, 6H-imidazo[3,2-d]izocsazol-3,6-yl, 1H-imidazo[1,5-a]imidazole-1,5-yl, imidazo[2,1-b]oxazol-2,5-yl, imidazo[2,1-b]thiazole-2,5-yl, 1H-imidazo[1,2-a]imidazole-2,5-yl, 1H-imidazo[1,2-a]imidazole-1,5-yl, thieno[3,2-b]furan-3,6-yl or thiazolo[5,4-d]thiazole-2,5-yl, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, E is a 3H-pyrrolizine-R3a, 4H-furo[3,2-b]pyrrolidin-R3a, furo[3,2-b]TuranAlem-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrolidin-R3a, 5H-imidazo[1,2-c]imidazolium-R3a, 4H-furo[3,2-b]pyrrolidin-R3a, 6H-imidazo[1,2-b]pyrazoline-R3a, 5H-imidazo[1,2-a]imidazolidin-R3a, thieno[3,2-b]TuranAlem-R3a, 1H-furo[3,2-c]pyrazoline-R3a, 1H-thieno[3,2-c]pyrazoline-R3a, 1,4-dihydropyrrolo[3,2-c]pyrazoline-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, Piras�lo[5,1-b]oxazoline-R3a, pyrazolo[5,1-b]thiazoline-R3a, 5H-imidazo[1,2-b]pyrazoline-R3a, imidazo[1,2-b]isoxazolin-R3a, imidazo[1,2-b]isothiazoline-R3a, imidazo[1,5-b]isoxazolin-R3a, imidazo[1,5-b]isothiazoline-R3a, imidazo[5,1-b]oxazoline-R3a, imidazo[5,1-b]thiazoline-R3a, 1H-imidazo[1,5-a]imidazolidin-R3a, 6H-imidazo[3,2-d]isoxazolin-R3a, 6H-imidazo[3,2-d]isothiazoline-R3a, imidazo[2,1-b][1,3,4]oxadiazolyl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-R3a, 1H-imidazo[1,2-b][1,2,4]triazolium-R3a, 3H-furo[2,3-d]imidazolidin-R3a, 3H-thieno[2,3-d]imidazolidin-R3a, 3,4-dihydropyrrolo[2,3-d]imidazolidin-R3a, furo[3,2-d]thiazolidin-R3a, thieno[3,2-d]thiazolidin-R3a, 4H-imidazo[3,2-d]thiazolidin-R3a, 4H-pyrazolo[3,4-d]isoxazolin-R3a, 4H-pyrazolo[3,4-d]isothiazoline-R3a, 1,4-dihydropyrazolo[4,3-c]pyrazoline-R3a, isoxazole[5,4-d]isoxazolin-R3a, isothiazole[5,4-d]isothiazoline-R3a, imidazo[2,1-b][1,3,4]thiadiazole-R3a, 1H-imidazo[1,5-a]imidazolidin-R3a, imidazo[2,1-b]oxazoline-R3a, imidazo[2,1-b]thiazoline-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, 1H-imidazo[1,2-a]imidazolidin-R3a, thieno[3,2-b]TuranAlem-R3a or thiazolo[5,4-d]thiazolidin-R3a, each optionally substituted by one or more substituents R3, where R3 is as as defined in this document.

In specific embodiments, E is imidazo[2,1-b]thiazole-5,6-yl-R3a, 3H-pyrrolizine-1,5-yl-R3a, 3H-pyrrolizine-2,6-yl-R3a, 4H-furo[3,2-b]pyrrol-2,5-yl-R3a, 4H-furo[3,2-b]pyrrole-3,6-yl-R3a, furo[3,2-b]furan-2,5-yl-R3a furo[3,2-b]furan-3,6-yl-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrol-2,5-yl-R3a, 1,4-dihydropyrrolo[3,2-b]pyrrole-3,6-yl-R3a, 5H-imidazo[1,2-c]imidazole-3,7-yl-R3a, 4H-furo[3,2-b]pyrrol-2,4-yl-R3a, 4H-furo[3,2-b]pyrrol-2,5-yl-R3a, 4H-furo[3,2-b]pyrrol-3,4-yl-R3a, 4H-furo[3,2-b]pyrrole-3,6-yl-R3a, 6H-imidazo[1,2-b]pyrazole-2,5-yl-R3a, 5H-imidazo[1,2-a]imidazole-2,6-yl-R3a, 5H-imidazo[1,2-a]imidazole-3,7-yl-R3a, thieno[3,2-b]furan-2,5-yl-R3a, thieno[3,2-b]furan-3,6-yl-R3a, 1H-furo[3,2-c]pyrazol-3,6-yl-R3a, 1H-thieno[3,2-c]pyrazol-3,6-yl-R3a, 1,4-dihydropyrrolo[3,2-c]pyrazol-3,6-yl-R3a, 1H-imidazo[1,2-a]imidazole-2,6-yl-R3a, pyrazolo[5,1-b]oxazol-2,6-yl-R3a, pyrazolo[5,1-b]oxazol-3,7-yl-R3a, pyrazolo[5,1-b]thiazole-2,6-yl-R3a, pyrazolo[5,1-b]thiazole-3,7-yl-R3a, 5H-imidazo[1,2-b]pyrazole-2,6-yl-R3a, 5H-imidazo[1,2-b]pyrazol-3,7-yl-R3a, imidazo[1,2-b]isoxazol-2,6-yl-R3a, imidazo[1,2-b]isoxazol-3,7-yl-R3a, imidazo[1,2-b]isothiazol-2,6-yl-R3a, imidazo[1,2-b]isothiazol-3,7-yl-R3a, imidazo[1,5-b]isoxazol-3,7-yl-R3a, imidazo[1,5-b]isothiazol-3,6-yl-R3a, imidazo[5,1-b]oxazol-3,7-yl-R3a, imidazo[5,1-b]thiazole-3,7-yl-R3a, 1H-imidazo[1,5-a]imidazole-3,7-yl-R3a, 6H-imidazo[3,2-d]izocsazol-3,6-yl-R3a, 6H-imidazo[3,2-d]isothiazol-3,6-yl-R3a, imidazo[2,1-b][1,3,4]oxidiazol-2,6-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl-R3a, 1H-imidazo[1,2-b][1,2,4]triazole-1,5-yl-R3a, 1H-imidazo[1,2-b][1,2,4]triazole-2,6-yl-R3a, 3H-furo[2,3-d]imidazole-2,5-yl-R3a, 3H-furo[2,3-d]imidazole-3,6-yl-R3a, 3H-thieno[2,3-d]imidazole-2,5-yl-R3a, 3H-thieno[2,3-d]imidazole-3,6-yl-R3a, 3,4-dihydropyrrolo[2,3-d]imidazole-2,-yl-R3a, 3,4-dihydropyrrolo[2,3-d]imidazole-3,6-yl-R3a, furo[3,2-d]thiazole-2,5-yl-R3a, thieno[3,2-d]thiazole-2,5-yl-R3a, 4H-imidazo[3,2-d]thiazole-2,5-yl-R3a, 4H-pyrazolo[3,4-d]izocsazol-3,6-yl-R3a, 4H-pyrazolo[3,4-d]isothiazol-3,6-yl-R3a, 1,4-dihydropyrazolo[4,3-c]the pyrazole-1,4-ilen-R3a, 1,4-dihydropyrazolo[4,3-c]pyrazol-3,6-yl-R3a, isoxazole[5,4-d]izocsazol-3,6-yl-R3a, isothiazole[5,4-d]isothiazol-3,6-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,5-yl-R3a, imidazo[2,1-b][1,3,4]thiadiazole-2,6-yl-R3a, 6H-imidazo[3,2-d]izocsazol-3,6-yl-R3a, 1H-imidazo[1,5-a]imidazole-1,5-yl-R3a, imidazo[2,1-b]oxazol-2,5-yl-R3a, imidazo[2,1-b]thiazole-2,5-yl-R3a, 1H-imidazo[1,2-a]imidazole-2,5-yl-R3a, 1H-imidazo[1,2-a]imidazole-1,5-yl-R3a, thieno[3,2-b]furan-3,6-yl-R3a or thiazolo[5,4-d]thiazole-2,5-yl-R3a, each optionally substituted by one or more substituents R3, where R3 is as defined herein.

In specific embodiments, E is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 independently represents chlorine, fluorine, nitro, amino, methyl, trifluoromethyl, phenyl or methoxy.

In specific embodiments, E is selected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, hydroxy, amino, methyl, trifluoromethyl, cyclohexyl, phenyl, methoxy, or methoxycarbonyl.

In specific embodiments, E or divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, hydroxy, amino, methyl, trifluoromethyl, cyclohexyl, phenyl, methoxy, or methoxycarbonyl.

In specific embodiments, E or divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined�eno in this document. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, hydroxy, amino, methyl, trifluoromethyl, cyclohexyl, phenyl, methoxy, or methoxycarbonyl.

In specific embodiments, E or divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, hydroxy, amino, methyl, trifluoromethyl, cyclohexyl, phenyl, methoxy, or methoxycarbonyl.

In specific embodiments, E or divalent groupselected from:

wherein each bivalent group is optionally substituted with one, two, three or four, in one embodiment, the implementation of one or two R3 groups, where R3 is as defined herein. In specific embodiments, each R3 represents, independently oxo, chloro, fluoro, nitro, hydroxy, amino, methyl, trifluoromethyl, cyclohexyl, phenyl, methoxy, or methoxycarbonyl.

p> In specific embodiments, E is C2-6 akinyan-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is echinilin-R3a, where R3a is as defined herein. In specific embodiments, E is phenylethynyl. In specific embodiments, E is a C3-7 cycloalkyl-R3a, optionally substituted with one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is cyclohexyl-R3a, optionally substituted with one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is a C6-14 Allen-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a monocyclic, Allen-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is with�fight the phenylene-R3a, optionally substituted by one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a phenyl or Dapsone base. In specific embodiments, E is a 4-Dapsone base. In specific embodiments, E is a bicyclic, Allen-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is C2-6 akinyan-C6-14 Allen-R3a, optionally substituted with one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin-C6-14 Allen-R3a, optionally substituted with one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin-phenylene-R3a, optionally substituted with one or more substituents R3, where R3 is as defined herein. In specific embodiments, E is echinilin-1,4-phenylene-R3a, optionally substituted with one or more substituents R3, where R3 is as defined�Elena in this document.

In specific embodiments, E is heteroaryl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a monocyclic, heteroaryl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a 5-membered, heteroaryl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is TuranAlem-R3a, isothiazoline-R3a, isoxazoline-R3a, imidazolidin-R3a, tienlen-R3a or thiazolidin-R3a, each optionally substituted by one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E represents thiazol-2,5-yl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a 6-membered, heteroaryl-R3a, optionally substituted with one or more� substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a bicyclic, heteroaryl-R3a, optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein.

In specific embodiments, E is a 5,5-condensed heteroaryl-R3a, optionally substituted with one or more substituents R3a, where R3a and R3, each, are as defined herein. In specific embodiments, E is a thieno[3,2-b]Tianjin-R3a, imidazo[3,4-c]pyrrolidin-R3a, 4H-thieno[3,2-b]pyrrolidin-R3a, 6H-thieno[2,3-b]pyrrolidin-R3a, imidazo[2,1-b]oxazoline-R3a, imidazo[2,1-b]thiazoline-R3a or 4H-imidazo[3,2-d]thiazolidin-R3a, each optionally substituted with one or more substituents R3, where R3a and R3, each, are as defined herein. In specific embodiments, E is a thieno[3,2-b]thienyl, imidazo[3,4-c]pyrrolyl, 4H-thieno[3,2-b]pyrrolyl, 6H-thieno[2,3-b]pyrrolyl, imidazo[2,1-b]oxazolyl, imidazo[2,1-b]thiazolyl or 4H-imidazo[3,2-d]thiazolyl, each optionally substituted by one or more substituents R3, where R3 is as defined herein. In specific embodiments implemented�I E is a thieno[3,2-b]Thien-3,6-yl-R3a, imidazo[3,4-c]pyrrol-1,4-ilen-R3a, 4H-thieno[3,2-b]pyrrol-2,5-yl-R3a, 6H-thieno[2,3-b]pyrrole-3,6-yl-R3a, imidazo[2,1-b]oxazol-2,6-yl-R3a, imidazo[2,1-b]thiazole-2,6-yl-R3a or 4H-imidazo[3,2-d]thiazole-2,5-yl-R3a, each optionally substituted by one or more substituents R3, where R3a and R3, each, are as defined herein.

In specific embodiments, L1 is a bond. In specific embodiments, L1 is not a bond. In specific embodiments, L1 is a C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, L1 is a C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, L1 is a C2-6 akinyan, optionally substituted by one or more substituents Q. In particular embodiments, L1 is a C3-7 cycloalkyl, optionally substituted by one or more substituents Q. In particular embodiments, L1 represents a C6-14 Allen, optionally substituted by one or more substituents Q. In particular embodiments, L1 represents a C6-14 Allen-heteroaryl, optionally substituted by one or more substituents Q. In concretisering implementation L1 represents a phenyl-heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, L1 is a phenyl-imidazolyl, optionally substituted by one or more substituents Q. In particular embodiments, L1 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, L1 represents a five - or six-membered, heteroaryl, each optionally substituted by one or more substituents Q. In particular embodiments, L1 is pyrazoline, imidazoline or triazolyl, each optionally substituted by one or more substituents Q. In particular embodiments, L1 is not thiazoline. In specific embodiments, L1 is pyrazoline, imidazoline, oxazoline, 1,3,4-oxadiazolyl, 1,2,3-triazolyl or 1,2,4-triazolyl, each optionally substituted by one or more substituents Q. In particular embodiments, L1 represents a pyrazole-3,5-ilen, oxazol-2,5-yl, imidazol-2,4-yl, 1,3,4-oxadiazol-2,5-yl, 1,2,3-triazole-1,4-yl, 1,2,3-triazole-2,4-yl or 1,2,4-triazole-3,5-yl, each optionally substituted by one or more substituents Q. In particular embodiments, L1 represents a hetero�Allen-C1-6 alkylen, optionally substituted by one or more substituents Q. In particular embodiments, L1 is imidazolyl-methylene, optionally substituted by one or more substituents Q. In particular embodiments, L1 is an imidazole-2,4-yl-methylene, optionally substituted by one or more substituents Q. In particular embodiments, L1 is heteroaryl-C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, L1 is heteroaryl-C2-6 akinyan, optionally substituted by one or more substituents Q. In particular embodiments, L1 is heterocyclyl; optionally substituted by one or more substituents Q.

In specific embodiments, L1 is a-C(O)-. In specific embodiments, L1 is a-C(O)O-. In specific embodiments, L1 is a-C(O)NR1a-, where R1a is as defined herein. In specific embodiments, L1 is a-C(O)NH-. In specific embodiments, L1 is a-C(=NR1a)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L1 a-O-. In specific embodiments, L1 represents-OC(O)O-. In specific embodiments, L1 represents-OC(O)NR1a-, where R1a is as defined herein. In specific embodiments, L1 is a-OC(=NR1a)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L1 is a-OP(O)(OR1a)-, where R1a is as defined herein. In specific embodiments, L1 is a-NR1a-, where R1a is as defined herein. In specific embodiments, L1 is a-NR1aC(O)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L1 is a-NR1aC(=NR1b)NR1c-, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, L1 is a-NR1aS(O)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L1 is a-NR1aS(O)2NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L1 represents-S-. In specific embodiments, L1 represents-S(O)-. In specific embodiments, is�the implementation L1 represents-S(O)2-. In specific embodiments, L1 represents-S(O)NR1a-, where R1a is as defined herein. In specific embodiments, L1 represents-S(O)2NR1a-, where R1a is as defined herein.

In specific embodiments, Allen and Allenova group, C6-14 Allen-heteroaryl to L1 represents a 5,6 - or 6,6-condensed arisen. In specific embodiments, heteroaryl and heteroarenes group, C6-14 Allen-heteroaryl, heteroaryl-C1-6 alkylene, heteroaryl-C2-6 Alcanena and heteroaryl-C2-6 albinyana to L1 represents a 5,6 - or 6,6-condensed heteroaryl.

In specific embodiments, L2 is a bond. In specific embodiments, L2 is not a bond. In specific embodiments, L2 is a C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a C2-6 akinyan, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a C3-7 cycloalkyl, not necessarily Vice�by one or more substituents Q. In specific embodiments, L2 is a C6-14 Allen, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a C6-14 Allen-heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a phenyl-heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a phenyl-imidazolyl, optionally substituted by one or more substituents Q. In particular embodiments, L2 is heteroaryl, optionally substituted by one or more substituents Q. In particular embodiments, L2 is a five - or six-membered, heteroaryl, each optionally substituted by one or more substituents Q. In particular embodiments, L2 is pyrazoline, imidazoline or triazolyl, each optionally substituted by one or more substituents Q. In particular embodiments, L2 is not thiazoline. In specific embodiments, L2 is pyrazoline, oxazoline, imidazoline, 1,3,4-oxadiazolyl, 1,2,3-triazolyl or 1,2,4-triazolyl, each not necessarily samewe� one or more substituents Q. In specific embodiments, L2 represents a pyrazole-3,5-ilen, oxazol-2,5-yl, imidazol-2,4-yl, 1,3,4-oxadiazol-2,5-yl, 1,2,3-triazole-1,4-yl, 1,2,3-triazole-2,4-yl or 1,2,4-triazole-3,5-yl, each optionally substituted by one or more substituents Q. In particular embodiments, L2 is heteroaryl-C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, L2 is imidazolyl-methylene, optionally substituted by one or more substituents Q. In particular embodiments, L2 is an imidazole-2,4-yl-methylene, optionally substituted by one or more substituents Q. In particular embodiments, L2 is heteroaryl-C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, L2 is heteroaryl-C2-6 akinyan, optionally substituted by one or more substituents Q. In particular embodiments, L2 is heterocyclyl; optionally substituted by one or more substituents Q.

In specific embodiments, L2 is a-C(O)-. In specific embodiments, L2 is a-C(O)O-. In specific embodiments, the OSU�of estline L2 represents-C(O)NR1a-, where R1a is as defined herein. In specific embodiments, L2 is a-C(O)NH-. In specific embodiments, L2 is a-C(=NR1a)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L2 represents-O-. In specific embodiments, L2 represents-OC(O)O-. In specific embodiments, L2 represents-OC(O)NR1a-, where R1a is as defined herein. In specific embodiments, L2 is a-OC(=NR1a)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L2 is a-OP(O)(OR1a)-, where R1a is as defined herein. In specific embodiments, L2 is a-NR1a-, where R1a is as defined herein. In specific embodiments, L2 is a-NR1aC(O)NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L2 is a-NR1aC(=NR1b)NR1c-, where R1a, R1b and R1c each, are as defined herein. In specific embodiments, L2 is a-NR1aS(O)NR1c-, where R1a and R1c, each, are as about�the determined herein. In specific embodiments, L2 is a-NR1aS(O)2NR1c-, where R1a and R1c, each, are as defined herein. In specific embodiments, L2 represents-S-. In specific embodiments, L2 represents-S(O)-. In specific embodiments, L2 represents-S(O)2-. In specific embodiments, L2 represents-S(O)NR1a-, where R1a is as defined herein. In specific embodiments, L2 represents-S(O)2NR1a-, where R1a is as defined herein.

In specific embodiments, Allen and Allenova group, C6-14 Allen-heteroaryl in L2 do not represent a 5,6 - or 6,6-condensed arisen. In specific embodiments, heteroaryl and heteroarenes group, C6-14 Allen-heteroaryl, heteroaryl-C1-6 alkylene, heteroaryl-C2-6 Alcanena and heteroaryl-C2-6 albinyana in L2 do not represent a 5,6 - or 6,6-condensed heteroaryl.

In specific embodiments, L1 and L2 each independently selected from:

In specific embodiments, L1 and L2 each independently selected from:

In specific embodiments, L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; (in each group indicates the point of attachment through which the group is associated withor; and where T3 is a bond, C, N, O, S, CR3a, or NR3a; U3, V3, W3, and X3 are each independently C, N, O, S, CR3a, or NR3a; and Y3 represents C or N; where each of R3a and R3 is as defined herein.

In specific embodiments, L1 and L2 each independently selected from:

where each group is optionally substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; (in each group indicates the point of attachment through which the group is associated withor; where each R3 is as defined herein.

In specific embodiments, L1 and L2 each independently selected from:

where each group neoblast�flax substituted with one, two, three or four R3; the star (*) in each group indicates the point of attachment through which the group is associated with U1, U2, V1, V2, W1 or W2 in; (in each group indicates the point of attachment through which the group is associated withor; where each R3 is as defined herein.

In specific embodiments, T3 is a bond. In specific embodiments, T3 is a C. In specific embodiments, T3 represents N. In specific embodiments, T3 represents O. In specific embodiments, T3 is a S. In specific embodiments, T3 is a CR3a, where R3a is as defined herein. In specific embodiments, T3 is a CH. In specific embodiments, T3 is a NR3a, where R3a is as defined herein. In specific embodiments, T3 is a NH.

In specific embodiments, U1 is a C. In specific embodiments, U1 represents N. In specific embodiments, U1 represents O. In specific embodiments, osushestvlenie� U1 represents S. In specific embodiments, U1 is a CR3a, where R3a is as defined herein. In specific embodiments, U1 is a CH. In specific embodiments, U1 is a NR3a, where R3a is as defined herein. In specific embodiments, U1 represents NH.

In specific embodiments, U2 represents a C. In specific embodiments, U2 represents N. In specific embodiments, U2 represents O. In specific embodiments, U2 represents S. In specific embodiments, U2 is a CR3a, where R3a is as defined herein. In specific embodiments, U2 represents CH. In specific embodiments, U2 represents NR3a, where R3a is as defined herein. In specific embodiments, U2 represents NH.

In specific embodiments, U3 represents a C. In specific embodiments, U3 represents N. In specific embodiments, U3 represents O. In specific embodiments, U3 represents S. In specific embodiments, U3 is a CR3a, where R3a is�tsya, as defined in the present document. In specific embodiments, U3 represents CH. In specific embodiments, U3 represents NR3a, where R3a is as defined herein. In specific embodiments, U3 represents NH.

In specific embodiments, V1 is a C. In specific embodiments, V1 represents N. In specific embodiments, V1 represents O. In specific embodiments, V1 represents S. In specific embodiments, V1 is a CR3a, where R3a is as defined herein. In specific embodiments, V1 is a CH. In specific embodiments, V1 is a NR3a, where R3a is as defined herein. In specific embodiments, V1 represents NH.

In specific embodiments, V2 is a C. In specific embodiments, V2 represents N. In specific embodiments, V2 represents O. In specific embodiments, V2 is a S. In specific embodiments, V2 is a CR3a, where R3a is as defined herein. In specific embodiments, the implementation�Oia V2 represents CH. In specific embodiments, V2 is a NR3a, where R3a is as defined herein. In specific embodiments, V2 is a NH.

In specific embodiments, V3 is a C. In specific embodiments, V3 represents N. In specific embodiments, V3 represents O. In specific embodiments, V3 is a S. In specific embodiments, V3 is a CR3a, where R3a is as defined herein. In specific embodiments, V3 is a CH. In specific embodiments, V3 is a NR3a, where R3a is as defined herein. In specific embodiments, V3 is a NH.

In specific embodiments, W1 represents a C. In specific embodiments, W1 represents N. In specific embodiments, W1 represents O. In specific embodiments, W1 represents S. In specific embodiments, W1 is a CR3a, where R3a is as defined herein. In specific embodiments, W1 represents CH. In specific embodiments, W1 is an NR3a, where R3a is�tsya, as defined in the present document. In specific embodiments, W1 represents NH.

In specific embodiments, W2 is a C. In specific embodiments, W2 represents N. In specific embodiments, W2 represents O. In specific embodiments, W2 represents S. In specific embodiments, W2 is a CR3a, where R3a is as defined herein. In specific embodiments, W2 represents CH. In specific embodiments, W2 is a NR3a, where R3a is as defined herein. In specific embodiments, W2 represents NH.

In specific embodiments, W3 is a C. In specific embodiments, W3 represents N. In specific embodiments, W3 represents O. In specific embodiments, W3 represents S. In specific embodiments, W3 is a CR3a, where R3a is as defined herein. In specific embodiments, W3 is a CH. In specific embodiments, W3 is a NR3a, where R3a is as defined herein. In specific embodiments, the implementation�Oia W3 represents NH.

In specific embodiments, X1 represents a C. In specific embodiments, X1 is N. a

In specific embodiments, X2 is a C. In specific embodiments, X2 is N. a

In specific embodiments, X3 represents a C. In specific embodiments, X3 is N. In a specific embodiments, X3 represents O. In specific embodiments, X3 represents S. In specific embodiments, X3 is a CR3a, where R3a is as defined herein. In specific embodiments, X3 represents CH. In specific embodiments, X3 is an NR3a, where R3a is as defined herein. In specific embodiments, X3 represents NH.

In specific embodiments, Y3 represents a C. In specific embodiments, Y3 represents N.

In specific embodiments, Z1 is a bond. In specific embodiments, Z1 represents-O-. In specific embodiments, Z1 represents-S-. In specific embodiments, Z1 represents-S(O)-. In specific embodiments, Z1 isone-S(O2)-. In specific embodiments, Z1 represents-N(R7) - where R7 is as defined herein. In specific embodiments, Z1 represents-NH-. In specific embodiments, Z1 represents-N(C(O)R1a)-, where R1a is as defined herein. In specific embodiments, Z1 represents-N(C(O)C1-6 alkyl)-. In specific embodiments, Z1 represents-N(C(O)CH3)-.

In specific embodiments, Z2 is a bond. In specific embodiments, Z2 represents-O-. In specific embodiments, Z2 represents-S-. In specific embodiments, Z2 represents-S(O)-. In specific embodiments, Z2 represents-S(O2)-. In specific embodiments, Z2 represents-N(R7) - where R7 is as defined herein. In specific embodiments, Z2 represents-NH-. In specific embodiments, Z2 represents-N(C(O)R1a)-, where R1a is as defined herein. In specific embodiments, Z2 represents-N(C(O)C1-6 alkyl)-. In specific embodiments, Z2 represents-N(C(O)CH3)-.

In specific embodiments, m is 0. In specific embodiments, the OS�span m equals 1. In specific embodiments, m is 2. In specific embodiments, m is 3. In specific embodiments, m is 4.

In specific embodiments, n is 0. In specific embodiments, n is 1. In specific embodiments, n is 2. In specific embodiments, n is 3. In specific embodiments, n is 4. In specific embodiments, n is 5. In specific embodiments, n is 6. In specific embodiments, n is 7.

In specific embodiments, p is 0. In specific embodiments, p is 1. In specific embodiments, p is 2. In specific embodiments, p is 3. In specific embodiments, p is 4. In specific embodiments, p is 5. In specific embodiments, p is 6. In specific embodiments, p is equal to 7.

In specific embodiments, q is 1. In specific embodiments, q is 2. In specific embodiments, q is 3. In specific embodiments, q is 4. In specific embodiments, q is an integer equal to 2, 3 or 4.

In specific embodiments, r is 1. In specific embodiments, r is 2. In specific embodiments, the implementation�t r is equal to 3. In specific embodiments, r is 4. In specific embodiments, r is an integer equal to 2, 3 or 4.

In specific embodiments, s is 0 and t is 1. In specific embodiments, s is 1 and t is 0. In specific embodiments, s and t are equal, both, 1. In specific embodiments, s is 2 and t is 1. In specific embodiments, s is 2 and t is 0.

In particular embodiments, u is 1. In particular embodiments, u is equal to 2.

In specific embodiments, the grouphas a structure corresponding to:orwhere Z1 and q each, are as defined herein; and each T1 is independently a bond, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 albaniles or C2-6 heteroalkyl, where R7 is as defined herein.

In specific embodiments, the grouphas a structure corresponding to:orwhere Z2 and r, each, are as defined herein; and each T2 is independently a bond, -O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 albaniles or C2-6 heteroalkyl, g�e R7 is as as defined in this document.

In one embodiment, the implementation of the grouphas a structure corresponding toand the grouphas a structure corresponding to; where T1, T2, Z1, Z2, q, and r each, are as defined herein.

In another embodiment, the implementation of the grouphas a structure corresponding toand the grouphas a structure corresponding to; where T1, T2, Z1, Z2, q, and r each, are as defined herein.

In yet another embodiment of the grouphas a structure corresponding toand the grouphas a structure corresponding to; where T1, T2, Z1, Z2, q, and r each, are as defined herein.

In another embodiment, the implementation of the grouphas a structure corresponding toand the grouphas a structure corresponding to; where T1, T2, Z1, Z2, q, and r each, are as defined herein.

In specific embodiments, �of sushestvennee T1 is a bond. In specific embodiments, T1 represents-O-. In specific embodiments, T1 represents-NR7-, where R7 is as defined herein. In specific embodiments, T1 represents-S-. In particular embodiments, T1 is a C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, T1 is a methylene or ethylene. In particular embodiments, T1 is a C1-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, T1 is a C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, T1 is a C2-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, each T1 independently represents-O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 albaniles or C2-6 heteroalkyl, where R7 is as defined herein.

In specific embodiments, T2 is a bond. In specific embodiments, T2 represents-O-. In specific embodiments, T2 represents-NR7-, where R7 is f�Xia, as defined in the present document. In specific embodiments, T2 represents-S-. In specific embodiments, T2 is a C1-6 alkylene, optionally substituted by one or more substituents Q. In particular embodiments, T2 is a methylene or ethylene. In specific embodiments, T2 is a C1-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, T2 is a C2-6 albaniles, optionally substituted by one or more substituents Q. In particular embodiments, T2 is a C2-6 heteroalkyl, optionally substituted by one or more substituents Q. In particular embodiments, each T2 independently represents-O-, -NR7-, -S-, C1-6 alkylene, C1-6 heteroalkyl, C2-6 albaniles or C2-6 heteroalkyl, where R7 is as defined herein.

In specific embodiments, the groupandeach independently selected from:

In one of the embodiments of the present invention relates to a compound selected from the group consisting of:

1. The compound of formula IIIB:

or its enantiomer, racemic mixture or a mixture of diastereomers; or its pharmaceutically acceptable salt;
where:
U2, V1V2and W1represent, each independently, O, N, NH, S, or CR3a;
U1and W2represent, each independently, C or N;
X1and X2represent, each independently, C or N;
each R1and R2represents independently hydrogen, -C(O)CH(NR1bR1c)R1a, -C(O)CH(N(R1c)C(O)OR1b)R1aor-C(O)OR1a;
each R3arepresents independently hydrogen or R3;
each R3represents independently a halogen or-C(O)OR1a; or
L1and L2each independently selected from:

where the asterisk (*) in each group indicates the point of attachment, which group is linked to U1or W2;in each group indicates the point of attachment through which the group is associated withor; and where T3represents a bond, C, N, O, S, CR3aor NR3a; U3V3, W3and X3represent, each independently, C, N, CR3aor NR3a; and Y3is a C;
each Z1and Z2represents independently a bond or-O-;
each Rla, R1band R1crepresents independently hydrogen, C1-6Alki� or C 6-14aryl; or Rlband Rlctogether with the N atom to which they are attached to form heterocyclyl where heterocyclyl represents a non-aromatic heterocyclic ring containing 5 to 6 ring atoms, where one non-aromatic ring atoms is a heteroatom independently selected from O, S and N;
each q and r is 1;
s and t is 1; and
u is 1.

2. The compound according to claim 1 having the structure of formula IIIBa:

3. The compound according to claim 1 having the structure of formula IIIBb:

where each Rlerepresents independently hydrogen, C1-6alkyl or C6-14aryl, or Rlcand Rletogether with the N atom to which they are attached to form heterocyclyl.

4. The compound according to claim 1 having the structure of formula IIIBc:

where each Rlerepresents independently hydrogen, C1-6alkyl or C6-14aryl, or Rlcand Rletogether with the N atom to which they are attached to form heterocyclyl.

5. The compound according to claim 1 having the structure of formula IIIBd:

where each Rlerepresents independently hydrogen, C1-6alkyl or C6-14aryl, or Rlcand Rletogether with the N atom to which they are attached to form heterocyclyl.

6. With�according to claim unity 1, where U2represents S.

7. The compound according to claim 1, where W1represents S.

8. The compound according to claim 1, where W1represents O.

9. The compound according to claim 1, where W1represents N.

10. The compound according to claim 1, where U1, W2, X1and X2represent C, and V1and V2represent, each independently, CR3a.

11. The compound according to claim 1, wherein each divalent groupindependently selected from:

12. The compound according to claim 1 having the structure of formula IC:

13. The compound according to claim 2 having the structure of formula ICa:

14. The compound according to claim 3 having the structure of formula ICb:

15. The compound according to claim 4 having the structure of formula ICc:

16. The compound according to claim 5 having the structure of formula ICd:

17. The compound according to claim 1, where L1and L2each independently selected from:

where the asterisk (*) in each group indicates the point of attachment, which group is linked to U1or W2;in each group indicates the point of attachment, through koto�th group is associated with or.

18. The compound according to claim 17, where L1and L2each independently selected from:

19. The compound according to claim 1 having the structure of formula IIC:

20. The compound according to claim 2 having the structure of formula IICa:

21. The compound according to claim 3 having the structure of formula IICb:

22. The compound according to claim 4 having the structure of formula IICc:

23. The compound according to claim 5 having the structure of formula IICd:

24. The compound according to claim 1, where R1represents-C(O)CH(NRlbRlc)Rlaor-C(O)CH[N(C(O)ORlb)Rlc]Rla.

25. The compound according to claim 24, where R1represents-C(O)CH[N(C(O)ORlb)Rlc]Rla.

26. The compound according to claim 1, where R2represents-C(O)CH(NRlbRlc)Rlaor-C(O)CH[N(C(O)ORlb)Rlc]Rla.

27. The compound according to claim 26, where R2represents-C(O)CH[N(C(O)ORlb)Rlc]Rla.

28. The compound according to claim 3, where Rlerepresents hydrogen.

29. The compound according to claim 1, where Rlarepresents hydrogen, methyl, isopropyl, 2-methylpropyl", 1-methylpropyl", phenyl or benzyl.

30. The compound according to claim 1, where Rlbis methyl, ethyl, propyl or butyl.

31. The compound according to claim 1, where Rlcrepresents hydrogen.

32. The compound according to claim 1, where R3arepresents hydrogen, chlorine or fluorine.

33. The compound according to claim 1, where the grouphas the structure:

34. The compound according to claim 1, where the grouphas the structure:

35. A compound selected from:












and its pharmaceutically acceptable salts.

36. Pharmaceutical composition possessing inhibitory activity against hepatitis C virus, containing a therapeutically effective amount of a compound according to any one of claims. 1-35 and one or more pharmaceutically acceptable carriers.

37. A method of treating or preventing HCV infection in a subject, which comprises administering to the subject the compound according to any one of claims. 1-35.

38. A method according to claim 37, where the subject is a person.

39. The compound of the following formula:

or its pharmaceutically acceptable salt.

40. The compound of the following formula:

41. Pharmaceutically acceptable salt of the compound

42. Pharmaceutical composition possessing inhibitory activity against hepatitis C virus, containing a therapeutically effective amount of a compound according to claim 39 or 40, or a therapeutically effective amount of its pharmaceutically acceptable salt according to claim 41 and one or more pharmaceutically acceptable carriers.

43. A method of treating or preventing HCV infection in a subject, which comprises administering to the subject the compound according to claim 39 or 40, or its pharmaceutically acceptable salt according to claim 41.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein R1 represents methyl or ethyl, R2 represents hydrogen, fluorine or methyl, R3 represents hydrogen, fluorine or methyl, each R4 represents hydrogen and R5 represents hydrogen, methyl. The invention also refers to a pharmaceutical composition for treating or relieving a degree of severity of a proliferative disorder by means of compounds of formula (I).

EFFECT: compounds are effective in preparing a drug for treating or reducing a degree of severity of metastatic cancer, glioblastoma, gastric carcinoma or cancer specified in colon cancer, breast cancer, prostate cancer, cerebral cancer, liver cancer, pancreatic cancer or lung cancer and hepatocellular carcinoma.

16 cl, 4 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula or its therapeutically acceptable salts, wherein A1 represents furyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, thienyl, triazolyl, piperidinyl, morpholinyl, dihydro-1,3,4-thiadiazol-2-yl, benzothien-2-yl, banzothiazol-2-yl, tetrahydrothien-3-yl, [1,2,4]triazolo[1,5-a]pyrimidin-2-yl or imidazo[2,1-b][1,3]-thiazol-5-yl; wherein A1 is unsubstituted or substituted by one, or two, or three, or four, or five substitutes independently specified in R1, OR1, C(O)OR1, NHR1, N(R1)2, C(N)C(O)R1, C(O)NHR1, NHC(O)R1, NR1C(O)R1, (O), NO2, F, Cl, Br and CF3; R1 represents R2, R3, R4 or R5; R2 represents phenyl; R3 represents pyrazolyl or isoxazolyl; R4 represents piperidinyl; R5 represents C1-C10alkyl or C2-C10alkenyl each of which is not specified or specified by substitutes specified in R7, SR7, N(R7)2, NHC(O)R7, F and Cl; R7 represents R8, R9, R10 or R11; R8 represents phenyl; R9 represents oxadiazolyl; R10 represents morpholinyl, pyrrolidinyl or tetrahydropyranyl; R11 represents C1-C10alkyl; Z1 represents phenylene; Z2 represents piperidine unsubstituted or substituted by OCH3, or piperazine; both Z1A and Z2A are absent; L1 represents C1-C10alkyl or C2-C10alkenyl each of which is unsubstituted or substituted by R37B; R37B represents phenyl; Z3 represents R38 or R40; R38 represents phenyl; R40 represents cyclohexyl or cyclohexenyl; wherein phenylene presented by Z1 is unsubstituted or substituted by the group OR41; R41 represents R42 or R43; R42 represents phenyl, which is uncondensed or condensed with pyrrolyl, imidazolyl or pyrazole; R43 represents pyridinyl, which is uncondensed or condensed with pyrrolyl; wherein each cyclic fragment presented by R2, R3, R4, R8, R9, R10, R38, R40, R42 and R43 is independently unsubstituted or substituted by one or more substitutes independently specified in R57, OR57, C(O)OR57, F, Cl CF3 and Br; R57 represents R58 or R61; R58 represents phenyl; R61 represents C1-C10alkyl; and wherein phenyl presented by the group R58 is unsubstituted or substituted by one or more substitutes independently specified in F and Cl.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, and to a method of treating diseases involving the expression of anti-apoptotic Bcl-2 proteins.

7 cl, 2 tbl, 48 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula IV, VIII-A and X, and to their pharmaceutical acceptable salts possessing the inhibitory activity on PI3-kinase (phosphoinositide-3-kinase). In compounds of formula IV and IX and Wd is specified in a group consisting of, , , and each of which can be substituted. In formula VIII-A, the group Wd represents the group or , wherein Ra is hydrogen, R11 is amino; in compound IV, Wa2 represents CR5; Wa3 represents CR6; Wa4 represents N or CR7; in compound IX, Wa1 and Wa2 independently represent CR5, N or NR4, and Wa4 independently represents CR7 or S, wherein no more than two neighbouring atoms in a ring represent atom or sulphur; Wb5 represents N; B represents a grouping of formula II, as well as in case of compound IV, B means C1-C10alkyl, C3-C10cycloalkyl, C3-C10heterocycloalkyl having one to six ring heteroatoms specified in N, O and S; in case of compound IX, B also means C1-C10alkyl, C3-C10cycloalkyl or 6-merous heterocycloalkyl having nitrogen atom; Wc represents C6-C10aryl or 5-18-merous heteroaryl having one or more ring heteroatoms specified in N, O and S, or phenyl or 6-merous heteroaryl respectively is equal to an integer of 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, respectively; z is equal to 1; Y is absent. The other radical values are specified in the patent claim.

EFFECT: compounds can be used for treating such diseases, as cancer, bone disorders, an inflammatory or immune disease, diseases of the nervous system, metabolic disorders, respiratory diseases, thrombosis or cardiac diseases mediated by PI3-kinase.

68 cl, 11 dwg, 7 tbl, 55 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new compounds of formula I or their pharmaceutically acceptable salts, wherein R1 means phenyl once or twice substituted by C1-6 alkyl, C1-6 alkoxy, halogen or 5-6-merous heteroaryl; R2 is phenyl once or twice substituted by C1-6 alkyl, C1-6 alkoxy, halogen, halogen-C1-6alkyl, halogen-C1-6alkoxy, C1-6 alkylsulphonyl, nitrile, etc. R3 means H or C1-6 alkyl; X - -O-, -NRa-,-S(O)m- or CRbRc, wherein Ra - H, C1-6 alkyl or C1-6 alkylcarbonyl; Rb and Rc mean H or together with the atom to which they are attached, form 5-merous cycle additionally containing 2 oxygen atoms; m is equal to 0-2; Y means -NRc-, wherein Rc - H or C1-6 alkyl.

EFFECT: compounds can find application in medicine for treating autoimmune and inflammatory diseases related to P2X7 purinoceptor.

15 cl, 1 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to piridazine derivatives of formula II

,

in which radicals and symbols have determinations, given in the invention formula, or to their pharmaceutically acceptable salts.

EFFECT: compounds of formula II demonstrate inhibiting effect with respect to proteinkinases such as c-met, ron, or ALK, or chimeric proteins, and can be useful for treatment of disorders, associated with abnormal activity of proteinkinases, such as cancer.

7 cl, 1 tbl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the chemical-pharmaceutical industry and represents a compound having a structure according to formula I:

,

compositions containing the compounds of the above formula applicable to stimulate neurogenesis and/or inhibition of neuron degeneration.

EFFECT: invention may be used in treating diseases and conditions characterised by neuron loss and lower neurogenesis, including Alzheimer's disease, stroke, traumatic brain injury, traumatic nerve injury and depression.

8 cl, 2 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to method of labelling paired helical filaments (PHF), which includes interaction of PHF with compound and detection of said compound presence, where compound has formula , in which -R- stands for , -Q- is selected from: -NHC(O)-, -N=N-, -CH=CH-; -P is selected from: ; -T is selected from: ; X represents N or CH; -W1-6, -G1-4, -P1-5 are such as given in the invention formula. Invention also relates to method of labelling aggregated tau-protein, which includes interaction of aggregated molecules of tau-protein with compounds and detection of said compound presence, and to compounds of formula , in which values of substituents are such as given in the invention formula.

EFFECT: formula compounds as labels of tau-protein and paired helical filaments (PHF).

28 cl, 5 dwg, 225 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of bicyclic heterocyclic compounds of formula (I), which can be applied in prevention or treatment of abnormal or pathological condition, mediated by FGFR kinase, such as cancer. In formula compound, (i) in case when R1 and R2 independently represent hydrogen or C3-8cycloalkyl; A is group Aa, which represents aromatic group, representing phenyl; R3 represents hydrogen or C1-6alkyl; R4 represents group R4a, which represents amino, halogen, C1-6alkyl, -X-R5, phenyl or aromatic heterocyclic group, where said heterocyclic group represents 5- or 6-membered heterocyclyl group and contains 1, 2 or 3 heteroatoms, independently selected from nitrogen, oxygen or sulphur, where said phenyl or said heterocyclyl group can be optionally substituted with one or two Rb groups; or (ii) when R1 represents hydrogen and R2 represents C1-6alkyl or halogenC1-6alkyl; A is group Ab, which represents aromatic 5-membered heterocyclic group; R3 represents hydrogen or C1-6alkyl; R4 is group R4a, which represents halogen; or (iii) when R1 represents hydrogen and R2 represents C1-6alkyl or halogenC1-6alkyl; A is group Ac, which represents aromatic 6-membered heterocyclic group, containing one nitrogen atom as heteroatom; R3 represents hydrogen or C1-6alkyl; R4 is group R4b, which represents halogen, C1-6alkyl, -X-R5 or aromatic heterocyclic group, containing 1, 2 or 3 heteroatoms, independently selected from nitrogen, oxygen and sulphur. Other values of radicals are given in the invention formula.

EFFECT: obtaining novel derivatives of bicyclic heterocyclic compounds.

21 cl, 7 tbl, 250 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein R1 represents an alkoxy group or halogen; each U and V independently represents CH or N; "----" means a bond or is absent; W represents CH or N, or if "----" is absent, then W represents CH2 or NH, provided not all U, V and W represent N; A represents a bond or CH2; R2 represents H, or provided A means CH2, then it also can represent OH; each m and n are independently equal to 0 or 1; D represents CH2 or a bond; G represents a phenyl group that is single or double substituted in meta- and/or para-position(s) by substitutes specified in alkyl, C1-3alkoxy group and halogen, or G represents one of the groups G1 and G2: wherein each Z1, Z2 and Z3 represents CH; and X represents N or CH and Q represents O or S; it should be noted that provided each m and n are equal to 0, then A represents CH2; or a pharmaceutically acceptable salt of such compound. Besides, the invention refers to a pharmaceutical composition for treating a bacterial infection containing an active ingredient presented by a compound of formula (I) or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert additive.

EFFECT: preparing the oxazolidine compounds applicable for preparing a drug for treating and preventing the bacterial infections.

14 cl, 8 dwg, 2 tbl, 33 ex

FIELD: chemistry.

SUBSTANCE: invention relates to antibacterial compounds of formula (I), where R1 represents alkoxygroup; U, V and W each represents CH or one of U, V and W represents N, and each other represents CH; A represents CH2 or O; G represents CH=CH-E, where E represents phenyl group, mono- or di-substituted with halogen, or G represents group of one of the formulas given below , , where Z represents CH or N, Q represents O or S and K represents O or S; or salt of such compound. In addition, invention also relates to pharmaceutical composition based on formula (I) compound for prevention or treatment of bacterial infection, as well as to application of claimed compounds for obtaining medication for prevention or treatment of bacterial infection.

EFFECT: novel compounds, which can be applied in treatment of bacterial infection, are obtained and described.

23 cl, 1 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel method of obtaining fluorescent catecholamines selected from dopamine and adrenalin, and their metabolites, selected from homovanillic and vanillin-mandelic acids, by a method of derivation. The compounds can be used as highly sensitive and selective markers for the determination of various diseases. The method of derivation includes oxidation of the initial compounds and their interaction with amines that form condensed structures in a medium of the CAPS-buffer solution or glycin - KOH 0.2 mM hydrogen peroxide in the presence of horseradish peroxidase as a catalyst. The process in preferably carried out in a 0.1 M buffer solution with the concentration of horseradish peroxidase 0.01-1 mcM; concentration of hydrogen peroxide - 100 mcM, amine concentration - 0.1-33 mM; concentration of catecholamines and metabolites - 0.03-1 mcM.

EFFECT: method is simple and producible as it does not require higher temperature and is realised in a water solution.

2 cl, 2 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a number of substituted dihydrobenzocycloalkyloxymethyl oxazolpyrimidinone of formula

wherein n represents 1, 2 or 3; R1 represents hydrogen, methyl, fluoromethyl, ethyl, 2-fluoroethyl and propyl; R2 is specified in a group consisting of hydrogen, methyl, fluoromethyl, ethyl, 2-fluoroethyl, propyl, 1,1-difluoropropyl, methoxymethyl and 2-fluoroethoxymethyl; R3 and R4 represent (C1-C4)alkyl; and R5 and R6 are identical or different and are independently specified in a group consisting of hydrogen, halogen, (C1-C4)alkyl and (C1-C4)alkoxy. The invention also refers to specific compounds specified in cl.8 of the patent claim, to compounds of formula

a pharmaceutical composition and the use of the declared compounds.

EFFECT: dihydrobenzocycloalkyl-oxymethyloxazolpyrimidinone as metabotropic glutamate receptor mGluR2 modulators.

14 cl, 1 tbl, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to nitroimidazoxazine derivatives of formula , wherein X represents O, OCH2, OCH2CH=CH or OCH2C≡C; Y represents a group of any of formulas IIa-IIc, wherein means an attachment point to X, and Z in formulas

represents CH2, CH=CH, C≡C or a direct bond; the numbers 2, 3 and 4 are positions of a terminal ring having R1 as a substitute; the terminal ring of formula I comprises C, CH or one nitrogen atom in each position, and each of R1 and R2 in formulas I and IIa represents one or two substitutes found in any accessible position of the ring and independently represents H, F, Cl, CF3, OCF2H, OCF3 or combinations thereof. Besides, the invention refers to a pharmaceutical compound based on a compound of formula I, a method of treating a microbial infection, specific compounds.

EFFECT: there are prepared new compound effective in treating the microbial infections, including in treating the diseases caused by Mycobacterium tuberculosis.

8 cl, 28 dwg, 3 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.

EFFECT: obtaining novel compounds with useful biological activity.

7 cl, 21 dwg, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to heterocyclic compounds of formula I

and to their pharmaceutically acceptable salts, where A is selected from CH or N; R1 is selected from the group, consisting of C3-6-cycloalkyl, C3-6-cycloalkyl-C1-7-alkyl, C1-7-alkoxy-C1-7-alkyl, halogen-C1-7-alkyl; R2 and R6 independently on each other represent hydrogen of halogen; R3 and R5 independently on each other are selected from the group, consisting of hydrogen, C1-7-alkyl and halogen; R4 is selected from the group, consisting of hydrogen, C1-7-alkyl, halogen and amino; R7 is selected from the group, consisting of C1-7-alkyl, C1-7alkoxy-C1-7-alkyl, C1-7-alkoxyimino-C1-7-alkyl, 4-6-membered heterocyclyl, containing one heteroatom O, phenyl, with said phenyl being non-substituted or substituted with one hydroxy group, and 5-10-membered heteroaryl, containing 1-3 heteroatoms, selected from N, S and O, said heteroaryl is not substituted or is substituted with one or two groups, selected from the group, consisting of C1-7-alkyl, hydroxy, C1-7-alkoxy, cyano, C1-7-alkylaminocarbonyl and halogen. Invention also relates to pharmaceutical composition based on formula I compound and to method of obtaining formula I compound.

EFFECT: obtained are novel heterocyclic compounds, which are agents, increasing level of LDLP.

17 cl, 2 tbl, 89 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to isoxazoline FAAH inhibitors of formula (I) or their pharmaceutically acceptable forms, wherein each of G, Ra, Rb, Rc and Rd has a value described in the present application, to pharmaceutical compositions, and methods of treating a FAAH-mediated condition.

EFFECT: developing the method of treating the FAAH-mediated condition.

32 cl, 22 tbl, 351 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula , where R1 represents hydroxyadamantyl, methoxycarbonyladamantyl, carboxyadamantyl, aminocarbonyladamantyl or aminocarbonylbicyclo[2.2.2]octanyl and where A represents CR5R6; or phenyl, chlorobenzyl, benzyl, chlorophenylethyl, phenylethyl, difluorobenzyl, dichlorophenyl, trifluoromethylphenyl or difluorophenylethyl and where A represents CR5R6; R2 and R3 together with nitrogen atom N* and carbon atom C*, which they are bount to, form group or ; R4 represents hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, arylalkyl, arylalkoxygroup, arylalkoxyalkyl, hydroxyalkyl, aryl, heteroarylalkyl, heteroaryloxyalkyl, substituted aryl, substituted heteroarylalkyl or substituted heteroaryloxyalkyl, where substituted aryl, substituted heteroarylalkyl and substituted heteroaryloxyalkyl are substituted with 1-3 substituents, independently selected from alkyl, cycloalkyl, cyanogroup, halogen, halogenalkyl, hydroxygroup and alkoxygroup; R5 represents hydrogen; R6represents hydrogen; as well as to their pharmaceutically acceptable salts and esters, which can be used as 11b-HSD1 inhibitors.

EFFECT: obtaining compounds which can be used as 11b-HSD1 inhibitors.

9 cl, 1 tbl, 103 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new compounds of formula I or their pharmaceutically acceptable salts, wherein R1 means phenyl once or twice substituted by C1-6 alkyl, C1-6 alkoxy, halogen or 5-6-merous heteroaryl; R2 is phenyl once or twice substituted by C1-6 alkyl, C1-6 alkoxy, halogen, halogen-C1-6alkyl, halogen-C1-6alkoxy, C1-6 alkylsulphonyl, nitrile, etc. R3 means H or C1-6 alkyl; X - -O-, -NRa-,-S(O)m- or CRbRc, wherein Ra - H, C1-6 alkyl or C1-6 alkylcarbonyl; Rb and Rc mean H or together with the atom to which they are attached, form 5-merous cycle additionally containing 2 oxygen atoms; m is equal to 0-2; Y means -NRc-, wherein Rc - H or C1-6 alkyl.

EFFECT: compounds can find application in medicine for treating autoimmune and inflammatory diseases related to P2X7 purinoceptor.

15 cl, 1 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene citrate salt. The invention also refers to pharmaceutical compositions containing the above citrate, and methods for using citrate in treating several conditions.

EFFECT: what is prepared is the new 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene salt and the pharmaceutical compositions on the basis thereof which can find application in medicine for treating a proliferative disorder.

17 cl, 30 dwg, 5 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I), wherein R1 represents an alkoxy group or halogen; each U and V independently represents CH or N; "----" means a bond or is absent; W represents CH or N, or if "----" is absent, then W represents CH2 or NH, provided not all U, V and W represent N; A represents a bond or CH2; R2 represents H, or provided A means CH2, then it also can represent OH; each m and n are independently equal to 0 or 1; D represents CH2 or a bond; G represents a phenyl group that is single or double substituted in meta- and/or para-position(s) by substitutes specified in alkyl, C1-3alkoxy group and halogen, or G represents one of the groups G1 and G2: wherein each Z1, Z2 and Z3 represents CH; and X represents N or CH and Q represents O or S; it should be noted that provided each m and n are equal to 0, then A represents CH2; or a pharmaceutically acceptable salt of such compound. Besides, the invention refers to a pharmaceutical composition for treating a bacterial infection containing an active ingredient presented by a compound of formula (I) or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert additive.

EFFECT: preparing the oxazolidine compounds applicable for preparing a drug for treating and preventing the bacterial infections.

14 cl, 8 dwg, 2 tbl, 33 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula , wherein Y and Z are independently specified in a group of a) or b) so that one of Y or Z is specified in the group a), and another one - in the group b); the group a) represents i) substituted C6-10aryl; ii) C3-8cycloalkyl; iii) trifluoromethyl or iv) heteroaryl specified in a group consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyridinyl, isoxazolyl, imidazolyl, furasan-3-yl, benzothienyl, thieno[3,2-b]thiophen-2-yl, pyrazolyl, triazolyl, tetrazolyl and [1,2,3]thiadiazolyl; the group b) represents i) C6-10aryl; ii) heteroaryl specified in a group consisting of thiazolyl, pyridinyl, indolyl, pyrrolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl, imidazo[1,2-a]pyridin-2-yl, furo[2,3-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thieno[2,3-b]pyridinyl, quinolinyl, quinazolinyl, thienyl and benzimidazolyl; iii) benzofused heterocyclyl attached through a carbon atom, and when a heterocyclyl component contains a nitrogen atom, the carbon atom is optionally substituted by one substitute specified in a group consisting of C3-7cycloalkylcarbonyl; C3-7cycloalkylsulphonyl; phenyl; phenylcarbonyl; pyrrolylcarbonyl; phenylsulphonyl; phenyl(C1-4)alkyl; C1-6alkylcarbonyl; C1-6alkylsulphonyl; pyrimidinyl and pyridinyl; C3-7cycloalkylcarbonyl, phenyl, phenylcarbonyl, phenyl(C1-4)alkyl and phenylsulphonyl are optionally substituted by trifluoromethyl, or by one or two fluor-substitutes; iv) phenoxatiynyl; vi) fluoren-9-on-2-yl; vii) 9,9-dimethyl-9H-fluorenyl; viii) 1-chlornaphtho[2,1-b]thiophen-2-yl; ix) xanthen-9-on-3-yl; x) 9-methyl-9H-carbazol-3-yl; xi) 6,7,8,9-tetrahydro-5H-carbazol-3-yl; xiii) 3-methyl-2-phenyl-4-oxochromen-8-yl; or xiv) 1,3-dihydrobenzimidazol-2-on-5-yl optionally substituted by 1-phenyl, 1-(2,2,2-trifluoroethyl), 1-(3,3,3-trifluoropropyl) or 1-(4,4-difluorocyclohexyl); 1-phenyl is optionally substituted by one or more fluor-substitutes or trifluoromethyl; or xv) 4-(3-chlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl; R1 represents C6-10aryl, C1-3alkyl, benzyloxymethyl, hydroxy(C1-3)alkyl, aminocarbonyl, carboxy, trifluoromethyl, spirofused cyclopropyl, 3-oxo or aryl(C1-3)alkyl; or when s is equal to 2 and R1 represents C1-3alkyl, the substitutes C1-3akyl is taken with a piperazine ring to form 3,8-diazabicyclo[3.2.1]octanyl or 2,5-diazabicyclo[2.2.2]octanyl ring system, and its pharmaceutical compositions.

EFFECT: preparing the new pharmaceutical compositions.

20 cl, 7 tbl, 72 ex

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