WO2011123419A1

WO2011123419A1 - Trycyclic compounds and pbk inhibitors containing the same

Info

Publication number: WO2011123419A1
Application number: PCT/US2011/030278
Authority: WO
Inventors: Yusuke Nakamura; Yo Matsuo; Shoji Hisada; Feryan Ahmed; Raymond Huntley; Zohreh Sajjadi-Hashemi; David M. Jenkins; Robert B. Kargbo; Wenge Cui; Polivina Jolicia F. Gauuan; Joel R. Walker; Helene Decornez; Mahender Gurram
Original assignee: Oncotherapy Science, Inc.
Priority date: 2010-03-29
Filing date: 2011-03-29
Publication date: 2011-10-06
Also published as: CA2792941A1; CN102917590B; JP5849302B2; MX2012011412A; EP2552206A4; EP2552206A1; KR101757502B1; CN102917590A; KR20130020666A; DK2552206T3; US20150183799A1; BR112012023836B1; HK1179114A1; ES2547571T3; US8962648B2; IL222080B; BR112012023836A2; CA2792941C; TWI503323B; AU2011235319B2

Abstract

Trycyclic compounds are provided. These compounds are PBK inhibitors, and are useful for the treatment of PBK related diseases, including cancer.

Description

Tricyclic compounds and PBK Inhibitors Containing the Same

Technical Field

The present invention relates to a compound for inhibiting PBK activity, a method for the preparation thereof, and a pharmaceutical composition containing the compound as an active ingredient.

Priority

The present application claims the benefit of U.S. Provisional Applications No. 61/318,606, filed on March 29, 2010, the contents of which are hereby incorporated herein by reference in their entirety for all purposes.

Background Art

Previous studies revealed that PDZ binding kinase (PBK) is a serine/threonine kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family (Abe Y, et al., J Biol Chem. 275: 21525-21531 , 2000, Gaudet S, et al., Proc Natl Acad Sci. 97: 5167-5172, 2000 and Matsumoto S, et al., Biochem Biophys Res Commun. 325: 997-1004, 2004). PBK was also indicated to be involved in mitosis as shown by its significant role in highly proliferating spermatocytes (Gaudet S, et al., Proc Natl Acad Sci. 97: 5167-5172, 2000 and Fujibuchi T, et al., Dev Growth Differ. 47:637-44, 2005). In fact, abundant expression of PBK was observed in testis, while almost no PBK expression was detected in other normal organs (Park JH, et al., Cancer Res. 66: 9186-95, 2006). PBK regulates cell cycle progression. In accordance with this, its significant overexpression was detected in clinical breast cancer samples (Park JH, et al., Cancer Res. 66: 9186-95, 2006), Burkitt's lymphoma (Simons-Evelyn M, et al., Blood Cells Mol Dis. 27: 825- 829, 2001) and a variety of hematologic malignancies (Nandi A, et al., Blood Cells Mol Dis. 32: 240-5, 2004).

Immunohistochemical analysis of testis revealed the expression of PBK protein around the outer region of seminiferous tubules where repeated mitosis of sperm germ cells followed by meiosis occurs (Fujibuchi T, et al., Dev Growth Differ. 47: 637-44, 2005). Especially, at prophase and metaphase, the subcellular localization of PBK was detected around the condensed chromosome in breast cancer cells (Park JH, et al., Cancer Res. 66: 9186-95, 2006). Moreover the knockdown of PBK expression with gene specific siRNAs caused dysfunction of cytokinesis and subsequently led to apoptosis of the cancer cells (Park JH, et al., Cancer Res. 66: 91 86-95, 2006). These indicated the critical function of PBK at mitosis, in testicular and cancer cells.

Taken together, PBK-specific inhibitors can be used as a drug applicable for a broad spectrum of cancers. PBK is an excellent target for cancer therapy for the following reasons: i) almost no expression in normal organs (except for testis); ii) frequent overexpression in clinical cancer samples; iii) a serine/threonine kinase related to the essential function for cell mitosis.

The present inventors have found that a Tricyclic compound can selectively inhibit the activity of PBK.

Summary of Invention

Accordingly, it is an object of the present invention to provide a PBK inhibitor having high inhibitory activity against PBK.

It is another object of the present invention to provide a method for preparing such inhibitor.

It is a further object of the present invention to provide a pharmaceutical composition including the compound, a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof.

In accordance with one aspect of the present invention, there is provided a compound of formula (I), and a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof:

A compound represented by general formula I:

I

or a pharmaceutically acceptable salt thereof,

wherein R¹, R², R³, and R⁴ are each independently a group selected from the group consisting of: hydrogen,

hydroxyl,

halogen,

cyano,

nitro,

amino,

Ci-C₆ alkyl,

C₂-C6 alkenyl,

C2-C6 alkynyl,

C3-C10 cycloalkyl,

C3-C10 cycloalkenyl,

Ci-C₆ alkoxy,

C₆-Cio aryl,

indanyl,

heteroaryl,

3- to 8-membered heterocycloalkyl,

-OSO2CH3,

-OSO2CF3, and

-CONH2,

wherein each of the groups of R¹ to R⁴ is optionally substituted with a substituent selected from the group consisting of substituent A below:

substituent A:

hydroxyl;

oxo (=0);

cyano;

halogen;

C1-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with a substituent selected from the group consisting of substituent B below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or Ci-C₆ alkyl substituted with -NR^{3 ,}R³² (wherein R³¹ and R³² each independently represent hydrogen or C1-C6 alkyl)];

-NR R [wherein R and R each independently represent hydrogen, or C1-C6 alkyl (wherein the Ci-C₆ alkyl is optionally substituted with di(Ci-C6 alkyl)amino, Q-C6 alkylsulfonyl (-S0₂(Ci-C6 alkyl)), or 3- to 8-membered heterocycloalkyl)];

C1-C6 alkoxy {wherein the Ci-Ce alkoxy is optionally substituted with halogen, 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-Q alkyl), or -NR³³R³⁴ [wherein R³³ and R³⁴ each independently represent hydrogen, Ci-C₆ alkyl (wherein the C1-C6 alkyl is optionally substituted with Q-C6 aikylsulfonyl or di(Ci-C6 alkyl)amino), or Ci-C₆ aikylsulfonyl] } ;

-S0₂NR²³R²⁴ {wherein R²³ and R²⁴ each independently represent hydrogen, C -Ce alkyl [wherein the Ci-C₆ alkyl is optionally substituted with hydroxyl, C1-C6 alkoxy, halogen, C3-C10 cycloalkyl, or -NR³⁵R³⁶ (wherein R³ and R³⁶ each independently represent hydrogen or Q-C6 alkyl)], C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with C1-C6 hydroxyalkyl), or 3- to 8-membered heterocycloalkyl; or R²³ and R²⁴ may together form 3- to 8-membered heterocycloalkyl wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with amino} ;

C1-C6 aikylsulfonyl (wherein the C1-C6 alkyl moiety is optionally substituted with hydroxyl);

C1-C6 alkylsulfonylamino (-NHS0₂(C)-C6 alkyl)) [wherein the Ci-C₆ alkyl moiety is optionally substituted with -NR³⁷R³⁸ (wherein R³⁷ and R each independently represent hydrogen or C1-C6 alkyl)];

3- to 8-membered heterocycloalkyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C]-Ce alkyl, or C1-C6 aikylsulfonyl), C1-C6 alkyl [wherein the C\-Ce alkyl is optionally substituted with -NR⁴¹R⁴² (wherein R⁴¹ and R⁴ each independently represent hydrogen or C1-C6 alkyl)], hydroxyl, or C1-C6 aikylsulfonyl} ;

heteroaryl;

-COOR^{1 1} (wherein R^{1 1} represents hydrogen or Q-C6 alkyl); and

-COR¹² [wherein R¹² represents Ci-C₆ alkyl, C3-C10 cycloalkyl, cyanomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen, or C1-C6 alkyl [wherein the Q-C6 alkyl is optionally substituted with hydroxyl or -NR⁴ R⁴⁴ (wherein R⁴³ and R⁴⁴ each

independently represent hydrogen or Ci-C₆ alkyl)]}, or 3- to 8-membered heterocycloalkyl which is optionally substituted with C1-C6 alkyl],

substituent B:

halogen;

hydroxyl;

cyano;

3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl, hydroxyl, amino, C)-C₆ aminoalkyl, or Ci-C₆ alkyl substituted with C₂-C₇ alkyloxycarbonylamino);

-NR^5IR⁵² {wherein R ¹ and R ² each independently represent hydrogen, Ci-C₆ alkyl [wherein the Ci-C₆ alkyl is optionally substituted with Cj-Ce aikylsulfonyl, or 3- to 8-membered heterocycloalkyl optionally substituted with -COOR⁵³ (wherein R⁵³ represents hydrogen or Ci-C₆ alkyl)], 3- to 8-membered heterocycloalkyl, C_\-Ce aikylsulfonyl, C3-Ci₀ cycloalkyl, -COR⁵⁵ (wherein R^5S represents Ci-C₆ alkyl), -COOR⁵⁶ (wherein R represents Ci-C₆ alkyl), or -CONR⁵ R⁵⁸ (wherein R⁵⁷ and R⁵⁸ each independently represent hydrogen or C1-C6 alkyl)} ; and -COOR⁵⁴ (wherein R⁵⁴ represents hydrogen or C|-C₆ alkyl)];

wherein R⁵ is hydrogen or C1-C6 alkyl; and

wherein is a structure selected from the group consisting of

^' (i) -S-CR⁷=CR⁶-,

(ii) -CH₂-CH₂-CH₂-,

(iii) -NH-CH=CCH₃-, and

(iv) -N=CH-S-,

wherein R⁶ is

hydrogen,

hydroxyl, Ci-C₆ alkyl,

C₆-Cio aryl (wherein the C6-C10 aryl is optionally substituted with hydroxyl), or

3- to 8-membered heterocycloalkyl [wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR⁶¹R⁶² (wherein R⁶¹ and R⁶² each independently represent hydrogen or C1-C6 alkyl)], and

wherein R⁷ is

hydrogen,

C1-C6 alkyl {wherein the C1-C6 alkyl is optionally substituted with hydroxyl, -NR^7IR⁷² [wherein R⁷¹ and R⁷² each independently represent hydrogen, C1-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with dimethylamino), C3-C10 cycioalkyl (wherein the C3-C10 cycioalkyl is optionally substituted with amino), or 3- to 8-membered heterocycloalkyl], or 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C]-Ce aminoalkyl)},

C6-C10 aryl (wherein the C₆-C|o aryl is optionally substituted with hydroxyl), or

-COR⁷³ {wherein R⁷³ represents 3- to 8-membered heterocycloalkyl (wherein the 3- to

8-membered heterocycloalkyl is optionally substituted with amino), or -NR⁷⁴R⁷⁵ [wherein R⁷⁴ and R⁷⁵ each independently represent hydrogen, 3- to 8-membered heterocycloalkyl, or C3-C10 cycioalkyl (wherein the C3-C10 cycioalkyl is optionally substituted with amino)]}.

It must be noted that as used in the specification and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to "a group" is a reference to one or more groups.

Description of Embodiments

In this invention, "alkyl" group refers to a straight chain or a branched chain hydrocarbon group which does not contain any hetero atoms or unsaturated carbon-carbon bonds. "C1-C6 alkyl" refers to an alkyl group which has 1-6 carbon atom(s). "C1-C4 alkyl" refers to an alkyl group which has 1-4 carbon atom(s).

Examples of "C1-C6 alkyl" include, but are not limited to, methyl, ethyl, 1 -propyl, 2-propyl, 2-methyl-l -propyl, 2-methyl-2-propyl ( teri-butyl(l,l-dimethyl-ethyl), 1-butyl, 2-butyl, 1-pentyl,

2- pentyl, 3-pentyl, 2-methyl-l -butyl, 3-methyl- 1-butyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 2,2-dimethyl-l -propyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-l -pentyl, 3-methyl- 1-pentyl,

4-methyl- 1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2-methy-3-pentyl,

3- methyl-3-pentyl, 2,3-dimethyl- 1-butyl, 3,3-dimethyl- 1-butyl, 2,2-dimethyl-l -butyl,

2-ethy 1-1 -butyl, 3,3-dimethyl-2-butyl, and 2,3-dimethyl-2-butyl.

In this invention, "alkenyl" group refers to a straight chain or a branched chain hydrocarbon group which contains one or more than one unsaturated carbon-carbon bond(s) and does not contain any hetero atoms. "C2-C6 alkenyl" refers to an alkenyl group which has 2-6 carbon atoms.

Examples of "C2-C6 alkenyl" include, but are not limited to, vinyl(ethenyl), 1-propenyl,

2-propenyl, 3-propenyl, 2-methyl-prop-l-en-l-yl (2-methyl- 1-propenyl),

2-methyl-prop-l-en-3-yl (2-methyl-2-propenyl), but-l-en-l-yl, but-l-en-2-yl, but-l-en-3-yl, but-2-en-l-yl, but-2-en-2-yl, pent-l-en-l-yl, pent-l-en-2-yl, pent-l-en-3-yl, pent-l-en-4-yl, pent-l-en-5-yl, pent-2-en-l-yl, pent-2-en-2-yl, pent-2-en-3-yl (1 -ethyl- 1-propenyl),

pent-2-en-4-yl, pent-2-en-5-yl, 2-methyl-but-l-en-l-yl, 2-methyl-but-l-en-2-yl,

2- methyl-but-l-en-3-yl, 2-methyl-but-l-en-4-yl, 2-methyl-but-2-en-l-yl, 2-methyl-but-2-en-3-yl, 2-methyl-but-2-en-4-yl, 3-methyl-but- 1 -en- 1-yl, 3-methyl-but- l-en-2-yl, 3-methyl-but- l-en-3-yl,

3- methyl-but- 1 -en-4-y 1, 2,2-dimethy 1-prop- 1 -en- 1 -y 1, 2,2-dimethy 1-prop- 1 -en-2-y 1,

hex- 1 -en- 1-yl, hex-l-en-2-yl, hex-l-en-3-yl, hex-l-en-4-yl, hex-l-en-5-yl, hex-l-en-6-yl, hex-2-en-l-yl, hex-2-en-2-yl, hex-2-en-3-yl, hex-2-en-4-yl, hex-2-en-5-yl, hex-2-en-6-yl, hex-3-en-l-yl, hex-3-en-2-yl, hex-3-en-3-yl, 2-methyl-pent-l-en-l-yl, 2-methyl-pent-l-en-3-yl, 2-methy 1-pent- 1 -en-4-y 1, 2-methy 1-pent- 1 -en-5-y 1,.2-methy l-pent-2-en- 1 -y 1,

2- methyl-pent-2-en-3-yl, 2-methyl-pent-2-en-4-yl, 2-methyl-pent-2-en-5-yl,

3- methy 1-pent- 1 -en- 1 -y 1, 3-methy 1-pent- 1 -en-2-y 1, 3-methy 1-pent- 1 -en-3-yl,

3-methyl-pent-l -en-4-yl, 3-methyl-pent-l-en-5-yl, 3-methyl-pent-2-en-l-yl,

3- methyl-pent-2-en-2-yl, 3-methyl-pent-2-en-4-yl, 3-methyl-pent-2-en-5-yl,

4- methy 1-pent- 1 -en- 1 -y 1, 4-methy 1-pent- 1 -en-2-y 1, 4-methy 1-pent- 1 -en-3-yl,

4-methy 1-pent- 1 -en-4-y 1, 4-methy 1-pent- 1 -en-5-y 1, 4-methy l-pent-2-en- 1 -yl,

4-methyl-pent-2-en-2-yl, 4-methyl-pent-2-en-3-yl, 4-methyl-pent-2-en-4-yl,

4-methyl-pent-2-en-5-yl, 2,3-dimethyl-but-l -en-l-yl, 2,3-dimethyl-but-l-en-3-yl,

2,3-dimethy 1-but- 1 -en-4-y 1, 2,3-dimethy l-but-2-en- 1 -y 1, 3,3-dimethyl-but- 1 -en- 1 -yl,

3,3-dimethyl-but-l-en-2-yl, 3,3-dimethyl-but-l -en-4-yl, 2-ethyl-but-l-en-l -yl,

2- ethyl-but-l-en-3-yl, 2-ethyl-but-l-en-4-yl, 3-ethyl-but-l -en-l-yl, 3-ethyl-but-l-en-2-yl,

3- ethyl-but-l -en-3-yl, 3-ethyl-but-l -en-4-yl, 2-ethyl-but-2-en-l -yl, 2-ethyl-but-2-en-3-yl and 2-ethyl-but-2-en-4-yl.

In this invention, "alkynyl" group refers to a straight chain or a branched chain hydrocarbon group which contains at least one triple carbon-carbon bond and does not contain any hetero atoms. "C₂-C6 alkynyl" refers to an alkynyl group which has 2-6 carbon atoms.

Examples of "C2-C6 alkynyl" include, but are not limited to, ethinyl, 1-propinyl, 2-propinyl, 3-propinyl, 2-methyl-prop-l -in-l -yl, 2-methyl-prop-l -in-3-yl, but- l-in-l -yl, but-l-in-2-yl, but-l -in-3-yl, but-2-in-l-yl, but-2-in-2-yl, pent-l -in-l-yl, pent-l-in-2-yl, pent-l-in-3-yl, pent-l -in-4-yl, pent-l-in-5-yl, pent-2-in-l-yl, pent-2-in-2-yl, pent-2-in-3-yl, pent-2-in-4-yl, pent-2-in-5-yl, 2-methyl-but-l-in-l-yl, 2-methyl-but-l-in-2-yl, 2-methyl-but-l-in-3-yl, 2-methyl-but-l -in-4-yl, 2-methyl-but-2-in-l-yl, 2-methyl-but-2-in-3-yl, 2-methyl-but-2-in-4-yl, 3-methyl-but-l -in- l-yl, 3-methyl-but-l-in-2-yl, 3-methyl-but- l-in-3-yl, 3-methyl-but-l -in-4-yl,

2.2- dimethyl-prop-l -in-l-yl, 2,2-dimethyl-prop-l -in-2-yl, hex-l-in-l-yl, hex-l-in-2-yl, hex-l-in-3-yl, hex-l -in-4-yl, hex-l -in-5-yl, hex-l-in-6-yl, hex-2-in-l-yl, hex-2-in-2-yl, hex-2-in-3-yl, hex-2-in-4-yl, hex-2-in-5-yl, hex-2-in-6-yl, hex-3-in-l -yl, hex-3-in-2-yl, hex-3-in-3-yl, 2-methyl-pent-l-in- l-yl, 2-methyl-pent-l-in-3-yl, 2-methyl-pent-l-in-4-yl, 2-methyl-pent-l -in-5-yl, 2-methy l-pent-2-in-l -yl, 2-methyl-pent-2-in-3-yl,

2- methyl-pent-2-in-4-yl, 2-methyl-pent-2-in-5-yl, 3-methyl-pent-l -in- l-yl,

3- methyl-pent- l-in-2-yl, 3-methyl-pent- l-in-3-yl, 3-methyl-pent-l -in-4-yl,

3-methyl-pent-l -in-5-yl, 3-methyl-pent-2-in-l-yl, 3-methyl-pent-2-in-2-yl,

3- methyl-pent-2-in-4-yl, 3-methyl-pent-2-in-5-yl, 4-methyl-pent-l -in- l -yl,

4-methyl-pent- l -in-2-yl, 4-methyl-pent- l -in-3-yl, 4-methyl-pent- l -in-4-yl,

4- methyl-pent- l -in-5-yl, 4-methyl-pent-2-in-l -yl, 4-methy l-pent-2-in-2-yl,

4-methyl-pent-2-in-3-yl, 4-methy l-pent-2-in-4-yl, 4-methy l-pent-2-in-5-yl,

2.3- dimethy 1-but- 1 -in- 1 -y 1, 2,3-dimethy 1-but- 1 -in-3-y 1, 2,3-dimethy 1-but- 1 -in-4-y 1,

2,3-dimethyl-but-2-in- l -yl, 3,3-dimethyl-but- 1 -in- 1 -yl, 3,3-dimethyl-but-l-in-2-yl,

3,3-dimethyl-but-l -in-4-yl, 2-ethyl-but-l-in- l-yl, 2-ethyl-but-l-in-3-yl, 2rethyl-but-l-in-4-yl, 3-ethyl-but-l -in-l-yl, 3-ethyl-but- l-in-2-yl, 3-ethyl-but-l -in-3-yl, 3-ethyl-but- l -in-4-yl, 2-ethyl-but-2-in-l-yl, 2-ethyl-but-2-in-3-yl and 2-ethyl-but-2-in-4-yl.

In the present invention, "alkoxy" group refers to a group represented by -OR, wherein R is alkyl.

"C1-C6 alkoxy" group refers to an alkoxy group which has 1-6 carbon atom(s). "C1-C4 alkoxy" refers to an alkoxy group which has 1 -4 carbon atom(s).

Examples of "C1-C6 alkoxy" include, but are not limited to, methoxy, ethoxy, 1 -propyloxy, 2-propyloxy, 2-methy 1- 1 -propyloxy, 2-methyl-2-propyloxy, and 1 -butyloxy, and 2- butyloxy. In the present invention, "cycloalkyl" group refers to a saturated carbon ring system. "C3-C10 cycloalkyl" group refers to 3-10 membered cycloalkyl.

Examples of "C3-C10 cycloalkyl" include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, and adamantyl. For example, 3-8 membered cycloalkyl is also included in "C3-C10 cycloalkyl".

In the present invention, "C3-Ci₀cycloalkenyl" group refers to a cyclic unsaturated aliphatic hydrocarbon group of 3 to 10 carbon atoms with at least one double bond (two adjacent SP² carbon atoms).

Specific examples of "C3-C]₀cycloalkenyl" include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl.

In the present invention, "C6-Cioaryl" refers to an aromatic cyclic hydrocarbon group of 6 to 10 carbon atoms.

Specific examples of "C6-Ci₀aryl" include phenyl, 1 -naphthyl, and 2-naphthyl.

In the present invention, "halogen" refers to a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

As used herein, "hetero atom" refers to a sulfur atom, an oxygen atom, or a nitrogen atom.

In this invention, "amino" refers to a group represented by -NH₂ whose hydrogens may each be optionally substituted by a substituent.

In the present invention, "C|-C6 alkylamino" refers to an amino group bound to the C1-C6 alkyl. Examples of "C1-C6 alkylamino" include, but are not limited to, methylamino, ethylamino, propylamine, isopropylamino, n-butylamino, s-butylamino, i-butylamino, and

2-ethylbutylamino.

In the present invention, "di(Ci-C6alkyl)amino" refers to an amino group bound to two

"Ci-C₆alkyls" defined above.

Specific examples of "di(Ci-C6alkyl)amino" include dimethylamino, diethylamino,

dipropylamino, diisopropylamino, di-rc-butylamino, di-s-butylamino, di-i-butylamino, and di-2-ethylbutylamino.

In the present invention, "C2-C7alkyloxycarbonylamino" refers to a group represented by (C)-C6alkyl)-0-C=0-NH-, or a group in which the "C|-C6alkyl" defined above is bound to -OCONH-.

In the present invention, "Ci-C6aminoalkyl" refers to a group in which an amino group is bound to the "C-Cealkyl" defined above.

In the present invention, "C|-C6hydroxyalkyl" refers to a group in which one or more hydroxy groups are bound to the "Ci-Cealkyl" defined above.

In this invention, "sulfonyl" is a group represented by -SO2-.

In this invention, "Ci-C₆ alkylsulfonyl" refers to R-SO2- wherein R is the Ci-C₆ alkyl. "C1-C4 alkylsulfonyl" refers to R-SO2- wherein R is C1-C4 alkyl.

Examples of "C1-C6 alkylsulfonyl" include, but are not limited to, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, s-butylsulfonyl, /-butylsulfonyl, and

2-ethylbutylsulfonyl.

In this invention, "C6-C10 arylsulfonyl" refers to R-S0₂- wherein R is the Ce-C\o aryl.

Examples of "C6-C10 arylsulfonyl" include, but are not limited to, phenylsulfonyl. In the present invention, "Ci-C6alkylsulfonylamino" refers to R-S0₂-NH- wherein R is "C1 -C6 alkyl". "C1-C4 alkylsulfonylamino" refers to R-S0₂-NH- wherein R is R-S0₂-NH- wherein R is "Ci-C₄ alkyr.

Examples of "C1 -C6 alkylsulfonylamino" include, but are not limited to, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, n-butylsulfonylamino, s-butylsulfonylamino, /-butylsulfonylamino, and 2-ethylbutylsulfonylamino.

In this invention, "sulfinyl" is a group represented by -SO-.

In this invention, "Ci-C₆ alkylsulfinyl" refers to R-SO- wherein R is the Ci-C₆ alkyl. "C1-C4 alkylsulfinyl" refers to R-SO- wherein R is C 1 -C4 alkyl.

Examples of "C1 -C6 alkylsulfinyl" include, but are not limited to, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, s-butylsulfinyl, i-butylsulfinyl, and

2-ethylbutylsulfinyl.

In the present invention, "heteroaryl" refers to a monocyclic or fused aromatic heterocyclic group that includes at least one hetero atom selected from O, S, and N. When the aromatic heterocyclic group is a fused ring, those including a partially hydrogenated ring are also included in "heteroaryl".

Examples of such heteroaryls include pyrazolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, furyl, thienyl, oxazolyl, isooxazoiyl, pyrrolyl, imidazolyl, ( 1 ,2,3)- and (l ,2,4)-triazolyl, tetrazolyl, pyranyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, tetrahydroisoquinolyl, benzofuranyl, isobenzofuranyl, indolynyl, indolyl, isoindolyl, indazolyl, benzoimidazolyl, benzotriazolyl, benzooxazolyl, benzothiazolyl, benzo[6]thiophenyl, (1 ,2)- and

(l ,3)-benzooxathiol, chromenyl, 2-oxochromenyl, benzothiadiazolyl, quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, carbazolyl, tetrahydroisoquinolyl, tetrazolyl, [l ,2,4]triazo[ 1.5-a]pyridyl, l H-pyrrolo[2,3-6]pyridyl, and 2,3-dihydrobenzooxazolyl. Preferable examples include pyrazolyl, furyl, thienyl, pyridyl, pyrimidinyl, tetrahydroisoquinolyl, indolynyl, indazolyl, benzoimidazolyl, benzooxazolyl, tetrahydroisoquinolyl, tetrazolyl,

[ l ,2,4]triazo[ 1.5-a]pyridyl, l H-pyrrolo[2,3-6]pyridyl, and 2,3-dihydrobenzooxazolyl.

In the present invention, "3- to 8-membered heterocycloalkyl" refers to a non-aromatic monovalent 3- to 8-membered ring that includes 1 to 3 hetero atoms in the atoms forming the ring, and that may have a double bond within the ring.

Examples of "3- to 8-membered heterocycloalkyl" include aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, azepanyl, morpholinyl, oxetanyl, and

1 ,2,5,6-tetrahydropyridyl.

A salt is defined as the product formed from the neutralisation reaction of acids and bases.

Salts are ionic compounds composed of cations (positively charged ions) and anions (negative ions) so that the product is electrically neutral. These component ions can be inorganic as well as organic.

Hydrate is a term used in inorganic chemistry and organic chemistry to indicate that a substance contains water. Solvate refers to a molecule in a solution complexed by solvent molecules. Isomers are compounds with the same molecular formula but different structural formulae.

More specifically, isomer includes geometric isomer, optical isomer, stereoisomer, tautomer of the compound, and mixtures thereof.

In a preferred embodiments, the present invention provides [ 1 ] a compound represented by formula (I) or a pharmaceutically acceptable salt thereof:

or a pharmaceutically acceptable salt thereof,

wherein R¹, R², R³, and R⁴ are each independently a group selected from the group consisting of:

hydrogen,

hydroxy 1,

halogen,

cyano,

nitro,

amino,

C,-C₆ alkyl,

C2-C6 alkenyl,

C₂-C₆ alkynyl,

C3-C10 cycloalkyl,

C3-C10 cycloalkenyl,

Ci-C₆ alkoxy,

C₆-Cio aryl,

indanyl,

heteroaryl,

3- to 8-membered heterocycloalkyl,

-OS0₂CH₃,

-OSO2CF3,

-CONH₂,

-OCONR^IOIR¹⁰², wherein R¹⁰¹ and R¹⁰² each independently is hydrogen, C,-C₆ alkyl, or R¹⁰' and R¹⁰² taken together form morpholinyl,

-OCOR¹⁰³, wherein R'⁰³ represents C|-C₆ alkyl, and

-OCOOR¹⁰⁴, wherein R¹⁰⁴ represents C]-C₆ alkyl,

wherein R¹, R², R³, and R⁴ are optionally substituted with a substituent independently selected from the group consisting of substituent A;

wherein substituent A is independently selected from the group consisting of:

hydroxyl;

oxo (=0);

cyano;

halogen;

C1-C6 alkyl optionally substituted with substituent B;

C3-C10 cycloalkyl optionally substituted with cyano or C|-C6 alkyl substituted with -NR^{3 I}R³², wherein R³¹ and R³² each independently represent hydrogen or C1-C6 alkyl;

-NR^2IR²², wherein R²¹ and R²² each independently represent hydrogen; C1 -C6 alkyl optionally substituted with hydroxyl, amino, di(Ci-C6 alkyl)amino, -S0₂(Ci-C6 alkyl), 3- to 8-membered heterocycloalkyl, or cyano; or a 3- to 8-membered heterocycloalkyl optionally substituted with -COOR¹⁰⁵ wherein R¹⁰⁵ represents C)-C₆ alkyl;

Ci-C₆ alkoxy optionally substituted with halogen, 3- to 8-membered heterocycloalkyl optionally substituted with C\-C₆ alkyl, or -NR³³R³⁴ wherein R³³ and R³⁴ each

independently represent hydrogen, C|-C₆ alkylsulfonyl, or C1-C6 alkyl optionally substituted with Ci-C₆ alkylsulfonyl or di(C|-C6 alkyl)amino;

-S02NR²³R²⁴, wherein R²³ and R²⁴ each independently represent hydrogen; C1-C6 alkyl optionally substituted with hydroxyl, Ci-C₆ alkoxy, halogen, C3-C10 cycloalkyl, heteroaryl, or -NR³⁵R³⁶ wherein R³⁵ and R³⁶ each independently represent hydrogen or Ci-C₆ alkyl; C3-C10 cycloalkyl optionally substituted with C1-C6 hydroxyalkyl; 3- to 8-membered heterocycloalkyl; or R²³ and R²⁴ taken together form 3- to 8-membered heterocycloalkyl optionally substituted with amino or halogen;

Ci-C₆ alkylsulfonyl optionally substituted with hydroxyl;

-NHS0₂(Ci-C6 alkyl), wherein the carbon atoms are optionally substituted with -NR³⁷R³⁸ wherein R³⁷ and R³⁸ each independently represent hydrogen or Ci-C₆ alkyl;

3- to 8-membered heterocycloalkyl optionally substituted with -NR³⁹R⁴⁰, wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or Ci-C₆ alkylsulfonyl; Q-C6 alkyl optionally substituted with -NR^4IR⁴², wherein R⁴¹ and R⁴²each independently represent hydrogen or C|-C₆ alkyl; hydroxyl; or C1-C6 alkylsulfonyl;

aryl optionally substituted with Ci-C₆ alkyl optionally substituted with cyano or amino; heteroaryl;

-COOR^{1 1}, wherein Rⁿ represents hydrogen or Ci-C₆ alkyl; and

-COR¹², wherein R¹² represents C1-C6 alkyl; C3-C10 cycloalkyl; cyanomethyl;

25 26 25 26

aminomethyl; -NR R wherein R and R each independently represent hydrogen or C1-C6 alkyl optionally substituted with hydroxyl or -NR ³R⁴⁴, wherein R⁴³ and R ⁴ each independently represent hydrogen or C1-C6 alkyl; or 3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ alkyl;

wherein substituent B is independently selected from the group consisting of:

halogen;

hydroxyl;

Ci-C₆ alkoxy;

cyano;

cycloalkyl;

C6-C10 aryl optionally substituted with cyano;

heteroaryl;

3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ alkyl, hydroxyl, amino, C1-C6 aminoalkyl, or Ci-C₆ alkyl substituted with C₂-C₇ alkyloxycarbonylamino;

-NR^{5 I}R⁵², wherein R⁵¹ and R⁵² each independently represent hydrogen; C1-C6 alkyl optionally substituted with C\-Ce alkylsulfonyl or 3- to 8-membered heterocycloalkyl optionally substituted with -COOR⁵³ wherein R⁵³ represents hydrogen or Ci-C₆ alkyl; 3- to

8-membered heterocycloalkyl; C1-C6 alkylsulfonyl; C3-C|₀ cycloalkyl; -COR⁵⁵ wherein R⁵⁵ represents Ci-Ce alkyl; -COOR⁵⁶ wherein R⁵⁶ represents C|-C₆ alkyl; or -CONR⁵⁷R⁵⁸

57 58

wherein R and R each independently represent hydrogen or Ci-Ce alkyl;

-COOR⁵⁴, wherein R⁵⁴ represents hydrogen or C1-C6 alkyl;

-CONH2;

-SO₂NR¹⁰⁶R¹⁰⁷, wherein R¹⁰⁶ and R¹⁰⁷ each independently represent hydrogen, d-C₆ alkyl, or C3-Ci₀ cycloalkyl;

C1-C6 alkylsulfinyl; and

C1-C6 alkylsulfonyl;

wherein R⁵ is hydrogen or C1-C6 alkyl; and wherein is a structure selected from the group consisting of

(i) -S-CR⁷=CR⁶-,

(ii) -CH2-CH2-CH2-,

(iii) -NR^,08-CH=CR¹⁰⁹-, wherein R¹⁰⁸ represents hydrogen, or Ci-C₆ alkyl optionally substituted with hydroxy 1, and R¹⁰⁹ represents hydrogen, CH3, or phenyl substituted with

C1-C6 aminoalkyl, and

(iv) -N=CH-S-,

wherein R⁶ is selected from the group consisting of:

hydrogen,

hydroxyl,

Ci-C₆ alkyl,

C₆-Cio aryl optionally substituted with hydroxyl, and

3- to 8-membered heterocycloalkyl optionally substituted with -NR⁶¹R⁶², wherein R⁶¹ and R⁶² each independently represent hydrogen or Ci-C₆ alkyl;

wherein R⁷ is selected from the group consisting of:

hydrogen;

halogen;

Ci-C₆ alkyl optionally substituted with hydroxyl, -NR⁷¹R⁷² wherein R⁷¹ and R⁷² each independently represent hydrogen; Q-C6 alkyl optionally substituted with dimethylamino; C3-C10 cycloalkyl optionally substituted with amino or 3- to 8-membered heterocycloalkyl; or 3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ aminoalkyl;

C₆-Cio aryl optionally substituted with hydroxyl;

C₆-Cio arylsulfonyl; and

-COR⁷³, wherein R⁷³ represents 3- to 8-membered heterocycloalkyl optionally substituted with amino; or -NR⁷⁴R⁷⁵ wherein R⁷⁴ and R⁷⁵ each independently represent hydrogen, 3- to 8-membered heterocycloalkyl, or C3-Q0 cycloalkyl optionally substituted with amino.

[2] The compound of [1], or a pharmaceutically acceptable salt thereof, wherein

X— yrrrrz ._§ __S._CR7_=CR6.

, [3] The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, cyano, Ci-C₆ alkyl optionally substituted with hydroxyl or halogen, C3-Ci₀ cycloalkyl, C2-C6 alkenyl, C₂-C6 alkynyl, or halogen.

[4] The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen, hydroxyl, halogen, C1-C6 alkoxy, or C₆-C|o aryl optionally substituted with hydroxyl.

[5] The compound of [2] or a pharmaceutically acceptable salt, wherein R² is hydrogen,

hydroxyl, halogen, C1-C6 alkoxy, or dihydroxyphenyl.

[6] The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R³ is selected from the group consisting of: hydrogen; hydroxyl; C1-C6 alkyl optionally substituted with hydroxyl, halogen, or hydroxyethylamino; halogen; Ci-C₆ alkoxy optionally substituted with dimethylamino or morpholinyl; C1-C6 alkylphenyl, wherein the aliphatic carbons are optionally substituted with -NR^{5 I}R⁵²; cyano; nitro; amino; 3- to 8-membered

heterocycloalkyl optionally substituted with amino; heteroaryl; -OSO2CH3; -OSO2CF3; -OCOR¹⁰³, wherein R¹⁰³ represents C,-C₆ alkyl; -OCOOR¹⁰⁴ wherein R¹⁰⁴ represents C,-C₆ alkyl; -OCONR¹⁰¹R¹⁰² wherein R¹⁰¹ and R¹⁰² each independentally represent hydrogen or Ci-C₆ alkyl, or R¹⁰¹ and R¹⁰² taken together form morpholinyl; and -CONH₂. [7] The compound of [6], or a pharmaceutically acceptable salt thereof, wherein when R³ is a 3- to 8-membered heterocycloalkyl, the 3- to 8-membered heterocycloalkyl is selected from the group consisting of piperidyl, pyrrolidinyl, morpholinyl, or piperazinyl and optionally substituted with amino; and when R³ is heteroaryl, the heteroaryl is pyridyl.

[8]. The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R⁴ is selected from the group consisting of hydrogen, hydroxy 1, halogen, amino, C1 -C6 alkyl, C₂-C6 alkenyl, C3-Cio cycloalkyl, C3-C10 cycloalkenyl, Ci-C₆ alkoxy, C6-Ci₀ aryl, indanyl, heteroaryl, and 3- to 8-membered heterocycloalkyl, and R⁴ is optionally substituted with substituent A.

[9] The compound of [8], or a pharmaceutically acceptable salt thereof, wherein when R⁴ is

heteroaryl, the heteroaryl is selected from the group consisting of pyridyl, lH-indazolyl, l H-tetrazolyl, [ l ,2,4]triazolo[l ,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-b]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and

tetrahydroisoquinolyl); and wherein the 3- to 8-membered heterocycloalkyl is selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, azepanyl, morpholinyl, and 1 ,2,3,6-tetrahydropyridyl; wherein each of the groups of R⁴ is optionally substituted with substituent A- l ;

wherein substituent A- l is selected from the group consisting of:

hydroxyl;

oxo;

cyano;

halogen;

C1-C6 alkyl optionally substituted with a substituent selected from the group consisting of substituent B- l ;

C3-C10 cycloalkyl optionally substituted with cyano, or C]-C alkyl substituted with -NR³¹R³²;

-NR^21AR^22A, wherein R^21A and R^{2 A} each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with amino, di (C|-C₆ alkyl) amino, -S0₂ (C1 -C6 alkyl), piperidyl, or cyano; or piperidyl optionally substituted with -COOR¹⁰⁵;

Ci-C₆ alkoxy optionally substituted with halogen; a 3- to 8-membered heterocycloalkyl selected from piperidyl and piperazinyl, either of which is optionally substituted with Ci-C₆ alkyl; or -NR R³⁴;

-S0₂NR^23AR^24A , wherein R^23A and R^24A each independently represent hydrogen, Ci-C₆ alkyl optionally substituted with hydroxyl, C1 -C6 alkoxy, halogen, C3-C10 cycloalkyl, pyrazolyl, imidazolyl, or -NR³⁵R³ ; C3-C10 cycloalkyl optionally substituted with C 1-C6 hydroxyalkyl; azetidinyl; pyrrolidinyl, or R^{2 A} and R^24A taken together form pyrrolidinyl optionally substituted with amino or halogen;

C1 -C6 alkylsulfonyl optionally substituted with hydroxyl;

-NHS0₂(C| -C6 alkyl), wherein the carbon atoms are optionally substituted with

-NR³⁷R³⁸;

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, and tetrahydropyridyl any of which is optionally substituted with -NR³⁹R⁴ ; Ci-C₆ alkyl optionally substituted with -NR⁴¹R , hydroxyl; or Ci-C₆ alkylsulfonyl;

l H-tetrazolyl;

aryl optionally substituted with C1-C6 alkyl, wherein C1-C6 is the aliphatic carbons are optionally substituted with cyano or amino;

-COOR" ; and

-COR^12A, wherein R^12A represents piperazinyl optionally substituted with C1 -C6 alkyl; C3-C10 cycloalkyl; cyanomethyl; aminomethyl; -NR²⁵R²⁶ wherein R²⁵ and R²⁶ each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with hydroxyl or -NR. R⁴⁴; or Ci-Qj alkylsulfonyl;

wherein substituent B-l is selected from the group consisting of:

halogen;

hydroxyl;

C1-C6 alkoxy;

cyano;

cycloalkyl;

phenyl optionally substituted with cyano;

heteroaryl selected from the group consisiting of imidazolyl, pyrazolyl, and thiazolyl;

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl any of which are optionally substituted with hydroxyl, amino, C1-C6 aminoalkyl, or Ci-Ce alkyl optionally substituted with C2-C7 alkyloxycarbonylamino;

-NR^51AR^52A, wherein R^{5 IA} and R^52A each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with Ci-C₆ alkylsulfonyl or piperidyl optionally substituted with -COOR⁵ ; piperidyl; Ci-C₆ alkylsulfonyl; C3-C10 cycloalkyl; -COR⁵⁵, -COOR⁵⁶, or -CONR⁵⁷R⁵⁸;

-COOR⁵⁴;

-CONHb;

-SO₂NR^l06R¹⁰⁷;

C1-C6 alkylsulfinyl; and

C1-C6 alkylysulfonyl.

The compound of [9], or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from group (p):

wherein group (p) is independently selected from the group consisting of:

hydrogen,

hydroxyl,

halogen,

amino optionally substituted with a substituent selected from the group consisting of substituent (g),

C1-C6 alkyl optionally substituted with a substituent selected from the group consisting of substituent (a),

C2-C6 alkenyl optionally substituted with a substituent selected from the group consisting of substituent (b),

C3-C10 cycloalkyl,

C3-Ci₀ cycloalkenyl,

C1-C6 alkoxy,

C6-C10 aryl optionally substituted with a substituent selected from the group consisting of substituent (c),

indanyl optionally substituted with a substituent selected from the group consisting of substituent (d),

heteroaryl selected from the group consisting of pyridyl, l H-indazolyl, l H-tetrazolyl, [ l ,2,4]triazolo[ l ,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-6]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and tetrahydroisoquinolyl any of which is optionally substituted with a substituent selected from the group consisting of substituent (e); and 3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and 1 ,2,3,6-tetrahydropyridyl any of which is optionally substituted with a substituent selected from the group consisting of substituent

(0;

wherein substituent (a) is selected from the group consisting of:

-NR^21AR^22A, wwherein R^{2 IA} and R^{2 A} each independently represent hydrogen; C1-C6 alkyl optionally substituted with piperidyl; or piperidyl optionally substituted with -COOR^{l <¾};

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl and piperidyl either of which is optionally substituted with Q-C6 alkyl optionally substituted with -NR⁴¹R⁴² or -NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ each independently represent hydrogen or Ci-C₆ alkyl; and

-NHS0₂(C,-C₆ alkyl);

wherein substituent (b) is selected from the group consisting of:

-COOR" ;

-NR^2laR^22a, wherein R^21a and R ^a each independently represent hydrogen, or Ci-C6 alkyl optionally substituted with di(Ci-C6 alkyl)amino or Q-C6 alkylsulfonyl;

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, and piperidyl any of which are optionally substituted with -NR³⁹R⁴⁰, Ci-C₆ alkyl optionally substituted with - R^4IR⁴², hydroxyl, or Ci-C₆ alkylsulfonyl;

cyano; and

Cj-Ce alkoxy;

wherein substituent (c) is selected from the group consisting of:

hydroxyl;

cyano;

halogen;

Ci-C₆ alkyl optionally substituted with a substituent selected from the group consisting of substituent B-c below;

C3-C10 cycloalkyl optionally substituted with cyano, or C)-C₆ alkyl substituted with -NR³¹R³²;

-NR^2,cR^22c , wherein R^2lc and R^22c each independently represent hydrogen or C1-C6 alkyl optionally substituted with amino or cyano;

C1-C6 alkoxy optionally substituted with halogen, 3- to 8-membered heterocycloalkyl selected from the group consistingn of piperidyl and piperazinyl either of which are optionally substituted with C1-C6 alkyl, or -NR³ R³⁴;

-S02NR^23cR^{2 c}, wherein R^23c and R^24c each independently represent hydrogen, Ci-C₆ alkyl optionally substituted with hydroxyl, C1-C6 alkoxy, halogen, C3-C10 cycloalkyl, pyrazolyl, imidazolyl, or -NR³⁵R³⁶; C3-Ciocycloalkyl optionally substituted with C1-C6 hydroxyalkyl; azetidinyl, pyrrolidinyl, or wherein R^23c and R^24c takent together form pyrrolidinyl which is optionally substituted with amino or halogen;

C1-C6 alkylsulfonyl optionally substituted with hydroxyl;

-NR³⁷R³⁸;

piperazinyl optionally substituted with C1-C6 alkyl or C1-C6 alkylsulfonyl; piperidyl optionally substituted with hydroxyl;

lH-tetrazolyl;

1 , 2, 3, 6-tetrahydropyridyl; and -COR^l2c, wherein R^12c represents piperazinyl which is optionally substituted with Ci-C₆ alkyl, C3-C10 cycloalkyl, cyanomethyl, aminomethyl, -NR²⁵R²⁶, or C1-C6 alkyl; and

wherein substituent B-c is selected from the group consisting of:

halogen;

hydroxyl;

methoxy;

cyano;

C3-C10 cycloalkyl;

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl, any of which is optionally substituted with C1-C6 alkyl, hydroxyl, amino, Q-C6 aminoalkyl, or Ci-C₆ alkyl substituted with C2-C7 alkyloxycarbonylamino;

-NR^51cR^{5 c}, wherein R^51c and R^52c each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with C1-C6 alkylsulfonyl, or piperidyl optionally substituted with -COOR⁵³; piperidyl; Ci-C₆alkylsulfonyl; C3-C10 cycloalkyl; -COR⁵⁵; or

-CONR^J'R^JO;

heteroaryl selected from the group consisting of imidazolyl, pyrazolyl, and thiazolyl;

-COOR⁵⁴;

-CONH2;

-SO₂NR¹⁰⁶R¹⁰⁷;

C1-C6 alkylsufinyl; and

Ci-C₆ alkylsulfonyl;

wherein substituent (d) is selected from the group consisting of:

-NR R , wherein R and R each independently represent hydrogen or Ci-C₆ alkyl;

wherein substituent (e) is selected from the group consisting of:

hydroxyl;

oxo;

cyano;

C3-C|₀ cycloalkyl optionally substituted with cyano;

-NR^21eR ^2e, wherein R^2,e and R^22e each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with amino;

piperidyl;

Ci-C₆ alkoxy optionally substituted with -NR³³R³⁴;

Ci-C₆ alkyl optionally substituted with cyano; -NR^{5 le}R^{5 e}, wherein R^51e and R^{5 e} each independently represent hydrogen, C1-C6 alkyl, or -COOR⁵⁶; moφholinyl; or cyanophenyl;

-CONH2;

wherein substituent (f) is selected from the group consisting of:

Ci-C₆ alkyl optionally substituted with -NR^{5l f}R^52f, wherein R^5If and R^52f each independently represent hydrogen, Q-C6 alkyl, or -COOR⁵⁶; and

C1-C6 alkylsulfonyl; wherein substituent (g) is aryl optionally substituted with Ci-C₆ alkyl having the aliphatic carbons optionally substituted with cyano or amino.

[ 1 1 ] The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R⁶ is

hydrogen; hydroxyl; C\-Ce alkyl; phenyl optionally substituted with 1 to 3 hydroxyls;

piperidyl optionally substituted with amino; or piperazinyl.

[ 12] The compound of [1 1 ], or a pharmaceutically acceptable salt thereof, wherein R⁷ is

hydrogen; Ci-C₆ alkyl optionally substituted with hydroxyl or piperidyl; or halogen.

[ 13] The compound of [2], or a pharmaceutically acceptable salt thereof, wherein R⁷ is

hydrogen;

Ci-Ce alkyl optionally substituted with hydroxyl; -NR^{71 A}R^72A wherein R^71A and

R^72Aeach independently represent hydrogen, Ci-C₆ alkyl optionally substituted with dimethylamino, C3-C10 cycloalkyl optionally substituted with amino, or piperidyl; or 3- to 8-membered heterocycloalkyl selected from the group consisting of piperidyl and morpholinyl either of which is optionally substituted with Ci-C₆ aminoalkyl;

phenyl optionally substituted with 1 to 2 hydroxyls;

phenylsulfonyl; or

-COR^73A, wherein R^73A represents piperidyl optionally substituted with amino, or -NR^74AR^75A, wherein R^74A and R^75A each independently represent hydrogen, piperidyl, or C3-C10 cycloalkyl optionally substituted with amino.

[ 14] The compound of [1 ], or a pharmaceutically acceptable salt thereof, wherein

x— - Y— -z _{is .CH2}._{CH CH2.}

[15] The comp poouunndd ooff [[1144]],, 0o1r a pharmaceutically acceptable salt thereof, wherein R¹ and R² are hydrogen.

[16] TThhee ccoomm]pound of [14], or a pharmaceutically acceptable salt thereof, wherein R is

hydroxyl or methoxy.

[ 17] The compound of [14], or a pharmaceutically acceptable salt thereof, wherein R⁴ is

hydrogen; phenyl substituted with C)-C₆ alkyl substituted with -NR^51AR^52A, wherein R^51A and R ^2A each independently represent hydrogen or Q-C6 alkyl, or -S0₂NR^53AR^54A, wherein R^53A and R^54A each independently represent hydrogen or Q-C₆ alkyl optionally substituted with halogen or hydroxy; 1 ,2,3,6-tetrahydropyridyl; hydroxypyridyl; or methoxypyridyl.

[ 1 8] The compound of [1 ], or a pharmaceutically acceptable salt thereof, wherein

ΧΓΓΓΤΥΓΓΤΓΖ ._s __NR108._CH=CR,09.₅

R' , R², and R⁴ are hydrogen, and

R³ is hydrogen, hydroxyl or C1-C6 alkoxy.

[ 19] The compound of [ 1 ], or a pharmaceutically acceptable salt thereof, wherein

χ— γ— z- is -N=CH-S-,

R¹, R², and R⁴ are hydrogen, and

R³ is methoxy.

Alternatively, in some embodiments, the present invention also provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof:

1. A compound represented by general formula I:

or a pharmaceutically acceptable salt thereof,

wherein R¹ , R², R³, and R⁴ are each independently a group selected from the group consisting of:

hydrogen,

hydroxyl,

halogen,

cyano,

nitro,

amino,

Ci-C₆ alkyl,

C2-C6 alkenyl,

C₂-C6 alkynyl,

C3-Ci₀ cycloalkyl,

C3-C10 cycloalkenyl,

C1-C6 alkoxy,

C₆-Cio aryl,

indanyl,

heteroaryl,

3- to 8-membered heterocycloalkyl,

-OS0₂CH₃,

-OSO2CF3,

-CONH2

-OCONR^,0lR¹⁰² (wherein R¹⁰¹ and R^!02 each independently represent hydrogen or Ci-C₆ alkyl, or R¹⁰¹ and R¹⁰² together form morpholinyl),

-OCOR¹⁰³ (wherein R¹⁰³ represents Ci-C₆ alkyl), and

-OCOOR¹⁰⁴ (wherein R¹⁰⁴ represents C,-C₆ alkyl)

substituent A:

hydroxyl;

oxo (=0);

cyano;

halogen;

C1-C alkyl (wherein the C_\-Ce alkyl is optionally substituted with a substituent selected from the group consisting of substituent B below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or C1-C6 alkyl substituted with -NR^{3 I} R³² (wherein R³¹ and R³² each independently represent hydrogen or C1-C6 alkyl)]; -NR²¹R²² [wherein R²¹ and R²² each independently represent hydrogen, C1 -C6 alkyl (wherein the Ci-C₆ alkyl is optionally substituted with hydroxyl, amino, di(Ci-C₆ alkyl)amino, Ci-C₆ alkylsulfonyl (-S0₂(Ci-C6 alkyl)), 3- to 8-membered heterocycloalkyl, or cyano), or 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -COOR¹⁰⁵ (wherein R¹⁰⁵ represents Ci-Ce))];

C1-C6 alkoxy {wherein the C1-C6 alkoxy is optionally substituted with halogen, 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl), or -NR³³R³⁴ [wherein R³³ and R³⁴ each independently represent hydrogen, Q-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with Ci-C₆ alkylsulfonyl or di(Q-C6 alkyl)amino), or Ci-C₆ alkylsulfonyl]} ;

-S0₂NR²³R²⁴ {wherein R²³ and R²⁴ each independently represent hydrogen, C1-C6 alkyl [wherein the Ci-C₆ alkyl is optionally substituted with hydroxyl, C]-C₆ alkoxy, halogen, C3-C10 cycloalkyl, heteroaryl, or -NR³⁵R³⁶ (wherein R³⁵ and R³⁶ each independently represent hydrogen or C1-C6 alkyl)], C3-C10 cycloalkyl (wherein the C₃-Ci₀ cycloalkyl is optionally substituted with Q-C6 hydroxyalkyl), or 3- to 8-membered heterocycloalkyl; or R²³ and R²⁴ may together form 3- to 8-membered heterocycloalkyl wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with amino or halogen} ;

C1-C6 alkylsulfonyl (wherein the C\-Ce alkyl moiety is optionally substituted with hydroxyl);

C1 -C6 alkylsulfonylamino (-NHS0₂(Ci-C6 alkyl)) [wherein the Ci-C₆ alkyl moiety is optionally substituted with -NR³⁷R³⁸ (wherein R³⁷ and R³⁸ each independently represent hydrogen or Ci-C₆ alkyl)];

3- to 8-membered heterocycloalkyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or C1-C6 alkylsulfonyl), C1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with -NR⁴¹R⁴² (wherein R⁴¹ and R⁴ each independently represent hydrogen or Ci-C₆ alkyl)], hydroxyl, or Ci-Ce alkylsulfonyl} ;

Aryl (wherein the aryl is optionally substituted with C1-C6 alkyl[wherein C1-C6 alkyl is optionally substituted with cyano or amino]);

heteroaryl;

-COOR ¹ (wherein R^{1 1} represents hydrogen or C1-C6 alkyl); and

-COR¹² [wherein R¹² represents Q-C6 alkyl, C3-Q0 cycloalkyl, cyanomethyl, aminomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen, or C 1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with hydroxyl or -NR⁴³R⁴⁴ (wherein R⁴ and R⁴⁴ each independently represent hydrogen or Q-C6 alkyl)] }, or 3- to 8-membered heterocycloalkyl which is optionally substituted with C1-C6 alkyl], substituent B:

halogen;

hydroxyl;

Ci-C₆ alkoxy;

cyano;

cycloalkyl;

C6-C10 aryl (wherein C6-Ci₀ aryl is optionally substituted with cyano)

heteroaryl;

3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C1-C6 alkyl, hydroxyl, amino, Q-C6 aminoalkyl, or C\-Ce alkyl substituted with C2-C7 alkyloxycarbonylamino);

-NR⁵¹R⁵² {wherein R⁵¹ and R⁵² each independently represent hydrogen, C -Ce alkyl [wherein the Ci-C₆ alkyl is optionally substituted with Ci-Ce alkylsulfonyl, or 3- to 8-membered heterocycloalkyl optionally substituted with -COOR^S3 (wherein R⁵³ represents hydrogen or Ci-C₆ alkyl)], 3- to 8-membered heterocycloalkyl, C1-C6 alkylsulfonyl, C3-C10 cycloalkyl, -COR (wherein R^S5 represents Ci-C₆ alkyl), -COOR (wherein R represents

57 58 57 58

Ci-C₆ alkyl), or -CONR R (wherein R and R each independently represent hydrogen or Ci-C₆ alkyl)};

-COOR⁵⁴ (wherein R⁵⁴ represents hydrogen or C₁ -C6 alkyl)];

-CONH2;

-SO₂NR¹⁰⁶R¹⁰⁷ {wherein R¹⁰⁶ and R¹⁰⁷ each independently represent hydrogen, Ci-C₆ alkyl, or C3-C₁₀ cycloalkyl}

C₁-C6 alkylsulfinyl; and

C₁-C6 alkylsulfonyl;

wherein R⁵ is hydrogen or C₁-C6 alkyl; and

wherein is a structure selected from the group consisting of

(i) -S-CR⁷=CR⁶-,

(ii) -CH₂-CH₂-CH₂-,

(iii) -NR¹⁰⁸-CH=CR¹⁰⁹- (wherein R¹⁰⁸ represents hydrogen, or Ci-C₆ alkyl that is optionally substituted with hydroxyl, and R^{1 9} represents hydrogen, CH3,, or phenyl that is substituted with CI -C6 aminoalkyl, and

(iv) -N=CH-S-,

wherein R⁶ is

hydrogen,

hydroxyl,

C,-C₆ alkyl,

C6-C₁₀ aryl (wherein the C6-C₁₀ aryl is optionally substituted with hydroxyl), or

3- to 8-membered heterocycloalkyl [wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR R (wherein R and R each independently represent hydrogen or C₁-C6 alkyl)];

wherein R⁷ is

hydrogen;

halogen;

C₁-C6 alkyl {wherein the C₁-C6 alkyl is optionally substituted with hydroxyl, -NR⁷¹R⁷² [wherein R⁷¹ and R⁷² each independently represent hydrogen, Ci-C₆ alkyl (wherein the C₁-C6 alkyl is optionally substituted with dimethylamino), C3-C₁₀ cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino), or 3- to 8-membered

heterocycloalkyl], or 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C₁-C6 aminoalkyl)},

C6-C₁0 aryl (wherein the C6-Ci₀ aryl is optionally substituted with hydroxyl);

C6-C10 arylsulfonyl; or

-COR⁷³ {wherein R⁷³ represents 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with amino), or -NR⁷ R⁷⁵ [wherein R⁷⁴ and R⁷⁵ each independently represent hydrogen, 3- to 8-membered heterocycloalkyl, or C3-C₁₀ cycloalkyl (wherein the C3-C₁₀ cycloalkyl is optionally substituted with amino)]} .e compound of above 1 , or a pharmaceutically acceptable salt thereof, wherein

X— Yrrrrz ^ __S__CR7_=CR6__ 3. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen, cyano, Ci-C₆ alkyl (wherein C\-Ce alkyl is optionally substituted with hydroxyl or halogen), C3-Ci₀ cycloalkyl, C₂-C₆ alkenyl, C₂-Ce alkynyl, or halogen.

4. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R² is

hydrogen, hydroxyl, halogen, Ci -C₆ alkoxy, or C₆-C|o aryl which is optionally substituted with hydroxyl.

5. The compound of above 2 or a pharmaceutically acceptable salt, wherein R² is hydrogen,

hydroxyl, halogen, Q-C6 alkoxy, or dihydroxyphenyl.

6. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R³ is

hydrogen; hydroxyl; C1-C6 alkyl (wherein alkyl is optionally substituted with hydroxyl, halogen, or hydroxyethylamino); halogen; Ci-C₆ alkoxy optionally substituted with dimethylamino or morpholinyl; Q-Ce alkylphenyljwherein Ci-C₆ alkyl of the Ci-C₆ alkylphenyl is optionally substituted with -NR⁵¹R ² {wherein R⁵¹ and R⁵² each

independently represent hydrogen, C1-C6 alkyl, or -COOR⁵⁶ (wherein R⁵⁶ represents C)-C6 alkyl)}]; cyano; nitro; amino; 3- to 8-membered heterocycloalkyl which is optionally substituted with amino; heteroaryl; -OS0₂CH₃; -OS0₂CF₃; -OCOR¹⁰³ (R¹⁰³ represents Ci-C₆ alkyl); -OCOOR¹⁰⁴ (wherein R¹⁰⁴ represents d-C₆ alkyl); -OCONR¹⁰¹R¹⁰² (wherein R¹⁰¹, R¹⁰² each independentally represent hydrogen or Q-C6 alkyl, or R¹⁰¹ and R¹⁰² together form moφholinyl); or -CONH₂.

7. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R is

hydrogen; hydroxyl; C1-C6 alkyl (wherein alkyl is optionally substituted with hydroxyl, halogen, or hydroxyethylamino); halogen; C1-C6 alkoxy that is optionally substituted with dimethylamino or morpholinyl; Ci-Ce alkylphenyl (wherein C1-C6 alkyl of the C1-C6

alkylphenyl is optionally substituted with -NR⁵¹R⁵² {wherein R⁵¹ and R⁵² each

independently represent hydrogen, C1-C6 alkyl, or -COOR⁵⁶ (wherein R⁵⁶ represents C C6 alkyl) cyano; nitro; amino; 3- to 8-membered heterocycloalkyl which is optionally substituted with amino (wherein the 3- to 8-membered heterocycloalkyl is piperidyl, pyrrolidinyl, morpholinyl, or piperazinyl); pyridyl; -OS0₂CH₃; -OS0₂CF₃; -OCOR¹⁰³ (R¹⁰³ represents C,-C₆ alkyl); -OCOOR¹⁰⁴ (wherein R¹⁰⁴ represents Ci-C₆ alkyl); -OCONR¹⁰¹R¹⁰² (wherein R¹⁰¹, R¹⁰² each independently represent hydrogen or C1-C6 alkyl, or R¹⁰¹ and R¹⁰² together form morpholinyl); or -CONH₂.

8. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a

group selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C1-C6 alkyl, C₂-C6 alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C1-C6 alkoxy, C6-Ci₀ aryl, indanyl, heteroaryl, and 3- to 8-membered heterocycloalkyl, wherein each of the groups of R⁴ is optionally substituted with a substituent selected from the group consisting of substituent A above.

9. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a

group selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C|-C₆ alkyl, C₂-C6 alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, C\-Ce alkoxy, C6-C10 aryl, indanyl, heteroaryl (wherein the heteroaryl is selected from the group consisting of pyridyl, l H-indazolyl, lH-tetrazolyl, [l ,2,4]triazolo[l ,5-a]pyridyl, benzoimidazolyl,

2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-b]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and tetrahydroisoquinolyl), and 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, azepanyl, morpholinyl, and 1 ,2,3,6-tetrahydropyridyl), wherein each of the groups of R is optionally substituted with a substituent selected from the group consisting of substituent A- l below: substituent A- l :

hydroxy 1;

oxo;

cyano;

halogen;

Ci-C₆ alkyl (wherein the Ci-C₆ alkyl is optionally substituted with a substituent selected from the group consisting of substituent B- l below);

C3-Ci₀ cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano,

31 32 31 32

or C1-C6 alkyl substituted with -NR R (wherein R and R each independently represent hydrogen or Ci-C₆ alkyl)];

-NR^21AR^22A [wherein R^21A and R^22A each independently represent hydrogen, Ci-C₆ alkyl jwherein C _\ -C₆ alkyl is optionally substituted with amino, di (C|-C₆ alkyl) amino, C|-C₆ alkylsulfonyl (-S0₂ (C|-C₆ alkyl)), piperidyl, or cyano} , or piperidyl {wherein piperidyl is optionally substituted with -COOR¹⁰⁵ (wherein R¹⁰⁵ represents Ci-C₆ alkyl)}];

Ci-Ce alkoxy {wherein the Ci-C₆ alkoxy is optionally substituted with 3- to

8-membered heterocycloalkyl selected from halogen, piperidyl, and piperazinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl), or -NR³³R³⁴ [wherein R³³ and R each independently represent hydrogen, Ci-C₆ alkyl (wherein the Q-C6 alkyl is optionally substituted with Ci-C₆ alkylsulfonyl or di (Ci-Ce alkyl) amino), or C1-C6 alkylsulfonyl]} ;

-S0₂NR^23AR^{2 A} {wherein R ^3A and R^24A each independently represent hydrogen, Ci-C₆ alkyl [wherein the Q-C6 alkyl is optionally substituted with hydroxyl, C1-C6 alkoxy, halogen, C3-Ci₀ cycloalkyl, pyrazolyl, imidazolyl, or -NR³⁵R³⁶ (wherein R³⁵ and R ⁶ each independently represent hydrogen or C1-C6 alkyl)], C3-Q0 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with Ci-C₆ hydroxyalkyl), azetidinyl, or pyrrolidinyl, or may together form pyrrolidinyl, wherein the pyrrolidinyl is optionally substituted with amino or halogen} ;

Ci-C₆ alkylsulfonyl (wherein the C1-C6 alkyl moiety is optionally substituted with hydroxyl);

Ci-C₆ alkylsulfonylamino (-NHS0₂ (Ci-C₆ alkyl)) [wherein the Ci-C₆ alkyl moiety is optionally substituted with -NR³⁷R³⁸ (wherein R³⁷ and R³⁸ each independently represent hydrogen or C1-C6 alkyl)];

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, and tetrahydropyridyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or Ci-C₆ alkylsulfonyl), C1-C6 alkyl

[wherein the Ci-C₆ alkyl is optionally substituted with -NR R⁴²(wherein R⁴¹ and R⁴² each independently represent hydrogen or C1-C alkyl)], hydroxyl, or C1-C6 alkylsulfonyl} ; lH-tetrazolyl;

aryl (wherein aryl is optionally substituted with C1-C6 alkyl [wherein Ci-C₆ alkyl is optionally substituted with cyano or amino] )

-COOR^{1 1} (wherein R^{1 1} represents hydrogen or Ci-C₆ alkyl); and

-COR^12A [wherein R^12A represents piperazinyl which is optionally substituted with Ci-C₆ alkyl, C3-C10 cycloalkyl, cyanomethyl, aminomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen or C1-C6 alkyl [wherein the Q-C6 alkyl is optionally substituted with hydroxyl or -NR⁴³R⁴⁴ (wherein R⁴³ and R⁴⁴ each independently represent hydrogen or C1-C6 alkyl)] }, or C1-C6 alkyl];

substituent B- l :

halogen;

hydroxyl; C1-C6 alkoxy;

cyano;

cycloalkyl;

phenyl (wherein phenyl is optionally substituted with cyano);

heteroaryl selected from the group consisiting of imidazolyl, pyrazolyl, and thiazolyl

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl, hydroxyl, amino, Ci-C₆ aminoalkyl, or C_\-Ce alkyl substituted with C2-C7 alkyloxycarbonylamino);

-NR R^52A {wherein R^5IA and R^52A each independently represent hydrogen, Ci-C₆ alkyl [wherein the C1-C6 alkyl is optionally substituted with C1-C6 alkylsulfonyl, or piperidyl which is optionally substituted with, -COOR⁵³ (wherein R⁵³ represents hydrogen or Ci-C₆ alkyl)], piperidyl, C|-C₆ alkylsulfonyl, C₃-C_]0 cycloalkyl, -COR⁵⁵ (wherein R^¾ represents Ci-C₆ alkyl), -COOR⁵⁶ (wherein R⁵⁶ represents Ci-C₆ alkyl), or -CONR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵ each independently represent hydrogen or C1-C6 alkyl)} ;

-COOR⁵⁴ (wherein R⁵⁴ represents hydrogen or Ci-C₆ alkyl);

-CONH₂;

-SO₂NR¹⁰⁶R^l07{wherein R¹⁰⁶ and R¹⁰⁷ each independently represent hydrogen, C|-C₆ alkyl, or C3-C10 cycloalkyl} ;

C1-C6 alkylsulfinyl; and

C1-C6 alkylysulfonyl

The compound of above 9, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from the group consisting of (p) below:

(p):

hydrogen,

hydroxyl,

halogen,

amino which is optionally substituted with a substituent selected from the group consisting of substituent (g) below

C1-C6 alkyl which is optionally substituted with a substituent selected from the group consisting of substituent (a) below,

C₂-C6 alkenyl which is optionally substituted with a substituent selected from the group consisting of substituent (b) below,

C3-C10 cycloalkyl,

C3-C10 cycloalkenyl,

C1-C6 alkoxy,

C6-C10 aryl which is optionally substituted with a substituent selected from the group consisting of substituent (c) below,

indanyl which is optionally substituted with a substituent selected from the group consisting of substituent (d) below,

heteroaryl which is optionally substituted with a substituent selected from the group consisting of substituent (e) below, and

3- to 8-membered heterocycloalkyl which is optionally substituted with a substituent selected from the group consisting of substituent (f) below,

wherein, in the group (p), the heteroaryl is selected from the group consisting of pyridyl, lH-indazolyl,

I H-tetrazolyl, [ l ,2,4]triazolo[ l ,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-6]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and

tetrahydroisoquinolyl;

the 3- to 8-membered heterocycloalkyl is selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and 1 ,2,3,6-tetrahydropyridyl;

substituent (a):

-NR ^AR^22A [where in R^21A and R^22A each independently represent hydrogen, C1-C6 alkyl {wherein Ci-C₆ alkyl is optionally substituted with piperidyl}, or piperidyl {wherein piperidyl is optionally substituted with -COOR¹⁰⁵ (wherein R^{1 s} represents Q-C6 alkyl)} ];

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl and piperidyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen or

C1-C6 alkyl), or C1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with

-NR⁴¹R⁴² (wherein R⁴¹ and R⁴² each independently represent hydrogen or Ci-C₆ alkyl)] } ; and

Ci-C₅ alkylsulfonylamino (-NHS0₂(Ci-C₆ alkyl));

substituent (b):

-COOR^{1 1} (wherein R^{1 1} represents hydrogen or C1-C6 alkyl);

-NR^21aR^22a [wherein R^21a and R^22a each independently represent hydrogen, or C1-C6 alkyl (wherein the C1 -C6 alkyl is optionally substituted with di(Ci-C₆ alkyl)amino or Ci-C₆ alkylsulfonyl)] ;

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, and piperidyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or C1-C6 alkylsulfonyl), Q-C6 alkyl [wherein the Q-C6 alkyl is optionally substituted with -NR ¹R⁴² (wherein R⁴¹ and R⁴² each independently represent hydrogen or C1-C6 alkyl)], hydroxyl, or C|-C6 alkylsulfonyl} ;

cyano; and

C1-C6 alkoxy;

substituent (c):

hydroxyl;

cyano;

halogen;

Ci-Ce alkyl (wherein the C1-C6 alkyl is optionally substituted with a substituent selected from the group consisting of substituent B-c below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or C|-C₆ alkyl substituted with -NR³¹ R³² (wherein R and R³² each independently represent hydrogen or Ci-C₆ alkyl)];

-NR^21cR^22c [wherein R and R^22c each independently represent hydrogen or C1-C6 alkyl (wherein C1-C6 alkyl is optionally substituted with amino, or cyano)]];

C1-C6 alkoxy {wherein the C1-C6 alkoxy is optionally substituted with 3- to 8-membered heterocycloalkyl selected from halogen, piperidyl, and piperazinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C1-C6 alkyl), or -NR³³R³⁴ [wherein R³³ and R each independently represent hydrogen, C1-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with di(C| -C6 alkyl)amino), or C1-C6 alkylsulfonyl] } ; -S0₂NR ^CR ^c {wherein R ⁰ and R ^c each independently represent hydrogen, C1-C6 alkyi [wherein the Ci-C₆ alkyi is optionally substituted with hydroxyl, Ci-C₆ alkoxy, halogen, C3-Q0 cycloalkyi, pyrazolyl, imidazolyl, or -NR³⁵R³⁶ (wherein R^3S and R³⁶ each independently represent hydrogen or C\-C(, alkyi)], C3-Ciocycloalkyl (wherein the C3-C10 cycloalkyi is optionally substituted with C1-C6 hydroxyalkyi), azetidinyl, or pyrrolidinyl, or wherein R^23c and R^24c may together form pyrrolidinyl which is optionally substituted with amino or halogen} ;

Ci-C₆ alkylsulfonyl (wherein the C1-C6 alkyi moiety is optionally substituted with hydroxyl);

Ci-C₆ alkylsulfonylamino (-NHS0₂(Ci-C₆ alkyi)) [wherein the Ci-C₆ alkyi moiety is optionally substituted with -NR³⁷R³⁸ (wherein R ⁷ and R³⁸ each independently represent hydrogen or C1-C6 alkyi)];

piperazinyl {wherein the piperazinyl is optionally substituted with Ci-C₆ alkyi or C1-C6 alkylsulfonyl} ;

piperidyl (wherein piperidyl is optionally substituted with hydroxyl); lH-tetrazolyl;

1 , 2, 3, 6-tetrahydropyridyl; and

-COR^12c [wherein R^{1 c} represents piperazinyl which is optionally substituted with C1-C6 alkyi, C3-C10 cycloalkyi, cyanomethyl, aminomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen or C1-C6 alkyi [wherein the C1-C6 alkyi is optionally substituted with hydroxyl, or -NR ³R⁴⁴ (wherein R⁴³ and R⁴⁴ each independently represent hydrogen or C|-C₆ alkyi)] } , or Ci-C₆ alkyi]; and

substituent B-c:

halogen;

hydroxyl;

methoxy;

cyano;

C3-CK) cycloalkyi

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl(wherein the 3- to

8-membered heterocycloalkyl is optionally substituted with C\-Ce alkyi, hydroxyl, amino, C1-C6 aminoalkyl, or C1-C6 alkyi substituted with C2-C7 alkyloxycarbonylamino); and

-NR^51cR^52c {wherein R^{5 lc} and R^52c each independently represent hydrogen, C1-C6 alkyi [wherein the C 1 -C6 alkyi is optionally substituted with C1-C6 alkylsulfonyl, or piperidyl which is optionally substituted with -COOR⁵³ (wherein R⁵³ represents hydrogen or C|-C₆ alkyi)], piperidyl, C|-C₆alkylsulfonyl, C₃-Ci₀cycloalkyl, -COR⁵⁵ (wherein R⁵⁵ represents Ci-C₆ alkyi), or -CONR R (wherein R and R each independently represent hydrogen or Q-Cg alkyi)} ];

heteroaryl selected from the group of imidazolyl, pyrazolyl, and thiazolyl;

-COOR⁵⁴ (wherein R⁵⁴ represents hydrogen, or C1-C6 alkyi)

-CONH2;

-SO₂NR^l06R¹⁰⁷{wherein R¹⁰⁶ and R¹⁰⁷ each independently represent hydrogen, C1-C6 alkyi, or Ci-C cycloalkyi} ;

Ci-C₆ alkylsufinyl; and

C1-C6 alkylsulfonyl; substituent (d):

-NR^21dR^22d (wherein R^21d and R ^2d each independently represent hydrogen or Ci-C₆ alkyl);

substituent (e):

hydroxy 1;

oxo;

cyano;

C3-C10 cycloalkyl [wherein C3-C10 cycloalkyl is optionally substituted with cyano];

-NR^2IR²² [wherein R²¹ and R²² each independently represent hydrogen or C1-C6 alkyl (wherein Ci-C₆ alkyl is optionally substituted with amino)];

piperidyl;

C|-C₆ alkoxy (wherein C1-C6 alkoxy is optionally substituted with -NR R [wherein R³³ and R³⁴ each independently represent hydrogen, or C -Ce alkyl]); and

Ci-C₆ alkyl {wherein the Ci-C₆ alkyl is optionally substituted with cyano, -NR^51eR^{5 e} [wherein R⁵'^e and R^52e each independently represent hydrogen, C 1 -C6 alkyl, or -COOR⁵⁶ (wherein R⁵⁶ represents C_\-Ce alkyl)], mo holinyl, or cyanophenyl} ;

-CONH2;

substituent (f):

51 f , 52f

C1-C6 alkyl {wherein the C1-C6 alkyl is optionally substituted with -NR^R

51 f^* 56

[wherein R and R " each independently represent hydrogen, C -Ce alkyl, or -COOR

(wherein R represents C1-C6 alkyl)] } ; and

Ci-C₆ alkylsulfonyl; substituent (g):

Aryl (wherein aryl is optionally substituted with C1-C6 alkyl [wherein C1-C6 alkyl is optionally substituted with cyano or amino]).

1 1. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen; hydroxyl; Ci-C₆ alkyl; phenyl which is optionally substituted with 1 to 3 hydroxy Is; piperidyl which is optionally substituted with amino; or piperazinyl.

12. The compound of above 1 1 , or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen, C1-C6 alkyl (wherein C1-C6 alkyl is optionally substituted by a substituent selected from the group comprising hydroxyl and piperidyl), or halogen.

13. The compound of above 2, or a pharmaceutically acceptable salt thereof, wherein R is hydrogen;

C| -C6 alkyl {wherein the C1-C6 alkyl is optionally substituted with hydroxyl,

-NR^71AR^72A [wherein R^{7I A} and R^72Aeach independently represent hydrogen, C| -C₆ alkyl (wherein the Q-C6 alkyl is optionally substituted with dimethylamino), C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino), or piperidyl], or 3- to

8-membered heterocycloalkyl selected from the group consisting of piperidyl and morpholinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C1-C6 aminoalkyl)} ;

phenyl which is optionally substituted with 1 to 2 hydroxyls;

phenylsulfonyl; or

-COR^73A {wherein R^73A represents piperidyl (wherein the piperidyl is optionally substituted with amino), or -NR^{7 A}R^75A [wherein R^{7 A} and R each independently represent hydrogen, piperidyl, or C3-C)₀ cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino)]} .

14. The compound of above 1 , or a pharmaceutically acceptable salt thereof, wherein

is -CH₂-CH₂-CH₂-.

15. The compound of above 14, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are hydrogen.

16. TThhee ccoommppoouunn<d of above 14, or a pharmaceutically acceptable salt thereof, wherein R³ is hydroxyl or methoxy.

17. The compound of above 14, or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen, phenyl [wherein the phenyl is substituted with C\-Ce alkyl substituted with

-NR R (wherein R^5,A and R^52A each independently represent hydrogen or Ci-C₆ alkyl), or -S0₂NR^53AR^54A(wherein R^53A and R^54A each independently represent hydrogen, or Ci-C₆ alkyl that is optionally substituted with halogen or hydroxyl₎], 1 ,2,3,6-tetrahydropyridyl, hydroxypyridyl, or methoxypyridyl.

18. The compound of above 1 , or a pharmaceutically acceptable salt thereof, wherein

X-—Y-—Z ._s __NRi 08 _CH=CRi 0 (_{wherein R}i08 _represents hydrogen, or

C 1-C6 alkyl that is optionally substituted with hydroxyl, and R¹⁰⁹ represents hydrogen, CH3, or phenyl group which is substituted with Cl -C6aminoalkyl),

R¹, R², and R⁴ are hydrogen, and

R³ is hydrogen, hydroxyl or Cl-C6alkoxy.

19. The compound of above 1 , or a pharmaceutically acceptable salt thereof, wherein

X— Y— z ._s

R¹, R², and R⁴ are hydrogen, and

R³ is methoxy.

20. A compound selected from the group consisting of:

(1 ) : 8-methoxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(2) : 8-hydroxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(3) : 7,8-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(4) : 7,8-dimethoxythieno[2,3-c]quinolin-4(5H)-one;

(5): 8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(6) : 7,9-dimethoxythieno[2,3-c]quinolin-4(5H)-one;

(7) : 7,9-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(8) : 7,8,9-trimethoxythieno[2,3-c]quinolin-4(5H)-one;

(9) : 8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(10): 7,8,9-trihydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 1 ) : 9-(3-(2-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(12) : 8-chlorothieno[2,3-c]quinolin-4(5H)-one;

(13) : 4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(14) : thieno[2,3-c]quinolin-4(5H)-one;

(15): 8-fluorothieno[2,3-c]quinolin-4(5H)-one; 8-nitrothieno[2,3-c]quinolin-4(5H)-one;

8-(3-aminopiperidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

l-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

l ,8-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

8-hydroxy- 1 -(4-hydroxypheny l)thieno[2,3-c]quinolin-4(5H)-one;

(R)-8-(3-aminopyrrolidin-l -yl)thieno[2,3-c]quinolin-4(5H)-one;

(S)-8-(3-aminopyrrolidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

8-(pyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

8-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

l -(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

l -(3-aminopiperidin-l-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

8-morpholinothieno[2,3-c]quinolin-4(5H)-one ;

8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

8-hydroxy-2-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(31) 8-hydroxy-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(32) 8-hydroxy- 1 -(piperazin- 1 -y l)thieno[2,3-c]quinolin-4(5H)-one;

(33)

N-((l r,4r)-4-aminocyclohexyl)-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-2-carbo xamide;

(34) : 2-(3-aminopiperidine-l-carbonyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(35) : 2-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(36) :

2-(((l r,4r)-4-aminocyclohexylamino)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(37) 8-(piperazin- 1 -yl)thieno[2,3-c]quinolin-4(5H)-one;

(38) 8-hydroxy- 1 -methylthieno[2,3-c]quinolin-4(5H)-one;

(39)

2-((2-(dimethylamino)ethylarnino)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(40) : 8-hydroxy-2-((piperidin-3-ylamino)methyl)thieno[2,3-c]quinolin-4(5H)-one;

(41 ) : 7-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(42) : 9-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(43) : 9-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(44) : l-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(45) : 7-(3,4-dihydroxyphenyI)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(46) : 8-hydroxy- l-methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(47) : 9-(3,5-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (48) : 8-hydroxy-9-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(49) : 8-hydroxy-9-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(50) : 9-(3,4-difluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(51) : (S)-8-(3-aminopyrrolidin-l-yl)-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one; (52): 5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)picolinonitrile;

(53) : 9-(6-aminopyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(54) : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

(55) : 9-(3-fluoro-4-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(56) : 8-hydroxy-2-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(57):

(R)-8-(3-aminopyrrolidin- l-yl)-2-(3,4-dihydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(58) : 9-(3,4-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(59) : 9-(4-fluoro-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(60) : 8-hydroxy-9-(3-hydroxy-5-(trifluoromethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (61): 8-hydroxy-9-(l H-indazol-6-yl)thieno[2,3-c]quinolin-4(5H)-one;

(62) : 8-hydroxy-9-(3,4,5-trihydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(63) : 9-(4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(64) : 9-(4-(lH-tetrazol-5-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(65) : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide; (66): 9-(3-chloro-4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(67) : 9-(4-chloro-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(68) : 9-(3,4-dichlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(69) : 9-(4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(70) : 8-hydroxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(71 ): 9-(4-(difluoromethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(72) : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(73) : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(74) : 9-(3-ariiinophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(75) : 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide; (76): 8-hydroxy-9-(3,4,5-trifluorophenyl)thieno[2,3-c]quinolin-4(5H)-one;

(77) :

N-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanesulfonamide;

(78) : 8-methoxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(79) : 8-hydroxy-9-(naphthalen-2-yl)thieno[2,3-c]quinolin-4(5H)-one;

(80): 8-hydroxy-9-(4-(hydroxymethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(81): 2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile; (82) : 8-hydroxy-9-(4-(methylsulfonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(83) : 8-hydroxy-9-(pyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(84) : 8-hydroxy-9-(l ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(85) : 8-hydroxy-9-(4-hydroxy-3-methoxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(86): 9-(3-fluoro-4-(morpholinomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(87) : 9-(3-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(88) : 9-(4-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(89) : 9-(3-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(90) : 9-(3-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one; (91 ): 9-cyclohexeny l-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(92) : 9-(3,5-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(93) : 9-(4-(2-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(94) : 9-(3-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(95) : 9-(4-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one; (96): 9-cyclopropyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(97) : 9-([l,2,4]triazolo[l ,5-a]pyridin-6-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(98) : 8-methoxy-9-(l ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(99) : 9-cyclohexeny l-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(100) :

8-methoxy-9-(4-(2-(piperidin- l -yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(101) :

9-(4-(aminomethyl)phenyl)-8-hydroxy-2-(mo holinomethyl)thieno[2,3-c]quinoΠn-4(5H)-o ne;

(102) : 9-(l H-benzo[d]imidazol-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(103): 9-(4-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(104) :

9-(4-(aminomethyl)phenyl)-8-methoxy-2-(mo holinomethyl)thieno[2,3-c]quinolin-4(5H)- one;

(105) :

8-hydroxy-9-(4-(2-(piperidin-l -yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(106) : 8-hydroxy-9-(4-(piperazin-l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(107) : 8-methoxy-2,3-dihydro-l H-cyclopenta[c]quinolin-4(5H)-one;

( 108) : 8-hydroxy-2,3-dihydro- 1 H-cyclopenta[c]quinolin-4(5H)-one;

(109) :

5-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzo[d]oxazol-2(3H)-one;

(1 10) : tert-butyl

4-(2-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylamino)ethyl)piperidine- l -carboxylate;

(1 1 1 ) : 8-methoxy-9-(4-(piperazin-l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 12) :

8-hydroxy-9-(4-(4-(methylsulfonyl)piperazin- l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 13) :

8- hydroxy-9-(4-((piperidin-3-ylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 14) :

N-(2-(dimethylamino)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ben zamide;

(1 15) :

9- (4-(3-(dimethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

( 1 16) : 8-methoxy-9-( l -(piperidin-4-yl)- l H-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(1 17) : 8-hydroxy-9-( l -(piperidin-4-yl)- lH-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(1 18) : 8-methoxythiazolo[4,5-c]quinolin-4(5H)-one; . . .. _

(1 19) :

2-((4-(aminomethyl)piperidin- l -yl)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(120) :

N-(2-(dimethylamino)ethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be n zamide;

(121 ) :

9-(4-(aminomethyl)phenyl)-8-hydroxy-2,3-dihydro- l H-cyclopenta[c]quinolin-4(5H)-one;

(122) : (E)-butyl 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)acrylate;

(123) : 8-methoxy-9-(l H-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(124) : 8-hydroxy-9-(l H-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(125) : N-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)acetamide;

(126) :

N-(2-aminoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

(127) :

N-(2-aminoethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

( 1 28) : N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)acetamide;

(1 29) :

4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro- l H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide;

(130) :

8-hydroxy-9-(4-(4-methylpiperazine- l -carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 131 ) :

8-methoxy-9-(4-(4-methylpiperazine- l -carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(132) :

8-hydroxy-9-(4-((4-methylpiperazin-l -yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(133) :

8-methoxy-9-(4-((4-methylpiperazin- l -yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 134) : (E)-9-(3-(diethylarnino)prop- l -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (135) :

(E)-9-(3-(4-(aminomethyl)piperidin-l -yl)prop-l -enyl)-8-rnethoxythieno[2,3-c]quinolin-4(5 H)-one;

(136) :

(E)-9-(3-(2-(diethylamino)ethylamino)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(137) :

N-(4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro-lH-cyclopenta[c]quinolin-9-yl)phenyl)methanes ulfonamide;

(138): 9-(2-(dimethylamino)pyrimidin-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(139) : tert-butyl

(l -(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)piperidin-4-yl)methylcarb amate;

(140) : 8-hydroxy-9-(4-(4-methylpiperazin-l -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (141): 8-methoxy-9-(4-(4-methylpiperazin- 1 -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(142) : 8-methoxy-9-(l-(methylsulfonyl)- l ,2,3,6-tetrahydropyridin-4-yl)thieno

[2,3-c]quinolin-4(5H)-one;

(143) : (E)-9-(3-(diethylamino)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(144) : 9-(3-(4-(aminomethyl)piperidin-l-yl)propyl)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(145) :

9-(4-(3-(2-(diethylamino)ethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(146) : 9-(4-(3-(diethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (147):

9-(4-(3-(2-(diethylamino)ethylamino)propoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(148) :

(E)-9-(3-(4-(aminomethyl)piperidin-l-yl)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin H)-one;

(149) :

9-(4-(3-(dimethylamino)propoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(150) : 8-hydroxy-9-(4-(2-(piperidin-l -yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(151 ) : 9-(4-(2-(ethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (152):

(E)-9-(3-(4-aminopiperidin-l-yl)prop-l -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (153):

9-(l -(2-aminoethyl)-l ,2,3,6-tetrahydropyridin-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(154): 9-(4-(2-(ethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(155) : 9-(4-(2-(diethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(156) : 9-(4-(2-(diethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (157) : 9-(4-(2-(dimethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(158) : 9-(4-(2-(dimethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(159) : 8-methoxy-9-(4 2-(piperidin-l -yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(160) :

8-methoxy-9-(3-(2-(4-methylpiperazin-l -yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(161) : 9-(3-(2-(diethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(162) : 9-(3-(3-(diethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(163) : 9-(4-(2-(dimethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (164): 9-(4-((dimethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(165) : 9-(4-((dimethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(166) : 9-(3-(2-(diethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(167) :

8- hydroxy-9-(3-(2-(4-methylpiperazin-l-yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one ;

(168) :

N-ethyl-N-(2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenylmethoxy- 4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenoxy)ethyl)methanesulfonamide;

( 169) : 9-(4-(2-aminoethy l)pheny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(170): 2-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(171) : 2-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(172) :

9- (l -(2-(dimethylamino)ethyl)-l ,2,3,6 etrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]quino lin-4(5H)-one;

(173):

N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yI)phenethyl)methanesulfonamide; (1 74):

9-(l -(2-(diethylamino)ethyl)-l ,2,3,6-tetrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]quinoli n-4(5H)-one;

(175): 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(176) : 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(177) :

N-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanesulfonamide;

(178) :

N-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)rnethanesulfonamide;

(179) :

N-(2-aminoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(1 80) :

8-hydroxy-9-(l ,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydro- l H-cyclopenta[c]quinolin-4(5H)- one; (181 ) :

9-(4-( 1 -(dimethylamino)ethy l)phenyl)-8-hydroxy-2,3-dihydro- 1 H-cyclopenta[c]quinolin-4( 5H)-one;

(182) :

9-(4-(2-(dimethylamino)ethy l)phenyl)-8-methoxy-2,3-dihydro- 1 H-cyclopenta[c]quinolin-4(

5H)-one;

(183) : 9-(4-((diethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(184) : 9-(4-((diethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(185) : 9-(3-(2-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (186): 9-(3-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(187) : 8-hydroxy-9-(4-((methylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(188) : 8-methoxy-9-(4-((methylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(189) : 9-(4-amino-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(190) : 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(191 ): 9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(192) : 9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(193) :

N-(l-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methanesulf onamide;

(194): 8-hydroxy-9-(4-(l-(pyrrolidin-l-yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(195) : 9-(4-(l -aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(196) : 9-(4-(l-(diethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(197) :

N-(2-aminoethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(198) :

N-(2-(dimethylamino)ethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzenesulfonamide;

(199) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(pyrrolidin-3-yl)benzenesulf onamide;

(200) :

N-(azetidin-3-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfon amide;

(201): 9-(4-(2-(diethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(202) :

2-amino-N-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfo namide;

(203) : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(204): 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile; (205) :

(E)-9-(3-(3-aminopyrrolidin-l -yl)prop-l -enyl)-8-mem^

(206) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesul ' fonamide;

(207) : 8-methoxy-9-(5-methoxypyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

(208) :

8- methoxy-9-(5-methoxypyridin-3-yl)-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(209) :

9-(4-(3-aminopyrrolidin- 1 -ylsulfonyl)pheny l)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(210) :

N-(2-bromoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(21 1) : 9-(4-((diisopropylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (212):

N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)methanesulfonamide;

(213) : 9-(4-((isopropy lamino)methy l)pheny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(214) :

2-(dimethylamino)-N-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)et hanesulfonamide;

(215) :

2-amino-N-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfo namide;

(216) : 8-methoxy-9-(4-(l -(pyrrolidin-l-yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (21 ): 9-(4-amino-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(218) :

N-(2-methoxy-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanes ulfonamide;

(219) : 9-(3,5-difluoro-4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(220):

N-(2-hydroxy-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanes ulfonamide;

(221 ) :

9- (4-((4-(aminomethyl)piperidin- l -yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quin olin-4(5H)-one;

(222) :

9-(4-(2-(dimethylamino)ethyl)phenyl)-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(223) : 9-(3,5-difluoro-4-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(224) :

6-fluoro-8-methoxy-9-(l ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(225) :

9-(4-(l -(dimethylamino)ethyl)phenyl)-6-fluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (226) :

9-(4-((diethylamino)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(227) :

(E)-9-(3-(3-hydroxypyrrolidin-l -yl)prop-l-enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-on e;

(228) :

(E)-8-hydroxy-9-(3-(3-hydroxypyrrolidin- l-yl)prop- l -enyl)thieno[2,3-c]quinolin-4(5H)-one

(229) : 8-hydroxy-9-(4-((isopropylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(230) :

(E)-9-(3-(3-aminoazetidin-l -yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(231) :

(E)-8-methoxy-9-(3-(2-(methylsulfonyl)ethylamino)prop-l-enyl)thieno[2,3-c]quinolin-4(5H )-one;

(232) : (S)-9-(4-(l -aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(233) : (S)-9-(4-(l-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(234) :

8- hydroxy-9-(5-hydroxypyridin-3-yl)-2,3-dihydro-l H-cyclopenta[c]quinolin-4(5H)-one;

(235) :

9- (4-((4-(aminomethyl)piperidin-l-yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quin olin-4(5H)-one;

(236) :

8- methoxy-9-(4-(l -(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(237) :

9- (4-((3-aminopyrrolidin- l -yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(238) :

(E)-9-(3-(3-aminoazetidin- 1 -y l)prop- 1 -eny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(239) : (E)-9-(3-(ethylamino)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(240) :

9-(4-((3-aminopiperidin-l-yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(241) :

9-(4-((3-aminopyrrolidin-l -yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(242) :

9-(4-((3-aminopiperidin- l-yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(243) :

8-hydroxy-9-(4-(l -(2-(methylsulfonyl)ethylarnino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one; (244) : (E)-9-(3-(3-aminopiperidin- 1 -y l)prop- 1 -eny l)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(245) :

(E)-9-(3-(3-aminopyrrolidin-l -yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (246):

(E)-9-(3-(3-aminopiperidin- l-yl)prop- l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (247):

(E)-8-hydroxy-9-(3-(2-(methylsulfonyl)ethylamino)prop-l-enyl)thieno[2,3-c]quinolin-4(5H )-one;

(248):

8- rnethoxy-9-(4-(2-(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(249):

2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile; (250):

(E)-N-(l-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)allyl)azetidin-3-yl)me thanesulfonamide;

(251 ) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesulfonarn ide;

(252) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-methylbenzenesulfonamide;

(253) : tert-butyl

(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)furan-2-yl)methylcarbamate; (254):

N-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylphenyl)methanesul fonamide;

(255) :

N-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylphenyl)methanesul fonamide;

(256) : 9-(4-(aminomethyl)phenyl)-6-fluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(257) : 9-(4-(aminomethyl)phenyl)-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(258) :

6-fluoro-8-hydroxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one; (259):

9- (4-((diethylamino)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(260) : 8-methoxy-9-(4-(l-(piperidin-l -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(261) :

2-(2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile; (262): 8-hydroxy-9-(4-(l -(piperidin-l -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(263):

(E)-9-(3-(3-(dimethylamino)piperidin-l -yl)prop- l -enyl)-8-hydroxythieno[2,3-c]quinolin-4( 5H)-one; (264) :

(E)-9-(3-(3-(dimethylamino)pyrrolidin- l -yl)pro^

(5H)-one;

(265) : 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (266): 9-(5-(aminomethyl)thiophen-2-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(267) : 9-(4-((ethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(268) :

(E)-9-(3-(4-aminopiperidin- l -yl)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(269) : 9-(4-((ethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(270): 9-(4-(aminomethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(271 ) :

9-(3-chloro-4-((diethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(272) :

(R)-9-(4-( l -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (273): 9-(4-(3-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(274) : (R)-9-(4-(l -aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(275) : (R)-9-(4-(l -aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(276) : 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(277) :

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(278) :

9-(3-fluoro-4-((3-hydroxypyrrolidin- l -yl)methyl)phehyl)-8-hydroxythieno[2,3-c]quinolin-4 (5H)-one;

(279) :

9-(3-fluoro-4-((3-hydroxypyrrolidin- l -yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4 (5H)-one;

(280) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2,2,2-trifluoroethyl)benzen esulfonamide;

(281 ):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2,2,2-trifluoroethyl)benzene sulfonamide;

(282) :

N-(2-(dimethylamino)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ben zenesulfonamide;

(283) :

8-hydroxy-9-(4-((2-(methylsulfonyl)ethylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H) -one;

(284) :

9-(3-(3-(dimethylamino)pyrrolidin- l -yl)propyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(285) : 9-(l -(2-aminoethyl)- l H-pyrazol-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (286) :

9-(3-chloro-4-((diethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(287) :

4-(7-fluoro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(288) : 9-(3-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(289) :

2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzamide;

(290): 3-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pheny l)propanenitrile;

(291) : 9-(4-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(292) :

2-fluoro-N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzamide;

(293):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)benzamide;

(294) : l,l-diethyl-3-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)urea;

(295) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide; (296): 9-(4-acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(297) :

N-(2-bromoethyl)-2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benz enesulfonamide;

(298) :

9-(3-(3-(dimethylamino)piperidin-l -yl)propyI)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(299) :

N-(2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanes ulfonamide;

(300) :

9-(3-fluoro-4-(2-(methylsulfonamido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin -8-yl methanesulfonate;

(301 ) :

(R)-N-(l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methane sulfonamide;

(302):

(R)-9-(4-(l -(methylsulfonamido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl methanesulfonate;

(303) :

2-fluoro-N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzenesulfonamide;

(304) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesulfonam ide; (305) :

9-(4 2-(dimethylamino)ethyl)phenyl)-7-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(306) :

N-(2-bromoethyl)-4-(7-fluoro-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benz enesulfonamide;

(307) :

4-(7-fluoro-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(308) :

9-(4-(l-(dimethylamino)-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(309) :

N-(2-chloro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)-N-methyl methanesulfonamide;

(3 10):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-methoxyethyl)benzenesul fonamide;

(31 1):

(E)-3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylacrylonitrile; (312):

N-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methane sulfonamide;

(313) : 8-hydroxy-9-(4-(l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(314) : 9-(4-(l -(cyclopentylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (315):

9-(4-(l -(cyclopentylamino)ethyl)phenyI)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (316):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)benzenesulf onamide;

(317): 9-(5-(aminomethyl)furan-2-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(318) :

9-(3-chloro-4-((methylamino)rnethyl)phenyl)-8-niethoxythieno[2,3-c]quinolin-4(5H)-one;

(319) : 9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(320) :

N-(3-hydroxypropyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenes ulfonamide;

(321 ) :

2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(322):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(3-hydroxypropyl)benzenesu lfonamide; (323) :

N-(3-bromopropyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulf onamide;

(324) :

2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-methoxyethyl)be nzenesulfonamide;

(325) :

9-(3-chloro-4-((methylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(326) : 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile; (327):

9-(4-(2-(dimethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(328) : 9-(4-(aminomethyl)phenyl)-6,7-dichloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(329) : 9-(4-(aminomethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(330) : 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl trifluoromethanesulfonate;

(331) : 9-(4-(2-(dimethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(332) :

N-(2-chloroethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(333):

N-(2-fluoroethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(334):

9-(4-(2-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (335):

(S)-9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(336) : 9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(337) : 9-(4-(l-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(338) : 9-(4-(l-(diethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (339): 9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(340) : 9-amino-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(341 ) :

9-(4-(l -(dimethylamino)ethyl)phenyl)-6,7-difluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(342):

9-(4-(l-(dimethylamino)ethyl)phenyl)-6,7-difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(343):

N-cyclopropyl-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfona mide; (344) :

N-cyclopropyl-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfona mide;

(345) : 9-(2-amino-2,3-dihydro- 1 H-inden-5-y l)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (346): 9-(4-(l -(dimethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(347) :

(S)-N-(l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methane sulfonamide;

(348) :

9-(4-( 1 -(aminomethyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(349) :

9-(4-(l-(dimethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(350) :

N-(l-(hydroxymethyl)cyclopentyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9 -yl)benzenesulfonamide;

(351) :

9-(2-(diethylamino)-2,3-dihydro-lH-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(352) :

9-(2-(dimethylamino)-2,3-dihydro-l H-inden-5-y^

ne;

(353) : 8-hydroxy-9-(l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(354) : 8-methoxy-9-(l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(355) : 3-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile; (356):

9-(4-(l-(diethyIarnino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (357):

l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropanecarbonit rile;

(358):

9-(2-ethyl-l,2,3,4-tetrahydroisoquinolin-7-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(359) : 9-(4-(l-aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(360) : 3-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile;

(361) :

l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropanecarbonit rile;

(362) : 9-(2-amino-2,3-dihydro- 1 H-inden-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(363) :

N-isopentyl-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamid e;

(364) :

9-(2-(dimethylamino)-2,3-dihydro-l H-inden-5^

ne; (365) : 9-(4-(l-(ethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(366) :

6-chloro-9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(367) : 9-(4-(cyclopropanecarbonyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(368) : 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carboxamide;

(369) : 9-(2-aminoethyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(370) : 8-hydroxy-9-(4-(2-hydroxyethylsulfonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(371) : 9-(4-(2-hydroxyethylsulfonyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(372) : 9-(l-ethylindolin-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(373) : 9-(4-(l -aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(374) : · -

8- hydroxy-9-(2-methyl-l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(375) : 9-(4-(l-aminoethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(376) : 8-hydroxy-9-(l -methylindolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(377) : 8-hydroxy-9-(indolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(378) : 9-(indolin-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; ,

(379) :

9- (4-(l -((dimethylamino)rnethyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(380) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoIin-9-yl)-N-propylbenzenesulfonamide;

(381) :

N-(cyclopropylmethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzene sulfonamide;

(382) :

N-(3,3-dimethylbutyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenes ulfonamide;

(383) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-isopentylbenzenesulfonamid e;

(384) :

N-(3,3-dimethylbutyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenes ulfonamide;

(385) : 9-(4-( l-(ethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(386) :

3-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-3-oxopropanenitrile;

(387) : (E)-9-(2-ethoxyvinyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(388) :

N-(l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)acetamide; (389) :

4-(8-methoxy-4-oxo-4,5-dihydrot ieno[2,3-c]quinolin-9-yl)-N-(3,3,3-trifluoropropyl)benze nesulfonamide;

(390) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(l-(hydroxymethyl)cyclopen tyl)benzenesulfonamide;

(391) :

N-(2,2-difluoroethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenes ulfonamide;

(1031): 8-methoxy-9-(4-(l-methoxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1032) : 9-(4-(l-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1033) :

8- methoxy-9-(2-((piperidin-3-ylmethyl)amino)ethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1034) :

9- (2-(4-((dimethylamino)methyl)piperidin-l -yl)ethyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1035) : tert-butyl

4-((2-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ethyl)amino)piperidine-l -ca rboxylate;

(1036) : 8-methoxy-9-(2-(piperidin-4-ylamino)ethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1037) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(3,3,3-trifluoropropyl)benze nesulfonamide;

(1038) : 3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1039) :

9-(4-(l-aminoethyl)phenyl)-6-cyclopropyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1040) :

9-(4-(l -aminoethyl)phenyl)-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-6-carbonit rile;

(1041 ) : 9-(4-(l-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1042) :

8-hydroxy-9-(2-(4-((methylamino)methyl)piperidin-l -yl)ethyl)thieno[2,3-c]quinolin-4(5H)- one;

( 1043) :

8- methoxy-9-(2-(4-((methylamino)methyl)piperidin-l -yl)ethyl)thieno[2,3-c]quinolin-4(5H) -one;

(1044) :

9- (2-(4-((dimethylamino)methyl)piperidin- l -yl)ethyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1045) : 9-(4-(l -hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1046) :

(R)-8-methoxy-9-(4-(l -(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 1047) : (R)-8-(4-( 1 -aminoethy l)pheny l)thieno[2,3-c]quinolin-4(5H)-one; (1048) : (R)-tert-butyl

(l-(4-(4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl)phenyl)ethyl)carbamate;

(1049) : 9-(4-(4-hydroxypiperidin-4-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1050) : (R)-8-(4-( l-(dimethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1051 ):

8- hydroxy-9-(4-(l ,2,3,6-tetrahydropyridin-4-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1052) :

(R)-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1053) : 8-hydroxy-9-(4-(l -hydroxypropyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1054): (R)-8-hydroxy-9-(4-(l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1055) : 8-hydroxy-9-(4-(4-hydroxypiperidin-4-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1056) : (S)-8-hydroxy-9-(4-(l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1057) :

N-(l-hydroxypropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benz enesulfonamide;

(1058) :

9- (4-(hydroxy(thiazol-2-yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1059) : 9-(6-(l -aminoethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1060) : 9-(4-(4-hydroxybutyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1061 ):

2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropanamid e;

( 1062) :

N-(l-bromopropan-2-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzen esulfonamide;

(1063) :

8- hydroxy-9-(4-(hydroxy(thiazol-2-yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1064) :

(S)-8-methoxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1065):

9- (6-(l-(diethylamino)ethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1066) : 9-(4-(l -arninoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1067) : 9-(6-(l -aminoethyl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1068) : 8-hydroxy-9-(4-(4-hydroxybutyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1069):

9-(4-(3-amino-l -hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1070) :

9-(6-( l -(dimethylamino)ethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1071 ) :

9-(6-(l -(dimethylamino)ethyl)pyridin-3-yl)-8-rnethoxythieno[2,3-c]quinolin-4(5H)-one; (1072) :

4-((4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-l H-pyrazol-l-yl)methyl)be nzonitrile;

(1073) : 8-aminothieno[2,3-c]quinolin-4(5H)-one;

(1074): 9-(4-((lH-pyrazol-l-yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1075) : 9-(6-(l -aminoethyl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1076) : 9-(4-(l -aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl d imethy lcarbamate ;

(1077) : 9-(4-(l -aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl isopropyl carbonate;

(1078) :

9-(4-((l H-imidazol-l-yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1079) :

N-(2-bromopropyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulf onamide;

(1080) :

(R)-9-(4-(l-aminoethyl)phenyl)-6,7-dichloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1081) :

(R)-9-(4-(l-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1082):

(S)-8-hydroxy-9-(4-(l -(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1083) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl diethylcarbamate;

(1084) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)-N-methylb enzenesulfonamide;

(1085) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-methylb enzenesulfonamide;

(1086): 9-(4-((l H-pyrazol-l -yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1087) :

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-on e;

(1088) : 9-(4-(l -aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1089): 9-(4-(l -aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl moφholine-4-carboxylate;

(1090):

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-2,3,4,5-tetrahydro-l H-cyclopenta[c]quinolin-9-yl) benzenesulfonamide;

(1091): 8-bromothieno[2,3-c]quinolin-4(5H)-one;

(1092) : 9-(4-(2-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1093) : 9-(4-(2-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1094) :

N-(2-bromoethyl)-4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro-lH-cyclopenta[c]quinolin-9-yl)be nzenesulfonamide;

(1095) : 9-(4-(2-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1096):

8- methoxy-9-(l-(2-moφholinoethyl)-lH-pyΓazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(1097) : 9-(4-(2-(diethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1098) :

9- (4-(l -aminoethyl)phenyl)-8-hydroxy-6-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one; (1099): 9-(4-(l -aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl acetate;

(1 100) :

9-(l-(l-(dimethylamino)propan-2-yl)-lH-pyrazol-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1 101) :

9-(4-((l H-imidazol-l -yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 102) :

9-(4-(aminomethyl)phenyl)-8-(2-morpholinoethoxy)thieno[2,3-c]quinolin-4(5H)-one;

(1 103) :

8-hydroxy-9-(l -(2-mo holinoethyl)-l H-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one; (1 104):

N-(2-(l H-pyrazol-l-yl)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzenesulfonamide;

(1 105):

8- hydroxy-9-(4-(2,2,2-trifluoro-l -hydroxy ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 106): 9-(4-(2-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 107) :

N-(2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropyl) methanesulfonamide;

(1 108) :

9-(4-(2-(dimethylamino)propyl)phenyl)-8-methoxythieno[2,3-c]quinoIin-4(5H)-one;

(1 109) : 9-(4-(l -aminoethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 1 10) :

9- (l -(l-(dimethylamino)propan-2-yl)- l H-pyrazol-4-yl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(1 1 1 1 ): 9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 1 12) :

9-(4-(l-(dimethylarnino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 1 13) :

8-methoxy-9-(4-(2,2,2-trifluoro- l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 1 14):

N-(2-bromoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-methylben zenesulfonamide; (1 1 15) :

N-(2-(lH-imidazol-l-yl)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)b enzenesulfonamide;

(1 1 16) :

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(1 1 17) :

3-(4-(8-(2-(dimethylamino)ethoxy)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pr opanenitrile;

(1 1 18): (R)-9-(4-(l -aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 1 19) :

N-(2-chloroethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-methylben zenesulfonamide;

(1 120) : (S)-9-(4-(l -aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; " (1 121): (S)-9-(4-(l -aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 122) :

(R)-9-(4-(l -aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1 123) :

(R)-9-(4-(l-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 124): 9-(4-(l -aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(1 125) : 9-(4-(l-aminoethyl)phenyl)-8-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 126) :

(R)-6-chloro-9-(4-(l -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1 127): (S)-9-(4-(l -(ethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 128) :

(S)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 129) :

6-chloro-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(1 130) : 9-(4-(l -aminoethyl)phenyl)-6-ethynyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 131 ) : (R)-9-(4-(l -aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 132) :

(R)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-on e;

(1 133) : 9-(4-(2-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 134) : 9-(4-(l -aminoethyl)phenyl)-8-(difluoromethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 135) :

(R)-6-bromo-8-hydroxy-9-(4-(l -(methyIaniino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne;

(1 1 36) :

9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1 137) : 9-(4-butylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 138) : 9-(4-butylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 139) :

N-(2-chloroethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(1 140) :

9-(4-((3-bromopyrrolidin-l-yl)sulfonyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 141) :

(S)-9-(4-(l-(methylsulfonamido)propyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8- yl methanesulfonate;

(1 142) : 9-(4-(2-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 143) :

9-(4-(3-(dimethylamino)- l -hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)- ^• one;

(1 144):

N-(2-bromoethyl)-4-(6-chloro-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoIin-9-yl)benz enesulfonamide;

(1 145) :

N-(2-chloroethyl)-4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro-lH-cyclopenta[c]quinolin-9-yl)be nzenesulfonamide;

(1 146) :

N-(2-bromoethyl)-4-(5-ethyl-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benze nesulfonamide;

(1 147) :

(S)-8-methoxy-9-(4-(l -(methylamino)propyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 148) :

(S)-8-hydroxy-9-(4-(l -(methylamino)propyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 149) :

9-(4-( l -aminoethyl)phenyl)-8-(((2-hydroxyethyl)amm^

-one;

(1 150) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 151 ) :

(R)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1 152): 8-hydroxy-9-(4-pentylphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 153) : 9-(4-(2-aminoacetyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 154) :

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)propyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne;

(1 155): 8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 156) : 8-methoxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 157) :

(R)-9-(4-( l -aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1 158) :

(R)-9-(4-(l -aminopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1 159) :

(R)-9-(4-(l -aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 160) : (R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 161 ) : (R)-9-(4-(l -aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 162) : 2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butanenitrile;

(1 163) : (S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 164) : (S)-9-(4-(l -aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 165) :

6-chloro-8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 166) :

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 167) :

9-(4-(2-aminoethyl)-3,5-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 168) :

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

(1 169) :

(1 170) :

6-chloro-8-rnethoxy-9-(4-(2-(methylaniino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 171) : 9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 172) :

(S)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-on

(1 173) :

6-bromo-8-methoxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 174) :

9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 175) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 176) :

(R)-9-(4-( l -aminopropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(1 177) :

9-(4-(2-aminoethyl)-3,5-difluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 178) :

9-(4-(2-(dimethylamino)ethyl)-3,5-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one; (1 179) :

9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1 180) :

(S)-9-(4-(l -aminopropan-2-yl)phenyl)-6,7-dichloro-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

( 1 1 81 ) :

(S)-9-(4-(l -aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 1 82) :

(S)-6-chloro-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(1 183) :

6-bromo-8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 185) :

N-(2-hydroxyethyl)-4-(8-methoxy-5-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)b enzenesulfonamide;

(1 186) : methyl

3-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanoate;

(1 1 87) :

(R)-8-hydroxy-9-(4-(l -(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 188):

(R)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-on e;

(1 1 89):

(R)-8-methoxy-9-(4-(l -(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 190):

9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H )-one;

(1 191) : 9-(4-(2-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1 192) : 9-(4-(2-aminoethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1 193):

9-(4-(l-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]qui nolin-4(5H)-one;

(1 194) :

(S)-6-chloro-8-hydroxy-9-(4-(l -(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4( 5H)-one;

(1 195) :

(S)-6-chloro-9-(4-(l -(diethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4( 5H)-one;

(1 196) :

(S)-8-methoxy-9-(4-(l -(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 197) :

(S)-8-hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 198) :

4-(8-hydroxy-5-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9^yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(1 199) :

N-(2-bromoethyl)-4-(8-hydroxy-5-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ben zenesulfonamide;

(1200) :

(R)-6-chloro-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin- 4(5H)-one;

(1201):

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

(1202) : 9-(4-(l -aminobUtan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1203) :

9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxy-2-(plienylsulfonyl)thieno[2,3-c]quinolin-4(5 H)-one;

(1204) :

N-(l -chloropropan-2-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzen esulfonamide;

(1205):

N-(l-chloropropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benze nesulfonamide;

(1206) : 9-(4-(2-aminoethyl)-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1207) : 9-(4-(2-aminoethyl)-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1208):

9-(4-(2-aminoethyl)-2-chloro-5-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-on e;

(1209):

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1210):

(R)-9-(4-(l -aminopropyl)phenyl)-8-hydroxy-5,6-dimethylthieno[2,3-c]quinolin-4(5H)-one; (121 1):

9-(4-(2-aminoethyl)-2-chloro-5-hydroxyphenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4 (5H)-one;

(1212): 9-(4-(aminomethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1213) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1214) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1215):

(S)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4( 5H)-one; (1216) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1217) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1218):

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1219) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1220) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-cyclopropyl-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(1221) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-cyclopropyl-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1222):

(S)-8-methoxy-6-rnethyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

(1223) :

(S)-9-(4-(l -aminopropan-2-yl)phenyl)-8-methoxy-6-rnethylthieno[2,3-c]quinolin-4(5?f)-one ;

(1224) :

9-(4-(2-aminoethyl)-2-bromo-5-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(1225) :

(S)-9-(4-(l -aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1226) :

3-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitri le;

(1227) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-8-rnethoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1228) :

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1229):

2-(2-fluoro-4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pro panenitrile;

(1230) :

6-cyclopropyl-9-(4-(2-(dimethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quino lin-4(5H)-one;

(1231) :

6-cyclopropyl-9-(4-(2-(dimethylamino)ethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quino lin-4(5H)-one; (1232) :

(S)-9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

(1233) :

(S)-9-(4-( 1 -(dimethy lamino)propan-2-y l)pheny l)-8-hydroxy-6-methylthieno[2,3-c]quinolin-

4(5H)-one;

(1234) :

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1235) :

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1236) :

9-(4-(2-amino-l-cyclopentylethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1237) :

9-(4-(2-amino-l ,l-dicyclopentylethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1238):

3-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propahenitr ile;

(1239):

9-(4-(2-amino-l-cyclopentylethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1240):

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-6-cyclopropyl-8-hydroxythieno[2,3-c]quinolin -4(5H)-one;

(1241 ) : 9-(4-(3-aminopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1242) : 9-(4-(2-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinoliri-4(5H)-one; (1243): 9-(4-(2-aminopropyI)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1244) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-cyclopropyl-8-methoxythieno[2,3-c]quinolin -4(5H)-one;

(1245) :

6-bromo-9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(1246) :

6-bromo-9-(3-fluoro-4-(2-(rnethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1247):

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1248) :

9-(4-(l -amino-2-rnethylpropan-2-yl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1249) :

(R)-9-(4-( l -aminopropan-2-yl)phenyl)-6-methy 1-4-0X0-4, 5-dihydrothieno[2,3-c]quinoline-8 -carbonitrile; (1250) : (R)-9-(4-(l -aminoethyl)phenyl)-8-hydroxy-6-vinylthieno[2,3-c]quinolin-4(5H)-one;

(1251) :

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H )-one;

(1252):

9-(4-(l -amino-3-methylbutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1253) :

9-(4-(l-amino-3-methylbutan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1254) :

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1255) : (R)-9-(4-(l -aminoethyl)phenyl)-6-ethyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1256) :

(R)-9-(4-(l-aminoethyl)phenyl)-6-(difluoromethyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1257) :

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1258) :

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1259) :

6-bromo-9-(4-(l -(dimethylamino)-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]qui nolin-4(5H)-one;

(1260):

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1261 ) : 9-(4-(3-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1262) :

(R)-8-hydroxy-6-methyl-9-(4-(l -(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne;

(1263) :

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1264) :

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1265) :

(R)-8-methoxy-6-methyl-9-(4-(l -(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne;

(1266) : 9-(4-(2-aminopropyl)phenyl)-6-ethyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1267): (R)-9-(4-(l -aminoethyl)phenyl)-6-butyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1268) :

9-(4-(2-aminoethyl)-3-chlorophenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1269) : 9-(4-(2-aminopropyl)phenyl)-6-ethyl-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1270) :

2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-(oxetan-3-yl)aceto nitrile;

(1271) :

9-(4-(l-amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1272) :

(R)-6-ethyl-8-hydroxy-9-(4-(l -(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one (1273):

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-rnethylthieno[2,3-c]quinolin-4(5H )-one;

(1274) :

9-(4-(l -amino-3-methylbutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1275) :

9-(4-(l-aminopropan-2-yl)-3-chlorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

( 1276) :

9-(4-(1 -aminopropan-2-yl)-3-chlorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1277) :

9-(4-(l-arninobutan-2-yl)pheny])-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1278) :

9-(4-(l -arnino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1279) :

9-(4-(l-aminopropan-2-yl)-3-chlorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H )-one;

(1280) :

9-(4-(l -aminopropan-2-yl)-3-chlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1281 ) : 9-(4-(2-amino-2-methylpropyl)phenyl)-8-rnethoxythieno[2,3-c]quinolin-4(5H)-one;

(1282) : 9-(4-(2-amino-2-methylpropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1283) :

9-(4-(l -amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1284) :

8- methoxy-6-rnethyl-9-(4-(3-methyl-l -(methylarnino)butan-2-yl)phenyl)thieno[2,3-c]quinol in-4(5H)-one;

(1285) :

8-hydroxy-6-methyl-9-(4-(3-methyl-l -(methylarnino)butan-2-yl)phenyl)thieno[2,3-c]quinol in-4(5H)-one;

(1286) :

9- (3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quino lin-4(5H -one; (1287) :

9-(4-(l -amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-niethoxythieno[2,3-c]quinolin-4(5H )-one;

(1288) :

9-(4-(l-amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinol in-4(5H)-one;

(1289) :

9-(4-(2-amino-2-methylpropyl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-on e;

(1290) :

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)- one;

- (1291 ): -

9-(4-(l-aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1292) :

9-(4-(2-amino-2-methylpropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(1293) :

9-(3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1294) :

9-(3-fluoro-4-(3-methyl-l -(methylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3 -c]quinolin-4(5H)-one;

(1295) :

9-(4-(l -(dimethylamino)-3-methylbutan-2-yl)phenyl)-8-niethoxy-6-rnethylthieno[2,3-c]quin olin-4(5H)-one;

(1296) :

9-(4-(l -(dimethylamino)-3-methylbutan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2 ,3-c]quinolin-4(5H)-one;

(1297) :

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)- one;

(1298) :

(R)-8-methoxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

(1299) :

9-(4-(l -(aminomethyl)cyclobutyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1300) :

9-(4-(l -(aminomethyl)cyclobutyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1301 ) : 8-methoxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1302) : 8-hydroxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1303) :

(S)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one; (1304) :

(S)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1305) :

(R)-9-(4-( l-aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-on

(1306) :

(R)-8-hydroxy-6-rnethyl-9-(4-( l -(methylarnino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

( 1307):

(R)-8-hydroxy-6-methyl-9-(4-( l -(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

(1308) : 8-methoxy-3-methyl-3H-pyrrGlo[2,3-c]quinolin-4(5H)-one;

(1309) : 9-(4-(l -aminobutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1310):

(S)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(131 1 ) :

(R)-9-(4-( l -(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one;

(1312) :

9-(4-(l -aminobutan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1313) : 8-hydroxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1314) : 9-amino-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1315):

(R)-9-(3-fluoro-4-(l -(methylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]q uinolin-4(5H)-one;

(1316) :

(R)-9-(3-fluoro-4-( l -(methylamino)propan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]q uinolin-4(5H)-one;

(1317) :

(R)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1318) :

(R)-9-(4-( l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1319) :

(R)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1320):

9-((4-(2-aminoethyl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1321 ):

9-(4-( l -(aminomethyl)cyclobutyl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)- one; (1322) :

(R)-l-(4-(l-aminopropan-2-yl)phenyl)-8-methoxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5 H)-one;

(1323) : 8-hydroxy-3-(hydroxymethyl)-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1324):

(R)-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1325):

9-((4-(aminomethyl)phenyl)amino)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1326):

9-((4-(aminomethyl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1327):

9-((4-(l-aminopropan-2-yl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1328):

9-((4-(l -aminopropan-2-yl)pheny])amino)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)- one;

(1329):

9-(4-(2-aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1330):

9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1331):

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1332):

9-(4-((R)-l -aminopropan-2-yl)phenyl)-8-hydroxy-2-(l -hydroxy ethyl)thieno[2,3-c]quinolin- 4(5H)-one;

(1333) :

9-(4-((R)- l -aminopropan-2-yl)phenyl)-2-(l -hydroxyethyl)-8-m

4(5H)-one;

(1334) :

3-(4-((8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)amino)phenyl)pro panenitrile;

(1335) :

9-((3-(2-aminoethyl)phenyl)amino)-8-methoxy-6-^

(1336) :

9-((4-(2-aminoethyl)phenyl)amino)-8-hydroxy-6-rnethylthieno[2,3-c]quinolin-4(5H)-one;

(1337) :

9-(4-(2-(ethylarnino)propyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1338):

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1339):

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one; (1340) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-2,6-dimethylthieno[2,3-c]quinolin-4(5H) -one;

(1341 ) :

(R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-8-methoxy-2,6-dimethy lthieno[2,3-c]quinolin-4(5H)

-one;

(1342) :

9-(4-((R)-l -aminopropan-2-yl)phenyl)-2-(l -hydroxyethyl)-8-methoxy-6-methylthieno[2,3-c ]quinolin-4(5H)-one;

(1343):

2-((4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)amino)acet onitrile;

(1344): . . . .. . . . . .

(R)-9-(4-(l-aminobutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1345):

9-(3-chloro-4-(2-(ethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1346):

9-(4-(3-((dimethylamino)methyl)pentan-3-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1347):

(R)-6-chloro-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(1348):

9-(4-(2-(ethylamino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1349):

9-(4-(2-(ethylamino)ethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1350):

9-(4-(2-(ethyl(methyl)amino)propyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1351):

2-(hydroxy(piperidin-4-yl)methyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1352) :

(R)-9-(4-(l -aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1353) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-2-chloro-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1354) :

(R)-9-(4-(l-aminopropan-2-yl)pheny!)-2-chloro-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1355):

8- methoxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1 356):

9- (4-(2-(ethyl(methyl)amino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one; (1357) :

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H) -one;

(1358) :

9-(4-(3-((dimethylamino)methyl)pentan-3-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1359) :

9-(6-(dimethylamino)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1360) :

(R)-9-(4-(l -(dimethylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin^ (5H)-one;

(1361 ) :

(R)-8-methoxy-6-methyl-9-(4-(l-(methylamino)butan-2-yl)phenyl)thieno[2,3-c]quinolin-4( 5H)-one;

(1362):

9-(4-(3-((diethylamino)methyl)pentan-3-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinol in-4(5H)-one;

(1363):

9-(3-chloro-4-(2-(ethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1364):

8- hydroxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1365):

(R)-9-(4-(l-(dimethylamino)butan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1366):

(R)-9-(4-(l -(ethyl(methyl)amino)butan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1367) :

(R)-9-(4-(l -(diethylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1368) :

(R)-9-(4-(l -(ethyl(methyl)amino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1369) :

2-((4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)(methyl)a mino)acetonitrile;

(1370) :

2-((4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)(methyl)a mino)acetonitrile;

(1371):

9- (3-chloro-4-(2-(ethyl(methyl)amino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1372):

9-(4-( l -((dimethylamino)methyl)cyclobutyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quino lin-4(5H)-one; (1373) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-bromo-8-niethoxythieno[2,3-c]quinolin-4(5H)-one;

(1374) :

9-(6-(2-aminoethoxy)pyridin-3-yl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1375):

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-2-fluoro-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1376):

9-(6-(2-aminoethoxy)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1377):

9-(4-(l-amino-2,2,2-trifluoroethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1378) : -

9-(4-(l-amino-2,2,2-trifluoroethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1379) :

(R)-9-(4-(l -(ethyl(rnethyl)amino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1380) :

(R)-8-hydroxy-6-methyl-9-(4-(l -(methylamino)butan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5 H)-one;

(1381) :

9-(4-(l -amino-2,2,2-trifluoroethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1382) :

(R)-l -(4-(l -aminopropan-2-yl)phenyl)-8-hydroxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5 H)-one;

(1383) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-2-fluoro-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1384):

9-(6-((2-aminoethyl)amino)pyridin-3-yl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-o ne;

(1385) :

9-(6-((2-aminoethyl)amino)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)- one;

( 1386) :

(S)-6-chloro-9-(4-(l -(ethyl(methyl)amino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quin olin-4(5H)-one;

(1387) :

(S)-9-(4-(l-(dimethylarnino)propan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c] quinolin-4(5H)-one;

(1388) :

(R)-9-(4-(l -(diethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one; (1389) :

9-(4-(l-amino-2,2,2-trifluoroethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1390) :

9-(4-( l-amino-2,2,2-trifluoroethyl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H) -one,

(1391 ) :

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H) -one;

(1392) :

(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanesulfo namide;

(1393) :

8-methoxy-6-methyl-9-(4-(2-(methylsulfinyl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1394) :

8- hydroxy-6-methyl-9-(4-((methylsulfonyl)methyl)phenyl)thieno[2,3-c]quinoIin-4(5H)-one;

(1395) :

(4 8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)rnethanesulfo namide;

(1396) :

9- (4-((2-arninoethyl)(rnethyl)arnino)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1397) :

(R)-N-(2-(2-fluoro-4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ph enyl)propyl)methanesulfonamide;

(1398) :

(R)-N-(2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ph enyl)propyl)methanesulfonamide;

(1399) :

(S)-9-(4-(l-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one;

(1400) :

9-(4-((2-aminoethyl)(methyl)amino)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1401 ) :

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-6-brorno-8-hydroxythieno[2,3-c]quinolin-4(5H)

-one;

(1402) :

2-(6-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-3-yl)aceton itrile;

(1403) :

8-hydroxy-6-methyl-9-(4-(2-(methylsulfinyl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1404) :

8-methoxy-6-methyl-9-(4-((methylsulfonyl)methyl)phenyl)thieno[2,3-c]quinoIin-4(5H)-one (1405) : 5-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)nicotinamide;

(1406) :

2-(5-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)propanenitrile;

(1407) :

2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanamid e;

(1408) :

9-(6-(l -aminopropan-2-yl)pyridin-3-yl)-8-met oxy-6-methylthieno[2,3-c]quinolin-4(5H)-o ne;

(1409):

2-(5-(8-methoxy-6-methy 1-4-0X0-4, 5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)-2-met hylpropanenitrile;

(1410) :

2-hydroxy-2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane- l- sulfonamide;

(141 1) :

N-(tert-butyl)-2-hydroxy-2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phe nyl)propane- 1 -sulfonamide;

(1412) :

2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanamid e;

0413):

2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane-l -sulfonamid e;

(1414):

9-(4-(2-amino- l-fluoroethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1415):

9-(6-(l-aminopropan-2-yl)pyridin-3-yl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-on e;

(1416):

2-(5-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)-2-met hylpropanenitrile;

(1417) :

2-(5-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)-2-methylpropan enitrile;

(1418) :

2-(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)-2-methylpropa nenitrile;

(1419) :

2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane- l-s ulfonamide;

(1420) :

9-(4-(2-amino- l -hydroxyethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-on e; (1421) :

9-(6-(l-amino-2-methylpropan-2-yl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-on

(1422) :

N-cyclopropyl- 1 -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phe nyl)methanesulfonamide;

(1423) :

2-(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)propanenitrile;

(1424) :

(R)-N-(2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pro pyl)methanesulfonamide;

(1425) :

N-ethyl-l -(4-(8-methGxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)me thanesulfonamide;

(1426):

9-(6-(l -aminopropan-2-yl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1427):

N-cyclopropyl- l-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phe nyl)methanesulfonamide;

(1428):

l -(5-(8-met oxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)cyclopropanecar bonitrile;

(1429) :

N-ethyl-l-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)met hanesulfonamide;

(1430) :

l-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfo namide;

(1431) :

l -(4-(8-rnethoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfonamide;

(1432) :

(R)-N-(2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoIin-9-yl)phenyl)propyl)metha nesulfonamide;

^" (1433):

(R)-N-(2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl)-N-met hylmethanesulfonamide;

(1434):

(R)-N-(2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)prop yl)methanesulfonamide;

(1435):

(R)-N-(2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl)metha nesulfonamide;

(1436):

(R)-N-(2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl)-N-me thylmethanesulfonamide; (1437) :

(R)-N 2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)prop yl)-N-methylmethanesulfonamide;

(1438) :

(R)-N-(2-(4 8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pro pyl)-N-methylmethanesulfonamide;

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising at least one compound of above 1 or 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

22. The pharmaceutical composition of above 21 which is available for preventing or

treating a PBK dependent disease.

23. The pharmaceutical composition of above 22, wherein the PBK dependent disease is cancer. -

24. A PBK inhibitor comprising at least one compound of above 1 or 2, or a

pharmaceutically acceptable salt thereof.

25. A method for treating a PBK dependent disease in a subject, comprising administering to said subject an effective amount of a compound or a pharmaceutically acceptable salt thereof of above 1 or 2.

26. A compound or pharmaceutically acceptable salt thereof of above 1 or 2 for use in

treatment of a PBK dependent disease.

27. Use of a compound of above 1 or 2 or a pharmaceutically acceptable salt thereof in

manufacturing a pharmaceutical composition for treating a PBK dependent disease.

Alternatively, the present invention also provides following embodiments:

101 . The present invention provides a compound represented by formula (I) or a

pharmaceutically acceptable salt thereof:

I

or a pharmaceutically acceptable salt thereof,

hydrogen,

hydroxyl,

halogen,

cyano,

nitro,

amino,

Ci-Ce alkyl,

C₂-C6 alkenyl, C2-C6 alkynyl,

C3-C10 cycloalkyl,

C3-C10 cycloalkenyl,

Cj-Ce alkoxy,

C₆-Cio aryl,

indanyl,

heteroaryl,

bered heterocycloalkyl,

-CONH2,

substituent A:

hydroxyl;

oxo (=0);

cyano;

halogen;

Ci-C₆ alkyl (wherein the C1-C6 alkyl is optionally substituted with a substituent selected from the group consisting of substituent B below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or C1-C6 alkyl substituted with -NR³¹ R³² (wherein R³¹ and R³² each independently represent hydrogen or C1-C6 alkyl)];

-NR²¹R²² [wherein R ¹ and R²² each independently represent hydrogen, or Ci-C₆ alkyl (wherein the Ci-C₆ alkyl is optionally substituted with di(Ci-C₆ alkyl)amino, Q-Ce alkylsulfonyl (-S0₂(Ci-C6 alkyl)), or 3- to 8-membered heterocycloalkyl)];

C_\-C alkoxy {wherein the C1-C6 alkoxy is optionally substituted with halogen, 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl), or -NR³³R³⁴ [wherein R³³ and R³⁴ each independently represent hydrogen, C1-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with Ci-C₆ alkylsulfonyl or di(Ci-C₆ alkyl)amino), or Ci -C₆ alkylsulfonyl]} ;

-S02 R ³R² {wherein R²³ and R²⁴ each independently represent hydrogen, C1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with hydroxyl, Q-C6 alkoxy, halogen, C3-C10 cycloalkyl, or -NR³⁵R³⁶ (wherein R³⁵ and R³⁶ each independently represent hydrogen or C1-C alkyl)], C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with C1-C6 hydroxyalkyl), or 3- to 8-membered heterocycloalkyl; or R²³ and R²⁴ may together form 3- to 8-membered heterocycloalkyl wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with amino} ;

C1-C6 alkylsulfonyl (wherein the C1-C6 alkyl moiety is optionally substituted with hydroxyl);

C1-C6 alkylsulfonylamino (-NHS0₂(C|-C6 alkyl)) [wherein the C1 -C6 alkyl moiety is optionally substituted with -NR³⁷R³⁸ (wherein R³⁷ and R³⁸ each independently represent hydrogen or Q-C6 alkyl)];

3- to 8-membered heterocycloalkyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or C_\-Ce alkylsulfonyl), C\-Ce alkyl [wherein the C1-C6 alkyl is optionally substituted with -NR^4IR⁴² (wherein R⁴¹ and R⁴ each independently represent hydrogen or C1-C6 alkyl)], hydroxyl, or C\-Ce alkylsulfonyl} ;

heteroaryl;

-COOR¹¹ (wherein Rⁿ represents hydrogen or C1-C6 alkyl); and -COR¹² [wherein R¹² represents Ci-C₆ alkyl, C3-C10 cycloalkyl, cyanomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen, or Ci-Ce alkyl [wherein the Ci-Ce alkyl is optionally substituted with hydroxyl or -NR ³R⁴⁴ (wherein R⁴³ and R⁴⁴ each independently represent hydrogen or C1-C6 alkyl)] } , or 3- to 8-membered heterocycloalkyi which is optionally substituted with C1-C6 alkyl],

substituent B:

halogen;

hydroxyl;

cyano;

3- to 8-membered heterocycloalkyi (wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with C1-C6 alkyl, hydroxyl, amino, C1-C6 aminoalkyl, or Ci-C₆ alkyl substituted with C2-C7 alkyloxycarbonylamino);

-NR R {wherein R and R each independently represent hydrogen, C1-C6 alkyl [wherein the C_\-Ce alkyl is optionally substituted with Qi-Ce alkylsulfonyl, or 3- to 8-membered heterocycloalkyi optionally substituted with -COOR⁵³ (wherein R⁵³ represents hydrogen or Ci-C₆ alkyl)], 3- to 8-membered heterocycloalkyi, Ci-C₆ alkylsulfonyl, C3-C10 cycloalkyl, -COR⁵⁵ (wherein R⁵⁵ represents C]-C₆ alkyl), -COOR⁵⁶ (wherein R⁵⁶ represents Ci-Ce alkyl), or -CONR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ each independently represent hydrogen or C1-C6 alkyl)} ; and

-COOR⁵⁴ (wherein R⁵⁴ represents hydrogen or Ci-C₆ alkyl)];

wherein R⁵ is hydrogen or C1-C6 alkyl; and

-χ— .γ— - wherein is a structure selected from the group consisting of

(i) -S-CR⁷=CR⁶-,

(ii) -CH₂-CH₂-CH₂-,

(iii) -NH-CH=CCH₃-, and

(iv) -N=CH-S-,

wherein R⁶ is

hydrogen,

hydroxyl,

Ci-C₆ alkyl,

C6-C10 aryl (wherein the Ce-Cio aryl is optionally substituted with hydroxyl), or

3- to 8-membered heterocycloalkyi [wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with -NR^6IR⁶² (wherein R⁶¹ and R⁶² each independently represent hydrogen or C1-C6 alkyl)], and

wherein R⁷ is

hydrogen,

Ci-Ce alkyl {wherein the C1-C6 alkyl is optionally substituted with hydroxyl, -NR^7IR⁷² [wherein R⁷¹ and R⁷² each independently represent hydrogen, C1-C6 alkyl (wherein the C 1-C6 alkyl is optionally substituted with dimethylamino), C₃-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino), or 3- to 8-membered

heterocycloalkyi], or 3- to 8-membered heterocycloalkyi (wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with C1-C6 aminoalkyl)} ,

C6-Cio aryl (wherein the Cg-Cio aryl is optionally substituted with hydroxyl), or -COR⁷³ {wherein R⁷³ represents 3- to 8-membered heterocycloalkyi (wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with amino), or -NR⁷ R⁷⁵ [wherein

R⁷⁴ and R⁷⁵ each independently represent hydrogen, 3- to 8-membered heterocycloalkyi, or C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino)] } . 102. The compound of above 101 , or a pharmaceutically acceptable salt thereof, wherein

II

103. The compound of above 102, or a pharmaceutically acceptable salt thereof, wherein R¹ is hydrogen or halogen.

104. The compound of above 102 or 103, or a pharmaceutically acceptable salt thereof, wherein R² is hydrogen, hydroxyl, halogen, C|-C₆ alkoxy, or C6-C10 aryl which is optionally substituted with hydroxyl.

105. The compound of any one of above 102- 104 or a pharmaceutically acceptable salt, wherein R² is hydrogen, hydroxyl, halogen, Q-C6 alkoxy, or dihydroxyphenyl.

106. The compound of any one of above 102- 105, or a pharmaceutically acceptable salt thereof, wherein R is hydrogen; hydroxyl; halogen; C1-C6 alkoxy; cyano; nitro; 3- to 8-membered heterocycloalkyl which is optionally substituted with amino; heteroaryl; -OSO2CH₃;

-OSO2CF3; or -CONH2.

107. The compound of any one of above 102- 106, or a pharmaceutically acceptable salt thereof, wherein R is hydrogen; hydroxyl; halogen; C1-C6 alkoxy; cyano; nitro; 3- to 8-membered heterocycloalkyl which is optionally substituted with amino (wherein the 3- to 8-membered heterocycloalkyl is piperidyl, pyrrolidinyl, morpholinyl, or piperazinyl); pyridyl; -OSO2CH3;

-OSO2CF3; or -CONH2.

1 08. The compound of any one of above 102- 107, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C1-C6 alkyl, C -C6 alkenyl, Ci-C\o cycloalkyl, C3-C10 cycloalkenyl, C\-Ce alkoxy, C6-C10 aryl, indanyl, heteroaryl, and 3- to 8-membered heterocycloalkyl, wherein each of the groups of R⁴ is optionally substituted with a substituent selected from the group consisting of substituent A above.

1 09. The compound of any one of above 102- 108, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from the group consisting of hydrogen, hydroxyl, halogen, amino, C1-C6 alkyl, Ci-C(, alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, Q-C6 alkoxy,

C₆-C|o aryl, indanyl, heteroaryl (wherein the heteroaryl is selected from the group consisting of pyridyl, l H-indazolyl, l H-tetrazolyl, [ l ,2,4]triazolo[ l ,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-b]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and tetrahydroisoquinolyl), and 3- to 8-membered heterocycloalkyl (wherein the 3- to 8-membered heterocycloalkyl is selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, azepanyl, morpholinyl, and 1 ,2,3,6-tetrahydropyridyl), wherein each of the groups of R⁴ is optionally substituted with a substituent selected from the group consisting of substituent A- l below:

substituent A- l :

hydroxyl;

oxo;

cyano;

halogen;

Ci-C₆ alkyl (wherein the C1 -C6 alkyl is optionally substituted with a substituent selected from the group consisting of substituent B- l below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or C1 -C6 alkyl substituted with -NR^{3 I}R³² (wherein R³ and R³² each independently represent hydrogen or Ci-Ce alkyl)];

-NR^2IAR^22A [wherein R^21A and R^22A each independently represent hydrogen or Ci-C₆ alkyl (wherein C1 -C6 alkyl is optionally substituted with di (Ci-C₆ alkyl) amino, Ci-C₆ alkylsulfonyl (-S0₂ (C|-C₆ alkyl)), or piperidyl)];

Ci-C₆ alkoxy {wherein the C1 -C6 alkoxy is optionally substituted with 3- to

8-membered heterocycloalkyl selected from halogen, piperidyl, and piperazinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with Ci-C₆ alkyl), or -NR³³R³⁴ [wherein R³³ and R³⁴ each independently represent hydrogen, Ci-C₆ alkyl (wherein the C1-C6 alkyl is optionally substituted with Ci-C₆ alkylsulfonyl or di (C\-Ce alkyl) amino), or Ci-C₆ alkylsulfonyl] } ;

-S0₂NR^23AR^24A {wherein R^23A and R^24A each independently represent hydrogen, C C₆ alkyl [wherein the C1-C6 alkyl is optionally substituted with hydroxyl, Q-Ce alkoxy, halogen, C3-C10 cycloalkyl, or -NR³⁵R³⁶ (wherein R³⁵ and R³⁶ each independently represent hydrogen or C1-C6 alkyl)], C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with C 1-C6 hydroxyalkyl), azetidinyl, or pyrrolidinyl, or may together form pyrrolidinyl, wherein the pyrrolidinyl is optionally substituted with amino} ;

C1 -C6 alkylsulfonyl (wherein the C1-C6 alkyl moiety is optionally substituted with hydroxyl);

C| -C₆ alkylsulfonylamino (-NHSO2 (C,-C₆ alkyl)) [wherein the Ci-C₆ alkyl moiety is optionally substituted with -NR³⁷R³⁸ (wherein R³⁷ and R³ each independently represent hydrogen or Q-C6 alkyl)];

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, piperidyl, and piperazinyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C1-C6 alkyl, or C 1-C6 alkylsulfonyl), C1 -C6 alkyl [wherein the Ci-C₆ alkyl is optionally substituted with -NR^4lR ²(wherein R⁴¹ and R⁴² each independently represent hydrogen or C1 -C6 alkyl)], hydroxyl, or Q-C6 alkylsulfonyl} ;

lH-tetrazolyl;

-COOR^{1 1} (wherein Rⁿ represents hydrogen or Q-C6 alkyl); and

-COR^12A [wherein R^12A represents piperazinyl which is optionally substituted with Ci-C₆ alkyl, C₃-C_]0 cycloalkyl, cyanomethyl, -NR R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen or C|-C₆ alkyl [wherein the Ci-C₆ alkyl is optionally substituted with hydroxyl or -NR⁴³R⁴⁴ (wherein R⁴³ and R⁴⁴ each independently represent hydrogen or C,-C₆ alkyl)] }, or Ci-C₆ alkyl];

substituent B-l :

halogen;

hydroxyl;

cyano; 3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, and morpholinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C1-C6 alkyl, hydroxyl, amino, C1-C6 aminoalkyl, or C1-C6 alkyl substituted with C2-C7 alkyloxycarbonylamino);

-NR^5IAR^52A {wherein R ^1A and R^52A each independently represent hydrogen, Ci-C₆ alkyl [wherein the Ci-C₆ alkyl is optionally substituted with C1-C6 alkylsulfonyl, or piperidyl which is optionally substituted with, -COOR⁵³ (wherein R⁵³ represents hydrogen or Ci-C₆ alkyl)], piperidyl, C -Ce alkylsulfonyl, C3-C10 cycloalkyl, -COR⁵⁵ (wherein R ⁵ represents C,-C₆ alkyl), -COOR⁵⁶ (wherein R⁵* represents C,-C₆ alkyl), or -CONR⁵⁷R⁵⁸ (wherein R⁵⁷ and R⁵⁸ each independently represent hydrogen or Ci-C₆ alkyl)} ; and

-COOR⁵⁴ (wherein R⁵⁴ represents hydrogen or C1-C6 alkyl).

1010. The compound of any one of above 102-109, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from the group consisting of (p) below:

(P):

hydrogen,

hydroxyl,

halogen,

amino,

C₁ -C6 alkyl which is optionally substituted with a substituent selected from the group consisting of substituent (a) below,

C2-C6 alkenyl which is optionally substituted with a substituent selected from the group consisting of substituent (b) below,

C3-C10 cycloalkyl,

C3-C10 cycloalkenyl,

Ci-C₆ alkoxy,

wherein, in the group (p),

the heteroaryl is selected from the group consisting of pyridyl, lH-indazolyl, l H-tetrazolyl, [ l ,2,4]triazolo[ l ,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-fe]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and

tetrahydroisoquinolyl;

substituent (a):

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl and piperidyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen or C|-C₆ alkyl), or C|-C₆ alkyl [wherein the Ci -C₆ alkyl is optionally substituted with -NR ^IR⁴² (wherein R⁴¹ and R⁴² each independently represent hydrogen or C1-C6 alkyl)] } ; and

Ci-C₆ alkylsulfonylamino (-NHS0₂(Ci-C₆ alkyl));

substituent (b):

-COOR^{1 1} (wherein R^{1 1} represents hydrogen or Ci-C₆ alkyl); -NR^2laR^22a [wherein R^21a and R^22a each independently represent hydrogen, or Ci-C₆ alkyl (wherein the Ci-C₆ alkyl is optionally substituted with di(C) -C6 alkyl)amino or C|-C₆ alkylsulfonyl)];

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, and piperidyl {wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with -NR³⁹R⁴⁰ (wherein R³⁹ and R⁴⁰ each independently represent hydrogen, C\-Ce alkyl, or C -Ce alkylsulfonyl), Ci-C₆ alkyl [wherein the C|-C6 alkyl is optionally substituted with -NR ¹R⁴² (wherein R⁴¹ and R⁴² each independently represent hydrogen or C1-C6 alkyl)], hydroxyl, or Ci-C₆ alkylsulfonyl} ;

cyano; and

C1-C6 alkoxy;

substituent (c):

hydroxyl;

cyano;

halogen;

C)-C6 alkyl (wherein the C1-C6 alkyl is optionally substituted with a substituent selected from the group consisting of substituent B-c below);

C3-C10 cycloalkyl [wherein the C3-C10 cycloalkyl is optionally substituted with cyano, or C1-C6 alkyl substituted with -NR³¹R³² (wherein R³¹ and R³ each independently represent hydrogen or Q-C6 alkyl)];

-NR ^1cR^22c [wherein R^21c and R^22c each independently represent hydrogen or

Ci-C₆ alkyl];

C1-C6 alkoxy {wherein the C1-C6 alkoxy is optionally substituted with 3- to 8-membered heterocycloalkyl selected from halogen, piperidyl, and piperazinyl (wherein the 3- to 8-membered heterocycloalkyl is optionally substituted with C1-C6 alkyl), or -NR³³R³⁴ [wherein R³³ and R³⁴ each independently represent hydrogen, Ci-C₆ alkyl (wherein the C1-C6 alkyl is optionally substituted with di(C]-C6 alkyl)amino), or Q-C6 alkylsulfonyl]} ;

-S0₂NR^23cR^24c {wherein R^23c and R^24c each independently represent hydrogen, C1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with hydroxyl, C1-C6 alkoxy, halogen, C3-C|₀ cycloalkyl, or -NR³⁵R³⁶ (wherein R³⁵ and R³⁶ each independently represent hydrogen or C1-C6 alkyl)], C3-Ciocycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with Q-C6 hydroxyalkyl), azetidinyl, or pyrrolidinyl, or wherein R^23c and R ^4c may together form pyrrolidinyl which is optionally substituted with amino} ;

C,-C₆ alkylsulfonylamino (-NHS0₂(C,-C₆ alkyl)) [wherein the C]-C₆ alkyl moiety is optionally substituted with -NR R (wherein R and R each independently represent hydrogen or Ci-C₆ alkyl)];

piperazinyl {wherein the piperazinyl is optionally substituted with C1-C6 alkyl or C|-C₆ alkylsulfonyl} ;

lH-tetrazolyl; and

-COR^,2c [wherein R^{l 2c} represents piperazinyl which is optionally substituted with C)-C₆ alkyl, C₃-C_]0 cycloalkyl, cyanomethyl, -NR²⁵R²⁶ {wherein R²⁵ and R²⁶ each independently represent hydrogen or C1-C6 alkyl [wherein the C1-C6 alkyl is optionally substituted with hydroxyl, or -NR⁴³R⁴⁴ (wherein R⁴³ and R⁴⁴ each independently represent hydrogen or Q-C6 alkyl)]}, or Q-C6 alkyl]; and

substituent B-c:

halogen;

hydroxyl;

cyano; 3- to 8-membered heterocycloalkyi selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, and morpholinyl (wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with C1-C6 alkyl, hydroxyl, amino, Ci-C6

aminoalkyl, or Ci-C₆ alkyl substituted with C2-C7 alkyloxycarbonylamino); and

-NR^{5 lc}R^52c {wherein R^slc and R^52c each independently represent hydrogen,

C1-C6 alkyl [wherein the Ci-C₆ alkyl is optionally substituted with Ci-C₆ alkylsulfonyl, or piperidyl which is optionally substituted with -COOR⁵³ (wherein R⁵³ represents hydrogen or C,-C₆ alkyl)], piperidyl, d-C₆alkylsulfonyl, C₃-Ciocycloalkyl, -COR⁵⁵ (wherein R⁵⁵

represents Ci-C₆ alkyl), or -CONR⁵⁷R⁵⁸ (wherein R⁵ and R ⁸ each independently represent hydrogen or C|-C₆ alkyl)}];

substituent (d):

^*^ 1 d ^ 21 d ^

-NR^" R^" (wherein R and R ^" each independently represent hydrogen or

Ci-Ce alkyl);

substituent (e):

hydroxyl;

oxo;

cyano;

2¹ 22 2 ] 22

-NR R [wherein R and R each independently represent hydrogen or

Ci-Ce alkyl];

piperidyl;

C|-C₆ alkoxy; and

Ci-C₆ alkyl {wherein the Ci-C₆ alkyl is optionally substituted with -NR^5leR^52e [wherein R^5le and R^52e each independently represent hydrogen or -COOR⁵⁶ (wherein R⁵⁶ represents Ci-Ce alkyl)]}; and

substituent (f):

Ci-C₆ alkyl {wherein the Ci-Ce alkyl is optionally substituted with -NR^5lfR^52f [wherein R^5lf and R^52f each independently represent hydrogen, C1-C6 alkyl, or -COOR⁵⁶ (wherein R⁵⁶ represents C1-C6 alkyl)]}; and

C1-C6 alkylsulfonyl.

1 1 1. The compound of any one of above 102- 1 10, or a pharmaceutically acceptable salt thereof, wherein R⁶ is hydrogen; hydroxyl; C1-C6 alkyl; phenyl which is optionally substituted with 1 to 3 hydroxyls; piperidyl which is optionally substituted with amino; or piperazinyl.

1 12. The compound of above 1 1 1 , or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen.

1 13. The compound of any one of above 102- 1 1 1 , or a pharmaceutically acceptable salt thereof, wherein R is

hydrogen;

C1-C6 alkyl {wherein the Ci-C₆ alkyl is optionally substituted with hydroxyl,

-NR^{7, A}R^72A [wherein R^71A and R^72A each independently represent hydrogen, Ci-C₆ alkyl (wherein the Ci-Ce alkyl is optionally substituted with dimethylamino), C₃-C10 cycloalkyl

(wherein the C3-C10 cycloalkyl is optionally substituted with amino), or piperidyl], or 3- to 8-membered heterocycloalkyi selected from the group consisting of piperidyl and morpholinyl (wherein the 3- to 8-membered heterocycloalkyi is optionally substituted with Ci-Ce aminoalkyl)} ;

phenyl which is optionally substituted with 1 to 2 hydroxyls; or

-COR^73A {wherein R^73A represents piperidyl (wherein the piperidyl is optionally substituted with amino), or -NR^74AR^75A [wherein R^74A and R⁷⁵ each independently represent hydrogen, piperidyl, or C3-C10 cycloalkyl (wherein the C3-C10 cycloalkyl is optionally substituted with amino)]} . 4. The compound of above 101, or a pharmaceutically acceptable salt thereof, wherein x— -Y— -z _is __CH2__CH2__CH2_

ich have a following formula III, or a

5. The compound of above 1 14, or a pharmaceutically acceptable salt thereof, wherein R¹, R² and R⁵ are hydrogen.

6. The compound of above 1 14 or 1 15, or a pharmaceutically acceptable salt thereof, wherein R³ is hydroxy 1 or methoxy.

7. The compound of any one of above 1 14-1 16, or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen, phenyl [wherein the phenyl is substituted with Ci-C₆ alkyl substituted with -NR^51AR^52A (wherein R^51A and R^{5 A} each independently represent hydrogen or Ci-C₆ alkyl), or -SO₂NH₂], 1 ,2,3,6-tetrahydropyridyl, hydroxypyridyl, or methoxypyridyl. 8. The compound of above 101 , or a pharmaceutically acceptable salt thereof, wherein

X— -Y— -Z is -NH-CH=CCH₃-,

R¹, R², R⁴ and R⁵ are hydrogen, and

R³ is hydroxy 1.

9. The compound of above 101 , or a pharmaceutically acceptable salt thereof, wherein

X— Y— z ._{s N=CH s}

R¹, R², R⁴ and R⁵ are hydrogen, and

R³ is methoxy.

0. A compound selected from the group consisting of:

(1 ) : 8-methoxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(2) : 8-hydroxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(3): 7,8-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(4) : 7,8-dimethoxythieno[2,3-c]quinolin-4(5H)-one;

(5) : 8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(6) : 7,9-dimethoxythieno[2,3-c]quinolin-4(5H)rone;

(7) : 7,9-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(8): 7,8,9-trimethoxythieno[2,3-c]quinolin-4(5H)-one;

(9) : 8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(10) : 7,8,9-trihydroxythieno[2,3-c]quinolin-4(5H)-one; (1 1 ) 9-(3-(2-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(12) 8-chlorothieno[2,3-c]quinolin-4(5H)-one;

(13) 4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(14) thieno[2,3-c]quinolin-4(5H)-one;

(1 5) 8-fluorothieno[2,3-c]quinolin-4(5H)-one;

(16) 8-nitrothieno[2,3-c]quinolin-4(5H)-one;

(17) 8-(3-aminopiperidin- l -yl)thieno[2,3-c]quinolin-4(5H)-one;

(18) l -(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(19) l ,8-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(20) 8-hydroxy-l -(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(21 ) (R)-8-(3-aminopyrrolidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

(22) (S)-8-(3-aminopyrrolidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

(23) 8-(pyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

(24) 8-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(25) l -(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(26) l -(3-aminopiperidin- l -yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(27) 8-morpholinothieno[2,3-c]quinolin-4(5H)-one ;

(28) 8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(29) 8-hydroxy-2-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(30)

8-hydroxy-4-oxo-N-(piperidin-3-yl)-4,5-dihydrothieno[2,3-c]quinoline-2-carboxamide;

(31 ) : 8-hydroxy-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(32) : 8-hydroxy- l-(piperazin-l -yI)thieno[2,3-c]quinolin-4(5H)-one;

(33) :

(34) : 2-(3-aminopiperidine-l -carbonyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(35) : 2-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(36) :

(37) : 8-(piperazin-l -yl)thieno[2,3-c]quinolin-4(5H)-one;

(38) : 8-hydroxy- l -methyIthieno[2,3-c]quinoIin-4(5H)-one;

(39) :

2-((2-(dimethylamino)ethylamino)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(41 ) : 7-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(42) : 9-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (43 : 9-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(44 : l -methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(45 : 7-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(46 : 8-hydroxy-l-methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(47 : 9-(3 , 5-dihy droxy pheny l)-8-hydroxythieno[2,3 -cjquinol in-4(5H)-one ;

(48 : 8-hydroxy-9-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(49 : 8-hydroxy-9-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(50 : 9-(3,4-difluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(51 : (S)-8-(3-aminopyrrolidin-l-yl)-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)- (52 : 5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)picolinonitrile;

(53 : 9-(6-aminopyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(54 : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

(55 : 9-(3-fluoro-4-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(56; : 8-hydroxy-2-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(57

(R) 8-(3-aminopyrrolidin-l-yl)-2-(3,4-dihydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-o

(58 : 9-(3,4-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(59 : 9-(4-fluoro-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(6o; : 8-hydroxy-9-(3-hydroxy-5-(trifluoromethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-(

(61 : 8-hydroxy-9-(l H-indazol-6-yl)thieno[2,3-c]quinolin-4(5H)-one;

(62 : 8-hydroxy-9-(3,4,5-trihydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(63 : 9-(4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(64 : 9-(4-(l H-tetrazol-5-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(65 : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide; (66 : 9-(3-chloro-4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(6 : 9-(4-chloro-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(68 : 9-(3,4-dichlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(69 : 9-(4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(70 : 8-hydroxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(71 : 9-(4-(difluoromethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (72 : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(73 : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(74 : 9-(3-aminophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(75 : 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide; (76 : 8-hydroxy-9-(3,4,5-trifluorophenyl)thieno[2,3-c]quinolin-4(5H)-one; (77):

(78) 8- -methoxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(79) 8- •hydroxy-9-(naphthalen-2-yl)thieno[2,3-c]quinolin-4(5H)-one;

(80) 8- •hydroxy-9-(4-(hydroxymethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(81) 2- (4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(82) 8- ■hydroxy-9-(4-(methylsulfonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(83) 8- ■hydroxy-9-(pyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(84) 8- ■hydroxy-9-(l ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(85) 8- •hydroxy-9-(4-hydroxy-3-methoxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(86) 9- (3-fluoro-4-(morpholinomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(87) 9- (3-(aminomet yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(88) 9- (4-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(89) 9- (3-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(90) 9- (3-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(91 ) 9- •cyclohexenyl-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(92) 9- (3,5-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(93) 9- (4-(2-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(94) 9- (3-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(95) 9- (4-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(96) 9- •cyclopropyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(97) 9· •([ l,2,4]triazolo[l ,5-a]pyridin-6-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(98) 8· ^■methoxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(99) 9- ^■cyclohexenyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(100):

8- methoxy-9-(4-(2-(piperidin-l -yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 101 ) :

9- (4-(aminomethyl)phenyl)-8-hydroxy-2-(morpholinomethyl)thieno[2,3-c]quinolin-4(5H)-c ne;

(102) : 9-(l H-benzo[d]imidazol-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(103) : 9-(4-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(104) :

(105) :

8-hydroxy-9-(4-(2-(piperidin- l -yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(106) : 8-hydroxy-9-(4-(piperazin-l -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 107) : 8-methoxy-2,3-dihydro- 1 H-cyclopenta[c]quinolin-4(5H)-one; (108) : 8-hydroxy-2,3-dihydro-l H-cyclopenta[c]quinolin-4(5H)-one;

(109) :

(1 10) : tert-butyl

4-(2-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylamino)ethyl)piperidine-l -carboxylate;

(1 1 1 ) : 8-methoxy-9-(4-(piperazin-l -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 12) :

8-hydroxy-9-(4-(4-(methylsulfonyl)piperazin-l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1 13) :

(1 14) :

(1 15) :

(1 16) : 8-methoxy-9-(l -(piperidin-4-yl)-l H-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H -one;

(1 17) : 8-hydroxy-9-( 1 -(piperidin-4-yl)-l H-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(1 18) : 8-methoxythiazolo[4,5-c]quinolin-4(5H)-one;

( 1 19) :

2-((4-(aminomethyl)piperidin-l -yl)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(120) :

N-(2-(dimethylamino)ethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzamide;

(121 ) :

9-(4-(aminomethyl)phenyl)-8-hydroxy-2,3-dihydro-l H-cyclopenta[c]quinolin-4(5H)-one;

(124) : 8-hydroxy-9 l H-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(126) :

(127) :

(128) : N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)acetamide;

(129) :

(130) :

8-hydroxy-9-(4-(4-methylpiperazine-l -carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(131 ) :

8-methoxy-9-(4-(4-methylpiperazine-l -carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (132) :

8-hydroxy-9-(4-((4-methylpiperazin-l-yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(133) :

8- methoxy-9-(4-((4-methylpiperazin-l -yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(134) : (E)-9-(3-(diethylamino)prop-l -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(135) :

(E)-9-(3-(4-(aminomethyl)piperidin-l -yl)prop-l -enyl)-8-methoxythieno[2,3-c]quinolm^ H)-one;

(136) :

(E)-9-(3-(2-(diethylamino)ethylamino)prop- l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(137) :

N-(4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro- l H-cyclopenta[c]quinolin-9-yl)phenyl)methanes ulfonamide;

(138) : 9-(2-(dimethylamino)pyrimidin-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(139) : tert-butyl

(l-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yI)benzyl)piperidin-4-yl)methylcarb amate;

(140) : 8-hydroxy-9-(4-(4-methylpiperazin-l -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(141) : 8-methoxy-9-(4-(4-methy lpiperazin- 1 -y l)pheny l)thieno[2,3-c]quinolin-4(5H)-one;

( 142) : 8-methoxy-9-( 1 -(methy lsulfony 1)- 1 ,2,3,6-tetrahydropyridin-4-yl)thieno

[2,3-c]quinolin-4(5H)-one;

(144) : 9-(3-(4-(aminomethyl)piperidin-l-yl)propyl)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(145) :

9- (4-(3-(2-(diethylamino)ethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

( 146) : 9-(4-(3-(diethy lamino)propoxy)pheny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

( 147) :

(148) :

(E)-9-(3-(4-(aminomethyl)piperidin-l -yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(149) :

(150) : 8-hydroxy-9-(4-(2-(piperidin-l-yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(151 ) : 9-(4-(2-(ethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(152) :

(E)-9-(3-(4-aminopiperidin- l -yl)prop- l-enyl)-8-methoxythieno[2,3-c]quinoIin-4(5H)-one; (153) :

9-(l -(2-aminoethyl)-l,2,3,6-tetrahydropyridin-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(154) : 9-(4-(2-(ethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1 5): 9-(4-(2-(diethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(156) : 9-(4-(2-(diethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(157) : 9-(4-(2-(dimethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(159) : 8-methoxy-9-(4-(2-(piperidin-l -yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (160):

8- methoxy-9-(3-(2-(4-methylpiperazin-l -yl)et oxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(161 ) : 9-(3-(2-(diethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(162) : 9-(3-(3-(diethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (163): 9-(4-(2-(dimethy lamino)ethy l)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(164) : 9-(4-((dimethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(167) :

8-hydroxy-9-(3-(2-(4-methylpiperazin- l-yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(168) :

(169): 9-(4-(2-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(170) : 2-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(1 72) :

9- (l-(2-(dimethylamino)ethyl)-l ,2,3,6-tetrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]quino lin-4(5H)-one;

( 1 73) :

N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanesulfonamide;

(174) :

9-(l-(2-(diethylamino)ethyl)-l ,2,3,6-tetrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]quinoli n-4(5H)-one;

(175) : 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1 76) : 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(177) :

N-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanesulfonamide; (1 78) :

(179) :

( 1 80) :

8- hydroxy-9-( l ,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydro- l H-cyclopenta[c]quinolin-4(5H)- one;

(1 81 ) :

9- (4-( l -(dimethylamino)ethyl)phenyl)-8-hydroxy-2,3-dihydro-l H-cyclopenta[c]quinolin-4( 5H)-one;

( 182) :

9-(4-(2-(dimethylamino)ethyl)phenyl)-8-methoxy-2,3-dihydro- l H-cyclopenta[c]quinolin-4( 5H)-one;

( 184) : 9-(4-((diethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

( 185) : 9-(3-(2-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

( 1 86) : 9-(3-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

( 1 87) : 8-hydroxy-9-(4-((methylamino)rnethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 188) : 8-methoxy-9-(4-((methylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 1 89) : 9-(4-amino-3-methoxypheny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

( 190) : 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

( 191 ) : 9-(4-( l -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

( 192) : 9-(4-( 1 -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(193) :

N-( l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methanesulf onamide;

(194) : 8-hydroxy-9-(4-(l -(pyrrolidin- l -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 195) : 9-(4-( l -aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(196) : 9-(4-( l -(diethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(197) :

( 198) :

( 199) :

(200) :

N-(azetidin-3-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfon amide; (201) : 9-(4-(2-(diethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(202) :

2-amino-N-(3-(8-rnethoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfo namide;

(203): 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(204) : 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(205) :

(E)-9-(3-(3-aminopyrrolidin-l -yl)prop-l -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(206) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesul fonamide;

(207) : 8-methoxy-9-(5-methoxypyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

(208) :

8- methoxy-9-(5-methoxypyridin-3-yl)-2,3-dihydro-l H-cyclopenta[c]quinolin-4(5H)-one; (209):

9- (4-(3-aminopyrrQlidin-l -ylsulfonyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (210):

(21 1): 9-(4-((diisopropylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(212) :

(213) : 9-(4-((isopropylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(214) :

(215) :

(216): 8-methoxy-9-(4-(l-(pyrrolidin-l-yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(217) : 9-(4-amino-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(218) :

(219): 9-(3,5-difluoro-4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(220) :

(221) :

9-(4-((4-(aminomethyl)piperidin-l-yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quin olin-4(5H)-one; (222) :

(224) :

6-fluoro-8-methoxy-9-( l ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(225) :

9-(4-(l -(dimethylamino)ethyl)phenyl)-6-fluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(226) :

9-(4-((diethylamino)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (227):

(E)-9-(3-(3-hydroxypyrrolidin-l-yI)prop-l -enyl)-8-rnethoxythieno[2,3-c]quinolin-4(5H)-on e;

(228) :

(E)-8-hydroxy-9-(3-(3-hydroxypyrrolidin-l -yl)prop-l-enyl)thieno[2,3-c]quinolin-4(5H)-one ;

(230) :

(E)-9-(3-(3-aminoazetidin-l-yl)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(231) :

(232) : (S)-9-(4-( 1 -aminoethy l)pheny l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(233) : (S)-9-(4-(l -aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(234) :

8-hydroxy-9-(5-hydroxypyridin-3-yl)-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(235) :

9-(4-((4-(aminomethyl)piperidin-l -yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quin olin-4(5H)-one;

(236) :

8-methoxy-9-(4-(l -(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(237) :

9-(4-((3-aminopyrrolidin- l -yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(238):

(E)-9-(3-(3-aminoazetidin-l-yl)prop-l-enyl)-8-methoxythierio[2,3-c]quinolin-4(5H)-one;

(239) : (E)-9-(3-(ethylamino)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(240) :

9-(4-((3-aminopiperidin- l -yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(241 ) :

9-(4-((3-aminopyiTolidin-l -yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one; (242) :

9-(4-((3-aminopiperidin- l -yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(243) :

8-hydroxy-9-(4-( l -(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(244) : (E)-9-(3-(3-aminopiperidin- l-yl)prop- l -enyl)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(245) :

(E)-9-(3-(3-aminopyrrolidin- l -yl)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(246) :

(E)-9-(3-(3-aminopiperidin- l -yl)prop- l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(247) : - (E)-8-hydroxy-9-(3-(2-(methylsulfonyl)ethylamino)prop- l -enyl)thieno[2,3-c]quinolin-4(5H )-one;

(248) :

8- methoxy-9-(4-(2-(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(249) :

2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(250) :

(E)-N-( l -(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)allyl)azetidin-3-yl)me thanesulfonamide;

(251 ) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesulfonam ide;

(252) :

(253) : tert-butyl

(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)furan-2-yl)methylcarbamate;

(254) :

(255) :

(258) :

6-fluoro-8-hydroxy-9-( 1 ,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(259) :

(260) : 8-rnethoxy-9-(4-(l -(piperidin- l -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (261 ) :

2-(2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(262) : 8-hydroxy-9-(4-(l-(piperidin-l-yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(263) :

(E)-9-(3-(3-(dimethylamino)piperidin-l -yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4( 5H)-one;

(264) :

(E)-9-(3-(3-(dimethylamino)pyrrolidin- l -yl)prop- l-enyl)-8-hydroxythieno[2,3-c]quinolin^ (5H)-one;

(265): 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(266) : 9-(5-(aminomethyl)thiophen-2-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(268) :

(E)-9-(3-(4-aminopiperidin- l -yl)prop-l -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (269): 9-(4-((ethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(270) : 9-(4-(aminomethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(271 ) :

9-(3-chloro-4-((diethylarnino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(272) :

(R)-9-(4-(l -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(273) : 9-(4-(3-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(276) : 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (277):

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (278):

9-(3-fluoro-4-((3-hydroxypyrrolidin- l -yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4 (5H)-one;

(279):

9-(3-fluoro-4-((3-hydroxypyirolidin-l -yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4 (5H)-one;

(280) :

(281 ) :

(282) :

N-(2-(dimethylamino)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ben zenesulfonamide; (283) :

8- hydroxy-9-(4-((2-(methylsulfonyl)ethylamino)methyl)phenyl)thieno[2,3-c]quinolin-4(5H) -one;

(284) :

9-(3-(3-(dimethylatnino)pyrrolidin-l -yl)propyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(285) : 9-( l-(2-aminoethyl)-l H-pyrazol-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(286) :

9- (3-chloro-4-((diethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(287) :

(288) : 9-(3-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(289) :

(290) : 3-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile;

(291 ) : 9-(4-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(292) :

(293) :

(295) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

(296) : 9-(4-acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(297) :

(298):

9-(3-(3-(dimethylamino)piperidin- l -y])propyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one^ (299):

(300):

9-(3-fluoro-4-(2-(methylsulfonarnido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin -8-yl methanesulfonate;

(301 ) :

(302) :

(R)-9-(4-(l -(methylsulfonamido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl methanesulfonate; (303) :

(304) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesulfonam ide;

(305) :

9-(4-(2-(dimethylamino)ethyl)phenyl)-7-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(306) :

(307) :

4-(7-fluoro-8-hydroxy-4-Gxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(308) :

9-(4-( l -(dimethylamino)-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(309) :

(310) :

(31 1 ) :

(E)-3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylacrylonitrile;

(312) :

(313) 8- hydroxy-9-(4-(l -hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(314) 9- (4-(l -(cyclopentylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(315) :

9-(4-(l-(cyclopentylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(31 6) :

(317) : 9-(5-(aminomethyl)furan-2-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(31 8) :

9-(3-chloro-4-((methylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(320) :

N-(3-hydroxypropyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenes ulfonamide; (321) :

(322) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(3-hydroxypropyl)benzenesu lfonamide;

(323) :

(324) :

(325) :

(326) : 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(327) :

(332) :

(333) :

N-(2-fluoroethyI)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide;

(334) :

9-(4-(2-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(335) :

(336) : 9-(4-(l -aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(337) : 9-(4-(l -aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(338) : 9-(4-(l -(diethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(339) : 9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(340) : 9-amino-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(341 ) :

9-(4-(l -(dimethylamino)ethyl)phenyl)-6,7-difluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)- one; (342) :

9-(4-(l -(dimethylamino)ethyl)phenyl)-6,7-difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(343) :

N-cyclopropyl-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfona mide;

(344) :

(345): 9-(2-amino-2,3-dihydro- 1 H-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(346) : 9-(4-(l -(dimethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(347) :

(348):

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(349) :

9-(4-(l -(dimethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(350) :

N-( 1 -(hydroxymethy l)cyclopentyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9

-yl)benzenesulfonamide;

(351 ) :

9-(2-(diethylamino)-2,3-dihydro- l H-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (352):

9-(2-(dimethylamino)-2,3-dihydro- l H-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-o ne;

(353) : 8-hydroxy-9-(l,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(354) : 8-methoxy-9-(l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one; (355): 3-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile;

(356) :

9-(4-( l -(diethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(357) :

(358) :

9-(2-ethyl- l ,2,3,4-tetrahydroisoquinolin-7-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(359) : 9-(4-( l-aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(360) : 3-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyI)propanenitrile; (361 ):

(362): 9-(2-amino-2,3-dihydro-l H-inden-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (363) :

(364) :

9-(2-(dimethylamino)-2,3-dihydro- l H-inden-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-o ne;

(365) : 9-(4-( l -(ethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(366) :

6-chloro-9-(4-( l -(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (367): 9-(4-(cyclopropanecarbonyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(369) : 9-(2-aminoethyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(371) : 9-(4-(2-hydroxyethylsulfonyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (372): 9-(l -ethylindolin-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; ^'

(373) : 9-(4-( l -aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(374) :

8- hydroxy-9-(2-methyl- l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(375) : 9-(4-( l -aminoethyl)-3- luorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (376): 8-hydroxy-9-(l -methylindolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(377) : 8-hydroxy-9-(indolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(378) : 9-(indolin-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(379) :

9- (4-( l -((dimethylamino)methyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(380) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-propylbenzenesulfonamide;

(381 ) :

(382) :

(383) :

(384) :

(385): 9-(4-( l -(ethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (386) :

3- (4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoHn-9-yl)phenyl)-3-oxopropanenitrile;

(387) : (E)-9-(2-ethoxyvinyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(388) :

N-(l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)acetamide;

(389) :

4- (8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(3,3,3-trifluoropropyl)benze nesulfonamide;

(390) :

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(l -(hydroxymethyl)cyclopen tyl)benzenesulfonamide;

(391 ) :

or a pharmaceutically acceptable salt thereof.

121 . A pharmaceutical composition comprising at least one compound of any one of above 101-120 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

122. The pharmaceutical composition of above 121 which is available for preventing or treating a PB dependent disease.

123. The pharmaceutical composition of above 122, wherein the PBK dependent disease is cancer.

124. A PBK inhibitor comprising at least one compound of any one of above 101 -120, or a pharmaceutically acceptable salt thereof.

125. A method for treating a PBK dependent disease in a subject, comprising administering to said subject an effective amount of a compound or a pharmaceutically acceptable salt thereof of any one of above 101 - 120.

126. A compound or a pharmaceutically acceptable salt thereof of any one of above 101 - 120 for use in a treatment of a PBK dependent disease.

127. Use of a compound of any one of above 101 -120 or a pharmaceutically acceptable salt thereof in manufacturing a pharmaceutical composition for treating a PBK dependent disease.

Preferred compounds include those selected from the group consisting of: Example Nos.1 -391 listed in Table 1 below; and the pharmaceutically acceptable salts, prodrugs, hydrates and solvates of the forgoing compounds.

8-hydroxy-9-(pyridin-4-yl)thieno

83

[2,3-c]quinolin-4(5H)-one

8-hydroxy-9-( l ,2,3,6-tetrahydro

84 pyridin-4-yl)thieno[2,3-c] quinolin-4(5H)-one

8-hydroxy-9-(4-hydroxy-3-methoxy

85 pheny l)thieno [2,3 -cjquinol in- 4(5H)-one

9-(3-fluoro-4-(mo holinomethyl)

86 pheny l)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

9-(3-(aminomethyl)phenyl)-8-

87 hydroxythieno[2,3-c]quinolin- 4(5H)-one

9-(4-(aminomethyl)phenyl)-8-

88 methoxythieno[2,3-c]quinolin- 4(5H)-one

9-(4-(aminomethyl)phenyl)-8-

121 hydroxy-2,3-dihydro- 1 H-cyclopenta

[c]quinolin-4(5H)-one hydrochloride o 'HCI

(E)-butyl 3-(8-hydroxy-4-oxo-4,5-

122 dihydrothieno[2,3-c]quinolin- 9-yl)acrylate

8-methoxy-9-(lH-pyrrolo[2,3-b]

123 pyridin-5-yl)thieno[2,3-c]quinolin- 4(5H)-one o

8-hydroxy-9-(l H-pyrrolo[2,3-b]

124 pyridin-5-yl)thieno[2,3-c]quinolin- 4(5H)-one

N-(methoxy-4-oxo-4,5-dihydrothieno

125 [2,3-c]quinolin-9-yl)phenethyl) acetamide

N-(2-aminoethyl)-4-(8-hydroxy-4-

126 oxo-4,5-dihydrothieno[2,3-c]quinolin

-9-yl)benzamide

o N-(2-aminoethyl)-4-(8-methoxy-4-

127 oxo-4,5-dihydrothieno[2,3-c]quinolin

-9-yl)benzamide

N-(hydroxy-4-oxo-4,5-dihydrothieno

128 [2,3-c]quinolin-9-yl)phenethyl) acetamide

4-(8-hydroxy-4-oxo-2,3,4,5-tetra

129 hydro- 1 H-cyclopenta[c]quinolin- 9-yl)benzenesulfonamide

8-hydroxy-9-(4-(4-methylpiperazine-

130 1 -carbonyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

8-methoxy-9-(4-(4-rnethylpiperazine-

131 1 -carbonyl)pheny l)thieno[2,3-c] quinolin-4(5H)-one

8-hydroxy-9-(4-((4-methylpiperazin-

132 l -yl)methyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

8-methoxy-9-(4-((4-methylpiperazin-

133 l -yl)methyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

(E)-9-(3-(4-aminopiperidin-l -yl)

152 prop-l-enyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one

9-( 1 -(2-aminoethy 1)- 1 ,2,3 ,6-tetra

153 hydropyridin-4-yl)-8-methoxythieno

[2,3-c]quinolin-4(5H)-one

/

9-(4-(2-(ethylamino)ethoxy)phenyl)-

154 8-methoxythieno[2,3-c]quinolin- 4(5H)-one

9-(4-(2-(diethylamino)ethoxy)phenyl)

155 -8-hydroxythieno[2,3-c]quinolin- 4(5H)-one

/

9-(4-(2-(diethylamino)ethoxy)phenyl)

1 56 -8-methoxythieno[2,3-c]quinolin- 4(5H)-one

9-(4-(2-(dimethylamino)ethoxy)

157 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

2-(3-(8-methoxy-4-oxo-4,5-dihydro

171 thieno[2,3-c]quinolin-9-yl)phenyl) acetonitrile

9-( 1 -(2-(dimethy lamino)ethyl)- 1 ,2,3,

172 6-tetrahydropyridin-4-yl)-8-hydroxy thieno[2,3-c]quinolin-4(5H)-one

N-(hydroxy-4-oxo-4,5-dihydrothieno

173 [2,3-c]quinolin-9-yl)phenethyl) methanesulfonamide

9-( 1 -(2-(diethy lamino)ethyl)- 1 ,2,3,6-t

174 etrahydropyridin-4-yl)-8-hydroxy thieno[2,3-c]quinolin-4(5H)-one

9-(4-(2-am inoethy l)pheny l)-8-

175 hydroxythieno[2,3-c]quinolin- 4(5H)-one

9-(4-(2-aminoethyl)phenyl)-8-

176 hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

-HCI

N-(methoxy-4-oxo-4,5-dihydrothieno

177 [2,3-c]quinolin-9-yl)phenethyl) methanesulfonamide

(E)-9-(3-(3-aminoazetidin- 1 -y 1) prop- 1 -enyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one dihydrochloride

(E)-9-(3-(ethy lamino)prop- 1 -enyl)-8- hydroxythieno[2,3-c]quinolin-4(5H)- one hydrochloride

9-(4-((3-aminopiperidin-l -yl)methyl) -3-fluorophenyl)-8-hydroxythieno[2,3 -c]quinolin-4(5H)-one dihydrochloride

9-(4-((3-aminopyrrolidin- 1 -y l)methy 1 )-3-fluorophenyl)-8-hydroxythieno[2, 3-c]quinolin-4(5H)-one

dihydrochloride

9-(4-((3-aminopiperidin- 1 -y l)methyl) -3-fluorophenyl)-8-methoxythieno[2, 3-c]quinolin-4(5H)-one

dihydrochloride

1)

9-(4-((ethylamino)rnethyl)phenyl)-8- hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

(E)-9-(3-(4-aminopiperidin- 1 -y 1) prop-l-enyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one dihydrochloride

9-(4-((ethylamino)methyl)phenyl)-8- methoxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

9-(4-(aminomethyl)phenyl)-6-bromo- 8-hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

9-(3-chloro-4-((diethylamino)methyl) phenyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -(dimethy !amino)ethy 1) phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one hydrochloride o .HC1

9-(3-chloro-4-((methylamino)methyl)

318 phenyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one hydrochloride

9-(4-(2-aminopropan-2-yl)phenyl)-8-

319 hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

/ N-(3-hydroxypropyl)-4-(8-methoxy-4

320 -oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)benzenesulfonamide

2-fluoro-4-(8-hydroxy-4-oxo-4,5-di

321 hydrothieno[2,3-c]quinolin-9-yl)-N-(

2-hydroxyethyl)benzenesulfonamide

4-(8-hydroxy-4-oxo-4,5-dihydro

322 thieno[2,3-c]quinolin-9-yl)-N-(3- hydroxypropyl)benzenesulfonamide

9-(4-(2-aminopropan-2-yl)phenyl)-6-

334 chloro-8-hydroxythieno[2,3-c] quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l -(dimethylamino)ethyl)

335 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one hydrochloride

9-(4-( 1 -aminopropyl)pheny l)-8-

336 hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride o -HCI

9-(4-( 1 -aminopropy l)pheny l)-8-

337 methoxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

9-(4-(l -(diethylamino)propyl)phenyl)

338 -8-hydroxythieno[2,3-c]quinolin- 4(5H)-one hydrochloride

9-(4-(l -(dimethylamino)propyl)

339 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one hydrochloride o -HCI

l-(4-(8-methoxy-4-oxo-4,5-dihydro

357 thieno[2,3-c]quinolin-9-yl)phenyl) eye lopropanecarbon itr i le

9-(2-ethyl- l ,2,3,4-tetrahydroiso

358 quinolin-7-yl)-8-hydroxythieno[2,3-c

]quinolin-4(5H)-one hydrochloride

9-(4-( 1 -aminoethy ^-fluoropheny -

359 S-hydroxythienoP^-c lquinolin- 4(5H)-one hydrochloride

0 -HC\

3-(3-(8-methoxy-4-oxo-4,5-dihydro

360 thieno[2,3-c]quinolin-9-yl)phenyl) propanenitrile

l -(4-(8-hydroxy-4-oxo-4,5-dihydro

361 thieno[2,3-c]quinolin-9-yl)phenyl) eye lopropanecarbon itri le 9-(2-amino-2,3-dihydro- 1 H-inden-5-

362 yl)-8-methoxythieno[2,3-c]quinolin-4

(5H)-one hydrochloride

N-isopentyl-4-(8-methoxy-4-oxo-4,5-

363 V dihydrothieno[2,3-c]quinolin-9-yl)be nzenesulfonamide

9-(2-(dimethylamino)-2,3-dihydro-l

364 H-inden-5-yl)-8-methoxythieno[2,3-c

]quinolin-4(5H)-one hydrochloride

9-(4-(l-(ethylamino)ethyl)phenyl)-8-

365 methoxythieno[2,3-c]quinolin-4(5H)- one hydrochloride

6-chloro-9-(4-( 1 -(dimethy lamino)eth

366 yl)phenyl)-8-hydroxythieno[2,3-c]qui nolin-4(5H)-one hydrochloride o -HCI

9-(4-(cyclopropanecarbonyl)phenyl)-

367 8-methoxythieno[2,3-c]quinoIin- 4(5H)-one

Table l-2(Examples 1031-1438)

N-( 1 -hydroxypropan-2-y l)-4-(8

-methoxy-4-oxo-4,5-dihydrothi

1057

eno[2,3-c]quinolin-9-yl)benzen esulfonamide

9-(4-(hydroxy(thiazol-2-yl)met

1058 hyl)phenyl)-8-methoxythieno[2

,3-c]quinolin-4(5H)-one

9-(6-( 1 -aminoethy l)pyridin-3-y 1

1059 )-8-hydroxythieno[2,3-c]quinol in-4(5H)-one

9-(4-(4-hydroxybutyl)phenyl)-8

1060 -methoxythieno[2,3-c]quinolin- 4(5H)-one

2-(4-(8-hydroxy-4-oxo-4,5-dih

1061 ydrothieno[2,3-c]quinolin-9-yl) phenyl)-2-methylpropanamide

N-( 1 -bromopropan-2-yl)-4-(8-h ydroxy-4-oxo-4,5-dihydrothien

1062

o[2,3-c]quinolin-9-yl)benzenes ulfonamide 8-hydroxy-9-(4-(hydroxy(thiaz

1063 ol-2-yl)methyl)phenyl)thieno[2,

3-c]quinolin-4(5H)-one

(S)-8-methoxy-9-(4-( 1 -(methyl

1064 amino)ethyl)phenyl)thieno[2,3- c]quinolin-4(5H)-one o

9-(6-( 1 -(diethy lamino)ethyl)pyr

1065 idin-3-yl)-8-hydroxythieno[2,3- c]quinolin-4(5H)-one

0

9-(4-( 1 -aminoethy l)phenyl)-8-h

1066 ydroxy-6-methylthieno[2,3-c]q uinolin-4(5H)-one o

9-(6-(l -aminoethyl)pyridin-3-yl

1067 )-8-methoxythieno[2,3-c]quinol in-4(5H)-one

0

8-hydroxy-9-(4-(4-hydroxybuty

1068 l)phenyl)thieno[2,3-c]quinolin- 4(5H)-one

0

II 1 1 9-(6-(l -aminoethyl)pyridin-3-yl

1075 )-8-methoxythieno[2,3-c]quinol in-4(5H)-one

9-(4-( 1 -aminoethyl)phenyl)-4-o

1076 xo-4,5-dihydrothieno[2,3-c]qui nolin-8-yl dimethylcarbamate

9-(4-( 1 -aminoethyl)pheny l)-4-o

1077 xo-4,5-dihydrothieno[2,3-c]qui nolin-8-yl isopropyl carbonate

9-(4-((l H-imidazol-l -yl)methy]

1078 )phenyl)-8-methoxythieno[2,3- c]quinolin-4(5H)-one

N-(2-bromopropyl)-4-(8-hydro xy-4-oxo-4,5-dihydrothieno[2,3

1079

-c]quinolin-9-yl)benzenesulfon amide

(R)-9-(4-( 1 -am inoethyl)pheny 1)

1080 -6,7-dichloro-8-hydroxythieno[

2,3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -aminoethy l)pheny 1)

1081 -6-chloro-8-hydroxythieno[2,3- c]quinolin-4(5H)-one

(S)-8-hydroxy-9-(4-(l -(methyla

1082 mino)ethyl)phenyl)thieno[2,3-c

]quinolin-4(5H)-one

9-(4-( 1 -aminoethy l)pheny l)-4-o

1083 xo-4,5-dihydrothieno[2,3-c]qui nolin-8-yl diethylcarbamate

4-(8-hydroxy-4-oxo-4,5-dihydr othieno[2,3-c]quinolin-9-yl)-N-

1084

(2-hydroxyethyl)-N-methylben zenesulfonamide

N-(2-hydroxyethy])-4-(8-metho xy-4-oxo-4,5-dihydrothieno[2,3

1085

-c]quinolin-9-yl)-N-methylbenz enesulfonamide

9-(4-((l H-pyrazol- 1 -yl)methy 1)

1086 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

8-hydroxy-9-(4-(2,2,2-trifluoro-

1 105 1 -hydroxyethyl)pheny l)thieno[

2,3-c]quinolin-4(5H)-one

9-(4-(2-aminopropyl)phenyl)-6-

1 106 chloro-8-hydroxythieno[2,3-c]q uinolin-4(5H)-one

N-(2-(4-(8-hydroxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-

1 107

y l)pheny l)-2-methy Ipropy l)met hanesulfonamide

9-(4-(2-(dimethylamino)propyl)

1 108 phenyl)-8-methoxythieno[2,3-c

]quinolin-4(5H)-one

9-(4-(l -aminoethyl)phenyl)thie

1 109

no[2,3-c]quinolin-4(5H)-one

9-(l -( 1 -(dimethylamino)propan -2-y 1)- 1 H-pyrazol-4-yl)-8-hydr

1 1 10

oxythieno[2,3-c]quinolin-4(5H)

-one

3-(4-(8-(2-(dimethylamino)etho xy)-4-oxo-4,5-dihydrothieno[2,

1 1 1 7

3-c]quinolin-9-yl)phenyl)propa nenitrile

(R)-9-(4-(l -aminopropyl)pheny

1 1 1 8 l)-8-methoxythieno[2,3-c]quino lin-4(5H)-one

N-(2-chloroethyl)-4-(8-hydroxy -4-oxo-4,5-dihydrothieno[2,3-c

1 1 19

]quinolin-9-yl)-N-methylbenze nesulfonamide

(S)-9-(4-(l -aminopropyl)pheny

1 1 20 l)-8-hydroxythieno[2,3-c]quino lin-4(5H)-one

(S)-9-(4-( l-aminopropyl)pheny

1 121 l)-8-methoxythieno[2,3-c]quino lin-4(5H)-one

(R)-9-(4-( 1 -aminoethyOphenyl)

1 122 -8-hydroxy-6-methylthieno[2,3

-c]quinolin-4(5H)-one

(S)-8-methoxy-9-(4-( 1 -(meth l

1 147 amino)propyl)phenyl)thieno[2,

3-c]quinolin-4(5H)-one

(S)-8-hydroxy-9-(4-( 1 -(methyla

1 148 mino)propyl)phenyl)thieno[2,3- c]quinolin-4(5H)-one

9-(4-( 1 -aminoethy l)pheny l)-8-( ((2-hy droxy ethy l)am ino)methy 1

1 149

)thieno[2,3-c]quinolin-4(5H)-o ne

(R)-9-(4-( 1 -aminopropy l)pheny

1 150 l)-6-bromo-8-hydroxythieno[2,

3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -(dimethy lamino)pr

1 151 opyl)phenyl)-8-hydroxythieno[

2,3-c]quinolin-4(5H)-one

8-hydroxy-9-(4-pentylphenyl)th

1 152

ieno[2,3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -am inopropy l)pheny

1 159 l)-6-chloro-8-hydroxythieno[2,

3-c]quinolin-4(5H)-one

·

(R)-9-(4-(l-aminopropan-2-yl)

1 160 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

(R)-9-(4-( 1 -aminopropan-2-y 1)

1 161 phenyl)-8-methoxythieno[2,3-c

]quinolin-4(5H)-one

^N 2-(4-(8-hydroxy-4-oxo-4,5-dih

1 162 ydrothieno[2,3-c]quinolin-9-yl) phenyl)butanenitrile

(S)-9-(4-( 1 -aminopropan-2-y l)p

1 163 henyl)-8-hydroxythieno[2,3-c]q uinolin-4(5H)-one

(S)-9-(4-( l-aminopropan-2-yl)p

1 164 henyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one

6-chloro-8-hydroxy-9-(4-(2-(m

1 165 ethylamino)ethyl)phenyl)thieno

[2,3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -aminopropan-2-y 1)

1 166 phenyl)-6-chloro-8-hydroxythie no[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-3,5-difluor

1 167 ophenyl)-8-hydroxythieno[2,3- c]quinolin-4(5H)-one

(R)-9-(4-( l -aminopropan-2-yl)

1 168 phenyl)-8-hydroxy-6-methylthi eno[2,3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -aminopropan-2-yl)

1 169 phenyl)-8-hydroxy-6-methylthi eno[2,3-c]quinolin-4(5H)-one

6-chloro-8-methoxy-9-(4-(2-(m

1 1 70 ethylamino)ethyl)phenyl)thieno

[2,3-c]quinolin-4(5H)-one

(S)-8-methoxy-9-(4-( 1 -(methyl

1 196 amino)propan-2-yl)phenyl)thie no[2,3-c]quinolin-4(5H)-one

(S)-8-hydroxy-9-(4-( 1 -(methy la

1 197 mino)propan-2-yl)phenyl)thien o[2,3-c]quinolin-4(5H)-one

4-(8-hydroxy-5-methyl-4-oxo-4 ,5-dihydrothieno[2,3-c]quinolin

1 198

-9-yl)-N-(2-hydroxyethyl)benze nesulfonamide

N-(2-bromoethyl)-4-(8-hydroxy -5-methyl-4-oxo-4,5-dihydrothi

1 199

eno[2,3-c]quinolin-9-yl)benzen esulfonamide

(R)-6-chloro-9-(4-( 1 -(dimethyl amino)propan-2-yl)phenyl)-8-

1200

methoxythieno[2,3-c]quinolin- 4(5H)-one

(R)-9-(4-( 1 -aminopropan-2-y 1)

1201 phenyl)-6-chloro-8-methoxythi eno[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-3-fluoroph

1214 enyl)-6-bromo-8-methoxythien o[2,3-c]quinolin-4(5H)-one

(S)-8-hydroxy-6-methy l-9-(4-( 1 -(methylamino)propan-2-yl)phe

1215

nyl)thieno[2,3-c]quinolin-4(5H

)-one

9-(4-(2-aminoethyl)-3-fluoroph

1216 enyl)-8-methoxy-6-methylthien o[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoet yl)-3-fluoroph

1217 enyl)-8-hydroxy-6-methylthien o[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-3-fluoroph

1218 enyl)-6-chloro-8-methoxythien o[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-3-fluoroph

1219 enyl)-6-chloro-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one 9-(4-(2-aminoethyl)-3-fluoroph enyl)-6-cyclopropyl-8-methoxy

1220

thieno[2,3-c]quinolin-4(5H)-on e

o

9-(4-(2-aminoethyl)-3-fluoroph

1221 enyl)-6-cyclopropyl-8-hydroxyt hieno[2,3-c]quinolin-4(5H)-one

(S)-8-methoxy-6-methyl-9-(4-( 1 -(methylamino)propan-2-yl)ph

1222

enyl)thieno[2,3-c]quinolin-4(5

H)-one

(S)-9-(4-( 1 -aminopropan-2-yl)p

1223 henyl)-8-methoxy-6-methylthie no[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-2-bromo-5

1224 -hydroxyphenyl)-8-hydroxythie no[2,3-c]quinolin-4(5H)-one

(S)-9-(4-(l -aminoethyl)phenyl)

1225 -8-hydroxy-6-methylthieno[2,3

-c]quinolin-4(5H)-one 3-(4-(8-hydroxy-6-methyl-4-ox

1226 o-4,5-dihydrothieno[2,3-c]quin olin-9-yl)phenyl)propanenitrile o

9-(4-(l -amino-2-methylpropan- 2-yl)phenyl)-8-methoxy-6-meth

1227

ylthieno[2,3-c]quinolin-4(5H)- one

9-(4-(l -amino-2-methylpropan- 2-yl)phenyl)-8-hydroxy-6-meth

1228

ylthieno[2,3-c]quinolin-4(5H)- one

2- (2-fluoro-4-(8-hydroxy-6-met hyl-4-oxo-4,5-dihydrothieno[2,

1229

3- c]quinolin-9-yl)phenyl)propa nenitrile

J

6-cyclopropyl-9-(4-(2-(dimethy lamino)ethyl)-3-fluorophenyl)-

1230

8-hydroxythieno[2,3-c]quinolin

-4(5H)-one

6-cyclopropyl-9-(4-(2-(dimethy lamino)ethyl)-3-fluorophenyl)-

1231

8-methoxythieno[2,3-c]quinoli n-4(5H)-one

3-(4-(8-methoxy-6-methyl-4-ox

1238 o-4,5-dihydrothieno[2,3-c]quin olin-9-yl)phenyl)propanenitrile

9-(4-(2-amino- 1 -cyclopentyleth

1239 yl)phenyl)-8-methoxythieno[2,

3-c]quinolin-4(5H)-one

9-(4-( 1 -amino-2-methy lpropan- 2-yl)phenyl)-6-cyclopropyl-8-h

1240

ydroxythieno[2,3-c]quinolin-4(

5H)-one

9-(4-(3-aminopropyl)phenyl)-8-

1241 methoxy-6-methy Ithieno [2,3 -c] quinolin-4(5H)-one

9-(4-(2-aminopropyl)phenyl)-8-

1242 hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one

9-(4-(2-aminopropyl)phenyl)-8-

1243 methoxy-6-methylthieno[2,3-c] quinolin-4(5H)-one

1

(R)-9-(4-( 1 -aminoethy l)pheny 1)

1256 -6-(difluoromethyl)-8-hydroxyt hieno[2,3-c]quinolin-4(5H)-one

9-(3-fluoro-4-(2-(methylamino) ethyl)phenyl)-8-methoxy-6-met

1257

hylthieno[2,3-c]quinolin-4(5H)

-one

9-(3-fluoro-4-(2-(methylamino) ethyl)phenyl)-8-hydroxy-6-met

1258

hylthieno[2,3-c]quinolin-4(5H)

-one

6-bromo-9-(4-(l -(dimethylamin o)-2-methy lpropan-2-y l)pheny 1

1259

)-8-hydroxythieno[2,3-c]quinol in-4(5H)-one

9-(4-(l -amino-2-methylpropan- 2-y l)pheny l)-6-ch loro-8-hydrox

1260

ythieno[2,3-c]quinolin-4(5H)-o ne

9-(4-(3-aminopropyl)phenyl)-8-

1261 hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one (R)-8-hydroxy-6-methyl-9-(4-(

1262 1 -(methylamino)ethyl)phenyl)t hieno[2,3-c]quinolin-4(5H)-one

0

9-(4-(2-aminoethyl)-3-chloroph

1263 enyl)-8-methoxy-6-methylthien o[2,3-c]quinolin-4(5H)-one

9-(4-(2-aminoethyl)-3-chloroph

1264 enyl)-8-hydroxy-6-methylthien o[2,3-c]quinolin-4(5H)-one

0

(R)-8-methoxy-6-methyl-9-(4-(

1265 1 -(methylamino)ethyl)phenyl)t hieno[2,3-c]quinolin-4(5H)-one

0

9-(4-(2-aminopropyl)phenyl)-6-

1266 ethyl-8-hydroxythieno[2,3-c]qu inolin-4(5H)-one o

(R)-9-(4-( l-aminoethyl)phenyl)

1267 -6-butyl-8-hydroxythieno[2,3-c

]quinolin-4(5H)-one

9-(4-(l -aminopropan-2-yl)-3-ch

1280 lorophenyl)-8-hydroxythieno[2,

3-c]quinolin-4(5H)-one

9-(4-(2-amino-2-methylpropyl)

1281 phenyl)-8-methoxythieno[2,3-c

]quinolin-4(5H)-one

9-(4-(2-amino-2-methylpropyl)

1282 phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

9-(4-( 1 -am ino-3 -methy lbutan-2 -yl)-3-fluorophenyl)-8-methoxy

1 283

-6-methylthieno[2,3-c]quinolin- 4(5H)-one

8-methoxy-6-methyl-9-(4-(3-m ethyl- 1 -(methy lamino)butan-2-

1284

yl)phenyl)thieno[2,3-c]quinolin

-4(5H)-one

8-hydroxy-6-methyl-9-(4-(3-me thyl- 1 -(methylamino)butan-2-yl

1285

)phenyl)thieno[2,3-c]quinolin-4

(5H)-one

3-(4-((8-methoxy-6-methyl-4-o xo-4,5-dihydrothieno[2,3-c]qui

1334

nolin-9-yl)amino)phenyl)propa nenitrile

9-((3-(2-aminoethyl)phenyl)am

1335 ino)-8-methoxy-6-methy 1th ieno

[2,3-c]quinolin-4(5H)-one o

9-((4-(2-aminoethyl)phenyl)am

1336 ino)-8-hydroxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one

9-(4-(2-(ethy lam ino)propy l)phe

1337 nyl)-8-hydroxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one

9-(4-(3-(aminomethyl)pentan-3

1338 -yl)phenyl)-8-methoxythieno[2,

3-c]quinolin-4(5H)-one

2-(hydroxy(piperidin-4-yl)meth

1351 yl)-8-methoxy-6-methylthieno[

2,3-c]quinolin-4(5H)-one

(R)-9-(4-(l-aminobutan-2-yl)ph

1352 enyl)-8-hydroxy-6-methylt ien o[2,3-c]quinolin-4(5H)-one

(R)-9-(4-( 1 -aminopropan-2-y 1) phenyl)-2-chloro-8-hydroxy-6-

1353

methylthieno[2,3-c]quinolin-4(

5H)-one

(R)-9-(4-( 1 -aminopropan-2-y 1) phenyl)-2-chloro-8-methoxy-6-

1354

methylthieno[2,3-c]quinolin-4(

5H)-one

8-methoxy-6-methy l-9-(4-(2-(

1355 methylamino)ethyl)phenyl)thie no[2,3-c]quinolin-4(5H)-one

9-(4-(2-(ethyl(methyl)amino)et hyl)phenyl)-8-hydroxy-6-methy

1356

lthieno[2,3-c]quinolin-4(5H)-o ne

8-methoxy-6-methyl-9-(4-(2-(

1393 methylsulfinyl)ethyl)phenyl)thi eno[2,3-c]quinolin-4(5H)-one

8-hy droxy-6-methy l-9-(4-((met

1394 hylsulfonyl)methyl)phenyl)thie no[2,3-c]quinolin-4(5H)-one o

(4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinoli

1395

n-9-yl)phenyl)methanesulfona mide

o

1

9-(4-((2-aminoethyl)(methyl)a mino)phenyl)-8-methoxy-6-met

1396

hylthieno[2,3-c]quinolin-4(5H)

-one

(R)-N-(2-(2-fluoro-4-(8-hydrox y-6-methyl-4-oxo-4,5-dihydrot

1397

hieno[2,3-c]quinolin-9-yl)phen yl)propyl)methanesulfonamide

(R)-N-(2-(2-fluoro-4-(8-methox y-6-methyl-4-oxo-4,5-dihydrot

1398

hieno[2,3-c]quinolin-9-yl)phen yl)propyl)methanesulfonamide

5-(8-methoxy-6-methyl-4-oxo-

1405 4,5-dihydrothieno[2,3-c]quinoli n-9-y l)n icotinam ide

« Γ 2-(5-(8-hydroxy-4-oxo-4,5-dih

1406 ydrothieno[2,3-c]quinolin-9-yl) pyridin-2-yl)propanenitrile

2-(4-(8-methoxy-6-methyl-4-ox

1407 o-4,5-dihydrothieno[2,3-c]quin olin-9-yl)phenyl)propanamide

9-(6-( 1 -aminopropan-2-y l)pyrid

1408 in-3-yl)-8-methoxy-6-methylthi eno[2,3-c]quinolin-4(5H)-one

^N 2-(5-(8-methoxy-6-methyl-4-ox o-4,5-dihydrothieno[2,3-c]quin

1409

olin-9-yl)pyridin-2-yl)-2-methy lpropanenitrile

2-hydroxy-2-(4-(8-hydroxy-4-o xo-4,5-dihydrothieno[2,3-c]qui

1410

nolin-9-yl)phenyl)propane- 1 -su lfonamide N-(tert-butyl)-2-hydroxy-2-(4-(

8-methoxy-4-oxo-4,5-dihydroth

141 1

ieno[2,3-c]quinolin-9-yl)phenyl )propane- 1 -sulfonamide

2-(4-(8-hydroxy-6-methyl-4-ox

1412 o-4,5-dihydrothieno[2,3-c]quin olin-9-yl)phenyl)propanamide

2-(4-(8-hydroxy-4-oxo-4,5-dih

1413 ydrothieno[2,3-c]quinolin-9-yl) pheny l)propane- 1 -sulfonamide

9-(4-(2-amino- 1 -fluoroethy l)ph

1414 enyl)-8-methoxy-6-methylthien o[2,3-c]quinolin-4(5H)-one

9-(6-(l -aminopropan-2-yl)pyrid

141 5 in-3-yl)-8-hydroxy-6-methylthi eno[2,3-c]quinolin-4(5H)-one

2-(5-(8-hydroxy-6-methyl-4-ox o-4,5-dihydrothieno[2,3-c]quin

1416

olin-9-yl)pyridin-2-yl)-2-methy Ipropanenitrile

N-ethy 1- 1 -(4-(8-hydroxy-6-met hyl-4-oxo-4,5-dihydrothieno[2,

1429

3-c]quinolin-9-yl)phenyl)metha nesulfonamide

1 -(4-(8-methoxy-6-methy 1-4-ox o-4,5-dihydrothieno[2,3-c]quin

1430

olin-9-yl)phenyl)ethanesulfona mide

1 -(4-(8-methoxy-4-oxo-4,5-dih

1431 ydrothieno[2,3-c]quinolin-9-yl) phenyl)ethanesulfonamide

(R)-N-(2-(4-(8-methoxy-4-oxo- 4,5-dihydrothieno[2,3-c]quinoli

1432

n-9-yl)phenyl)propyl)methanes ulfonamide

(R)-N-(2-(4-(8-hydroxy-4-oxo- 4,5-dihydrothieno[2,3-c]quinoli

1433

n-9-yl)phenyl)propyl)-N-methy lmethanesulfonamide o

(R)-N-(2-(4-(8-hydroxy-6-meth yl-4-oxo-4,5-dihydrothieno[2,3

1434

-c]quinolin-9-yl)phenyl)propyl) methanesulfonamide (R)-N-(2-(4-(8-hydroxy-4-oxo- 4,5-dihydrothieno[2,3-c]quinoli

1435

n-9-y l)pheny l)propy l)methanes

ulfonamide

o

(R)-N-(2-(4-(8-methoxy-4-oxo- 4,5-dihydrothieno[2,3-c]quinoli

1436

n-9-yl)phenyl)propyl)-N-methy

Imethanesulfonamide

o

(R)-N-(2-(4-(8-hydroxy-6-meth yl-4-oxo-4,5-dihydrothieno[2,3

1437

-c]quinolin-9-yl)phenyl)propyl) -N-methy Imethanesulfonamide

0

(R)-N-(2-(4-(8-methoxy-6-met hyl-4-oxo-4,5-dihydrothieno[2,

1438 3-c]quinolin-9-yl)phenyl)propy

l)-N-methylmethanesulfonamid

e

0

The compound of formula (I) of the present invention may be in the form of a pharmaceutically acceptable salt derived from an inorganic or organic acid. Representative examples of the pharmaceutically acceptable salt derived from an inorganic or organic acid include salts obtained by adding to the compound of formula (I) an inorganic acid including, but not limited to hydrochloric acid, hydrobromic acid, phosphoric acid or sulfonic acid, or organic carboxylic acids such as acetic acid, trifluoroacetic acid, citric acid, formic acid, maleic acid, oxalic acid, succinic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, ascorbic acid or malic acid, methanesulfonic acid, or para toluenesulfonic acid, which do not limit its scope. Such acids may be prepared by the conventional processes, and other acids, which themselves are not pharmaceutically acceptable, including oxalic acid may be employed in the preparation of the salts.

Alternatively, the compound of formula (I) of the present invention may also be in the form of a pharmaceutically acceptable salt derived from an inorganic or organic base include salts obtained by adding an inorganic or organic base. For example, alkalis including sodium hydroxide or potassium hydroxide, or alkaline earth metal hydroxides including calcium hydroxide, magnesium hydroxide, aluminum hydroxide or ammonium hydroxide may be used for the preparation of inorganic salt of the compound. Further, organic bases including triethylamine or diisopropylethylamine may also be used for the preparation of organic salt of the compound.

The compounds of formula (1) may be prepared as in Scheme (I) and (II).

Cy, Cy₂ Cy₃

A variety of acids A whose structure is defined by the cycles (Cyi.3) shown in Scheme I, were converted to the corresponding acid chloride and then coupled with the requisite aniline to afford coupled products B. In the case where R5 = H, the amide was protected to obtain intermediates C which subsequently underwent the key intramolecular Heck cyclization using bis-tri-t-butyl phosphine as the catalyst of choice. This provided tricycles D which included some compounds of Formula I, II and III. In some instances tricycles D were brominated using NBS or nitrated using potassium nitrate and trifluoroacetic anhydride to provide products E (Scheme I).

Scheme (II)

Formula I, II and I II Formula I, II and III Formula I, H and III

R₃ = OCH₃ or OH

and R , = CI or Br

cy₂ cy₃

The aryl bromides F were either purchased or prepared and then converted to the corresponding boronic acids or boronate esters G via standard conditions. Bromides E underwent Suzuki or Buchwald type cross-coupling eactions with the requisite boronate esters or boronic acids G to afford compounds H some of which are compounds of Formula I, II and III. In cases where R3 = OCH3, treatment of compounds H (via path ) with boron tribromide or aluminum chloride provided the de-methylated compounds I which includes compounds of Formula I, II and III (Scheme II). Additionally, treatment of compounds H (via path /^' ) with NCS or NBS afforded compounds I containing a halogen at Ri . These halogenated compounds were treated with boron tribromide or aluminum chloride to provide the de-methylated compounds I. Finally, compounds with R| = Br were reacted with trimethylboroxine and palladium catalyst to afford compounds J of formula I, II and III where R| = CH₃. Treatment of these compounds with boron tribromide afforded compounds of formula I, II and III.

A salt, hydrate, solvate and isomer of the inventive compound of formula (I) or (II) may be prepared by employing any of the known methods. The inventive compound of formula (I) or (II), or a salt, hydrate, solvate or isomer thereof, may be used for the treatment of

PB -dependent diseases such as cancer. The treatment of PB -dependent diseases can be accomplished by way of inhibiting PB activity. The inventive compound typically have an IC5₀ value (micro M) in the range of 0.0001 to 100, for example 0.001 to 50, preferably 0.001 to 10, more preferably 0.001 to 5.

Accordingly, the present invention includes a pharmaceutical composition that includes a therapeutically effective amount of the compound of formula (I) or (II), a salt, hydrate, solvate or isomer thereof as an active ingredient and a pharmaceutically acceptable carrier. The pharmaceutical composition of the present invention can be used to treat or prevent

PBK-dependent diseases. A pharmaceutical formulation may be prepared in accordance with any of the conventional procedures. In preparing the formulation, the active ingredient is preferably admixed or diluted with a carrier, or enclosed within a carrier, sachet or other container. The carrier may be a solid, semi-solid or liquid material acting as a vehicle, excipient or medium for the active ingredient. The formulations may be in the form of a tablet, pill, powder, sachet, elixir, suspension, emulsion, solution, syrup, aerosol, soft and hard gelatin capsule, sterile injectable solution, sterile packaged powder and the like.

Examples of suitable carriers, excipients, and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose,

polyvinylpyrrolidone, water, and mineral oil. The formulations may additionally include fillers, antiemulsifiers, preservatives and the like. The compositions of the invention may be formulated to provide immediate, sustained or delayed release of the active ingredient after their administration to a mammal by employing any of the procedures well known in the art.

The pharmaceutical composition of the present invention can be administered via various routes including oral, transdermal, subcutaneous, intravenous and intramuscular administration.

In addition to the above, the present composition may contain other pharmaceutical active ingredients so long as they do not inhibit the in vivo function of the compound of the present invention. The compounds as disclosed herein can be co-administered with a second therapeutic agent, such as a chemotherapeutic agent. The term "co-administer" means to administer more than one active agent, such that the duration of physiological effect of one active agent overlaps with the physiological effect of a second active agent. For systematic agents, the term co-administer means that more than one active agent is present in the

bloodstream during at least one time point. Co-administration includes administering two active agents simultaneously, approximately simultaneously, or sequentially in any order. In some embodiments, co-administration can be accomplished by co-formulation, i.e., preparing a single dosage unit including both active agents.

"Treating" the disease includes one or more of: addressing a physiological cause of the disease, addressing a physiological cause of a disease symptom, reducing the severity of the disease, ameliorating a symptom of the disease, and shortening the duration of the

disease. "Preventing" the disease includes eliminating or delaying the onset of a disease or its symptoms.

The compounds disclosed herein can be used to treat or prevent PBK-dependent diseases, including cancer. It has been shown that PBK is a target for treating cancers, such as breast cancer (Example 504 of the present specification), bladder cancer (WO2006/085684), and small cell lung cancer (WO2007/013665). Accordingly, cancers to be targeted include, but are not limited to, breast cancer, bladder cancer, and small cell lung cancer. For example, the present invention provides methods for treating or preventing PBK-dependent diseases, including cancer, in a subject by administering to said subject the compounds disclosed herein. In a preferred embodiment, such compound can be administered to the subject in the form of pharmaceutical composition including the compound of the present invention and

pharmaceutically or physiologically acceptable carrier. The pharmaceutical composition of the present invention can be administered via various routes including oral, transdermal,

subcutaneous, intravenous and intramuscular introduction for treating PBK dependent diseases, including cancer, in a subject.

In another embodiment, the present invention also provides the use of the compound of the present invention in manufacturing a pharmaceutical composition for treating a PBK dependent diseases including cancer. For example, the present invention relates to a use of the compound of the present invention for manufacturing a pharmaceutical composition for treating PBK dependent diseases, including cancer. In another embodiment, the compounds of the present invention can be used in treating PBK dependent diseases, including cancer.

In another embodiment, the present invention also provides a method or process for manufacturing a pharmaceutical composition for treating a PBK dependent diseases including cancer, wherein the method or process includes a step for admixing an active ingredient with a pharmaceutically or physiologically acceptable carrier, wherein the active ingredient is the compound of the present invention.

The dosage and method of administration vary according to the body weight, age, and symptoms of the patient; however, one skilled in the art can suitably select them.

For example, the dose is generally about 0.1 mg to about 100 mg per day, preferably about 1.0 mg to about 50 mg per day and more preferably about 1 .0 mg to about 20 mg per day, when administered orally to a normal adult human (weight 60 kg).

When administering the compound parenterally, in the form of an injection to a normal adult human (weight 60 kg), although there are some differences according to the patient, target organ, symptoms and method of administration, it is convenient to intravenously inject a dose of about 0.01 mg to about 30 mg per day, preferably about 0.1 to about 20 mg per day and more preferably about 0.1 to about 10 mg per day. In the case of other animals, the appropriate dosage amount may be routinely calculated by converting to 60 kg of body weight. Examples

The following examples are intended to further illustrate the present invention without limiting its scope.

General Procedure A (Scheme I):

Step 1 : To a suspension of the requisite carboxylic acid A (1 mol) in CH2CI2 (0.1 - 0.5 M) at room temperature was added (COC\)₂ (2 mol) followed by the addition of catalytic DMF. The reaction mixture was stirred at room temperature for 1 8 h, concentrated and dried under high vacuum to obtain the intermediate acid chloride. The acid chloride was dissolved in CH2CI2 (0.1-0.3 M) followed by the addition of Et₃N ( 1 .5 - 2 mol) and the requisite aniline (1 .1 mol) and the reaction was stirred at room temperature for 1 8 h. The reaction mixture was concentrated, triturated with an appropriate solvent or purified by flash chromatography to obtain amide B as a solid.

Step 2: To a solution of amide B ( 1 mol) in THF (0.1 - 0.3 M) at 0 °C was added NaH (1.2 mol) and the reaction was warmed up to 45 °C for 15 min and cooled to 0 °C followed by the addition of (Boc)₂0 (2 mol). The reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was quenched by slowly pouring it into a stirred solution of water and satd aq NaHC0₃ at 0 °C. The mixture was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over Na2S0₄ and concentrated. The residue was triturated with an appropriate solvent or purified by flash chromatography to obtain C as a solid.

Step 3 : Intermediate C (1 mol), bis(tri-tert-butylphosphine)palladium (5 mol%) and potassium acetate ( 4 mol) were added to a Parr pressure reactor followed by the addition of dimethyl acetamide (0.3 M). The reaction mixture was sparged with nitrogen for 30 min followed by heating at 140- 1 50 °C for 4 h. The reaction mixture was cooled and quenched by pouring into brine at 0 °C. The resulting precipitate was filtered and the filter cake was washed with water and ether to obtain crude D as a solid. Step 4: To a solution of crude D (1 mol) in CH₂Cl₂:AcOH (1 : 1) was added NBS (1 mol) and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was quenched by pouring slowly into a stirred solution of ice and satd aq Na₂C(¾. Once the aqueous layer was at pH 8 the layers were separated and the CH₂C1₂ layer was concentrated, triturated with acetonitrile and filtered to obtain E as solid.

Example 392

4-(tert-Butyldimethylsilyloxy)aniline

To a solution of 4-aminophenol (1 1 g, 100 mmol) and imidazole (10 g, 150 mmol) in THF (250 mL) was added tert-butyldimethylsilyl chloride (18 g, 120 mmol) and the reaction was stirred at room temperature for 18 h. The reaction mixture was poured into water and extracted with diethyl ether. The combined organic layers were dried over Na S0₄, filtered, concentrated and the residue was purified by column chromatography to afford the desired product (15 g, 67%): ESI MS m/z 224 [C,₂H₂₁NOSi + H]⁺.

Example 393

3-Bromo-N-[4-(tert-butyldimethylsilyloxy)phenyl]thiopherie-2-carboxamide

Following Step 1 from General Procedure A, 5-bromothiophene-2-carboxylic acid (3.0 g, 14 mmol) was reacted with 4-(tert-butyldimethylsilyloxy)aniline (4.2 g, 19 mmol) to afford the desired product (4.4 g, 73%) as a solid: ESI MS m/z 413 [C_]7H₂₂BrN0₂SSi + H]⁺.

Example 394

tert-Butyl 3-Bromothiophene-2-carbonyl[4-(tert-butyldimethylsilyloxy)phenyl]carbamate

Following Step 2 from General Procedure A,

3-bromo-N-[4-(tert-butyldimethylsilyloxy)phenyl]thiophene-2-carboxamide (4.4 g, 1 1 mmol) was reacted with di-tert-butyl dicarbonate (4.6 g, 21 mmol) to afford the desired product (1 .5 g, 28%) as a solid: ESI MS m/z 513 [C₂₂H₃₀BrNO₄SSi + H]⁺.

Example 395

8-(tert-Butyldimethylsilyloxy)thieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A, tert-butyl

3-bromothiophene-2-carbonyl[4-(tert-butyldimethylsilyloxy)phenyl]carbamate (1.0 g, 2.0 mmol) was reacted with bis(tri-tert-butylphosphine)palladium (50 mg, 0.098 mmol) to afford the product (740 mg, quant.) as a solid: ESI MS m/z 332 [C₁₇H₂iN0₂SSi + H]⁺.

Example 396

9-Bromo-8-(tert-butyldimethylsilyloxy)thieno[2,3-c]quinolin-4(5H)-one

Following Step 4 from General Procedure A,

8-(tert-butyldimethylsilyloxy)thieno[2,3-c]quinolin-4(5H)-one (740 mg, 2.2 mmol) was reacted with N-bromosuccinimide (480 mg, 2.7 mmol) to afford the desired product (340 mg, 37%) as a brown solid: ESI MS m/z 41 1 [C₁₇H₂₀BrNO₂SSi + H]⁺.

Example 397

N-(2-Bromo-4-methoxyphenyl)-5-methyl-N-(5-methylthiophene-2-carbonyl)thiophene-2-carbox amide

Following Step 1 from General Procedure A, 5-methylthiophene-2-carboxylic acid (8.5 g, 60 mmol) was reacted with 2-bromo-4-methoxyaniline (6.7 g, 30 mmol) to afford the desired product (5.0 g, 57%) as a solid: ESI MS m/z 327 [C,₃H₁₂BrN0₂S + H]⁺.

Example 398

8-Methoxy-2-methylthieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A,

N-(2-bromo-4-methoxyphenyl)-5-methyl-N-(5-methylthiophene-2-carbonyl)thiophene-2-carbox amide (500 mg, 1.1 mmol) was reacted with bis(tri-tert-butylphosphine)palladium (45 mg, 0.089 mmol) to afford the desired product (1.3 g, 48%) as a green solid: ESI MS m/z 246

[C13Hi ,N0₂S + H]⁺.

Example 399

9-Bromo-8-methoxy-2-methylthieno[2,3-c]quinolin-4(5H)-one

Following Step 4 from General Procedure A,

8-methoxy-2-methylthieno[2,3-c]quinolin-4(5H)-one (1.4 g, 5.7 mmol) was reacted with

N-bromosuccinimide (1.2 g, 6.9 mmol) to afford the desired product (740 mg, 40%) as a brown solid: ESI MS m/z 325 [C,₃H|₀BrNO₂S + H]⁺.

Example 400

3-bromo-N-(2-fluoro-4-methoxyphenyl)thiophene-2-carboxamide

Following Step 1 from General Procedure A, 3-bromothiophene-2-carboxylic acid (7.3 g, 35 mmol) was reacted with 2-fluoro-4-methoxyaniline (5.0 g, 35 mmol) to afford the desired product (10 g, 90%) as an orange solid: ESI MS m/z 331 [Ci₂H₁₀FNO₂S + H]⁺.

Example 401

tert-butyl 3-bromothiophene-2-carbonyl(2-fluoro-4-methoxyphenyl)carbamate

Following Step 2 from General Procedure A, 3-bromo-N-(2-fluoro-4-methoxyphenyl) thiophene-2-carboxamide(12 g, 35 mmol) was reacted with di-tert-butyl dicarbonate (12 g, 53 mmol) to afford the desired product (14 g, >99%) as an orange solid: ESI MS m/z 331

Example 402

6-Fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A, tert-butyl 3-bromothiophene-2-carbonyl(2- fluoro-4-methoxyphenyl)carbamate (2.0 g, 4.6 mmol) was reacted with

bis(tri-tert-butylphosphine)palladium ( 100 mg, 0.20 mmol) to afford the desired product (950 mg, 80%) as a dark brown solid: ESI MS m/z 250

+ H]⁺.

Example 403

9-Bromo-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following Step 4 from General Procedure A,

6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.0 g, 4.0 mmol) was reacted with N-bromosuccinimide (570 mg, 4.8 mmol) to afford the desired product (800 mg, 61%) as a brown solid: ESI MS m/z 329 [C,₂H₇BrFN0₂S + H]⁺.

Example 404

3-Bromo-N-(2,3-difluoro-4-methoxyphenyl)thiophene-2-carboxamide

Following Step 1 from General Procedure A, 3-bromothiophene-2-carboxylic acid (1.3 g, 6.3 mmol) was reacted with 2,3-difluoro-4-methoxyaniline (960 mg, 7.5 mmol) to afford the desired product (2.2 g, >99%): ESI MS m/z 349 [C^HsBrFzNC^S + H]⁺.

Example 405

tert-Butyl 3-Bromothiophene-2-carbonyl(2,3-difluoro-4-methoxyphenyl)carbamate

Following Step 2 from General Procedure A,

3-bromo-N-(2,3-difluoro-4-methoxyphenyl)thiophene-2-carboxamide (2.4 g, 7.00 mmol) was reacted with di-tert-butyl dicarbonate (330 mg, 14 mmol) to afford the desired product (2.1 g, 67%) as a white solid: ESI MS m/z 448 [Ci₇H,₆BrF₂N0₄S + H]⁺.

Example 406

6,7-Difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A, tert-butyl

3-bromothiophene-2-carbonyl(2,3-difluoro-4-methoxyphenyl)carbamate ( 1.4 g, 3.1 mmol) was reacted with bis(tri-tert-butylphosphine)paIladium (80 mg, 0.15 mmol) to afford the desired product (58 mg, 65%) as a brown solid: ESI MS m/z 268 [Ci2H₇F₂N0₂S + H]⁺.

Example 407

9-Bromo-6,7-difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following Step 4 from General Procedure A,

6,7-difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (300 mg, 1.1 mmol) was reacted with N-bromosuccinimide (400 mg, 2.2 mmol) to afford the desired product (200 mg, 57%) as a yellow solid: ESI MS m/z 347 [CnHeBrFjNChS + H]⁺.

Example 510

3-bromo-N-(4-methoxy-2-methylphenyl)thiophene-2-carboxamide

Following Step 1 from General Procedure A, 3-bromothiophene-2-carboxylic acid (6.7 g, 49 mol) was reacted with 2-methyl-4-methoxyaniline (12 g, 53 mmol) to afford the desired product (13 g, 80%) as an orange solid: ESI MS m/z 331 [C₁₂H,oFN0₂S + H]⁺.

Example 51 1

tert-butyl 3-bromothiophene-2-carbonyl(4-methoxy-2-methylphenyl)carbamate

Following Step 2 from General Procedure A, 3-bromo-N-(4-methoxy-2-methylphenyl) thiophene-2-carboxamide (12 g, 37 mmol) was reacted with di-tert-butyl dicarbonate (9.6 g, 44 mmol) to afford the desired product (15 g, 96%) as an orange solid: ESI MS m z 331

[C,2H₁₀FNO2S + H]⁺.

Example 512

8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A, tert-butyl 3-bromothiophene-2-carbonyl(4- methoxy-2-methylphenyl)carbamate (14 g, 33 mmol) was reacted with

bis(tri-tert-butylphosphine)palladium (750 mg, 1 .5 mmol) to afford the desired product (7.0 g, 85%) as a dark brown solid: ESI MS m/z 250 [Ci₂H₈FN0₂S + H]⁺.

Example 513

9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Following Step 4 from General Procedure A, 8-methoxy-6-methylthieno[2,3-c]

quinolin-4(5H)-one (6.4 g, 26 mmol) was reacted with N-bromosuccinimide (5.0 g, 26 mmol) to afford the desired product (7.0 g, 82%) as a brown solid: ESI MS m/z 329 [Ci₂H₇BrFN0₂S + H]⁺.

Example 514

3-Bromo-N-(4-methoxyphenyl)thiophene-2-carboxamide

Following Step 1 from General Procedure A, 5-bromothiophene-2-carboxylic acid (75 g, 360 mmol) was reacted with 4-methoxyaniline (54 g, 430 mmol) to afford the desired product (1 1 0 g, 93%) as a solid: ESI MS m/z 313 [Ci₂Hi₀BrNO₂S + H]⁺. Example 515

tert-Butyl 3-bromothiophene-2-carbonyl(4-methoxyphenyl)carbamate

Following Step 2 from General Procedure A, 3-Bromo-N-(4-methoxyphenyl)thiophene-2- carboxamide (60 g, 190 mmol) was reacted with di-tert-butyl dicarbonate (83 g, 380 mmol) to afford the desired product (65 g, 82%) as a solid: ESI MS m/z 413 [Ci₇Hi₈BrN0₄S + H]⁺.

Example 516

8-Methoxythieno[2,3-c]quinolin-4(5H)-one

Following Step 3 from General Procedure A, tert-butyl 3-bromothiophene-2-carbonyl (4-methoxyphenyl)carbamate (62 g, 150 mmol) was reacted with bis(tri-tert-butylphosphine) palladium (3.7 g, 5 mol%) to afford the crude desired product (26 g) as a grey-brown solid: ESI MS m/z 232 [Ci₂H₉N0₂S + H]⁺.

Example 517

9-Bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one

General Procedure B (Scheme II):

To a solution of bromides E (1 mmol) in DMF was added Cs₂C0₃ (3 mmol), Pd(dppf)Cl2 (0.1 mmol) and boronate esters or acids G (1 - 2 mmol) and the reaction was heated at 80 °C for 18 h. The reaction mixture was cooled, concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) or preparatory HPLC (CI 8 silica, acetonitrile/water with 0.05% TFA gradient) to obtain the desired products H. In some instances the desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure C (Scheme II):

The compound from General Procedure B (1 mmol) was dissolved in TFA (10 mmol) and stirred at room temperature for 2 h and concentrated. The residue was eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia) to obtain the desired product as the free base. In some instances the desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure D- l (Scheme II):

The requisite compound (1 mmol) was dissolved in methanol followed by the addition of 2 N HC1 in diethylether (100 mmol). The reaction mixture was stirred at room temperature for 2 h and filtered or concentrated to obtain the desired product as the hydrochloride salt.

General Procedure D-2 (Scheme II):

The requisite compound was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure D-3 (Scheme II):

The requisite compound (1 mmol) was dissolved in aqueous HC1 (100 mmol) and stirred concentrated at room temperature for 2 h, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure E - One Pot (Scheme II):

To a solution of aryl bromides F ( 1 mmol) in dioxane was added KOAc (2 mmol), Pd(dppf)Cb (0.1 mmol) and bis(pinacolato)diboron (1.5 mmol) and the reaction was heated at 90 °C until the aryl bromide was consumed. To the reaction mixture was added Cs₂CC>3 (2 mmol) and bromides E (0.5 mmol) and heating was continued for 18 h. The reaction mixture was cooled, concentrated and purified by chromatography (silica, ethyl acetate/hexanes gradient) or preparatory HPLC (CI 8 silica, acetonitrile/water with 0.05% TFA gradient) to obtain the desired products I. In some instances the desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure F (Scheme 11):

To a solution or suspension of compounds H, I, or J (R3 = OCH3) ( 1 mmol) in CH2CI2 at 0 °C was added BBr₃ (6 - 10 mmol) and the reaction was warmed to room temperature for 18 h or until the starting material disappeared by LCMS analysis. The reaction was quenched by pouring onto ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (C I 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and eluted through an ion-exchange column (using methanol and 7 N methanol in ammonia) to obtain the desired product. In some instances the desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt.

General Procedure G (Scheme II):

To a solution of aryl bromides F ( 1 mmol) in dioxane was added KOAc (2 mmol), Pd(dppf)Cl₂ (0.1 mmol) and bis(pinacolato)diboron (1 .5 mmol) and the reaction was heated at 90 °C for 1 8 h. The reaction mixture was cooled, concentrated and the residue was purified by column chromatography (silica, ethyl acetate hexanes gradient) to obtain the desired product.

General Procedure H (Scheme II):

To a solution requisite compound H ( 1 .0 mmol) in DMF was added N-chlorosuccinimide ( 1 .2 mmol) and the reaction was stirred at room temperature for 30 min and heated at 60 °C for 2 h. The reaction mixture was concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product I.

General Procedure I (Scheme II):

To a solution requisite compound H (1 .0 mmol) in DMF was added N-bromosuccinimide ( 1 .2 mmol) and the reaction was stirred at room temperature for 30 min and heated at 50 °C for 2 h. The reaction mixture was concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product I.

General Procedure J (Scheme II):

To a solution requisite compound I (1 .0 mmol) in toluene, was added tripotassium phosphate (4.0 mmol), trimethylboroxine (3.0 mmol), water (0.60 M) and Pd(PPh₃)₄ (0.10 mmol) the reaction mixture degassed and heated at 120 °C for 2 hr. The reaction mixture was cooled, concentrated and the residue was purified by column chromatography (silica, ethyl

acetate/hexanes gradient) to afford the desired product J.

Example 518

(S)-tert-Butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (670 mg, 2.2 mmol) was reacted with (S)-tert- butyl methyl(l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan- 2-yl)phenyl) propyl) carbamate (1.3 g, 3.4 mmol) to afford the desired product (700 mg, 48%) as a light brown solid: ESI MS m/z 479

+ H]⁺. Example 519

(S)-tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

mate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (240 mg, 0.32 mmol) was reacted with (S)-tert-butyl 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)phenyl)propylcarbamate (3.5 g, 9.7 mmol) to afford the desired product ( 1.4 g, 32%) as a light brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 520

tert-Butyl ( l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (830 mg, 2.7 mmol) was reacted with tert-butyl( l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2

-yl)phenyl)cyclopropyl)methylcarbamate ( 1 .5 g, 4.0 mmol) to afford the desired product (670 mg, 52%) as a light brown solid: ESI MS m/z 477 [C27H28N2O4S + H]⁺.

Example 521

-Butyl ( l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno

quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ( 1 50 mg, 0.46 mmol) was reacted with tert-butyl( l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2 -yl)phenyl)cyclopropyl)methylcarbamate (260 mg, 0.69 mmol) to afford the desired product ( 150 mg, 68 %) as a light brown solid: ESI MS m/z 491 [C28H30N2O4S + H]⁺. Example 522

(£)-tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one( 2.5 g, 8.1 mmol) was reacted with (S)-tert-butylmethyl(2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan -2-yl)phenyl)propyl)carbamate (4.6 g, 12 mmol) to afford the desired product (1 .9 g, 50%) as a light brown solid: ESI MS m/z 479 [C27H₃₀N2O4S + H]⁺.

Example 523

(S)-tert-Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ( 150 mg, 0.46 mmol) was reacted with (S)-tert-butyl-2-(4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (251 mg, 0.69 mmol) to afford the desired product (140 mg, 62%) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 524

(S)-tert-Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno

quinolin-9-yI)phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ( 1 50 mg, 0.46 mmol) was reacted with (S)-tert-butyl2-(4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan- 2-yl)phenyl)propylcarbamate (251 mg, 0.69 mmol) to afford the desired product (135 mg, 62%) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 525 tert-Butyl 2-chloro-4-(8-methoxy-4-oxo-4,5-dihydrothi<

quinolin-9-yl)phenethylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (3.0 g, 9.7 mmol) was reacted with tert-butyl 2-chloro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan

-2-yl)phenethylcarbamate (5.53 g, 14.5 mmol) to afford the desired product (2.65 g, 57%) as a light brown solid. ESI MS m/z 485 [C25H25CIN2O4S + H]⁺.

Example 526

(R)-tert-Butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (1 50 mg, 0.46 mmol) was reacted with (R)-tert-butylmethyl(l -(4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl)ethyl)carbamate (250 mg, 0.69 mmol) to afford the desired product (145 mg, 66 %) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 527

(R)-tert-Butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)ethyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1 .4 g, 4.4 mmol) was reacted with (R)-tert-butylmethyl( l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) phenyl)ethyl)carbamate (2.4 g, 6.6 mmol) to afford the desired product ( 1 .4 g, 66%) as a light brown solid: ESI MS m/z 465 [C₂₆H2₈ 20₄S + H]⁺.

Example 528

tert-Butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)-2-methylpropylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one ( 1.4 g, 4.3 mmol) was reacted with tert-butyl2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)-2-methylpropylcarbamate (2.5 g, 6.4 mmol) to afford the desired product (1.7 g, 79%) as a light brown solid. ESI MS m/z 497 [C27H29FN2O4S + H]⁺.

Example 529

tert-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)-2-methylpropylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.46 mmol) was reacted with tert-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)-2-methylpropylcarbamate (270 mg, 0.64 mmol) to afford the desired product (130 mg, 56 %) as a light brown solid: ESI MS m/z 51 1 [C28H31FN2O4S + H]⁺.

Example 530

tert-Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)butylcarbamate

BocHN

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.46 mmol) was reacted with tert-butyl 2-(4-(4,4,5,5-tetramethyI-l ,3,2-dioxaborolan- 2-yl)phenyl)butylcarbamate (240 mg, 0.64 mmol) to afford the desired product (75 mg, 33 %) as a light brown solid: ESI MS m/z 493 [C28H32N2O4S + H]⁺.

Example 531

(S)-tert-Butyl l -(4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (640 mg, 2.1 mmol) was reacted with (S)-tert-butyl l -(4-(4,4,5,5-tetrameth l- l ,3,2-dioxaborolan- 2-yl)phenyl)propylcarbamate (1.13 g, 3.12 mmol) to afford the desired product (680 mg, 71%) as a light brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 532

tert-Butyl (l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)cyclobutyl)methylcarbamate

BocHN

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.46 mmol) was reacted with tert-butyl (l -(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)cyclobutyl)methylcarbamate (270 mg, 0.70 mmol to afford the desired product (105 mg, 45 %) as a light brown solid: ESI MS m/z 505 [C29H32N2O4S + H]⁺.

Example 533

tert-Butyl (l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)cyclobutyl)methylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.9 g, 6.0 mmol) was reacted with tert-butyl (l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)cyclobutyl)methylcarbamate (3.5 g, 9.0 mmol) to afford the desired product (1 .5 g, 33%) as a light brown solid: ESI MS m/z 491 [C28H30N2O4S + H]⁺.

Example 534

tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)butylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (840 mg, 2.7 mmol) was reacted with tert-butyl 2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl) phenyl)butylcarbamate (1.5 g, 4.0 mmol) to afford the desired product (820 mg, 43%) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 535

tert-Butyl ethyl(l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)ethyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (770 mg, 2.5 mmol) was reacted with tert-butyl ethyl(l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2

-yl)phenyl)ethyl)carbamate ( 1.4 g, 3.7 mmol) to afford the desired product (450 mg, 40%) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 536

tert-Butyl4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenethyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.4 g, 7.6 mmol) was reacted with tert-butyl methyl(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2- yl)phenethyl)carbamate (4.2 g, 1 1 mmol) to afford the desired product (2.1 g, 40%) as a light brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 537

(S)-tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.6 g, 8.2 mmol) was reacted with (S)-tert-butyl methyl(2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan -2-yl)phenyl)propyl)carbamate (4.6 g, 12 mmol) to afford the desired product (1.9 g, 50%) as a light brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 538

(S)-tert-Buty\ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl) pheny l)propy lcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (380 mg, 1 .2 mmol) was reacted with fS /eri-butyl2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl)propy lcarbamate (400 mg, 1.1 mmol) to afford the desired product (190 mg, 36%) as a yellow solid: ESI MS m/z 497 [C27H29FN2O4S + H]⁺.

Example 539

/err-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)-3-methylbuty lcarbamate

Following General Procedure B, 9-bromo-8-methoxy-thieno[2,3-c]quinolin-4(5H)-one ) (800 mg, 2.58 mmol) was reacted with /eri-butyl 3-methyl-2-(4-(4,4,5,5-tetrarnethyl-l ,3,2-dioxaborolan- 2-yl)phenyl)butylcarbamate (1.2 g, 3.09 mmol) to afford the desired product (250 mg, 20%) as a yellow solid: ESI MS m/z 493 [C28H32N2O4S + H]⁺.

Example 540

/eri-Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)-3 -methy lbuty lcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (500 mg, 1.54 mmol) was reacted with ½r/-butyl 3-methyl-2-(4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl) phenyl)butylcarbamate (590 mg, 1.9 mmol) to afford the desired product ( 120 mg, 1 5%) as a yellow solid: ESI MS m/z 507 [C29H34N2O4S + H]⁺.

Example 541

(7? r/-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (770 mg, 2.4 mmol) was reacted with

2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2 -dioxaborolan-2-yl)phenyl)propylcarbamate (770 mg, 2.0 mmol) to afford the desired product (500 mg, 49%) as a yellow solid: ESI MS m/z 497 [C27H29FN2O4S + H]⁺.

Example 542

(R)-iert-Ruly\ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl) phenyl)propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (180 mg, 0.57 mmol) was reacted with (R)-tert-bu\y\ 2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)propyl(methyl)carbamate (1 50 mg, 0.38 mmol) to afford the desired product ( 190 mg, 36%) as a yellow solid: ESI MS m/z 51 1 [C28H₃1F 2O4S + H]⁺.

Example 543

(R)-tert- uty\ 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)butylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5FT)-one ) (900 mg, 2.9 mmol) was reacted with (R)-tert-but \ 2-(4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)butylcarbamate (900 mg, 2.7 mmol) to afford the desired product (190 mg, 1 5%) as a yellow solid: ESI MS m/z 493 [C28H32N2O4S + H]⁺.

Example 544

½r/-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothi<

quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure B,9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one) (900 mg, 2.8 mmol) was reacted with ie -butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (1 .3 g, 3.3 mmol) to afford the desired product (200 mg, 27%) as a yellow solid: ESI MS m/z 497 [C27H29FN2O4S + H]⁺.

Example 545

ter/-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)-3-methylbutylcarbamate

Fol lowing General Procedure B, 9-bromo-8-methoxy-6-methylth ieno[2,3-c]quinol in-4(5 H)-one (170 mg, 0.50 mmol) was reacted with fer/-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl)-3-methylbutylcarbamate (200 mg, 0.50 mmol) to afford the desired product (65 mg, 25%) as a yellow solid: ESI MS m/z 525 [C2₉H33FN2O4S + H]⁺.

Example 546

½ /-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one) (380 mg, 1.16 mmol) was reacted with ieri-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl

-l ,3,2-dioxaborolan-2-yl)phenyl)propyl(methyl)carbamate (400 mg, 1.1 mmol) to afford the desired product (190 mg, 36%) as a yellow solid: ESI MS m/z 51 1 [C28H₃₁FN₂0₄S + H]⁺.

Example 547

½ri-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)-3-methylbutyl(methyl)carbamate

Following General Procedure, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (265 mg, 0.81 mmol) was reacted with tert-but \ 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2

-dioxaborolan-2-yl)phenyl)-3-methylbutyl(methyl)carbamate (300 mg, 0.89 mmol) to afford the desired product (80 mg, 1 8%) as a yellow solid: ESI MS m/z 539 [C₃oH35FN₂0₄S + H]⁺.

Example 548

(R)-tert-Buty\ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl) phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (1.0 g, 3.3 mmol) was reacted with (R)-tert-but \ 2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2 -dioxaborolan-2-yl)phenyl)propylcarbamate (1 .1 g, 3.0 mmol) to afford the desired product (510 mg, 34%) as a yellow solid: ESI MS m/z 497 [C2₇H2₉FN2O4S + H]⁺.

Example 549

/e -Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)-3-methylbutyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (440 mg, 1.4 mmol) was reacted with tert-b ty\ methyl(3-methyl-2-(4-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyl)butyl)carbamate (600 mg, 1 .5 mmol) to afford the desired product (100 mg, 14%) as a yellow solid: ESI MS m/z 521 [C30H36N2O4S + H]⁺.

Example 550

f5^-/er/-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl) pheny propy lcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ) (840 mg, 2.6 mmol) was reacted with (S)-tert-buty\ 2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)propylcarbamate (900 mg, 2.4 mmol) to afford the desired

Example 551

(R)-tert-Buty\ 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)propy lcarbamate

Following General Procedure B, 9-bromo-8-methoxy-thieno[2,3-c]quinolin-4(5H)-one (1 .2 g, 4.0 mmol) was reacted with (R)-tert-but \ 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaboroIan

-2-yl)phenyl)propylcarbamate (2.2 g, 6.1 mmol) to afford the desired product (900 mg, 48%) as a yellow solid: ESI MS m/z 465 [C₂6H28N₂0₄S + H]⁺.

Example 1057

N-(l-Hydroxypropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)benzenesulfonamide

Following General Procedure B, 9-bromo-8-methoxy-thieno[2,3-c]quinolin-4(5H -one ) (530 mg, 1.8 mmol) was reacted with N-(l-hydroxypropan-2-yl)-4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)benzenesulfonamide (750 mg, 2.02 mmol) to afford the desi red product (150 mg, 20%) as a yellow solid: ESI MS m/z 445 [C21H20N2O5S2 + H]⁺.

Example 1238

3-(4-(8-Methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propanenitrile

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one) (325 mg, 1.0 mmol) was reacted 3-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan- 2-yl)phenyl)propanenitrile (330 mg, 1.3 mmol) to afford the desired product (140 mg, 37%) as a yellow solid: ESI MS m/z 375 [C₂₂H,₈N₂0₂S + H]⁺.

Example 552

ter/-Butyl 2-cyclopentyl-2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)ethylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-thieno[2,3-c]quinolin-4(5H)-one ) (500 mg, 1.6 mmol) was reacted with /erf-butyl 2-cyclopentyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)ethylcarbamate (1.3 g, 3.2 mmol) to afford the desired product (150 mg, 19%) as a yellow solid: ESI MS m/z 519 [C30H34N2O4S + H]⁺.

Example 553

/erf-Butyl 3-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)piperidine- 1 -carboxylate

Following General Procedure B, 9-bromo-8-methoxy-thieno[2,3-c]quinolin-4(5H)-one ) (190 mg, 0.58 mmol) was reacted with terr-butyl 3-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2- yl)phenyl)piperidine-l -carboxylate (180 mg, 0.46 mmol) to afford the desired product (79 mg, 34%) as a yellow solid: ESI MS m/z 505 [C29H32N2O4S + H]⁺.

Example 554

½ri-Butyl 2-((4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)(methyl)amino)ethylcarbamate

Following General Procedure B, 9-bromo-8-methoxy— 6-methylthieno [2,3-c]quinolin- 4(5H)-one ) (86 mg, 0.26 mmol) was reacted with ierf-butyl 2-(methyl(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)amino)ethylcarbamate ( 100 mg, 0.26 mmol) to afford the desired product (100 mg, 78%) as a yellow solid: ESI MS m/z 494 [C27H31N3O4S + H]⁺.

Example 1310

¾-9-(4-(l-Aminopropan-2-yl)-3-fluorophenyI)-8-methoxy-6-methylthieno

[2,3-c]quino!in-4(5H)-one Hydrochloride

Following General Procedure Dl , (S)-tert-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propylcarbamate (100 mg, 0.20 mmol) was reacted with HC1 in ether (10 mL) to afford the desired product (80 mg, 98%) as an off-white solid: ESI MS m/z 397 [C22H21FN2O2S + H]⁺

Example 1253

9-(4-(l-Amino-3-methylbutan-2-yl)phenyI)-8-methoxythieno[2,3-c|quinolin-4(5H)-one

Hydrochloride

Following General Procedure Dl , tert-buty\ 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)-3-methylbutylcarbamate (30 mg, 0.060 mmol) was reacted with HCl in ether (3 mL) to afford the desired product (22 mg, 97%) as an off-white solid; 'HNMR (500 MHz, DMSO-iiie) δ 7.93 (s, 3H), 7.62 (d, J = 5.4 Hz, 1 H), 7.53 (d, J = 9.1 Hz, 1 H), 7.41 (d, J = 9.0 Hz, 2H), 7.38 - 7.33 (m, 1 H), 7.24 (d, J= 8.2 Hz, 2H), 5.72 (d, J= 5.4 Hz, 1 H), 3.70 (s, 3H), 3.38 - 3.26 (m, 2H), 2.87 (dt, J= 12.9, 6.3 Hz, 1H), 2.01 (dq, J = 13.3, 6.6 Hz, 1 H), 0.97 (t, J = 7.8 Hz, 3H), 0.82 (t, J = 9.9 Hz, 3H).; ESI MS m/z 393 [C23H24N2O2S + H]⁺. HPLC 98.4% (AUC), t = 1 1.65 min.

Example 555

9-(4-( l -Amino-3-methylbutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , tert-buX \ 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)-3-methylbutylcarbamate (50 mg, 0.060 mmol) was reacted with HCl in ether (3 mL) to afford the desired product (37 mg, 92%) as an off-white solid: ESI MS m/z 407 [C24H26N2O2S + H]⁺.

Example 1317

R 9-(4-(l-Aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c] quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , (R)-tert-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (150 mg, 0.30 mmol) was reacted with HCl in ether (15 mL) to afford the desired product (105 mg, 81 %) as an off-white solid: Ή NMR (500 MHz, MeOD) δ 7.63 (dd, J = 5.4, 2.4 Hz, 1 H), 7.52 (dt, J = 24.8, 7.8 Hz, 1 H), 7.30 (s, 1 H), 7.09 (m, 2H), 6.1 1 (dd, J = 26.4, 5.4 Hz, 1 H), 3.76 (s, 3H), 3.63 - 3.43 (m, 1 3.42 - 3.16 (m, 2H), 2.64 (s, 3H), 1.51 (d, J = 7.0 Hz, 3H). ESI MS m/z 397 [C22H21FN2O2S + H]⁺; HPLC >99% (AUC), t_R = 1 1.57 min.

Example 1316

(K -9-(3-Fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-methoxy-6- methylthieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure D

ethoxy-6-methyl-4-oxo -4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (50 mg, 0.10 mmol) was reacted with HCl in ether (5 mL) to afford the desired product (35 mg, 85%) as an yellow solid; 'H NMR (500 MHz, CD₃OD) δ 7.63 (d, J = 5.4.Hz, 1H), 7.53 (dt, J = 28.7, 7.8 Hz, 1H), 7.29 (s, 1 H), 7.17 - 7.04 (m, 2H), 6.10 (dd, J= 3 1.6, 5.4 Hz, 1 H), 3.75 (s, 3H), 3.68 - 3.24 (m, 3H), 2.78 (d, J = 13.3 Hz, 3H), 2.64 (s, 3H), 1.52 (dd, J = 7.0, 3.2 Hz, 3H).; ESI MS m/z 41 1 [C23H23FN2O2S + H]⁺; HPLC 98.2% (AUC), t_R = 1 1.79 min.

Example 1344

R -9-(4-(l-Aminobutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure Dl , (R)-tert-bu y\ 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (100 mg, 0.20 mmol) was reacted with HCl in ether (10 mL) to afford the desired product (75 mg, 94%) as an off-white solid: ESI MS m/z 393 [C2₃H24N2O2S + H]⁺.

Example 1273

9-(4-(l-Aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno

|2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , /erf-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (200 mg, 0.40 mmol) was reacted with HCl in ether (20 mL) to afford the desired product (145 mg, 91 %) as an off-white solid: 'H NMR (500 MHZ, DMSO-C¾ δ 10.80 (s, 1 H), 8.06 (s, 3H), 7.74 (dd, J= 14.6, 5.4 Hz, 1 H), 7.52 (t, J = 7.9 Hz, 1 H), 7.30 (s, 1 H), 7.16 - 7.02 (m, 2H), 5.87 (dd, J = 43.2, 5.4 Hz, 1 H), 3.70 (s, 3H), 3.51 - 3.40 (m, 1 H), 3.26 - 3.07 (m, 2H), 2.59 (s, 3H), 1 .39 (t, J = 7.6 Hz, 3H); ESI MS m/z 397 [C22H21FN2O2S + H]⁺; HPLC 98.8% (AUC), t_R = 1 1 .60 min.

Example 1283

9-(4-(l-Amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c] quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , ieri-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo

-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-3-methylbutylcarbamate (52 mg, 0.10 mmol) was reacted with HCl in ether (5 mL) to afford the desired product (25 mg, 59%) as an off-white solid; 'H NMR (500 MHz, DMSO-i/e) 5 7.69 (dd, J= 16.1 , 5.4 Hz, 1 H), 7.41 (dt, J= 13.3, 8.0 Hz, 1 H), 7.29 (d, J = 3.4 Hz, 1 H), 7.10 - 6.98 (m, 2H), 5.89 - 5.72 (m, 1H), 3.71 (t, J = 6.8 Hz, 3H), 3.19 - 2.83 (m, 3H), 2.59 (s, 3H), 2.03 (dt, J= 13.5, 6.7 Hz, 1H), 0.99 (t, J= 10.0 Hz, 3H), 0.82 (dd, J = 9.9, 6.8 Hz, 3H): ESI MS m/z 425 [C24H25FN2O2S + H]⁺; HPLC 93.4% (AUC), t_R = 1 1.20 min.

Example 556

8-Methoxy-6-methyl-9-(4-(3-methyl-l -(methylamino)butan-2-yl) phenyl)thieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , tert-buX \ 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-3-methylbutyl(methyl)carbamate (100 mg, 0.2 mmol) was reacted with HCl in ether (8 mL) to afford the desired product (40 mg, 47%) as an off-white solid: ESI MS m/z 421 [C25H28N2O2S + H]⁺

Example 1286

9-(3-Fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-methoxy-6- methylthieno[2,3-c|quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , ter/-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (100 mg, 0.20 mmol) was reacted with HCl in ether (5 mL) to afford the desired product (75 mg, 93%) as an off-white solid: 'H NMR (500 MHZ, OMSO-d₆) δ 10.80 (s, 1 H), 7.75 (dd, J = 1 1.7, 5.4 Hz, 1 H), 7.52 (t, J = 7.8 Hz, l H), 7.30 (s, 1H), 7.17 - 7.04 (m, 2H), 5.87 (dd, J = 35.8, 5.4 Hz, 1H), 3.71 (s, 3H), 3.55 (dd, J = 14.0, 6.8 Hz, 1 H), 3.28 (m, 2H), 2.63 (d, J= 5.5 Hz, 3H), 2.59 (s, 3H), 1.39 (dt, J = 17.4, 7.6 Hz, 3H); ESI MS m/z 41 1 [C23H23FN2O2S + H]⁺; HPLC 98.9% (AUC), t_R = 10.75 min.

Example 557

9-(3-Fluoro-4-(3-methyl- l -(methylamino)butan-2-yl)phenyl)-8-methoxy-6- methylthieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , tert-buty \ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-3-methylbutyl(methyl)carbamate (100 mg, 0.18 mmol) was reacted with HCl in ether (6 mL) to afford the desired product (55 mg, 70%) as an off-white solid: ESI MS m/z 439 [C25H27FN2O2S + H]⁺

Example 1317

R -9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno

(2,3-c|quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , (R)-tert-buty\ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (510 mg, 1.1 mmol) was reacted with HCl in ether (25 mL) to afford the desired product (312 mg, 78%) as an off-white solid: ESI MS m/z 397 [C22H21FN2O2S + H]⁺

Example 1310

5 -9-(4-(l-Aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c) quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , (S)-tert-but \ 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (520 mg, 1.1 mmol) was reacted with HCl (25 ml) to afford desire product (300 mg, 74%) as an off-white solid: 'HNMR (500 MHz, MeOD) δ 7.63 (d, J= 5.4 Hz, 1H), 7.51 (dt, J = 23.5, 7.8 Hz, 1H), 7.29 (s, 1 H), 7.14 - 7.02 (m, 2H), 6.16 - 6.05 (m, 1H), 3.76 (s, 3H), 3.54 (ddd, J = 46.9, 14.5, 7.3 Hz, 1 H), 3.43 - 3.20 (m, 2H), 1.51 (d, J = 7.0 Hz, 3H); ESI MS m/z 397 [C22H21FN2O2S + H]⁺; HPLC 98.9% (AUC), t_R = 10.75 min.

Example 1387

¾)-9-(4-(l-(dirnethylamino)propan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c] quino!in-4(5H)-one Hydrochloride

To a solution of (iS -9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno [2,3-c]quinolin-4(5H)-one hydrochloride (1 10 mg, 0.27 mmol)) in a 1 : 1 mixture of MeOH/THF (3 mL) was added paraformaldehyde (7.5 mg, 0.24 mmol) followed by NaCNBH3 (70 mg 1.2 mmol) and stirred at rt for 16 h. The reaction mixture was quenched by the addition of 2 N

NaHCCb (1 mL), eluted through an SCX ion-exchange column and converted to HCl salt using General Procedure D-2 (Scheme II) to obtain the desired product (67 mg, 60%) as a white solid: ESI MS m/z 425 [C24H25FN2O2S + H]⁺;

Example 558

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure C (R)-tert-buty\ 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (2.5 g, 5.4 mmol) was reacted with TFA (10 mL) to afford the desired product (1.6 g, 81 %) as an off-white solid: ESI MS m/z 365 [C21H20N2O2S + H]⁺

Example 1205 N-(l-Chloropropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)benzenesulfonamide

To a mixture of N-( l -hydroxypropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)benzenesulfonamide (140 mg, 0.30 mmol) and triphenylphosphine (160 mg, 0.62 mmol) in DMF/CCU (1 mL /3 mL) was added NCS (41 mg, 0.31 mmol) and the reaction mixture was stirred at room remperature for 15 h. The reaction mixture was diluted with water (ca. 20 mL), and extracted with DCM (1 x 50 mL). The extract was washed with water (2 x 20 mL), brine (1 10 mL), dried over sodium sulfate, and evaporated under vacuum. The residue was purified by flash chromatography to afford the desired product (100 mg, 74%) as light yellow solid; ESI MS m/z 464 [C₂IHI₉C1N₂0₄S + H]⁺

Example 1239

9-(4-(2-Amino-l-cyclopentylethyl)phenyl)-8-methoxythieno [2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure Dl , ½r?-butyl 2-cyclopentyl-2-(4-(8-methoxy-4- oxo-4, 5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (50 mg, 0.10 mmol) was reacted with HC1 in ether (5 mL) to afford the desired product (29 mg, 69%) as an off-white solid: ESI MS m/z 419 [C₂₅H₂₆N₂0₂S + H]⁺; 'H NMR (500 MHz, DMSO-efe) δ 7.59 (d, J = 5.4 Hz, 1 H), 7.59 (d, J= 5.4 Hz, 1 H), 7.54 (d, J = 9.0 Hz, 1 H), 7.54 (d, J= 9.0 Hz, 1 H), 7.48 (d, J = 7.9 Hz, 1 H), 7.48 (d, J= 7.9 Hz, 1 H), 7.44 - 7.36 (m, 2H), 7.45 - 7.35 (m, 2H), 7.28 - 7.19 (m, 2H), 7.28 - 7.19 (m, 2H), 5.72 (d, J = 5.4 Hz, 1 H), 5.72 (d, J= 5.4 Hz, 1 H), 3.70 (s, 3H), 3.33 - 3.20 (m, 2H), 2.84 (td, J = 9.2, 6.0 Hz, 1 H), 2.20 - 2.03 (m, 1 H), 1.98 - 1 .84 (m, 1 H), 1.76 - 1.35 (m, 5H), 1.28 (dq, J= 18.0, 8.9 Hz, 1 H), 1.18 - 1.02 (m, 1 H). HPLC >99% (AUC), t_R = 12.45 min.

Example 1301

8-Methoxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno [2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure Dl , tert-butyl 3-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)piperidine-l-carboxylate (50 mg, 0.10 mmol) was reacted with HC1 in ether (2.5 mL) to afford the desired product (31 mg, 77%) as an off-white solid: ESI MS m/z 405 [C24H24N2O2S + H]⁺

Example 1396

9-(4-((2-aminoethyl)(methyl)amino)phenyl)-8-methoxy-6-niethyIthieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure Dl , ieri-butyl 2-((4-(8-methoxy-6-methyl-4-oxo-4,5-d ihydrothieno[2,3-c]quinolin-9-yl)phenyl)(methyl)amino)ethylcarbamate (100 mg, 0.20 mmol) was reacted with HC1 in ether (10 mL) to afford the desired product (65 mg, 83%) as an off-white solid: ESI MS m/z 394 [C22H23N3O2S + H]⁺

Example 559

tert-Butyl l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (600 mg, 1.9 mmol) was reacted with tert-butyl l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan

-2-yl)phenyl)ethylcarbamate (1.34g, 3.87 mmol) to afford the desired product (340 mg, 39%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

Example 560

(R)-tert-Butyl 1 -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)ethy l(methy l)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (300 mg, 0.97 mmol) was reacted with (R)-tert-butyl methyl(l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan -2-yl)phenyl)ethyl)carbamate (520 mg, 1.45 mmol) to afford the desired product (120 mg, 27%) as a brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

^• Example 561

tert-butyl l -(4-(8-methdxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propan-2-ylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.5 g, 4.4 mmol) was reacted with tert-butyl l-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) phenyl)propan-2-ylcarbamate (2.6 g, 7.3 mmol) to afford the desired product (1.1 g, 50%) as a brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 562

tert-butyl 2-(2-chloro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (3.0 g, 9.7 mmol) was reacted with tert-butyl 2-(2-chloro-4-(4,4,5,5-tetramethyl-l ₎3,2-dipxaborolan -2-yl)phenyl)propylcarbamate (5.7 g, 14 mmol) to afford the desired product (2.7 g, 56%) as a brown solid: ESI MS m/z 499 [C26H27 CIN2O4S + H]⁺

Example 563 2-(4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (500 mg, 1.6 mmol) was reacted with 2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl) propanenitrile (600 g, 2.2 mmol) to afford the desired product (350 mg, 62%) as a brown solid: ESI MS m/z 361 [C2iHi₆N₂0₂S + H]⁺.

Example 564

tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2- methylpropylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.0 g, 6.4 mmol) was reacted with tert-butyl 2-methyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan -2-yl)phenyl)propylcarbamate (3.6 g, 9.7 mmol) to afford the desired product (864 mg, 28%) as a brown solid: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 565

(R)-tert-Butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)ethy lcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (3.0 g, 9.7 mmol) was reacted with (R)-tert-butyl l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)ethylcarbamate (5.0 g, 14 mmol) to afford the desired product (2.0 g, 47%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

Example 566

tert-Butyl 2-ethyl-2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)buty lcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (120 mg, 0.39 mmol) was reacted with 2-ethyl-2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) phenyl)butan- l -amine (220 mg, 0.58 mmol) to afford the desired product (50 mg, 27%) as a brown solid: ESI MS m/z 507 [C29H34N2O4S + H]⁺.

Example 567

tert-Butyl 2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenethylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one ( 1.5 g, 4.8 mmol) was reacted with tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) phenethylcarbamate (2.6 g, 7.3 mmol) to afford the desired product ( 1.5 g, 65%) as a brown ^■ solid: ESI MS m/z 469 [C25H25FN2O4S + H]⁺.

Example 568

(R)-tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1 .5 g, 4.4 mmol) was reacted with (R)-tert-butyl 2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) phenyl)propylcarbamate (2.0 g, 6.4 mmol) to afford the desired product ( 1 .4 g, 48%) as a brown solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 569

tert-Butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.2 g, 3.8 mmol) was reacted with tert-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (2.2 g, 5.8 mmol) to afford the desired product (905 mg, 51 %) as a brown solid: ESI MS m/z 483 [C26H27FN2O4S + H]⁺.

Example 570

(R)-tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl) propyl(methyl)carbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (700 mg, 2.3 mmol) was reacted with (R)-tert-butyl methyl(2-(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)propyl)carbamate (1.3 g, 3.4 mmol) to afford the desired product (383 mg, 38%) as a yellow solid: ESI MS m/z 479 [C27H₃₀N2O4S + H]⁺.

Example 571

tert-Butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.0 g, 6.4 mmol) was reacted with tert-butyl 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)

phenethylcarbamate (3.4 g, 9.4 mmol) to afford the desired product ( 1.93 g, 65%) as a brown solid: ESI MS m/z 451 [C25H26 2O4S + H]⁺.

Example 572

2-(4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.5 g, 4.84 mmol) was reacted with 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl) propanenitrile ( 1.87 g, 7.26 mmol) to afford the desired product (1.45 g, 82%) as a brown solid: ESI MS m/z 361 [QnH^C S + H]⁺.

Example 573

(R)-tert- Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (3.0 g, 9.26 mmol) was reacted with (R)-tert-butyl 2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan -2-yl)phenyl)propylcarbamate (5.2 g, 13.89 mmol) to afford the desired product (1.60 g, 35%) as a brown solid: ESI MS m/z 479 [C₂7H3₀N2O₄S + H]⁺.

Example 574

tert-Butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (800 mg, 4.84 mmol) was reacted with tert-butyl 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)propylcarbamate (1.5 g, 4.16 mmol) to afford the desired product (550 mg, 46%) as a brown solid: ESI MS m/z 465 [C₂6H_2gN₂0₄S + H]⁺.

Example 575

tert-Butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)-2-methylpropylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (200 mg, 0.62 mmol) was reacted with tert-butyl 2-methyl-2-(4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (350 mg, 0.93 mmol) to afford the desired product (95 mg, 62%) as a brown solid: ESI MS m/z 493 [C28H32N2O4S + H]⁺.

Example 576

tert-Butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propan-2-ylcarbamate

Following General Procedure B, 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (260 mg, 0.80 mmol) was reacted with tert-butyl l -(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)propan-2-ylcarbamate (430 g, 1.2 mmol) to afford the desired product (212 mg, 55%) as a yellow oil: ESI MS m/z 479 [C27H30N2O4S + H]⁺.

Example 577

tert-Butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)ethylcarbamate

Following General Procedure H, tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenylethylcarbamate) ( 130 mg, 0.37 mmol) was reacted with NCS (64 mg, 0.48 mmol) to afford the desired product (58 mg, 32%) as a yellow solid. ESI MS m/z 485

[C25H2SCIN2O4S + H]⁺.

Example 578

(S)-tert-Butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny l)propy l(methy l)carbamate -4-oxo-4,5-dihydrothieno[2,3-c] mmol) was reacted with NCS (68 yellow solid: ESI MS m/z 513

Example 579

(S)-tert-Butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

Following General Procedure H, (S)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (500 mg, 1 .08 mmol) was reacted with NCS (175 mg, 1.29 mmol) ) to affor the desired product (310 mg, 58%) as a yellow solid:

ESI MS m/z 499 [C26H27CIN2O4S + H]⁺.

Example 580

tert-Butyl (l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)cyclopropyl)methylcarbamate

Following General Procedure H, tert-butyl (l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (300 mg, 0.629 mmol) was reacted with NCS (85 mg, 0.629 mmol) to affor the desired product (250 mg, 78%) as a yellow solid: ESI MS m/z 51 1 [C27H27CIN2O4S + H]⁺.

Example 581

tert-Butyl 2-chloro-4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenethylcarbamate

Following General Procedure H, tert-butyl 2-chloro-4-(8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenethylcarbamate ( 127 mg, 0.26 mmol) was reacted with NCS (43 mg, 0.312 mmol) to afford the desired product (70 mg, 52%) as a yellow solid: ESI MS m/z 519

Example 582

tert-Butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)butylcarbamate

Following General Procedure H, tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (100 mg, 0.21 mmol) in (DMF) was reacted with NCS (34 mg, 0.25 mmol) to afford the desired product (65 mg, 61%) as a yellow solid: ESI MS m/z 513 [C27H29CIN2O4S + H]⁺.

Example 583

tert-Butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenethy l(methy l)carbamate

Following General Procedure H, tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenethyl(methyl)carbamate (200 mg, 0.43 mmol) in (DMF) was reacted with NCS (70 mg, 0.50 mmol) to afford the desired product (120 mg, 55%) as a yellow solid: ESI MS m z 500 [C26H27CIN2O4S + H]⁺.

Example 584

(R)-tert-Butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)ethylcarbamate

Following General Procedure H, (R)-tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno

mg, 0.67 mmol) was reacted with NCS (1 10 mg, 1 1%) as a yellow solid: ESI MS m/z 485

Example 585

tert-Butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

-2-fluorophenethylcarbamate

Following General Procedure H, tert-butyl 2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenethylcarbamate (300 mg, 0.64 mmol) was reacted with NCS (94 mg, 0.71 mmol) to afford the desired product (150 mg, 46%) as a yellow solid. ESI MS m/z 503 [C25H24CIFN2O4S + H]⁺.

Example 586

tert-Butyl l -(4-(6-chloro-8-methdxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)propan-2-y lcarbamate

Following General Procedure H, tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propan-2-ylcarbamate (220 mg, 0.47 mmol) was reacted with NCS (69 mg, 0.52 mmol) to afford the desired product (60 mg, 26%) as a brown solid. ESI MS m/z 499

Example 1041

9-(4-(l-Aminoethyl)phenyl)-6-chIoro-8-hydroxythieno[2,3-clquinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl l-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl) phenyl)ethylcabamate (50 mg, 0.10 mmol) was treated with BBr₃ (1.0 M in CH2CI2, 2 mL, 2 mmol) to afford the desired product (21 mg, 58%) as a light yellow solid (21 mg, 58%): Ή NMR (500 MHz, CD₃OD) δ 7.65 (dt, J = 5.2, 3.4 Hz, 2H), 7.59 (d, J = 5.4 Hz, 1 H), 7.41 (dt, J = 4.0, 2.6 Hz, 2H), 7.30 (s, lH), 6.07 (d, J= 5.4 Hz, 1H), 4.62 (q, J= 6.8 Hz, 1 H), 1.76 (d, J= 6.9 Hz, 3H); ESI MS m/z 371 [C19H15CIN2O2S + H]⁺; HPLC 97.8% (AUC), t_R = 9.72 min.

Example 1052

(R)-8-Hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (R)-tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)ethyl(methyl)carbamate ( 120 mg, 0.25 mmof was treated with BBr₃ ( 1 .0 M in CH2CI2, 3 mL, 3 mmol) to afford the desired product (50 mg, 56%) as a light yellow solid: Ή NMR (500 MHz, CD3OD) δ 7.64 (ddd, J = 7.1 , 5.6, 2.3 Hz, 2H), 7.57 (d, J = 5.4 Hz, 1 H), 7.49 - 7.39 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 6.04 (d, J = 5.4 Hz, 1H), 4.48 (q, J= 7.0 Hz, 1H), 2.72 (s, 3H), 1.80 (d, J= 6.9 Hz, 3H); ESI MS m/z 351 [C2₀Hi₈N₂O₂S + H]⁺; HPLC 97.6% (AUC), t_R = 7.82 min.

Example 1081

(R)-9-(4-(l-Aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure F, tert-butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (35 mg, 0.07 mmol) was treated with BBr₃ (1.0 M in CH₂C1_2, 2 mL, 2 mmol) to afford the desired product (23 mg, 84%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.67 - 7.61 (m, 2H), 7.59 (d, J= 5.4 Hz, 1H), 7.44 - 7.39 (m, 2H), 7.30 (s, 1 H), 6.07 (d, J = 5.4 Hz, 1 H), 4.62 (q, J= 6.8 Hz, 1H), 1.76 (d, J= 6.9 Hz, 3H); ESI MS m/z 371 [C₁₉H,₅C1N₂0₂S + H]⁺; HPLC 97.2% (AUC), t_R = 9.58 min.

Example 1209

9-(4-(3-(Aminomethyl)pentan-3-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure F, tert-butyl 2-ethyl-2-(4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (20 mg, 0.05 mmol) was treated with BBr₃ (1.0 M in^' CH₂C1_2> 3 mL, 3 mmol) to afford the desired product (7.0 mg, 36%) as a light yellow solid: 'HNMR (500 MHz, CD₃OD) δ 7.63 (d, J= 8.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1H), 7.45 - 7.37 (m, 3H), 7.19 (dd, J = 8.9, 2.2 Hz, 1H), 6.08 (d, J= 5.4 Hz, 1H), 3.29 (s, 2H), 1.97 (dt, J= 14.6, 7.2 Hz, 4H), 0.93 (t, J = 7.4 Hz, 6H). ESI MS m/z 393 [C₂₃H₂₄N₂0₂S + H]⁺; HPLC 99.6% (AUC), t_R = 9.47 min.

Example 1213

9-(4-(2-Aminoethyl)-3-fluorophenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 4-(6-bromo-8-methoxy-4-oxo-4,

5-dihydrothieno[2,3-c]quinolin-9-yl)-2-fluorophenethylcarbamate (100 mg, 0.18 mmol) was treated with BBr₃ (1.0 M in CH₂C1₂, 5 mL, 5 mmol) to afford the desired product as an off-white solid (24 mg, 30%): 'H NMR (500 MHz, CD₃OD) δ 7.69 (d, J = 5.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.48 (s, 1H), 7.14 (d, J= 9.0 Hz, 2H), 6.18 (d, J = 5.4 Hz, 1H), 3.37 - 3.20 (m, 3H), 3.14 - 3.04 (m, 1H); ESI MS m/z 433 [C, 9H,₄BrFN₂0₂S + H]⁺; HPLC 98.6% (AUC), t_R = 9.12 min.

Example 1217

9-(4-(2-Aminoethyl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-fluoro-4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (78 mg, 0.16 mmol) was treated with BBr₃ (1.0 M in CH2CI2_, 3 mL, 3 mmol) to afford the desired product as a yellow solid (16 mg, 27%): 'H NMR (500 MHz, CD₃OD) δ 7.62 (d, J = 5.4 Hz, 1 H), 7.49 (t, J = 7.9 Hz, 1H), 7.14 - 7.05 (m, 3H), 6.21 (d, J = 5.4 Hz, 1 H), 3.36 - 3.21 (m, 2H), 3.1.3 - 3.04 (m, 1H), 2.57 (s, 3H); ESI MS m/z 369 [C₂oH,7FN20₂S + H]⁺; HPLC 97.3% (AUC), t_R = 8.47 min.

Example 1166

( ?)-9-(4-(l-Aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (R)-tert-butyl

2-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (100 mg, 0.20 mmol) was treated with BBr₃ (1.0 M in CH₂C1_2, 5 mL, 5 mmol) to afford the desired product as a white solid (23 mg, 30%): 'HNMR (500 MHz, CD₃OD) δ 7.63 (d, J = 5.4 Hz, 1 H), 7.56 (dd, J = 7.9, 1.9 Hz, 1 H), 7.47 (dd, J = 7.8, 1.9 Hz, 1H), 7.39 - 7.28 (m, 3H), 6.12 (d, J = 5.4 Hz, 1 H), 3.36 - 3.13 (m, 3H), 1 .49 (d, J = 6.5 Hz, 3H); ESI MS m/z 385

[C2oH,₇ClN₂02S + H]⁺; HPLC 98.4% (AUC), t_R = 9.19 min.

Example 1174

9-(4-(l-Aminopropan-2-yl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (120 mg, 0.25 mmol) was treated with BBr₃ (1.0 M in CH2CI2_, 5 mL, 5 mmol) to afford the desired product as an off-white solid (35 mg, 37%). 'H MR (500 MHz, CD₃OD) δ 7.65 (dd,J= 5.4, 3.4 Hz, 1H), 7.59 (s, 1H), 7.51 (s, 1H), 7.43 (dd, J= 8.9, 2.3 Hz, 1H), 7.24 - 7.09 (m, 2H), 6.22 (dd, J= 9.4, 5.4 Hz, 1H), 3.62 (d, J= 7.2 Hz, 1H), 3.49 - 3.25 (m, 2H), 1.52 (t, J= 6.7 Hz, 3H); ESI MS m/z 369

[C₂oH,₇FN₂02S + H]⁺; HPLC 99.3% (AUC), t_R = 8.37 min.

Example 1187

(R)-8-Hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-cjquinolin-4(5H)-

Hydrochloride

Following General Procedure F (R)-tert-butyl

2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (250 mg, 0.52 mmol) was treated with BBr₃ (1.0 M in CH₂C1_2, 4 mL, 4 mmol) to afford the desired product as an light yellow solid (39 mg, 42%). 'HNMR (500 MHz, CD₃OD) δ 7.58 (dd, J= 10.8,3.6 Hz, 2H), 7.50-7.46 (m, 1H), 7.42 (d,J=8.9 Hz, 1H), 7.38 (dd, J= 7.9, 1.8 Hz, 1H), 7.32 (dd, J= 7.7, 1.7 Hz, 1H), 7.18 (d,J= 8.9 Hz, 1H), 6.14 (d,J= 5.4 Hz, 1H), 3.37- 3.28 (m, 3H), 2.75 (s, 3H), 1.50 (d,J= 6.7 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC 97.1 % (AUC), t_R = 8.43 min.

Example 1190

9-(4-(l-Aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno

oride

Following General Procedure F, tert-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (120 mg, 0.25 mmol) was treated with BBr₃ (1.0 M in CH2CI2_, 5 mL, 5 mmol) to afford the desired product as an off-white solid (39 mg, 42%). 'HNMR (500 MHz, CD₃OD) δ 7.64 (dd, J= 5.4, 4.6 Hz, 1H), 7.57 (t, J= 7.8 Hz, 1H), 7.48 (t,J= 7.8 Hz, 1H), 7.22 - 7.05 (m, 3H), 6.23 (dd,J= 8.4, 5.4 Hz, 1H), 3.61 (dd,J = 14.4, 7.2 Hz, 1H), 3.51-3.23 (m, 2H), 2.57 (s, 3H), 1.52 (t,J= 7.0 Hz, 3H); ESI MS m/z 383 [C21H19FN2O2S + H]⁺; HPLC 96.1% (AUC), t_R = 8.85 min.

Example 1133 9-(4-(2-Aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

hydrochloride

Following General Procedure F, tert-butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenethylcarbamate (79 mg, 0.25 mmol) was treated with BBr3 (1.0 M in CH₂C1_2, 9 mL, 9 mmol) to afford the desired product as a yellow solid (12 mg, 20%). 'HNMR (500 MHz, CD₃OD) δ 7.61 (d, J = 5.4 Hz, 1 H); 7.49 (d, J= 8.1 Hz, 2H), 7r31 (d, J = 7.0 Hz, 3H), 6.10 (d, J= 5.4 Hz, 1H), 3.37-3.27 (m, 2H), 3.12 (t, J= 7.6 Hz, 2H ; ESI MS m/z 371

[Ci₉H,₅ClN₂0₂S + H]⁺; HPLC 96.9% (AUC), t_R = 8.83 min.

Example 1142

9-(4-(2-Aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure F, tert-butyl 4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (410 mg, 0.76 mmol) was treated with BBr₃ (1.0 M in CH₂CI_2, 10 mL, 10 mmol) to afford the desired product as an off-white solid (58 mg, 18%): "H NMR (500 MHz, CD3OD) δ 7.62 (d, J= 5.4 Hz, 1H), 7.53 - 7.45 (m, 3H), 7.31 (d, J= 8.1 Hz, 2H), 6.10 (d, J = 5.4 Hz, 1H), 3.31-3.28 (m, 2H), 3.1 1 (t, J= 7.6 Hz, 2H); ESI MS m/z 41 5 [C,9H| 5BrN₂0₂S + H]⁺; HPLC 94.9% (AUC), t_R = 9.02 min.

Example 1176

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (R)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate (60 mg, 0.1 1 mmol) was reacted with BBr₃ (1.0 M in

CH2CI2, 6 mL, 6 mmol) to afford the desired product as an off-white solid (24 mg, 51 %): 'HNMR (500 MHz, CD3OD) δ 7.64 (d, J = 5.4 Hz, 1 H), 7.56 (dd, J = 7.9, 1.9 Hz, 1H), 7.50 - 7.45 (m, 2H), 7.37 (dd, J = 7.9, 1.8 Hz, 1 H), 7.32 (dd, J = 7.7, 1.7 Hz, 1 H), 6.12 (d, J = 5.4 Hz, 1 H), 3.36 - 3.1 8 (m, 3H), 1 .49 (d, J = 6.5 Hz, 3H); ESI MS m/z 429 [C₂₀H,₇BrN2O₂S + H]⁺; HPLC >99% (AUC), t_R = 9.30 min.

Example 1136

9-(4-(l-Aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (40 mg, 0.08 mmol) was treated with BBr₃ (1.0 M in CH₂O_2, 3 mL, 3 mmol) to afford the desired product as an yellow solid (13 mg, 40%): 'HNMR (500 MHz, CD₃OD) δ 7.63 (d, J = 5.4 Hz, 1H), 7.56 (dd, J= 7.9, 1.8 Hz, 1 H),

7.48 (dd, J= 7.8, 1.8 Hz, 1 H), 7.40 - 7.28 (m, 3H), 6.12 (d, J = 5.4 Hz, 1 H), 3.29 - 3.19 (m, 3H),

1.49 (d, J= 6.3 Hz, 3H); ESI MS m/z 385 [C₂oHi₇ClN₂0₂S + H]⁺; HPLC 99% (AUC), t_R = 8.12 ^' min.

Example 1132

(R)-6-Chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyI)thieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (R)-tert-butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (43 mg, 0.09 mmol) was treated with BBr3 (1.0 M in CH₂CI_2, 4 mL, 4 mmol) to afford the desired product as a white solid (15 mg, 45%): 'H NMR (500 MHz,^'CD₃OD) δ 7.69 - 7.59 (m, 3H), 7.45 (ddd, J = 7.0, 5.8, 2.1 Hz, 2H), 7.30 (s, 1 H), 6.03 (d, J = 5.4 Hz, 1 H), 4.48 (q, J = 6.9 Hz, 1 H), 2.72 (s, 3H), 1.79 (d, J = 6.9 Hz, 3H); ESI MS m/z 385 [C₂oH|₇ClN₂0₂S + H]⁺; HPLC 97.1 % (AUC), t_R = 8.85 min.

Example 1219

9-(4-(2-Aminoethyl)-3-fluorophenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)-2-fluorophenethylcarbamate (70 mg, 0.14 mmol) was treated with BBr3 (1.0 M in CH2CI2_, 6 mL, 6 mmol) to afford the desired product as a white solid (26 mg, 48%); Ή NMR (500 MHz, CD3OD) δ 7.67 (d, .7 = 5.4 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 1 H), 7.30 (s, 1 H), 7.17 - 7.11 (m, 2H), 6.18 (d, J= 5.4 Hz, 1 H), 3.35 - 3.20 (m, 2H), 3.14 - 3.04 (m, 1H); ESI MS m/z 389. [C,₉Hi₄ClFN₂0₂S + H]⁺; HPLC >.99% (AUG), t_R = 8.93 min_

Example 1228

9-(4-(l-Amino-2-methylpropan-2-yl)phenyl)-8-hydroxy-6-methylthieno

[2,3-c] quinolin-4(5H)-one Hyd rochloride

Following General Procedure F, tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropylcarbamate (40 mg, 0.08 mmol) was treated with BBr3 (1.0 M in CH2CI2_, 4 mL, 4 mmol) to afford the desired product as a brown solid (21 mg, 67%); 'H NMR (500 MHz, CD3OD.) δ 7.64 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 5.4 Hz, 1H), 7.36 (d, J= 8.3 Hz, 2H), 7.09 (s, 1H), 6.18 (d, J= 5.4 Hz, 1H), 3.28 (s, 2H), 2.58 (s, 3H), 1.58 (s, 6H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 96.5% (AUC), t_R = 9.04 min.

Example 1242

9-(4-(2-Aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)pheny l)propan-2-ylcarbamate (90 mg, 0.19 mmol) was treated with BBr3 (1.0 M in CH2CI2_, 8 mL, 8 mmol) to afford the desired product as a light brown solid (25 mg, 53%): 'H NMR (500 MHz, CD₃OD) δ 7.57 (d, J = 5.4 Hz, 1 H), 7.45 (dd, J = 20.6, 7.8 Hz, 2H), 7.32 - 7.26 (m, 2H), 7.09 (s, 1H), 6.12 (d, J = 5.4 Hz, 1H), 3.65 (dd, J= 13.7, 6.9 Hz, 1 H), 3.14 - 2.99 (m, 2H), 2.57 (s, 3H), 1.41 (d, J = 6.6 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + Hf; HPLC 98.6% (AUC), t_R = 8.68 min.

Example 1191

9-(4-(2-Aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenethylcarbamate (30 mg, 0.06 mmol was treated with BBr₃ (1 .0 M in CH₂CI_2, 4 mL, 4 mmol) to afford the desired product as a light yellow solid (20 mg, 90%): Ή NMR (500 MHz, CD₃OD) δ 7.55 (d, J = 5.4 Hz, 1H), 7.47 (d, J= 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 0.8 Hz, 1 H), 6.14 (d, J = 5.4 Hz, 1 H), 3.34 - 3.27 (m, 2H), 3.1 1 (t, J = 7.5 Hz, 2H), 2.57 (s, 3H); ESI MS m/z 351 [C₂oH_{I 8}N₂0₂S + H]⁺; HPLC 98.4% (AUC), t_R = 8.32 min.

Example 1364

8-Hydroxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure F, 8-methoxy-6-methyl-9-(4-(2-(methylamino)ethyl)

phenyl)thieno[2,3-c]quinolin-4(5H)-one (32 mg, 0.06 mmol) was treated with BBr₃ (1.0 M in CH2CI2_, 3 mL, 3 mmol) to afford the desired product as a light yellow solid (15 mg, 62%): Ή NMR (500 MHz, CD₃OD) δ 7.55 (d, J = 5.4 Hz, 1 H), 7.47 (d, J = 8.1 Hz, 2H), 7.34 - 7.27 (m, 2H), 7.07 (d, J = 0.7 Hz, 1 H), 6.12 (d, J = 5.4 Hz, 1H), 3.39 (t, J = 7.6 Hz, 2H), 3.18 - 3.10 (m, 2H), 2.79 (s, 3H), 2.57 (s, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.41 min.

Example 1307

(R)-8-Hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno

[2,3-c]quinolin-4(5H)-one Hydrobromide

Following General Procedure F, (R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (2.08 g, 4.23 mmol) was treated with BBr₃ (1 .0 M in CH₂C1_2, 40 mL, 40 mmol) to afford the desired product as a yellow solid (1.05 g, 65%); 'H NMR (500 MHz, CD₃OD) δ 7.60 - 7.54 (m, 2H), 7.46 (dd, J = 7.8, 1.9 Hz, 1 H), 7.37 (dd, J = 7.9, 1 .8 Hz, 1 H), 7.31 (dd, J = 7.7, 1.7 Hz, 1 H), 7.08 (d, J = 0.8 Hz, 1 H), 6.16 (d, J = 5.4 Hz, 1 H), 3.37 - 3.24 (m, 3H), 2.74 (s, 3H), 2.57 (s, 3H), 1.50 (d, J = 6.8 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.74 min.

Example 1169

(R)-9-(4-(l-Aminopropan-2-yl)phenyI)-8-hydroxy-6-methylthieno

|2,3-c]quinolin-4(5H)-one Hydrobromide

Following General Procedure F, (R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (2.20 g, 4.60 mmol) was treated with BBr₃ (1.0 M in CH₂C1_2, 50 mL, 50 mmol) to afford the desired product as a yellow solid (1.50 g, 73%): 'HNMR (500 MHz, CD₃OD) δ 7.58 (d, J = 5.4 Hz, 1 H), 7.55 (dd, J= 7.9, 1 .8 Hz, 1 H), 7.45 (dd, J = 7.8, 1 .9 Hz, 1 H), 7.35 (dd, J = 7.9, 1.7 Hz, 1 H), 7.30 (dd, J= 7.7, 1.6 Hz, 1 H), 7.08 (d, J= 0.8 Hz, 1 H), 6.17 (d, J = 5.4 Hz, 1 H), 3.36 - 3.19 (m, 3H), 2.57 (d, J = 0.6 Hz, 3H), 1.50 (d, J = 6.4 Hz, 3 H); ESI MS m/z 365 [C₂|H2oN₂0₂S + H]⁺; HPLC 98.3% (AUC), tR = 8.64 min.

Example 587

tert-Butyl 4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin

-2-fluorophenethylcarbamate

Following General Procedure I, tert-butyl 2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenethylcarbamate (1.1 g, 2.3 mmol) was reacted with NBS (540 mg, 3.1 mmol) to afford the desired product (920 mg, 70%) as a brown solid. ESI MS m/z 547

[C₂5H24BrFN₂0₄S + H]⁺.

Example 588

tert-Butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)-2-methy lpropy lcarbamate

Following General Procedure I, tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)-2-methylpropylcarbamate (600 mg, 1.3 mmol) was reacted with NBS (330 mg, 1.9 mmol) to afford the desired product (350 mg, 51%) as a yellow solid: ESI MS m/z 557 [C₂₇H₂9BrN₂0₄S + H]⁺.

Example 589

tert-Butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)-2-fluorophenyl)propy lcarbamate

Following General Procedure I, tert-butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (500 mg, 1.0 mmol) was reacted with NBS (220 mg, 1.2 mmol) to afford the desired product (280 mg, 48%) as a brown oil. ESI MS m/z 561 [C₂6H₂₆BrFN₂04S + H]⁺.

Example 590

tert-Butyl 4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenethy lcarbam ate

Following General Procedure I, tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenethylcarbamate (600 mg, 1.3 mmol) was reacted with NBS (280 mg, 1.5 mmol) to afford the desired product (410 mg, 60%) as a reddish brown solid. ESI MS m/z 529 [C₂₅H2sBrN₂0₄S + H]⁺.

Example 591

(R)-tert-Butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny])propylcarbamate

Following General Procedure I, (R)-tert-butyl

2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (220 mg, 0.39 mmol) was reacted with NBS (90 mg, 0.51 mmol) to afford the desired product (60 mg, 28%) as a reddish oil: ESI MS m/z 543 [C26H₂₇BrN₂0₄S + H]⁺.

Example 592

tert-Butyl 2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenethylcarbamate

Following General Procedure I, tert-butyl 4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)-2-fluorophenethylcarbamate (300 mg, 0.55 mmol) was reacted with trimethylboroxine (207 mg, 1.65 mmol) and Pd(pph₃)₄ (63 mg, 0.05 mmol) to afford the desired product (1 55 mg, 58%) as a brown solid. ESI MS m/z 483 [C26H27FN2O4S + H]⁺.

Example 593

tert-Butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure I, tert-butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)-2-fluorophenyl)propylcarbamate (282 mg, 0.50 mmol) was reacted with trimethylboroxine (170 mg, 1.35 mmol) and Pd(ppli3)₄ (50 mg, 0.04 mmol) to afford the desired product (130 mg, 52%) as a yellow solid. ESI MS m/z 497 [C27H₂9FN₂0₄S + H]⁺.

Example 1216

9-(4-(2-Aminoethyl)-3-fluorophenyl)-8-methoxy-6-methylthieno [2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, tert-butyl 2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (50 mg, 0.10 mmol) was reacted with TFA (2 mL) to afford the desired product (32 mg, 80%) as a yellow solid: 'H NMR (500 MHz, CD₃OD) 5 7.62 (d, J = 5.4 Hz, 1 H), 7.48 (dd, J= 9.7, 6.1 Hz, 1 H), 7.29 (s, 1 H), 7.08 (ddd, J = 9.0, 6.2, 1.6 Hz, 2H), 6.12 (d, J = 5.4 Hz, 1H), 3.75 (s, 3H), 3.34 - 3.27 (m, 1H), 3.27 - 3.06 (m, 3H), 2.64 (s, 3H); ESI MS m/z 383 [C₂iH,₉FN₂0₂S + H]⁺; HPLC 97.6% (AUC), t_R = 9.22 min.

Example 1161

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, (R)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate (200 mg, 0.55 mmol) was reacted with TFA (10 mL) to afford the desired product (51 mg, 26%) as a white solid: 'HNMR (500 MHz, CD₃OD) δ 7.61 - 7.44 (m, 4H), 7.39 (d, j = 9.1 Hz, 1 H), 7.30 (ddd, J = 13.2, 7.9, 1.7 Hz, 2H), 6.00 (d, J = 5.4 Hz, 1 H), 3.33 - 3.1 8 (m, 3H), 1.49 (d, J = 6.6 Hz, 3H); ESI MS m/z 365 [C₂,H₂oN₂0₂S + H]⁺; HPLC 97.6% (AUC), t_R = 8.88 min

Example 1305

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno

[2,3-cJquinolin-4(SH)-one Hydrochloride

Following General Procedure C, (R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (1.5 g, 3.1 mmol) was reacted with TFA (30 mL) to afford the desired product (520 mg, 47%) as a yellow solid: Ή NMR (500 MHz, CD3OD) δ 7.56 (d,J=5.4 Hz, 1H), 7.50 (dd,J=7.8, 1.8 Hz, lH), 7.45 (dd,J=7.7, 1.9 Hz, lH), 7.28 (ddd,J= 9.4, 7.0, 1.7 Hz, 3H), 6.01 (d,J= 5.4 Hz, 1H), 3.75 (s, 3H), 3.36-3.18 (m, 3H), 2.64 (s, 3H), 1.48 (d, J= 6.6 Hz, 3H); ESI MS m/z 379 [C22H22 2O2S + H]⁺; HPLC 99% (AUC), t_R = 8.81 min.

Example 1201

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, (R)-tert-butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (60 mg, 0.12 mmol) was reacted with TFA (4 mL) to afford the desired product (28 mg, 52%) as a yellow solid: 'HNMR (500 MHz, CD3OD) δ 7.61 (d,J=5.4 Hz, 1H), 7.54 - 7.50 (m, 2H), 7.48 (dd,J=7.8, 1.7 Hz, 1H), 7.32- 7.25 (m, 2H), 5.97 (d, J= 5.4 Hz, 1H), 3.76 (s, 1H), 3.29 - 3.17 (m, 3H), 1.48 (d, J= 6.5 Hz, 2H); ESI MS m/z 399 [C21H19CIN2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.65 min.

Example 1298

(R)-8-Methoxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure C, (R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (600 mg, 1.2 mmol) was reacted with TFA (20 mL) to afford the desired product (330 mg, 69%) as a light yellow solid: 'HNMR (500 MHz, CD3OD) δ 7.56 (d, J= 5.4 Hz, 1H), 7.52 (dd, J= 7.9, 1.9 Hz, 1H), 7.47 (dd, J = 7.7, 1.9 Hz, 1 H), 7.28 (ddd, J = 14.7, 7.9, 1.7 Hz, 3H), 6.00 (d, J = 5.4 Hz, 1 H), 3.36 - 3.26 (m, 3H), 2.76 (s, 3H), 2.64 (s, 3H), 1.48 (d, J = 6.7 Hz, 3H); ESI MS m/z 393 [C23H24N2O2S + H]⁺; HPLC 98.6% (AUC), t_R = 8.96 min.

Example 594

(R)-tert-Butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny l)propy lcarbamate

Following General Procedure H, (R)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate (400 mg, 0.86 mmol) was reacted with NCS (138 mg, 1.03 mmol) to afford the desired product (210 mg, 49%) as a brown solid. ESI MS m/z 499

[C2₆H2₇CIN2O4S + H]⁺.

Example 595

tert-Butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenethylcarbamate

Following General Procedure H, tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenethylcarbamate (200 mg, 0.43 mmol) was reacted with NCS (68 mg, 0.52 mmol) to afford the desired product (79 mg, 38%) as a brown solid. ESI MS m/z 485

[C₂5H25C1N₂0₄S + H]⁺.

Example 596

tert-Butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propylcarbamate

Following General Procedure H, tert-butyl

2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (180 mg, 0.39 mmol) was reacted with NCS (57 mg, 0.42 mmol) to afford the desired product (110 mg, 56%) as a yellowish solid. ESI MS m/z 499 [C26H27CIN2O4S + H]⁺.

Example 597

(R)-tert-Butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethyl(methyl)carbamate

[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (200 mg, 0.43 mmol) was reacted with NCS (69 mg, 0.52 mmol) to afford the desired product (43 mg, 20%) as a yellowish solid. ESI MS m/z 499 [C26H27CIN2C S + H]⁺.

Example 598

tert-Butyl 4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

Following General Procedure H, tert-butyl 2-fluoro-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (300 mg, 0.64 mmol) was reacted with desired product ( 1 50 mg, 46%) as a yellow solid. ESI

Example 373

9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxythieno |2,3-c]quinolin-4(5H)-

Hydrochloride

To a solution of 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl) propanenitrile (1.4 g, 4.0 mmol) in toluene (10 mL) at 0 °C was added BH₃ ^«THF (1.0 M in THF, 10 mL, 10 mmol) and the reaction was warmed to room temperature and heated at reflux for 4 h. The reaction was quenched by adding methanol (1 mL) at 0 °C. The resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product (352 mg, 24%) as a brown solid: ESI MS m/z 365

Example 1112

9-(4-(l-(Dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno [2,3-c]quinolin-4(5H)-one

Hydrochloride

Following the procedure outlined for Example 1387, 9-(4-(l -aminopropan-2-yl)phenyl)-8- hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (15 mg, 0.040 mmol) was reacted with paraformaldehyde (4.0 mg, 0.13 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product ( 12 mg, 75%) as a light yellow solid: ^]H NMR (500 MHz, CD₃OD) δ 7.66 - 7.51 (m, 3H), 7.47 - 7.30 (m, 3H), 7.18 (d, J= 8.9 Hz, 1 H), 6.12 (d, J= 5.4 Hz, 1 H), 3.67 - 3.57 (m, 1 H), 3.51 - 3.38 (m, 2H), 2.95 (d, J= 16.0 Hz, 6H), 1 .49 (d, J= 6.5 Hz, 3H); ESI MS m/z 379

[C22H₂2 ₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.46 min.

Example 1126

(R)-6-Chloro-9-(4-(l-(dimethyIamino)ethyl)phenyl)-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 1387,

(R)-9-(4-( l -aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride ( 120 mg, 0.32 mmol) was reacted with paraformaldehyde (29 mg, 0.97 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (21 mg, 16%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.71 (dd, J = 10.5, 7.8 Hz, 2H), 7.64 (d, J = 5.4 Hz, 1 H), 7.47 (t, J = 7.1 Hz, 2H), 7.31 (s, 1 H), 6.01 (d, J = 5.4 Hz, 1 H), 4.66 (q, J = 6.9 Hz, 1 H), 2.97 (s, 3H), 2.86 (s, 3H), 1 .86 (d, J = 7.0 Hz, 3H). ESI MS m/z 399 [C21H19CIN2O2S + H]⁺; HPLC 97.5% (AUC), t_R = 9.96 min.

Example_1188

(R)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Examplel 387,

(R)-8-methoxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thienb[2,3-c]quinolin-4(5H)-one hydrochloride (40 mg, 0.11 mmol) was reacted with paraformaldehyde (7 mg, 0.21 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (28 mg, 67%) as a white solid: 'HNMR (500 MHz, CD3OD) δ 7.65 - 7.52 (m, 3H), 7.44 - 7.32 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 6.12 (d, J = 5.4 Hz, 1 H), 3.62 (d, J = 3.1 Hz, 1H), 3.46 (dd, J = 13.2, 4.7 Hz, 2H), 2.97 (s, 3H), 2.94 (s, 3H), 1.49 (d, J = 6.6 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.57 min.

Example 1193

9-(4-(l-(Dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 1387,

9-(4-(l -Aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-on e Hydrochloride (30 mg, 0.08 mmol) was reacted with paraformaldehyde (9 mg, 0.31 mmol) and after purification the resulting material was converted to the Hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (25 mg, 75%) as a light yellow solid: Ή NMR (500 MHz, CD3OD) δ 7.67 - 7.51 (m, 2H), 7.26 - 7.10 (m, 2H), 7.08 (dd, J= 1.6, 0.8 Hz, 1 H), 6.20 (dd, J= 8.1 , 5.4 Hz, 1 H), 3.88 - 3.40 (m, 3H), 3.0 - 2.96 (m, 6H), 2.57 (s, 3H), 1.57 - 1.46 (m, 3H); ESI MS m/z 41 1 [C23H23FN2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.14 min.

Example 1347

(R)-6-chloro-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno

|2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 1387,

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (30 mg, 0.10 mmol) was reacted with paraformaldehyde (6 mg, 0.20 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (12 mg, 29%) as a yellow solid: 'HNMR (500 MHz, CDjOD) δ 7.66 - 7.57 (m, 2H), 7.55 (d, J = 7.8 Hz, 1 H), 7.40 - 7.27 (m, 3H), 6.07 (d, J= 5.4 Hz, 1 H), 3.62 (dd, J = 12.2, 8.9 Hz, l H), 3.46 (ddd, 1 1.7, 9.3, 6.3 Hz, 2H), 2.98 (s, 3H), 2.94 (s, 3H), 1.48 (d, J= 6.5 Hz^3H); ESI MS m/z 413 [C22H21CIN2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.46 min.

Example 1379

(R)-9-(4-(l-(ethyl(methyl)amino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 1387,

((R)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H) -one hydrochloride (15 mg, 0.04 mmol) was reacted with acetaldehyde (5 uL, 0.08 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (8 mg, 50%) as a yellow solid: *HNMR (500 MHz, CD3OD) δ 7.66 - 7.49 (m, 3H), 7.42 - 7.27 (m, 2H), 7.08 (s, 1 H), 6.13 (dd, J= 19.9, 5.4 Hz, 1H), 3.70 (dd, J = 12.8, 10.3 Hz, 1 H), 3.58 - 3.14 (m, 4H), 2.91 (d, J= 23.4 Hz, 3H), 2.57 (s, 3H), 1.49 (dd, J = 6.8, 3.3 Hz, 3H), 1.36 (dt, J = 12.8, 7.3 Hz, 3H); ESI MS m/z 407 [C24H26N2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.16 min.

Example 1324

(R)-9-(4-(l-(Dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-

4(5H)-one Hydrochloride

Following the procedure outlined for Example 1387,

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrobromide (100 mg, 0.26 mmol) was reacted with paraformaldehyde (24 mg, 0.80 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (34 mg, 34%) as a white solid: *HNMR (500 MHz, CD3OD) δ 7.61 - 7.55 (m, 1H), 7.53 (dd,J=7.8, 1.8 Hz, 1H), 7.36 (dd, J= 7.9, 1.7 Hz, 1H), 7.31 (dd,J=7.7, 1.7 Hz, lH), 7.08 (s, 1H), 6.12 (d,J= 5.4 Hz, 1H),3.61 (dd,J= 12.3, 9.3 Hz, lH), 3.45 (dt,J= 9.1, 6.2 Hz, 2H), 2.97 (s, 1H), 2.94 (s, 1H), 2.57 (s, 1H), 1.48 (d,J = 6.6 Hz, 1 H); ESI MS m/z 393 [C23H24N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.90 min.

Example 1306

(R)-8-Hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure D-3, (R)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)

propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one hydrobromide (120 mg, 0.26 mmol) was dissolved in aqueous HC1 (100 mmol) and stirred concentrated at room temperature for 2 h, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt. The desired product was dried under high vacuum to afford the desired product as a light yellow solid (27 mg, 28%): 'HNMR (500 MHz, CD₃OD) δ 7.61 - 7.53 (m, 2H), 7.46 (dd, J= 7.8, 1.8 Hz, 1H), 7.36 (dd, J =7.9, 1.6 Hz, 1H), 7.31 (dd,J=7.7, 1.7 Hz, 1H), 7.08 (s, 1H), 6.16 (d, J = 5.4 Hz, 1H),3.41 -3.24 (m,3H), 2.74 (s,3H), 2.57 (s,3H), 1.50 (d, J= 6.8 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 98.7% (AUC), t_R = 8.82 min.

Example 408

N-tert-Butyl-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)benzenesulfonamide

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (5.0 g, 16 mmol) was reacted with 4-(TM-tert-butylsulfamoyl)phenylboronic acid (5.4 g, 21 mmol) to afford the desired product (4.3 g, 60%) as a yellow solid: ESI MS m/z [C22H22N2O4S2 + H]⁺.

Example 409

9-( 1 H-Indazol-6-y l)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.32 mmol) was reacted with 6-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-l H-indazole (120 mg, 0.48 mmol) to afford the desired product (35 mg, 31 %) as brown solid: ESI MS m/z 348 [CigHi iN₃02S + H]⁺

9-[4-(2-Aminoethyl)ph c]quinolin-4(5H)-one

Following General Procedure C, tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenethylcarbamate (310 mg, 0.69 mmol) was reacted with TFA (2 mL) to afford the desired product (220 mg, 90%) as an off-white solid: Ή NMR (500 MHz, DMSO-de) δ 7.91 (s, 1 H), 7.91 (br s, 2H), 7.71 (d, J = 5.4 Hz, 1H), 7.52 (d, J = 9.1 Hz, 1 H), 7.40 (m, 3H), 7.22 (d, J = 8.1 Hz, 2H), 5.80 (d, J = 5.4 Hz, 1 H), 3.68 (s, 3H), 3.20-3.17 (m, 2H), 3.02-2.99 (m, 2H); ESI MS m/z 351 [C₂oH,₈N₂0₂S + H]⁺; HPLC 98.8% (AUC), t_R = 8.32 min.

Example 145

9-(4-{3-[2-(Diethylamino)ethylamino]propoxy}phenyl)-8- methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.33 mmol) was reacted with N^l,N¹-diethyl-N²-{3-[4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenoxy]propyl} ethane- 1 ,2-diamine (250 mg, 0.67 mmol) to afford the desired product (58 mg, 37%) as a brown solid: Ή NMR (500 MHz, CD3OD) δ 7.56 (d, J = 5.4 Hz, 1 H), 7.52 (d, J = 9.1 Hz, 1 H), 7.36 (d, J = 9.1 Hz, 1 H), 7.18 (d, J = 8.6 Hz, 2H), 7.12 (d, J = 8.6 Hz, 2H), 6.1 1 (d, J = 5.4 Hz, 1H), 4.25 (t, J = 5.7 Hz, 2H), 3.74 (s, 3H), 3.74-3.43 (m, 4H), 3.42 (t, J = 7.4 Hz, 2H), 3.34-3.33 (m, 4H), 2.35-2.25 (m, 2H), 1.37 (t, J = 7.3 Hz, 6H); ESI MS m/z 480 [C27H33N3O3S + H]⁺; HPLC 98.6%, t_R = 8.42 min.

Example 410

tert-Butyl 4-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-y l)phenyl]piperazine- 1 -carboxylate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (80 mg, 0.26 mmol) was reacted with tert-butyl 4-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan

-2-yl)phenyl]piperazine-l -carboxylate (170 mg, 0.44 mmol) to afford the desired product (68 mg, 32%) as a yellow solid: ESI MS m/z 492 [C27H29N3O4S + H]⁺.

Example 41 1

8-Methoxy-9-[4-(piperazin-l -yl)phenyl]thieno[2,3-c]quinolin-4(5H)-one

Following General Procedure C, tert-butyl 4-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl]piperazine- l-carboxylate (160 mg, 0.33 mmol) was reacted with TFA (4 mL) to afford the desired product (23 mg, 22%) as a light yellow solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.84 (s, 1H), 8.72 (s, 2H), 7.76 (d, J = 5.4 Hz, 1 H), 7.49 (d, J = 9.0 Hz, 1 H), 7.37 (d, J = 9.1 Hz, 1 H), 7.20-7.03 (m, 4H), 5.95 (d, J = 5.4 Hz, 1H), 3.68 (s, 3H), 3.52-3.41 (m, 4H), 3.31 (s, 4H).

Example 412

8-Methoxy-9-{4-[4-(methylsulfonyl)piperazin-l -yl]phenyl}thieno[2,3-c]quinolin-

4(5H)-one

To a solution of 8-methoxy-9-[4-(piperazin- l-yl)phenyl]thieno[2,3-c]quinolin-4(5H)-one (89 mg, 0.23 mmol) in methylene chloride (2 mL) was added N, N-diisopropylethylamine (0.42 mL, 0.68 mmol) and methanesulfonyl chloride (45 μί, 0.27 mmol) and the reaction mixture was stirred for 1 h. The reaction mixture was quenched with water and the layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over Na₂S04, filtered, concentrated and the residue was purified by preparatory HPLC (CI 8 silica, acetonitrile/water w/0.05% TFA gradient) to afford the desired product (72 mg, 68%) as a brown solid: ESI MS m/z 470 [C23H23N3O4S2 + H]⁺.

Example 413

tert-Butyl 4-(8-Methoxy-2-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

9-y l)benzy lcarbamate

Following General Procedure B A, 9-bromo-8-methoxy-2-methylthieno[2,3-c]

quinolin-4(5H)-one (100 mg, 0.31 mmol) was reacted with 4-[(tert-butoxycarbonylamino) methyl]phenylboronic acid (120 mg, 0.40 mmol) to afford desired product (80 mg, 55%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

Example 414

N-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]methanesulfonamide

Following Step 1 from General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)- one (50 mg, 0.10 mmol) was reacted with 4-(methylsulfonamido)phenylboronic acid (52 mg, 0.24 mmol) to afford the desired product (40 mg, 62%) as a brown solid: ESI MS m/z 400

[Ci₉Hi6N20 S2 + H]⁺.

Example 415

tert-Butyl l-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (600 mg, 2.0 mmol) was reacted with tert-butyl l -[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl]ethylcarbamate (340 mg, 39%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

8-Methoxy-9-{4-[l -(piperidi no[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.48 mmol) was reacted with 4-[l-(piperidin-l-yl)ethyl]phenylboronic acid (170 mg, 0.73 mmol) to afford the desired product (10 mg, 5%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.74-7.66 (m, 2H), 7.62-7.53 (m, 2H), 7.49-7.34 (m, 3H), 5.94 (d, J = 5.4 Hz, 1H), 4.61 (q, J = 6.9 Hz, 1 H), 3.86-3.78 (m, 1 H), 3.76 (s, 1 H), 3.47 (d, J = 12.6 Hz, 1H), 3.10-2.98 (m, 1H), 2.96-2.82 (m, 1 H , 2.1 1-1 .91 (m, 2H), 1.89 (d, J = 7.0 Hz, 2H), 1.85-1.70 (m, 1 H).

Example 417

2-[2-Fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl]acetonitrile

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (350 mg, 1 .1 mmol) was reacted with 2-[2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan

-2-yl)phenyl]acetonitrile (440 mg, 1 .7 mmol) to afford the desired product (400 mg, >99%) as a brown solid: ESI MS m/z 365 [C20H13FN2O2S + H]⁺

Example 265

9-|4-(2-Aminoethyl)-3-fluorophenyl]-8-methoxythieno|2,3-c]quinolin- 4(5H)-one Hydrochloride

•HCl

To a solution of 2-[2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-y 1) phenyljacetonitrile (49 mg, 0.14 mmol) in toluene (3 mL) was added borane (1.0 M in THF, 3.0 mL, 0.30 mmol) and the reaction was stirred at reflux for 3 h. The reaction mixture was cooled to room temperature, concentrated and the residue was purified by preparatory HPLC. The residue was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the hydrochloride salt (4.5 mg, 9%) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.63 (d, J = 5.4 Hz, 1 H), 7.56 (d, J = 9.0 Hz, 1 H), 7.50 (t, J = 7.8 Hz, 1 H), 7.40 (d, J = 9.1 Hz, 1 H), 7.1 1-7.05 (m, 2H), 6.1 1 (d, J = 5.4 Hz, 1 H), 3.76 (s, 3H), 3.25-3.08 (m, 4H), 2.75 (br s, 3H); ESI MS m/z 369 [C₂₀H,7F 2O₂S + H]⁺; HPLC 95.0% (AUC), t_R = 7.89 min.

Example 418

(S)-tert-Butyl l-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl]ethylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (280 mg, 0.89 mmol) was reacted with (S)-tert-butyl l-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl]ethylcarbamate (320 mg, 1.1 mmol) to afford the desired product (220 mg, 55%) as a white solid: ESI MS m/z 351 [C25H26 2O4S - Boc]⁺.

Example 232

(S)-9-[4-(l-Aminoethyl)phenyl]-8-methoxythieno[2,3-c]quinolin-

Following General Procedure C, (S)-tert-butyl l -[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl]ethylcarbamate (90 mg, 0.12 mmol) was reacted with TFA (3 mL) to afford the desired product (1 1 mg, 15%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.65-7.62 (m, 2H), 7.56-7.54 (m, 2H), 7.40-7.38 (m, 3H), 6.04 (d, J = 5.5 Hz, 1 H), 4.62 (q, J = 7.0 Hz, 1 H), 7.73 (s, 3H), 1.77 (d, J = 6.9 Hz, 3H); ESI MS m/z 351 [C20H18N2O2S + H]⁺; HPLC 97.6% (AUC), t_R = 8.33 min.

Example 216

8-Methoxy-9-{4-[l-(pyrrolidin-l-yl)ethyl]phenyl}thieno[2,3-c]quinoIin-

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (120 mg, 0.39 mmol) was reacted with 4-[ l -(pyrrolidin-l -yl)ethyl]phenylboronic acid (170 mg, 0.77 mmol) to afford the desired product (70 mg, 45%) as a white solid: Ή NMR (500 MHz,

CD3OD) δ 7.69-7.67 (m, 2H), 7.60 (d, J = 5.4 Hz, 1 H), 7.56 (d, J = 9.0 Hz, 1 H), 7.44-7.40 (m, 3H), 5.96 (d, J = 5.4 Hz, 1H), 4.54 (q, J = 6.8 Hz, 1 H), 3.89-3.84 (m, 1 H), 3.76 (s, 3H), 3.38-3.16 (m, 3H), 2.29-2.00 (m, 4H), 1.87 (d, J = 6.9 Hz, 3H); ESI MS m/z 405 [C24H24N2O2S + H]⁺; HPLC >99%, t_R = 8.98 min.

8-Methoxy-9-{4-[l -(piperidi no[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.48 mmol) was reacted with 4-[l -(piperidin- l -yl)ethyl]phenylboronic acid ( 170 mg, 0.73 mmol) to afford the desired product (10 mg, 5%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.74-7.66 (m, 2H), 7.62-7.53 (m, 2H), 7.49-7.34 (m, 3H), 5.94 (d, J = 5.4 Hz, 1 H), 4.61 (q, J = 6.9 Hz, 1 H), 3.86-3.78 (m, 1 H), 3.76 (s, 1 H), 3.47 (d, J = 12.6 Hz, 1 H), 3.10-2.98 (m, 1 H), 2.96-2.82 (m, 1 H), 2.1 1-1.91 (m, 2H), 1.89 (d, J = 7.0 Hz, 2H), 1.85-1.70 (m, 1 H).

Example 420

Following Step 1 from General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin

-4(5H)-one (350 mg, 1 .1 mmol) was reacted with 2-[2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2_ryl)phenyl]acetonitrile (440 mg, 1.7 mmol) to afford the desired product (400 mg, >99%) as a brown solid: ESI MS m/z 365 [C20H13FN2O2S + H]⁺

Example 421

9-[4-(3-Aminopropyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following the procedure outlined for Example 265, 3-[4-(8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl]propanenitrile (250 mg, 0.69 mmol) was reacted with borane (1.0 M in THF, 10 mL, 10 mmol) to afford the desired product (150 mg, 60%) as a brown oil: ESI MS m/z 365 [C21H20N2O2S + H]⁺.

Example 274

(R)-9-[4-(l-Aminoethyl)phenyl]-8-methoxythieno[2,3-c]quinolin- ¹

4(5H)-one Hydrochloride

Following General Procedure C, (R)-tert-butyl l-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl]ethylcarbamate (50 mg, 0.1 1 mmol) was reacted with TFA (3 mL) to afford the desired product (1 1 mg, 26%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ

7.63-7.62 (m, 2H), 7.56-7.55 (m, 2H), 7.40-7.37 (m, 3H), 6.04 (d, J = 5.4 Hz, 1 H), 4.62 (q, J = 6.9 Hz, 1 H), 3.79 (s, 3H), 2.77 (br s, 3H), 1.76 (d, J = 6.9 Hz, 3H); ESI MS m/z 351

[C₂oH,₈N₂0₂S + H]⁺; HPLC 98.7% (AUC), t_R = 8.24 min.

Example 422

(R)-tert-Butyl l -[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl]ethylcarbamate

-4(5H)-one (480 mg, 1.5 mmol) was reacted with (R)-tert-butyl l-[4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate (800 mg, 2.3 mmol) to afford the desired product (410 mg, 59%) as a brown solid: ESI MS m/z 451 [C₂₅H₂6N₂0₄S + H]⁺.

Example 423

2-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]- 2-methylpropanenitrile

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (380 mg, 1.2 mmol) was reacted with 2-methyl-2-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan

-2-yl)phenyl]propanenitrile (500 mg, 1.9 mmol) to afford the desired product (260 mg, 56%) as a brown solid: ESI MS m/z 375 [C₂₂H,₈N₂0₂S + H]⁺.

Example 424

9-[4-( 1 -Amino-2-methy lpropan-2-yl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following the procedure outlined for Example 265, 2-[4-(8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl]-2-methylpropanenitrile (250 mg, 0.67 mmol) was reacted with borane (1 .0 M in THF, 10 mL, 10.0 mmol) to afford the desired product (100 mg, 40%) as a yellow solid: ESI MS m/z 379 [C₂₂H₂₂N₂0₂S + H]⁺.

Example 425

9-{3-Fluoro-4-[(3-hydroxypyrrolidin-l -yl)methyl]phenyl}-8-methoxythieno

[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (180 mg, 0.58 mmol) was reacted with l -[2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) benzyl]pyrrolidin-3-ol (280 mg, 0.87 mmol) to afford the desired product (130 mg, 48%) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.79-7.72 (m, lH), 7.66 (d, J = 5.4 Hz, 1 H), 7.58 (d, J = 9.1 Hz, 1 H), 7.42 (d, J = 9.1 Hz, 1 H), 7.33-7.21 (m, 2H), 6.09 (td, J = 5.3, 2.4 Hz, 1 H), 4.75-4.53 (m, 3H), 3.91 -3.66 (m, 4H), 3.66-3.34 (m, 3H), 2.55-2.44 (m, 1 H), 2.28-2.1 5 (m, 1 H), 2.14-2.04 (m, 1 H).

Example 426

tert-Butyl 5-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2,3- dihydro-lH-inden-2-ylcarbamate

BocH

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.1 g, 3.6 mmol) was reacted with tert-butyl 5-bromo-2,3-dihydro-l H-inden-2-ylcarbamate (2.0 g, 5.6 mmol) to afford the desired product (250 mg, 15%) as a brown solid: ESI MS m/z 363

[C26H26 2O4S + H - 100]⁺. l -[4-(8-Methoxy-4-oxo-4,5-dihyd -yl)phenyl]cyclopropanecarbonitrile

Following General Procedure B, l -(4-bromophenyl)cyclopropanecarbonitrile (1.5 g, 7.1 mmol) was reacted with bis(pinacolato)diboron (2.7 g, 10 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.3 g, 4.2 mmol) to afford the desired product (378 mg, 29%) as a white solid: ESI MS m/z 373 I^H^C^S + H]⁺.

Example 428

tert-Butyl 7-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)- 3,4-dihydroisoquinoline-2(lH)-carboxylate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1 g, 3.3 mmol) was reacted with tert-butyl 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)

-3,4-dihydroisoquinoline-2(l H)-carboxylate (1.8 g, 5.0 mmol) to afford the desired product (720 mg, 48%) as a brown solid: ESI MS m/z 463 [C26H26N2O4S + H]⁺.

Example 429

8-Methoxy-9-(l ,2,3,4-tetrahydroisoquinolin-7-yl)thienof2,3-c]quinolin-4(5H)-one

Following General Procedure C, tert-Butyl 7-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)-3,4-dihydroisoquinoline-2(lH)-carboxylate (260 mg, 0.53 mmol) was reacted with TFA (5 mL) afford the desired product (180 mg, 20%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.61-7.56 (m, 1 H), 7.55 (dd, J = 9.0, 3.2 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1 H),

7.41-7.36 (m, 1 H), 7.22 (d, J = 7.8 Hz, 1 H), 7.16 (s, 1 H), 6.13 (d, J = 5.4 Hz, 1 H), 4.42 (s, 2H), 3.73 (s, 3H), 3.68-3.54 (m, 2H), 3.29-3.20 (m, 2H).

Example 430

tert-Butyl l-[2-Fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (800 mg, 2.6 mmoL) was reacted with tert-butyl l -[2-flu0ro-4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl]ethylcarbamate (1.4 g, 3.9 mmol) to afford the desired product (480 mg, 40%) as a brown solid: ESI MS m/z 469 [C25H25FN2O4S + H]⁺.

Example 431

3-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propanenitrile

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (400 mg, 1.3 mmol) was reacted with 3-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)

phenyl]propanenitrile (600 mg, 1.9 mmol) to afford the desired product (320 mg, 69%) as a brown solid: ESI MS m/z 361 [C₂iH_{16 2}0₂S + H]⁺.

Example 432

9-(4-Acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.0 g, 3.2 mmol) was reacted with l-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]ethanone (1.2 g, 4.8 mmol) to afford the desired product (520 mg, 46%) as a brown solid: Ή NMR (500 MHz, CD3OD) S 8.16 (d, J = 8.1 Hz, 2H), 7.61-7.54 (m, 2H), 7.45-7.39 (m, 3H), 6.05 (d, J = 5.4 Hz, 1 H), 3.75 (s, 3H), 2.71 (s, 3H).

9-{4-[ l -(Cyclopentylamino)e ieno[2,3-c]quinolin-4(5H)-one

Following General Procedure E, N-[ l-(4-bromophenyl)ethyl]cyclopentanamine (600 mg, 2.3 mmol) was reacted with bis(pinacolato)diboron (410 mg, 1.6 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (250 mg, 0.81 mmol) to afford the desired product (330 mg, 97%) as a brown solid: Ή NMR (300 MHz,

CD₃OD) δ 7.73-7.64 (m, 2H), 7.60-7.50 (m, 2H), 7.47-7.34 (m, 3H), 6.01 (d, J = 5.4 Hz, 1H), 4.57 (q, J = 6.8 Hz, 1 H), 3.74 (s, 3H), 3.62-3.45 (m, 1 H), 2.30-2.02 (m, 2H), 1.93-1.85 (m, 2H), 1 .81 (d, J = 6.7 Hz, 3H), 1 .77-1.51 (m, 4H).

Example 434

tert-Butyl l -[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl]propylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.1 g, 3.7 mmol) was reacted with tert-butyl l-[4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl) phenyl]propylcarbamate (2.0 g, 5.5 mmol) to afford the desired product (1.2 g, 68%) as a white solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

9-[4-(l-Aminopropyl)phenyl]-8 nolin-4(5H)-one Hydrochloride

Following General Procedure C, tert-butyl l -[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl]propylcarbamate (30 mg, 0.064 mmol) was reacted with TFA (2 mL) to afford the desired product (17 mg, 72%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.64-7.57 (m, 2H), 7.54 (d, J = 2.0 Hz, 1H), 7.53 (d, J = 1.6 Hz, 1H), 7.39-7.35 (m, 3H), 5.98 (d, J = 5.4 Hz, 1H), 4.32 (q, J = 5.1 Hz, 1H), 5.53 (s, 3H), 2.17-2.07 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H); ESI MS m/z 365 [C₂iH₂oN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 9.47 min.

Example 435

(S)-tert-Butyl l-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (760 mg, 2.4 mmol) was reacted with (S)-tert-butyl l -[4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl]ethylcarbamate (1.3 g, 3.7 mmol) to afford the desired product (730 mg, 66%) as a light yellow solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

9-{4-[l -(Dimethylamino)eth o[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.5 g, 4.8 mmol) was reacted with 4-[l-(dimethylamino)ethyl]phenylboronic acid (1.5 g, 6.3 mmol) to afford the desired product (1.1 g, 58%) as a white solid: ESI MS m/z 379 [C22H22 2O2S + H]⁺ _.

Example 139

tert-Butyl {l-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl] piperidin-4-yl}methylcarbamate

- Following General Procedure B, 9-bromo-8-methoxythieno[2,3_^c]quinolin-4(5H)-one~(l 10 mg,~ 0.31 mmol) was reacted with 4-({4-[(tert-butoxycarbonylamino)methyl]piperidin-l -yl} methyl)phenylboronic acid (80 mg, 0.26 mol) to afford the desired product (25 mg, 20%) as a yellow glass: Ή NMR (500 MHz, CD3OD) δ 7.69-7.66 (m, 2H), 7.57-7.54 (m, 2H), 7.41-7.38 (m, 3H), 5.96-5.95(m, 1 H), 4.48-^.44 (m, 2H), 3.75 (s, 3H), 3.70-3.64 (m, 2H), 3.27-2.91 (m, 4H), 2.25-1 .95 (m, 2H), 1.57 (s, 1 H), 1.52-1 .42 (m, 10 H); ESI MS m/z 534 [C30H₃5N3O4S + H]⁺; HPLC 97.6% (AUC), t_R = 14.10 min.

Example 437

(E)-tert-Butyl l -[3-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)allyl] piperidin-4-ylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (180 mg, 0.48 mmol) was reacted with (E)-tert-butyl l -[3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-

2-yl)allyl]piperidin-4-ylcarbamate (100 mg, 0.32 mmol) to afford the desir,ed product (86 mg, 57%) as a brown solid: ESI MS m/z 470 [C25H31N3O4S + H]⁺.

Example 152

(E)-9-[3-(4-Aminopiperidin-l-yl)prop-l-enyl]-8-methoxythieno

[2,3-c]quinolin-4(5H)-one

Following General Procedure C, (E)-tert-butyl l -[3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)allyl]piperidin-4-ylcarbamate (40 mg, 0.085 mmol) was reacted with TFA (1 mL) to afford the desired product (15 mg, 86%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.94 (d, J = 5.3 Hz, 1 H), 7.86 (d, J = 5.3 Hz, 1H), 7.34 (d, J = 9.1 Hz, 1 H), 7.24 (d, J = 9.1 Hz, 1 H), 7.06 (d, J = 16.0 Hz, 1 H), 6.14-6.08 (m, 1 H), 4.12 (d, J = 7.1 Hz, 2H), 3.84 (br s, 2H), 3.55 (br s, 1 H), 3.26 (br s, 3H), 2.38 (d, J = 13.3 Hz, 2H), 2.12-2.07 (m, 2H), 1.35-1.31 (m, 1 H), 0.96-0.90 (m, 1 H); ESI MS m/z 370 [C20H23N3O2S + H]⁺; HPLC 95.6% (AUC), t_R = 6.78 min.

Example 164

9-{4-[(Dimethylamino)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following the procedure outlined for Example 460,

9-[4-(aminomethyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.27 mmol) was reacted with formaldehyde (37% in water, 20 mg, 0.67 mmol) to afford the desired product (45 mg, 47%): Ή NMR (500 MHz, CD₃OD) δ 7.67 (d, J = 8.2 Hz, 2H), 7.58-7.54 (m, 2H), 7.42-7.38 (m, 3H), 5.96 (d, J = 5.5 Hz, 1 H), 4.47 (s, 2H), 3.75 (s, 3H), 2.98 (s, 6H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.50 min.

Example 438

9-{4-[(Diethylamino)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure E, N-(4-bromobenzyl)-N-ethylethanamine (200 mg, 0.83 mmol) was reacted with bis(pinacolato)diboron (230 mg, 0.91 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (260 mg, 0.83 mmol) to afford the desired product (58 mg, 25%) as a white solid: Ή NMR (500 MHz,

CD3OD) δ 7.69 (d, J = 8.2 Hz, 2H), 7.60-7.54 (m, 2H), 7.46-7.43 (m, 2H), 7.41 (d, J = 9.1 Hz, 1 H), 5.99 (d, J = 5.4 Hz, 1 H), 4.50 (s, 2H), 3.75 (s, 3H), 3.41-3.32 (m, 4H), 1.44 (t, J = 7.3 Hz, 6H).

Example 188

8-Methoxy-9-{4-[(methylamino)methyI] phenyl} thieno[2,3-c|quinolin-4(5H)-one

Following General Procedure E, 1 -(4-bromophenyl)-N-methylmethanamine (200 mg, 1.0 mmol) was reacted to bis(pinacoato)diboron (280 mg, 1.1 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (310 mg, 1 .0 mmol) to afford the desired product ( 145 mg, 42%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.65 (d, J = 8.1 Hz, 2H), 7.58-7.52 (m, 2H), 7.42-7.35 (m, 3H), 6.02 (d, J = 5.4 Hz, 1 H), 4.33 (s, 2H), 3.73 (s, 3H), 2.83 (s, 3H).

Example 439

tert-Butyl 4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.48 mmol) was reacted with 4-[(tert-butoxycarbonylamino)methyl]phenylboronic acid (180 mg, 0.73 mmol) to afford the desired product (180 mg, 83%) as a brown solid: ESI MS m/z 437 [C24H24N2O4S + H]⁺.

9- {4-[(Isopropylamino)met [2,3-c]quinolin-4(5H)-one

Following General Procedure E, N-(4-bromobenzyl)propan-2-amine (200 mg, 0.88 mmol) was reacted with bis(pinacolato)diboron (240 mg, 0.96 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (270 mg, 0.88 mmol) to afford the desired product (190 mg, 57%) as a light brown solid: Ή NMR (500 MHz,

CD₃CD₂OD) δ 7.68-7.63 (m, 2H), 7.56-7.49 (m, 2H), 7.41-7.34 (m, 3H), 6.04 (dd, J = 5.4, 2.4 Hz, 1 H), 4.33 (s, 2H), 3.72-3.67 (m, 3H), 3.56-3.50 (m, 1 H), 1.45 (dd, J = 6.6, 2.2 Hz, 6H).

Example 269

9-{4-|(Ethylamino)methyl]phenyl}-8-methoxythieno|2,3-c|quinolin- 4(5H)-one Hydrochloride

Following General Procedure E, N-(4-bromobenzyl)ethanamine (300 mg, 1.4 mmol) was reacted with bis(pinacolato)diboron (390 mg, 1.5 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (430 mg, 1 .4 mmol) to afford the desired product (160 mg, 31 %) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.67 (d, J = 8.1 Hz, 2H), 7.57-7.54 (m, 2H), 7.39-7.36 (m, 3H), 6.03 (d, J = 5.5 Hz, 1 H), 4.34 (s, 2H), 3.72 (s, 3H), 3.23 (q, J = 7.3 Hz, 2H), 1 .97 (s, 2H), 1.42 (t, J = 7.3 Hz, 3H); ESI MS m/z 365

[C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.61 min.

Example 441

(E)-tert-Butyl l -[3-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-y l)al ly 1] piperid in-3 -y lcarbamate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (530 mg, 1 .7 mmol) was reacted with (E)-tert-Butyl l -[3-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) allyl]piperidin-3-ylcarbamate (320 mg, 0.88 mmol) to afford the desired product (190 mg, 47%) as a light brown solid: ESI MS m/z 456 [C24H29N3O4S + Hf.

Example 442

tert-Butyl 4-(6-Fluoro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

9-y l)benzy lcarbamate

Following General Procedure B, 9-bromo-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1 50 mg, 0.50 mmol) was reacted with tert-butyl 4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) benzy lcarbamate (200 mg, 0.60 mmol) to afford the desired product (100 mg, 48%) as a brown solid: ESI MS m/z 455 [C24H23FN2O4S + H]⁺.

Example 257

9-[4-(Aminomethyl)phenyl|-6-fluoro-8-methoxythieno[2,3-c]quinolin- 4(5H)-one Hydrochloride

Following General Procedure D-l , tert-butyl 4-(6-fluoro-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)benzylcarbamate (15 mg, 0.030 mmol) was reacted with HCI (2 N in diethyl ether, 1 .5 mL) to afford the desired product ( 10 mg, 90%) as a white solid: Η NMR (500 MHz, CD3OD) δ 7.63 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 5.4 Hz, 1 H), 7.36 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 12.7 Hz, 1 H), 6.04 (d, J = 5.4 Hz, 1 H), 4.27 (s, 2H), 3.72 (s, 3H); ESI MS m/z 355

[Ci9H _{l 5}F ₂02S + H]⁺; HPLC 99% (AUC), t_R = 10.64 min.

Example 443

9-{4-[l -(Dimethylamino)ethyl]phenyl}-6,7-difluoro-8-methoxythieno

[2,3-c]quinolin-4(5H)-one

Following General Procedure B, 9-bromo-6,7-difluoro-8-methoxythieno[2,3-c]quinolin- 4(5H)-one ( 150 mg, 0.40 mmol) was reacted with 4-[ l-(dimethylamino)ethyl]phenylboronic acid (120 mg, 0.50 mmol) to afford the desired product (55 mg, 35%) as an off-white solid: ESI MS m/z 415 [C22H20F2N2O2S + H]⁺.

9-{4-[2-(Dimethylamino)et [2,3-c]quinolin-4(5H)-one

Following the procedure outlined for Example 460, 9-[4-(2-aminoethyl)phenyl]-8- methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with formaldehyde (100 mg, 1.0 mmol) to afford the desired product (85 mg, 84%) as a white solid: Ή NMR (500 MHz, CD₃CN+D2O) δ 7.54-7.50 (m, 2H), 7.42 (d, J = 7.8 Hz, 2H , 7.32 (d, J = 9.1 Hz, 1 H), 7.13 (d, 7.8 Hz, 2H), 5.83 (d, J = 5.3 Hz, 1 H), 3.69 (s, 3H), 3.43-3.40 (m, 2H), 3.16-3.13 (m, 2H), 2.92 (s, 6H).

Example 445

9-(4-Amino-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure B,-9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with 2-methoxy-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)aniline (150 mg, 0.50 mmol) to afford the desired product (64 mg, 60%) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.61 (d, J = 5.3 Hz, 1H), 7.58-7.53 (m, 2H), 7.41 (d, J = 5.3 Hz, 1 H), 7.16 (s, 1 H), 7.01 (d, J = 5.3 Hz, 1 H), 6.09 (d, J = 5.1 Hz, 1 H), 3.93 (s, 3H), 3.77 (s, 3H).

Example 222

9-{4-[l-(Dimethylamino)ethyl|phenyl}-6-fluoro-8-methoxythieno

[2,3-c)quinolin-4(5H)-one Hydrochloride

Following General Procedure B, 9-bromo-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with 4-[l-(dimethylamino)ethyl]phenylboronic acid (100 mg, 0.45 mmol) to afford the desired product (49 mg, 41 %) as a white solid: Ή NMR (500 MHz, DMSO-d₆) δ 10.28 (s, 1 H), 7.77 (d, J = 5.4 Hz, 1 H), 7.71 (q, J = 8.0 Hz, 2H), 7.46 (d, J = 12.8 Hz, 1 H), 7.38 (d, J = 8.2 Hz, 2H), 5.69 (d, J = 5.4 Hz, 1 H), 4.64 (t, J = 6.0 Hz, 1 H), 3.71 (s, 3H), 2.82 (d, J = 4.2 Hz, 3H), 2.70 (d, J = 4.4 Hz, 3H), 1.74 (d, J = 6.8 Hz, 3H); ESI MS m/z 397 [C22H21FN2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.85 min.

Example 446

tert-Buty 1 { 1 -[ ieno[2,3-c] quinol ate

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with tert-butyl

{ l -[2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzyl]piperidin-4-yl}methylcarba mate (150 mg, 0.36 mmol) to afford the desired product (81 mg, 49%0 was a yellow solid: ESI MS m/z 552 [C30H34FN3O4S + H]⁺.

Example 447

tert-Buty 1 [5-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)thiophen-

2-yl]methylcarbamate

BocHN

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (150 mg, 0.48 mmol) was reacted with 5-[(tert-butoxycarbonylamino)methyl]thiophen-2-ylboronic acid (130 mg, 0.53 mmol) to afford the desired product (30 mg, 18%) as a off-white solid: Ή NMR (500 MHz, CD3OD) δ 7.74 (d, J = 5.4 Hz, 1 H), 7.56 (d, J = 9.1 Hz, 1 H), 7.36 (d, J = 9.1 Hz,

1 H), 6.49 (d, J = 3.1 Hz, 1 H), 6.40 (br s, 1 H), 6.01 (d, J = 5.4 Hz, 1 H), 4.27 (s, 2H), 3.82 (s, 3H), 1.39 (s, 9H).

Example 448

2-Fluoro-N-(2-hydroxyethyI)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)benzenesulfonamide

Following General Procedure E, 4-bromo-2-fluoro-N-(2-hydroxyethyl)benzenesulfonamide (3.30 mg, 1.1 mmol) was reacted with bis(pinacolato)diborane (300 mg, 1.2 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (310 mg, 1.0 mmol) to afford the desired product (68 mg, 13%) as an off-white solid: Ή NMR (300 MHz, DMSO-d₆) δ 1 1.95 (s, lH), 8.04 (t, J = 5.8 Hz, 1H), 7.93 (t, J = 7.8 Hz, 1H), 7.93 (d, J = 5.4 Hz, 1 H), 7.57 (d, J = 9.1 Hz, 1H), 7.49-7.43 (m, 2H), 7.30 (dd, J = 8.0, 1.5 Hz, 1H), 5.89 (d, J = 5.4 Hz, 1H), 4.78 (t, J = 5.6 Hz, 1H), 3.72 (s, 3H), 3.46 (q, J = 6.2 Hz, 2H), 3.05 (m, 2H).

Example 449

4-(8-Methoxy-4-oxo-4,5-dihydrot ,N-dimethylbenzenesulfonamide

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.32 mmol) was reacted with N,N-dimethyl-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) benzenesulfonamide (1 10 mg, 0.35 mmol) to afford the desired product (33 mg, crude) as a brown solid: ESI MS m/z 415 ^oHig^O^ + H]⁺.

Example 450

N-(2-Hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (500 mg, 1 .5 mmol) was reacted with N-(2-hydroxyethyl)-4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl) benzenesulfonamide (450 mg, 1.5 mmol) to afford the desired product (130 mg, 20%) as an off-white solid: Ή NMR (300 MHz, DMSO-d₆) δ 1 1 .93 (s, 1 H), 7.94 (d, J = 8.4 Hz, 2H), 7.78-7.74 (m, 2H), 7.58-7.42 (m, 4H), 5.74 (d, J = 5.4 Hz, 1 H), 4.78 (t, J = 5.6 Hz, 1 H), 3.71 (s, 3H), 3.45 (q, J = 6.1 Hz, 2H), 2.93 (q, J = 6.2 Hz, 2H).

Example 333

N-(2-Fluoroethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

9-yl)benzenesulfonamide

To a solution of N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)benzenesulfonamide (120 mg, 0.28 mmol) in methylene chloride (10 mL) and THF (6 mL) under nitrogen at -78 °C was added DAST (89 mg, 0.56 mmol) and the reaction mixture was stirred at -78 °C for 2 h and warmed to room temperature and stirred for 16 h. The reaction mixture was concentrated and the residue was purified by column chromatography (silica gel, ethyl acetate/hexanes gradient). The resulting crude residue was triturated in methylene chloride and filtered to afford the desired product (90 mg, 75%) as a off-white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.92 (s, 1 H), 8.10 (t, J = 5.9 Hz, 1H), 7.95 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 5.4 Hz, 1 H), 7.56 (d, J = 9.1 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 9.2 Hz, 1 H), 5.75 (d, J = 5.4 Hz, 1 H), 4.51 (t, J = 4.9 Hz, 1H), 4.42 (t, J = 4.9 Hz, 1H), 3.71 (s, 3H), 3.24 (q, J = 5.2 Hz, 1 H), 3.19 (q, J = 5.2 Hz, 1H); ESI MS m/z 433 [C20H17FN2O4S2 + H]⁺;

HPLC 93.4% (AUC), t_R = 15.64 min.

Example 451

Following General Procedure E, tert-butyl 4-bromobenzylcarbamate (2.9 g, 10 mmol) was reacted with bis(pinacolato)diborane (2.8 g, 1 1 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.8 g, 9.0 mmol) to afford the desired product (2.7 g, 68%) as a brown solid: ESI MS m/z 437 [C₂₄H2 N₂0 S + H]

Example 452

tert-Butyl 4-(6-Bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

9-yl)benzylcarbamate

To a solution of tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) benzylcarbamate (29 mg, 0.055 mmol) in DMF ( 1 mL) was added N-bromosuccinimide (12 mg, 0.066 mmol) and the reaction was stirred at room temperature for 1 h and heated at 50 °C for 2 h. The reaction mixture was concentrated and the residue was purified by preparatory TLC (silica, methanol/methylene chloride gradient) to afford the desired product ( 10 mg, 35%): ESI MS m/z 516 [C₂₄H23Br 20₄S + H]⁺.

Example 453

tert-Butyl 2-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl] propan-2-ylcarbamate

Following General Procedure E, tert-butyl 2-(4-bromophenyl)propan-2-ylcarbamate (160 mg, 0.50 mmol) was reacted with bis(pinacolato)diboron (140 mg, 0.55 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one ( 140 mg, 0.45 mmol) to afford the desired product (1 10 mg, 47%) as a brown solid: ESI MS m/z 465 [C26H28 2O4S + H]⁺.

Example 454

tert-Butyl 4-(6-Chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

9-yl)benzylcarbamate

A solution of tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

benzylcarbamate (45 mg, 0.10 mmol) and N-chlorosuccinimide ( 17 mg, 0.13 mmol) in DMF ( 1 mL) was heated at 50 °C for 3 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by preparatory HPLC (water/acetonitrile w 0.05% TFA gradient) to afford the desired product (15 mg, 32%) as a brown solid: ESI MS m/z 471

[C₂4H23C1N₂0₄S + H]⁺.

Example 455

tert-Butyl 2-[4-(6-Chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-y l)phenyl] pro pan-2-y lcarbamate

A solution of tert-butyl 2-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl]propan-2-y lcarbamate (130 mg, 0.27 mmol) and N-chlorosuccinimide (47 mg, 0.35 mmol) in DMF (3 mL) was heated at 70 °C for 2 h. The reaction mixture was cooled to room temperature, quenched with water and the aqueous layer was extracted with methylene chloride/methanol (9: 1). The combined organic layers were dried over sodium sulfate, filtered, concentrated and the residue was purified by column chromatography (silica,

methanol/methylene chloride gradient) to afford the desired product (42 mg, 31 %) as a brown solid: ESI MS m z 500 [C26H27CIN2O4S + H]⁺.

Example 456

N-[4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylphenyl]methanesulfona mide

Following General Procedure E, N-(4-bromo-2-methylphenyl)methanesulfonamide (130 mg, 0.50 mmol) was reacted with bis(pinacolato)diboron (140 mg, 0.55 mmol) to afford the crude boronic ester which was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (140 mg, 0.45 mmol) to afford the desired product (51 mg, 27%) as a brown solid: ESI MS m/z 415 [C2oH₁₈N₂0₄S₂ + H]⁺.

Example 599

(R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

Following General Procedure E, (R) -tert-butyl 2-(4-bromophenyl)propylcarbamate (60 mg, 0.20 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.20 mmol) to afford the desired product (52 mg, 62%) as a brown solid: ESI MS m/z 479 [C₂₇H3oN₂0₄S]⁺

Example 600

tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny l)propan-2-y lcarbamate

Following General Procedure E, feri-butyl 2-(4-bromophenyl)propan-2-ylcarbamate (0.44 g, 1.4 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (0.45 g, 1.4 mmol) to afford the desired product (0.53 g, 79%) as a brown solid: ESI MS m/z 479

[C27H30N2O4S + H]⁺.

Example 601

Following General Procedure E, tert-butyl 4-bromobenzylcarbamate (0.78 g, 2.7 mmol) was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (0.76 g, 2.5 mmol) to afford the desired product (0.66 g, 62%) as a brown solid: ESI MS m/z 437 [C24H24N2O4S + H]⁺.

Example 602

(R)-tert-B ty\ l-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethylcarbamate

Following General Procedure E, (R) -te t-buty\ l-(4-bromophenyl)ethylcarbamate (60 mg, 0.20 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.20 mmol) to afford the desired product (52 mg, 62%) as a brown solid:

Example 603

(R)-tert-Buty\ l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)ethy lcarbamate

Following General Procedure E, (R)-tert-buty\ l -(4-bromophenyl)ethylcarbamate (1.5 g, 5 mmol) was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1.4 g, 4.6 mmol) to afford the desired product (0.90 g, 43%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

Example 604

(S)-tert-Butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny l)ethy lcarbamate

Following General Procedure E, (S)-tert-bu y\ l -(4-bromophenyl)ethylcarbamate (60 mg, 0.20 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.20 mmol) to afford the desired product (52 mg, 62%) as a brown solid: ESI MS m/z 465

Example 605

tert-Butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethylcarbamate

Following General Procedure E, /eri-butyl l -(4-bromophenyl)ethylcarbamate (3.0 g, 10 mmol) was reacted with 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (2.8 g, 9.0 mmol) to afford the desired product (2.0 g, 50%) as a brown solid: ESI MS m/z 45 1 [C25H26N2O4S + H]⁺.

Example 606

(R)-tert-Butyl 1 -(4-(6-chloro-8-methoxy-4 -oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propylcarbamate

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (0.67 g, 1.5 mmol) was reacted with

N-chlorosuccinimide (0.29 g, 1.6 mmol) in DMF ( 10 mL) to afford the desired product (0.28 g, 35%) as a brown solid: ESI MS m/z 499 [C26H₂7C1N₂0₄S + H]⁺.

Example 607

tert-Butyl l -(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)ethylcarbamate

Following General Procedure I, tert-buty\ l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)ethylcarbamate (1.0 g, 2.2 mmol) was reacted with N-bromosuccinimide (0.45 g, 2.5 mmol) in DMF (10 mL) to afford the desired product (0.35 g, 29%) as a brown solid: ESI MS m/z 529 [C₂₅H₂5BrN₂0₄S + H]⁺. c]quinolin-9-yl) benzylcarbamate

Following General Procedure I, tert-butyl 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)benzylcarbamate (0.66 g, 1.5 mmol) was reacted with N-bromosuccinimide (0.30 g, 1.7 mmol) in DMF (10 mL) to afford the desired product (0.39 g, 51%) as a brown solid: ESI MS m/z 515 [C24H₂3BrN₂0₄S + H]⁺.

Example 609

tert-Butyl 4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

benzylcarbamate

Following General Procedure J, tert-butyl

4-(6-bromo-8-methoxy-4-oxo-4,-5-dihydrothieno[2,3-c] quinolin-9-yl)benzylcarbamate (52 mg, 0.10 mmol) was reacted with trimethylboroxine (13 mg, 0.10 mmol) to afford the desired product (43 mg, 95%) as a grey solid: ESI MS m/z 451 [C^r^^O^S + H]⁺.

Example 610

tert-Butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

phenyl)ethylcarbamate

Following General Procedure J, /er/-butyl l -(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (32 mg, 0.060 mmol) was reacted with

trimethylboroxine (8 mg, 0.060 mmol) to afford the desired product (20 mg, 61 %) as a grey solid: ESI MS m/z 465 [C26H28N2O4S + H]⁺.

Example 1168

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, (R)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (43 mg, 0.095 mmol) was reacted with tribromoborane (1 .0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (18 mg, 51 %) as a grey solid: Ή NMR (300 MHz, DMSO-cfc) δ 10.75 - 10.65 (m, 1 H), 9.14 (s, 1 H), 8.09 (s, 3H), 7.68 (d, J = 5.4 Hz, 1 H), 7.43 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.05 (s, 1 H), 5.86 (d, J = 5.4 Hz, 1 H), 3.27 - 2.95 (m, 3H), 1.38 (d, J = 6.6 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC 98.6%, t_R = 8.42 min.

( ?)-9-(4-(l-Aminoethyl)phe no[2,3-c]quinolin-4(5H)-one

Following General Procedure F, (R)-tert-buty\ l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (43 mg, 0.095 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (18 mg, 51 %) as a grey solid: Ή NMR (300 MHz, DMSO-i/₆) δ 10.72 (s, 1 H), 8.52 (s, 3H), 7.65 (dd, J = 13.3, 6.8 Hz, 3H), 7.30 (d, J = 8.2 Hz, 2H), 7.06 (s, 1 H), 5.87 (d, J = 5.4 Hz, 1 H), 4.64 - 4.45 (m, 1 H), 2.50 (s, 3H), 1.63 (d, J= 6.8 Hz, 3H); ESI MS m/z 480 [C27H33N3O3S + H]⁺; HPLC 98.6%, t_R = 8.42 min.

Example 1212 9-(4-(Aminomethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (43 mg, 0.095 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (18 mg, 51%) as a grey solid: Ή MR (500 MHz, CD₃OD) δ 7:62 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 5.4 Hz, 1 H), 7.39 (d, J = 8.0 Hz, 2H), 7.07 (s, 1 H), 6.10 (d, J = 5.4 Hz, l H), 4.26 (s, 1 H), 2.57 (s, 3H); ESI MS m/z 335

- H]^"; HPLC 96.7%, t_R = 7.99 min.

Example 1225

(S)-9-(4-(l-Aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, (S)-9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno [2,3-c]quinolin-4(5H)-one (52 mg, 0.1 1 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (20 mg, 46%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.62 (d, J = 7.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, l H), 7.39 (d, J = 7.4 Hz, 2H), 7.07 (s, 1 H), 6.09 (d, J = 5.4 Hz, 1 H), 4.61 (q, J = 6.9 Hz, 1 H), 2.57 (s, 3H), 1 .76 (d, J = 6.9 Hz, 3H); ESI MS m/z 35 1 ^oH^C^S + H]⁺; HPLC > 99%, t_R = 8.40 min.

Example 1032

9-(4-(l-Aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c)quinolin-4(5H)-one hydrochloride

Following General Procedure F, tert-butyl l -(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (1 7 mg, 0.032 mmol) was reacted with

tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (8 mg, 55%) as a light yellow solid: 1 H NMR (500 MHz, MeOD) δ 7.62 (d, J = 7.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1H), 7.42 - 7.37 (m, 2H), 7.07 (d, J= 0.7 Hz, 1H), 6.09 (d, J= 5.4 Hz, 1H), 4.67-4.56 (m, 1H), 2.57 (s, 3H), 1.76 (d,J= 6.9 Hz, 3H); ESI MS m/z 415 [Ci₉H₁₅BrN₂0₂S + H]⁺; HPLC 95.0%, t_R = 12.16 min.

Example 1066

9-(4-(l-Aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinoIin-4(5H)-one

Following General Procedure F,

9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (20 mg, 0.043 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (10 mg, 60%) as a light grey solid: 1H NMR (500 MHz, MeOD) δ 7.62 (d, J= 7.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1H), 7.42 - 7.37 (m, 2H), 7.07 (d, J= 0.7 Hz, 1H), 6.09(d,J=5.4Hz, 1H), 4.67 - 4.56 (m, 1H), 2.57 (s, 3H), 1.76 (d, J = 6.9 Hz, 3H); ESI MS m/z 351 [C20H18N2O2S + H]⁺; HPLC > 99%, t_R = 8.40 min.

Example 1123

(R)-9-(4-(l-Aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-

Following General Procedure F, (R)-tert-butyl l-(4-(6-bromo-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (24 mg, 0.045 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (18 mg, 88%) as a light grey solid: Ή NMR (500 MHz, MeOD) δ 7.64 (dd,J= 10.4, 3.5 Hz, 3H), 7.61 (d, 7=5.4 Hz, 1H), 7.47 (s, 1H), 7.42 (d, .7=7.5 Hz, 2H), 6.07 (d,J=5.4 Hz, 1H), 4.65-4.59 (m, 1H), 1.76 (d, J= 6.9 Hz, 3H); ESI MS m/z 415 [Ci₉Hi₅BrN₂0₂S + H]⁺; HPLC 97.0%, tR = 8.74 min.

Example 1159

(R)-9-(4-(l-Aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2_r3-c]quinolin-4(5H)- hydrochloride

Following General Procedure F, (R)-tert-butyl l-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (30 mg, 0.063 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (22 mg, 87%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.63 - 7.56 (m, 2H), 7.53 (d,J= 5.4 Hz, 1H), 7.40 (t,J= 6.6 Hz, 3H), 7.08 (s, 1H), 6.04 (d,J= 5.4 Hz, 1H), 4.31 (dd,J= 9.2, 5.9 Hz, 1H), 2.57 (s, 3H), 2.21 - 2.01 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H); ESI MS m/z 383 [C₂₀H₁₇ClN2O2S - H]^"; HPLC 96.9%, t_R = 8.69 min.

Example 1157

(/f)-9-(4-(l-Aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

Following General Procedure F, (R)-tert-b ty\ l-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (30 mg, 0.063 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (22 mg, 87%) as a light grey solid: Ή NMR (500 MHz, CD₃OD) δ 7.63 - 7.56 (m, 2H), 7.53 (d,J=5.4 Hz, 1H), 7.40 (t,J= 6.6 Hz, 3H), 7.08 (s, 1H), 6.04 (d,J=5.4 Hz, 1H), 4.31 (dd, J= 9.2, 5.9 Hz, 1H), 2.57 (s, 3H), 2.21 - 2.01 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC > 99%, t_R = 8.69 min.

Example 1330

9-(4-(2-Aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno|2,3-c]quinoIin-4(5H)-

Following General Procedure F, (S)-9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno [2,3-c]quinolin-4(5H)-one (52 mg, 0.11 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (20 mg, 46%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.68 (d, J= 8.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1H), 7.41 (d,J=8.4 Hz, 2H), 7.07 (s, 1H), 6.08 (d,J=5.4 Hz, 1H), 2.57 (s, 3H), 1.86 (s, 6H); ESI MS mz 363 [C21H20N2O2S - H]^"; HPLC 98.7%, t_R = 8.51 min: Example 61 1 982

9-bromo-8-methoxy-6-methyl-5-((2-(trimethylsilyl)ethoxy)methyl)thieno[2,3-c]

quinolin-4(5H)-one

To a suspension of 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (2.2 g, 6.8 mmol) in a mixture of DMF (15 mL) and THF (15 mL) at 0 °C was added sodium hydride (60%, 0.54 g, 13.6 mmol). The reaction mixture was stirred at 0 °C for 30 min before

(2-(chloromethoxy)ethyl)trimethylsilane (3.4 g, 20 mmol) was added. The resulting mixture was stirred at rt overnight and then poured into ice-water (50 mL). The resulting precipitate was filtered and purified by column chromatography (silica, heptane/ethyl acetate) to afford the desired product (2.7 g, 87%) as a light yellow solid: ESI MS m/z 454 [Ci₉H₂₄Br 0₃SSi + H]⁺.

Example 612

9-Bromo-8-methoxy-2,6-dimethyl-5-((2-(trimethylsilyl)ethoxy)methyl)thieno

[2,3-c]quinolin-4(5H)-one

To a stirred solution of diidopropylamine (85 ί, 0.6 mmol) in THF (2.5 mL) at -78 °C was added n-BuLi (2.5 M, 0.24 mL, 0.60 mmol) and the reaction mixture was stirred at 0 °C for 10 min then cooled to -78 °C. A solution of 9-bromo-8-methoxy-6-methyl-5-((2- (trimethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)-one (0.23 g, 0.50 mmol) in THF (1 mL) was added dropwise and the reaction mixture was stirred at -78 °C for 30 min.

lodomethane (93 ί, 1.5 mmol) was added and the reaction mixture was stirred at -78 °C for 2 h and quenched by the addition of satd. aq. ammonium chloride and extracted with

dichloromethane. The organics were dried over a S0₄, filtered, concentrated in vacuoand the residue was purified by column chromatography (silica, heptane/ethyl acetate) to afford the desired product (0.13 g, 55%) as a white solid: ESI MS m/z 468 [C₂₀H₂₆BrNO₃SSi + H]⁺.

Example 613

(R)-tert-Butyl 2-(4-(8-methoxy-2,6-dimethyl-4-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure B, (R)-tert-but \ 2-(4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (0.12 g, 0.33 mmol) was reacted with 9-bromo-8- rnethoxy-2,6-dirnethyl-5-((2-(trirnethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)-one (0.12 g, 0.33 mmol) to afford the desired product (78 mg, 45%) as a solid: ESI MS m/z 623

[C34H46N2O5SS1 + H]⁺.

Example 1341

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-8-methoxy-2,6-dimethylthieno

|2,3-c]quinolin-4(5H)-one hydrochloride

To a solution of (R)-tert-butyl 2-(4-(8-methoxy-2,6-dimethyl-4-oxo-5-((2-(trimethylsilyl) ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (24 mg, 0.039 mmol) in CH2CI2 (1 mL) at rt was added trifluoroacetic acid (1 .0 mL) and the reaction was stirred at that temperature for 2 h. The mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH4OH (2 mL). The resulting mixture was stirred at rt for 2h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product (5 mg, 30%) as a hydrochloride salt: Ή NMR (500 MHz, CD₃OD) δ 7.52 (dd, J = 7.8, 1.5 Hz, 1 H), 7.47 (dd, J = 7.7, 1.5 Hz, l H), 7.32 (s, 1 H), 7.31 - 7.22 (m, 2H), 5.30 (d, J = 2.7 Hz, 1H), 3.29 - 3.18 (m, 3H), 2.63 (s, 3H), 1.47 (d, J = 6.1 Hz, 3H); ESI MS m/z 392 [C₂₃H24 ₂0₂S + H]⁺.

Example 1340

(R)-9-(4-(l-Aminopropan-2-yI)phenyl)-8-hydroxy-2,6-dimethylthieno[2,3-c]

quinolin-4(5H)-one

To a solution of (R)-tert-butyl 2-(4-(8-methoxy-2,6-dimethyl-4-oxo-5-((2-(trimethylsilyl) ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (40 mg, 0.064 mmol) in CH₂C1₂ (1 mL) at 0 °C was added BBr₃ (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) and the reaction was stirred at that temperature for 1 h and quenched by pouring onto water or ice-water.The resulting mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH₄OH (2 mL). The resulting mixture was stirred at rt for 2h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt: Ή NMR (500 MHz, CD₃OD) δ 7.55 (dd, J = 7.9, 1.9 Hz, 1 H), 7.45 (dd, J= 7.7, 1.9 Hz,

1 H), 7.34 (dd, J= 7.9, 1.8 Hz, 1 H), 7.28 (dd, J = 7.7, 1 .7 Hz, 1 H), 7.06 (d, .7 = 0.7 Hz, 1H), 5.70 (d, J = 1.1 Hz, 1 H), 3.29 - 3.13 (m, 3H), 2.55 (s, 3H), 2.30 (d, J = 1.0 Hz, 3H), 1.50 (d, J = 6.5 Hz, 3H); ESI MS m/z 378 [C₂2H₂₂N₂0₂S + H]⁺.

Example 614

9-Bromo-2-chloro-8-methoxy-6-methyl-5-((2-(trimethyIsilyl)ethoxy)methyl)thieno

[2,3-c]quinolin-4(5H)-one

To a stirred solution of diidopropylamine (85 μί, 0.6 mmol) in THF (2.5 mL) at -78 °C was added n-BuLi (2.5M, 0.24 mL, 0.6 mmol).The resulting mixture was stirred at 0 °C for 10 min and then cooled at -78 °C. A solution of 9-bromo-8-methoxy-6-methyl-5-((2- (trimethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)-one (0.23 g, 0.50 mmol) in THF (1 mL) was added dropwise and the resulting mixture was stirred at -78 °C for 30 min.

Hexachloroethane (0.24 g, 1.0 mmol) was added dropwise and the mixture was stirred at -78 °( for 2h and allowed to warm to rt. The reaction was quenched by adding saturated ammonium chloride and extracted with dichloromethane (2*). The combined extracts were dried over Na₂S04, filtered and concentrated in vacuo, he residue was purified by column

chromatography (heptane/ethyl acetate) to afford the desired product (0.13 g, 52%) as a white solid: ESI MS m/z 488 [C,₉H₂₃BrClN0₃SSi+ H]⁺.

Example 615

(R)-tert-Butyl 2-(4-(2-chloro-8-methoxy-6-methyl-4-oxo-5-((2-(trimethylsilyl)ethoxy) methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure E, (R)-tert-buty\ 2-(4-bromophenyl)propylcarbamate (97 mg, 0.31 mmol) was reacted with 9-bromo-8-methoxy-2,6-dimethyl-5-((2-(trimethylsilyl)ethoxy) methyl)thieno[2,3-c]quinolin-4(5H)-one (0.10 g, 0.21 mmol) to afford the desired product (62 mg, 46%) as a solid: ESI MS m/z 643 [C33H4₃CIN2O5SS1 + H]⁺.

Example 1354

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-2-chloro-8-methoxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one hydrochloride

To a solution of (R)-tert-butyl 2-(4-(2-chloro-8-methoxy-6-methyl-4-oxo-5-((2- (trimethylsilyl)ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (1 1 mg, 0.017 mmol) in CH2CI2 (1 mL) at rt was added trifluoroacetic acid (1.0 mL) and the reaction was stirred at that temperature for 2 h. The mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH4OH (2 mL). The resulting mixture was stirred at rt for 2h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HCI, concentrated and dried under high vacuum to afford the desired product (7 mg, 92%) as a hydrochloride salt: Ή NMR (500 MHz, CD₃OD) δ 7.52 (dd, J = 7.8,

1.5 Hz, 1 H), 7.47 (dd, J = 7.7, 1.5 Hz, l H), 7.32 (s, 1H), 7.31 - 7.22 (m, 2H), 5.30 (d, J = 2.7 Hz, 1 H), 3.29 - 3.18 (m, 3H), 2.63 (s, 3H), 1.47 (d, J = 6.1 Hz, 3H); ESI MS m/z 413

[C₂2H₂₁C1 ₂02S + H]⁺.

Example 1353

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-2-chloro-8-hydroxy-6-methylthieno

|2,3-c]quinolin-4(5H)-one hydrochloride

To a solution of (R)-tert-butyl 2-(4-(2-chloro-8-methoxy-6-methyl-4-oxo-5-((2-(trimethylsilyl) ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (32 mg, 0.050 mmol) in CH₂C1₂ at 0 °C was added BBr₃ (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) and the reaction was stirred at that temperature for 1 h and quenched by pouring onto water or ice-water. The resulting mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH4OH (2 mL). The resulting mixture was stirred at rt for 2 h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HCI, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt: l H NMR (500 MHz, MeOD) 5 7.57 (dd, J = 7.9, 1.8 Hz, 1 H), 7.48 (dd, J = 7.8, 1.8 Hz, 1 H), 7.35 (dd, J = 7.9, 1.7 Hz, 1 H), 7.29 (dd, J = 7.8, 1.6 Hz, 1 H), 7.10 (d, J = 0.7 Hz, 1 H), 5.75 (s, 1 H), 3.28 - 3.19 (m, 3H), 2.55 (s, 3H), 1.50 (d, J = 6.4 Hz, 3H). ESI MS m/z 399

[C2i H₁₉CIN20₂S + H]⁺.

Example 616

9-Bromo-2-fluoro- 8-methoxy-6-methy 1- 5 -((2-(trimethy Is i ly l)ethoxy )

methyl)thieno[2,3-c]quinolin-4(5H)-one

To a stirred solution of diidopropylamine (84 0.6 mmol) in THF (2.5 mL) at -78 °C was added n-BuLi (2.5M, 0.24 mL, 0.6 mmol). The resulting mixture was stirred at 0 °C for 10 min and then cooled at -78 °C. A solution of

9-bromo-8-methoxy-6-methyl-5-((2-(trimethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)- one (0.23 g, 0.50 mmol) in THF (1 mL) was added dropwise and the resulting mixture was stirred at -78 °C for 30 min. A solution of N-fluorobenzenesulfonimide (0.32, 1.0 mmol) in THF (1 mL) was added and the mixture was stirred at -78 °C for 2h. The reaction was quenched by adding saturated ammonium chloride and extracted with dichloromethane (2x). The combined extracts were dried over Na₂S0₄, filtered and concentrated in vacuo. The residue was purified by column chromatography (heptane/ethyl acetate) to afford the desired product (98 mg, 41%) as a white solid: ESI MS m/z 472 [Ci H₂₃BrFN0₃SSi + H]⁺.

Example 617

(R)-tert-butyl 2-(4-(2-fluoro-8-methoxy-6-methyl-4-6xo-5-((2-(trimethylsilyl)ethoxy) methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate

Following General Procedure B, (R)-tert-bvtiy\ 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan -2-yl)phenyl)propylcarbamate (0.1 1 g, 0.31 mmol) was reacted with 9-bromo-2-fluoro

-8-methoxy-6-methyl-5-((2-(trimethylsilyl)ethoxy)methyl)thieno[2,3-c]quinolin-4(5H)-one (98 mg, 0.21 mmol) to afford the desired product (0.1 1 g, 85%) as a solid: ESI MS m/z 627

[C₃₃H₄₃FN₂0₅SSi + H]⁺.

Example 1375

(R)-9-(4-(l-Aminopropan-2-yl)phenyl)-2-fluoro-8-methoxy-6-methyIthieno[2,3-c] quinolin-4(5H)-one

To a solution (R)-tert-butyl

2-(4-(2-fluoro-8-methoxy-6-methyl-4-oxo-5-((2-(trimethylsilyl)ethoxy)methyl)-4,5-dihydrothien o[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (17 mg, 0.027 mmol) in CH₂CI₂ (1 mL) at rt was added trifluoroacetic acid (1.0 mL) and the reaction was stirred at that temperature for 2 h. The mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with

NH4OH (2 mL). The resulting mixture was stirred at rt for 2h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions ere combined, concentrated and the residue was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product (5 mg, 43%) as a hydrochloride salt: Ή NMR (500 MHz, CD₃OD) 5 7.52 (dd, J= 7.8, 1.5 Hz, 1H), 7.47 (dd, J = 7.7, 1.5 Hz, 1 H), 7.32 (s, 1 H), 7.31 - 7.22 (m, 2H), 5.30 (d, J = 2.7 Hz, 1H), 3.29 - 3.18 (m, 3H), 2.63 (s, 3H), 1.47 (d, J = 6.1 Hz, 3H); ESI MS m/z 397 [C₂₂H₂,FN₂0₂S + H]⁺.

Example 1383

(R)-9-(4-(l-Aminopropan-2-y))phenyl)-2-fluoro-8-hydroxy-6-methylthieno

To a solution of (R)-tert-butyl 2-(4-(2-fluoro-8-methoxy-6-methyl-4-oxo-5-((2- (trimethylsilyl)ethoxy)methyl)-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (60 mg, 0.096 mmol) in CH₂C1₂ (1 mL) at 0 °C was added BBr₃ (1 .0 M in methylene chloride, 1.0 mL, 1.0 mmol) and the reaction was stirred at that temperature for 1 h and quenched by pouring onto water or ice-water. The resulting mixture was concentrated and the residue was dissolved methanol (2 mL) and treated with NH₄OH (2 mL). The resulting mixture was stirred at rt for 2h and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired fractions were combined, concentrated and the residue was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a hydrochloride salt: Ή NMR (500 MHz, CD₃OD) δ 7.55 (dd, J = 7.9, 1.7 Hz, 1 H), 7.46 (dd, J = 7.8, 1.8 Hz, 1 H), 7.32 (dd, J= 23.9, 7.9 Hz, 2H), 7.10 (s, 1 H), 5.46 (d, J = 2.9 Hz, 1 H), 3.28 - 3.15 (m, 3H), 2.55 (s, 3H), 1.49 (d, J = 6.3 Hz, 3H); ESI MS m/z 383 [C₂iH,₉FN₂0₂S + H]⁺.

Example 618

tert-butyl l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)ethylcarbamate BocHN

NH

O

To a solution of tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)ethylcarbamate (0.96 g, 2.1 mmol) in dichloromethane (15 mL) at 0 °C was added BBr3 (1.0 M in methylene chloride, 15 mL, 15 mmol) and the reaction was stirred at that temperature for 1 h and quenched by pouring onto water or ice-water. The precipitate was filtered and suspened in DMF (8 mL). Di-tert-butyl dicarbonate (0.85 g, 3.9 mmol) and triethylamine (1.1 mL, 7.8 mmol) were added and the mixture was stirred at rt for 2h. Water was added and the precipitate was filtered and purified by column chromatography to afford the desired product as a solid: ESI MS m/z 437 [C24H24N2O4S + H]⁺.

Example 619

tert-butyl l -(4-(8-(isopropoxycarbonyloxy)-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)ethylcarbamate

To a solution of tert-butyl l -(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl)ethylcarbamate (44 mg, 0.10 mmol) in THF (2 mL) at 0 °C was added NaH (60%, 6 mg, 0.1 5 mmol) and the reaction was stirred at that temperature for 1 h. Isopropyl chloroformate (21 μί, 0.15 mmol) was added and the resulting mixture was stirred at rt for 3 h. Water was added and the mixture was extracted with dichloromethane (2 x 15 mL). The combined extracts were dried over Na₂S04, filtered and concentrated in vacuo. The residue was purified by column chromatography (heptane/ethyl acetate) to afford the desired product (26 mg, 50%) as a solid: ESI MS m/z 523 [C2₈H₃₀N2O₆S + H]⁺.

Exmaple 1077

9-(4-(l-Aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl isopropyl

Following General Procedure C, tert-butyl l -(4-(8-(isopropoxycarbonyloxy)-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate (20 mg, 0.038 mmol) was reacted with trifluoroacetic acid (3 mL) to afford the desired product (18 mg, quant.) as a light yellow solid: ESI MS m/z 423 [C23H22N2O4S + H]⁺.

Example 620

9-(4-(l -(tert-Butoxycarbonylamino)ethyl)phenyl)-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-8-yl acetate

Following Procedure Preparing tert-butyl l-(4-(8-(isopropoxycarbonyloxy)-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethylcarbamate, (44 mg, 0.10 mmol) was reacted with acetic anhydride (1 1 μί, 0.12 mmol) to afford the desired product (30 mg, 63%) as a solid: ESI MS m/z 479 [C26H26N2O5S + H]⁺.

Example 1099

9-(4-(l-Aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl acetate

Hydrochloride

Example 621

2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propane-l -sulfonamide

Following General Procedure E, 2-(4-bromophenyl)propane- l -sulfonamide (0.12 g, 0.43 mmol) was reacted with 9-bromo-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one (0.14 g, 0.44 mmol) to afford the desired product (1 6 mg, 8%) as a brown solid: ESI MS m/z 443

[C₂2H22N₂0₄S2 + H] ⁺ .

Example 1419

2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propane-l-sulfonamide

Following General Procedure F, 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propane- l -sulfonamide (16 mg, 0.036 mmol) was reacted with tribromoborane (1 .0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (7.0 mg, 44%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.68 (d, J = 8.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1 H), 7.41 (d, J= 8.4 Hz, 2H), 7.07 (s, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 2.57 (s, 3H), 1.86 (s, 6H); ESI MS m/z 429 [C₂iH₂₀N₂O₄S₂ + H]⁺; HPLC 98.7%, t_R = 8.51 min.

Exmaple 1057 '

N-(l-hydroxypropan-2-yl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)benzenesulfonamide

Following General Procedure B, N-( l -hydroxypropan-2-yl)-4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)benzenesulfonamide (570 mg, 1.7 mmol) was reacted with 9-bromo-8- methoxythieno[2,3-c]quinolin-4(5H)-one, (471 mg, 1 .5 mmol) to afford the desired product (109 mg, 16%) as an off-white powder. ESI MS m/z 445 [C21 H20N2O5S2 + H]⁺;

Example 1062

N-(l-bromopropan-2-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)benzenesulfonamide

Following Genreal Procedure F, N-(l -hydroxypropan-2-yl)-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide (55 mg, 0.12 mmol) was reacted with tribromoborane (0.2 mL) to afford the desired product (48 mg, 79%) as an off-white solid: Ή NMR (500 MHz, CD3OD); ESI MS m/z 494 [C₂oH,7Br ₂04S2 + H]⁺; HPLC 99.0% (AUC), t_R = 1 1.39 min;

N-(2-Hydroxyethyl)- ro-lH-cyclopenta[c]

Following General Procedure B, N-(2-hydroxyethyl)-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)benzenesulfonamide (268 mg, 0.82 mmol) was reacted with 9-bromo-8- methoxy-2,3-dihydro- l H-cyclopenta[c]quinolin-4(5H)-one, (268 mg, 0.68 mmol) to afford the desired product (68 mg, 1 6%) as an off-white solid: Ή NMR: (300 MHz, DMSO-c/6) ESI MS m/z 41 5[C₂ iH22N20₅S + H]⁺; HPLC >99% (AUC), t_R = 1 1 .73 min;

Exmaple 1094

N-(2-Bromoethyl)-4-(8-hyd roxy-4-oxo-2,3,4,5-tetrahyd ro- 1 H-cycIopenta [c J

quinolin-9-yl)benzenesulfonamide

Following Genreal Procedure F, N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-2,3,4,5- tetrahydro-l H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide (55 mg, 0.13 mmol) was reacted with tribromoborane (0.2 mL) to afford the desired product ( 1 1 mg, 18%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) ESI MS m/z 464 [C2oHi₉BrN₂0₄S+ H]⁺; HPLC 94.9% (AUC), t_R = 14.88 min;

Example 622

2-(4-(8-Methoxy-4-oxo-2,3,4,5-tetrahydro-l H-cyclopenta[c]quinolin-9-yl) phenylsulfonamido)ethyl methanesulfonate

To a stirred solution of N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-2,3,4,5-tetrahydro

-1 H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide (230 mg, 0.555 mmol) and triethylamine (168 mg, 1.66 mmol) in anhydrous tetrahydrofuran (10 mL) was added methane sulfonyl chloride (88 mg, 0.666 mmol). The reaction mixture was stirred for 20 h at room temperature. After this time the reaction mixture was filtered to remove a white precipitate, which was washed with tetrahydrofuran (30 mL). The filtrate was concentrated under reduced pressure to an orange solid. The residue was purified by flash chromatography to afford the desired product as a brown solid (141 mg, 51 %). ESI MS m/z 493 [C₂2H24N₂0₇S2 + H]⁺

Example 1145

N-(2-chloroethyl)-4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro-lH-cyclopenta[c]

quinolin-9-yI)benzenesulfonamide

To a stirred solution of 2-(4-(8-methoxy-4-oxo-2,3,4,5-tetrahydro- l H-cyclopenta [cjquinolin -9-yl)phenylsulfonamido)ethyl methanesulfonate (141 mg, 0.286 mmol) in anhydrous dichloroethane (10 mL) was added aluminum chloride (190 mg, 1.43 mmol). The reaction mixture was stirred at reflux for 20 h. After this time the reaction was cooled to room temperature and concentrated under reduced pressure. The residue was treated with methanol (10 mL) and allowed to stand at room temperature for 1 h. Upon standing a precipitate formed and was subsequently filtered from the mother liquor. The precipitate was purified by preparatory HPLC (CI 8 silica, acetonitrile/water with 0.05% TFA gradient) to obtain the desired product (9 mg, 7.5%) as an off-white solid: Ή NMR (500 MHz, DMSO-< ) ESI MS m/z 419 [C₂oH,9CIN₂0₄S + H]⁺; HPLC 97.6% (AUC), /_R = 15.94 min.

Example 1154

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)propyl)phenyl)thieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

•HCl

Following General Procedure F, (S)-tert-butyl l-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propyl(methyl)carbamate (100 mg, 0.194 mmol was reacted with tribromoborane (1.0 M in methylene chloride 1.16 mL, 1.16 mmol) to afford the desired product (35 mg, 45%) as a white solid: Ή NMR (500 MHz, DMSO) δ 10.81 (d, J = 10.5 Hz, 1 H), 9:83 (s, 1 H), 9.70 - 9.45 (m, 1 H), 9.28 (s, 1 H), 7.73 (d, J = 5.4 Hz, 1 H), 7.70 - 7.60 (m, 2H), 7.38 (dd, J = 12.4, 4.7 Hz, 3H), 5.70 (d, J = 5.4 Hz, 1 H), 4.19 (dt, J = 12.1 , 6.0 Hz, 1 H), 2.51 (s, 3H), 2.20 (ddd, J = 14.4, 9.5, 5.9 Hz, 1 H), 2.02 - 1.89 (m, 1 H), 0.84 (t, J = 7.4 Hz, 3H); ESI MS m/z 399 [C22H22N2O2S + H]⁺; HPLC 96.9% (AUC), t_R = 9.36 min.

Example 1148

(5)-8-hydroxy-9-(4-(l-(methylamino)propyl)phenyl)thieno[2,3-c] quinolin-4(5H)-

Hydrochloride

Following General Procedure F, (S)-tert-butyl l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl) phenyl) propyl(methyl)carbamate(135 mg, 0.282 mmol) was reacted with tribromoborane ( 1.0 M in methylene chloride, 1 .69 mL, 1.69 mmol) to afford the desired product (48 mg, 47%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.62 (ddd, J = 1 1.7, 8.0, 1 .7 Hz, 2H), 7.56 (d, J = 5.4 Hz, 1 H), 7.51 - 7.40 (m, 3 H), 7.19 (d, J = 8.9 Hz, 1 H), 5.97 (d, J = 5.4 Hz, l H), 4.22 (dd, J = 10.7, 4.6 Hz, 1 H), 2.70 (s, 3H), 2.34 - 2.02 (m, 2H), 1 .04 - 0.96 (m, 3H); ESI MS m/z 365 [C21 H20N2O2S + H]⁺; HPLC 95.9% (AUC), t_R = 8.38 min. Example 1181

(_iS)-9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (S)-tert-butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (100 mg, 0.20 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.2 mL, 1.2 mmol) to afford the desired product (35 mg, 46%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.62 (d, J = 5.4 Hz, 1 H), 7.56 (dd, J = 7.9, 1.9 Hz, 1 H), 7.48 (dd, J = 7.8, 1.9 Hz, 1 H), 7.36 (dd, J = 7.9, 1.7 Hz, 1 H), 7.34 - 7.29 (m, 2H), 6.12 (d, J = 5.4 Hz, 1 H), 3.29 - 3.15 (m, 3H), 1.49 (d, J = 6.5 Hz, 3H); ESI MS m/z 385 [C₂oH₁₇ClN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.74 min.

Example 1163

(5)-9-(4-(l-Aminopropan-2-yI)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (S)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate (1 10 mg, 0.236 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1 .42 mL, 1.42 mmol) to afford the desired product (38 mg, 47%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.61 - 7.53 (m, 2H), 7.47 (dd, J = 7.8, 1.9 Hz, 1 H), 7.41 (dd, J = 10.9, 6.1 Hz, 1H), 7.37 (dd, J = 7.9, 1.7 Hz, 1 H), 7.32 (dd, J= 7.7, 1.7 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1 H), 6.15 (d, J = 5.4 Hz, 1 H), 3.29 - 3.17 (m, 3H), 1.50 (d, J = 6.4 Hz, 3H); ESI MS m/z 351 [C₂oH₁₈N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.58 min.

Example 1116

9-(4-(l-(Aminomethyl)cyclopropyl)phenyl)-6-chloro-8-hydroxythieno[2_v3-c]quinolin-4(5H)- one Hydrochloride

Following General Procedure F, tert-butyl (l-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (50 mg, 0.09 mmol) was reacted with tribromoborane ( 1.0 M in methylene chloride, 0.58 mL, 0.58mmol) to afford the desired product (19 mg, 48%) as a white solid: Ή NMR; (500 MHz, MeOD) δ 7.66 - 7.58 (m, 3H), 7.38 - 7.27 (m, 3H), 6.14 (d, J = 5.4 Hz, 1H), 3.26 (s, 2H), 1.19 (t, J= 5.5 Hz, 2H), 1.11 (t, J= 5.5 Hz, 2H); ESI MS m/z 397 [C2iHi₇ClN₂0₂S + H]⁺; HPLC 98.4% (AUC), t_R = 9.24 min.

Example 1401

9-(4-(l-(Aminomethyl)cyclopropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)- one Hydrochloride

Following General Procedure F, 9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-6-bromo

-8-methoxythieno[2,3-c]quinolin-4(5H)-orie hydrochloride (100 mg, 0.22 mmol was reacted with tribromoborane (1.0 M in methylene chloride, 1.32 mL, 1.32 mmol) to afford the desired product (52 mg, 54%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.63 (t, J = 6.8 Hz, 3H), 7.48 (s, 1 H), 7.33 (d, J = 8.2 Hz, 2H), 6.14 (d, J = 5.4 Hz, 1H), 3.26 (s, 2H), 1.19 (t, J = 5.6 Hz, 2H), 1.12 (t, J= 5.5 Hz, 2H); ESI MS m/z 442 [C₂iHi₇BrN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 9.25 min.

Example 1254

9-(4-(l-(aminomethyI)cyclopropyl)pheny.)-8-hydroxy-6-methylthieno

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl (l-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (120 mg, 0.24 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.46 mL, 1.46mmol) to afford the desired product (38 mg, 42%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.60 (ddd, J = 12.3, 7.1, 3.6 Hz, 3H), 7.34-7.29 (m, 2H), 7.08 (d,J= 0.6 Hz, 1H), 6.19 (d,J= 5.4 Hz, 1H), 3.25 (s, 2H), 2.57 (s, 3H), 1.22 - 1.06 (m, 4H); ESI MS m/z 377 [C23H22 2O2S + H]⁺; HPLC 98.6% (AUC), t_R = 8.97 min.

Example 1215

(S)-8-Hydroxy-6-methyl-9-(4-(l-(methyIamino)propan-2-yl)phenyl)thieno

[2,3-c]quinoIin-4(5H)-one Hydrochloride

Following General Procedure F, (S)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (50 mg, 0.10 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.61 mL, 0.61 mmol) to afford the desired product (12 mg, 32%) as a light yellow solid: Ή NMR(500 MHz, MeOD) δ 7.60 - 7.53 (m, 2H), 7.47 (dd, J = 7.8, 1.8 Hz, 1 H), 7.35 (dd, J= 7.9, 1.7 Hz, 1 H), 7.30 (dd, J= 7.7, 1.7 Hz, 1H), 7.08 (s, 1H), 6.15 (d, J =5.4 Hz, 1 H), 3.40 - 3.27 (m, 3H), 2.74 (s, 3H), 2.57 (s, 3H), 1.50 (d, J= 6.6 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.88 min.

Example 1232

(5)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (S)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (100 mg, 0.209 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.25 mL, 1.25 mmol) to afford the desired product (38 mg, 52%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.60 - 7.52 (m, 2H), 7.45 (dd,J=7.8, 1.9 Hz, 1H), 7.35 (dd, J= 7.9, 1.7Hz, 1H), 7.29 (dd,J=7.7, 1.7Hz, 1H),7.08 (s, 1 H), 6.16 (d, J = 5.4 Hz, 1 H), 3.29 - 3.17 (m, 3H), 2.57 (s, 3H), 1.50 (d, J = 6.4 Hz, 3H); ESI MS m/z 365 [C₂|H2₀N₂O2S + H]⁺; HPLC 98.0% (AUC), t_R = 8.63 min.

Example 1264 9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin

Hydrochloride

Following General Procedure F, tert-butyl

2-chloro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbam ate (120 mg, 0.24 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1 .45 mL, 1 .45 mmol) to afford the desired product (52 mg, 57%) as a white solid: Ή NMR (500 MHz, MeOD) 5 7.64 (d, J = 5.4 Hz, 1 H), 7.54 (d, J = 7.8 Hz, 1 H), 7.37 (d, J = 1.4 Hz, 1 H), 7.23 (dd, J = 7.7, 1.4 Hz, 1 H), 7.08 (s, 1 H), 6.19 (d, J = 5.4 Hz, 1 H), 3.42 - 3.14 (m, 4H), 2.56 (s, 3H); ESI MS m/z 385 [C20H17CIN2O2S + H]⁺; HPLC 98.2% (AUC), t_R = 8.55 min.

Example 1268

9-(4-(2-aminoethyl)-3-chlorophenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-chloro-4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (80 mg, 0.154 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.92 mL, 0.92 mmol) to afford the desired product (37 mg, 59%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.68 (d, J = 5.4 Hz, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 1 .7 Hz, l H), 7.30 (s, 1H), 7.27 (dd, J = 7.8, 1.7 Hz, 1 H), 6.17 (d, J = 5.4 Hz, 1 H), 3.39 - 3.25 (m, 4H); ESI MS m/z 405 [C₉H14CI2N2O2S + H]⁺; HPLC 98.1 % (AUC), t_R = 9.17 min.

Example 1262

( f)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (R)-tert-butyl l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (150 mg, 0.313 mmol) was reacted with tribromoborane ( 1.0 M in methylene chloride, 1 .9 mL, 1 .9 mmol) to afford the desired product (85 mg, 74%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.63 (ddd, J= 7.0, 5.5, 2.2 Hz, 2H), 7.57 (d,J= 5.4 Hz, 1H), 7.43 (ddd,J= 7.4, 6.1, 2.1 Hz, 2H), 7.08 (s, 1H), 6.05 (d,J=5.4 Hz, 1H), 4.47 (q,J=6.9 Hz, 1H), 2.71 (s, 3H), 2.57 (s, 3H), 1.79 (d,J= 6.9 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.40 min.

Example 1135

(^)-6-bromo-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (R)-tert-butyl l-(4-(6-bromo-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyI(methyl)carbamate (100 mg, 0.18 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.1 mL, 1.1 mmol) to afford the desired product (38 mg, 48%) as a white solid: Ή NMR (500 MHz, DMSO) δ 10.20 (s, 1H), 9.88 (s, 1H), 9.76-9.59 (m, 1H), 9.37-9.21 (m, 1H), 7.78 (d,J=5.4 Hz, 1H), 7.74 - 7.64 (m, 2H), 7.54 (s, 1H), 7.40- 7.33 (m, 2H), 5.77 (d,J=5.4 Hz, 1H), 4.44 (dd,J= 12.5, 6.4 Hz, 1H), 2.50 (s, 3H), 1.68 (d, J= 6.8 Hz, 3H); ESI MS m/z 429 [C₂oH,₇BrN₂0₂S + H]⁺; HPLC >99% (AUC), t = 9.00 min.

Example 1271

9-(4-(l-Amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydroxythieno[i

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropylcarbamate (130 mg, 0.26 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.57 mL, 1.57 mmol) to afford the desired product (35 mg, 35%) as a white solid: Ή NMR (500 MHz, DMSO) δ 11.81 (s, lH), 9.34 (s, 1H), 7.98 (s, 3H), 7.72 (d,J= 5.4 Hz, 1H), 7.49 (t,J= 8.5 Hz, 1H), 7.40 (d, J = 8.9 Hz, 1 H), 7.17 (t,J= 9.0 Hz, 1H), 7.12 (ddd,J= 10.7, 9.7, 1.7 Hz, 2H), 6.02 (d,J=5.4 Hz, 1H), 3.25 (s, 2H), 1.51 (d, J= 9.1 Hz, 6H); ESI MS m/z 383 [C₂iH,₉FN₂0₂S + H]⁺; HPLC >99% (AUC), tR = 8.77 min.

Example 1278

9-(4-(l-Amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo- 4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropylcarbamate (50 mg, 0.10 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.58 mL, 0.58 mmol) to afford the desired product (22 mg, 58%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.64 (d, J = 5.4 Hz, 1H), 7.57 (t, J =8.4 Hz, 1H), 7.15(ddd,J= 15.1, 10.7, 1.7 Hz, 2H), 7.08 (d,J=0.7Hz, 1H), 6.26 (d,J= 5.4 Hz, 1H), 3.31 (s, 2H), 2.57 (s, 3H), 1.62 (d,J= 5.6 Hz, 6H); ESI MS m/z 397 [C₂₂H₂₁FN₂O₂S + H]⁺; HPLC >99% (AUC), t_R = 9.07 min.

Example 1291

9-(4-(l-Aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c) quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (100 mg, 0.23 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.4 mL, 1.4 mmol) ) to afford the desired product (42 mg, 55%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.57 - 7.50 (m, 2H), 7.40 (ddd,J= 18.8,7.8, 1.8Hz,2H), 7,31 (dd,J=7.7, 1.7Hz, 1H), 7.09 (d, J= 0.8 Hz, 1H), 6.13 (d, J=5.4 Hz, 1H), 3.25 (ddd,J=26.6, 13.1,7.1 Hz, 2H), 2.93 (dq,J= 15.3, 5.2 Hz, lH),2.57(d,J = 0.6 Hz, 3H), 1.97 - 1.74 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); ESI MS m/z 379 [C₂₂H₂₂N₂O₂S + H]⁺; HPLC >99% (AUC), t_R = 9.21 min.

Example 1120

(_lS)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno|2,3-c)quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (S)-tert-butyl l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate(100 mg, 0.22 mmol) was reacted with

tribromoborane (1.0 M in methylene chloride, 1.3 mL, 1.3 mmol) to afford the desired product (28 mg, 38%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.65 - 7.58 (m, 2H), 7.54 (d, J = 5.4 Hz, 1 H), 7.46 - 7.40 (m, 3H), 7.18 (d, J= 8.9 Hz, 1H), 6.03 (d, J= 5.4 Hz, 1 H), 4.32 (dd, J = 9.2, 5.9 Hz, 1H), 2.21 -2.03 (m, 2H), 1.04 (t, J= 7.4 Hz, 3H); ESI MS m/z 351 [C₂oHi₈N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.24 min.

Example 1290

9-(4-(l-(Aminomethyl)cyclobutyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl (l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclobutyl)methylcarbamate(130 mg, 0.32 mmol was reacted with tribromoborane (1.0 M in methylene chloride, 1.9 mL, 1.9 mmol to afford the desired product (82 mg, 65%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.63 (d, J = 5.4 Hz, 1 H), 7.46 - 7.41 (m, 2H), 7.38 - 7.32 (m, 2H), 7.09 (d, J= 0.7 Hz, 1 H), 6.26 (d, J = 5.4 Hz, 1 H), 3.36 - 3.33 (m, 2H), 2.65 (dd, J = 21.2, 9.3 Hz, 2H), 2.58 (s, 3H), 2.45 - 2.37 (m, 2H), 2.27 (ddd, J = 17.7, 1 1 .5, 8.6 Hz, 1H), 2.12 - 2.01 (m, 1 H); ESI MS m/z 391 [C23H22N2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.37 min.

Example 1300

9-(4-(l-(Aminomethyl)cyclobutyl)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl (l -(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)cyclobutyl)methylcarbamate ( 100 mg, 0.20 mmol) was reacted with tribromoborane (1 .0 M in methylene chloride, 1 .23 mL, 1 .23 mmol) to afford the desired product (52 mg, 68%) as a white solid: Ή NMR (500 MHz, MeOD) 6 7.64 (d, J = 5.4 Hz, 1H), 7.44 (ddd, J= 17.8, 10.5, 3.8 Hz, 3H), 7.39 - 7.35 (m, 2H), 7.19 (d, J = 8.9 Hz, 1 H), 6.25 (d, J = 5.4 Hz, 1 H), 3.44 (s, 2H), 2.65 (dd, J= 21.3, 9.4 Hz, 2H), 2.46 - 2.36 (m, 2H), 2.33 - 2.20 (m, 1 H), 2.14 - 2.00 (m, 1H); ESI MS m/z 377 [C22H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.00 min.

Example 1309

9-(4-(l-Aminobutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(8-methoxy-4-oxo-4,5

dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate(100 mg, 0.21 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.25 mL, 1.25 mmol) to afford the desired product (45 mg, 60%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.58 - 7.50 (m, 2H), 7.46 -7.36(m,3H), 7.32(dt,J= 12.4, 6.2 Hz, 1H), 7.19 (d, J= 8.9 Hz, 1H), 6.11 (d,J=5.4Hz, 1H), 3.40- 3.19 (m, 2H), 2.95 (dq,J= 15.3, 5.2 Hz, 1H), 1.98- 1.85 (m, 1H), 1.86-1.71 (m, 1H), 1.06 - 0.91 (m, 3H); ESI MS m/z 365 [C₂iH₂₀N2O₂S + H]⁺; HPLC >99% (AUC), t_R = 8.15 min.

Example 1312

9-(4-(l-Aminobutan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (65 mg, 0.13 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.76 mL, 0.76 mmol) to afford the desired product (28 mg, 56%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.60 (d, J= 5.4 Hz, 1H), 7.54 (dd,J=7.9, 1.8 Hz, 1H), 7.44 (dd,J=7.7, 1.8 Hz, 1H), 7.39 (dd, J= 7.9, 1.8 Hz, 1H), 7.35 - 7.30 (m, 2H), 6.08 (d, J= 5.4 Hz, 1H), 3.38 - 3.22 (m, 2H), 2.98 - 2.89 (m, 1H), 1.97 - 1.85 (m, 1H), 1.85 - 1.72 (m, 1H), 0.98 (t, J= 7.4 Hz, 3H); ESI MS m/z 399 [C21H1 CIN2O2S + H]⁺; HPLC >99% (AUC), t_R = 10.29 min.

Example 385

9-(4-(l-(Ethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-

Hydrochloride

Following General Procedure F, tert-butyl

ethyl(l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)carbamate (150 mg, 0.31 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.9 mL, 1.9 mmol) to afford the desired product (37 mg, 33%) as a white glass: Ή NMR(500 MHz, MeOD); δ 7.65 (dd, J = 13.2, 4.9 Hz, 2H), 7.57 (d, J= 5.4 Hz, 1H), 7.48 - 7.39 (m, 3H), 7.18 (d, J= 8.9 Hz, 1 H), 6.04 (d, J = 5.4 Hz, 1H), 4.53 (q, J= 6.8 Hz, 1 H), 3.20 - 3.08 (m, 1H), 3.08 - 2.96 (m, 1 H), 1.79 (d, J= 6.9 Hz, 3H), 1.36 (t, J = 7.3 Hz, 3H). ESI MS m/z 365 [+ H]⁺; HPLC >99% (AUC), t_R = 12.05 min.

Example 1165

6-chloro-8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethyl(methyl)carbamate (60 mg, 0.12 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.72 mL, 0.72 mmol) to afford the desired product (22 mg, 50%) as a white solid: Ή NMR(500 MHz, DMSO-cfe) δ 10.77 (s, 1 H), 9.72 (s, 1 H), 8.72 (s, 1 H), 7.76 (d, J = 5.4 Hz, 1H), 7.42 (d, J = 8.1 Hz, 2H), 7.31 (s, 1H), 7.24 (d, J= 8.1 Hz, 2H), 5.85 (d, J = 5.4 Hz, 1 H), 3.30 - 3.23 (m, 2H), 3.09 - 3.02 (m, 2H), 2.65 (s, 3H); ESI MS m/z 385 [C₂oH|₇CIN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 9.03 min.

Example 1197

(S)-8-hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c] quinolin-4(5H)-

Hydrochloride

Following General Procedure F, (S)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)propyl(methyl)carbamate (100 mg, 0.21 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.25 mL, 1.25 mmol) to afford the desired product (31 mg, 41%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.61 - 7.53 (m, 2H), 7.48 (dd, J - 7.8, 1.9 Hz, 1 H), 7.44 - 7.37 (m, 2H), 7.33 (dd, J = 7.7, 1.7 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1 H), 6.14 (d, J = 5.4 Hz, 1 H), 3.41 - 3.25 (m, 3H), 2.75 (s, 3H), 1.50 (d, J = 6.8 Hz, 3H); ESI MS m/z 365 [C21 H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.36 min.

Example 1224

9-(4-(2-aminoethyl)-2-bromo-5-hydroxyphenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Following General Procedure F, (tert-butyl 5-bromo-2-hydroxy-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (50 mg, 0.90 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.54 mL, 0.54 mmol) to afford the desired product (18 mg, 48%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.68 (d, J= 5.5 Hz, 1H), 7.58 (s, 1H), 7.44 (d, J= 9.0 Hz, 1 H), 7.18 (d, J= 9.0 Hz, 1 H), 6.82 (s, 1H), 6.33 (d, J = 5.5 Hz, 1 H), 3.25 (m, 2H), 2.95 (m, 2H); ESI MS m/z 432 [Ci₉Hi5BrN₂0₃S + H]⁺; HPLC 96.9% (AUC), t_R = 8.10 min.

Example 1082

(S)-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (100 mg, 0.22 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1 .30 mL, 13.0 mmol) to afford the desired product (50 mg, 66%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.68 - 7.61 (m, 2H), 7.57 (d, J = 5.4 Hz, 1 H), 7.49 - 7.39 (m, 3H), 7.18 (d, J = 8.9 Ηζ,ΙΗ), 6.04 (d, J = 5.4 Hz, 1H), 4.48 (q, J = 6.8 Hz, 1 H), 2.72 (s, 3H), 1.80 (d, J = 6.9 Hz, 3H); ESI MS m/z 351 [C₂oH₁₈N₂0₂S + H]^"* HPLC 96.9% (AUC), t_R = 7.68 min.

Example 1088

9-(4-(l-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (40 mg, 0.08 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.48 mL, 0.48 mmol) to afford the desired product (12 mg, 40%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.65 - 7.56 (m, 3H), 7.46 - 7.39 (m, 2H), 7.30 (s, 1 H), 6.02 (d, J = 5.4 Hz, 1H), 4.32 (dd, J = 9.1 , 6.0 Hz, 1 H), 2.21 - 2.02 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H); ESI MS m/z 385 [C₂₀H,₇ClN₂O₂S + H]⁺; HPLC 95.9% (AUC), t_R = 9.15 min. Example 1087

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (S)-tert-butyl l-(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (40 mg, 0.08 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.48 mL, 0.48 mmol) to afford the desired product (1 8 mg, 60%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.72 - 7.60 (m, 3H), 7.49 - 7.39 (m, 2H), 7.30 (s, 1 H), 6.03 (d, J = 5.4 Hz, 1 H), 4.49 (q, J= 6.9 Hz, 1 H), 2.73 (d, J = 4.3 Hz, 3H), 1 .80 (d, ./ = 6.9 Hz, 3H); ESI MS m/z 385 [C₂oH,₇ClN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 13.60 min.

Example 1209

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxythieno[2,3-c] quino!in-4(5H)-one

Following General Procedure F, tert-butyl 2-ethyl-2-(4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (200 mg, 0.40 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 2.37 mL, 2.37 mmol) to afford the desired product (120 mg, 78%) as a white solid: Ή NMR(500 MHz, MeOD) δ 7.62 (d, J = 8.4 Hz, 2H), 7.54 (d, J= 5.4 Hz, 1 H), 7.41 (dd, J = 15.2, 8.6 Hz, 3 H), 7.19 (d, J = 8.9 Hz, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 3.34 (s, 2H), 2.05 - 1.88 (m, 4H), 0.93 (t, J = 7.4 Hz, 6H); ESI MS m/z 393

[C₂3H24N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 9.38 min.

Example 1271

9-(4-(l-amino-2-methylpropan-2-yl)-3-fluorophenyI)-8-hydroxythieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-2-methylpropylcarbamate (80 mg, 0.16 mmol) was reacted with tribromoborane ( 1.0 M in methylene chloride, I .O mL, 1 .0 mmol) to afford the desired product (35 mg, 56%) as a yellow glass: Ή NMR(500 MHz, MeOD) δ 7.67 (d, J= 5.4 Hz, 1 H), 7.59 (t, J= 8.4 Hz, 1 H), 7.44 (d, J= 8.9 Hz, 1 H), 7.20 (d, J = 8.9 Hz, 3H), 6.25 (d, J = 5.4 Hz, 1 H), 3.54 (d, J= 13.0 Hz, 2H), 3.28 (s, 1 H), 1.63 (d, J = 4.6 Hz, 6H); ESI MS m/z 383 [C₂iH₁₉FN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.89 min.

Example 623

tert-butyl (l-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)cy c lopropy l)methy lcarbamate

Following General Procedure I , tert-butyl (l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (750 mg, 1.57 mmol) was reacted with NBS (280 mg, 1.57 mmol) ) to affor the desired product (473 mg, 54%) as a yellow solid ESI MS m/z 555 [C27H₂₇BrN₂04S + H]⁺.

Example 624

(S)-tert-butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)

pheny l)propy l(methy l)carbamate

Following General Procedure I, (S)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl) propyl(methyl)carbamate (1.0 g, 2.0 mmol was reacted with NBS (446 mg, 2.5 mmol) to afford the desired product (500 mg, 43%) as a yellow solid: ESI MS m/z 557

[C27H₂9BrN₂0₄S + H]⁺.

Example 625

(R)-tert-butyl l -(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) pheny l)ethyl(methyl)carbamate

Following General Procedure I, (R)-tert-butyl l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (400 mg, 0.86 mmol) was reacted with NBS (184 mg, 1.03 mmol) to afford the desired product (285 mg, 61%) as a yellow solid: ESI MS m/z 543 [C₂6H3oBr 20₄S + H]⁺.

Example 1263

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-methoxy-6-methylthieno|2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, tert-butyl 2-chloro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethylcarbamate (50 mg, 0.10 mmol) was reacted with TFA (3.0 mL) to afford the desired product as a light yellow solid (27 mg, 68%): Ή NMR (500 MHz, MeOD) δ 7.62 (t,J=5.8Hz, 1H), 7.53 (d,J=7.8Hz, 1H), 7.35 (d, J= 1.6 Hz, 1H), 7.29 (s, 1H), 7.21 (dd,J=7.7, 1.7 Hz, 1H), 6.11 (d,J=5.4 Hz, 1H), 3.75 (d, 7=7.4 Hz, 3H), 3.38- 3.16 (m, 4H), 2.64 (s, 3H); ESI MS m/z 399 [C21H1₉CIN2O2S + H]⁺; HPLC 98.8% (AUC), t_R = 9.50 min.

Example 1265

(?)-8-methoxy-6-methyl-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one Hydrochloride

Following General Procedure C, (R)-tert-butyl l-(4-(8-methoxy-6-methyl-4-oxo-4,5- ' dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (50 mg, 0.10 mmol) was reacted with TFA (3.0 mL) to afford the desired product as a yellow solid 25 mg, 63%): Ή NMR (500 MHz, MeOD) δ 7.64 (d, J= 8.4 Hz, 2H), 7.57 (d, J= 5.4 Hz, 1 H), 7.38 (d, J= 8.6 Hz, 2H), 7.29 (s, 1H), 5.99 (d, J= 5.4 Hz, 1H), 4.48 (q, J= 6.8 Hz, 1H), 3.73 (s, 3H), 2.72 (s, 3H), 2.64 (s, 3H), 1.80 (d, J= 6.9 Hz, 3H). ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 98.0% (AUC), t_R = 9.51 min. Example 1277

9-(4-(l-aminobutan-2-yl)phenyl)-8-methoxy-6-methyIthieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butylcarbamate (40 mg, 0.08 mmol) was reacted with TFA (3.0 mL) to afford the desired product as a white solid 14 mg, 44%): Ή NMR (500 MHz, MeOD) δ 7.54 - 7.47 (m, 2H), 7.42 (dd, J = 7.7, 1.8 Hz, 1 H), 7.35 - 7.25 (m, 3H), 5.96 (d, J = 5.4 Hz, 1 H), 3.75 (s, 3H), 3.37 - 3.26 (m, 2H), 3.02 - 2.89 (m, 1 H), 2.64 (s, 3H), 1.97 - 1 .85 (m, 1 H), 1.81 - 1.67 (m, 1 H), 0.96 (t, J = 7.3 Hz, 3H); ESI MS m/z 393 [C23H24 2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.74 min.

Example 1064

(S)-8-methoxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following General Procedure C, (S)-tert-butyl l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenyl)ethyl(methyl)carbamate (30 mg, 0.06 mmol) was reacted with TFA (1.5 mL) to afford the desired product (15 mg, 65%) as a white solid: Ή NMR (500 MHz, MeOD); δ 7.64 (d, J = 8.5 Hz, 2H), 7.61 - 7.52 (m, 2H), 7.45 - 7.36 (m, 3H), 5.98 (d, J = 5.4 Hz, 1 H), 4.48 (q, J = 6.8 Hz, 1 H), 3.74 (s, 3H), 2.73 (s, 3H), 1.79 (t, J = 8.0 Hz, 3H). ESI MS m/z 365 [C2iH2₀N₂O₂S+ H]⁺; HPLC >99% (AUC), t_R = 13.69 min.

Example 1121

(S)-9-(4-(l-aminopropyl)phenyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one Hydrochloride

[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (40 mg, 0.09 mmol) was reacted with TFA (2.0 mL) to afford the desired product (15 mg, 49%) as a light yellow glass: Ή NMR (500 MHz, MeOD) ) δ 7.60 (rt, J = 7.1 , 3.6 Hz, 2H), 7.57 - 7.51 (m, 2H), 7.42 - 7.36 (m, 3H), 6.00 (d, J = 5.4 Hz, 1 H), 4.32 (dd, J = 9.2, 6.0 Hz, 1 H), 3.73 (s, 3H), 2.1 1 (qdd, J = 13.6, 8.3, 6.7 Hz, 3H), 1 .08 - 0.98 (m, 3H); ESI MS m/z 365 [C₂iH_{20 2}O₂S + H]⁺; HPLC >99% (AUC), t_R = 8.74 min

Example 1391

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-6-bromo-8-methoxythieno[2,3-c] quinolin-4(5H)-one Hydrochloride

Following General Procedure C, tert-butyl (l-(4-(6-bromo-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (50 mg, 0.09 mmol) was reacted with TFA (5.0 mL) to afford the desired product (19 mg, 47%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.71 - 7.65 (m, 1 H), 7.65 - 7.57 (m, 3H), 7.32 - 7.27 (m, 2H), 5.99 (t, J = 6.4 Hz, 1 H), 3.75 (s, 3H), 3.29 (s, 2H), 1.21 - 1.10 (m, 4H); ESI MS m/z 456

[C₂₂H,9BrN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 10.83 min.

Example 1251

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c] quinoIin-4(5H)-one Hydrochloride

Following General Procedure C, tert-butyl (l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropyl)methylcarbamate (70 mg, 0.14 mmol) was reacted with TFA (4.0 mL) to afford the desired product (32 mg, 56%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.63 - 7.51 (m, 3H), 7.32 - 7.23 (m, 3H), 6.02 (d, J = 5.4 Hz, 1 H), 3.74 (s, 3H), 3.28 (s, 2H), 2.64 (s, 3H), 1.21 - 1.08 (m, 4H); ESI MS m/z 391 [C₂₃H₂₂N₂0₂S + H]⁺; HPLC 95.7% (AUC), t_R = 9.15 min.

Example 1297

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure C, tert-butyl (l -(4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclobutyl)methylcarbamate (200 mg, 0.42 mmol) was reacted with TFA (5.0 mL) to afford the desired product ( 150 mg, 89%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.61 (d, J = 5.4 Hz, 1 H), 7.47 - 7.41 (m, 2H), 7.35 - 7.30 (m, 3H), 6.07 (d, J = 5.4 Hz, 1 H), 3.76 (s, 3H), 3.46 (s, 2H), 2.65 (s, 3H), 2.64 - 2.57 (m, 2H), 2.47 - 2.37 (m, 2H), 2.32 - 2. 1 5 (m, 1 H), 2.12 - 1.97 (m, 1 H); ESI MS m/z 405 [C24H24N2O2S + H]⁺; HPLC >99% (AUC), t_R = 12.27 min.

Example 1321

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-6-chloro-8-methoxythieno

quinolin-4(5H)-one Hydrochloride

Following General Procedure C, tert-butyl ( l -(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclobutyl)methylcarbamate (25 mg, 0.05 mmol) was reacted with TFA (2.5 mL) to afford the desired product ( 16 mg, 80%) as a white solid: Ή NMR (500 MHz, MeOD) δ 7.66 (s, 1 H), 7.55 (s, 1 H), 7.47 (s, 2H), 7.34 (s, 2H), 6.04 (s, 1 H), 3.77 (s, 3H), 3.47 (s, 2H), 2.68 - 2.54 (m, 2H), 2.47 - 2.35 (m, 2H), 2.31 - 2.20 (m, 1 H), 2.12 - 2.02 (m, 1 H); ESI MS m/z 426 [C23H21CIN2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.87 min.

Example 1154

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)propyl)phenyl)thieno

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (S)-tert-butyl l -(4-(6-chloro-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl) phenyl)propyl(methyl)carbamate (100 mg, 0.194 mmol was reacted with tribromoborane ( 1.0 M in methylene chloride 1 .2 mL, 1 .16 mmol) to afford the desired product (35 mg, 45%) as a white solid: 'HNMR(500 MHZ, DMSO) δ 10.81 (d,J= 10.5 Hz, 1H),9.83 (s, 1H), 9.70-9.45 (m, 1H),9.28 (s, 1H),7.73 (d,J=5.4Hz, 1H), 7.70 - 7.60 (m, 2H), 7.38(dd,J= 12.4, 4.7 Hz, 3H), 5.70 (d,J=5.4 Hz, 1H), 4.19(dt,J= 12.1,6.0 Hz, 1H), 2.51 (s, 3H), 2.20 (ddd, J= 14.4, Z

Example 626

(S)-tert-butyl 2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]

quinolin-9-yl)phenyl)propyl(methyl)carbamate

4-oxo-4,5- mg, 0.269 mmol) was

product (95 mg, 75%) as a brown solid: ESI MS m/z 493 [C₂8H32BrN20₄S + H] .

Example 1372

9-(4-(l-((dimethylamino)methyl)cyclobutyl)phenyl)-8-hydroxy-6-methylthieno

[2,3-c)quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 460, 9-(4-(l-(aminomethyl)cyclobutyl)phenyl) -8-hydroxy -6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride (110 mg, 0.28 mmol) ) was reacted with formaldehyde (37% in water, 22 mg, 0.70 mmol) to afford the desired product as a white solid (28 mg, 25%): Ή NMR (500 MHz, MeOD) δ 7.65 (t, J= 7.4 Hz, 3H), 7.43 (d, J = 8.1 Hz, 2H), 7.12 (s, 1H), 6.24 (d,J= 5.3 Hz, 1H), 3.80 (s, 2H), 2.86 (s, 6H), 2.77-2.67 (m, 2H), 2.60 (s, 3H), 2.52 (dt,J= 11.9, 8.8 Hz, 2H), 2.30 - 2.17 (m, 1H), 2.17 - 2.05 (m, 1H); ESI MS m/z 419 [C25H26N2O2S + H]⁺; HPLC >99% (AUC), t_R = 9.51 min.

Example 1172

(S)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following the procedure outlined for Example 460, (S)-9-(4-(l-aminopropan-2-yl)phenyl)-8- hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (20 mg, 0.06 mmol) ) was reacted with formaldehyde (37% in water, 5.0 mg, 0.15 mmol) to afford the desired product as a white solid (15 mg, 70%): Ή NMR (500 MHz, MeOD) δ 7.64 - 7.51 (m, 3H), 7.45 - 7.37 (m, 2H), 7.34 (dd,J= 7.7, 1.7 Hz, 1H), 7.19 (t, J = 7.7 Hz, 1H), 6.12 (d, J = 5.4 Hz, 1H), 3.62 (td,J= 11.5,2.6 Hz, 1 H), 3.50 - 3.40 (m, 2H), 2.97 (s, 3H), 2.94 (s, 3H), 1.48 (d, J= 6.6 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.63 min.

Example 1128

(S)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-

Hydrochloride

Following the procedure outlined for Example 460, (S)-9-(4-(l-aminopropyl)phenyl)-8- hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (25 mg, 0.07 mmol) ) was reacted with formaldehyde (37% in water, 5.5 mg, 0.18 mmol) to afford the desired product as a white solid (12 mg, 45%): "HNMR (500 MHz, MeOD) δ 7.66 (ddd,J= 19.7, 7.7, 1.6 Hz, 2H), 7.55 (d,J = 5.4 Hz, 1 H), 7.52 - 7.45 (m, 2H), 7.43 (d, J= 8.9 Hz, 1 H), 7.20 (d, J= 8.9 Hz, 1 H), 5.95 (d, J = 5.4 Hz, 1 H), 4.38 (dd, J= 11.3, 4.4 Hz, 1 H), 2.99 (d, J= 2.1 Hz, 3H), 2.85 (d, J = 3.2 Hz, 3H), 2.40 - 2.18 (m, 2H), 1.03 - 0.93 (m, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 98.4% (AUC), t_R = 8.14 min.

Example 1127

(S)-9-(4-(l-(ethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c] quinolin-4(5H)-one

Hydrochloride

Following the procedure outlined for Example 460, (S)-9-(4-(l-aminopropyl)phenyl)-8- hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (30 mg, 0.09 mmol) ) was reacted with formaldehyde (37% in water, 9.5 mg, 0.21 mmol) to afford the desired product as a white solid (15 mg, 46%): Ή NMR (500 MHz, MeOD) δ 7.68 - 7.57 (m, 2H), 7.54 (d, J= 5.4 Hz, 1H), 7.45 (ddd,J= 17.0, 10.1, 5.3 Hz, 3H), 7.19 (d, 7=8.9 Hz, 1H), 5.97 (d,J= 5.4 Hz, 1H), 4.26(dd,J = 11.1, 4.3 Hz, 1H), 3.11 (tt,J = 14.6, 7.3 Hz, 1 H), 3.05 - 2.95 (m, 1H), 2.25 (ddd,J= 13.0, 7.4, 4.4 Hz, 1H), 2.09(ddd,J= 13.1, 11.2, 7.4 Hz, 1H), 1.35 (t,J= 7.3 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 98.4% (AUC), t_R = 8.51 min. Example 1095

-(4-(2-aminopropyl)phenyl)-8-hydroxythieno[2-3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propan-2-ylcarbamate (650 mg, 1.40 mmol) was reacted with BBr₃ (1.0 M in CH₂C1_2, 10 mL, 10 mmol) to afford the desired product (152 mg, 31%) as a light yellow solid: 'HNMR (500 MHz, CD₃OD) 57.56 (d, J = 5.4 Hz, 1H), 7.49 (d,J= 7.9 Hz, 1H), 7.43 (dd,J= 13.3, 8.3 Hz, 2H), 7.34 (d,J= 7.9 Hz, 2H), 7.18(d,J=8.9Hz, 1H), 6.11 (d,J=5.4Hz, 1H), 3.71 - 3.60 (m, 1H),3.05 (dd, J = 7.2, 2.2 Hz, 2H), 1.40 (d, J= 6.6 Hz, 3H); ESI MS m/z 351 [C₂₀Hi₈N₂O₂S + H]⁺; HPLC 98.6% (AUG), t_R = 8.08 min.

Example 1106

9-(4-(2-aminopropyl)phenyl)-6-chloro-8-hydroxythieno|2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, a tert-butyl

l-(4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propan-2-ylcarba mate (55 mg, 0.11 mmol) was reacted with BBr₃ (1.0 M in CH₂C1_2, 2 mL, 2 mmol) to afford the desired product (28 mg, 66%) as a white solid: "HNMR (500 MHz, CD₃OD) δ 7.61 (d, J= 5.4 Hz, 1H), 7.47 (dd, J= 22.8, 7.8 Hz, 2H), 7.36 - 7.29 (m, 3H), 6.08 (d, J= 5.4 Hz, 1H), 3.65 (dd, J= 13.7, 6.9 Hz, 1H), 3.05 (ddd,J=34.9, 13.6, 7.3 Hz, 2H), 1.39 (d,J= 6.6 Hz, 3H); ESI MS m/z 385 [C₂oH,7ClN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.77 min.

Example 379

9-(4-(l-((dimethylamino)methyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(SH)

-one Hydrochloride

Following the procedure outlined for Example 1387,

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (10 mg, 0.03 mmol) was reacted with paraformaldehyde (8 mg, 0.1 1 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (7.0 mg, 87%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.70 (d, J = 7.9 Hz, 2H), 7.58 (d, J = 5.4 Hz, 1H), 7.39 (dd, J= 25.8, 8.4 Hz, 3H), 7.18 (d, J= 8.9 Hz, 1 H), 6.12 (d, J= 5.4 Hz, 1H), 2.94 (s, 6H), 1.34 - 1.25 (m, 2H), 1.23 - 1.14 (m, 2H); ESI MS m/z 391 [C23H22N2O2S + H]⁺; HPLC 96.7% (AUC), t_R = 8.72 min.

Example 373

9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one

To a solution of 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl) propanenitrile (50 mg, 0.14 mmol) in tolune (13 mL) at 0 °C was added BH₃ ^«THF (1 .0 M, 13 mL, 13 mmol) and the reaction was warmed to room temperature and heated at re

flux for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a light yellow solid (5.4 mg, 10%): Ή NMR (500 MHz, CD₃OD) δ 7.60 - 7.49 (m, 3H), 7.47 (dd, J = 7.7, 1.7 Hz, 1 H), 7.39 (d, J = 9.1 Hz, 1 H), 7.34 - 7.25 (m, 2H), 6.00 (d, J= 5.4 Hz, 1 H), 3.75 (s, 3H), 3.30 - 3.18 (m, 3H), 1 .49 (d, J = 6.5 Hz, 3H); ESI MS m/z 365 [C₂₁H₂₀N₂O₂S + H]⁺; HPLC 99% (AUC), t_R = 8.76 min.

Example 1218

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-

Hydrochloride

Following General Procedure F, tert-butyl 2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-yl)phenethylcarbamate (70 mg, 0.14 mmol) was treated with BBr₃ (1.0 M in CH₂C1_2, 5 mL, 5 mmol) to afford the desired product as a white solid (17 mg, 30%): 'H NMR (500 MHz, CD3OD) δ 7.66 (d, J = 5.4 Hz, 1 H), 7.54 (s, 1 H), 7.50 (t, J = 7.9 Hz, 1 H), 7.10 (d, J 7.9 Hz, 2H), 6.09 (d, J = 5.4 Hz, 1H), 3.76 (s, 3H), 3.25 - 3.06 (m, 4H); ESI MS m/z 403 [C2oH_{l 6}ClFN20₂S + H]⁺; HPLC 97.9% (AUC), t_R

Example 1247

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)

-one Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)-2-methylpropylcarbamate (1 10 mg, 0.20 mmol) was treated with BBr3 (1.0 M in CH2CI2_, 10 mL, 10 mmol) to afford the desired product as a brown solid (39 mg, 45%): ESI MS m/z 443

+ H]⁺; HPLC 96.3% (AUC), t_R = 9.56 min.

Example 1245

6-bromo-9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following Genera! Procedure F, tert-butyl 4-(6-bromo-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)-2-fluorophenethyl(methyl)carbamate (90 mg, 0.16 mmol) in CH2CI2 at 0 °C was added BBr₃ (1.0 M in CH2CI2_, 6 mL, 6 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product as a white solid ( 15 mg, 21%): ESI MS m/z 447 [C₂oH,6BrFN₂02S + H]⁺; HPLC >99% (AUC), t_R = 9.26 min.

Example 1258

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenethyl(methyl)carbamate (60 mg, 0.12 mmol) in CH2CI2 at 0 °C was added BBr₃ ( 1 .0 M in CH2CI2_, 6 mL, 6 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (C I 8 silica,

acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product as a off-white solid (31 mg, 67%): "H NMR (500 MHZ, CD₃OD) δ 7.63 (d, J = 5.4 Hz, 1 H), 7.51 (t, J= 7.9 Hz, 1 H), 7.15 - 7.06 (m, 3H), 6.20 (d, J = 5.4 Hz, 1 H), 3.42 - 3.35 (m, 2H), 3.30 - 3.10 (m, 2H), 2.80 (s, 3H), 2.57 (s, 3H); ESI MS m/z 383 [C2i H,₉FN₂02S + H]⁺; HPLC >99% (AUC), t_R = 8.65 min.

Example 1260

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno

[2,3-c]quinolin-9-y l)pheny l)-2-methy Ipropy lcarbamate (70 mg, 0.14 mmol) in CH₂C1₂ at 0 °C was added BBr3 ( 1 .0 M in CH₂C1_2, 5 mL, 5 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (C I 8 silica,

acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCl, concentrated and dried under high vacuum to afford the desired product as a brown solid (12 mg, 38%): ^]H NMR (500 MHz, CD₃OD) δ 7.66 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 5.4 Hz, 1 H), 7.36 (d, J= 8.4 Hz, 2H), 7.32 (s, 1 H), 6.13 (d, J= 5.4 Hz, 1 H), 3.29 (s, 2H), 1.58 (s, 6H); ESI MS m/z 399 [C21H19CIN2O2S + H]⁺; HPLC 98.8% (AUC), t_R = 9.26 min. Example 1280

9-(4-(l-aminopropan-2-yl)-3-chlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, tert-butyl 2-(2-chloro-4-(8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (120 mg, 0.24 mmol) in CH2CI2 at 0 °C was added BBn (1.0 M in CH2CI2, 15 mL, 15 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica,

acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a brown solid (40 mg, 43%): 'H NMR (500 MHz, CD₃OD) δ 7.65 (ddd, J = 9.9, 9.3, 6.1 Hz, 2H), 7.46 - 7.36 (m, 2H), 7.33 - 7.27 (m, 1 H), 7.18 (t, J = 9.0 Hz, 1H), 6.10 (dd, J = 28.8, 5.4 Hz, 1H), 3.86 - 3.66 (m, 1 H), 3.29 - 3.12 (m, 2H), 1 .44 - 1.28 (m, 3H); ESI MS m/z 385 [C2₀H₁₇ClN₂O₂S + H]⁺; HPLC >99% (AUC), t_R = 9.07 min. Example 1111

9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, 9-(4-(l -aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c] quinolin-4(5H)-one (120 mg, 0.33 mmol) in CH₂C1₂ at 0 °C was added BBr₃ (1.0 M in CH₂C1_2, 5 mL, 5 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCI, concentrated and dried under high vacuum to afford the desired product as a light yellow solid (48 mg, 42%): Ή NMR (500 MHz, CD₃OD) δ 7.57 (dd, J = 12.7, 6.7 Hz, 2H), 7.47 (d, J = 6.9 Hz, 1 H), 7.42 (d, J = 8.9 Hz, 1 H), 7.37 (d, J = 7.9 Hz, 1 H), 7.32 (d, J = 7.7 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1 H), 6.1 5 (d, J = 5.4 Hz, 1 H), 3.28 - 3.1 7 (m, 3H), 1 .50 (d, J = 6.1 Hz, 3H); ESI MS m/z 351 [C20H 18N2O2S + H]⁺; HPLC >99% (AUC), tR = 8.25 min.

Example 1151

(R)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno(2,3-c|quinolin-4(5H)-one

Hydrochloride

Following the procedure outlined for Example 1387,

(R)-9-(4-(l -aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one hydrochloride (20 mg, 0.06 mmol) was reacted with paraformaldehyde (10 mg, 0.17 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (5 mg, 24%) as a light yellow solid: 'H NMR (500 MHz,

CD₃OD) δ 7.71 (dd, J= 10.5, 7.8 Hz, 2H), 7.64 (d, J= 5.4 Hz, 1H), 7.47 (t, J = 7.1 Hz, 2H), 7.31 (d, J= 8.9 Hz, 2H), 6.01 (d, J= 5.4 Hz, 1H), 4.66 (q, J= 6.9 Hz, 1H), 2.97 (s, 3H), 2.86 (s, 3H), 2.20 - 2.00 (m, 2H), 1.86 (d, J = 7.0 Hz, 3H); ESI MS m/z 379 [C22H22N2O2S + H]⁺; HPLC 95.6% (AUC), t_R = 8.92 min.

Example 1162

2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butanenitrile

Following General Procedure F, 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl) phenyl)butanenitrile (80 mg, 0.21 mmol) in CH₂C1₂ at 0 °C was added BBr₃ (1.0 M in CH₂C1_2, 3 mL, 3 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a light yellow solid (4.3 mg, 6%): 'H NMR (500 MHz, CD₃OD) δ 7.56 (dd, J= 10.8, 4.6 Hz, 3H), 7.43 - 7.31 (m, 3H), 7.17 (d, J = 8.9 Hz, 1 H), 6.00 (d, J = 5.4 Hz, l H), 4.15 (t, J= 7.2 Hz, 1 H), 2.07 (p, J = 7.3 Hz, 2H), 1.16 (t, J = 7.4 Hz, 3H); ESI MS m/z 361 [C₂iH,₆N20₂S + H]⁺; HPLC 98.5% (AUC), t_R = 12.2 min.

Example 1174

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-hydroxythieno|2,3-c|quinolin-4(5H)-one

Hydrochloride

Following General Procedure C tert-butyl 2-(2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno [2,3-c]quinolin-9-yl)phenyl)propylcarbamate (120 mg, 0.25 mmol) was reacted with TFA (10 mL) to afford the desired product (35 mg, 37%) as a off-white solid: 'HNMR (500 MHz, CD₃OD) δ 7.64 (dd,J= 5.4, 3.1 Hz, 1H), 7.54 (ddd, J= 25.0, 11.7, 5.2 Hz, 2H), 7.40 (dd, J= 9.1, 1.1 Hz, 1H), 7.18 -7.06 (m,2H), 6.10 (dd,J= 27.5, 5.4 Hz, 1H), 3.77 (s, 3H), 3.64 - 3.43 (m, 1H), 3.42 - 3.22 (m, 2H), 1.51 (d, J= 7.0 Hz, 3H); ESI MS m/z 383 [C₂iH,₉FN₂0₂S + H]⁺;

HPLC 96.5% (AUC), t_R = 9.07 min.

Example 1189

(R)-8-methoxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-

Hyd roc hlo ride

Following General Procedure C (R)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propyl(methyl)carbamate (120 mg, 0.25 mmol) was reacted with TFA (8 mL) to afford the desired product (56 mg, 59%) as a white solid: 'HNMR (500 MHz, CD₃OD) δ 7.60-7.51 (m,3H), 7.48 (dd,J=7.8, 1.9 Hz, 1H), 7.39 (d, J= 9.1 Hz, 1H), 7.31 (ddd,J= 15.8, 7.8, 1.8 Hz, 2H), 5.99 (d, J =5.4 Hz, 1H), 3.75 (s, 3H), 3.46 - 3.36 (m, 1H), 3.37 - 3.24 (m, 2H), 2.76 (s, 3H), 1.49 (d, J= 6.7 Hz, 3H); ESI MS m/z 379 [C₂₂H₂₂N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.96 min.

Example 1131

(R)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (R)-tert-butyl l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c] quinolin-9-yl)phenyl)propylcarbamate (70 mg, 0.15 mmol) in CH₂C1₂ at 0 °C was added BBr₃ (1.0 M in CH₂C1₂_ 3 mL, 3 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica, acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HC1, concentrated and dried under high vacuum to afford the desired product as a light yellow solid (35 mg, 67%): 'HNMR (500

MHz, CD3OD) δ 7.61 (s, 2H), 7.55 (d,J= 5.4 Hz, 1H), 7.45-7.40 (m, 3H), 7.18 (d, J = 8.9 Hz, 1H), 6.03 (d,J=5.4 Hz, 1H), 4.32 (dd, J= 9.2, 5.9 Hz, 1H), 2.23-2.01 (m, 2H), 1.04 (t,J=7.4 Hz, 3H); ESI MS m/z 351 [C₂oH|₈N₂0₂S + H]⁺; HPLC >99% (AUC), t = 8.06 min. Example 1150

(R)-9-(4-(l-aminopropyI)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Hydrochloride

Following General Procedure F, (R)-tert-butyl l -(4-(6-bromo-8-methoxy-4-oxo-4,5- dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (50 mg, 0.09 mmol) in CH2CI2 at 0 °C was added BBr3 (1 .0 M in CH2CI?_, 5 mL, 5 mmol) and the reaction was warmed to room temperature for 4 h. The reaction was quenched by pouring onto water or ice-water and the resulting mixture was concentrated and purified by preparatory HPLC (CI 8 silica,

acetonitrile/water (with 0.05% TFA) gradient). The desired product was dissolved in aqueous HCI, concentrated and dried under high vacuum to afford the desired product as a light yellow solid (36 mg, 92%): 'H NMR (500 MHz, CD₃OD) δ 7.65 - 7.57 (m, 3H), 7.50 - 7.46 (m, 1 H), 7.45 - 7.39 (m, 2H), 6.02 (d, J = 5.4 Hz, 1 H), 4.32 (dd, J = 9.2, 6.0 Hz, 1 H), 2.20 - 2.00 (m, 2H), 1 .03 (t, J= 7.4 Hz, 3H); ESI MS m/z 429 [C₂oH,₇BrN₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 9.1 7 min.

Example 254

N-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylphenyl]

Following General Procedure F,

N-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2-methylphenyl]methanesulfona mide (47 mg, 0.1 1 mmol) was reacted with tribromoborane ( 1 .0 M in methylene chloride, 3.0 mL, 3.0 mmol) to afford the desired product ( 17 mg, 39%) as an off-white solid: Ή NMR (500 MHz, CD3OD) δ 7.58 (d, J = 5.4 Hz, 1 H), 7.55 (d, J = 8.1 Hz, 1 H), 7.39 (d, J = 8.9 Hz, 1 H), 7.21 (s, 1 H), 7.17-7.14 (m, 2H), 6. 10 (d, J = 5.4 Hz, 1 H), 3.40 (s, 3H), 2.43 (s, 3H); ESI MS m/z 401 [C|₉H , 6 ₂04S2 + H ; HPLC 96.4% (AUC), t_R = 10.23 min.

Example 334

9-[4-(2-Aminopropan-2-yl)phenyl]-6-chloro-8-hydroxythieno[2,3-c]quinolin-

4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

2-[4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propan-2-ylcarba mate (10 mg, 0.020 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (9.7 mg, 97%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.71 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 5.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.30 (s, 1 H), 6.06 (d, J = 5.4 Hz, 1 H), 1.86 (s, 6H); ESI MS m/z 385 [C₂₀H,₇ClN2O₂S + H]⁺; HPLC >99% (AUC), t_R = 10.89 min

Example 329

9-(4-(Aminomethyl)phenyl]-6-chloro-8-hydroxythieno[2,3-c]quinolin-

4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

4-(6-chloro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (15 mg, 0.032 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1 mL, 1 mmol) to afford the desired product (10 mg, 80%) as a brown solid: Ή NMR (500 MHz, CD3OD) δ 7.64 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 5.4 Hz, 1 H), 7.43-7.38 (m, 2H), 7.30 (s, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 4.27 (s, 2H); ESI MS m/z 357 [C8H1₃CI 2O2S + H]⁺; ESI MS m/z 357 [Ci8Hi₃ClN₂0₂S + H]⁺; HPLC 98.4% (AUC), t_R = 8.62 min.

Example 457

tert-Butyl 4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate

Following the procedure from Example 463,

9-[4-(aminomethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (320 mg, 1.0 mmol) was reacted with di-tert-butyl dicarbonate (260 mg, 1.2 mmol) to afford the desired product (150 mg, 36%): ESI MS m/z 323 [C23H22 2O4S + H]⁺.

Example 319

9-|4-(2-Aminopropan-2-yl)phenyl]-8-hydroxythieno[2,3-c|quinolin- 4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

2-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propan-2-ylcarbamate (29 mg, 0.063 mmol) was reacted with tribromoborane ( 1.0 M, 1.0 mL, 0.10 mmol) to afford the desired product ( 12 mg, 52%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.70 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 5.4 Hz, 1 H), 7.46 - 7.37 (m, J = 8.6, 7.7 Hz, 3H), 7.17 (d, J = 8.9 Hz, 1 H), 6.07 (d, J = 5.4 Hz, 1 H), 1.86 (s, 6H); ESI MS m/z 351 [C₂oHi₈N₂0₂S + H]⁺; HPLC 98.3% (AUC), t_R = 10.48 min.

Example 270

9-[4-(AminomethyI)phenyl]-6-bromo-8-hydroxythieno[2,3-c]quinoIin-

4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

4-(6-bromo-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (10 mg, 0.019 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.0 mL, 1.0 mmol) to afford the desired product (3.9 mg, 47%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.64 (d, J = 8.1 Hz, 2H), 7.60 (d, J = 5.4 Hz, 1 H), 7.47 (s, lH), 7.42-7.40 (m, 2H), 6.08 (d, J = 5.5 Hz, 1 H), 4.27 (s, 2H); ESI MS m/z 403 [(Ci₈H,₃BrN₂0₂S + 2) + H]⁺; HPLC 97.1 % (AUC), t_R = 7.90 min.

Example 210

N-(2-Bromoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-

Following General Procedure F,

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfona mide (1.7 g, 3.9 mmol) was reacted with tribromoborane (3.7 mL, 24 mmol) to afford the desired product (1.7 g, 91 %) as an off-white solid: Ή NMR (500 MHz, DMSO-d_fi) δ 1 1.84 (s, 1 H), 9.43 (s, 1 H), 8.16 (t, J = 5.9 Hz, 1 H), 7.94 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 5.4 Hz, 1 H), 7.52 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.9 Hz, 1 H), 7.19 (d, J = 8.9 Hz, 1 H), 5.83 (d, J = 5.4 Hz, 1H), 3.51 (t, J = 6.4 Hz, 2H), 3.28 (q, J = 6.2 Hz, 2H); ESI MS m/z 478 [Ci₉H₁₅BrN₂0₄S₂ + H]⁺; HPLC 98.5% (AUC), t_R = 15.23 min. Example 458

2-{4-[8-Hydroxy-4-oxo-4,5-dihydrothieno(2,3-c)quinolin-9-yl]

nate

To a solution of

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfona mide (390 mg, 0.90 mmol) and triethylamine (450 mg, 4.5 mmol) in anhydrous THF (20 mL) was added methane sulfonyl chloride (0.21 mL, 2.7 mmol) and the reaction mixture was stirred for 20 h at room temperature. The resulting precipitate was filtered and the filter cake was washed with THF (50 mL). The filtrate was concentrated and the residue was purified by flash chromatography (silica, ethyl acetate/hexanes gradient) to afford the desired product as a brown solid (250 mg, 55%). Ή NMR (300 MHz, DMSO-d₆) δ 1 1 .93 (s, 1 H), 8.14 (t, J = 1 1.7 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 5.4 Hz, 1 H), 7.56 (d, J = 9.0 Hz, 1 H), 7.53 (d, J = 8.4 Hz, 2H), 7.43 (d, J = 9.0 Hz, 1 H), 5.74 (d, J = 5.4 Hz, 1 H), 4.24 (t, J = 10.5 Hz, 2H), 3.71 (s, 3H), 3.20 (q, J = 1 1.7 Hz, 2 H) ESI MS m/z 509 [C21H20N2O7S3 + H]⁺

Example 332

N-(2-Chloroethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]

To a solution of

2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenylsulfonamido)ethyl methanesulfonate (250 mg, 0.49 mmol) in anhydrous dichloroethane was added aluminum chloride (330 mg, 2.5 mmol) and the reaction mixture was heated at reflux for 20 h. The reaction was cooled to room temperature, concentrated and quenched with methanol ( 10 mL). The resulting mixture was allowed to stand at room temperature for 1 h and the resulting precipitate was filtered and dried to afford the desired product (88 mg, 41 %) as an off-white solid: ¹ H NMR (500 MHz, DMSO-d₆) δ 1 1 .83 (s, 1 H), 9.42 (s, 1 H), 8.13 (t, J = 7.2 Hz, 1 H), 7.94 (d, J = 5.1 Hz, 2H), 7.74 (d, J = 3.3 Hz, 1 H), 7.51 (d, J = 5.1 Hz, 2H), 7.41 (d, J = 5,4 Hz, 1 H), 7.18 (d, J = 5.4 Hz, 1 H), 5.82 (d, J = 3.3 Hz, 1 H), 3.65 (t, J = 3.9 Hz, 2H), 3.22 (q, J = 3.6 Hz, 2H); ESI MS m/z 435 [C19H1SCIN2O4S2 + H]⁺; HPLC 97.2% (AUC), t_R = 14.98 min,

Example 304

4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesuIfonami

Following General Procedure F, the crude material from Example 74,

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N,N-dimethylbenzenesulfonamide (33 mg, 0.080 mmol), was reacted with tribromoborane (0.2 mL) to afford the desired product (9 mg, 7% over 2 steps) as a brown solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.85 (s, 1H), 9.44 (s, 1 H), 7.88 (dd, J = 6.8, 1.6 Hz, 2H), 7.79 (d, J = 5.4 Hz, 1H), 7.57 (dd, J = 6.6, 1.7 Hz, 2H), 7.42 (d, J = 8.9 Hz, 1H), 7.20 (d, J = 8.9 Hz, 1H), 5.69 (d, J = 5.4 Hz, lH), 2.71 (s, 6H); ESI MS m/z 401 [C19H16N2O4S2 + H]⁺; HPLC 94.5% (AUC), t_R = 14.84 min.

Example 297

N-(2-Bromoethyl)-2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]

Following General Procedure F,

2-fluoro-N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzen esulfonamide (52 mg, 0.12 mmol) was reacted with tribromoborane (0.80 mL, 0.23 mmol) to afford the desired product (47 mg, 81%) as a white solid: Ή NMR (500 MHz, DMSO-d*) δ 1 1.86 (s, 1H), 9.52 (s, 1 H), 8.45 (t, J = 5.7 Hz, 1H), 7.92 (t, J = 7.8 Hz, 1 H), 7.80 (d, J = 5.5 Hz, 1H), 7.46 (d, J = 10.9 Hz, 1 H), 7.42 (d, J = 8.9 Hz, 1 H), 7.30 (dd, J = 8.0, 1.4 Hz, 1 H), 7.19 (d, J = 9.0 Hz, 1H), 6.00 (d, J = 5.4 Hz, 1 H), 3.53 (t, J = 6.3 Hz, 2H), 3.42 (q, J = 6.0 Hz, 2H); ESI MS m/z 499 [C^HnBrF^C^ + H]⁺; HPLC 98.3% (AUC), t_R = 15.61 min.

Example 266

9-[5-(Aminomethyl)thiophen-2-yl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, tert-butyl

[5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)thiophen-2-yl]methylcarbamate (30 mg, 0.067 mmol) was reacted with tribromoborane (0.50 mL) to afford the desired product (25 mg, 91%) as a off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.67 (d, J = 5.4 Hz, 1 H), 7.43 (d, J = 9.0 Hz, 1 H), 7.16-7.14 (m, 2H), 6.86 (d, J = 3.5 Hz, 1H), 6.35 (d, J = 5.4 Hz, 1H), 4.12 (s, 2H); ESI MS m/z 329 [C16H12N2O2S2 + H]⁺; HPLC 95.6% (AUC), t_R = 9.59 min.

Example 235

9-{4-[(4-(Aminomethyl)piperidin-l-yl)methyl]-3-fluorophenyl-8-hydroxythieno

Following General Procedure F, tert-Butyl

{ l-[2-Fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl]piperidin-4-yl} methylcarbamate (10 mg, 0.020 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.20 mL, 0.20 mmol) to afford the desired product (6.0 mg, 65%) as a light yellow solid: Ή NMR (500 MHz, CD₃CN + D₂0) δ 7.73 (t, J = 7.8 Hz, 1H), 7.63 (d, J = 5.4 Hz, 1H), 7.46 (d, J = 8.9 Hz, 1H), 7.24 (d, J = 8.9 Hz, 1H), 7.21-7.18 (m, 2H), 6.07 (d, J = 5.4 Hz, 1H), 4.45 (q, 14.0 Hz, 2H), 3.15-3.1 1 (m, 2H), 2.94-2.90 (m, 2H), 2.51 (s, 2H), 2.09-2.06 (m, 3H), 2.00-1.96 (m, 4H); ESI MS m/z 438 [C24H24FN3O2S + H]⁺; HPLC 94.6% (AUC), t_R = 7.26 min.

Example 225

9-{4-[2-(Dimethylamino)ethyl]phenyl}-6-fluoro-8-hydroxythieno[2,3-c]

Following General Procedure F,

9-{4-[l -(dimethylamino)ethyl]phenyl}-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (6.0 mg, 0.015 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.10 mL, 0.075 mmol) to afford the desired product (5.2 mg, 90%) as an off-white solid: Ή NMR (500 MHz, CD3OD) δ 7.72 (t, J = 9.4 Hz, 2H), 7.63 (d, J = 5.4 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 2H), 7.04 (d, J = 12.0 Hz, 1 H), 6.02 (d, J = 5.4 Hz, 1 H), 4.68 (q, J = 4.3 Hz, 1 H), 2.98 (s, 3H), 2.87 (s, 3H), 1 .87 (d, J = 7.0 Hz, 3H); ESI MS m/z 383 [C₂iH,9FN₂02S + H]⁺; HPLC 96.0 % (AUC), t_R = 9.97 min.

Example 217

9-(4-Amino-3-hydroxyphenyl)-8-hydroxythieno[2 3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F,

9-(4-Amino-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one (20 mg, 0.060 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.20 mL, 0.18 mmol) to afford the desired product (16 mg, 84%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.62 (d, J = 5.4 Hz, 1 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.9 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1 H), 6.97 (d, J = 1.7 Hz, 1 H), 6.91 (dd, J = 8.0, 1.7 Hz, 1 H), 6.21 (d, J = 5.4 Hz, 1 H); ESI MS m/z 325 [C|₇H,2N20₃S + H]⁺; HPLC 94.3% (AUC), t_R = 8.17 min.

9-{4-[2-(Dimethylamino)et o[2,3-c]quinolin-4(5H)-one

Following General Procedure F,

9- {4-[2-(dimethylamino)ethyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5 H)-one (25 mg, 0.060 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.20 mL, 0.18 mmol) to afford the desired product (20 mg, 89%) as a yellow solid: Ή NMR (500 MHz, CD₃CN + D₂0) δ 7.55 (d, J = 5.4 Hz, 1 H), 7.43-7.41 (m, 3H), 7.22-7.18 (m, 3H), 5.99 (d, J = 5.4 Hz, 1 H), 3.00 (s, 4H), 2.56 (s, 6H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC 98.3%

(AUC), t_R = 9.24 min.

Example 341

9-{4-[l-(Dimethylamino)ethyl]phenyl}-6,7-dilluoro-8-hydroxythieno[2 3-c]

quinolin-4(5H)-one Hydrochloride

Following General Procedure F,

9-{4-[ l -(dimethylamino)ethyl]phenyl}-6,7-difluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (20 mg, 0.050 mmol) was reacted with tribromoborane (1 .0 M in methylene chloride, 0.50 mL, 0.50 mmol) to afford the desired product (15 mg, 72%) as an off-white solid: Ή NMR (500

MHz, CD₃CN + D₂0) δ 7.68-7.67 (m, 2H), 7.61 -7.59 (m, I H), 7.43-7.41 (m, 2H), 5.86-5.84 (m, 1 H), 4.58-4.54 (m, 1 H), 2.86 (s, 3H), 2.76 (s, 3H), 1.79-1.77 (m, 3H); ESI MS m/z

401 [C₂iH, 8F₂N202S + H ⁺; HPLC 97.8% (AUC), t_R = 9.35 min.

\-

Example 256

9-[4-(Aminomethyl)phenyl]-6-fluoro-8-hydroxythieno[2,3-c]quinolin-

4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

4-(6-fluoro-8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (30 mg, 0.075 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.75 mL, 0.75 mmol) to afford the desired product (22 mg, 88%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.64 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 5.4 Hz, lH), 7.39 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 12.0 Hz, 1 H), 6.07 (d, J = 5.4 Hz, 1 H), 4.28 (s, 2H); ESI MS m/z 341 [C 8H13FN2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.34 min.

Example 335

(S)-9-{4-[l-(Dimethylamino)ethyl]phenyl}-8-hydroxythieno[2,3-c]quinolin-

Following the procedure outlined for Example 460,

(S)-9-[4-( l -aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with formaldehyde (37% in water, 27 mg, 0.89 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (43 mg, 40%) as a white solid: Ή NMR (500 MHz, CD₃OD) . δ 7.69 (q, J = 7.8 Hz, 2H), 7.58 (d, J = 5.4 Hz, 1 H), 7.48-7.42 (m, 3H), 7.18 (d, J = 8.9 Hz, 1H), 6.01 (d, J = 5.4 Hz, 1H), 4.65 (q, J = 6.6 Hz, 1 H), 2.97 (s, 3H), 2.87 (s, 3H), 1.86 (d, J = 7.0 Hz, 3H); ESI MS m/z 365 [C₂₁H₂₀N₂O₂S + H]⁺; HPLC >99% (AUC), t_R = 9.30 min.

Example 459

(E)-9-[3-(3-Aminopiperidin-l-yl)prop-l-enyl]-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one

Following General Procedure F, (E)-tert-Butyl

l -[3-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)allyl]piperidin-3-ylcarbamate (320 mg, 0.88 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 4.0 mL, 4.0 mmol) to afford the desired product (100 mg, 41 %) as a yellow solid: Ή NMR (500 MHz, CD3OD) δ 8.00 (dd, J = 19.3, 5.4 Hz, 2H), 7.32 (d, J = 8.9 Hz, 1 H), 7.24 (d, J = 16.0 Hz, 1 H), 7.12 (d, J = 8.9 Hz, 1H), 6.39-6.25 (m, 1H), 4.25 (d, J = 6.8 Hz, 1 H), 3.94 (d, J = 1 1.4 Hz, 1 H), 3.83 (d, J = 1 1.9 Hz, 1H), 3.76-3.65 (m, 1H), 3.28-3.10 (m, 2H), 2.24 (dd, J = 35.1 , 13.6 Hz, 2H), 2.06-1.98 (m, 1 H), 1.81-1.68 (m, 1H).

Example 460

(E)-9-{3-[3-(Dimethylamino)piperidin-l-yl]prop-l -enyl}-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one

A solution of

(E)-9-[3-(3-aminopiperidin-l -yl)prop-l-enyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (60 mg, 0.15 mmol) and formaldehyde (37% in water, 13 mg, 0.44 mmol) in methanol (1 mL) was stirred at room temperature for 30 min followed by the addition of sodium cyanoborohydride (28 mg, 0.44 mmol). The reaction mixture was stirred at room temperature overnight, concentrated and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with methylene chloride. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/0.05% TFA gradient) to afford the desired product (30 mg, 53%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.97 (dd, J = 19.4, 5.3 Hz, 2H), 7.30 (d, J = 8.9 Hz, 1 H), 7.23 (d, J = 15.9 Hz, 1 H), 7.07 (d, J = 8.9 Hz, 1 H), 6.33-6.22 (m, 1 H), 4.32^1.18 (m, 3H), 3.90-3.77 (m, 2H), 3.47 (t, J = 1 1.6 Hz, 1 H), 3.18 (t, J = 1 1.3 Hz, 1 H), 3.01 (s, 6H), 2.40-2.23 (m, 2H), 2.10-1.84 (m, 2H).

Example 298

9-{3-[3-(Dimethylamino)piperidin-l-yl]propyl}-8-hydroxythieno[2,3-c]quinolin-

4(5H)-one Hydrochloride

To a solution of

(E)-9-{3-[3-(dimethylamino)piperidin- l-yl]prop-l -enyl}-8-hydroxythieno[2,3-c]quinolin-4(5H)- one (20 mg, 0.052 mmol) in methanol (10 mL) under nitrogen was added Pd on carbon (10 wt %, 12 mg) and the reaction mixture was placed in a Parr shaker for 18 h under an atmosphere of hydrogen (40 psi). The reaction mixture was filtered over diatomaceous earth and the filtrate was concentrated. The residue was purified by preparatory HPLC (CI 8 Silica,

water/acetonitrile w/0.05% TFA gradient) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (5.6 mg, 40%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 8.08 (d, J = 5.4 Hz, 1 H), 8.03 (d, J = 5.4 Hz, 1 H), 7.27 (d, J = 8.8 Hz, 1 H), 7.1 1 (d, J = 8.8 Hz, 1 H), 3.94-3.87 (m, 1 H), 3.72-3.61 (m, 2H), 3.45-3.35 (m, 4H), 2.99-2.94 (m, 1 H), 2.94 (s, 6H), 2.26-2.14 (m, 4H), 1.90-1.72 (m, 2H), 1 .24 (s, 2H), 1 .20 (s, 1 H); ESI MS m/z 386 [C21H27 3O2S + H]⁺; HPLC >99% (AUC), t_R = 6.71 min.

Example 267

9-{4-[(Ethylamino)methylJphenyl}-8-hydroxythieno[2,3-c]quinolin- 4 e

Following General Procedure F,

9-{4-[(ethylamino)rnethyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one (70 mg, 0.19 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.2 mL, 1.2 mmol) to afford the desired product (42 mg, 63%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.66 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 5.4 Hz, 1 H), 7.43-7.41 (m, 3H), 7.17 (d, J = 8.9 Hz, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 4.34 (s, 2H), 3.22 (q, J = 7.3 Hz, 2H), 1.41 (t, J = 7.3 Hz, 3H); ESI MS m/z 351 [C20H18 2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.01 min.

Example 229

8-Hydroxy-9-{4-[(isopropylamino)methyl]phenyl}thieno

hloride

Following General Procedure F,

9-{4-[(isopropylamino)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one was reacted with tribromoborane (1.0 M in methylene chloride, 1.6 mL, 1.6 mmol) to afford the desired product (48 mg, 50%) as a light brown glass: Ή NMR (500 MHz, CD₃OD) δ 7.70 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 9.7 Hz, 1 H), 7.44-7.41 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 6.12 (d, J = 5.1 Hz, 1 H), 4.37 (s, 2H), 3.59-3.55 (m, 1 H), 1 .48 (d, J = 6.5 Hz, 6H); ESI MS m/z 365

[C21H20N2O2S + H]⁺; HPLC >97.8% (AUC), t_R = 7.93 min.

Example 212

N-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno|2,3-c]quinolin-9-yl)benzyl]methanesulfonamide

A solution of 9-[4-(aminomethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (50 mg, 0.16 mmol) and methanesulfonyl chloride (43 mg, 0.37 mmol) in methylene chloride (5 mL) was stirred at room temperature for 10 min. N,N-diisopropylethylamine (48 mg, 0.37 mmol) was added and the reaction mixture was stirred for 1.5 h, concentrated under reduced pressure and the residue was purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient) to afford the desired product (28 mg, 45%) as a white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.77 (s, 1 H), 9.22 (s, 1 H), 7.70-7.67 (m, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.9 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 8.9 Hz, 1H), 5.89 (d, J = 5.4 Hz, 1H), 4.29 (d, J = 6.4 Hz, 2H), 2.94 (s, 3H); ESI MS m/z 401 [C19H16N2O4S + H]⁺; HPLC >99% (AUC), t_R = 12.12 min.

Example 187

8-Hydroxy-9-{4-[(methylamino)methyl]phenyl}thieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F,

8-methoxy-9-{4-[(methylamino)methyl]phenyl}thieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.29 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 1.7 mL, 1.7 mmol) to afford the desired product (28 mg, 30%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.65 (d, J = 8.1 Hz, 2H), 7.55 (d, J = 5.4 Hz, 1H), 7.44-7.41 (m, 3H), 7.17 (d, J = 8.9 Hz, 1H), 6.05 (d, J = 5.4 Hz, 1 H), 4.33 (s, 2H), 2.83 (s, 3H); ESI'MS m/z 337 [Ci₉H₁₆N₂0₂S + H]⁺; HPLC > 99% (AUC), t_R = 10.02 min. 9-{4-[(Diethylamino)methyl]p ieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F,

9- {4-[(diethylamino)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one (30 mg, 0.076 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.46 mL, 0.46 mmol) to afford the desired product (12 mg, 42%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.69 (d, J = 8.1 Hz, 2H), 7.56 (d, J = 5.4 Hz, 1H), 7.48-7.42 (m, 3H), 7.18 (d, J = 8.9 Hz, 1H), 6.03 (d, J = 5.4 Hz, 1 H), 4.50 (s, 2H), 3.36-3.31 (m, 4H), 1.43 (t, J = 7.3 Hz, 6H); ESI MS m/z 379

[C22H22N2O2S + H]⁺; HPLC 97.2 % (AUC), t_R = 8.27 min.

Example 165

9-{4-[(Dimethylamino)methyl]phenyl}-8-hydroxythieno|2,3-c|quinolin-4(5H)-one

Following General Procedure F,

9-{4-.[(dimethylamino)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one (30 mg, 0.082 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.49 mL, 0.49 mmol) to afford the desired product (1 1 mg, 40%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.54-7.50 (m, 3H), 7.39 (d, J = 8.9 Hz, lH), 7.29 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.9 Hz, 1 H), 5.99 (d, J = 5.5 Hz, 1 H), 3.64 (s, 2H), 2.36 (s, 6H); ESI MS m/z 351 [C20H18 2O2S + H]⁺; HPLC 98.5% (AUC), t_R = 7.71 min.

9-{4-[l-(Dimethylamino)ethy eno[2,3-c]quinolin-4(5H)-one

Following the procedure outlined for Example 460,

9-[4-(l-Aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (40 mg, 0.12 mmol) was reacted with formaldehyde (37% in water, 14 mg, 0.50 mmol) and after purification the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (20 mg, 42%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.71-7.67 (m, 2H), 7.58 (d, J = 4.4 Hz, 1 H), 7.48-7.41 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 6.01 (d, J = 5.4 Hz, 1 H), 4.65 (q, J = 7.0 Hz, 1H), 2.97 (s, 3H), 2.87 (s, 3H), 1.86 (d, J = 7.0 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 7.86 min.

Example 192

9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno

|2,3-c]

Following General Procedure F,

9-{4-[l-(dimethylamino)ethyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one (3.2 g, 7.1 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 43 mL, 43 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (1.3 g, 92%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.71-7.67 (m, 2H), 7.58 (d, J = 4.4 Hz, 1 H), 7.48-7.41 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 6.01 (d, J = 5.4 Hz, 1 H), 4.65 (q, J = 7.0 Hz, 1 H), 2.97 (s, 3H), 2.87 (s, 3H), 1.86 (d, J = 7.0 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC >99% (AUC), t_R = 7.86 min.

Example 72

9-|4-(Aminomethyl)phenyl|-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, tert-Butyl

4-(8-Methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (70 mg, 0.16 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.96 mL, 0.96 mmol) to afford the desired product (37 mg, 60%) as a white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.80 (s, 1 H), 9.28 (s, 1 H), 8.25 (br s, 2H), 7.68 (d, J = 5.4 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.9 Hz, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.8 Hz, 1H), 5.92 (d, J = 5.4 Hz, 1 H), 4.18 (m, 2H); ESI MS m/z 323 [C|₈HuN₂0₂S + H]⁺; HPLC 98.3% (AUC), t_R = 10.74 min. 9-[4-(Aminomethyl)phenyl]-8-h inolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (260 mg, 0.60 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 3.6 mL, 3.6 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (120 mg, 50%) as a off-white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.80 (s, 1H), 9.28 (s, 1H), 8.25 (br s, 2H), 7.68 (d, J = 5.4 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.9 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.8 Hz, 1H), 5.92 (d, J = 5.4 Hz, 1H), 4.18 (m, 2H); ESI MS m/z 323 [C18H14N2O2S + H]⁺; HPLC 98.3% (AUC), t_R = 10.74 min.

Example 233

(S)-9-[4-(l-Aminoethyl)phenyl]-8-hydroxythieno[2,3-c]

quino

Following General Procedure F,

(S)-9-[4-(l -aminoethyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.22 mmol) was reacted with tribromoborane (3.0 mL) to afford the desired product (16 mg, 22%) as a yellow solid: Ή NMR (500 MHz, CD3OD) δ 7.63-7.61 (m, 2H), 7.56-7.55 (m, 1 H), 7.43-7.41 (m, 3H), 7.17 (d, J = 8.9 Hz, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 4.61 (q, J = 4.7 Hz, 1H), 1.76 (d, J = 6.9 Hz, 3H); ESI MS m/z 337 [C^H^OzS + H]⁺; HPLC 98.6% (AUC), t_R = 7.62 min. Example 347

(S)-N-{l-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]ethyI}methanes

Following the procedure outlined for Example 301 ,

(S)-9-[4-(l -aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.30 mmol) was reacted with methanesulfonyl chloride (100 mg, 0.89 mmol) to afford the desired product (70 mg, 56%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 5.89-7.55 (m, 2H), 7.52 (d, J = 5.4 Hz, 1H), 7.38 (d J = 8.9 Hz, 1H), 7.30-7.28 (m, 2H), 7.15 (d, J = 8.9 Hz, 1 H), 6.00 (d, J = 5.4 Hz, 1 H), 4.71 (q, J = 7.1 Hz, 1 H), 2.82 (s, 3H), 1.61 (d, J = 7.0 Hz, 3H); ESI MS m/z 415 [C₂oH₁₈N₂04S2 + H]⁺; HPLC >99% (AUC), t_R = 12.43 min.

Example 339

9-{4-|l-(DimethyIamino)propyl|phenyl}-8-hydroxythieno[2,3-c]quinoIin-

Following the procedure outlined for Example 460,

9-[4-(l -aminopropyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.29 mmol) was reacted with formaldehyde (26 mg, 0.86 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (62 mg, 58%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.69-7.64 (m, 2H), 7.56 (d, J = 5.4 Hz, 1 H), 7.51-7.47 (m, 2H), 7.43 (d, J = 8.9 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 5.95 (d, J = 5.4 Hz, 1H), 4.38 (dd, J = 1 1.3, 4.3 Hz, 1 H), 2.99 (s, 3H), 2.85 (s, 3H), 2.32-2.25 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H); ESI MS m/z 379 [C₂₂H₂₂N₂0₂S + H]⁺; HPLC 97.2% (AUC), t_R = 9.45 min.

Example 338

9-{4-[l-(Diethylamino)propyl]phenyl}-8-hydroxythieno[2,3-c]quinolin-

Following the procedure outlined for Example 460,

(9-[4-(l -aminopropyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.29 mmol) was reacted with formaldehyde (38 mg, 0.86 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (52 mg, 45%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.71 (dd, J = 7.7, 1.8 Hz, I H), 7.66 (dd, J = 7.9 Hz, 1.9 Hz, IH), 7.54 (d, J = 5.5 Hz, I H), 7.49-7.45 (m, 2H), 7.42 (d, J = 5.5 Hz, I H), 7.19 (d, J = 4.2 Hz, I H), 5.95 (d, J = 5.4 Hz, IH), 4.48 (dd, J = 1 1.7, 3.8 Hz, I H), 3.47-3.40 (m, 3H), 3.12-3.08 (m, I H), 2.35-2.21 (m, 2H), 1.45 (t, J = 7.3 Hz, 3H), 1.35 (t, J = 7.3 Hz, 3H), 0.95 (t, J = 7.3 Hz, 3H); ESI MS m/z 407 [C24H26N2O2S + H]⁺; HPLC 96.3% (AUC), t_R = 10.74 min.

Example 336

9-[4-(l-Aminopropyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, tert-butyl

1 -[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propy lcarbamate (70 mg, 0.15 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 0.90 mL, 0.90 mmol) to afford the desired product (35 mg, 52%) as a light yellow solid: Ή NMR (500 MHz, CD3OD) δ 7.63-7.58 (m, 2H), 7.53 (d, J = 5.4 Hz, IH), 7.42-7.39 (m, 3H), 7.17 (d, J = 8.9 Hz, I H), 6.02 (d, J = 5.4 Hz, I H), 4.32 (q, J = 5.9 Hz, I H), 2.17-2.08 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H); ESI MS m/z 351 [C₂oHi₈N₂02S + H]⁺; HPLC >99% (AUC), t_R = 9.39 min.

9-{4- [ 1 -(Cyclopentylami oxythieno[2,3-c]quinolin- e

Following General Procedure F,

9-{4-[ l -(cyclopentylamino)ethyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H)-one (200 mg, 0.48 mmol) was reacted with tribromoborane (15 mL) to afford the desired product (25 mg, 13%) as a brown solid: Ή NMR (300 MHz, CD₃OD) δ 7.71-7.64 (m, 2H), 7.56 (d, J = 5.4 Hz, I H), 7.48-7.41 (m, 3H), 7.18 (d, J = 8.9 Hz, IH), 6.06 (d, J = 5.4 Hz, IH), 4.57 (q, J = 6.8 Hz, IH), 3.59-3.49 (m, I H), 2.26-2.08 (m, 2H), 1.87-1.62 (m, 9H); ESI MS m/z 405 [C24H24N2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.84 min.

Example 313

8-Hydroxy-9-[4-(l-hydroxyethyl)phenyl]thieno[2,3-c]quinolin-4(5H)-one

A solution of 9-(4-acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (200 mg, 0.59 mmol) in ethanol (4 mL) was cooled to 0 °C and sodium borohydride (45 mg, 1.2 mmol) was added. The reaction mixture was stirred at room temperature for 18 h however starting material was present. The reaction was cooled to 0 °C and lithium aluminum hydride (1.0 M in THF, 1 .2 mL, 1.2 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The reaction was cooled to 0 °C, quenched with methanol and concentrated. The residue was purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient) to afford the desired product (2.6 mg, 1 %) as a light brown solid: Ή NMR (300 MHz, CD₃OD) δ 7.59-7.52 (m, 3H), 7.39 (d, J = 8.9 Hz, 1 H), 7.29-7.25 (m, 2H), 7.16 (d, J = 8.9 Hz, 1 H), 6.03 (d, J = 5.4 Hz, 1 H), 4.97 (q, J = 6.4 Hz, 1 H), 1.56 (d, J = 6.5 Hz, 3H); ESI MS m/z 338

[C|₉H,5N0₃S + H]⁺; HPLC 98.6% (AUC), t_R = 9.78 min.

Example 308

9-{4-[l-(Dimethylamino)-2-methylpropan-2-yl]phenyl}-8-hydroxythieno

[2,3-c|quinoIin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 460,

9-[4-(l -amino-2-methylpropan-2-yl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (30 mg, 0.082 mmol) was reacted with formaldehyde (7.4 mL, 0.25 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (7 mg, 22%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.71 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 5.4 Hz, 1 H), 7.40 (q, J = 6.6 Hz, 3H), 7.17 (d, J = 8.9 Hz, 1H), 6.07 (d, J = 5.4 Hz, 1 H), 3.68 (s, 2H), 2.81 (s, 6H), 1.62 (s, 6H); ESI MS m/z 393 [C2₃H24N2O2S + H]⁺; HPLC 97.5% (AUC), t_R = 8.46 min.

Example 301

(R)-N- { 1 - [ 3-c] quinolin-

A solution of (R)-9-[4-(l-aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (28 mg, 0.83 mmol) and methanesulfonyl chloride (82 μί, 1.0 mmol) in 1 : 1 methylene chloride/THF (6 mL) and DMF ( 1.5 mL) was stirred at room temperature for 10 min followed by the addition of Ν,Ν-diisopropylethylamine (170 μί, 1 .0 mmol). The reaction mixture was stirred for 1.5 h, concentrated and purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient) to afford the desired product (8.9 mg, 2%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.59-7.55 (m, 2H), 7.53 (d, J = 5.5 Hz, 1 H), 7.39 (d, J = 8.9 Hz, 1 H), 7.31-7.30 (m, 2H), 7.16 (d, J = 8.9 Hz, 1 H), 6.02 (d, J = 5.4 Hz, 1H), 4.71 (q, J = 4.6 Hz, 1 H), 2.82 (s, 3H), 1.62 (d, J = 7.0 Hz, 3H); ESI MS m/z 415 [C₂oHi 8N₂0₄S₂ + H]⁺; HPLC 96.4% (AUC), t_R = 10.14 min.

Example 296

9-(4-Acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, 9-(4-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one (450 mg, 1.3 mmol) was reacted with tribromoborane (15 mL) to afford the desired product (320 mg, 74%) as a light brown solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1 .82 (s, 1 H), 9.38 (s, 1 H), 8.10 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 5.4 Hz, 1 H), 7.44-7.39 (m, 3H), 7.18 (d, J = 8.9 Hz, 1 H), 5.90 (d, J = 5.4 Hz, 1 H), 2.68 (s, 3H); ESI MS m/z 336 [C9H13NO3S + H]⁺; HPLC 98.3 % (AUC), t_R = 10.59 min. 3-[4-(8-Hydroxy-4-oxo-4,5-di in-9-yl)phenyl]propanenitrile

Following General Procedure F,

3-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propanenitrile (45 mg, 0.13 mmol) was reacted with tribromoborane (3 mL) to afford the desired product (5.6 mg, 13%) as a white solid: Ή NMR (500 MHz, CD₃OD) δ 7.53 (d, J = 5.4 Hz, 1 H), 7.48 (d, J = 7.9 Hz, 2H), 7.39 (d, J = 8.9 Hz, 1 H), 7.28 (d, J = 7.9 Hz, 2H), 7.16 (d, J = 8.9 Hz, 1 H), 5.96 (d, J = 5.4 Hz, 1 H), 3.10 (t, J = 3.8 Hz, 2H), 2.89 (t, J = 7.1 Hz, 2H); ESI MS m/z 347 [C₂oHi₄N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 10.99 min.

Example 356

9-{4-[l-(Diethylamino)ethyl]-3-fluorophenyl}-8-hydroxythieno

[2,3-c)quinoIin-4(5H)-one Hydrochloride

₍

A solution of 9-(4-(l -aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (40 mg, 0.1 1 mmol) and acetaldehyde (25 mg, 0.45 mmol) in methanol (2 mL) was stirred at room temperature for 30 min followed by the addition of sodium cyanoborohydride (28 mg, 0.452 mmol) and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated, partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was extracted with methylene chloride and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (30 mg, 65%) as a yellow solid: Ή NMR (500 MHz, CDjOD) δ 7.84-7.82 (m, 1 H), 7.67-7.65 (m, lH , 7.44 (dd, J = 9.1 , 1.5 Hz, 1H), 7.34-7.28 (m, 2H), 7.19 (dd, J = 8.9, 2.5 Hz, l H), 6.14 (t, J = 5.1 Hz, 1H), 5.16-5.06 (m, 1 H), 3.46-3.35 (m, 3H), 3.30-3.15 (m, 1 H), 2.79 (s, 1 H), 1.88 (t, J = 6.2 Hz, 3H), 1.48-1.37 (m, 6H); ESI MS m/z 41 1 [C23H23FN2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.57 min.

Example 359

9-[4-(l-Aminoethyl)-3-fluorophenyl]-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

•HC1

Following General Procedure F, tert-butyl

l -[2-fluoro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]ethylcarbamate (400 mg, 0.856 mmol) was reacted with tribromoborane (4 mL) to afford the desired product (99 mg, 33%) as a white solid: Ή NMR (300 MHz, CD₃OD) δ 7.70-7.60 (m, 2H), 7.43 (d, J = 8.9 Hz, 1 H), 7.27-7.15 (m, 3H), 6.1 8 (q, J = 3.0 Hz, 1 H), 1.78 (t, J = 6.5 Hz, 3H); ESI MS m/z 355 [Ci₉H,₅FN₂02S + H]⁺; HPLC >99% (AUC), t_R = 7.84 min.

Example 353

8-Hydroxy-9-(l 2,3,4-tetrahydroisoquinolin-7-yl)thieno

rochloride

Following General Procedure F,

8-methoxy-9-(l ,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one (40 mL, 0.1 1 mmol) was reacted with tribromoborane (2 mL) to afford the desired product (26 mg, 68%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.56 (d, J = 5.5 Hz, 1 H), 7.45 (d, J = 8.0 Hz, 1 H), 7.40 (d, J = 8.9 Hz, 1H), 7.27-7.25 (m, 1 H), 7.19 (br s, 1 H), 7.16 (d, J = 8.9 Hz, 1 H), 6.17 (d, J = 5.4 Hz, 1H), 4.12 (s, 2H), 3.67-3.57 (m, 2H), 3.29-3.22 (m, 2H); ESI MS m/z 349

[C20H16N2O2S + H]⁺; HPLC >99% (AUC), t_R = 7.82 min.

Example 349

9-{4-[l-(Dimethylamino)ethyl]-3-fluorophenyI}-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

•HC1

Following the procedure outlined for Example 460,

9-[4-( l -aminoethyl)-3-fluorophenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (40 mg, 0.1 1 mmol) was reacted with formaldehyde ( 14 mg, 0.45 mmol) to afford the desired product (23 mg, 53%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.81-7.73 (m, 1 H), 7.66 (q, J = 4.3 Hz, 1 H), 7.44 (dd, J = 8.9, 2.3 Hz, 1 H), 7.34-7.29 (m, 2H), 7.20-7.18 (m, 1 H), 6.14 (t, J = 6.0 Hz, 1H), 5.03-4.92 (m, l H), 3.03-2.86 (m, 6H), 2.78 (br s, 1 H), 1.88 (dd, J = 7.0, 2.4 Hz, 3H); ESI MS m/z 383 [C21 H19F 2O2S + H]⁺; HPLC >99% (AUC), t_R = 8.04 min.

Example 361

l-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]cyclopropanecarbonit rile

Following General Procedure F,

l-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]cyclopropanecarbonitrile (340 mg, 0.91 mmol) was reacted with tribromoborane (1 .3 mL) to afford the desired product (90 mg, 28%) as a light brown solid: ESI MS.m/z 359 [C₂] H,₄N202S + H]⁺.

Example 348

9-{4-(l-(Aminomethyl)cyclopropyl]phenyl}-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 265,

l -[4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]cyclopropanecarbonitrile (80 mg, 0.1 1 mmol) was reacted with borane (3 mL) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (20 mg, 28%) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.62 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 5.4 Hz, 1 H), 7.41 (d, J = 8.9 Hz, I H), 7.34 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.9 Hz, 1 H), 6.17 (d, J = 5.4 Hz, 1 H), 3.25 (s, 2H), 1.21-1.12 (m, 4H); ESI MS m/z 363 [C21H18N2O2S + H]⁺; HPLC 97.3% (AUC), t_R = 8.38 min.

Example 345

9-(2-Amino-2,3-dihydro-lH-inden-5-yl)-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following Genreal Procedure F, tert-butyl

5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-2,3-dihydro-l H-inden-2-ylcarbamat e (210 mg, 0.59 mmol) was reacted tribromoborane (10 mL) to afford the desired product (55 mg, 27%) as a yellow solid:

Major Isomer: Ή NMR (500 MHz, CD₃OD) δ 7.56 (d, J = 2.4 Hz, I H), 7.49 (d, J = 7.7 Hz, 1 H), 7.39 (d, J = 1.3 Hz, 1 H), 7.26 (s, 1 H), 7.19-7.15 (m, 2H), 6.14 (d, J = 5.4 Hz, 1 H),

4.24-4.20 (m, IH), 3.62-3.49 (m, 2H), 3.22-3.07 (m, 2H); ESI MS m/z 349 [C₂oHi₆N₂0₂S + H]⁺; HPLC 60.4% (AUC), t_R = 7.89 min;

Minor Isomer: Ή NMR (500 MHz, CD₃OD) δ 7.55 (d, J = 2.4 Hz, IH), 7.46 (d, J = 7.7 Hz, I H), 7.41 (d, J = 1.3 Hz, I H), 7.24 (s, I H), 7.19-7.15 (m, 2H), 6.26 (d, J = 5.4 Hz, I H),

4.24-4.20 (m, I H), 3.62-3.49 (m, 2H), 3.22-3.07 (m, 2H); ESI MS m/z 349 [C₂₀Hi₆N₂O₂S + H]⁺; HPLC 39.5% (AUC), t_R = 7.65 min.

Example 327

9-{4-[2-(Dimethylamino)ethyl]-3-fluorophenyl}-8-hydroxythieno

|2,3-c]quinolin-4(5H)-one Hydrochloride

^•HCI

Following General Procedure F,

9-[4-(2-aminoethyl)-3-fluorophenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (25 mg, 0.063 mmol) was reacted with tribromoborane (3 mL) to afford the desired product (3.5 mg, 13%) as a brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.62 (d, J = 5.4 Hz, 1 H), 7.55 (t, J = 7.9 Hz, I H), 7.42 (d, J = 8.9 Hz, 1 H), 7.18-7.1 1 (m, 3H), 6.15 (d, J = 5.4 Hz, 1 H), 3.52 (t, J = 8.2 Hz, 2H), 3.26-3.19 (m, I H), 3.04 (s, 6H); ESI MS m/z 383 [C₂iH₁₉FN₂0₂S + H]; HPLC 96.2% (AUC), t_R = 8.06 min.

Example 278 9-{3-Fluoro-4-[(3-hydroxypyrrol hydroxythieno[2,3-c]quinolin-4

Following General Procedure F,

9-{3-fluoro-4-[(3-hydroxypyrrolidin- l -yl)methyl]phenyl}-8-methoxythieno[2,3-c]quinolin-4(5H )-one (90 mg, 0.21 mmol) was reacted with tribromoborane (2 mL) to afford the desired product (32 mg, 34%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.78-7.75 (m, 1H), 7.65 (d, J = 5.3 Hz, 1 H), 7.44 (d, J = 8.9 Hz, 1 H), 7.30-7.27 (m, 2H), 7.19 (d, J = 8.9 Hz, 1 H), 6.15-6.13 (m, 1 H), 4.76-4.57 (m, 3H), 3.86-3.72 (m, 1 H), 3.62-3.53 (m, 1 H), 3.49-3.40 (m, l H), 2.78 (br s, l H), 2.54-2.46 (m, l H), 2.22-2.20 (m, 1H), 2.15-2.05 (m, 1 H); ESI MS m/z 41 1 [C22H19FN2O3S + H]⁺; HPLC >99% (AUC), t_R = 7.58 min.

Example 277

9-[4-(l-Amino-2-methylpropan-2-yl)phenyl]-8-hydroxythieno

| hloride

Following General Procedure F,

9-[4-(l -amino-2-methylpropan-2-yl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (100 mg, 0.27 mmol) was reacted with tribromoborane (3 mL) to afford the desired product (25 mg, 22%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.66 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 5.4 Hz, 1 H), 7.42 (d, J = 8.9 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.9 Hz, 1 H), 6.16 (d, J = 5.4 Hz, 1 H), 3.28 (s, 2H), 1.59 (s, 6H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC 96.9 % (AUC), t_R = 9.47 min.

Example 276

9-[4-(2-Aminoethyl)-3-fluorophenyl]-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F,

9-[4-(2-aminoethyl)-3-fluorophenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (260 mg, 0.71 mmol) was reacted with tribromoborane (6 mL) to afford the desired product (12 mg, 12%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.63 (d, J = 5.4 Hz, 1H), 7.52-7.49 (m, 1H), 7.42 (d, J = 8.9 Hz, 1H), 7.17 (d, J = 8.9 Hz, 1 H), 7.15-7.12 (m, 2H), 6.20 (d, J = 5.4 Hz, 1H), 3.30-3.23 (m, 2H), 3.12-3.06 (m, 2H), 2.79 (br s, 3H); ESI MS m/z 355 [C19H15FN2O2S + H]⁺; HPLC 94.9% (AUC), t_R = 7.80 min.

Example 275

(R)-9-[4-(l-Aminoethyl)phenyl]-8-hydroxythieno

[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F, (R)-tert-butyl

1 -[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]ethylcarbamate (350 mg, 0.78 mmol) was reacted with tribromoborane ( 15 inL) to afford the desired product (120 mg, 42%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.65-7.62 (m, 2H), 7.55 (d, J = 5.4 Hz, 1 H), 7.42-7.41 (m, 3H), 7.17 (d, J = 8.9 Hz, 1H), 6.08 (d, J = 5.4 Hz, 1H), 4.61 (q, J = 4.5 Hz, 1 H), 2.78 (br s, 3H), 1.76 (d, J = 6.9 Hz, 3H); ESI MS m/z 337[C,9H₁₆N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 7.49 min.

Example 273

9-[4-(3-Aminopropyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one Hydrochloride

Following General Procedure F,

9-[4-(3-aminopropyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (140 mg, 0.39 mmol) was reacted with tribromoborane (6 mL) to afford the desired product (18 mg, 12%) as a light yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.53 (d, J = 5.5 Hz, 1 H), 7.43 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.9 Hz, 1 H), 7.26 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.9 Hz, 1H), 6.02 (d, J = 5.5 Hz, l H), 3.04 (t, J = 7.7 Hz, 2H), 2.88 (t, J = 7.7 Hz, 2H), 2.1 1-2.08 (m, 2H); ESI MS m/z 351

[C₂oH, 8N20₂S + H]⁺; HPLC 96.2%, t_R = 8.91 min.

Example 65

4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yI)benzenesulfonamide

Following General Procedure F,

N-tert-butyl-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide (4.3 g, 9.9 mmol) was reacted with tribromoborane (1.0 M in methylene chloride, 48 mL, 48 mmol) to afford the desired product (3.4 g, 94%) as a light red solid: Ή NMR (300 MHz, DMSO-de) δ 1 1.83 (s, 1 H), 9.12 (s, 1 H), 7.96-7.95 (m, 2H), 7.76 (d, J = 5.4 Hz, 1 H), 7.48-7.47 (m, 4H), 7.41 (d, J = 8.9 Hz, 1 H), 7.18 (d, J = 8.9 Hz, 1 H), 5.91 (d, J = 5.4 Hz, 1 H); ESI MS m/z 373 [C^H^C^ + H]⁺; HPLC 98.1 % (AUC),

t_R = 10.29 min.

Example 61

8-Hydroxy-9-(lH-indazol-6-yl)thieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, 9-(l H-indazol-6-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one (35 mg, 0.10 mmol) was reacted with tribromoborane (1.5 mL, 0.15 mmol) to afford the desired product (3.6 mg, 1 1%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 8.17 (s, 1 H), 7.75-7.73 (m, 2H), 7.48 (d, J = 5.5 Hz, 1H), 7.42 (d, J = 8.9 Hz, 1 H), 7.34 (d, J = 9.2 Hz, 1 H), 7.19 (d, J = 8.9 Hz, 1H), 5.91 (d, J = 5.5 Hz, 1 H); ESI MS m/z 334 [CgHnNsOzS + H]⁺; HPLC 96.3% (AUC), t_R = 9.20 min.

Example 193

N-{l-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]ethyl}methanesuIf

A solution of 9-[4-(l-aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (30 mg, 0.089 mmol) and methanesulfonyl chloride (9.0 μΕ, 0.1 1 mmol) in 2: 1 methylene chloride/THF (3 mL) was stirred at room temperature for 10 min followed by the addition of

N,N-diisopropylethylamine ( 19 μί, 0.1 1 mmol). The reaction mixture was stirred for 1.5 h, concentrated and purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient)to afford the desired product (7.2 mg, 20%) as an amorphous brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.57-7.56 (m, 2H), 7.53 (d, J = 5.4 Hz, 1H), 7.39 (d, J = 8.9 Hz, 1 H), 7.32-7.30 (m, 2H), 7.16 (d, J = 8.9 Hz, 1 H), 6.02 (d, J = 5.4 Hz, 1 H), 4.71 (q, J = 4.6 Hz, 1 H), 2.82 (s, 3H), 1.62 (d, J = 7.0 Hz, 3H); ESI MS m/z 415 [C20H18 2O4S2 + H]⁺; HPLC >99%, t_R = 10.18 min.

Example 175

9-[4-(2-Aminoethyl)phenyl]-8-hydroxythhiieeno[2,3-c]quinolin-4(5H)-

Following General Procedure F,

9-[4-(2-aminoethyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (800 mg, 1.8 mmol) was reacted with tribromoborane (10 mL) to afford the desired product (520 mg, 88%) as an off-white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.78 (s, 1H), 9.20 (s, 1H), 7.88 (br s, 2H), 7.69 (d, J = 5.4 Hz, 1 H), 7.41-7.36 (m, 3H), 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.9 Hz, 1 H), 5.88 (d, J = 5.4 Hz, 1 H), 3.21-3.14 (m, 2H), 3.01-2.98 (m, 2H); ESI MS m/z 337 [Ci₉H,6N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 7.72 min.

Example 176

9-[4-(2-Aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin

-4(5H)-one Hydrochloride

Following General Procedure F,

9-[4-(2-aminoethyl)phenyl]-8-methoxythieno[2,3-c]quinolin-4(5H)-one (800 mg, 1.8 mmol) was reacted with tribromoborane (10 mL) and the resulting material was converted to the

hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (520 mg, 88%) as an off-white solid: Ή NMR (500 MHz, DMSO-d₆) δ 1 1.78 (s, 1 H), 9.20 (s, 1 H), 7.88 (br s, 2H), 7.69 (d, J = 5.4 Hz, 1H), 7.41-7.36 (m, 3H), 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.9 Hz, 1H), 5.88 (d, J = 5.4 Hz, 1H), 3.21-3.14 (m, 2H), 3.01-2.98 (m, 2H); ESI MS m/z 337

[C, 9H, 6N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 7.72 min.

Example 112

8-Hydroxy-9-{4-[4-(methylsulfonyl)piperazin-l-yI]phenyl}thieno

[2 ,3-c] quinolin-4(5H)-one

Following General Procedure F,

8-methoxy-9-{4-[4-(methylsulfonyl)piperazin-l-yl]phenyl}thieno[2,3-c]quinolin-4(5H)-one (32 mg, 0.068 mmol) was reacted with tribromoborane (1.0 mL) to afford the desired product (5.2 mg, 17%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.58 (d, J = 5.4 Hz, 1 H), 7.37 (d, J = 8.9 Hz, 1 H), 7.20 (s, 4H), 7.15 (d, J = 8.9 Hz, 1 H), 6.16 (d, J = 5.4 Hz, 1 H), 3.44-3.43 (m, 8H), 2.92 (s, 3H); ESI MS m/z 456[C₂₂H₂|N30₄S₂ + H]⁺; HPLC >99%, t_R = 10.47 min.

Example 95

9-|4-(Aminomethyl)phenyl]-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one

Following General Procedure F, tert-butyl

4-(8-methoxy-2-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (80 mg, 0.17 mmol) was reacted with tribromoborane (2.0 mL) to afford the desired product (20 mg, 37%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.63 (d, J = 8.9 Hz, 2H), 7.40-7.37 (m, 3H), 7.15 (d, J = 8.1 Hz, 1 H), 5.76 (s, 1 H), 4.28 (s, 2H), 2.33 (s, 3H); ESI MS m/z 337

[C9H16N2O2S + H]⁺; HPLC >99%, t_R = 5.91 min.

Example 84

8-Hydroxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one

Following General Procedure B,

9-bromo-8-(tert-butyldimethylsilyloxy)thieno[2,3-c]quiholin-4(5H)-one (80 mg, 0.20 mmol) was reacted with tert-butyl 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)cyclohex-3-enylcarbamate (90 mg, 0.29 mmol) to afford the desired product (140 mg, 23%) as an off-white solid: Ή NMR (500 MHz, CD3OD) δ 8.01-7.98 (m, 2H), 7.35 (d, J = 8.9 Hz, 1 H), 7.12 (d, J = 8.9 Hz, 1 H), 5.80 (s, 1 H), 4.01-3.91 (m, 2H), 3.63-3.60 (m, 2H), 2.88-2.84 (m, 1 H), 2.57-2.53 (m, 1 H); ESI MS m/z 299 [Ci6H₁₄N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 6.70 min.

Example 77

N-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]methanesulfonamide

Following General Procedure F,

N-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]methanesulfonamide (40 mg, 0.10 mmol) was reacted with tribromoborane (3.0 mL) to afford the desired product (3.8 mg, 10%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.61 (d, J = 5.4 Hz, lH), 7.44-7.43 (m, 2H), 7.39 (d, J = 5.4 Hz, 1H), 7.29-7.27 (m, 2H), 7.16 (d, J = 8.4 Hz, 1 H), 6.12 (d, J = 5.0 Hz, 1 H), 3.09 (s, 3); ESI MS m/z 387 [Ci₈Hi N₂0₄S₂ + H]⁺; HPLC >99%, t_R = 9.69 min.

Example 196

9-{4-[l-(Diethylamino)ethyl)phenyl}-8-hydroxythieno

|2,3-c]quinolin-4(5H)-one Hydrochloride ^•HCI

Following the procedure outlined for Example 460,

9-[4-(l-aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinoiin-4(5H)-one (30 mg, 0.081 mmol) was reacted with formaldehyde (37% in water, 15 mg, 0.26 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (7.2 mg, 21 %) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.73 (q, J = 6.9 Hz, 2H), 7.58 (d, J = 5.4 Hz, 1H), 7.48-7.45 (m, 2H), 7.43 (d, J = 8.9 Hz, 1 H), 7.19 (d, J = 8.9 Hz, 1 H), 6.02 (d, J = 5.4 Hz, 1 H), 4.78 (q, J = 4.7 Hz, 1 H), 3.51-3.34 (m, 3H), 3.19-3.12 (m, 1H), 1.86 (d, J = 6.9 Hz, 3H), 1.43 (t, J = 7.3 Hz, 3H), 1.37 (t, J = 7.3 Hz, 3H); ESI MS m/z 393 [C2₃H₂4N₂0₂S + H]⁺; HPLC >99% (AUC), t_R = 8.29 min.

Example 195

9- [4-( 1- Ami noethy l)phenyl| -8-hyd roxythieno[2,3-c] quinolin-4(5H)-one Hyd rochloride

Following General Procedure F, tert-butyl

1 -[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]ethylcarbamate (320 mg, 0.71 mmol) was reacted with tribromoborane (10 mL) to afford the desired product (160 mg, 59%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.64-7.63 (m, 2H), 7.55 (d, J = 5.4 Hz, 1H), 7.43-7.40 (m, 3H), 7.17 (d, J = 8.9 Hz, 1 H), 6.08 (d, J = 5.4 Hz, 1 H), 4.61 (q, J = 6.9 Hz, 1 H), 1.76 (d, J = 6.9 Hz, 3H); ESI MS m/z 337 [Ci₉H,₆N₂02S + H]⁺; HPLC 98.1% (AUC), t_R = 7.63 min.

Example 194

8-Hydroxy-9-{4-[l-(pyrrolidin-l-yl)ethyllphenyl}thieno

Following General Procedure F,

8-methoxy-9-{4-[l -(pyrrolidin-l -yl)ethyl]phenyl}thieno[2,3-c]quinolin-4(5H)-one (70 mg, 0.17 mmol) was reacted with tribromoborane (2.0 mL) to afford the desired product (43 mg, 58%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.70-7.66 (m, 2H), 7.59 (d, J = 5.4 Hz, 1 H),

7.48-7.44 (m, 2H), 7.42 (d, J = 8.9 Hz, 1H), 7.18 (d, J = 8.9 Hz, 1 H), 6.01 (d, J = 5.4 Hz, 1 H), 4.53 (q, J = 6.8 Hz, 1 H), 3.45 (br s, 1 H), 3.20-3.10 (m, 1 H), 2.20-2.00 (m, 4H), 1.87 (d, J Hz, 3H); ESI MS m/z 391 [C23H22N2O2S + H]⁺; HPLC >99%, t_R = 8.21 min.

Example 272

(R)-9-{4-[l-(Dimethylamino)ethyI]phenyl}-8-hydro

[2,3-c|quinolin-4(5H)-one Hydrochloride

Following the procedure outlined for Example 460,

(R)-9-[4-(l -aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (50 mg, 0.15 mmol) was reacted with formaldehyde (14 mL, 0.45 mmol) and the resulting material was converted to the hydrochloride salt as outlined in General Procedure D-2 to afford the desired product (12 mg, 20%) as an off-white solid: Ή NMR (500 MHz, CD₃OD) δ 7.71 (q, J = 2.6 Hz, 2H), 7.59 (d, J = 5.4 Hz, 1 H), 7.48 (t, J = 7.5 Hz, 2H), 7.43 (d, J = 8.9 Hz, 1H), 7.19 (d, J = 8.9 Hz, 1 H), 6.02 (d, J = 5.4 Hz, 1 H), 4.66 (q, J = 7.1 Hz, 1 H), 2.97 (s, 3H), 2.87 (s, 3H), 1.86 (d, J = 7.0 Hz, 3H); ESI MS m/z 365 [C21H20N2O2S + H]⁺; HPLC 97.1 % (AUC), t_R = 8.57 min.

Example 262

8-Hydroxy-9-{4-[l-(piperidin-l-yl)ethyl]phenyl}thieho

hloride

Following General Procedure F,

8-methoxy-9-{4-[l -(piperidin-l -yl)ethyl]phenyl}thieno[2,3-c]quinolin-4(5H)-one (40 mg, 0.096 mmol) was reacted with tribromoborane (1.0 mL) to afford the desired product (4.9 mg, 13%) as a yellow solid: Ή NMR (500 MHz, CD₃OD) δ 7.73 (d, J = 8.4 Hz, 1 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.58 (d, J = 5.5 Hz, 1H), 7.48-7.42 (m, 3H), 7.19 (d, J = 8.9 Hz, 1H), 6.01 (d, J = 3.4 Hz, 1 H), 4.60 (q, J = 4.5 Hz, 1 H), 3.79 (d, J = 12.0 Hz, 1 H), 3.50 (d, J = 1 1.7 Hz, 1H), 3.02 (t, J = 1 1.3 Hz, 1 H), 2.89 (t, J = 6.0 Hz, 1 H), 2.09-1.72 (m, 8H), 1.55-1.45 (m, 1 H); ESI MS m z 405 [C24H24N2O2S + H]⁺; HPLC 95.0% (AUC), t_R = 7.83 min.

Example 261

2-[2-Fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin- 9-yl)phenyl]acetonitrile

Following General Procedure F,

2-[2-fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]acetonitrile (42 mg, 1.2 mmol) was reacted with tribromoborane (12 mL, 12 mmol) to afford the desired product (22 mg, 55%) as a light brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.65 (m, 2H), 7.42 (d, J = 8.9 Hz, 1 H), 7.19-7.14 (m, 3H), 6.16 (d, J = 5.5 Hz, 1H), 4.07 (s, 2H); ESI MS m/z 351

[C|₉H, ,FN₂0₂S + H]⁺; HPLC 97.1 % (AUC), t_R = 13.67 min.

2-[4-(8-Hydroxy-4-oxo-4,5-dih inolin-9-yl)phenyl]acetonitrile

Following General Procedure B,

9-bromo-8-(tert-butyldimethylsilyloxy)thieno[2,3-c]quinolin-4(5H)-one (50 mg, 0.12 mmol) was reacted with 4-(cyanomethyl)phenylboronic acid (26 mg, 0.18 mmol) to afford the TBS protected intermediate which was treated with aqueous lithium hydroxide to afford the desired product (20 mg, 50%) as an off-white solid: Ή NMR (500 MHz, DMSO-de) δ 9.28 (s, 1H), 7.73 (d, J = 5.4 Hz, 1 H), 7.50 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.9 Hz, 1H), 7.29 (d, J = 8.1 Hz, 2H), 7.18 (m, 1H), 5.90 (d, J = 5.4 Hz, 1 H), 4.19 (s, 2H); ESI MS m/z 333 [C19H12N2O2S + H]⁺; HPLC 96.2% (AUC), t_R = 12.07 min.

9-{4-[l-(Dimethylamin -c]quinolin-4(5H)-one

To a solution of

9-{4-[ l -(dimethylamino)ethyl]phenyl}-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (350 mg, 1.0 mmol) in anhydrous THF (20 mL) at 0 °C was added sodium hydride (60 wt %, 160 mg, 5.0 mmol) and the reaction mixture was heated to 60 °C for 1 h. The reaction mixture was cooled to 0 °C and trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide (450 mg, 1.1 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was quenched with satd. aq. ammonium chloride and the layers were separated. The aqueous layer was extracted with 3: 1 chloroform/isopropanol and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to afford the crude triflate (400 mg) as a brown solid. The crude triflate was dissolved in anhydrous DMF (30 mL) was degassed for 10 min followed by the addition of triethylamine (1.7 mL, 12 mmol), l ,l '-bis(diphenylphosphino)ferrocene dichloropalladium(II) (70 mg, 0.080 mmol), and formic acid (0.3 mL, 8.00 mmol). The reaction mixture was heated at 100 °C for 24 h, cooled, concentrated, and the residue was purified by preparatory HPLC (CI 8 silica, water/acetonitrile w/ 0.05% TFA gradient) to afford the desired product (60 mg, 21% for two steps) as a white solid: Ή NMR (500 MHz, CDCI3) δ 12.00 (s, 1 H), 7.61 (d, J = 8.0 Hz, 1H), 7.51 (t, J = 7.7 Hz, 1 H), 7.45-7.42 (m, 3H), 7.35-7.34 (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 6.30 (d, J = 5.4 Hz, 1H), 3.45 (d, J = 6.3 Hz, 1H), 2.32 (s, 6H), 1.50 (d, J = 6.6 Hz, 3H); ESI MS m/z 349 [C₂iH₂oN₂OS + H]⁺; HPLC 98.5% (AUC), t_R = 10.86 min.

Example 461

9-{4-[(tert-Butoxycarbonylamino)methyl]phenyl}-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl

Trifluoromethanesulfonate

To a solution of tert-butyl

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (150 mg, 0.36 mmol) in THF (3 mL)_.at 0 °C was added sodium hydride (60 wt %, 18 mg, 0.44 mmol) and the reaction mixture was stirred at 0 °C for 1 h. N-Phenyl-bis(trifluoromethanesulfonimide) (160 mg, 0.44 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 18 h. The reaction mixture was quenched with water and the aqueous layer was extracted with methylene chloride. The combined organic layers were dried over anhydrous sodium sulfate, filtered, concentrated and the residue was purified by column chromatography (silica, methanol/methylene chloride gradient) to afford the desired product (200 mg, 98%): ESI MS m/z 555 [C₂₄H₂,F₃N₂0₆S₂ + H]⁺. ,

Example 462

tert-Butyl 4-(8-Cyano-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate

A solution of

9-{4-[(tert-butoxycarbonylamino)methyl]phenyl}-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl trifluoromethanesulfonate (176 mg, 0.320 mmol), zinc chloride (75 mg, 0.640 mmol),

1 ,1 '-bis(diphenylphosphino)ferrocene (1 8 mg, 0.032 mmol), and

tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.016 mmol) in anhydrous DMF (4 mL) was heated at 130 °C for 3 h. The reaction mixture was cooled, quenched with water and the resulting precipitate was filtered and purified by column chromatography (silica,

methanol/methylene chloride gradient) to afford the desired product ( 120 mg, 87%) as a brown solid: ESI MS m/z 432 [C₂₄H₂₁N₃0₃S + H]⁺.

Example 326

9-[4-(Aminomethyl)phenyl]-4-oxo-4,5-dihydrothieno[2,3-c]quinoline- 8-carbonitrile Hydrochloride

Following General Procedure D-3, tert-butyl

4-(8-cyano-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzylcarbamate (10 mg, 0.023 mmol) was reacted with 4 N HCI (3 mL) to afford the desired product (7.4 mg, 74%) as a dark brown solid: Ή NMR (500 MHz, CD₃OD) δ 7.89 (d, J = 8.6 Hz, 1H), 7.74 (t, J = 9.5 Hz, 2H), 7.65 (dd, J = 14.4, 7.0 Hz, 2H), 7.55-7.53 (m, 2H), 6.08 (d, J = 5.4 Hz, 1 H), 4.32 (s, 2H); ESI MS m/z 330 [C₁₉H₁₃N₃OS - ΗΓ; HPLC 98.3% (AUC), t_R = 9.36 min.

Example 627

(¾ -4-benzyl-3-(2-(4-bromo-2-fluorophenyl)acetyl)oxazolidin-2-one

To a solution of (2-(4-bromo-2-fluorophenyl)acetic acid) (3 g, 13 mmol) and triethylamine (2.5 mL, 14 mmol) in toluene (50 mL) at 0 °C was added trimethylacetyl chloride (6.1 mL, 65 mmol) dropwise. After 10 mins the reaction mixture was cooled to -78 °C. In a separate flask, to a solution of (S -(+)-4-benzyl-2-oxazolidinone (2.5 g, 14 mmol) in tetrahydrofuran (50 mL ) at -78 °C was added LiHMDS (1 M in hexane, 17 mL, 17 mmol)) until yellowish color persisted. After 10 mins the resulting solution was transferred through a cannula into the suspension of mixed anhydride prepared as described above. The reaction mixture was allowed to reach rt over the period of 4 h, then diluted with saturated aqueous sodium bisulfate (ca. 20 mL), and extracted with ethyl acetate (ca. 100 mL). The extract was washed with brine (2 x 50 mL), dried over sodium sulfate, and evaporated under vacuum. Flash chromatography of the residue followed by trituration (hexanes) afforded the desired product (2.1 g, 42 %) as white solid. ESI MS miz 393 [CsH.sBrFNOs + H]⁺

Example 628

(R -4-benzyl-3-(2-(4-bromo-2-fluorophenyl)acetyl)oxazolidin-2-one

Following the procedure outlined for Example 627, (2-(4-bromo-2-fluorophenyl)acetic acid) (10.8 g, 30.7 mmol) reacted with CS -(+)-4-benzyl-2-oxazolidinone (5.44 g, 30.7 mmol) to obtain the desired product (4.5 g, 36%) as white solid. ESI MS m/z 393 [QsH^BrFNC + H]⁺

Example 629

(5^-4-benzyl-3-((S -2-(4-bromo-2-fluorophenyl)propanoyl)oxazolidin-2-one

To a solution of f¾ -4-benzyl-3-(2-(4-bromo-2-fluorophenyl)acetyl)oxazolidin-2-one (3.6 g, 9.2 mmol) in THF (40 mL) was added a solution of methyl iodide ( 1 M solution in toluene, 9.6 mL, 9.6 mmol). The mixture was cooled to -78 °C and a solution of sodium bis(trimethylsilyl)amide ( 1 M in THF, 9.6 mL, 9.6 mmol) was added dropwise. The resultant dark red mixture was stirred for 15 min at ca. -78 °C and allowed to warm up to room temperature. After 3.5 h the reaction mixture was diluted with saturated aqueous sodium bisulfate (ca. 20 mL), and extracted with ethyl acetate ( 1 x 50 mL): The extract was washed with brine (2 x 50 mL), dried over sodium sulfate, and evaporated under vacuum. Flash chromatography of the residue afforded the desired product ( 1.7 g, 45%) as light yellow solid: ESI MS m/z 407 [C,₉H|₇BrFN0₃ + H]⁺

Example 630

(¾ -4-benzyl-3-(( ? -2-(4-bromo-2-fluorophenyl)propanoyl)oxazolidin-2-one

Following the procedure outlined for Example 628, (7? 4-benzyl-3-(2-(4-bromo-2-fluorophenyl) acetyl)oxazolidin-2-one (4.6 g, 12 mmol) was reacted with methyl iodide ( 1 M solution in toluene, 12.3 mL, 12.3 mmol) to obtain the desired product (3.0 g, 60%) as light yellow solid: ESI MS m/z 407 [C, 9H, ₇BrFN03 + H]⁺

Example 63 1

(S)-2-(4-bromo-2-fluorophenyl)propan-l -ol

To a solution of ((¾)-4-benzyl-3-((¾)-2-(4-bromo-2-fluorophenyl)propanoyl)oxazolidin-2-one) ( 1 .7 g, 4.2 mmol) in THF ( 12 mL) was added a solution of sodium borohydride (700 mg, 21 mmol) in water (2 mL). The reaction mixture was stirred for 3 h at room temperature. The excess hydride was quenched by slow addition of aqueous hydrochloric acid (1 N, ca. 2.9 mL). The mixture was further diluted with water (10 mL) and extracted with ethyl acetate (1 x 30 mL). The combined organics were washed with brine (2 x 10 mL), dried over sodium sulfate, and evaporated under vacuum. The residue was puified by flash chromatography of the residue afforded the desired product (0.8 g, 82%) as light yellow oil: ESI MS m/z 234 [C₉H₎₀BrFO + H]⁺

Example 632

CR)-2-(4-bromo-2-fluoropheny l)propan- 1 -ol

Following the procedure outlined for Example 630, (7? -4-benzyl-3-((7? -2-(4-brorno-2- fluorophenyl) propanoyl)oxazolidin-2-one (3 g, 7.4 mmol) was reacted with sodium borohydride (1 .2 g, 37 mmol) to obtain the desired product (1.5 g, 87%) as light yellow oil; ESI MS m/z 234 [C₉H|₀BrFO + H]⁺

Example 633

f¾)-2-(2-(4-bromo-2-fluorophenyl)propyl)isoindoline-l ,3-dione

To a solution of (S^-2-(4-bromo-2-f!uorophenyl)propan-l -ol (800 mg, 3.43 mmol), phthalimide (554 mg, 3.77 mmol), and triphenylphosphine (1.34 g, 5.14 mmol) in THF (2 mL) was added DIAD (1 mL, 5.14 mmol) dropwise. The reaction mixture was stirred at room temperature for 18 h and evaporated under vacuum. Flash chromatography of the residue afforded the desired product ( 1 g, 81 %) as a white solid ESI MS m/z 363 [Ci₇Hi₃BrFN0₂ + H]⁺

Example 634

(7? -2-(2-(4-bromo-2-fluoropheny l)propy l)isoindoline- 1 ,3-dione

Following the procedure described for Example 633,

(7?)-2-(4-bromo-2-fluorophenyl)propan-l -ol (1 .5 mg, 6.4 mmol) was reacted wtih phthalimide (1 .0 mg, 7.008 mmol) to obtain the desired product (1.6 g, 69%) as a white solid: ESI MS m/z 363 [Ci₇H_{) 3}BrFN0₂ + H]⁺

Example 635

(S)-tert-buty\ 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)propylcarbamate

To a solution of ((¾)-2-(2-(4-bromo-2-fluorophenyl)propyl)isoindoline-l ,3-dione) (1.0 g, 2.8 mmol) in toluene (10 mL) was added hydrazine (1.3 mL, 41.5 mmol) dropwise. The reaction mixture was heated at 80-90 °C for 1 h and cooled to room temperature. The supernatant was decanted, and the residual solid was washed with toluene. The combined solution was evaporated under vacuum ,dissolved in DCM (10 mL) and cooled to 0 °C. Next, Boc₂0 (870 mg, 4 mmol) and Et₃N (0.5 mL, 4 mmol) were added and the reaction mixture stirred for 30 min at room temperature. The reaction mixture diluted with DCM (20 mL) and washed with IN HC1 (1 xl O mL), water (1 x 20 mL) followed by brine (1 x 10 mL), dried over sodium sulfate, and evaporated under vacuum to afford the desire product (860 mg, 99%) which was taken to next step without furthure purification. ESI MS m/z 333 [C|₄Hi₉BrFN0₂ + H]⁺

The next step carried out following the procedure G (Scheme II): (S)-tert-bu\y\

2-(4-bromo-2-fluorophenyl)propylcarbamate (860 mg, 2.66) was reacted with KOAc (833 mg, 8.5 mmol), Pd(dppf)Cl₂ (200 mg, 0.26 mmol) and bis(pinacolato)diboron (863 mg, 3.4 mmol) to afford (S)-tert-bu y\ 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl) propylcarbamate as a colourless paste (900 mg, 89%): ESI MS m/z 380 [C₂₀H₃iBFNO₄ + H]⁺

Example 636

(R)-tert-bu y\ 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)propylcarbamate

Followed the prodecure outlined for Example 635 fR -2_'(2-(4-bromo-2-fluorophenyl)propyl) isoindoline- l ,3-dione) (1.6 g, 4.42 mmol) was reacted with hydrazine (2.1 g, 66 mmol), Boc₂0 (2.0 g, 8.8 mmol) followed by bis(pinacolato)diboron (1.0 g, 4.0 mmol) to obtain the desired product (1.1 g, 80%) as a colourless paste: ESI MS m/z 380 [C₂oH₃₁BFN0₄ + H]⁺

Example 637

(R)-tert-but \ 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)

propyl(methyl)carbamate ¹

Following the prodecure described for Example 647, (R)-tert-buty\

2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2- dioxaborolan-2-yl)phenyl)propylcarbamate (400 mg, 1 mmol) was reacted with methyl iodide (1 M solution in toluene, 2 mL, 2 mmol) and NaHMDS (1 M solution, 2 mL, 2 mmol) to afford the desired product (330 mg, 82%) as viscous mass. ESI MS m/z 394 [C₂iH₃₈BFN0₄ + H]⁺

Example 638

terf-butyl 3-methyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)butylcarbamate

Following the prodecure described for Example 647, 2-(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)acetonitrile (5.6 g, 23 mmol) was reacted with iso proypl iodide (4 g, 24 mmol) NaHMDS (1 M solution, 24 mL, 24 mmol) to afford the desired product (2.1 g, 23%) as viscous mass. ESI MS m/z 390 [C22H36BNO4 + H]⁺.

Example 639

/er/-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)-3- methylbutylcarbamate

Following the prodecure described for Example 647,

2-(2-fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan -2-yl)phenyl)acetonitrile (1.7 g, 6.5 mmol) was reacted with iso proypl iodide (1.1 g, 6.8 mmol) NaHMDS (1 M solution, 7.1 mL, 7.1 mmol) to afford the desired product (0.65 g, 24%) as viscous mass. ESI MS m/z 408

[C22H36FBNO4 + H]⁺

Example 640

feri-butyl 2-cyclopentyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl) phenyl)ethylcarbamate

Following the prodecure described for Example 647, 2-(4-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl)acetonitrile (1.7 g, 7.16 mmol) was reacted with cyclopentyl iodide (1 M solution in toluene, 7.16 mL, 7.16 mmol) and NaHMDS (1 M solution, 7.16 mL, 7.16 mmol) to afford the desired product (1.6 g, 53%) as viscous mass. ESI MS m/z 415 [C24H38BNO4 + H]⁺.

Example 641

½r/-butyl methyl(3-methyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan

-2-yl)phenyl)butyl)carbamate

Example 642

Following the prodecure described for Example 647,

ieri-butyl 3-methyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)butylcarbamate (400 mg, 1 mmol) was reacted with methyl iodide (1 M solution in toluene, 2 mL, 2 mmol) and NaHMDS ( 1 M solution, 2 mL, 2 mmol) to afford the desired product (350 mg, 84%) as viscous mass. ESI MS m/z 403 [C₂₃H₃8BN0₄ + H]⁺.

Example 643

-butyl 2-(2-fluoro-4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)-3-methylbutyl

(methy l)carbamate

Following the prodecure described for Example 647, fer/-butyl

2-(2-fluoro-4-(4,4,5,5-tetramethyl- 1 ,3,2- dioxaborolan-2-yl)phenyl)-3-methylbutylcarbamate (650 mg, 1.6 mmol) was reacted with methyl iodide (1M solution in toluene, 3.2 mL, 3.2 mmol) and NaHMDS (1 M solution, 4.8 mL, 4.8 mmol) to afford the desired product (650 mg, 94%) as viscous mass.. ESI MS m/z 421 [C23H₃₈FBN0 + H]⁺

Example 644

teri-butyl 3-(4-bromophenyl)piperidine-l-carboxylate

To a solution of 3-(4-bromophenyl)pyridine (0.4 g, 1.68 mmol) and HCl (1 .0 N solution in water, 1 .7 mL, 1 .7 mmol) in MeOH (20 mL) was added Pt0₂ (0.5 g) and stirred for 24 h at room temperature under H₂ atmosphere (50 psi) in a Parr hydrogenation apparatus. The mixture was filtered through Celite, and the filtrate was evaporated under reduced pressure. The resulting white solid was dissolved in EtOAc (50 mL) and washed with 1 N NaOH ( 10 mL). The aqueous phase was extracted with EtOAc (3 x 50 mL), and the combined organic phase was dried

(Na₂S04). Evaporation of the solvent gave a white solid which was redissolved in DCM and added Boc₂0 followed by Et₃N at 0 °C. After stirring the reaction mixture for 1 h at room remperature diluted with DCM and washed sequentially with 1 N HCl, water and brine, dried over sodium sulfate, and evaporated under vacuum. Flash chromatography of the residue afforded the desired product as viscous mass (350 mg, 61 %) ESI MS m/z 341 [Ci6H₂2BrN0₂ + H]⁺.

Example 645

feri-butyl 3-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phen l)piperidine-l -carboxylate

General Procedure G, ier/-butyl 3-(4-bromophenyl)piperidine- l -carboxylate (350 mg, 1 ) was reacted with bis(pinacolato)diboron (275, 1.2 mmol) to to afford the desired product (190 mg, 48%) as a viscous mass: ESI MS m/z 388 [C22H34BNO4 + H]⁺.

Example 646

3-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)propanenitrile

General Procedure G, teri-butyl 3-(4-bromophenyl)piperidine- l -carboxylate (350 mg, 1 ) was reacted with bis(pinacolato)diboron (275, 1 .2 mmol) to to afford the desired product (190 mg, 48%) as a viscous mass: ESI MS m/z 388 [C22H34BNO4 + H]⁺.

Example 647

N-methyl(R)-tert-buty 1 methy 1( 1 -(4-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-y l)pheny 1) ethyl)carbamate

To a solution of (R)-tert-butyl l -(4-(4,4,5,5-tetramethyl- l ,^'3,2-dioxaborolan-2-yl)

phenyl)ethylcarbamate (1 .0 g, 2.88 mmol) in anhydrous THF (20 mL) was cooled to 0 °C and sodium hydride (60 wt %, 330 mg, 8.64 mmol) added portion wise. The mixture was stirred for 10 min and then heated at 60 °C for 1 h. The flask was then cooled down to room temperature and methyl iodide (277 mL, 4.32 mmol) was added. The mixture was heated again at 60 °C for 12 h. LCMS showed completion of reaction. The reaction mixture was quenched with water and diluted with ethyl acetate (200 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (520 mg, 43%) as a white solid: ESI MS m/z 306 [C20H32BNO4 - 56]⁺.

Example 648

(R)-tert-butyl methyl(2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)

propy l)carbamate

A solutionof (R)-tert-butyl 2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)

phenyl)propylcarbamate (9.0 g, 24.93 mmol) in anhydrous THF (120 mL) was cooled to 0 °C and NaHMDS (30 mL, 29.9 mmol) was added. The mixture was stirred for 1 h, methyl iodide (1.9 mL, 29.9) in THF (40 mL) added and stirred for 14 h.. The reaction mixture was quenched with water (20 mL) and diluted with ethyl acetate (250 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (6.2 g, 66%) as light yellow oil: ESI MS m/z 376 [C21H34BNO4 +H]⁺.

Example 649

2-(4-bromophenyl)propanenitrile

To a solution of 2-(4-bromophenyl)acetonitrile (5.0 g, 25.5 mmol) in anhydrous THF (70 mL) was cooled to 0 °C and sodium hydride (60 wt %, 1.5 g, 38.3 mmol) added portion wise. The mixture was stirred at room temperature for 1 h. After which methyl iodide (1.8 mL, 28.1 mmol) was added and the mixture stirred for 14 h. The reaction mixture was carefully quenched with water at 0 °C and diluted with ethyl acetate (200 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (3.8 g, 72%) as a yellow oil: ESI MS m/z 210 [C H₈BrN +H]⁺.

Example 650

2-(2-chlorophenyl)propanenitrile

Following the prodedure outlined for Example 649, 2-(2-chlorophenyl)acetonitrile (15 g, 98.9 mmol) was reacted with NaHMDS (1 18 mL, 1 18 mmol), and methyl iodie (7.0 mL, 108 mmol) to afford the desired product (14 g, 87%) as a brown oil: ESI MS m/z 166 [QjHgClN + H]⁺.

Example 651

2-(2-chlorophenyl)propan- 1 -amine

To a solution of 2-(2-chlorophenyl) propanenitrile (14 g, 84.8 mmol) in tolune at 0 °C was added BFL/THF (127, 255 mmol) and the reaction was warmed to room temperature and heated at reflux for 4 h. The reaction mixture was cooled; queched with water, concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (13.9 g, 97%) as a reddish oil: ESI MS m/z 170 [C9H12CIN + H]⁺.

Example 652

N-(2-(4-bromo-2-chlorophenyl)propyl)-2,2,2-trifluoroacetamide

A solution of trifluoro acetic anhydride (12.8 mL, 90.1 mmol) in anhydrous methylene chloride (82 mL) was cooled to 0 °C and 2-(2-chlorophenyl)propan-l -amine (14 g, 82.8 mmol) in anhydrous methylene chloride (30 mL) was added dropwise. The mixture was stirred at room temperature for 1 .5 h. The flask was again cooled to 0 °C and methane sulfonic acid (13 mL) followed by l ,3-Dibromo-5,5-Dimethylhydantoin (1 1.8 g, 41.4 mmol) was added in one portion.. The mixture was stirred for 14 h and quenched with water (30 mL) and diluted with methylene chloride ( 150 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (14 g, 50%) as a yellowish oil: ESI MS m/z 344 [C, , H|₀BrClF₃NO + H]⁺.

Example 653

tert-butyl 2-(2-chloro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl) propylcarbamate

A mixture of N-(2-(4-bromo-2-chlorophenyl)propyl)-2,2,2-trifluoroacetamide (14 g, 40.6 mmol), methanol (200 mL) and sodium hydroxide (2M, 200 mL, 81.2 mmol) was stirred at room temperature for 14 h. LCMS showed completion of the reaction. The solvent was removed, extraction with methylene chloride (200 mL) and concentrated to give an oil. The residue was dissolved in methylene chloride (100 mL) and cooled to 0 °C. Triethylamine (8.3 mL, 61.0 mmol) and di-tert-butyl dicarbonate (13.3 g, 61.0 mmol) and the reaction mixture stirred at room temperature for 18 h. The reaction mixture concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (13.8 g, 90%) as white solid: ESI MS m/z 293 [Ci₄H₁₉BrClN02 - 56]⁺.

Example 654

tert-butyl 2-(2-chloro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)propylcarbamate

Following General Procedure G, tert-butyl 2-(4-bromo-2-chlorophenyl)propylcarbamate ( 12.0 34.5 mmol) was reacted with bis(pinacolata)diboron (13.2 g, 51.7 mmol) to afford the desired product (8.0 g, 58%) as a amorphous reddish oil: ESI MS m/z 396 [C₂₀H₃iBClNO + H]⁺.

Example 655

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)propanenitrile

Following General Procedure G, 2-(4-bromophenyl)propanenitrile (3.5 g, 18.2 mmol) was reacted with bis(pinacolata)diboron (4.6 g, 27.1 mmol) to afford the desired product (2.5 g, 53%) as a brown solid: ESI MS m/z 258 [Ci₅H₂oBN0₂ + H]⁺.

Example 656

2-ethyl-2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)butanenitrile

To a solution of 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)acetonitrile (2.0 g, 8.23 mmol) in DMF (40 mL) was cooled to 0 °C and sodium hydride (60 wt %, 1.2 g, 32.9 mmol) added portion wise. The mixture was stirred for 10 min and ethyl iodide (0.74 mL, 9.05 mmol) iri THF (10 mL) was added. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with water and diluted with ethyl acetate. The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (950 mg, 38%) as a brown solid: ESI MS m/z 300 [Ci8H₂6BN0₂ +H]⁺.

Example 657

2-(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)propanenitrile

Following General Procedure G, 2-(4-bromophenyl)propanenitrile (5.0 g, 22.3 mmol) was reacted with bis(pinacolata)diboron (8.7 g, 33.5 mmol) to afford the desired product (5.8 g, 95%) as a white solid: ESI MS m/z 272 [C|₆H₂₂BN0₂ + H]⁺.

Example 658

(R)-N-(2-(4-bromophenyl)propyl)-2,2,2-trifluoroacetamide

A solution of trifluoro acetic anhydride (1 1.4 mL, 81.4 mmol) in anhydrous methylene chloride (73 mL) was cooled to 0 °C and (R)-2-phenylpropan- l -amine (10 g, 73.9 mmol) in

anhydrous methylene chloride (20 mL) was added dropwise. The mixture was stirred at room temperature for 1.5 h. The flask was again cooled to 0 °C and methane sulfonic acid (12 mL) followed by l ,3-Dibromo-5,5-Dimethylhydantoin (1 1 g, 36.9 mmol) was added in one portion.. The mixture was stirred for 14 h and quenched with water (30 mL) and diluted with methylene chloride (100 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (21 g, 91%) as a yellow solid: ESI MS m/z 310 [CHnBrFsNO + Hf.

Example 659

(R)-tert-butyl 2-(4-bromophenyl)propylcarbamate

A mixture of (R)-N-(2-(4-bromophenyl)propyl)-2,2,2-trifluoroacetamide (21 g, 68.3 mmol), methanol (40 mL) and sodium hydroxide (2M, 68 mL, 136 mmol) was stirred at room temperature for 14 h. LCMS showed completion of the reaction. The solvent was removed, extraction with methylene chloride (250 mL) and concentrated to give an oil. The residue was dissolved in methylene chloride (100 mL) and cooled to 0 °C. Triethylamine (14 mL, 102 mmol) and di-tert-butyl dicarbonate (22 g, 102 mmol) and the reaction mixture stirred at room temperature for 18 h. The reaction mixture concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (19 g, 91%) as yellow oil: ESI MS m/z 257 [C,₄H₂oBrN02 - 56]⁺.

Example 660

(R)-tert- butyl 2-(4-(4,4,5,5-tetramethy 1- 1 ,3,2-dioxaborolan-2-yl)pheny l)propylcarbamate

Following General Procedure G, (R)-tert-butyl 2^(4-bromophe^'nyl)propylcarbamate (19 g, 60.5 mmol) was reacted with bis(pinacolata)diboron (24 g, 94.4 mmol) to afford the desired product (22 g, 99%) as a light yellow solid: ESI MS m/z 362 [C20H32BNO4 + H]⁺.

Example 661

(R)-N-(l-(4-bromophenyl)propyl)-2,2,2-trifluoroacetamide

A solution of trifluoro acetic anhydride (5.7 mL, 40.7 mmol) in anhydrous methylene chloride (40 mL) was cooled to 0 °C and (R)- l-phenylpropan-l -amine (5 g, 36.9 mmol) in

anhydrous methylene chloride (10 mL) was added dropwise. The mixture was stirred at room temperature for 1.5 h. The flask was again cooled to 0 °C and methane sulfonic acid (6.3 mL) followed by l ,3-dibromo-5,5-dimethylhydantoin (5.3 g, 18.5 mmol) was added in one portion.. The mixture was stirred for 14 h and quenched with water (30 mL) and diluted with methylqne chloride (50 mL). The layers were seperated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (8.1 g, 73%) as a white solid: ESI MS m/z 310 [CuH| ,BrF₃NO + H]⁺.

Example 662

(R)-tert-buty 1 1 -(4-bromopheny l)propylcarbamate

A mixture of (R)-N-(l -(4-bromophenyl)propyl)-2,2,2-trifluoroacetamide (8.1 g, 68.3 mmol), methanol (20 mL) and sodium hydroxide (2M, 15 mL, 30.6 mmol) was stirred at room temperature for 14 h. LCMS showed completion of the reaction. The solvent was removed, extraction with methylene chloride (150 mL) and concentrated to give an oil. The residue was dissolved in methylene chloride (100 mL) and cooled to 0 °C. Triethylamine (2.2 mL, 15.3 mmol) and di-tert-butyl dicarbonate (3.3 g, 15.3 mmol) and the reaction mixture stirred at room temperature for 18 h. The reaction mixture concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (5.8 g, 70%) as off-white solid: ESI MS m/z 257 [Ci4H₂oBrN0₂ - 56]⁺.

Example 663

(R)-tert-butyl l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)propylcarbamate

Following General Procedure G, (R)-tert-butyl l -(4-bromophenyl)propylcarbamate (5.8 g, 18.4 mmol) was reacted with bis(pinaco!ata)diboron (7.03 g, 27.7 mmol) to afford the desired product (6.18 g, 92%) as yellow oil: ESI MS m/z 362 [C₂₀H₃₂BNO + H]⁺.

Example 664

tert-butyl 1 -(4-bromopheny l)propan-2-ylcarbamate

To a solution of l -(4-bromophenyl)propan-2-one (5.0 g, 23.4 mmol) in ethanol (1 15 mL) was added ammonia in methanol (9 N, 20.2 mL, 140 mmol) followed by Titanium isoproxide (13.3 mL, 46.9 mmol). The mixture was heated at 50 °C overnight. The flask was cooled to 0 °C and NaBH) (142 mg, 3.76 mmol) was added in portions. After stirring for 1 h, NH4OH (2 N, 4.0 mL) was added and the mixture stirred for 1 h. The white solid was filtered off and the filtrate extrated with methylene chloride. Solvent was removed and oil obtained was dissolved in methylene chloride (100 mL) and cooled to 0 °C. Triethylamine (4.8 mL, 35.2 mmol) and di-tert-butyl dicarbonate (10.2 g, 46.9 mmol) and the reaction mixture stirred at room

temperature for 18 h. The reaction mixture concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (4.2 g, 57%) as white solid: ESI MS m/z 257 [Ci4H₂oBrN0₂ - 56]⁺.

Example 665

tert-buty 1 1 -(4-(4,4,5,5-tetramethy I- 1 ,3,2-dioxaborolan-2-yl)pheny l)propan-2-y lcarbamate

Following General Procedure G, tert-butyl l -(4-bromophenyl)propan-2-ylcarbamate (8.8 g, 28.03 mmol) was reacted with bis(pinacolata)diboron (10.7 g, 42.0 mmol) to afford the desired product (10.5 g, 99%) as a brown oil: ESI MS m/z 362 [C₂oH₃₂BN0₄ + H]⁺.

Example 666

tert-butyl 2-ethyl-2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)butylcarbamate

To a solution of cyano compound (500 mg, 1 .67 mmol) in tolune (10 mL) at 0 °C was added BH3^»THF ( 1.0 M in THF 16 mL, 10 mmol) and the reaction was warmed to room temperature and heated at reflux for 4 h. The reaction mixture was cooled; queched with water, concentrated. The residue was dissolved in methylene chloride (30 mL) and cooled to 0 °C. Triethylamine (0.36 mL, 2.51 mmol) and di-tert-butyl dicarbonate (547 mg, 2.51 mmol) and the reaction mixture stirred at room temperature for 18 h. The reaction mixture concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (480 mg, 71 %) as a brown solid: ESI MS m/z 404 [Q3H38BNO4 +H]⁺. Example 667

tert-buty 1 2-methy l-2-(4-(4,4,5,5-tetramethy 1- 1 ,3,2-dioxaborolan-2-yl) phenyl)propy lcarbamate

Following the procedure outlined for Example 666,

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)propanenitrile (5.8 g, 2L4 mmol) was reacted with BH₃ ^«THF (1.0 M in THF_, 64 mL, 64 mmol) and di-tert-butyl dicarbonate (7.0 g, 32.1 mmol) to give the desired product (6.9 g, 86%) as a white solid: ESI MS m/z 310

[C21H34BNO4 - 56]⁺.

Example 668

l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)cyclobutanecarbonitrile

To a solution of 2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl) acetonitrile (7.0 g, 29 mmol) in THF at 0 °C was added NaHMDS (1 .0 M, 120 mL , 120mmol). After stirring for 20 min 1 ,3-diiodopropane (26 g, 86 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was cooled to 0 °C, quenched with MeOH (5.0 mL) and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to afford the desired product (4.0 g, 47%) as a yellow oil: ESI MS m/z 286 [Ci₇H₂₂BN0₂ + H]⁺.

Example 669

(l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)methanamine

Following the procedure outlined for Example 666,

l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl) cyclobutane carbonitrile (4.0 g, 14 mmol) was reacted with Bfy'THF (1.0 M in THF, 60 mL, 60 mmol) to afford the desired product (3.7 g, 91 %) as a yellow oil: ESI MS m/z 288 [Ci₇H₂₆BN0₂ + H]⁺.

Example 670

tert-butyl (l -(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)

eye lobuty l)methy lcarbamate .

Following the procedure outlined for Example 463,

(l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl) methanamine (3.7 g, 13 - mmol) ) was reacted with di-tert-butyl dicarbonate (3.4 g,16 mmol) to afford the desired product (3.5 g, 71 %) as a yellow oil: ESI MS m/z 388 [C22H34BNO4 + H]⁺.

Example 671

4-bromo-2-chloro- 1 -(2-nitroviny l)benzene

To a solution of 4-bromo-2-chlorobenzaldehyde (7.5 g, 34 mmol) in nitromethane was added methylamine hydrochloride (1 .3 g, 22 mmol), NaOAc (1.8 g, 22 mmol). The mixture was vigorously stirred for 18 h at room temperature. The reaction mixture was diluted with water (60 mL) and extracted with CH2CI2 (3x100 mL), organic phases dried (Na₂S0₄), evaporated to afford the desired product (8.5 g, 95%) as a light yellow oil: ESI MS m/z 262 [C₈H₅BrClN0₂ + H]⁺.

Example 672

2-(4-bromo-2-chlorophenyl)ethanamine

To a stirred suspension of L1BH4 (2.0 M, 73 mL, 145 mmol) in THF (60 mL) at room temperature was added chlorotrimethylsilane (32 g, 290 mmol), dropwise over 10 min. After stirring at room temperature for 20 min, nitrogen gas was bubbled through the mixture for 5 min to remove the remaining trimethylsilane that had formed. A solution of

4-bromo-2-chloro-l -(2-nitroviny l)benzene (9.5 g, 36.2 mmol) in THF (60 mL) was added dropwise over 10 min with stirring at room temperature. The resulting mixture was heated at reflux for 1 h. The reaction mixture was cooled in an ice bath and carefully quenched with MeOH ( 100 mL). The solvent was evaporated and the residue was partitioned between 20 % OH (120 mL) and CH₂CI₂ (60 mL). The organic layer was dried, concentrated, purified by column chromatography (silica, ethyl acetate/hexanes gradient) to obtain the desired product (8.5 g, 95%) as a light yellow oil: ESI MS m/z 234 [C₈H₉BrClN + H]⁺.

Example 673

tert-butyl 4-bromo-2-chlorophenethylcarbamate BocHN

Following the procedure outlined for Example 463, 2-(4-bromo-2-chlorophenyl)ethanamine(7.5 g, 32 mmol) was reacted with di-tert-butyl dicarbonate (8.3 g, 38 mmol) to afford the desired product (9.7 g, 90%) as a white solid: ESI MS m/z 334 [Ci₃H₁₇BrCLN0₂ + H]⁺.

Example 674

tert-butyl 2-chloro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenethylcarbamate

BocHN

Following General Procedure G, tert-butyl 4-bromo-2-chlorophenethylcarbamate

(9.6 g, 30 mmol) was reacted with bis(pinacolato)diboron (1 lg, 45 mmol) to afford the desired product (8.2 g, 73%) as a colorless oil: ESI MS m/z 382 [C19H29BCLNO2 + H]⁺.

Example 675

2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)butanenitrile

Following the procedure outlined for Example 649,

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)acetonitrile (5.2 g, 21 mmol) ) was reacted with ethyl bromide (2.6 g, 24 mmol) to afford the desired product (3.4 g, 59%) as colorless oil: ESI MS m/z 272 [C6H22BNO2 + H]⁺..

Example 676

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)butan-l-amine

Following the procedure outlined for Example 666,

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)butanenitrile(3.4 g, 12.5 mmol) was reacted with BH₃*THF (1.0 M in THF, 64 mL, 64 mmol) to afford the desired product (3.2 g, 93%) as light yellow oil: ESI MS m/z 276 [CeP eBNCb + H]⁺.

Example 677 (l -(4-bromophenyl)cyclopropyl)methanamine

Following the procedure outlined for Example 666, l-(4-bromophenyl)cyclopropane carbonitrile (2.0 g, 9.0 mmol) was reacted with BH₃ ^«THF (1.0 M in THF, 50 mL, 50 mmol) to afford the desired product (1.9 g, 94%) as a yellow oil: ESI MS m/z 226 [Ci₀Hi₂BrN+ H]⁺.

Example 678

tert-butyl 2-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)

phenyl)butylcarbamate

Following the procedure outlined for Example 463,

2-(4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl)butan-l -amine (2.9 g, 10.5 mmol) was reacted with di-tert-butyl dicarbonate (2.8 g, 12.6 mmol) to afford the desired product (2.4 g, 62%) as a light yellow oil: ESI MS m/z 376 [C₂iH₃₄BN0₄ + H]⁺.

Example 679

tert-butyl ( 1 -(4-bromopheny l)cyclopropyl)methy lcarbamate

Following the procedure outlined for Example 463,

(l -(4-bromophenyl)cyclopropyl)methanamine (2.2 g, 9.5 mmol) was reacted with di-tert-butyl dicarbonate (2.5 g, 12 mmol) to afford the desired product (1.5 g, 52%) as a yellow oil: ESI MS m/z 326 [Ci5H₂₀BrNO₂ + H]⁺.

Example 680

tert-butyl (l -(4-(4,4,5,5-tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl)cyclopropyl)

methy lcarbamate

Following General Procedure G, tert-butyl (l-(4-bromophenyl)cyclopropyl) methyl carbamate (1.3 g, 4.0 mmol) was reacted with bis(pinacolato)diboron (1.55 g, 6.1 mmol) to afford the desired product (1.8 g, 60%) as a colorless oil: ESI MS m/z 374 [C21H32BNO4 + H]⁺.

Example 463

tert-Butyl 4-Bromophenethylcarbamate

To a solution of 2-(4-bromophenyl)ethanamine (3.0 g, 15 mmol) in methylene chloride (75 mL) at 0 °C was added triethylamine (2.5 mL, 18 mmol) and di-tert-butyl dicarbonate (3.9 g, 18 mmol) and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated and the residue was triturated with acetonitrile and filtered to afford the desired product (3.5 g, 75%) as a yellow solid: ESI MS m/z 301 [Ci₃H₁₈BrN0₂ + H]⁺.

Example 464

tert-Butyl 4-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)phenethylcarbamate

Following General Procedure G, tert-butyl 4-bromophenethylcarbamate (1.3 g, 4.3 mmol) was reacted with bis(pinacolato)diboron (1.3 g, 5.1 mmol) to afford the desired product (1.1 g, 70%) as a light brown solid: ESI MS m/z 348 [Ci9H₃₀BNO₄ + H]⁺.

Example 465

Following General Procedure B, 9-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one (780 mg, 2.5 mmol) was reacted with tert-butyl

4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenethylcarbamate (1.5g, 4.3 mmol) to afford the desired product (1.0 g, 90%) as a brown solid: ESI MS m/z 451 [C25H26N2O4S + H]⁺.

Example 466

2-[4-(3-Bromopropoxy)phenyl]-4,4,5,5-tetramethyl- l ,3,2-dioxaborolane

To a solution of 4-(3-bromopropoxy)phenylboronic acid (1.0 g, 3.9 mmol) in diethyl ether (40 mL) was added pinacol (1.4 g, 12 mmol) and the reaction mixture was stirred for 18 h and concentrated to afford the desired product (1.5 g, crude) as a light brown oil which carried onto the next step without further purification: ESI MS m/z 247 [Ci₅H₂₂BBr0₃ - 94]⁺.

N¹,N¹-Diethyl-N²-{3-[4-(4,4,5,5-tetr rolan-2-yl)phenoxy]propyl}ethane-l ,

A solution of 2-[4-(3-bromopropoxy)phenyl]-4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolane (500 mL, 2.02 mmol), N'jN'-diethylethane-l , 2-diamine (0.87 mL, 6.1 mmol), and potassium carbonate (550 mg, 4.0 mmol) in acetonitrile (15 mL) was heated to 50 °C for 3 h. The reaction mixture was cooled, filtered and the filtrate was concentrated to afford the desired product (400 mg, 53%) as a yellow oil: ESI MS m/z 377 [C₂iH₃₇BN₂0₃ + H]⁺.

Example 468

tert-Butyl l -(4-Bromophenyl)ethylcarbamate

Following the procedure outlined for Example 463, l-(4-bromophenyl)ethanamine (3.0 g, 15 mmol) was reacted with di-tert-butyl dicarbonate (3.9 g, 18 mmol) to afford the desired product (4.2 g, 93%) as a white solid: ESI MS m/z 301 [Ci₃Hi₈BrN0₂ + H]⁺.

Example 469

tert-Butyl l -[4-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

Following General Procedure G, tert-butyl l -(4-bromophenyl)ethylcarbamate (2.2 g, 7.3 mmol) was reacted with bis(pinacolata)diboron (3.9 g, 1 1 mmol) to afford the desired product (1.3 g, 53%) as an off-white solid: ESI MS m/z 247 [C₁₉H₃oBN04 + H]⁺.

Example 470

(S)-tert-Butyl 1 -(4-Bromopheny l)ethylcarbamate

Following the procedure outlined for Example 463, (S)-l -(4-bromophenyl)ethanamine (500 mg, 2.5 mmol) was reacted with di-tert-butyl dicarbonate (650 mg, 3.0 mmol) to afford the desired product (640 mg, 82%) as a white solid: ESI MS m/z 247 [CnHigBrNC^ + H]⁺.

Example 471

(S)-tert-Butyl l -[4-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

Following General Procedure G, (S)-tert-butyl l -(4-bromophenyl)ethylcarbamate (630 mg, 2.1 mmol) was reacted with bis(pinacolato)diboron ( 1.1 g, 3.1 mmol) to afford the desired product (320 mg, 44%) as a brown solid: ESI MS m/z 347 [C19H30BNO4 - Bocf.

Example 472

2-[2-Fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]acetonitrile

Following General Procedure G, 2-(4-bromo-2-fluorophenyl)acetonitrile (4.0 g, 19 mmol) was reacted with bis(pinacolato)diboron (7.1 g, 28 mmol) to afford the desired product (2.5 g, 57%) as a brown solid: ESI MS m/z 232 [C|₄H₁₇BFN0₂ + H]⁺.

Example 473 (R)-tert-Buty 1 1 -(4-Bromopheny l)ethy lcarbamate

Following the procedure outlined for Example 463, (R)-l-(4-bromophenyl)ethanamine (1.0 g, 5.0 mmol) was reacted with di-tert-butyl dicarbonate (1.3 g, 5.9 mmol) to afford the desired product (1.2 g, 86%) as an off-white solid: ESI MS m/z 301 [Ci₃H₁₈BrN0₂ + H]⁺.

Example 474

(R)-tert-Butyl l -[4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

Following General Procedure G, (R)-tert-butyl l -(4-bromophenyl)ethylcarbamate (1.2 g, 4.0 mmol) was reacted with bis(pinacolato)diboron (1.5 g, 6.0 mmol) to afford the desired product (1.0 g, 77%) as a colorless oil: ESI MS m/z 292 [Ci₉H₃₀BNO₄ - 55]⁺.

Example 475

2-Methyl-2-[4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]propanenitrile

Following General Procedure G, 2-(4-bromophenyl)-2-methylpropanenitrile (1.0 g, 4.5 mmol) was reacted with bis(pinacolato)diboron (1.7 g, 6.7 mmol) to afford the desired product (980 mg, 81 %) as an off-white solid: ESI MS m/z 272 [Ci₆H₂2BN0₂ + H]⁺.

Example 476

l -[2-Fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzyl]pyrrolidin-3-ol

H

A solution of 2-[4-(bromomethyl)-3-fluorophenyl]-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane (300 mg, 0.95 mmol), pyrrolidin-3-ol (99 mg, 1.1 mmol), and potassium carbonate (160 mg, 1.1 mmol) in acetonitrile (5 mL) was heated to 50 °C for 3 h. The reaction mixture was cooled, filtered and the filtrate was concentrated to afford the desired product (280 mg, 92%) as a red oil: ESI MS m/z 322 [C17H25BFNO3 + H]⁺.

Example 477

tert-Butyl 5-Bromo-2,3-dihydro-l H-inden-2-ylcarbamate

BocH

Following the procedure outlined for Example 463, 5-bromo-2,3-dihydro- l H-inden-2-amine (2.5 g, 8.5 mmol) was reacted with di-tert-butyl dicarbonate (2.8 g, 13 mmol) to afford the desired product (2.5 g, 96 %) as a white solid: ESI MS m/z 313 [C|₄H,₈BrN02 + H]⁺.

Example 478

tert-Butyl 5-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)-2,3-dihydro- 1 H-inden-2-ylcarbamate

BocHN

Following General Procedure G, tert-butyl 5-bromo-2,3-dihydro-l H-inden-2-ylcarbamate (2.5 g, 8.0 mmol) was reacted with bis(pinacolato)diboron (3.0 g, 12 mmol) to afford the desired product (2.1 g, 72%) as a colorless oil: ESI MS m z 360 [C20H30BNO4 + H]⁺.

Example 479

tert-Butyl

7-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(l H)-carboxylate

Following General Procedure G, tert-butyl 7-bromo-3,4-dihydroisoquinoline-2(l H)-carboxylate (1.3 g, 4.4 mmol) was reacted with bis(pinacolato)diboron (1.7 g, 6.6 mmol) to afford the desired product (1.1 g, 72%) as a colorless oil: ESI MS m/z 360 [C₂₀H₃₀BNO4 + H]⁺.

Example 480

l -(4-Bromo-2-fluorophenyl)ethanamine

To a solution of 1 -(4-bromo-2-fluorophenyl)ethanone (2.0 g, 9.2 mmol) in methanol (50 mL) was added ammonia (7 N in methanol, 8.0 mL, 55 mmol) and titanium(IV) isopropoxide (5.4 mL, 1 8 mmol). The reaction mixture was stirred at room temperature for 18 h, cooled to 0 °C and sodium borohydride (520 mg, 14 mmol) was added. The reaction mixture was warmed to room temperature, stirred for 20 min, quenched with 2 M ammonium hydroxide and filtered. The reaction mixture was extracted with methylene chloride and the combined organic layers were dried over sodium sulfate, filtered, and concentrated to afford the desired product (1.2 g, 63%) as an oil: ESI MS m/z 219 [C₈H₉BrFN + H]⁺.

Example 481

tert-Butyl l -(4-Bromo-2-fluorophenyl)ethylcarbamate

Following the procedure outlined for Example 463, l -(4-bromO-2-fluorophenyl)ethanamine (1.2 g, 5.6 mmol) was reacted with di-tert-butyl dicarbonate (1.4 g, 6.7 mmol) to afford the desired product ( 1.3 g, 73%) as a white solid: ESI MS m/z 219 [Ci₃H,₇BrFN0₂ + H - 100]⁺.

Example 482

tert-Butyl l -[2-Fluoro-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

Following General Procedure G, tert-butyl l-(4-bromo-2-fluorophenyl)ethylcarbamate (1.3 g, 4.4 mmol) was reacted with bis(pinacolato)diboron (1.7 g, 6.6 mmol) to afford the desired product (1.5 g, 93%) as a white solid: ESI MS m/z 266 [C1₉H29BFNO4 + H - 100]⁺.

Example 483

3-[4-(4,4,5,5-Tetramethyl- l ,3,2-dioxaborolan-2-yl)phenyl]propanenitrile

Following General Procedure G, 3-(4-bromophenyl)propanenitrile (1.0 g, 4.8 mmol) was reacted with bis(pinacolato)diboron (1.8 g, 7.1 mmol) to afford the desired product (1.1 g, 97%) as a light brown solid: ESI MS m/z 258 [Ci₅H₂oBN0₂ + H]⁺.

Example 484

N-(l-[4-Bromophenyl)ethyl]cyclopentanamine

To a solution of l -(4-bromophenyl)ethanone (500 mg, 2.5 mmol) in ethanol ( 16 mL) was added cyclopentanamine (320 mg, 3.8 mmol) and the reaction mixture was heated at 50 °C for 18 h. The reaction mixture was cooled to 0 °C and sodium borohydride (140 mg, 3.8 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 30 min. The reaction mixture was quenched with 2 M aqueous ammonium hydroxide and extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and

concentrated to afford the desired product (600 mg, 90%) as a red oil: ESI MS m/z 269

[Ci₃H₁₈BrN + H]⁺.

Example 485

tert-Butyl l-[4-(4,4,5,5-^' Tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]propylcarbamate

Following General Procedure G, tert-butyl l-(4-bromophenyl)propylcarbamate (2.0 g, 6.4 mmol) was reacted with bis(pinacolato)diboron (2.4 g, 9.6 mmol) to afford the desired product (2.1 g, 93%) as a yellow solid: ESI MS m/z 305 [C2oH32BN0₄ - 56]⁺.

Example 486

(S)-tert-Buty 1 1 -(4-Bromopheny l)ethylcarbamate

B

Following the procedure outlined for Example 463, (S)- l-(4-bromophenyl)ethanamine (1.0 g, 5.0 mmol) was reacted with di-tert-butyl dicarbonate (1.3 g, 6.0 mmol) to afford the desired product (1.3 g, 88%) as a white solid: ESI MS m/z 300 [Ci₃H,₈Br 0₂ + H]⁺.

Example 487

(S)-tert-Butyl 1 -[4-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

Following General Procedure G, (S)-tert-butyl l-(4-bromophenyl)ethylcarbamate (1 .3 g, 4.4 mmol) was reacted with bis(pinacolato)diboron (1.7 g, 6.6 mmol) to afford the desired product (1 .4 g, 96%) as a brown solid: ESI MS m/z 348 [C|₉H₃oBN0₄ + H]⁺.

Example 488

N-(4-Bromobenzyl)propan-2-amine

A solution of l-bromo-4-(bromomethyl)benzene (2.0 g, 8.0 mmol), isopropylamine (950 mg, 16 mmol) and potassium carbonate (2.2 g, 16 mmol) in acetonitrile (40 mL) was stirred at room temperature for 18 h. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (silica, 0-100% methylene chloride/methanol) to afford the desired product (1.4 g, 78%) as a brown solid: ESI MS m/z 228 [Ci₀Hi₄BrN + H]⁺.

4-({4-[(tert-Butoxycarbo l-yl}methyl)phenylboronic acid

(OH)₂

Following the procedure outlined for Example 488, 4-formylphenylboronic acid (100 mg, 0.47 mmol) was reacted with tert-butyl piperidin-4-ylmethylcarbamate (70 mg, 0.47 mmol) to afford the desired product (120 mg, 77%) as a brown solid: ESI MS m/z 349 [C18H29BN2O4 + H]⁺.

Example 490

(E)-tert-Butyl l-[3- xaborolan-2-yl)allyl]

Following the procedure outlined for Example 488,

(Z)-2-(3-chloroprop-l-enyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane (210 mg, 1.1 mmol) was reacted with tert-butyl piperidin-4-ylcarbamate (640 mg, 3.2 mmol) to afford the desired product (100 mg, 30%) as a brown solid: ESI MS m z 367 [C14H27BN2O2 + H]⁺.

Example 491

l -(4-Bromophenyl)-N-methylmethanamine

Following the procedure outlined for Example 488, l -bromo-4-(bromomethyl)benzene (1.0 g, 4.0 mmol) was reacted with methanamine (620 mg, 20 mmol) to afford the desired product (750 mg, 93%) as a brown solid: ESI MS m/z 201 [C₈Hi₀BrN + H] . N-(4-B anamine

Following the procedure outlined for Example 488, l-bromo-4-(bromomethyl)benzene (2.0 g, 8.0 mmol) was reacted with ethanamine (720 mg, 16 mmol) to afford the desired product (1.3 g, 75%) as a brown solid: ESI MS m/z 215 [C₉Hi₂BrN + H]⁺.

(E)-2-(3-Chloroprop-l - l-l ₎3,2-dioxaborolane

A solution of (E)-3-chloroprop-l-enylboronic acid (5 g, 41 mmol), pinacol (4.9 g, 41 mmol), and magnesium sulfate (15 g, 120 mmol) in methylene chloride (100 mL) was stirred at room temperature for 18 h. The reaction mixture was filtered through silica gel and the filter cake was washed with methylene chloride. The filtrate was concentrated to afford the desired product (4.8 g, 60%) as a colorless oil: ESI MS m/z 203 [C₉Hi₆BC10₂ + H]⁺.

Example 494

(E)-tert-Butyl l -[3-(4,4,5,5-Tetramethyl-l ,3,2-dioxaborolan-2-yl)allyl] piperidin-3-ylcarbamate

Following the procedure outlined for Example 488,

(E)-2-(3-chloroprop- l-enyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (500 mg, 2.5 mmol) was reacted with tert-butyl piperidin-3-ylcarbamate (740 mg, 3.7 mmol) to afford the desired product (320 mg, 24%) as a yellow oil: ESI MS m/z 367 [C19H35BN2O4 + H]⁺.

4-Bromo-2-fluo zenesulfonamide

To a solution of 2-aminoethanol (0.24 mL, 4.0 mmol), and triethylamine (1.5 mL, 1 1 mmol) in anhydrous THF (15 mL) was added 4-bromo-2-fluorobenzene-l-sulfonyl chloride (1.0 g, 3.7 mmol) portion wise and the reaction mixture stirred at room temperature for 16 h. The reaction was filtered, the filtrate was concentrated and the residue was purified by column

chromatography (silica, ethyl acetate/hexanes gradient) to afford the desired product (850 mg, 77%): ESI MS m/z 298 [C₈H₉BrFN0₃S + H]⁺.

Example 496

4-Bromo-N-(2-hydroxyethyl)benzenesulfonamide

To a solution of 2-aminoethanol (2.3 mL, 39 mmol), and triethylamine (16 mL, 120 mmol) in anhydrous THF (100 mL) was added 4-bromobenzene-l -sulfonyl chloride (10 g, 39 mmol) portion wise and the reaction mixture stirred at room temperature for 16 h. The reaction was filtered, the filtrate was concentrated and the residue was purified by column chromatography (silica, ethyl acetate/hexanes gradient) to afford the desired product (5.5 g, 50%): Ή NMR (500 MHz, CDC ) δ 7:74 (td, J = 9.0, 2.1 Hz, 2H), 7.67 (td, J = 9.0, 2.1 Hz, 2H), 5.08 (s, 1 H), 3.72 (t, J = 5.1 Hz, 2H), 3.12 (t, J = 4.8 Hz, 2H), 1.83 (s, 1H).

N-(2-Hydroxyethyl)-4-(4,4,5 lan-2-yl)benzenesulfonamide

Following General Procedure G, 4-bromo-N-(2-hydroxyethyl)benzenesulfonamide (5.0 g, 18 mmol) was reacted with bis(pinacolato)diboron (4.9 g, 20 mmol) to afford the desired product (4.2 g, 40%) as a yellow solid: Ή NMR (300 MHz, CDCb) δ 7.95 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 8.3 Hz, 2H), 5.14 (t, J = 6.1 Hz, 1 H), 3.68 (t, J = 5.0 Hz, 2H), 3.09 (q, J = 5.4 Hz, 2H), 1.36 (s, 12H).

Example 498

(S)-tert-Butyl 1 -(3-Bromo-4-nitrophenyl)pyrrolidin-3-ylcarbamate

A solution of 2-bromo-4-fiuoro-l -nitrobenzene (1.5 g, 6.8 mmol), (S)-tert-butyl

pyrrolidin-3-ylcarbamate (1.9 g, 10 mmol), and sodium bicarbonate (1.7 g, 20 mmol) in DMSO (40 mL) was heated at 80 °C for 1 h. The reaction mixture was cooled to room temperature, poured into excess water and the resulting precipitate was filtered. The solids were washed with aqueous ammonium chloride, brine and water to afford the desired product (2.5 g, 96%>) as a yellow solid: 387 [Ci₅H₂oBrN₃04 + H]⁺.

Example 499

(S)-tert-Butyl 1 -(4-Amino-3-bromophenyl)pyrrolidin-3-ylcarbamate

A solution of (S)-tert-butyl l -(3-bromo-4-nitrophenyl)pyrrolidin-3-ylcarbamate (2.5 g, 6.5 mmol), ammonium chloride (380 mg, 7.1 mmol), and iron (1.8 g, 32 mmol) in ethanol (20 mL) and water (10 mL) was heated to reflux for 1 h. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth. The filtrate was concentrated to afford the desired product (2.3 g, >99%) as a blue solid: ESI MS m/z 357 [C|₅H22BrN₃02 + H]⁺.

Example 500

Methyl 5-Bromothiophene-2-carboxylate

A solution of 5-bromothiophene-2-carboxylic acid (5.0 g, 24 mmol), methyl iodide (5.1 g, 30 mmol), and potassium carbonate (6.7 g, 48 mmol) in DMF (50 mL) was stirred at room temperature for 64 h. The reaction was quenched with water and the aqueous layer was extracted multiple times with ethyl acetate. The combined organic layers were washed with aqueous lithium chloride and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (silica, ethyl

acetate/hexanes gradient) to afford the desired product (4.2 g, 79%): Ή NMR (500 MHz, CDC ) δ 7.54 (d, J = 4.0 Hz, 1 H), 7.07 (d, J = 4.0 Hz, 1 H), 3.87 (s, 3H).

Methyl 5-(4 carboxylate

Following General Procedure B, 4-methoxyphenylboronic acid (2.7 g, 18 mmol) was reacted with methyl 5-bromothiophene-2-carboxylate (2.0 g, 9.0 mmol) to afford the desired product (1 .4 g, 61 %): Ή NMR (300 MHz, CDC1₃) δ 7.71 (d, J = 3.9 Hz, 1H), 7.53 (td, J = 9.7, 2.5 Hz, 2H), 7.14 (d, J = 3.9 Hz, 1 H), 6.89 (td, J = 9.7, 2.5 Hz, 2H), 3.87 (s, 3H), 3.80 (s, 3H).

Example 502

5-(4-Methoxyphenyl)thiophene-2-carboxylic Acid

A solution of methyl 5-(4-methoxyphenyl)thiophene-2-carboxylate (1.4 g, 5.6 mmol), and 1 M sodium hydroxide (55 mL) in methanol (55 mL) was heated at 80 °C for 18 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was . washed with 1 N hydrochloric acid and aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated to afford the desired product ( 1.2 g, 93%) as an off-white solid: ESI MS m/z 325 [C2H10O3S + H]⁺.

Example 503

5-(4-Methoxyphenyl)thiophene-2-carbonyl chloride

To a solution of 5-(4-methoxyphenyl)thiophene-2-carboxylic acid (0.60 g, 2.5 mmol) in toluene (4 mL) was added thionylchloride (560 mL, 7.7 mmol) and the reaction mixture was heated at 100 °C for 18 h. The reaction mixture was cooled to room temperature and concentrated to afford the desire product (642 mg, crude): ESI MS m/z 253 [C|₂H₉C10₂S + H]⁺.

Example 504

(S)-tert-Butyl

l -{3-Bromo-4-[5-(4-methoxyphenyl)thiophene-2-carboxamido]phenyl}pyrrolidin-3-ylcarbamate

Following Step 1 from General Procedure A, 5-(4-methoxyphenyl)thiophene-2-carbonyl chloride (640 mg, 2.5 mmol) was reacted with (S)-tert-butyl

l -(4-amino-3-bromophenyl)pyrrolidin-3-ylcarbamate (800 mg, 2.2 mmol) to afford the desired product (500 mg, 39%) as a light yellow solid: ESI MS m/z 573 [C27H₃₀BrN₃O4S + H]⁺.

Example 505

(S)-tert-Butyl

l -{3-Bromo-4-[5-(4-methoxyphenyl)-N-{[2-(trimethylsilyl)ethoxy]methyl}thiophene-2-carboxa mido]phenyl}

pyrrolidin-3-ylcarbamate

A solution of (S)-tert-butyl

l -{3-bromo-4-[5-(4-methoxyphenyl)thiophene-2-carboxamido]phenyl}pyrrolidin-3-ylcarbamate (400 mg, 0.69 mmol) in THE (20 mL) was cooled to 0 °C and sodium hydride (60 wt %, 140 mg, 3.5 mmol) was added. The reaction was warmed to room temperature followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (370 mL, 2.1 mmol) and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was quenched with water and diluted with ethyl acetate. The layers were separated and the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated and the residue was purified by column chromatography (silica, 0-30% ethyl acetate/heptane) to afford the desired product (400 mg, 87%): ESI MS m/z 703 [C₃₃H44BrN₃0₅SSi + H]⁺.

Example 506

(S)-8-(3-Aminopyrrolidin-l -yl)-2-(4-methoxyphenyl)-5-{[2-(trimethylsilyl)ethoxy]methyl}thien

Following Step 3 from General Procedure A, (S)-tert-butyl

l -{3-bromo-4-[5-(4-methoxyphenyl)-N-{[2-(trimethylsilyl)ethoxy]methyl}thiophene-2-carboxa mido]phenyl}pyrrolidin-3-ylcarbamate (210 mg, 0.29 mmol) was reacted with

bis(tri-tert-butylphosphine)palladium (15 mg, 0.029 mmol) to afford the desired product (25 mg, 14%): ESI MS m/z 622 [C28H35N3O3SS1 + H]⁺.

Example 51

(S)-8-(3-Aminopyrrolidin-l-yI)-2-(4-hydroxyphenyl)thieno[2,3-c]

qu

Following General Procedure F,

(S)-8-(3-aminopyrrolidin-l -yl)-2-(4-methoxyphenyl)-5-{[2-(trimethylsiIyl)ethoxy]methyl}thieno [2,3-c]quinolin-4(5H)-one (25 mg, 0.040 mmol) was reacted with tribromoborane (38 mL, 0.40 mmol) to afford the desired product (6.4 mg, 43%) as a yellow-green solid: Ή NMR (500 MHz, CD₃OD) δ 8.06 (s, 1 H), 7.71 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 9.0 Hz, 1 H), 7.26 (s, 1H), 6.99 (d, J = 8.4 Hz, 1 H), 6.90 (d, J = 8.5 Hz, 2H), 4.09 (s, 1H), 3.74-3.69 (m, 2H), 3.59-3.57 (m, 1H), 3.48-3.39 (m, 1 H), 2.57-2.52 (m, 1 H), 2.25-2.23 (m, 1H); ESI MS m/z 378 [C21H19N3O2S + H]⁺; HPLC 97.1 % (AUC), t_R = 10.89 min.

Compounds of the invention of this application that the specific procedure for producing the compound was not particularly described in the Examples above were also synthesized by the similar or analogous methods by referring to the above-mentioned general procedures for producing the present compounds, Examples and such.

Examples 507

Kinase assay

PBK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman JR, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01 % Tween-20, 0.3 mM MgCl₂, 2 mM dithiothreitol, 50micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature, fluorescence polarization was measured by Wallac EnVision 2103 multilabel reader (PerkinElmer). IC50 values were calculated by nonlinear four parameter fit using SigmaPlot, version 10.0 (Systat Software, Inc.).

IC50 values of the typical compounds of the present invention are shown in following table 2:

Table 2

IC50 (microM)

ID. Compound

(kinase assay)

N- { l -[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoli

193 0.0037 n-9-yl)phenyl]ethyl}methanesulfonamide

8-Hydroxy-9- {4-[l -(pyrrolidin- l-yl)ethyl]phenyl}thieno[2,3

194 0.0028 -c]quinolin-4(5H)-one Hydrochloride

9-[4-(l -Aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quinolin

195 0.00073 -4(5H)-one Hydrochloride

9-{4-[l -(Diethylamino)ethyl]phenyl}-8-hydroxythieno[2,3-c

196 0.0045 lquinolin-4(5H)-one Hydrochloride

N-(2-Bromoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,

210 0.01 13

3-c]quinolin-9-yl)benzenesulfonamide

N-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-

212 0.0055 yl)benzyllmethanesulfonamide

8-Methoxy-9- {4-[l -(pyrrolidin-l-yl)ethyl]phenyl}thieno[2,3

216 0.021 -c]quinolin-4(5H)-one Hydrochloride

9-(4-Amino-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quino

217 0.0023 lin-4(5H)-one Hydrochloride

9-{4-[l -(Dimethylamino)ethyl]phenyl}-6-fluoro-8-methoxyt

222 0.082 hieno[2,3-c]quinolin-4(5H)-one Hydrochloride

9- {4-[2-(Dimethylamino)ethyl]phenyl}-6-fluoro-8-hydroxyt

225 0.023 hieno[2,3-c]quinolin-4(5H)-one

8-Hydroxy-9- {4-[(isopropylamino)methyl]phenyl}thieno[2,

229 0.0042

3-c]quinolin-4(5H)-one Hydrochloride

(S)-9-[4-(l -Aminoethyl)phenyl]-8-methoxythieno[2,3-c]qui

232 0.0074 nolin-4(5H)-one Hydrochloride

(S)-9-[4-(l -Aminoethyl)phenyl]-8-hydroxythieno[2,3-c]quin

233 0.00081 olin-4(5H)-one Hydrochloride

9-(4- { [4-( Aminomethy l)piperidin- 1 -y l]methy 1 } -3 -fluorophe

235 0.00057 nyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

N-[4-(8-Hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-

254 0.003 yl)-2-methylphenyl]methanesulfonamide

9-[4-(Aminomethyl)phenyl]-6-fluoro-8-hydroxythieno[2,3-c

256 0.0025

]quinolin-4(5H)-one Hydrochloride

9-[4-(Aminomethyl)phenyl]-6-fluoro-8-methoxythieno[2,3-

257 0.026 c]quinolin-4(5H)-one Hydrochloride

2-[2-Fluoro-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]qu

261 0.015 inolin-9-yl)phenyl]acetonitrile

8-Hydroxy-9-{4-[ l-(piperidin- l -yl)ethyl]phenyl}thieno[2,3-

262 0.0043 c]quinolin-4(5H)-one Hydrochloride

9-[4-(2-Aminoethyl)-3-fluorophenyl]-8-methoxythieno[2,3-

265 0.0038 c]quinolin-4(5H)-one Hydrochloride

9-[5-(Aminomethyl)thiophen-2-yl]-8-hydroxythieno[2,3-c]q

266 0.00078 uinolin-4(5H)-one

9- {4-[(Ethylamino)methyl]phenyl}-8-hydroxythieno[2,3-c]q

267 0.002 uinolin-4(5H)-one Hydrochloride

9-{4-[(Ethylamino)methyl]phenyl} -8-methoxythieno[2,3-c]

269 0.006 quinolin-4(5H)-one Hydrochloride

9-[4-(Aminomethyl)phenyl]-6-bromo-8-hydroxythieno[2,3-

270 0.03 1 c]quinolin-4(5H)-one Hydrochloride

(R)-9- {4- [ 1 -(Dimethy lam ino)ethy ljpheny 1 } -8-hydroxy thien

272 0.00088 o[2,3-clquinolin-4(5H)-one Hydrochloride

9-(4-( 1 -aminopropy l)pheny l)-6-chloro-8-hydroxythieno[2,3-

1088 0.016 clquinolin-4(5H)-one hydrochloride

N-(2-bromoethyl)-4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro- l

1094 0.01

H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide

9-(4-(2-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinoli

1095 0.0013 n-4(5H)-one hydrochloride

9-(4-(l -aminoethy l)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]

1099 0.033 quinojin-8-yl acetate hydrochloride

9-(4-(2-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-

1 106 0.041 clquinolin-4(5H)-one hydrochloride

9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]q

1 1 1 1 0.0013 uinolin-4(5H)-one hydrochloride

9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythie

1 1 12 0.0033 no [2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-6-chloro-8-hydr

1 1 16 0.022 oxythieno[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]qui

1 120 0.00088 nolin-4(5H)-one hydrochloride

(S)-9-(4-(l -aminopropy l)phenyl)-8-methoxythieno[2,3-c]qui

1 121 0.0029 nolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminoethyl)phenyl)-8-hydroxy-6-methylthieno[

1 122 0.0059

2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminoethy l)phenyl)-6-bromo-8-hydroxythieno[2

1 123 0.033

,3-c]quinolin-4(5H)-one hydrochloride

(R)-6-chloro-9-(4-(l -(dimethylamino)ethyl)phenyl)-8-hydro

1 126 0.042 xythieno [2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l-(ethylamino)propyl)phenyl)-8-hydroxythieno[2,

1 127 0.0014

3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-( 1 -(dimethy lamino)propy l)phenyl)-8-hydroxythien

1 128 0.0022 of2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]qui

1 131 0.0013 nolin-4(5H)-one hydrochloride

(R)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)

1 132 0.014 thieno [2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c

1 133 0.02

]quinolin-4(5H)-one hydrochloride

(R)-6-bromo-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl

1 135 0.03

)thieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(1 -aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythien

1 136 0.0086 o[2,3-c]quinolin-4(5H)-one hydrochloride

N-(2-chloroethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,

1 139 0.07

3-c]quinolin-9-yl)benzenesulfonamide

9-(4-(2-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c

1 142 0.045

]quinolin-4(5H)-one hydrochloride

N-(2-chloroethyl)-4-(8-hydroxy-4-oxo-2,3,4,5-tetrahydro-l

1 145 0.013

H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide

(S)-8-hydroxy-9-(4-( 1 -(methy lamino)propy l)pheny l)thieno[

1 148 0.0013

2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropy l)phenyl)-6-bromo-8-hydroxythieno

1 150 0.047

[2,3-c]quinolin-4(5H)-one hydrochloride (R)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythien

1 151 0.0025 o[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)propyl)pheny

1 154 0.0094 l)thieno[2,3-clquinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropy l)phenyl)-8-hydroxy-6-methylthieno

1 157 0.018

[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropy l)phenyl)-6-chloro-8-hydroxythieno[

1 159 0.026

2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-

1 160 0.00064 c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-8-methoxythieno[2,3

1 161 0.002

-c]quinolin-4(5H)-one hydrochloride

2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-y

1 162 0.013 l)phenyl)butanenitrile

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-

1 163 0.0013 c]quinolin-4(5H)-one hydrochloride

6-chloro-8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thie

1 165 0.058 no[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxyt

1 166 0.0044 hieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)phenyl)-8-hydroxy-6-methy It

1 168 0.0026 hieno[2,3-clquinolin-4(5H)-one hydrochloride

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylt

1 169 0.0089 hieno [2,3-c]quinolin-4(5H)-one hydrobromide

(S)-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxyt

1 172 0.004 hieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxythieno

1 174 0.0015

[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( l-aminopropan-2-yl)phenyl)-6-bromo-8-hydroxyt

1 176 0.017 hieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxythien

1 179 0.003 o[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxyth

1 181 0.033 ieno[2,3-c|quinolin-4(5H)-one hydrochloride

(R)-8-hydroxy-9-(4-( 1 -(methy lamino)propan-2-y l)pheny l)th

1 187 0.0013 ieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -(dimethylamino)propan-2-yl)phenyl)-8-hydroxy

1 188 0.0025 thieno [2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-methoxy-9-(4-(l -(methy lamino)propan-2-yl)phenyl)th

1 189 0.003 ieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-me

1 190 0.0051 thylthieno [2,3-clquinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c

1 191 0.019

]quinolin-4(5H)-one hydrochloride

9-(4-(l -(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hyd

1 193 roxy-6-methylthieno [2,3-c]quinolin-4(5H)-one 0.046 hydrochloride

(S)-8-hydroxy-9-(4-(l -(methy lamino)propan-2-yl)phenyl)thi

1 197 0.0028 eno[2,3-c]quinolin-4(5H)-one hydrochloride (R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-6-chloro-8-methoxyt

1201 0.02 ' hieno[2,3-c]quinolin-4(5H)-one hydrochloride

N-( 1 -chloropropan-2-y l)-4-(8-hydroxy-4-oxo-4,5-dihydrothi

1204 0.015 eno[2,3-c]quinolin-9-yl)benzenesulfonamide

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxythieno

1209 0.0018

[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(aminomethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c

1212 0.016

]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-bromo-8-hydroxythi

1213 0.019 eno[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-8-hydroxy-6-methy l-9-(4-( 1 -(methy lamino)propan-2-y 1)

1215 0.06 phenyl)thieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophenyl)-8-methoxy-6-methylthi

1216 0.057 eno [2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxy-6-methylthi

121 7 0.0047 eno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-methoxythi

121 8 0.087 eno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-hydroxythie

1219 0.0055 no[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-2-bromo-5-hydroxyphenyl)-8-hydroxyt

1224 0.0064 hieno[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l -aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2

1225 0.016

,3-c]quinolin-4(5H)-one hydrochloride

3-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]qu

1226 0.092 inolin-9-yl)phenyl)propanenitrile

9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-8-hydroxy-6-m

1228 0.039 ethylthieno [2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxy-6-methylt

1232 0.016 hieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-amino- l -cyclopentylethyl)phenyl)-8-hydroxythieno[

1236 0.0046

2,3-c]quinolin-4(5H)-one

9-(4-(2-amino- l -cyclopentylethyl)phenyl)-8-methoxythieno[

Ί 239 0.023

2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3

1242 0.037

-c]quinolin-4(5H)-one hydrochloride

6-bromo-9-(3-flu0ro-4-(2-(methylamino)ethyl)phenyl)-8-hy

1245 0.045 droxythieno[2,3-clquinolin-4(5H)-one hydrochloride

9-(4-( 1 -amino-2-methy lpropan-2-y l)pheny l)-6-bromo-8-hyd

1247 0.072 roxythieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-methoxy-6-me

1251 0.055 thylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -amino-3-methylbutan-2-yl)phenyl)-8-hydroxythieno

1252 0.0014

[2,3-c]quinolin-4(5H)-one

9-(4-( 1 -amino-3-methy lbutan-2-y l)pheny l)-8-methoxythieno

1253 0.0041

[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-hydroxy-6-me

1254 0.0096 thylthienof2,3-c]quinolin-4(5H)-one hydrochloride

9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxy-6-

1258 0.025 methylthienof2,3-c]quinolin-4(5H)-one hydrochloride 9-(4-(l -amino-2-methylpropan-2-yl)phenyl)-6-chloro-8-hyd

1260 0.075 roxythienor2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-hydroxy-6-methy l-9-(4-( 1 -(methy lamino)ethy l)pheny 1

1262 0.012

)thieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-methoxy-6-methylth

1263 0.033 ieno[2,3-clquinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxy-6-methylthi

1264 0.003 enor2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-methoxy-6-methyl-9-(4-(l -(methy lamino)ethyl)pheny

1265 0.067 l)thieno[2,3-clquinolin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-chlorophenyl)-6-chloro-8-hydroxythi

1268 0.0039 eno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydr

1271 0.001 oxythien0[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-( 1 -aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-m

1273 0.04 ethylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -amino-3-methylbutan-2-yl)phenyl)-8-hydroxy-6-met

1274 0.018 hylthienor2,3-c]quinolin-4(5H)-one

9-(4-( l -aminobutan-2-yl)phenyl)-8-methoxy-6-methylthieno

1277 0.063

[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-( 1 -amino-2-methy lpropan-2-y l)-3-fluoropheny l)-8-hydr

1278 0.022 oxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -aminopropan-2-yl)-3-chlorophenyl)-8-hydroxythien

1280 0.01 o[2,3-c|quinolin-4(5H)-one hydrochloride

9-(4-(l-amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-meth

1283 0.047 oxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

8-hydroxy-6-methyl-9-(4-(3-methy 1- 1 -(methy lamino)butan-

1285 0.05

2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one

9-(3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-meth

1286 0.043 oxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-hydro

1288 0.02 xy-6-methylthieno[2,3-c]quinolin-4(5H)-one

9-(4-(l -(aminomethyl)cyclobutyl)phenyl)-8-hydroxy-6-meth

1290 0.01 ylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthieno

1291 0.015

[2,3-c]quinolin-4(5H)-one hydrochloride

9-(3-fluoro-4-(l -(methylamino)propan-2-yl)phenyl)-8-hydro

1293 0.0089 xy-6-methylthieno[2,3-c]quinolin-4(5H)-one

9-(3-fluoro-4-(3-methyl-l-(methylamino)butan-2-yl)phenyl)

1294 0.017

-8-hydroxy-6-methylthieno[2,3-clquinolin-4(5H)-one

9-(4-( 1 -(aminomethyl)cyclobutyl)pheny l)-8-methoxy-6-met

1297 0.035 hylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-methoxy-6-methyl-9-(4-(l -(methy lamino)propan-2-yl

1298 0.032

)phenyl)thieno [2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(l -(aminomethyl)cyclobutyl)phenyl)-8-hydroxythieno[

1300 0.0017

2,3-c]quinolin-4(5H)-one hydrochloride

8-hydroxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno[2,3-

1302 0.075 c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-( 1 -aminopropan-2-y l)-3-fluoropheny l)-8-hydroxy-6

1303 0.014

-methy lthienor2,3-c]quinolin-4(5H)-one (S)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6

1304 0.013

-methylthieno[2,3-c]quinolin-4(5H)-one hydrobromide

(R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-8-methoxy-6-methy It

1305 0.015 hieno [2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-hydroxy-6-methy l-9-(4-( 1 -(methy lamino)propan-2-y 1)

1306 0.0073 phenyl)thieno [2,3-c]quinolin-4(5H)-one hydrochloride

(R)-8-hydroxy-6-methyl-9-(4-(l -(methy lamino)propan-2-yl)

1307 0.018 phenyl)thieno [2,3-c]quinolin-4(5H)-one hydrobromide

9-(4-(l -aminobutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]qui

1309 0.00074 nolin-4(5H)-one hydrochloride

(S)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-

1310 0.054

6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -(dimethy lamino)propan-2-y l)-3-fluoropheny l)-8

131 1 -hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one 0.017 hydrochloride

9-(4-(l -aminobutan-2-yl)phenyl)-6-chloro-8-hydroxythieno[

1312 0.019

2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(3-fluoro-4-(l -(methy lamino)propan-2-yl)phenyl)-8-h

1315 ydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one 0.0081 hydrochloride

(R)-9-(3-fluoro-4-(l -(methy lamino)propan-2-yl)phenyl)-8-

1316 methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one 0.033 hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)-3-fluorophenyl)-8-methoxy-

1317 0.022

6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6

1318 0.0036

-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6

1319 0.0034

-methylthienof2,3-c]quinolin-4(5H)-one hydrobromide

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-6-chloro-8-metho

1321 0.096 xythieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy

1324 0.032

-6-methylthieno[2,3-clquinolin-4(5H)-one hydrochloride

9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthien

1330 0.0083 o[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-8-hydroxy-2,6-dimet

1340 0.012 hylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-8-methoxy-2,6-dimet

1341 0.038 hylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-6-chloro-9-(4-(l -(dimethy lamino)propan-2-yl)phenyl)-8

1347 0.043

-hydroxythieno [2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( l -aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthi

1352 0.04 enof2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-2-chloro-8-hydroxy-

1353 0.004

6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-2-chloro-8-methoxy-

1354 0.01 1

6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

8-hydroxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thi

1364 0.055 eno[2,3-c]quinolin-4(5H)-one hydrochloride 9-(4-(l-((dimethylamino)methyl)cyclobutyl)phenyl)-8-hydr

1372 0.042 oxy-6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)pheny l)-2-fluoro-8-methoxy-

1375 0.022

6-methylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -(ethy l(methy l)amino)propan-2-y l)pheny l)-8-hyd

1379 roxy-6-methylthieno [2,3-c]quinolin-4(5H)-one 0.076 hydrochloride

(R)-8-hydroxy-6-methyl-9-(4-( 1 -(methy lamino)butan-2-y l)p

1380 ^' 0.085 henyl)thieno[2,3-c]quinolin-4(5H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)phenyl)-2-fluoro-8-hydroxy-6

1383 0.0037

-methy lthienof2,3-clquinolin-4(5H)-one hydrochloride

9-(4-( 1 -(aminomethyl)cyclopropy l)phenyl)-6-bromo-8-meth

1391 0.07

oxythieno[2,3-c]quinolin-4(5H)-one hydrochloride

(S)-9-(4-(l -(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-

1399 hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one 0.058 hydrochloride

9-(4-((2-aminoethyl)(methyl)amino)phenyl)-8-hydroxy-6-m

1400 0.06

ethylthieno[2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-( 1 -(aminomethyl)cyclopropy l)pheny l)-6-bromo-8-hydr

1401 0.051 oxythieno[2,3-c]quinolin-4(5H)-one hydrochloride

2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]qu

1419 0.082

inolin-9-y l)pheny l)propane- 1 -sulfonamide

Examples 508

Western blot analysis

To evaluate the expression status of PBK in several cell lines, western blot analysis was performed using crude cell lysate collected from those cells. Anti-PBK antibody (clone 31 , BD Biosciences) was used to visualize the expression. Breast cancer cell lines, T47D and BT-549 expressed PBK significantly although Bladder cancer cell line and HT-1 197 showed no expression of PBK.

Examples 509

Cell-based assay

Active candidate inhibitors against PBK were evaluated for their target-specific cytotoxicity using T47D, A549, BT-549, and HT-1 197 cells was used for negative control. 100 micro-L of cell suspension was seeded onto 96-well microtiter plate (ViewPlate-96FTC, PerkinElmer). The initial cell concentration of T47D, BT-549 and HT-1 197 were 3,000 cells/well, 2,000 cells/well and 2,500 cells/well, respectively. Cellular growth was determined using Cell

Counting Kit-8 (DOJINDO) at 72 hours after the exposure of the candidate inhibitors. IC50 was used as an indicator of the anti-proliferative activity of the inhibitors, and calculated by serial dilution method (0, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 micro-M). Accurate IC50 values were calculated as described previously.

ICso values of the typical compounds of the present invention are shown in following table 3:

Table 3- 1 ;

H)-one 9- { 4- [ 1 -(Cy clopenty lam ino)ethy 1]

phenyl } -8-hydroxythieno[2,3-c]q 1 .9 4.1 1.5 3.7 uinolin-4(5H)-one Hydrochloride

9-[4-(2-Aminopropan-2-yl)phenyl

]-8-hydroxythieno[2,3-c]quinolin- 0.55 0.9 0.64 2.3 4(5H)-one Hydrochloride

9-[4-(Aminomethyl)phenyl]-4-ox

o-4,5-dihydrothieno[2,3-c]quinoli 4.3 5.9 7.9 10 ne-8-carbonitrile Hydrochloride

9- {4-[2-(Dimethylamino)ethyl]-3- fluorophenyl}-8-hydroxythieno[2,

3.3 6.4 3.7 7.8 3-c]quinolin-4(5H)-one

Hydrochloride

9-[4-(Aminomethyl)phenyl]-6-chl

oro-8-hydroxythieno[2,3-c]quinol 0.32 0.63 0.36 1.4 in-4(5H)-one Hydrochloride

N-(2-Chloroethyl)-4-(8-hydroxy-4

-oxo-4,5-dihydrothieno[2,3-c]quin 0.012 0.3 1 0.034 24 olin-9-yl)benzenesulfonamide

N-(2-Fluoroethyl)-4-(8-methoxy-4

-oxo-4,5-dihydrothieno[2,3-c]quin 2.5 9.3 2 24 olin-9-yl)benzenesulfonamide

9-[4-(2-Aminopropan-2-yl)phenyl

]-6-chloro-8-hydroxythieno[2,3-c]

0.48 1.1 0.49 1 .3 quinolin-4(5H)-one

Hydrochloride

(S)-9- { 4- [ 1 -(Di methy lam i no)ethy 1

]phenyl} -8-hydroxythieno[2,3-c]q 1 .1 2.4 1 .2 3.3 uinolin-4(5H)-one Hydrochloride

9-[4-( 1 -Aminopropyl)phenyl]-8-h

ydroxythieno[2,3-c]quinolin-4(5H 0.21 0.35 0.32 0.97 )-one Hydrochloride

9-[4-( l -Aminopropyl)phenyl]-8- methoxythieno[2,3-c]quinolin-4(5 1 .5 3.4 1.4 3.9 H)-one Hydrochloride

9- {4-[l -(Diethylamino)propyl]ph

enyl}-8-hydroxythieno[2,3-c]quin 2 7.1 1.8 4.5 olin-4(5H)-one Hydrochloride

9- {4-[l -(Dimethylamino)propyl]p

henyl} -8-hydroxythieno[2,3-c]qui 0.35 0.79 0.36 - 0.98 nolin-4(5 )-one Hydrochloride

9-{4-[ l -(Dimethylamino)ethyl]ph

enyl}-6,7-difluoro-8-hydroxythien

1 .4 2.9 1.5 3.3 o[2,3-c]quinolin-4(5H)-one

Hydrochloride

9-(2-Amino-2,3-dihydro- 1 H-inde

n-5-yl)-8-hydroxythieno[2,3-c]qui 3.1 4.4 5.7 7.1 nolin-4(5H)-one Hydrochloride

9- {4-[ l -(Dimethylamino)ethyl]ph

enyl}thieno[2,3-c]quinolin-4(5H)- 2.5 7.2 6.8 one (S)-N- { 1 -[4-(8-Hydroxy-4-oxo-4,

5-dihydrothieno[2,3-c]quinolin-9-

347 1 0.75 5.6 29 yl)phenyl]ethyl} methanesulfonam

ide

9- {4-[ 1 -( Aminomethy l)cy c loprop

yl]phenyl}-8-hydroxythieno[2,3-c

348 0.31 3.2 0.38 1.2

]quinolin-4(5H)-one

Hydrochloride

9-{4-[l -(Dimethylamino)ethyl]-3- fluoropheny 1 } -8-hydroxythieno[2,

349 0.58 1 .3 0.48 1 .3

3-c]quinolin-4(5H)-one

Hydrochloride

8-Hydroxy-9-( l ,2,3,4-tetrahydrois

353 oquinolin-7-yl)thieno[2,3-c]quino 1 .9 3.7 3.2 4.2 lin-4(5H)-one Hydrochloride

9- {4-[l -(Diethylamino)ethyl]-3-fl

uorophenyl}-8-hydroxythieno[2,3

356 1 .5 3.3 1.3 3.5

-c]quinolin-4(5H)-one

Hydrochloride

9-[4-( l -Aminoethyl)-3-fluorophen

359 yl]-8-hydroxythieno[2,3-c]quinoli 0.35 0.64 0.62 4 n-4(5H)-one Hydrochloride

1 -[4-(8-Hydroxy-4-oxo-4,5-dihyd

361 rothieno[2,3-c]quinolin-9-yl)phen 0.94 2.5 0.96 2.7 yl]cyclopropanecarbonitrile

"> 1 00" in the table means over 100 micro M.

Table 3-2;

(R)-8-hydroxy-9-(4-(l -(methyla

mino)ethyl)phenyl)thieno[2,3-c]

1052 0.17 0.32 0.17 0.45 - quinolin-4(5H)-one

hydrochloride

N-( 1 -bromopropan-2-y l)-4-(8-hy

droxy-4-oxo-4,5-dihydrothieno[2

1 062 0.15 1.9 0.88 12 - ,3-c]quinolin-9-yl)benzenesulfon

amide

(S)-8-methoxy-9-(4-( 1 -(methy la

mino)ethyl)phenyl)thieno[2,3-c]

1064 1 2.2 0.89 2.9 - quinolin-4(5H)-one

hydrochloride

9-(4-(l -aminoethyl)phenyl)-8-hy

1066 droxy-6-methylthieno[2,3-c]quin 0.065 0.13 0.12 0.34 - olin-4(5H)-one hydrochloride

9-(4-( 1 -aminoethyl)pheny l)-4-ox

o-4,5-dihydrothieno[2,3-c]quinol

1077 0.41 0.45 0.66 2.5 - in-8-yl isopropyl carbonate

hydrochloride

(R)-9-(4-( 1 -aminoethy l)pheny 1)- 6-chloro-8-hydroxythieno[2,3-c]

1 081 0.086 0.17 0.1 0.39 - quinolin-4(5H)-one

hydrochloride

(S)-8-hydroxy-9-(4-( 1 -(methy la

mino)ethyl)phenyl)thieno[2,3-c]

1 082 0.36 0.6 0.43 1 - quinolin-4(5H)-one

hydrochloride

(S)-6-chloro-8-hydroxy-9-(4-(l -(

methylamino)ethyl)phenyl)thien

1087 0.23 0.5 0.26 0.66 - o[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -aminopropy l)pheny l)-6-c

1 088 hloro-8-hydroxythieno[2,3-c]qui 0.24 0.52 0.24 0.66 - nolin-4(5H)-one hydrochloride

N-(2-bromoethyl)-4-(8-hydroxy- 4-oxo-2,3,4,5-tetrahydro- l H-cyc

1094 0.0071 0.29 0.028 21 - lopenta[c]quinolin-9-yl)benzenes

ulfonamide

9-(4-(2-aminopropyl)phenyl)-8-h

1095 ydroxythieno[2,3-c]quinolin-4(5 0.81 0.54 0.95 0.93 - H)-one hydrochloride

9-(4-( l -aminoethyl)phenyl)-4-ox

1099 o-4,5-dihydrothieno[2,3-c]quinol 0.46 0.37 0.54 1.9 - in-8-yl acetate hydrochloride

9-(4-(2-aminopropyl)phenyl)-6-c

1 106 hloro-8-hydroxythieno[2,3-c]qui 0.13 0.26 0.15 0.62 - nolin-4(5H)-one hydrochloride 9-(4-(l -aminopropan-2-yl)pheny

1 1 1 1 l)-8-hydroxythieno[2,3-c]quinoli 0.12 0.072 0.12 0.37 - n-4(5H)-one hydrochloride

9-(4-(l -(dimethylamino)propan- 2-yl)phenyl)-8-hydroxythieno

1 1 12 0.21 0.47 0.25 0.64 - [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -(aminomethyl)cycloprop

yl)phenyl)-6-chloro-8-hydroxyth

1 1 16 0.098 0.17 0.12 0.54 - ieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-(l -aminopropyl)phenyl)

1 120 -8-hydroxythieno[2,3-c]quinolin- 0.093 0.15 0.13 0.33 - 4(5H)-one hydrochloride

(S)-9-(4-(l -aminopropyl)phenyl)

1 121 -8-methoxythieno[2,3-c]quinolin 0.42 0.7 0.36 1.5 - -4(5H)-one hydrochloride

(R)-9-(4-(l-aminoethyl)phenyl)- 8-hydroxy-6-methylthieno[2,3-c]

1 122 - 0.065 0.049 0.17 0.065 quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminoethy l)pheny 1)- 6-bromo-8-hydroxythieno[2,3-c]

1 123 0.1 8 0.34 0.16 0.76 - quinolin-4(5H)-one

hydrochloride

(R)-6-chloro-9-(4-( 1 -(dimethy la

mino)ethyl)phenyl)-8-hydroxythi

1 126 0.14 0.29 0.1 1 0.32 - eno [2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-(l -(ethylamino)propyl)p

1 127 henyl)-8-hydroxythieno[2,3-c]qu 0.3 0.63 0.22 0.65 - inolin-4(5H)-one hydrochloride

(S)-9-(4-(l -(dimethylamino)prop

yl)phenyl)-8-hydroxythieno[2,3-

1 128 0.43 1 0.37 1.2 - c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-(l-aminopropyl)phenyl)

1 131 -8-hydroxythieno[2,3-c]quinolin- 0.51 0.71 0.68 4.8 - 4(5H)-one hydrochloride

(R)-6-chloro-8-hydroxy-9-(4-(l- (methylamino)ethyl)phenyl)thien

1 132 0.097 0.19 0.09 0.32 - o [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)phenyl)-6-ch

1 133 loro-8-hydroxythieno[2,3-c]quin 0.15 0.23 0.1 8 0.87 - olin-4(5H)-one hydrochloride (R)-6-bromo-8-hydroxy-9-(4-(l- (methylamino)ethyl)phenyl)thien

1 135 0.14 0.28 0.13 0.41 - o[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -aminopropan-2-y l)pheny

l)-6-chloro-8-hydroxythieno[2,3-

1 136 0.032 0.057 0.035 0.18 - c]quinolin-4(5H)-one

hydrochloride

N-(2-ch loroethy l)-4-(8-methoxy-

1 139 4-oxo-4,5-dihydrothieno[2,3-c]q 0.01 7 0.2 0.023 14 - uinolin-9-yl)benzenesulfonamide

9-(4-(2-aminoethyl)phenyl)-6-br

1 142 omo-8-hydroxythieno[2,3-c]quin 0.17 0.25 0.21 1 - olin-4(5H)-one hydrochloride

N-(2-chloroethyl)-4-(8-hydroxy- 4-oxo-2,3 ,4,5-tetrahydro-lH-cyc

1 145 0.01 0.18 0.051 31 - lopenta[c]quinolin-9-yl)benzenes

ulfonamide

(S)-8-hydroxy-9-(4-(l -(methyla

mino)propyl)phenyl)thieno[2,3-c

1 148 0.13 0.25 0.12 0.26 - ]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-(l-aminopropyl)phenyl)

-6-bromo-8-hydroxythieno[2,3-c

1 150 - 1.1 0.51 1.3 0.88 ]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -(dimethy lam ino)pro

pyl)phenyl)-8-hydroxythieno[2,3

1 151 0.39 0.85 0.32 1 - -c]quinolin-4(5H)-one

hydrochloride

(S)-6-chloro-8-hydroxy-9-(4-( 1 -(

methylamino)propyl)phenyl)thie

1 154 0.14 0.29 . 0.13 0.32. - no[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-(l -aminopropyl)phenyl)

-8-hydroxy-6-methylthieno[2,3-c

1 157 0.16 0.32 0.22 0.58 - ]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-(l -aminopropyl)phenyl)

-6-chloro-8-hydroxythieno[2,3-c

1 1 59 0.38 0.76 0.4 1.1 - ]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

1 160 henyl)-8-hydroxythieno[2,3-c]qu 0.054 0.057 0.056 0.23 0.069 inolin-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

1 161 henyl)-8-methoxythieno[2,3-c]q ' 0.22 0.45 0.27 0.82 - uinolin-4(5H)-one hydrochloride 2-(4-(8-hydroxy-4-oxo-4,5-dihyd

1 162 rothieno[2,3-c]quinolin-9-yl)phe 0.51 1.2 0.65 1.3 - nyl)butanenitrile

(S)-9-(4-(l -aminopropan-2-yl)ph

1 163 enyl)-8-hydroxythieno[2,3-c]qui 0.33 0.24 0.32 0.96 - nolin-4(5H)-one hydrochloride

6-chloro-8-hydroxy-9-(4-(2-(met

hylamino)ethyl)phenyl)thieno[2,

1 165 0.37 0.65 0.41 1.2 - 3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

henyl)-6-chloro-8-hydroxythieno

1 166 0.013 0.026 0.017 0.12 - [2,3-c]quinolin-4(5 H)-one

hydrochloride

(R)-9-(4-( 1 -am inopropan-2-y l)p

henyl)-8-hydroxy-6-methylthien

1 168 - 0.0084 0.0065 0.027 0.008 o[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

henyl)-8-hydroxy-6-methylthien

1 169 0.013 0.024 0.023 0.079 0.022 o [2,3-c]quinolin-4(5H)-one

hydrobromide

(S)-9-(4-( 1 -(dimethy lamino)prop

an-2-yl)phenyl)-8-hydroxythieno

1 172 0.31 0.65 0.33 0.65 - [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(l-aminopropan-2-yl)-3-flu

orophenyl)-8-hydroxythieno[2,3-

1 174 0.16 0.12 0.27 1.2 - c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

henyl)-6-bromo-8-hydroxythieno

1 176 0.024 0.038 0.027 0.1 - [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -aminopropan-2-yl)-3-flu

orophenyl)-8-methoxythieno[2,3

1 179 0.45 0.86 0.63 1.9 - -c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-( 1 -aminopropan-2-yl)ph

enyl)-6-chloro-8-hydroxythieno[

1 181 0.1 0.21 0.1 1 0.6 - 2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-hydroxy-9-(4-( 1 -(methy la

mino)propan-2-yl)phenyl)thieno[

1 187 0.19 0.19 0.2 0.32 - 2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-(l -(dimethylamino)pro

pan-2-yl)phenyl)-8-hydroxythien

1 188 0.16 0.29 0.16 0.43 - o [2,3-c]quinolin-4(5H)-one

hydrochloride (R)-8-methoxy-9-(4-( 1 -(methy la

mino)propan-2-yl)phenyl)thieno[

1 189 0.69 1.3 0.59 1.3 - 2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(l -aminopropan-2-yl)-3-flu

orophenyl)-8-hydroxy-6-methylt

1 190 0.015 0.019 0.021 0.1 1 - hieno [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)phenyl)-8-hy

1 191 droxy-6-methylthieno[2,3-c]quin 0.064 0.073 0.12 0.48 - olin-4(5H)-one hydrochloride

9-(4-(l -(dimethylamino)propan-

2-yl)-3-fluorophenyl)-8-hydroxy

1 193 -6-methylthieno 0.14 0.24 0.13 0.33 -

[2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-8-hydroxy-9-(4-( 1 -(methy la

mino)propan-2-yl)phenyl)thieno[

1 197 0.43 0.54 0.62 1 - 2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)p

henyl)-6_:chloro-8-methoxythien

1201 0.053 0.12 0.046 0.14 - o[2,3-c]quinolin-4(5H)-one

hydrochloride

N-(l -chloropropan-2-yl)-4-(8-hy

droxy-4-oxo-4,5-dihydrothieno[2

1204 0.16 1.9 0.71 15 - ,3-c]quinolin-9-yl)benzenesulfon

amide

9-(4-(3-(aminornethyl)pentan-3- yl)phenyl)-8-hydroxythieno[2,3-

1209 0.49 1 0.48 1.2 - c]quinolin-4(5H)-one

hydrochloride

9-(4-(aminomethyl)phenyl)-8-hy

1212 droxy-6-methylthieno[2,3-c]quin 0.12 0.2 0.15 0.63 - olin-4(5H)-one hydrochloride

9-(4-(2-aminoethyl)-3-fluorophe

nyl)-6-bromo-8-hydroxythieno[2

1213 0.23 0.38 0.36 1.7 - ,3-c]quinolin-4(5H)-one

hydrochloride

(S)-8-hydroxy-6-methyl-9-(4-(l - (methy lamino)propan-2-y l)phen

121 5 0.14 0.26 0.15 0.5 - yl)thieno[2,3-c]quinolin-4(5H)-o

ne hydrochloride

9-(4-(2-aminoethyl)-3-fluorophe

nyl)-8-methoxy-6-methylthieno

1216 0.21 0.46 0.28 0.64 - [2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-am inoethy l)-3-fluorophe

121 7 nyl)-8-hydroxy-6-methylthieno[ 0.065 0.084 0.14 0.48 - 2,3-c]quinolin-4(5H)-one hydrochloride

9-(4-(2-am inoethy l)-3 -fluorophe

nyl)-6-chloro-8-methoxythieno[2

1218 0.55 1.2 0.62 1.3 - ,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)-3-fluorophe

nyl)-6-chloro-8-hydroxythieno[2

1219 0.1 0.18 0.17 0.88 - ,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)-2-bromo-5- hydroxyphenyl)-8-hydroxythien

1224 0.98 0.77 0.49 1.5 - o[2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-( 1 -aminoethy l)pheny 1)- 8-hydroxy-6-methylthieno[2,3-c]

1225 0.091 0.16 0.1 0.38 - quinolin-4(5H)-one

hydrochloride

3-(4-(8-hydroxy-6-methy 1-4-oxo

1226 -4,5-dihydrothieno[2,3-c]quinoli 0.59 1.2 0.49 1 .3 - n-9-yl)phenyl)propanenitrile

9-(4-( 1 -amino-2-methy lpropan-2

-yl)phenyl)-8-hydroxy-6-methylt

1228 0.15 0.33 0.16 0.81 - hieno [2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-( 1 -aminopropan-2-y l)ph

enyl)-8-hydroxy-6-methylthieno[

1232 0.037 0.062 0.041 0.2 - 2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-amino- 1 -cyclopenty lethy

1236 l)phenyl)-8-hydroxythieno[2,3-c] 0.51 0.8 0.46 1 - quinolin-4(5H)-one

9-(4-(2-amino- l -cyclopenty lethy

l)phenyl)-8-methoxythieno[2,3-c

1239 1.5 1 .1 0.89 1 .7 - ]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminopropyl)phenyl)-8-h

1242 ydroxy-6-methylthieno[2,3-c]qui 0.1 1 0.15 0.12 0.42 - nolin-4(5H)-one hydrochloride

6-bromo-9-(3-fluoro-4-(2-(meth

1245 ylamino)ethyl)phenyl)-8-hydrox 0.72 1.3 0.85 2.5 - ythieno[2,3-c]quinolin-4(5H)-on

e hydrochloride

9-(4-( 1 -amino-2-methy lpropan-2

-yl)phenyl)-6-bromo-8-hydroxyt

1247 0.52 0.94 0.47 1.3 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride 9-(4-( 1 -(aminomethyl)cycloprop

yl)phenyl)-8-methoxy-6-methylt

1251 0.26 0.52 0.2 0.65 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(l -amino-3-methylbutan-2-

1252 yl)phenyl)-8-hydroxythieno[2,3- 0.25 0.21 0.16 0.42 - c]quinolin-4(5H)-one i

9-(4-( 1 -amino-3-methy lbutan-2- yl)phenyl)-8-methoxythieno[2,3-

1253 1.5 0.87 0.76 1.9 - c]quinolin-4(5H -one

hydrochloride

9-(4-( 1 -(aminomethyl)cycloprop

yl)phenyl)-8-hydroxy-6-methylt

1254 0.035 0.053 0.039 0.24 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(3-fluoro-4-(2-(methylamino)e

thyl)phenyl)-8-hydroxy-6-methy

1258 0.43 0.6 0.66 1.5 - lthieno[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(l -amino-2-methylpropan-2

-yl)phenyl)-6-chloro-8-hydroxyt

1260 0.43 0.93 0.5 1.7 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-hydroxy-6-methy l-9-(4-( 1 - (methylamino)ethyl)phenyl)thien

1262 0.039 -0.078 0.045 0.13 - o[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)-3-chlorophe

nyl)-8-methoxy-6-methylthieno[

1263 0.2 0.41 0.23 0.58 - 2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)-3-chlorophe

nyl)-8-hydroxy-6-methylthieno[

1264 0.032 0.046 0.075 0.17 - 2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-methoxy-6-methyl-9-(4-(l

-(methylamino)ethyl)phenyl)thie

1265 0.1 1 0.26 0.1 1 0.32 - no[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(2-aminoethyl)-3-chlorophe

nyl)-6-chloro-8-hydroxythieno[2

1268 0.077 0.12 0.13 0.38 - ,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-(l -amino-2-methylpropan-2

-yl)-3-fluorophenyl)-8-hydroxyt

1271 0.3 0.57 0.47 1.6 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -aminopropan-2-y l)-3-flu

orophenyl)-8-methoxy-6-methylt

1273 0.073 0.17 0.071 0.2 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

hydrochloride

(R)-8-methoxy-6-methy l-9-(4-( 1

-(methylamino)propan-2-yl)phen

1298 yl)thieno 0.064 0.14 0.068 0.16 -

[2,3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -(aminomethy l)cyc lobuty 1

)phenyl)-8-hydroxythieno[2,3-c]

1300 0.1 0.12 0.077 0.23 - quinolin-4(5H)-one

hydrochloride

8-hydroxy-6-methy l-9-(4-(piperi

1302 din-3-yl)phenyl)thieno[2,3-c]qui 0.74 0.83 0.97 1.5 - nolin-4(5H)-one hydrochloride

(S)-9-(4-( 1 -aminopropan-2-y l)-3

-fluorophenyl)-8-hydroxy-6-met

1303 0.081 0.13 0.092 0.51 - hylthieno[2,3-c]quinolin-4(5H)-o

ne

(S)-9-(4-( 1 -aminopropan-2-y l)-3

-fluorophenyl)-8-hydroxy-6-met

1304 - 0.12 0.099 0.34 0.074 hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrobromide

(R)-9-(4-( 1 -aminopropan-2-y l)p

henyl)-8-methoxy-6-methylthien

1305 0.021 0.04 0.02 0.064 - o [2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-hy droxy-6-methy l-9-(4-( 1 -

(methylamino)propan-2-yl)phen

1306 yl)thieno - 0.035 0.02 0.073 0.033

[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-hydroxy-6-methyl-9-(4-( l -

(methylamino)propan-2-yl)phen

1307 yl)thieno 0.042 0.085 0.057 0.15 0.073

[2,3-c]quinolin-4(5H)-one

hydrobromide

9-(4-( 1 -aminobutan-2-y Opheny 1)

1309 -8-hydroxythieno[2,3-c]quinolin- 0.094 0.066 0.065 0.21 - 4(5H)-one hydrochloride

(S)-9-(4-(l -aminopropan-2-yl)-3

-fluorophenyl)-8-methoxy-6-met

1310 0.4 0.8 0.37 0.89 - hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrochloride

(R)-9-(4-( 1 -(dimethy lam ino)pro

pan-2-yl)-3-fluorophenyl)-8-hyd

131 1 0.037 0.07 0.045 0.1 1 - roxy-6-methylthieno[2,3-c]quino

lin-4(5H)-one hydrochloride 9-(4-( 1 -aminobutan-2-y l)phenyl)

-6-chloro-8-hydroxythieno[2,3-c

1312 0.058 0.076 0.054 0.23 - ]quinolin-4(5H)-one

hydrochloride

(R)-9-(3-fluoro-4-(l -(methylami

no)propan-2-yl)phenyl)-8-hydro

1315 0.024 0.041 0.034 0.1 - xy-6-methylthieno[2,3-c]quinoli

n-4(5H)-one hydrochloride

(R)-9-(3-fluoro-4-(l -(methylami

no)propan-2-yl)phenyl)-8-metho

1316 0.083 0.16 0.086 0.23 - xy-6-methylthieno[2,3-c]quinoli

n-4(5H)-one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)-3

-fluorophenyl)-8-methoxy-6-met

1317 0.036 0.072 0.042 0.1 - hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)-3

-fluorophenyl)-8-hydroxy-6-met

1 31 8 0.0084 0.015 0.01 5 0.063 - hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrochloride

(R)-9-(4-( 1 -aminopropan-2-y l)-3

-fluorophenyl)-8-hydroxy-6-met

1319 - 0.016 0.014 0.054 0.014 hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrobromide

9-(4-(l -(aminomethyl)cyclobutyl

)phenyl)-6-chloro-8-methoxythie

1321 1 . 2.2 0.8 2 - no[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -(d imethy lam ino)pro

pan-2-yl)phenyl)-8-hydroxy-6-m

1324 0.03 0.066 0.024 0.069 - ethylthieno[2,3-c]quinolin-4(5H)

-one hydrochloride

9-(4-(2-am inopropan-2-y l)pheny

l)-8-hydroxy-6-methylthieno[2,3

1330 0.19 0.43 0.1 8 0.76 - -c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)p

henyl)-8-hydroxy-2,6-dimethylth

1340 0.1 7 0.25 0.19 0.65 - ieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( l -aminopropan-2-yl)p

henyl)-8-methoxy-2,6-dimethylt

1341 0.86 0.98 0.57 0.88 - hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-6-chloro-9-(4-(l -(dimethyla

mino)propan-2-yl)phenyl)-8-hyd

1347 roxythieno 0.1 1 0.26 0.1 0.26 -

[2,3-c]quinolin-4(5H -one

hydrochloride (R)-9-(4-( 1 -aminobutan-2-y l)phe

nyl)-8-hydroxy-6-methylthieno[

1352 0.071 0.099 0.055 0.34 - 2,3-c]quiriolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)p

henyl)-2-chloro-8-hydroxy-6-me

1353 0.079 0.087 0.045 0.1 1 - thylthieno[2,3-c]quinolin-4(5H)- one hydrochloride

(R)-9-(4-( 1 -aminopropan-2-yl)p

henyl)-2-chloro-8-methoxy-6-me

1354 0.29 0.53 0.15 0.23 - thylthieno[2,3-c]quinolin-4(5H)- one hydrochloride

8-hydroxy-6-methy l-9-(4-(2-(me

thy lam ino)ethy l)pheny l)thieno[2,

1364 0.26 0.3 0.27 0.66 - 3-c]quinolin-4(5H)-one

hydrochloride

9-(4-( 1 -((dimethy lamino)methyl)

1372 cyclobutyl)phenyl)-8-hydroxy-6- - 0.084 0.035 0.1 0.075 methylthieno[2,3-c]quinolin-4(5

H)-one hydrochloride

(R)-9-(4-(l -aminopropan-2-yl)p

henyl)-2-fluoro-8-methoxy-6-me

1375 - 0.42 0.16 0.37 0.35 thylthieno[2,3-c]quinolin-4(5H)- one hydrochloride

(R)-9-(4-( 1 -(ethy l(methy l)amino

)propan-2-yl)phenyl)-8-hydroxy-

1379 6-methylthieno - 0.28 0.1 1 0.31 0.22

[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-8-hydroxy-6-methyl-9-(4-(.l- (methy lam ino)butan-2-y l)pheny 1

1380 - 0.24 0.096 0.37 0.19 )thieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(R)-9-(4-( 1 -am inopropan-2-y l)p

henyl)-2-fluoro-8-hydroxy-6-met

1383 - 0.057 0.029 0.1 0.048 hylthieno[2,3-c]quinolin-4(5H)-o

ne hydrochloride

9-(4-( 1 -(aminomethy l)cycloprop

yl)phenyl)-6-bromo-8-methoxyt

1391 - 1.2 0.67 1.4 0.99 hieno[2,3-c]quinolin-4(5H)-one

hydrochloride

(S)-9-(4-( 1 -(dimethylamino)prop

an-2-yl)-3-fluorophenyl)-8-hydr

1399 - 0.45 0.1 8 0.47 0.3 oxy-6-methylthieno[2,3-c]quinol

in-4(5H)-one hydrochloride

9-(4-((2-aminoethyl)(methyl)ami

no)phenyl)-8-hydroxy-6-methylt

1400 - 1 .4 0.9 2.8 1.1 hieno[2,3-c]quinolin-4(5H)-one

hydrochloride Our Ref.: ONC-A0925P

">100" in the table means over 100 micro M.

Industrial Applicability

The present invention provides a novel Tricyclic compound having PBK inhibitory effect. The compounds of the present invention may be used for pharmaceutical composition for inhibiting PBK. Such pharmaceutical compositions are suitable for treating or preventing cancer.

Claims

Claims:

1. A compound represented by general formula I:

I

or a pharmaceutically acceptable salt thereof,

hydrogen,

hydroxyl,

halogen,

cyano,

nitro,

amino,

Ci-C₆ alkyl,

C₂-C₆ alkenyl,

C₂-C₆ alkynyl,

C₃-C₁0 cycloalkyl,

C₃-C₁0 cycloalkenyl,

Ci-C₆ alkoxy,

Ce-Cio aryl,

indanyl,

heteroaryl,

3- to 8-membered heterocycloalkyl,

-OS0₂CH₃,

-OS0₂CF₃,

-CONH₂,

-OCONR¹⁰¹R¹⁰², wherein R¹⁰¹ and R¹⁰² each independently is hydrogen, Ci-C₆ alkyl, or R¹⁰¹ and R¹⁰² taken together form morpholinyl,

-OCOR¹⁰³, wherein R¹⁰³ represents Ci-C₆ alkyl, and

-OCOOR¹⁰⁴, wherein R¹⁰⁴ represents Ci-C₆ alkyl,

wherein substituent A is independently selected from the group consisting of:

hydroxyl;

oxo (=0);

cyano;

halogen;

Ci-C₆ alkyl optionally substituted with substituent B;

C₃-Cio cycloalkyl optionally substituted with cyano or Ci-C₆ alkyl substituted with -NR 31 R32 , wherein R 31 and R 32 each independently represent hydrogen or Ci-C₆ alkyl; -NR R , wherein R and R each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with hydroxyl, amino, di(Ci-C₆ alkyl)amino, -S0₂(Ci-C₆ alkyl), 3- to 8-membered heterocycloalkyl, or cyano; or a 3- to 8-membered heterocycloalkyl optionally substituted with -COOR¹⁰⁵ wherein R¹⁰⁵ represents Ci-C₆ alkyl;

Ci-C₆ alkoxy optionally substituted with halogen, 3- to 8-membered heterocycloalkyl

33 34 33 34

optionally substituted with Ci-C₆ alkyl, or -NR R wherein R and R each

independently represent hydrogen, Ci-C₆ alkylsulfonyl, or Ci-C₆ alkyl optionally substituted with Ci-C₆ alkylsulfonyl or di(Ci-C₆ alkyl)amino;

23 24

R , wherein 23 24

-SO₂NR R and R each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with hydroxyl, Ci-C₆ alkoxy, halogen, C₃-C₁₀ cycloalkyl, heteroaryl, or 35 36 wherein 35 36

-NR R R and R each independently represent hydrogen or Ci-C₆ alkyl; C₃-C₁₀ cycloalkyl optionally substituted with Ci-C₆ hydroxyalkyl; 3- to 8-membered heterocycloalkyl; or R²³ and R²⁴ taken together form 3- to 8-membered heterocycloalkyl optionally substituted with amino or halogen;

Ci-C₆ alkylsulfonyl optionally substituted with hydroxyl;

-NHS0₂(Ci-C₆ alkyl), wherein the carbon atoms are optionally substituted with

37 38 wherein 37 38

-NR R R and R each independently represent hydrogen or Ci-C₆ alkyl;

3- to 8-membered heterocycloalkyl optionally substituted with -NR³⁹R⁴⁰, wherein R³⁹ and R⁴⁰ each independently represent hydrogen, Ci-C₆ alkyl, or Ci-C₆ alkylsulfonyl; Ci-C₆ alkyl optionally substituted with -NR⁴¹R⁴², wherein R⁴¹ and R⁴²each independently represent hydrogen or Ci-C₆ alkyl; hydroxyl; or Ci-C₆ alkylsulfonyl;

-COOR¹¹, wherein R¹¹ represents hydrogen or Ci-C₆ alkyl; and

-COR¹², wherein R¹² represents Ci-C₆ alkyl; C₃-C₁₀ cycloalkyl; cyanomethyl;

aminomethyl; 25 26 25 26

-NR R wherein R and R each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with hydroxyl or -NR⁴³R⁴⁴, wherein R⁴³ and R⁴⁴ each independently represent hydrogen or Ci-C₆ alkyl; or 3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ alkyl;

wherein substituent B is independently selected from the group consisting of:

halogen;

hydroxyl;

Ci-C₆ alkoxy;

cyano;

cycloalkyl;

C₆-Cio aryl optionally substituted with cyano;

heteroaryl;

3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ alkyl, hydroxyl, amino, Ci-C₆ aminoalkyl, or Ci-C₆ alkyl substituted with C₂-C7 alkyloxycarbonylamino;

51 52 wherein 51 52

-NR R , R and R each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with Ci-C₆ alkylsulfonyl or 3- to 8-membered heterocycloalkyl optionally substituted with -COOR⁵³ wherein R⁵³ represents hydrogen or Ci-C₆ alkyl; 3- to 8-membered heterocycloalkyl; Ci-C₆ alkylsulfonyl; C₃-C₁₀ cycloalkyl; -COR⁵⁵ wherein R⁵⁵ represents C C₆ alkyl; -COOR⁵⁶ wherein R⁵⁶ represents C C₆ alkyl; or -CONR⁵⁷R⁵⁸ wherein R⁵⁷ and R⁵⁸ each independently represent hydrogen or Ci-C₆ alkyl;

-COOR⁵⁴, wherein R⁵⁴ represents hydrogen or Ci-C₆ alkyl;

wherein R¹⁰⁶ and R¹⁰⁷ each independently represent hydrogen, C C₆ alkyl, or C₃-C₁₀ cycloalkyl;

Ci-C₆ alkylsulfmyl; and Ci-C₆ alkylsulfonyl;

wherein R⁵ is hydrogen or Ci-C₆ alkyl; and

-χ— γ:

wherein is a structure selected from the group consisting of

(i) -S-CR⁷=CR⁶-,

(ii) -CH₂-CH₂-CH₂-,

(iii) -NR¹⁰⁸-CH=CR¹⁰⁹-, wherein R¹⁰⁸ represents hydrogen, or Ci-C₆ alkyl optionally substituted with hydroxyl, and R¹⁰⁹ represents hydrogen, CH₃, or phenyl substituted with Ci-C₆ aminoalkyl, and

(iv) -N=CH-S-,

wherein R⁶ is selected from the group consisting of:

hydrogen,

hydroxyl,

Ci-C₆ alkyl,

C₆-Cio aryl optionally substituted with hydroxyl, and

wherein R⁷ is selected from the group consisting of:

hydrogen;

71 72 71 72 halogen; Ci-C₆ alkyl optionally substituted with hydroxyl, -NR R wherein R and R each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with

dimethylamino; C3-C₁₀ cycloalkyl optionally substituted with amino or 3- to 8-membered heterocycloalkyl; or 3- to 8-membered heterocycloalkyl optionally substituted with Ci-C₆ aminoalkyl;

C₆-Cio aryl optionally substituted with hydroxyl;

C₆-Cio arylsulfonyl; and

-COR⁷³, wherein R⁷³ represents 3- to 8-membered heterocycloalkyl optionally substituted with amino; or -NR⁷⁴R⁷⁵ wherein R⁷⁴ and R⁷⁵ each independently represent hydrogen, 3- to 8-membered heterocycloalkyl, or C₃-Cio cycloalkyl optionally substituted with amino.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

χ^γ^ζτττζ _is ._S-CR⁷=CR⁶-.

3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R¹ is

hydrogen, cyano, Ci-C₆ alkyl optionally substituted with hydroxyl or halogen, C₃-Cio cycloalkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, or halogen.

4. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R² is

hydrogen, hydroxyl, halogen, Ci-C₆ alkoxy, or C₆-Cio aryl optionally substituted with hydroxyl.

5. The compound of claim 2 or a pharmaceutically acceptable salt, wherein R² is hydrogen, hydroxyl, halogen, Ci-C₆ alkoxy, or dihydroxyphenyl.

6. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R³ is

selected from the group consisting of: hydrogen; hydroxyl; Ci-C₆ alkyl optionally substituted with hydroxyl, halogen, or hydroxyethylamino; halogen; Ci-C₆ alkoxy optionally substituted with dimethylamino or morpholinyl; Ci-C₆ alkylphenyl, wherein the aliphatic carbons are optionally substituted with -NR⁵¹R⁵²; cyano; nitro; amino; 3- to 8-membered heterocycloalkyl optionally substituted with amino; heteroaryl; -OSO₂CH₃; -OSO₂CF₃;

-OCOR¹⁰³, wherein R¹⁰³ represents Ci-C₆ alkyl; -OCOOR¹⁰⁴ wherein R¹⁰⁴ represents Ci-C₆ alkyl; -OCONR¹⁰¹R¹⁰² wherein R¹⁰¹ and R¹⁰² each independentally represent hydrogen or Ci-C₆ alkyl, or R¹⁰¹ and R¹⁰² taken together form morpholinyl; and -CONH₂.

The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein when R³ is a 3- to 8-membered heterocycloalkyl, the 3- to 8-membered heterocycloalkyl is selected from the group consisting of piperidyl, pyrrolidinyl, morpholinyl, or piperazinyl and optionally substituted with amino; and when R³ is heteroaryl, the heteroaryl is pyridyl.

The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R⁴ is selected from the group consisting of hydrogen, hydroxyl, halogen, amino, Ci-C₆ alkyl, C₂-C6 alkenyl, C₃-C10 cycloalkyl, C₃-C10 cycloalkenyl, Ci-C₆ alkoxy, C₆-Cio aryl, indanyl, heteroaryl, and 3- to 8-membered heterocycloalkyl, and R⁴ is optionally substituted with substituent A.

The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein when R⁴ is heteroaryl, the heteroaryl is selected from the group consisting of pyridyl, lH-indazolyl, lH-tetrazolyl, [l,2,4]triazolo[l,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-b]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and

tetrahydroisoqumolyl); and wherein the 3- to 8-membered heterocycloalkyl is selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, azepanyl, morpholinyl, and 1,2,3,6-tetrahydropyridyl; wherein each of the groups of R⁴ is optionally substituted with substituent A-l;

wherein substituent A-l is selected from the group consisting of:

hydroxyl;

oxo;

cyano;

halogen;

Ci-C₆ alkyl optionally substituted with a substituent selected from the group consisting of substituent B-l;

C₃-C10 cycloalkyl optionally substituted with cyano, or Ci-C₆ alkyl substituted with -NR³¹R³²;

-NR^21AR^22A, wherein R^21A and R^22A each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with amino, di (Ci-C₆ alkyl) amino, -S0₂ (Ci-C₆ alkyl), piperidyl, or cyano; or piperidyl optionally substituted with -COOR¹⁰⁵;

Ci-C₆ alkoxy optionally substituted with halogen; a 3- to 8-membered heterocycloalkyl selected from piperidyl and piperazinyl, either of which is optionally substituted with Ci-C₆ alkyl; or -NR³³R³⁴;

-S0₂NR^23AR^24A , wherein R^23A and R^24A each independently represent hydrogen, Ci-C₆ alkyl optionally substituted with hydroxyl, Ci-C₆ alkoxy, halogen, C₃-C10 cycloalkyl, pyrazolyl, imidazolyl, or -NR³⁵R³⁶; C₃-C10 cycloalkyl optionally substituted with Ci-C₆ hydroxyalkyl; azetidinyl; pyrrolidinyl, or R^23A and R^24A taken together form pyrrolidinyl optionally substituted with amino or halogen;

Ci-C₆ alkylsulfonyl optionally substituted with hydroxyl;

-NHS0₂(Ci-C6 alkyl), wherein the carbon atoms are optionally substituted with

-NR³⁷R³⁸;

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, and tetrahydropyridyl any of which is optionally substituted with -NR³⁹R⁴⁰; Ci-C₆ alkyl optionally substituted with -NR⁴¹R⁴²; hydroxyl; or Ci-C₆ alkylsulfonyl;

lH-tetrazolyl; aryl optionally substituted with Ci-C₆ alkyl, wherein Ci-C₆ is the aliphatic carbons are optionally substituted with cyano or amino;

-COOR¹¹; and

-COR^12A, wherein R^12A represents piperazinyl optionally substituted with Ci-C₆ alkyl;

25 26 25 26

C₃-C₁₀ cycloalkyl; cyanomethyl; aminomethyl; -NR R wherein R and R each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with hydroxyl or -NR⁴³R⁴⁴; or Ci-C₆ alkylsulfonyl;

wherein substituent B-l is selected from the group consisting of:

halogen;

hydroxyl;

Ci-C₆ alkoxy;

cyano;

cycloalkyl;

phenyl optionally substituted with cyano;

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl any of which are optionally substituted with hydroxyl, amino, Ci-C₆ aminoalkyl, or Ci-C₆ alkyl optionally substituted with C₂-C₇ alky loxy carbony lamino ;

-NR^51AR^52A, wherein R^51A and R^52A each independently represent hydrogen; C C₆ alkyl optionally substituted with Ci-C₆ alkylsulfonyl or piperidyl optionally substituted with -COOR⁵³; piperidyl; C C₆ alkylsulfonyl; C₃-C₁₀ cycloalkyl; -COR⁵⁵, -COOR⁵⁶, or

-CONR⁵⁷R⁵⁸;

-COOR⁵⁴;

Ci-C₆ alkylsulfmyl; and

Ci-C₆ alkylysulfonyl.

The compound of claim 9, or a pharmaceutically acceptable salt thereof, wherein R⁴ is a group selected from group (p):

wherein group (p) is independently selected from the group consisting of:

hydrogen,

hydroxyl,

halogen,

Ci-C₆ alkyl optionally substituted with a substituent selected from the group consisting of substituent (a),

C₂-C₆ alkenyl optionally substituted with a substituent selected from the group consisting of substituent (b),

C₃-C₁₀ cycloalkyl,

C₃-C₁₀ cycloalkenyl,

Ci-C₆ alkoxy,

C₆-Cio aryl optionally substituted with a substituent selected from the group consisting of substituent (c),

indanyl optionally substituted with a substituent selected from the group consisting of substituent (d), heteroaryl selected from the group consisting of pyridyl, lH-indazolyl, lH-tetrazolyl, [l,2,4]triazolo[l,5-a]pyridyl, benzoimidazolyl, 2,3-dihydrobenzooxazolyl, pyrazolyl, pyrrolo[2,3-£]pyridyl, pyrimidinyl, indolinyl, furyl, thienyl, and tetrahydroisoqumolyl any of which is optionally substituted with a substituent selected from the group consisting of substituent (e); and

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and 1,2,3,6-tetrahydropyridyl any of which is optionally substituted with a substituent selected from the group consisting of substituent

(f);

wherein substituent (a) is selected from the group consisting of:

-NR^21AR^22A, wwherein R^21A and R^22A each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with piperidyl; or piperidyl optionally substituted with -COOR¹⁰⁵;

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl and piperidyl either of which is optionally substituted with Ci-C₆ alkyl optionally substituted with -NR⁴¹R⁴² or -NR³⁹R⁴⁰ wherein R³⁹ and R⁴⁰ each independently represent hydrogen or Ci-C₆ alkyl; and

-NHS0₂(Ci-C₆ alkyl);

wherein substituent (b) is selected from the group consisting of:

-COOR¹¹;

-NR^21aR^22a, wherein R^21a and R^22a each independently represent hydrogen, or Ci-C₆ alkyl optionally substituted with di(Ci-C₆ alkyl)amino or Ci-C₆ alkylsulfonyl;

3- to 8-membered heterocycloalkyl selected from the group consisting of azetidinyl, pyrrolidinyl, and piperidyl any of which are optionally substituted with -NR³⁹R⁴⁰, Ci-C₆ alkyl optionally substituted with -NR⁴¹R⁴², hydroxyl, or Ci-C₆ alkylsulfonyl;

cyano; and

Ci-C₆ alkoxy;

wherein substituent (c) is selected from the group consisting of:

hydroxyl;

cyano;

halogen;

-NR^21cR^22c , wherein R^21c and R^22c each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with amino or cyano;

Ci-C₆ alkoxy optionally substituted with halogen, 3- to 8-membered heterocycloalkyl selected from the group consistingn of piperidyl and piperazinyl either of which are optionally substituted with Ci-C₆ alkyl, or -NR³³R³⁴;

-S0₂NR^23cR^24c, wherein R^23c and R^24c each independently represent hydrogen, Ci-C₆ alkyl optionally substituted with hydroxyl, Ci-C₆ alkoxy, halogen, C₃-C10 cycloalkyl, pyrazolyl, imidazolyl, or -NR³⁵R³⁶; C₃-Ciocycloalkyl optionally substituted with Ci-C₆ hydroxyalkyl; azetidinyl, pyrrolidinyl, or wherein R^23c and R^24c takent together form pyrrolidinyl which is optionally substituted with amino or halogen;

Ci-C₆ alkylsulfonyl optionally substituted with hydroxyl;

-NR³⁷R³⁸;

piperazinyl optionally substituted with Ci-C₆ alkyl or Ci-C₆ alkylsulfonyl; piperidyl optionally substituted with hydroxyl;

lH-tetrazolyl;

1 , 2, 3, 6-tetrahydropyridyl; and

-COR^12c, wherein R^12c represents piperazinyl which is optionally substituted with Ci-C₆ alkyl, C₃-C₁₀ cycloalkyl, cyanomethyl, aminomethyl, -NR²⁵R²⁶, or Ci-C₆ alkyl; and

wherein substituent B-c is selected from the group consisting of:

halogen;

hydroxyl;

methoxy;

cyano;

C₃-C₁₀ cycloalkyl;

3- to 8-membered heterocycloalkyl selected from the group consisting of pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, and oxetanyl, any of which is optionally substituted with Ci-C₆ alkyl, hydroxyl, amino, Ci-C₆ aminoalkyl, or Ci-C₆ alkyl substituted with C₂-C7 alkyloxycarbonylamino;

-NR^51cR^52c, wherein R^51c and R^52c each independently represent hydrogen; Ci-C₆ alkyl optionally substituted with Ci-C₆ alkylsulfonyl, or piperidyl optionally substituted with -COOR⁵³; piperidyl; Ci-Cealkylsulfonyl; C₃-C₁₀ cycloalkyl; -COR⁵⁵; or -CONR⁵⁷R⁵⁸;

-COOR⁵⁴;

-CONH₂;

-SO₂NR¹⁰⁶R¹⁰⁷;

Ci-C₆ alkylsufmyl; and

Ci-C₆ alkylsulfonyl; wherein substituent (d) is selected from the group consisting of:

-NR^21dR^22d, wherein R^21d and R^22d each independently represent hydrogen or Ci-Q alkyl;

wherein substituent (e) is selected from the group consisting of:

hydroxyl;

oxo;

cyano;

C3-C₁₀ cycloalkyl optionally substituted with cyano;

-NR^21eR^22e, wherein R^21e and R^22e each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with amino;

piperidyl;

Ci-C₆ alkoxy optionally substituted with -NR³³R³⁴;

Ci-Ce alkyl optionally substituted with cyano; -NR^51eR^52e, wherein R^51e and

R^52e each independently represent hydrogen, Ci-C₆ alkyl, or -COOR⁵⁶; morpholinyl; or cyanophenyl;

wherein substituent (f) is selected from the group consisting of:

Ci-C₆ alkyl optionally substituted with -NR^51fR^52f, wherein R^51f and R^52f each independently represent hydrogen, Ci-C₆ alkyl, or -COOR⁵⁶; and

Ci-C₆ alkylsulfonyl; wherein substituent (g) is aryl optionally substituted with Ci-C₆ alkyl having the aliphatic carbons optionally substituted with cyano or amino.

1 1. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R⁶ is

hydrogen; hydroxyl; Ci-C₆ alkyl; phenyl optionally substituted with 1 to 3 hydroxyls;

piperidyl optionally substituted with amino; or piperazinyl.

12. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R⁷ is hydrogen; Ci-C₆ alkyl optionally substituted with hydroxyl or piperidyl; or halogen.

13. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R⁷ is

hydrogen;

Ci-Ce alkyl optionally substituted with hydroxyl; -NR^71AR^72A wherein R^71A and

R^72Aeach independently represent hydrogen, Ci-C₆ alkyl optionally substituted with dimethylamino, C3-C₁₀ cycloalkyl optionally substituted with amino, or piperidyl; or 3- to 8-membered heterocycloalkyl selected from the group consisting of piperidyl and morpholinyl either of which is optionally substituted with Ci-C₆ aminoalkyl;

phenyl optionally substituted with 1 to 2 hydroxyls;

phenylsulfonyl; or

-COR^73A, wherein R^73A represents piperidyl optionally substituted with amino, or -NR^74AR^75A, wherein R^74A and R^75A each independently represent hydrogen, piperidyl, or C3-C₁₀ cycloalkyl optionally substituted with amino.

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

x— -Y— -z _is __CH2__CH2__CH2_

15. The compound of claim 14, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are hydrogen.

16. The compound of claim 14, or a pharmaceutically acceptable salt thereof, wherein R³ is hydroxyl or methoxy.

17. The compound of claim 14, or a pharmaceutically acceptable salt thereof, wherein R⁴ is hydrogen; phenyl substituted with Ci-C₆ alkyl substituted with -NR^51AR^52A, wherein R^51A and R^52A each independently represent hydrogen or Ci-C₆ alkyl, or -S0₂NR^53AR^54A, wherein R^53A and R^54A each independently represent hydrogen or Ci-C₆ alkyl optionally substituted with halogen or hydroxy; 1,2,3,6-tetrahydropyridyl; hydroxypyridyl; or methoxypyridyl.

18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

ΧΙΓΠΥΓΓΓΓΖ _is __NR108__CH=CR109_₅

R¹, R², and R⁴ are hydrogen, and

R³ is hydrogen, hydroxyl or Ci-C₆ alkoxy.

19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

X— Y— z _is __{N=CH S}_₅

R¹, R², and R⁴ are hydrogen, and

R³ is methoxy.

20. A compound selected from the group consisting of:

(1) 8-methoxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(2) 8-hydroxy-5-methylthieno[2,3-c]quinolin-4(5H)-one;

(3) 7 , 8 -dihy droxythieno [2 , 3 -c] quinolin-4(5H)-one;

(4) 7,8-dimethoxythieno[2,3-c]quinolin-4(5H)-one; (5) : 8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(6) : 7,9-dimethoxythieno[2,3-c]quinolin-4(5H)-one;

(7) : 7,9-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(8) : 7,8,9-trimethoxythieno[2,3-c]quinolin-4(5H)-one;

(9): 8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(10) : 7,8,9-trihydroxythieno[2,3-c]quinolin-4(5H)-one;

(11) : 9-(3-(2-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(12) : 8-chlorothieno[2,3-c]quinolin-4(5H)-one;

(13) : 4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(14): thieno[2,3-c]quinolin-4(5H)-one;

(15) : 8-fluorothieno[2,3-c]quinolin-4(5H)-one;

(16) : 8-nitrothieno[2,3-c]quinolin-4(5H)-one;

(17) : 8-(3-aminopiperidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

(18) : l-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(19): l,8-dihydroxythieno[2,3-c]quinolin-4(5H)-one;

(20) : 8-hydroxy-l-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(21) : (R)-8-(3-aminopyrrolidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

(22) : (S)-8-(3-aminopyrrolidin-l-yl)thieno[2,3-c]quinolin-4(5H)-one;

(23) : 8-(pyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

(24): 8-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(25) : l-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(26) : l-(3-aminopiperidin-l-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(27) : 8-morpholinothieno[2,3-c]quinolin-4(5H)-one ;

(28) : 8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(29): 8-hydroxy-2-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(30) :

(31) : 8-hydroxy-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(32) : 8-hydroxy- 1 -(piperazin- 1 -yl)thieno[2,3-c]quinolin-4(5H)-one;

(33):

N-((lR,4R)-4-aminocyclohexyl)-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-2-car boxamide;

(35) : 2-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(36):

2-(((lR,4R)-4-aminocyclohexylamino)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (37): 8-(piperazin-l-yl)thieno[2,3-c]quinolin-4(5H)-one; (38) : 8-hydroxy- 1 -methylthieno[2,3-c]quinolin-4(5H)-one;

(39) :

8- hydroxy-2-((piperidin-3-ylamino)methyl)thieno[2,3-c]quinolin-4(5H)-one;

7-hydroxythieno[2,3-c]quinolin-4(5H)-one;

9- bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

9-(3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

l-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

7- (3,4-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

8- hydroxy- 1 -methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

9- (3,5-dihydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

8-hydroxy-9-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

8- hydroxy-9-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

9- (3,4-difluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(S)-8-(3-aminopyrrolidin-l-yl)-2-(4-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one; 5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)picolinonitrile;

9-(6-aminopyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide;

9-(3-fluoro-4-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

8-hydroxy-2-(3-hydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(58) 9-(3,4-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(59) 9-(4-fluoro-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(60) 8-hydroxy-9-(3-hydroxy-5-(trifluoromethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (61) 8-hydroxy-9-(lH-indazol-6-yl)thieno[2,3-c]quinolin-4(5H)-one;

(62) 8- hydroxy-9-(3,4,5-trihydroxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(63) 9- (4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(64) 9-(4-(lH-tetrazol-5-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(65) 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfonamide; (66) 9-(3-chloro-4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(67) 9-(4-chloro-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(68) 9-(3,4-dichlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(69) 9-(4-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(70) 8- hydroxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(71) 9- (4-(difluoromethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (72) : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(73) : 9-(4-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(74) : 9-(3-aminophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(77) :

(78) : 8-methoxy-9-phenylthieno[2,3-c]quinolin-4(5H)-one;

(79) : 8-hydroxy-9-(naphthalen-2-yl)thieno[2,3-c]quinolin-4(5H)-one;

(80): 8-hydroxy-9-(4-(hydroxymethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(81) : 2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)acetonitrile;

(82) : 8-hydroxy-9-(4-(methylsulfonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(83) : 8-hydroxy-9-(pyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(84) : 8-hydroxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(85): 8-hydroxy-9-(4-hydroxy-3-methoxyphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(86) : 9-(3-fluoro-4-(morpholinomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(87) : 9-(3-(aminomethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(88) : 9-(4-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(89) : 9-(3-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(90): 9-(3-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(91) : 9-cyclohexenyl-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(92) : 9-(3,5-difluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(94) : 9-(3-(aminomethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(95): 9-(4-(aminomethyl)phenyl)-8-hydroxy-2-methylthieno[2,3-c]quinolin-4(5H)-one;

(96) : 9-cyclopropyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(97) : 9-([l,2,4]triazolo[l,5-a]pyridin-6-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(98) : 8-methoxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(99) : 9-cyclohexenyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(100):

8- methoxy-9-(4-(2-(piperidin-l-yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (101):

9- (4-(aminomethyl)phenyl)-8-hydroxy-2-(morpholinomethyl)thieno[2,3-c]quinolin- ne;

(102): 9-(lH-benzo[d]imidazol-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(103): 9-(4-(difluoromethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (104) :

9-(4-(aminomethyl)phenyl)-8-methoxy-2-(morpholinomethyl)thieno[2,3-c]quino one;

(105) :

8-hydroxy-9-(4-(2-(piperidin-l-yl)ethylamino)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(106) : 8-hydroxy-9-(4-(piperazin-l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(107) : 8-methoxy-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(108) : 8-hydroxy-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(109) :

(110) : tert-butyl

(111) : 8-methoxy-9-(4-(piperazin-l-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(112):

(113) :

(114) :

(115) :

(116) : 8-methoxy-9-(l-(piperidin-4-yl)-lH-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one; (117): 8-hydroxy-9-(l-(piperidin-4-yl)-lH-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(118) : 8-methoxythiazolo[4,5-c]quinolin-4(5H)-one;

(119) :

2-((4-(aminomethyl)piperidin-l-yl)methyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(120) :

(121) :

9-(4-(aminomethyl)phenyl)-8-hydroxy-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(123): 8-methoxy-9-(lH-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(124) : 8-hydroxy-9-(lH-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(126) :

N-(2-aminoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide; (127):

N-(2-aminoethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzamide; (128) : N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)acetamide;

(129) :

4-(8-hydroxy-4-oxo-2,3 ,4,5-tetrahydro- 1 H-cyclopenta[c]quinolin-9-yl)benzenesulfonamide;

(130) :

8-hydroxy-9-(4-(4-methylpiperazine- 1 -carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(131) :

8-methoxy-9-(4-(4-methylpiperazine-l-carbonyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(132) :

8-hydroxy-9-(4-((4-methylpiperazin-l-yl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (133):

8- methoxy-9-(4-((4-methylpiperazin- 1 -y^

(134) : (E)-9-(3-(diethylamino)prop-l-enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(135) :

(E)-9-(3-(4-(aminomethyl)piperidin^

H)-one;

(136) :

(E)-9-(3-(2-(diethylamino)ethylamino)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(137) :

N-(4-(8-hydroxy-4-oxo-2, 3 ,4,5-tetrahydro- 1 H-cyclopenta[c]quinolin-9-yl)phenyl)methanes ulfonamide;

(139) : tert-butyl

(l-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)piperidin-4-yl)methylcarb amate;

( 140) : 8-hydroxy-9-(4-(4-methylpiperazin- 1 -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(141) : 8-methoxy-9-(4-(4-methylpiperazin- 1 -yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

( 142) : 8-methoxy-9-( 1 -(methylsulfonyl)- 1 ,2,3 ,6-tetrahydropyridin-4-yl)thieno

[2,3-c]quinolin-4(5H)-one;

(143): (E)-9-(3-(diethylamino)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(144) : 9-(3-(4-(aminomethyl)piperidin-l-yl)propyl)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(145) :

(146) : 9-(4-(3-(diethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(147) :

(148):

(E)-9-(3-(4-(aminomethyl)piperidin-l-yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one; (149) :

(151) : 9-(4-(2-(ethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (152):

(E)-9-(3-(4-aminopiperidin-l-yl)prop-l-enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (153):

9-(l-(2-aminoethyl)-l,2,3,6-tetrahydropyridin-4-yl)-8-methoxythieno[2,3-c]quinolin-4( one;

(158) : 9-(4-(2-(dimethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (159): 8-methoxy-9-(4-(2-(piperidin- 1 -yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(160) :

8-methoxy-9-(3-(2-(4-methylpiperazin-l-yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(161) : 9-(3-(2-(diethylamino)ethoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (162): 9-(3-(3-(diethylamino)propoxy)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(163) : 9-(4-(2-(dimethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(166) : 9-(3-(2-(diethylamino)ethoxy)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (167):

8-hydroxy-9-(3-(2-(4-methylpiperazin-l-yl)ethoxy)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(168) :

(169) : 9-(4-(2-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(172) :

9-(l-(2-(dimethylamino)ethyl)-l,2,3,6-tetrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]qui^^ lin-4(5H)-one;

(173) :

N-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanesulfonamide; (174) :

9-( 1 -(2-(diethylamino)ethyl)- 1 ,2,3 ,6-tetrahydropyridin-4-yl)-8-hydroxythieno[2,3-c]quinoli n-4(5H)-one;

(175) : 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(176): 9-(4-(2-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(177) :

(178) :

N-(methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenethyl)methanesulfonamide; (179):

(180) :

8- hydroxy-9-(l,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)- one;

(181) :

9- (4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxy-2,3-dihydro-lH-cyclopenta[c]quinolin-4( 5H)-one;

(182) :

9-(4-(2-(dimethylamino)ethyl)phenyl)-8-methoxy-2,3-dihydro-lH-cyclopenta[c]quinolin-4( 5H)-one;

(188) : 8 -methoxy-9-(4-((methylamino)methyl)phenyl)thieno[2,3 -c] quinolin-4(5H)-one;

(189) : 9-(4-amino-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(190) : 3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(191): 9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(193) :

(194): 8-hydroxy-9-(4-(l -(pyrrolidin- 1 -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(195) : 9-(4-(l-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(197) :

N-(2-aminoethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzenesulfo namide; (198) :

N-(2-(dimethylamino)ethyl)-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)b nzenesulfonamide;

(199) :

(200) :

(202) :

(203) : 4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(204): 4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzonitrile;

(205) :

(E)-9-(3-(3-aminopyrrolidin- 1 -yl)prop- 1 -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(206) :

(207) : 8-methoxy-9-(5-methoxypyridin-3-yl)thieno[2,3-c]quinolin-4(5H)-one;

(208) :

8-methoxy-9-(5-methoxypyridin-3-yl)-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(209) :

9-(4-(3-aminopyrrolidin- 1 -ylsulfonyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(210) :

(211) : 9-(4-((diisopropylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (212):

(214) :

(215) :

(216) : 8-methoxy-9-(4-(l -(pyrrolidin- 1 -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (217): 9-(4-amino-3-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(218):

N-(2-methoxy-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanes ulfonamide; (219) : 9-(3,5-difluoro-4-hydroxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(220) :

(221):

9-(4-((4-(aminomethyl)piperidin-l-yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]qu olin-4(5H)-one;

(222):

9-(4-(2-(dimethylamino)ethyl)phenyl)-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one (223): 9-(3,5-difluoro-4-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(224) :

6-fluoro-8-methoxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(225) :

9-(4-(l-(dimethylamino)ethyl)phenyl)-6-fluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (226):

(E)-9-(3-(3-hydroxypyrrolidin- 1 -yl)prop- 1 -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-on e;

(228):

(E)-8-hydroxy-9-(3-(3-hydroxypyrrolidin-l-yl)prop-l-enyl)thieno[2,3-c]quinolin-4(5H)-one

(230) :

(E)-9-(3-(3-aminoazetidin- 1 -yl)prop- 1 -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(231) :

(232) : (S)-9-(4-(l-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(233): (S)-9-(4-(l-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(234) :

8- hydroxy-9-(5-hydroxypyridin-3-yl)-2,3-dihydro-lH-cyclopenta[c]quinolin-4(5H)-one;

(235) :

(236) :

8-methoxy-9-(4-(l-(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(237) :

9-(4-((3-aminopyrrolidin-l-yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(238) :

(E)-9-(3-(3-aminoazetidin- 1 -yl)prop- 1 -enyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (239) : (E)-9-(3-(ethylamino)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(240) :

(241):

9-(4-((3-aminopyrrolidin-l-yl)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(242) :

9-(4-((3-aminopiperidin-l-yl)methyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(243) :

8-hydroxy-9-(4-(l-(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(244) : (E)-9-(3-(3-aminopiperidin-l-yl)prop-l-enyl)-8-methoxythieno[2,3-c]

quinolin-4(5H)-one;

(245) :

(E)-9-(3-(3-aminopyrrolidin- 1 -yl)prop- 1 -enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(246) :

(E)-9-(3-(3-aminopiperidin-l-yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (247):

(248) :

8-methoxy-9-(4-(2-(2-(methylsulfonyl)ethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H )-one;

(249) :

(250) :

(251) :

(252) :

(253) : tert-butyl

(254) :

(255) :

(256) : 9-(4-(aminomethyl)phenyl)-6-fluoro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (257) : 9-(4-(aminomethyl)phenyl)-6-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(258) :

6-fluoro-8-hydroxy-9-(l,2,3,6-tetrahydropyridin-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(259) :

9-(4-((diethylamino)methyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(260) : 8-methoxy-9-(4-(l-(piperidin-l-yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(261) :

(262) : 8-hydroxy-9-(4-( 1 -(piperidin- 1 -yl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (263):

(E)-9-(3-(3-(dimethylamino)piperidin-l-yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinoH 5H)-one;

(264) :

(E)-9-(3-(3-(dimethylamino)pyrrolidin- 1 -yl)prop- 1 -enyl)-8-hydroxythieno[2,3-c]quinolin-4 (5H)-one;

(265) : 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(268) :

(E)-9-(3-(4-aminopiperidin-l-yl)prop-l-enyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(271) :

9-(3-chloro-4-((diethylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (272):

(R)-9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(273) : 9-(4-(3-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(274) : (R)-9-(4-(l-aminoethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(275) : (R)-9-(4-(l-aminoethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(276): 9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(277) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(278) :

9-(3-fluoro-4-((3-hydroxypyrrolidin-l-yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4 (5H)-one;

(279) :

9-(3 -fluoro-4-((3 -hydroxypyrrolidin- 1 -yl)methyl)phenyl)-8 -methoxythieno[2,3 -c] quinolin-4 (5H)-one;

(280) :

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2,2,2-trifluoroethyl)benzen esulfonamide; (281) :

(282) :

(283) :

(284):

9- (3-(3-(dimethylamino)pyrrolidin-l-yl)propyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(285) : 9-(l-(2-aminoethyl)-lH-pyrazol-4-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(286) :

9-(3-chloro-4-((diethylamino)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (287):

(288) : 9-(3-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(289) :

(291) : 9-(4-acetylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(292) :

(293) :

(294) : l,l-diethyl-3-(hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)urea; (295):

(296) : 9-(4-acetylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(297) :

(298) :

9-(3-(3-(dimethylamino)piperidin-l-yl)propyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(299) :

(300) :

9-(3-fluoro-4-(2-(methylsulfonamido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin -8-yl methanesulfonate; (301) :

(R)-N-(l-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methane sulfonamide;

(302) :

(R)-9-(4-(l-(methylsulfonamido)ethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl methanesulfonate;

(303) :

(304):

(305):

9-(4-(2-(dimethylamino)ethyl)phenyl)-7-fluoro-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (306):

(307) :

(308) :

(309) :

N-(2-chloro-4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzyl)-N -methyl methanesulfonamide;

(310) :

(311):

(313): 8-hydroxy-9-(4-(l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(314) : 9-(4-(l-(cyclopentylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(315) :

(316) :

(317) : 9-(5-(aminomethyl)furan-2-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(318) :

9-(3-chloro-4-((methylamino)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (319) : 9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(320) :

(321):

(322) :

(323) :

(324) :

(325) :

(330) : 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl

trifluoromethanesulfonate;

(332) :

(333):

(334):

(336) : 9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(337) : 9-(4-(l-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(340): 9-amino-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (341) :

9-(4-(l-(dimethylamino)ethyl)phenyl)-6,7-difluoro-8-hydroxythieno[2,3-c]quinolin one;

(342) :

(343) :

(344):

(345) : 9-(2-amino-2,3-dihydro-lH-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(346) : 9-(4-(l-(dimethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(347):

(S)-N-(l-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)methane sulfonamide;

(348):

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (349):

9-(4-(l-(dimethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (350):

(351):

(352) :

9-(2-(dimethylamino)-2,3-dihydro-lH-inden-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-o ne;

(354) : 8-methoxy-9-(l,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(5H)-one;

(355) : 3-(3-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile;

(356) :

9-(4-(l-(diethylamino)ethyl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(357) :

l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropanecarbonit rile;

(358) :

(360) : 3-(3-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitrile; (361) :

l-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)cyclopropanecarbonit rile;

(362) : 9-(2-amino-2,3-dihydro-lH-inden-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (363):

(364) :

9-(2-(dimethylamino)-2,3-dihydro-lH-m^

ne;

(365) : 9-(4-(l-(ethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(366) :

6-chloro-9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)

(367) : 9-(4-(cyclopropanecarbonyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (368): 9-(4-(aminomethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carboxami

(369) : 9-(2-aminoethyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(372) : 9-(l-ethylindolin-5-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(373): 9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(374) :

8- hydroxy-9-(2-methyl-l,2,3,4-tetrahydroisoquinolin-7-yl)thieno[2,3-c]quinolin-4(

(376) : 8-hydroxy-9-(l-methylindolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(377): 8-hydroxy-9-(indolin-5-yl)thieno[2,3-c]quinolin-4(5H)-one;

(378) : 9-(indolin-5-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(379) :

9- (4-(l-((dimethylamino)methyl)cyclopropyl)^

)-one;

(380):

4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-propylbenzenesulfonamide; (381):

(382):

(383):

4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-isopentylbenzenesulfonamid e; (384) :

(385) : 9-(4-(l-(ethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(386):

3- (4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)-3-oxopropanenitrile;

(387) : (E)-9-(2-ethoxyvinyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(388) :

N-(l-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethyl)acetamide; (389):

(390) :

(391) :

(1031): 8-methoxy-9-(4-(l-methoxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1032): 9-(4-(l-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1033) :

(1034) :

9- (2-(4-((dimethylamino)methyl)piperidin-l-yl)ethyl)-8-methoxythieno[2,3-c]quinolin-4 H)-one;

(1035) : tert-butyl

4-((2-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ethyl)amino)piperidine-l-ca rboxylate;

(1037):

(1038) : 3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1039) :

(1040) :

9-(4-(l-aminoethyl)phenyl)-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-6-carbonit rile;

(1041) : 9-(4-(l-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1042):

8-hydroxy-9-(2-(4-((methylamino)methyl)piperidin-l-yl)ethyl)thieno[2,3-c]quinolin-4(5H)- one; (1043) :

8-methoxy-9-(2-(4-((methylamino)methyl)piperidin-l-yl)ethyl)thieno[2,3-c]quinoH -one;

(1044) :

9-(2-(4-((dimethylamino)methyl)piperidin-l-yl)ethyl)-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1045) : 9-(4-(l-hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1046) :

(R)-8-methoxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1047): (R)-8-(4-(l -aminoethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1048) : (R)-tert-butyl

(l-(4-(4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl)phenyl)ethyl)carbamate;

(1050) : (R)-8-(4-(l-(dimethylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1051):

8- hydroxy-9-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1052) :

(1053) : 8-hydroxy-9-(4-(l-hydroxypropyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1057) :

(1058) :

(1059) : 9-(6-(l-aminoethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1060) : 9-(4-(4-hydroxybutyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1061):

(1062) :

(1063) :

(1064) :

(1065):

9- (6-(l-(diethylamino)ethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1066) 9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1067) 9-(6-(l-aminoethyl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1068) 8-hydroxy-9-(4-(4-hydroxybutyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1069) :

9-(4-(3-amino-l-hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1070) :

9-(6-(l-(dimethylamino)ethyl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1071) :

9-(6-(l-(dimethylamino)ethyl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1072):

4-((4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-lH-pyrazol-l-yl)methyl)be nzonitrile;

(1073) : 8-aminothieno[2,3-c]quinolin-4(5H)-one;

(1074) : 9-(4-((lH-pyrazol-l-yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1075): 9-(6-(l-aminoethyl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1076) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl dimethy lc arb amate ;

(1077) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl isopropyl carbonate;

(1078):

9-(4-((lH-imidazol-l-yl)methyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1079):

(1080):

(1081) :

(1082) :

(S)-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1084) :

(1085) :

(1086) : 9-(4-((lH-pyrazol-l-yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1087):

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-on e; (1088) : 9-(4-(l-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1089) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl morpholine-4-carboxylate;

(1090) :

N-(2-hydroxyethyl)-4-(8-methoxy-4-oxo-2,3 ,4,5-tetrahydro- 1 H-cyclopenta[c]quinolin-9-yl) benzenesulfonamide;

(1091) : 8-bromothieno[2,3-c]quinolin-4(5H)-one;

(1092) : 9-(4-(2-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one

(1093) : 9-(4-(2-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1094):

(1095) : 9-(4-(2-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1096) :

8-methoxy-9-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-^

(1098) :

9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1099) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-8-yl acetate; (1100):

9-(l-(l-(dimethylamino)propan-2-yl)-lH-pyrazol-4-yl)-8-methoxythieno[2,3-c]quinolin^ H)-one;

(1101):

9-(4-((lH-imidazol-l-yl)methyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1102):

9-(4-(aminomethyl)phenyl)-8-(2-morpholinoethoxy)thieno[2,3-c]quinolin-4(5H

(1103) :

8-hydroxy-9-(l-(2-morpholinoethyl)-lH-pyrazol-4-yl)thieno[2,3-c]quinolin-4(5H)-one;

(1104) :

N-(2-(lH-pyrazol-l-yl)ethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)be nzenesulfonamide;

(1105) :

8- hydroxy-9-(4-(2,2,2-trifluoro-l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1106) : 9-(4-(2-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1107):

(1108):

9- (4-(2-(dimethylamino)propyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1109): 9-(4-(l-aminoethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1110):

9-(l-(l-(dimethylamino)propan-2-yl)-lH-pyrazol-4-yl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(1111): 9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1112):

9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1113) :

8- methoxy-9-(4-(2,2,2-trifluoro-l-hydroxyethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1114) :

N-(2-bromoethyl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-methylben zenesulfonamide;

(1115) :

(1116):

9- (4-(l-(aminomethyl)cyclopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(1117) :

(1118) : (R)-9-(4-(l-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1119) :

(1120): (S)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1121) : (S)-9-(4-(l-aminopropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1122) :

(R)-9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1123) :

(1124) : 9-(4-(l-aminoethyl)phenyl)-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8-carbonitrile;

(1125) : 9-(4-(l-aminoethyl)phenyl)-8-(hydroxymethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1126) :

(R)-6-chloro-9-(4-(l-(dimethylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1127) : (S)-9-(4-(l-(ethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1128) :

(1129) :

6-chloro-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one;

(1130) : 9-(4-(l-aminoethyl)phenyl)-6-ethynyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1131) : (R)-9-(4-(l-aminopropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1132) :

(1133): 9-(4-(2-aminoethyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1134) : 9-(4-(l-aminoethyl)phenyl)-8-(difluoromethyl)thieno[2,3-c]quinolin-4(5H)-one;

(1135) :

(R)-6-bromo-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne;

(1136):

9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1137) : 9-(4-butylphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1138) : 9-(4-butylphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1139) :

(1140) :

(1141) :

(1142) : 9-(4-(2-aminoethyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1143) :

9-(4-(3-(dimethylamino)-l-hydroxypropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(1144) :

N-(2-bromoethyl)-4-(6-chloro-8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benz enesulfonamide;

(1145) :

(1146) :

(1147):

(S)-8-methoxy-9-(4-(l-(methylamino)propyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1148) :

(S)-8-hydroxy-9-(4-(l-(methylamino)propyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1149) :

9-(4-(l-aminoethyl)phenyl)-8-(((2-hydroxyethyl)amino)methyl)thieno[2,3-c]quinolin-4(5H) -one;

(1150) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1151) :

(R)-9-(4-(l-(dimethylamino)propyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1152) : 8-hydroxy-9-(4-pentylphenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1153) : 9-(4-(2-aminoacetyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1154) :

(1155) : 8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1156) : 8-methoxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1157) :

(R)-9-(4-(l-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1158) :

(R)-9-(4-(l-aminopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1159) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1160) : (R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1161) : (R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1162) : 2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)butanenitrile;

(1163) : (S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1164) : (S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1165) :

(1166) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1167) :

(1168) :

(1169) :

(1170) :

6-chloro-8-methoxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1171) : 9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1172) :

(S)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-on e;

(1173) :

6-bromo-8-methoxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1174) :

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1175) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1176):

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (1177):

(1178):

9-(4-(2-(dimethylamino)ethyl)-3,5-difluoro

one;

(1179):

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1180):

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-6,7-dichloro-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(1181):

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1182):

(S)-6-chloro-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(1183):

6-bromo-8-hydroxy-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1185):

(1186): methyl

3-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanoate;

(1187):

(R)-8-hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1188):

(1189):

(R)-8-methoxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1190):

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H )-one;

(1191): 9-(4-(2-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1192): 9-(4-(2-aminoethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1193) :

(1194) :

(S)-6-chloro-8-hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4( 5H)-one;

(1195) :

(S)-6-chloro-9-(4-(l-(diethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4( 5H)-one;

(1196):

(S)-8-methoxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1197) :

(S)-8-hydroxy-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1198) :

4-(8-hydroxy-5-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)-N-(2-hydroxyethyl)be nzenesulfonamide;

(1199) :

(1200):

(1201) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)-one ;

(1202) : 9-(4-(l-aminobutan-2-yl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1203) :

9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxy-2-(phenylsulfonyl)thieno[2,3-c]quinolin-4(5 H)-one;

(1204):

N-(l-chloropropan-2-yl)-4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)benzen esulfonamide;

(1205) :

(1207) : 9-(4-(2-aminoethyl)-3-methoxyphenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1208) :

(1209) :

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1210) :

(R)-9-(4-(l-aminopropyl)phenyl)-8-hydroxy-5,6-dimethylthieno[2,3-c]quinolin-4(5H)-one; (1211) :

(1212) : 9-(4-(aminomethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1213):

(1214) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1215) :

(S)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4( 5H)-one;

(1216) :

(1217) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1218) :

(1219) :

9-(4-(2-aminoethyl)-3-fluorophenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1220):

(1221) :

(1222) :

(S)-8-methoxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

(1223) :

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one

(1224) :

9-(4-(2-aminoethyl)-2-bromo-5-hydroxyphenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one (1225):

(S)-9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1226):

(1227):

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one; (1228) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1229) :

(1230) :

(1231):

6-cyclopropyl-9-(4-(2-(dimethylamino)ethyl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quino lin-4(5H)-one;

(1232) :

(S)-9-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one ;

(1233) :

(S)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1234) :

(1235) :

(1236) :

9-(4-(2-amino-l-cyclopentylethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1237):

9-(4-(2-amino-l,l-dicyclopentylethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one (1238):

3-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propanenitr ile;

(1239):

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-cyclopropyl-8-hydroxythieno[2,3-c]quinolin -4(5H)-one;

(1241): 9-(4-(3-aminopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1242) : 9-(4-(2-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1243) : 9-(4-(2-aminopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1244) :

(1245) :

6-bromo-9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5 H)-one; (1246) :

6-bromo-9-(3-fluoro-4-(2-(methylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1247) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1248) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5 H)-one;

(1249):

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinoline-8 -carbonitrile;

(1250) : (R)-9-(4-(l-aminoethyl)phenyl)-8-hydroxy-6-vinylthieno[2,3-c]quinolin-4(5H)-one;

(1251) :

9-(4-(l -(aminomethyl)cyclopropyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H

)-one;

(1252) :

9-(4-(l-amino-3-methylbutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1253) :

(1254) :

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1255) : (R)-9-(4-(l-aminoethyl)phenyl)-6-ethyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1256):

(1257) :

(1258) :

(1259) :

6-bromo-9-(4-(l-(dimethylamino)-2-methylpropan-2-yl)phenyl)-8-hydroxythieno[2,3-c]qui nolin-4(5H)-one;

(1260) :

9-(4-(l-amino-2-methylpropan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H )-one;

(1261): 9-(4-(3-aminopropyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1262):

(R)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-o ne; (1263) :

(1264) :

9-(4-(2-aminoethyl)-3-chlorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1265):

(R)-8-methoxy-6-methyl-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H ne;

(1266) : 9-(4-(2-aminopropyl)phenyl)-6-ethyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1267) : (R)-9-(4-(l-aminoethyl)phenyl)-6-butyl-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1268):

(1269) : 9-(4-(2-aminopropyl)phenyl)-6-ethyl-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1270) :

(1271) :

(1272) :

(R)-6-ethyl-8-hydroxy-9-(4-(l-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(1273) :

9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H )-one;

(1274):

9-(4-(l-amino-3-methylbutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1275) :

(1276) :

9-(4-(l-aminopropan-2-yl)-3-chlorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1277) :

9-(4-(l-aminobutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1278):

9-(4-(l-amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1279) :

(1280) :

9-(4-(l-aminopropan-2-yl)-3-chlorophenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1281) : 9-(4-(2-amino-2-methylpropyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1282) : 9-(4-(2-amino-2-methylpropyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1283) :

9-(4-(l-amino-3-methylbutan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1284):

8-methoxy-6-methyl-9-(4-(3-methyl-l-(methyk

in-4(5H)-one;

(1285) :

8- hydroxy-6-methyl-9-(4-(3-methyl-l-(methylamino)butan-2-yl)phenyl)thieno[2,3-c]quinol in-4(5H)-one;

(1286) :

9- (3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1287) :

9-(4-(l-amino-2-methylpropan-2-yl)-3-fluorophenyl)-8-methoxythieno[2,3-c]quinolin-4(5^ )-one;

(1288) :

(1289):

(1290) :

(1291) :

(1292) :

9-(4-(2-amino-2-methylpropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H)-one ;

(1293) :

(1294) :

9-(3-fluoro-4-(3 -methyl- 1 -(methylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3

-c]quinolin-4(5H)-one;

(1295) :

9-(4-(l-(dimethylamino)-3-methylbutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1296):

9-(4-(l-(dimethylamino)-3-methylbutan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2 ,3-c]quinolin-4(5H)-one;

(1297):

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)- one; (1298) :

(1299) :

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1300) :

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1301) : 8-methoxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1302) : 8-hydroxy-6-methyl-9-(4-(piperidin-3-yl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1303):

(S)-9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1304) :

(1305) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-on

(1306) :

(R)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)propan-2-yl)phenyl)thieno[2,3-c]quinolin-4 (5H)-one;

(1307) :

(1308): 8-methoxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1309) : 9-(4-(l-aminobutan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-one;

(1310) :

(S)-9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1311):

(R)-9-(4-(l-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c] quinolin-4(5H)-one;

(1312):

9-(4-(l-aminobutan-2-yl)phenyl)-6-chloro-8-hydroxythieno[2,3-c]quinolin-4(5H)-one; (1313): 8-hydroxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1314) : 9-amino-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1315) :

(R)-9-(3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]q uinolin-4(5H)-one;

(1316):

(R)-9-(3-fluoro-4-(l-(methylamino)propan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]q uinolin-4(5H)-one; (1317) :

(R)-9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1318) :

(R)-9-(4-(l-aminopropan-2-yl)-3-fluorophenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1319) :

(1320):

9-((4-(2-aminoethyl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1321):

9-(4-(l-(aminomethyl)cyclobutyl)phenyl)-6-chloro-8-methoxythieno[2,3-c]quinolin-4(5H)- one;

(1322):

(R)- 1 -(4-(l -aminopropan-2-yl)phenyl)-8-methoxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5 H)-one;

(1323) : 8-hydroxy-3-(hydroxymethyl)-3H-pyrrolo[2,3-c]quinolin-4(5H)-one;

(1324) :

(R)-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1325) :

9-((4-(aminomethyl)phenyl)amino)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1326) :

9-((4-(aminomethyl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-o^

(1327) :

(1328) :

9-((4-(l-aminopropan-2-yl)phenyl)amino)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)- one;

(1329) :

9-(4-(2-aminopropan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1330) :

9-(4-(2-aminopropan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1331) :

(1332) :

9-(4-((R)- 1 -aminopropan-2-yl)phenyl)-8-hydroxy-2-(l -hydroxyethyl)thieno[2,3-c]quinolin-

4(5H)-one;

(1333) :

9-(4-((R)-l-aminopropan-2-yl)phenyl)-2-(l-hydroxyethyl)-8-methoxythieno[2,3-c]quinolin- 4(5H)-one; (1334) :

(1335) :

9-((3-(2-aminoethyl)phenyl)amino)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1336) :

9-((4-(2-aminoethyl)phenyl)amino)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1337) :

9-(4-(2-(ethylamino)propyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1338):

9-(4-(3-(aminomethyl)pentan-3-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1340):

(1341) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-8-methoxy-2,6-dimethylthieno[2,3-c]quinolin-4(5H) -one;

(1342) :

9-(4-((R)-l-aminopropan-2-yl)phenyl)-2-(l-hydroxyethyl)-8-methoxy-6-methylthieno[2,3-c ]quinolin-4(5H)-one;

(1343) :

(1344) :

(R)-9-(4-(l-aminobutan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1345) :

9-(3-chloro-4-(2-(ethylamino)ethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1346) :

(1347) :

(R)-6-chloro-9-(4-(l-(dimethylamino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quinolin- 4(5H)-one;

(1348) :

9-(4-(2-(ethylamino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1349) :

9-(4-(2-(ethylamino)ethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1350) :

9-(4-(2-(ethyl(methyl)amino)propyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one; (1351) :

2-(hydroxy(piperidin-4-yl)methyl)-8-m

(1352) :

(R)-9-(4-(l-aminobutan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1353):

(1354) :

(R)-9-(4-(l-aminopropan-2-yl)phenyl)-2-chloro-8-methoxy-6-methylthieno[2,3-c]quinolin- 4(5H)-one;

(1355) :

8- methoxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1356) :

9- (4-(2-(ethyl(methyl)amino)ethyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H) -one;

(1357) :

(1358) :

(1359) :

(1360) :

(R)-9-(4-(l-(dimethylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1361) :

(1362):

(1363):

8-hydroxy-6-methyl-9-(4-(2-(methylamino)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1365):

(1366):

(R)-9-(4-(l-(ethyl(methyl)amino)butan-2-yl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quin olin-4(5H)-one; (1367) :

(R)-9-(4-(l-(diethylamino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1368) :

(R)-9-(4-(l-(ethyl(methyl)amino)butan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1369) :

(1370):

(1371) :

9-(3-chloro-4-(2-(ethyl(methyl)amino)ethyl)phenyl)-8-hydroxythieno[2,3-c]quinolin-4(5H)- one;

(1372) :

9-(4-(l-((dimethylamino)methyl)cyclobutyl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quino lin-4(5H)-one;

(1373) :

(R)-9-(4-(l-aminopropyl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1374) :

9-(6-(2-aminoethoxy)pyridin-3-yl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1375) :

(1376) :

9-(6-(2-aminoethoxy)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one;

(1377) :

(1378) :

(1379) :

(R)-9-(4-(l-(ethyl(methyl)amino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quin olin-4(5H)-one;

(1380) :

(R)-8-hydroxy-6-methyl-9-(4-(l-(methylamino)butan-2-yl)phenyl)thieno[2,3-c]quinolin-4(5 H)-one;

(1381):

9-(4-(l-amino-2,2,2-trifluoroethyl)phenyl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one; (1382):

(R)-l-(4-(l-aminopropan-2-yl)phenyl)-8-hydroxy-3-methyl-3H-pyrrolo[2,3-c]quinolin-4(5 H)-one; (1383) :

(1384) :

(1385) :

9-(6-((2-aminoethyl)amino)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H one;

(1386):

(S)-6-chloro-9-(4-(l-(ethyl(methyl)amino)propan-2-yl)phenyl)-8-hydroxythieno[2,3-c]quin olin-4(5H)-one;

(1387) :

(S)-9-(4-(l-(dimethylamino)propan-2-yl)-3-fluorophenyl)-8-methoxy-6-methylthieno[2,3-c] quinolin-4(5H)-one;

(1388) :

(R)-9-(4-(l-(diethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4 (5H)-one;

(1389) :

(1390) :

9-(4-(l-amino-2,2,2-trifluoroethyl)phenyl)-6-bromo-8-methoxythieno[2,3-c]quinolin-4(5H) -one;

(1391) :

(1392) :

(1393):

(1394) :

8- hydroxy-6-methyl-9-(4-((methylsulfonyl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one;

(1395) :

(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)methanesulfo namide;

(1396) :

9- (4-((2-aminoethyl)(methyl)amino)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5 H)-one;

(1397):

(1398):

(R)-N-(2-(2-fluoro-4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)ph enyl)propyl)methanesulfonamide; (1399) :

(1400) :

9-(4-((2-aminoethyl)(methyl)amino)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4( H)-one;

(1401) :

9-(4-(l-(aminomethyl)cyclopropyl)phenyl)-6-bromo-8-hydroxythieno[2,3-c]quinolin-4(5H) -one;

(1402):

(1403):

8-hydroxy-6-methyl-9-(4-(2-(methylsulfinyl)ethyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one; (1404):

8- methoxy-6-methyl-9-(4-((methylsulfonyl)methyl)phenyl)thieno[2,3-c]quinolin-4(5H)-one

(1405) : 5-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)nicotinamide;

(1406) :

(1407) :

(1408) :

9-(6-(l-aminopropan-2-yl)pyridin-3-yl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-o ne;

(1409) :

2-(5-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)-2-met hylpropanenitrile;

(1410):

2-hydroxy-2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane-l- sulfonamide;

(1411) :

(1412) :

(1413) :

2-(4-(8-hydroxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane- 1 -sulfonamid e;

(1414) :

9- (4-(2-amino-l-fluoroethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-one; (1415) :

(1416) :

(1417) :

(1418):

(1419) :

2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propane-l-s ulfonamide;

(1420) :

9-(4-(2-amino-l-hydroxyethyl)phenyl)-8-methoxy-6-methylthieno[2,3-c]quinolin-4(5H)-on e;

(1421) :

9-(6-(l-amino-2-methylpropan-2-yl)pyridin-3-yl)-8-hydroxythieno[2,3-c]quinolin-4(5H)-on e;

(1422) :

N-cyclopropyl-l-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phe nyl)methanesulfonamide;

(1423):

2-(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)propanenitrile; (1424):

(R)-N-(2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pro py l)methanesulfonamide ;

(1425):

N-ethyl-l-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)me thanesulfonamide;

(1426):

9-(6-(l-aminopropan-2-yl)pyridin-3-yl)-8-methoxythieno[2,3-c]quinolin-4(5H)-one;

(1427):

N-cyclopropyl-l-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phe ny l)methanesulfonamide ;

(1428) :

l-(5-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)pyridin-2-yl)cyclopropanecar bonitrile;

(1429) :

N-ethyl-l-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)met hanesulfonamide; (1430) :

(1431) :

l-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)ethanesulfonamide;

(1432) :

(R)-N-(2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl)metha nesulfonamide;

(1433) :

(1434) :

(R)-N-(2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)prop y l)methanesulfonamide ;

(1435):

(1436) :

(R)-N-(2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propyl)-N-me thylmethanesulfonamide;

(1437) :

(R)-N-(2-(4-(8-hydroxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)prop yl)-N-methylmethanesulfonamide;

(1438) :

(R)-N-(2-(4-(8-methoxy-6-methyl-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)pro pyl)-N-methylmethanesulfonamide;

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising at least one compound of claim 1 or 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

22. The pharmaceutical composition of claim 21 which is available for preventing or

treating a PBK dependent disease.

23. The pharmaceutical composition of claim 22, wherein the PBK dependent disease is cancer.

24. A PBK inhibitor comprising at least one compound of claim 1 or 2, or a

pharmaceutically acceptable salt thereof.

25. A method for treating a PBK dependent disease in a subject, comprising administering to said subject an effective amount of a compound or a pharmaceutically acceptable salt thereof of claim 1 or 2.

26. A compound or pharmaceutically acceptable salt thereof of claim 1 or 2 for use in

treatment of a PBK dependent disease.

27. Use of a compound of claim 1 or 2 or a pharmaceutically acceptable salt thereof in