KR20010014369A - Urokinase inhibitors - Google Patents

Urokinase inhibitors Download PDF

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Publication number
KR20010014369A
KR20010014369A KR1019997012528A KR19997012528A KR20010014369A KR 20010014369 A KR20010014369 A KR 20010014369A KR 1019997012528 A KR1019997012528 A KR 1019997012528A KR 19997012528 A KR19997012528 A KR 19997012528A KR 20010014369 A KR20010014369 A KR 20010014369A
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South Korea
Prior art keywords
salt
trifluoroacetate
mono
aminoiminomethyl
naphthalenyl
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KR1019997012528A
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Korean (ko)
Inventor
게이어앤드류지.
맥클레란윌리엄제이.
락웨이토드더블유.
스튜어트켄트디.
웨이츠버그모쉬
웬트마이클디.
Original Assignee
스티븐 에프. 웨인스톡
아보트 러보러터리즈
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Publication of KR20010014369A publication Critical patent/KR20010014369A/en

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Abstract

화학식 Ⅰ의 화합물은 유로키나제 억제제이고 유로키나제가 역할을 하는 질환의 치료에 유용하다. 본원에는 또한, 유로키나제 억제용 조성물 및 포유동물에서 유로키나제를 억제하는 방법이 기재되어 있다.Compounds of formula I are urokinase inhibitors and are useful for the treatment of diseases in which urokinase plays a role. Also described herein are compositions for urokinase inhibition and methods for inhibiting urokinase in mammals.

화학식 ⅠFormula I

Description

유로키나제 억제제{Urokinase inhibitors}Eurokinase inhibitors

관련 출원 참조See related application

본원은 현재 계류중인 미국 특허원 제08/901,040호(1997. 7. 25. 출원)의 부분 연속 출원이다.This application is a partial consecutive application of pending US patent application Ser. No. 08 / 901,040, filed Jul. 25, 1997.

발명의 배경Background of the Invention

본 발명은 유로키나제 효소를 억제하는 나프트아미딘 화합물, 이러한 화합물을 함유하는 약제학적 조성물, 및 이들 화합물을 이용하는 의학적 치료 방법을 제공한다.The present invention provides naftamidine compounds that inhibit urokinase enzymes, pharmaceutical compositions containing such compounds, and methods of medical treatment using these compounds.

기술분야Technical Field

유로키나제[뇨-유형 플라스미노겐 활성인자 또는 uPA(생화학 국제 연합 분류 번호: EC3.4.21.31)]는 플라스미노겐 내의 단일 펩티드 결합에 고도로 특이적인 단백질 분해 효소이다. 플라스미노겐 활성화(유로키나제 효소에 의해 상기 결합이 절단됨)로 인해 강력한 일반 프로테아제인 플라스민이 형성된다.Eurokinase [urine-type plasminogen activator or uPA (University of Biochemistry Classification No. EC3.4.21.31)] is a protease that is highly specific for binding a single peptide in plasminogen. Plasminogen activation (the bond is cleaved by the eurokinase enzyme) forms plasmin, a potent general protease.

많은 세포 유형들은 세포외 매트릭스(ECM) 및 기저 막(BM) 등의 세포외 지지체 구조물의 플라스민 매개된 단백질 분해적 분해 또는 변형에 대한 주요 개시인자로서 유로키나제를 이용하고 있다. 세포들은 ECM 및 BM에 의해 제공된 신체 골격 내의 조직과 기관에 존재하고, 이동하며 서로 상호작용한다. ECM 내에서 또는 BM을 가로질러 세포가 이동하기 위해서는, 이러한 구조물을 국부적으로 단백질 분해적 분해시키거나 변형시킬 필요가 있으며, 이로써 세포가 상기 분해나 변형 이전에는 이용할 수 없었던 인접 영역을 침입하게 된다.Many cell types use urokinase as a major initiator for plasmin mediated proteolytic degradation or modification of extracellular support structures such as extracellular matrix (ECM) and basal membrane (BM). The cells are present in tissues and organs within the body skeleton provided by the ECM and BM, migrate and interact with each other. In order for cells to migrate within or across the ECM, these constructs need to be locally proteolytically degraded or modified, thereby invading adjacent regions that were not available prior to such degradation or modification.

유로키나제에 의해 개시된 세포 침입이 각종의 정상적인 생리학적 과정과 질병 상태의 생리학적 과정의 중심이 된다[참조: Blasi, F., Vassalli, J.D., and Dano, K.J. Cell Biol. 104:801-804, 1987; Dano, K., Anderson, P.A., Grondahl-Hansen, J., Kristensen, P., Nielsen, L.S., and Skriver, L.A dv. Cancer Res. 44:139-266, 1985; Littlefield, B.A. Ann. N.Y. Acad. Sci. 622:167-175, 1991; Saksela, O., Biochim. Biophys. Acta 823:35-65, 1985; Testa, J.E. and Quigley, J.P. Cancer Metast. Rev. 9:353-367, 1990]. 이러한 과정으로는 맥관형성(신생혈관화), 뼈 재구성, 자궁에 배 착상, 면역 세포의 염증 부위로의 침윤, 배란, 정자형성, 상처 치유 및 기관 분화 동안의 조직 개조, 섬유증, 종양 침입, 종양 세포의 1차 부위로부터 2차 부위로의 전이 확산 및 관절염에서의 조직 파열이 있지만, 이에 제한되지는 않는다. 예를 들면, 중간 정도의 효능만을 지닌 공지된 유로키나제 억제제인 아밀로라이드가 생체내에서 종양 전이를 억제하고[참조; Kellen, J.A., Mirakian, A. Kolin, A. Anticancer Res. 8:1373-1376, 1988] 시험관내에서 맥관형성/모세혈관망 형성을 억제하는 것으로 보고되었다[참조: Alliegro, M.C. and Glaser, B.M. J. Cell Biol. 115[3 Pt 2]:402a, 1991].Cell invasion initiated by urokinase is central to various normal physiological processes and physiological processes of disease states. Blasi, F., Vassalli, J.D., and Dano, K.J. Cell Biol. 104: 801-804, 1987; Dano, K., Anderson, P.A., Grondahl-Hansen, J., Kristensen, P., Nielsen, L.S., and Skriver, L.A dv. Cancer Res. 44: 139-266, 1985; Littlefield, B.A. Ann. N.Y. Acad. Sci. 622: 167-175, 1991; Saksela, O., Biochim. Biophys. Acta 823: 35-65, 1985; Testa, J.E. and Quigley, J.P. Cancer Metast. Rev. 9: 353-367, 1990. These processes include angiogenesis (neovascularization), bone reconstruction, implantation into the uterus, infiltration of immune cells into inflammatory sites, ovulation, spermatogenesis, tissue remodeling during wound healing and organ differentiation, fibrosis, tumor invasion, tumors Metastasis spread from primary site to secondary site of cells and tissue rupture in arthritis include, but are not limited to. For example, amylolide, a known urokinase inhibitor with only moderate efficacy, inhibits tumor metastasis in vivo [see; Kellen, J.A., Mirakian, A. Kolin, A. Anticancer Res. 8: 1373-1376, 1988] have been reported to inhibit angiogenesis / capillary network formation in vitro [Alliegro, M.C. and Glaser, B.M. J. Cell Biol. 115 [3 Pt 2]: 402a, 1991].

따라서, 유로키나제의 억제제는 기전에 근거한 혈관형성 억제, 관절염 치료, 소염, 망막증 치료(맥관형성 의존성 망막증에 대한 치료), 피임 및 종양 억제에 사용된다.Thus, inhibitors of urokinase are used for mechanism-based angiogenesis inhibition, arthritis treatment, anti-inflammatory, retinopathy treatment (treatment for angiogenic dependent retinopathy), contraception and tumor suppression.

발명의 요지The gist of the invention

본 발명의 주요 국면에서, 본 발명은 다음 화학식 Ⅰ의 화합물, 또는 이의 약제학적으로 허용되는 염, 에스테르 또는 프로드럭(prodrug)을 제공한다:In a main aspect of the invention, the invention provides a compound of formula (I), or a pharmaceutically acceptable salt, ester or prodrug thereof:

상기식에서,In the above formula,

Z는 (1) 질소;Z is (1) nitrogen;

(2) 메틴; 및(2) methine; And

(3) -NR1R2로 치환된 메틴으로 이루어진 그룹 중에서 선택되고;(3) selected from the group consisting of methine substituted with -NR 1 R 2 ;

A는 (1) 수소 및A is (1) hydrogen and

(2) -LARA로 이루어진 그룹 중에서 선택되며;(2) -L A R A is selected from the group consisting of;

B는 (1) 수소 및B is (1) hydrogen and

(2) -LBRB로 이루어진 그룹 중에서 선택되고;(2) -L B R B is selected from the group consisting of;

C는 (1) 수소 및C is (1) hydrogen and

(2) -LCRC로 이루어진 그룹 중에서 선택되며,(2) -L C R C is selected from the group consisting of

단 A, B 및 C 중의 하나 이상은 수소가 아니며, A가 수소가 아닌 경우, B 및 C 중의 하나 이상이 수소가 아니고;Provided that at least one of A, B and C is not hydrogen, and when A is not hydrogen, at least one of B and C is not hydrogen;

A, B 및 C에 대한 LA, LB및 LC는L A , L B and L C for A, B and C

(1) 공유 결합,(1) covalent bonds,

(2) -(CH2)m-,(2)-(CH 2 ) m- ,

(3) -NR1-,(3) -NR 1- ,

(4) -NR2C(X)NR3-,(4) -NR 2 C (X) NR 3- ,

(5) -C(X)-,(5) -C (X)-,

(6) -NR2C(X)-,(6) -NR 2 C (X)-,

(7) -C(X)NR2-,(7) -C (X) NR 2- ,

(8) -CH=CH-,(8) -CH = CH-,

(9) -C≡C-,(9) -C≡C-,

(10) -O-,(10) -O-,

(11) -S(O)t-(11) -S (O) t-

(12) -C≡C(CH2)nNR2C(X)-,(12) -C≡C (CH 2 ) n NR 2 C (X)-,

(13) -C(X)NR2(CH2)nC≡C-,(13) -C (X) NR 2 (CH 2 ) n C≡C-,

(14) -(CH2)nNSO2-,(14)-(CH 2 ) n NSO 2- ,

(15) -NR2SO2(CH2)nC≡C-,(15) -NR 2 SO 2 (CH 2 ) n C≡C-,

(16) -C≡C(CH2)nNR2SO2NR3-,(16) -C≡C (CH 2 ) n NR 2 SO 2 NR 3- ,

(17) -NR2SO2NR3(CH2)nC≡C-,(17) -NR 2 SO 2 NR 3 (CH 2 ) n C≡C-,

(18) -SO2NR2-,(18) -SO 2 NR 2- ,

(19) -NR2SO2-,(19) -NR 2 SO 2- ,

(20) -NR2SO2NR3-,(20) -NR 2 SO 2 NR 3- ,

(21) -N=N-,(21) -N = N-,

(22) -C(X)N(OR2)-,(22) -C (X) N (OR 2 )-,

(23) -N(OR2)C(X)-,(23) -N (OR 2 ) C (X)-,

(24) -HC=CH(CH2)nNR2C(X)-,(24) -HC = CH (CH 2 ) n NR 2 C (X)-,

(25) -(CH2)nNR2C(X)CH=CH-,(25)-(CH 2 ) n NR 2 C (X) CH = CH-,

(26) -CH=CH(CH2)nNSO2-,(26) -CH = CH (CH 2 ) n NSO 2- ,

(27) -NR2SO2(CH2)nCH=CH-,(27) -NR 2 SO 2 (CH 2 ) n CH = CH-,

(28) -(CH2)nNR2SO2NR3-,(28)-(CH 2 ) n NR 2 SO 2 NR 3- ,

(29) -NR2SO2NR3(CH2)nCH=CH-,(29) -NR 2 SO 2 NR 3 (CH 2 ) n CH = CH-,

(30) -NR2C(O)O-,(30) -NR 2 C (O) O-,

(31) -OC(O)NR2-,(31) -OC (O) NR 2- ,

(32) -CH=NO-,(32) -CH = NO-,

(33) -ON=CH- 및(33) -ON = CH- and

(34)[여기서, W는 (a) -O-, (b) -S-, (c) -NR1- 및 (d) -(CH2)m-으로 이루어진 그룹 중에서 선택된다]으로 이루어진 그룹 중에서 독립적으로 선택되며 (여기서, 각각의 작용성 그룹은 나프틸 또는 퀴놀릴 환에 결합된 말단인 오른쪽 말단과 RA, RB또는 RC에 결합된 말단인 왼쪽 말단으로 나타낸다);(34) Are independently selected from the group consisting of (a) -O-, (b) -S-, (c) -NR 1 -and (d)-(CH 2 ) m- . Wherein each functional group is represented by a right end which is the end bonded to a naphthyl or quinolyl ring and a left end which is the end bonded to R A , R B or R C ;

RA, RB및 RC는R A , R B and R C are

(1) 아릴;(1) aryl;

(2) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(2) arylalkoxy, wherein the alkylene group is a group of 1 to 6 carbon atoms;

(3) 탄소수 1 내지 10의 알킬;(3) alkyl having 1 to 10 carbon atoms;

(4) 탄소수 2 내지 10의 알케닐;(4) alkenyl having 2 to 10 carbon atoms;

(5) 탄소수 1 내지 6의 알콕시카보닐;(5) alkoxycarbonyl having 1 to 6 carbon atoms;

(6) 탄소수 2 내지 10의 알키닐;(6) alkynyl having 2 to 10 carbon atoms;

(7) 할로겐;(7) halogen;

(8) -NR1R2;(8) -NR 1 R 2 ;

(9) 헤테로사이클;(9) heterocycles;

(10) 탄소수 4 내지 12의 사이클로알케닐;(10) cycloalkenyl having 4 to 12 carbon atoms;

(11) 탄소수 3 내지 12의 사이클로알킬;(11) cycloalkyl having 3 to 12 carbon atoms;

(12) -NR1C(O)NR2R3; 및(12) -NR 1 C (O) NR 2 R 3 ; And

(13) -NR1C(O)R50(여기서, R50은 탄소수 1 내지 6의 알킬이다)로 이루어진 그룹 중에서 독립적으로 선택되며;(13) -NR 1 C (O) R 50 wherein R 50 is alkyl having 1 to 6 carbon atoms;

각 경우에, R1은In each case, R 1 is

(1) 수소;(1) hydrogen;

(2) N-보호 그룹;(2) N-protecting groups;

(3) 탄소수 1 내지 6의 알킬;(3) alkyl of 1 to 6 carbon atoms;

(4) 탄소수 2 내지 6의 알케닐;(4) alkenyl having 2 to 6 carbon atoms;

(5) 탄소수 2 내지 6의 알키닐;(5) alkynyl having 2 to 6 carbon atoms;

(6) 아릴;(6) aryl;

(7) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(7) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms;

(8) 탄소수 3 내지 8의 사이클로알킬; 및(8) cycloalkyl having 3 to 8 carbon atoms; And

(9) 사이클로알킬알킬[여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다]으로 이루어진 그룹 중에서 선택되고;(9) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms;

각 경우에, R2및 R3은In each case, R 2 and R 3 are

(1) 수소;(1) hydrogen;

(2) 탄소수 1 내지 6의 알킬;(2) alkyl having 1 to 6 carbon atoms;

(3) 탄소수 2 내지 6의 알케닐;(3) alkenyl having 2 to 6 carbon atoms;

(4) 탄소수 2 내지 6의 알키닐;(4) alkynyl having 2 to 6 carbon atoms;

(5) 아릴;(5) aryl;

(6) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(6) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms;

(7) 탄소수 3 내지 8의 사이클로알킬; 및(7) cycloalkyl having 3 to 8 carbon atoms; And

(8) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며;(8) independently selected from the group consisting of cycloalkylalkyl, wherein the cycloalkyl group is a group having 3 to 8 carbon atoms and the alkylene group is a group having 1 to 10 carbon atoms;

각 경우에, X는In each case, X is

(1) O 및(1) O and

(2) S로 이루어진 그룹 중에서 선택되고;(2) is selected from the group consisting of S;

각 경우에, m은 1 내지 5이고;In each case m is 1 to 5;

n은 0 내지 4이며;n is 0 to 4;

t는 0 내지 2이고,t is from 0 to 2,

각 경우에, 알킬, 알케닐, 알키닐, 아릴, 헤테로사이클, 사이클로알킬 및 사이클로알케닐 그룹은 임의로 치환된다.In each case, the alkyl, alkenyl, alkynyl, aryl, heterocycle, cycloalkyl and cycloalkenyl groups are optionally substituted.

본 발명은 또한, 화학식 Ⅰ의 화합물을 포함하는 치료학적 유효량의 조성물을 투여함으로써, 포유동물, 특히 사람에게서 유로키나제를 억제하는 방법에 관한 것이다.The invention also relates to a method of inhibiting urokinase in a mammal, in particular a human, by administering a therapeutically effective amount of a composition comprising a compound of formula (I).

본 발명은 또한, 치료학적 유효량의 화학식 Ⅰ의 화합물을 약제학적으로 허용되는 담체와 배합된 상태로 포함하는 약제학적 조성물에 관한 것이다.The invention also relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) in combination with a pharmaceutically acceptable carrier.

발명의 상세한 설명Detailed description of the invention

본 명세서 및 첨부된 청구의 범위 전반에 걸쳐 사용된 바와 같이, 다음 용어는 명시된 의미를 갖는다:As used throughout this specification and the appended claims, the following terms have the specified meanings:

본원에 사용된 바와 같은 용어 "알킬"은 단일 수소 원자의 제거에 의해 직쇄 또는 측쇄 포화 탄화수소로부터 유도된 1가 그룹을 나타내고, 메틸, 에틸, n- 및 이소-프로필, n-, 2급-, 이소- 및 3급-부틸, 네오펜틸 등으로 예시되며, (1) 탄소수 1 내지 6의 알콕시; (2) 탄소수 1 내지 6의 알킬설피닐; (3) 탄소수 1 내지 6의 알킬설포닐; (4) 아미노; (5) 아릴; (6) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (7) 아릴로일; (8) 아지도; (9) 카복스알데히드; (10) 탄소수 3 내지 8의 사이클로알킬; (11) 할로; (12) 헤테로사이클; (13) (헤테로사이클)옥시; (14) (헤테로사이클)오일; (15) 하이드록시; (16) N-보호된 아미노; (17) 니트로; (18) 옥소; (19) 탄소수 3 내지 8의 스피로알킬; (20) 탄소수 1 내지 6의 티오알콕시; (21) -CO2R2; (22) -C(O)NR2R3; (23) -SO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (24) -SO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (25) -NR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개, 3개 또는 4개의 치환체로 임의로 치환될 수 있다.The term "alkyl" as used herein denotes a monovalent group derived from straight or branched chain saturated hydrocarbons by the removal of a single hydrogen atom, and represents methyl, ethyl, n- and iso-propyl, n-, secondary-, Exemplified by iso- and tert-butyl, neopentyl and the like, (1) alkoxy having 1 to 6 carbon atoms; (2) alkylsulfinyl having 1 to 6 carbon atoms; (3) alkylsulfonyl having 1 to 6 carbon atoms; (4) amino; (5) aryl; (6) arylalkoxy, wherein the alkylene group is a group of 1 to 6 carbon atoms; (7) aryloyl; (8) azido; (9) carboxaldehyde; (10) cycloalkyl having 3 to 8 carbon atoms; (11) halo; (12) heterocycles; (13) (heterocycle) oxy; (14) (heterocycle) oils; (15) hydroxy; (16) N-protected amino; (17) nitro; (18) oxo; (19) spiroalkyl having 3 to 8 carbon atoms; (20) thioalkoxy having 1 to 6 carbon atoms; (21) -CO 2 R 2 ; (22) -C (O) NR 2 R 3 ; (23) —SO 2 R 4 wherein R 4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms ]; (24) -SO 2 NR 5 R 6 , wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the alkylene group has 1 to 6 carbon atoms Is independently selected from the group consisting of (25) -NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. And only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group] and optionally substituted with one, two, three or four substituents independently selected from the group consisting of: .

본원에 사용된 바와 같은 용어 "알카노일"은 본원에서 정의되는 바와 같은 카보닐 그룹을 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 알킬 그룹을 의미하고, 이의 예로는 포밀, 아세틸, 프로피오닐, 부타노일 등이 있다.As used herein, the term “alkanoyl” refers to an alkyl group, as defined herein, attached to a parent molecular group through a carbonyl group, as defined herein, examples of which are formyl, acetyl, propy O'Neill, Butanoyl and the like.

본원에 사용된 바와 같은 용어 "알케닐"은 1개의 수소 원자 제거에 의해 알켄으로부터 유도된 탄소-탄소 이중 결합을 함유하는 1가 직쇄 또는 측쇄 그룹을 나타내고, 에테닐, 1-프로페닐, 2-프로페닐, 2-메틸-1-프로페닐, 1-부테닐, 2-부테닐 등으로 예시되며, (1) 탄소수 1 내지 6의 알콕시; (2) 탄소수 1 내지 6의 알킬설피닐; (3) 탄소수 1 내지 6의 알킬설포닐; (4) 아미노; (5) 아릴; (6) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (7) 아릴로일; (8) 아지도; (9) 카복스알데히드; (10) 탄소수 3 내지 8의 사이클로알킬; (11) 할로; (12) 헤테로사이클; (13) (헤테로사이클)옥시; (14) (헤테로사이클)오일; (15) 하이드록시; (16) N-보호된 아미노; (17) 니트로; (18) 옥소; (19) 탄소수 3 내지 8의 스피로알킬; (20) 탄소수 1 내지 6의 티오알콕시; (21) -CO2R2; (22) -C(O)NR2R3; (23) -SO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (24) -SO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (25) -NR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개, 3개 또는 4개의 치환체로 임의로 치환될 수 있다.The term "alkenyl" as used herein denotes a monovalent straight or branched group containing carbon-carbon double bonds derived from alkenes by removal of one hydrogen atom, ethenyl, 1-propenyl, 2- Exemplified by propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like; (1) alkoxy having 1 to 6 carbon atoms; (2) alkylsulfinyl having 1 to 6 carbon atoms; (3) alkylsulfonyl having 1 to 6 carbon atoms; (4) amino; (5) aryl; (6) arylalkoxy, wherein the alkylene group is a group of 1 to 6 carbon atoms; (7) aryloyl; (8) azido; (9) carboxaldehyde; (10) cycloalkyl having 3 to 8 carbon atoms; (11) halo; (12) heterocycles; (13) (heterocycle) oxy; (14) (heterocycle) oils; (15) hydroxy; (16) N-protected amino; (17) nitro; (18) oxo; (19) spiroalkyl having 3 to 8 carbon atoms; (20) thioalkoxy having 1 to 6 carbon atoms; (21) -CO 2 R 2 ; (22) -C (O) NR 2 R 3 ; (23) —SO 2 R 4 wherein R 4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms ]; (24) -SO 2 NR 5 R 6 , wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the alkylene group has 1 to 6 carbon atoms Is independently selected from the group consisting of (25) -NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. And only two groups are not bonded to the nitrogen atom via a carbonyl group or a sulfonyl group] and optionally substituted with one, two, three or four substituents independently selected.

본원에 사용된 바와 같은 용어 "알콕시"는 산소 원자를 통하여 모 분자 그룹에 결합된 알킬 그룹을 나타낸다.The term "alkoxy" as used herein refers to an alkyl group bonded to the parent molecular group via an oxygen atom.

본원에 사용된 바와 같은 용어 "알콕시알킬"은 알콕시 그룹에 결합되어 있는 알킬 그룹을 나타낸다.The term "alkoxyalkyl" as used herein denotes an alkyl group which is bound to an alkoxy group.

본원에 사용된 바와 같은 용어 "알콕시카보닐"은 카보닐 그룹을 통하여 모 분자 그룹에 결합된 에스테르 그룹, 즉 알콕시 그룹을 나타내고, 메톡시카보닐, 에톡시카보닐 등으로 예시된다.The term "alkoxycarbonyl" as used herein refers to an ester group, ie, an alkoxy group, bonded to the parent molecular group via a carbonyl group, and is exemplified by methoxycarbonyl, ethoxycarbonyl and the like.

본원에 사용된 바와 같은 용어 "알킬렌"은 2개의 수소 원자 제거에 의해 직쇄 또는 측쇄 포화 탄화수소로부터 유도된 포화 2가 탄화수소 그룹을 나타내고, 메틸렌, 에틸렌, 이소프로필렌 등으로 예시된다.As used herein, the term “alkylene” refers to a saturated divalent hydrocarbon group derived from straight or branched chain saturated hydrocarbons by the removal of two hydrogen atoms, exemplified by methylene, ethylene, isopropylene and the like.

본원에 사용된 바와 같은 용어 "알킬설피닐"은 -S(O)- 그룹을 통하여 모 분자 그룹에 결합된 알킬 그룹을 나타낸다.The term "alkylsulfinyl" as used herein refers to an alkyl group bonded to the parent molecular group via an -S (O)-group.

본원에 사용된 바와 같은 용어 "알킬설피닐알킬"은 설피닐 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다.The term "alkylsulfinylalkyl" as used herein refers to an alkyl group, as defined herein, substituted with a sulfinyl group.

본원에 사용된 바와 같은 용어 "알킬설포닐"은 -SO2- 그룹을 통하여 모 분자 그룹에 결합된 알킬 그룹을 나타낸다.The term "alkylsulfonyl" as used herein refers to an alkyl group bonded to the parent molecular group via an -SO 2 -group.

본원에 사용된 바와 같은 용어 "알킬설포닐알킬"은 설포닐 그룹으로 치환된, 본원에 사용된 바와 같은 알킬 그룹을 나타낸다.The term "alkylsulfonylalkyl" as used herein refers to an alkyl group as used herein, substituted with a sulfonyl group.

본원에 사용된 바와 같은 용어 "알키닐"은 1개의 수소 원자 제거에 의해 알킨으로부터 유도된 탄소-탄소 삼중 결합을 함유하는, 탄소수 2 내지 6의 1가 직쇄 또는 측쇄 그룹을 나타내고, 에티닐, 1-프로피닐 등으로 예시되며, (1) 탄소수 1 내지 6의 알콕시; (2) 탄소수 1 내지 6의 알킬설피닐; (3) 탄소수 1 내지 6의 알킬설포닐; (4) 아미노; (5) 아릴; (6) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (7) 아릴로일; (8) 아지도; (9) 카복스알데히드; (10) 탄소수 3 내지 8의 사이클로알킬; (11) 할로; (12) 헤테로사이클; (13) (헤테로사이클)옥시; (14) (헤테로사이클)오일; (15) 하이드록시; (16) N-보호된 아미노; (17) 니트로; (18) 옥소; (19) 탄소수 3 내지 8의 스피로알킬; (20) 탄소수 1 내지 6의 티오알콕시; (21) -CO2R2; (22) -C(O)NR2R3; (23) -SO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (24) -SO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (25) -NR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개, 3개 또는 4개의 치환체로 임의로 치환될 수 있다.As used herein, the term “alkynyl” refers to a monovalent straight or branched chain group having 2 to 6 carbon atoms, containing carbon-carbon triple bonds derived from alkyne by removal of one hydrogen atom, ethynyl, 1 Exemplified by propynyl and the like, (1) alkoxy having 1 to 6 carbon atoms; (2) alkylsulfinyl having 1 to 6 carbon atoms; (3) alkylsulfonyl having 1 to 6 carbon atoms; (4) amino; (5) aryl; (6) arylalkoxy, wherein the alkylene group is a group of 1 to 6 carbon atoms; (7) aryloyl; (8) azido; (9) carboxaldehyde; (10) cycloalkyl having 3 to 8 carbon atoms; (11) halo; (12) heterocycles; (13) (heterocycle) oxy; (14) (heterocycle) oils; (15) hydroxy; (16) N-protected amino; (17) nitro; (18) oxo; (19) spiroalkyl having 3 to 8 carbon atoms; (20) thioalkoxy having 1 to 6 carbon atoms; (21) -CO 2 R 2 ; (22) -C (O) NR 2 R 3 ; (23) —SO 2 R 4 wherein R 4 is selected from the group consisting of (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms ]; (24) -SO 2 NR 5 R 6 , wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl, wherein the alkylene group has 1 to 6 carbon atoms Is independently selected from the group consisting of (25) -NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. And only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group] and optionally substituted with one, two, three or four substituents independently selected from the group consisting of: .

본원에 사용된 바와 같은 용어 "아미노"는 -NH2그룹을 나타낸다.The term "amino" as used herein refers to a -NH 2 group.

본원에 사용된 바와 같은 용어 "아미노알킬"은 아미노 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다.As used herein, the term “aminoalkyl” refers to an alkyl group, as defined herein, substituted with an amino group.

본원에 사용된 바와 같은 용어 "아릴"은 1개 또는 2개의 방향족 환을 갖는 모노- 또는 바이사이클릭 카보사이클릭 환 시스템을 나타내고, 페닐, 나프틸, 1,2-디하이드로나프틸, 1,2,3,4-테트라하이드로나프틸, 플루오레닐, 인다닐, 인데닐 등으로 예시되며, (1) 탄소수 1 내지 6의 알카노일; (2) 탄소수 1 내지 6의 알킬; (3) 탄소수 1 내지 6의 알콕시; (4) 알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (5) 탄소수 1 내지 6의 알킬설피닐; (6) 알킬설피닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (7) 탄소수 1 내지 6의 알킬설포닐; (8) 알킬설포닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (9) 아릴; (10) 아릴알킬(여기서, 알킬 그룹은 탄소수 1 내지 6의 그룹이다); (11) 아미노; (12) 탄소수 1 내지 6의 아미노알킬; (13) 아릴; (14) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (15) 아릴로일; (16) 아지도; (17) 탄소수 1 내지 6의 아지도알킬; (18) 카복스알데히드; (19) (카복스알데히드)알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (20) 탄소수 3 내지 8의 사이클로알킬; (21) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다); (22) 할로; (23) 탄소수 1 내지 6의 할로알킬; (24) 헤테로사이클; (25) (헤테로사이클)옥시; (26) (헤테로사이클)오일; (27) 하이드록시; (28) 탄소수 1 내지 6의 하이드록시알킬; (29) 니트로; (30) 탄소수 1 내지 6의 니트로알킬; (31) N-보호된 아미노; (32) N-보호된 아미노알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (33) 옥소; (34) 탄소수 1 내지 6의 티오알콕시; (35) 티오알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (36) -(CH2)qCO2R2(여기서, q는 0 내지 4이다); (37) -(CH2)qC(O)NR2R3; (38) -(CH2)qSO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (39) -(CH2)qSO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (40) -(CH2)qNR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]; (41) 옥소; (42) 퍼플루오로알킬; (43) 퍼플루오로알콕시; (44) 아릴옥시; (45) 사이클로알콕시; (46) 사이클로알킬알콕시; 및 (47) 아릴알콕시로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개, 3개 또는 4개의 치환체로 임의로 치환될 수 있다.As used herein, the term “aryl” refers to a mono- or bicyclic carbocyclic ring system having one or two aromatic rings, wherein phenyl, naphthyl, 1,2-dihydronaphthyl, 1, Exemplified by 2,3,4-tetrahydronaphthyl, fluorenyl, indanyl, indenyl, and the like, (1) alkanoyl having 1 to 6 carbon atoms; (2) alkyl having 1 to 6 carbon atoms; (3) alkoxy having 1 to 6 carbon atoms; (4) alkoxyalkyl, wherein alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (5) alkylsulfinyl having 1 to 6 carbon atoms; (6) alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (7) alkylsulfonyl having 1 to 6 carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (9) aryl; (10) arylalkyl, wherein the alkyl group is a group of 1 to 6 carbon atoms; (11) amino; (12) aminoalkyl of 1 to 6 carbon atoms; (13) aryl; (14) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (15) aryloyl; (16) azido; (17) azidoalkyl having 1 to 6 carbon atoms; (18) carboxaldehyde; (19) (carboxaldehyde) alkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; (20) cycloalkyl having 3 to 8 carbon atoms; (21) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms; (22) halo; (23) haloalkyl having 1 to 6 carbon atoms; (24) heterocycle; (25) (heterocycle) oxy; (26) (heterocycle) oils; (27) hydroxy; (28) hydroxyalkyl having 1 to 6 carbon atoms; (29) nitro; (30) nitroalkyl having 1 to 6 carbon atoms; (31) N-protected amino; (32) N-protected aminoalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (33) oxo; (34) thioalkoxy having 1 to 6 carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (36)-(CH 2 ) q CO 2 R 2 , where q is 0 to 4; (37)-(CH 2 ) q C (O) NR 2 R 3 ; (38)-(CH 2 ) q SO 2 R 4 , wherein R 4 is (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having from 1 to 6 carbon atoms Selected from the group consisting of; (39)-(CH 2 ) q SO 2 NR 5 R 6 wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl (where alkylene groups Is independently selected from the group consisting of 1 to 6 carbon atoms; (40)-(CH 2 ) q NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. Wherein only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group; (41) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy; (45) cycloalkoxy; (46) cycloalkylalkoxy; And (47) arylalkoxy, which may be optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of arylalkoxy.

본원에 사용된 바와 같은 용어 "아릴알킬"은 알킬 그룹을 통하여 모 분자 그룹에 결합된 알킬 그룹을 나타낸다.As used herein, the term “arylalkyl” refers to an alkyl group bonded to the parent molecular group through an alkyl group.

본원에 사용된 바와 같은 용어 "아릴알콕시"는 산소 원자를 통하여 모 분자 그룹에 결합된 아릴알킬 그룹을 나타낸다.The term "arylalkoxy" as used herein refers to an arylalkyl group bonded to the parent molecular group via an oxygen atom.

본원에 사용된 바와 같은 용어 "아릴옥시"는 산소 원자를 통하여 모 분자 그룹에 결합된 아릴 그룹을 나타낸다.The term "aryloxy" as used herein refers to an aryl group bonded to the parent molecular group via an oxygen atom.

본원에 사용된 바와 같은 용어 "아릴로일"은 카보닐 그룹을 통하여 모 분자 그룹에 결합된 아릴 그룹을 나타낸다.The term "aryloyl" as used herein refers to an aryl group bonded to the parent molecular group via a carbonyl group.

본원에 사용된 바와 같은 용어 "아지도"는 -N3그룹을 나타낸다.The term "azido" as used herein refers to a -N 3 group.

본원에 사용된 바와 같은 용어 "아지도알킬"은 아지도 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다.The term “azidoalkyl,” as used herein, refers to an alkyl group, as defined herein, substituted with an azido group.

본원에 사용된 바와 같은 용어 "카보닐"은 C=O 그룹을 나타낸다.As used herein, the term “carbonyl” refers to a C═O group.

본원에 사용된 바와 같은 용어 "카복스알데히드"는 -CHO 그룹을 나타낸다.As used herein, the term "carboxaldehyde" refers to a -CHO group.

본원에 사용된 바와 같은 용어 "(카복스알데히드)알킬"은 카복스알데히드 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다.As used herein, the term “(carboxaldehyde) alkyl” refers to an alkyl group, as defined herein, substituted with a carboxaldehyde group.

본원에 사용된 바와 같은 용어 "카복시"는 -CO2H 그룹을 나타낸다.The term "carboxy" as used herein refers to a -CO 2 H group.

본원에 사용된 바와 같은 용어 "카복시알킬"은 카복시 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다.The term "carboxyalkyl" as used herein, refers to an alkyl group, as defined herein, substituted with a carboxy group.

본원에 사용된 바와 같은 용어 "사이클로알킬"은 1가 포화 사이클릭 탄화수소 그룹을 나타내고, 사이클로프로필, 사이클로부틸, 사이클로펜틸, 사이클로헥실, 사이클로헵틸, 바이사이클로[2.2.1]헵틸 등으로 예시된다. 본 발명의 사이클로알킬 그룹은 (1) 탄소수 1 내지 6의 알카노일; (2) 탄소수 1 내지 6의 알킬; (3) 탄소수 1 내지 6의 알콕시; (4) 알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (5) 탄소수 1 내지 6의 알킬설피닐; (6) 알킬설피닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (7) 탄소수 1 내지 6의 알킬설포닐; (8) 알킬설포닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (9) 아릴; (10) 아릴알킬(여기서, 알킬 그룹은 탄소수 1 내지 6의 그룹이다); (11) 아미노; (12) 탄소수 1 내지 6의 아미노알킬; (13) 아릴; (14) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (15) 아릴로일; (16) 아지도; (17) 탄소수 1 내지 6의 아지도알킬; (18) 카복스알데히드; (19) (카복스알데히드)알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (20) 탄소수 3 내지 8의 사이클로알킬; (21) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다); (22) 할로; (23) 탄소수 1 내지 6의 할로알킬;(24) 헤테로사이클; (25) (헤테로사이클)옥시; (26) (헤테로사이클)오일; (27) 하이드록시; (28) 탄소수 1 내지 6의 하이드록시알킬; (29) 니트로; (30) 탄소수 1 내지 6의 니트로알킬; (31) N-보호된 아미노; (32) N-보호된 아미노알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (33) 옥소; (34) 탄소수 1 내지 6의 티오알콕시; (35) 티오알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (36) -(CH2)qCO2R2(여기서, q는 0 내지 4이다); (37) -(CH2)qC(O)NR2R3; (38) -(CH2)qSO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (39) -(CH2)qSO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (40) -(CH2)qNR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]; (41) 옥소; (42) 퍼플루오로알킬; (43) 퍼플루오로알콕시; (44) 아릴옥시; (45) 사이클로알콕시; (46) 사이클로알킬알콕시; 및 (47) 아릴알콕시로 이루어진 그룹 중에서 독립적으로 선택된 치환체로 임의로 치환될 수 있다.The term "cycloalkyl" as used herein refers to a monovalent saturated cyclic hydrocarbon group and is exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo [2.2.1] heptyl and the like. Cycloalkyl groups of the invention include (1) alkanoyl of 1 to 6 carbon atoms; (2) alkyl having 1 to 6 carbon atoms; (3) alkoxy having 1 to 6 carbon atoms; (4) alkoxyalkyl, wherein alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (5) alkylsulfinyl having 1 to 6 carbon atoms; (6) alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (7) alkylsulfonyl having 1 to 6 carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (9) aryl; (10) arylalkyl, wherein the alkyl group is a group of 1 to 6 carbon atoms; (11) amino; (12) aminoalkyl of 1 to 6 carbon atoms; (13) aryl; (14) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (15) aryloyl; (16) azido; (17) azidoalkyl having 1 to 6 carbon atoms; (18) carboxaldehyde; (19) (carboxaldehyde) alkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; (20) cycloalkyl having 3 to 8 carbon atoms; (21) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms; (22) halo; (23) haloalkyl of 1 to 6 carbon atoms; (24) heterocycle; (25) (heterocycle) oxy; (26) (heterocycle) oils; (27) hydroxy; (28) hydroxyalkyl having 1 to 6 carbon atoms; (29) nitro; (30) nitroalkyl having 1 to 6 carbon atoms; (31) N-protected amino; (32) N-protected aminoalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (33) oxo; (34) thioalkoxy having 1 to 6 carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (36)-(CH 2 ) q CO 2 R 2 , where q is 0 to 4; (37)-(CH 2 ) q C (O) NR 2 R 3 ; (38)-(CH 2 ) q SO 2 R 4 , wherein R 4 is (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having from 1 to 6 carbon atoms Selected from the group consisting of; (39)-(CH 2 ) q SO 2 NR 5 R 6 wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl (where alkylene groups Is independently selected from the group consisting of 1 to 6 carbon atoms; (40)-(CH 2 ) q NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. Wherein only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group; (41) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy; (45) cycloalkoxy; (46) cycloalkylalkoxy; And (47) may be optionally substituted with a substituent independently selected from the group consisting of arylalkoxy.

본원에 사용된 바와 같은 용어 "사이클로알케닐"은 1개 이상의 탄소-탄소 이중 결합을 갖는 1가 사이클릭 탄화수소 그룹을 나타낸다. 본 발명의 사이클로알케닐 그룹은 (1) 탄소수 1 내지 6의 알카노일; (2) 탄소수 1 내지 6의 알킬; (3) 탄소수 1 내지 6의 알콕시; (4) 알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (5) 탄소수 1 내지 6의 알킬설피닐; (6) 알킬설피닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (7) 탄소수 1 내지 6의 알킬설포닐; (8) 알킬설포닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (9) 아릴; (10) 아릴알킬(여기서, 알킬 그룹은 탄소수 1 내지 6의 그룹이다); (11) 아미노; (12) 탄소수 1 내지 6의 아미노알킬; (13) 아릴; (14) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (15) 아릴로일; (16) 아지도; (17) 탄소수 1 내지 6의 아지도알킬; (18) 카복스알데히드; (19) (카복스알데히드)알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (20) 탄소수 3 내지 8의 사이클로알킬; (21) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다); (22) 할로; (23) 탄소수 1 내지 6의 할로알킬; (24) 헤테로사이클; (25) (헤테로사이클)옥시; (26) (헤테로사이클)오일; (27) 하이드록시; (28) 탄소수 1 내지 6의 하이드록시알킬; (29) 니트로; (30) 탄소수 1 내지 6의 니트로알킬; (31) N-보호된 아미노; (32) N-보호된 아미노알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (33) 옥소; (34) 탄소수 1 내지 6의 티오알콕시; (35) 티오알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (36) -(CH2)qCO2R2(여기서, q는 0 내지 4이다); (37) -(CH2)qC(O)NR2R3; (38) -(CH2)qSO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (39) -(CH2)qSO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (40) -(CH2)qNR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]; (41) 옥소; (42) 퍼플루오로알킬; (43) 퍼플루오로알콕시; (44) 아릴옥시; (45) 사이클로알콕시; (46) 사이클로알킬알콕시; 및 (47) 아릴알콕시로 이루어진 그룹 중에서 독립적으로 선택된 치환체로 임의로 치환될 수 있다.As used herein, the term "cycloalkenyl" refers to a monovalent cyclic hydrocarbon group having at least one carbon-carbon double bond. Cycloalkenyl groups of the invention include (1) alkanoyl of 1 to 6 carbon atoms; (2) alkyl having 1 to 6 carbon atoms; (3) alkoxy having 1 to 6 carbon atoms; (4) alkoxyalkyl, wherein alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (5) alkylsulfinyl having 1 to 6 carbon atoms; (6) alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (7) alkylsulfonyl having 1 to 6 carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (9) aryl; (10) arylalkyl, wherein the alkyl group is a group of 1 to 6 carbon atoms; (11) amino; (12) aminoalkyl of 1 to 6 carbon atoms; (13) aryl; (14) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (15) aryloyl; (16) azido; (17) azidoalkyl having 1 to 6 carbon atoms; (18) carboxaldehyde; (19) (carboxaldehyde) alkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; (20) cycloalkyl having 3 to 8 carbon atoms; (21) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms; (22) halo; (23) haloalkyl having 1 to 6 carbon atoms; (24) heterocycle; (25) (heterocycle) oxy; (26) (heterocycle) oils; (27) hydroxy; (28) hydroxyalkyl having 1 to 6 carbon atoms; (29) nitro; (30) nitroalkyl having 1 to 6 carbon atoms; (31) N-protected amino; (32) N-protected aminoalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (33) oxo; (34) thioalkoxy having 1 to 6 carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (36)-(CH 2 ) q CO 2 R 2 , where q is 0 to 4; (37)-(CH 2 ) q C (O) NR 2 R 3 ; (38)-(CH 2 ) q SO 2 R 4 , wherein R 4 is (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having from 1 to 6 carbon atoms Selected from the group consisting of; (39)-(CH 2 ) q SO 2 NR 5 R 6 wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl (where alkylene groups Is independently selected from the group consisting of 1 to 6 carbon atoms; (40)-(CH 2 ) q NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. Wherein only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group; (41) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy; (45) cycloalkoxy; (46) cycloalkylalkoxy; And (47) may be optionally substituted with a substituent independently selected from the group consisting of arylalkoxy.

본원에 사용된 바와 같은 용어 "사이클로알콕시"는 산소 원자를 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 사이클로알킬 그룹을 나타낸다.The term "cycloalkoxy" as used herein denotes a cycloalkyl group, as defined herein, appended to the parent molecular group via an oxygen atom.

본원에 사용된 바와 같은 용어 "사이클로알킬알콕시"는 사이클로알킬 그룹에 결합된, 본원에 정의된 바와 같은 알콕시 그룹을 나타낸다.The term "cycloalkylalkoxy" as used herein refers to an alkoxy group, as defined herein, attached to a cycloalkyl group.

본원에 사용된 바와 같은 용어 "사이클로알킬알킬"은 알킬 그룹을 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 사이클로알킬 그룹을 나타낸다.As used herein, the term “cycloalkylalkyl” refers to a cycloalkyl group, as defined herein, appended to the parent molecular group through an alkyl group.

본원에 사용된 바와 같은 용어 "할로알킬"은 1개, 2개 또는 3개의 할로겐 원자로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타내고, 클로로메틸, 브로모메틸, 트리플루오로메틸 등으로 예시된다.The term "haloalkyl" as used herein refers to an alkyl group as defined herein, substituted with one, two or three halogen atoms, exemplified by chloromethyl, bromomethyl, trifluoromethyl and the like. do.

본원에 사용된 바와 같은 용어 "할로겐"은 F, Cl, Br 및 I를 나타낸다.The term "halogen" as used herein refers to F, Cl, Br and I.

본원에 사용된 바와 같은 용어 "헤테로사이클"은 질소, 산소 및 황으로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개 또는 3개의 헤테로 원자를 함유하는 5원, 6원 또는 7원 환을 나타낸다. 5원 환은 0 내지 2개의 이중 결합을 가지며 6원 및 7원 환은 0 내지 3개의 이중 결합을 갖는다. 용어 "헤테로사이클"에는 아릴 환, 사이클로헥산 환, 사이클로헥센 환, 사이클로펜탄 환, 사이클로펜텐 환 및 또 다른 모노사이클릭 헤테로사이클릭 환, 예를 들면, 인돌릴, 퀴놀릴, 이소퀴놀릴, 테트라하이드로퀴놀릴, 벤조푸릴, 벤조티에닐 등으로 이루어진 그룹 중에서 독립적으로 선택된 1개 또는 2개의 환에 융합되는, 바이사이클릭, 트리사이클릭 및 테트라사이클릭 그룹이 포함된다. 헤테로사이클로는 피롤릴, 피롤리닐, 피롤리디닐, 피라졸릴, 피라졸리닐, 피라졸리디닐, 이미다졸릴, 이미다졸리닐, 이미다졸리디닐, 피리딜, 피페리디닐, 호모피페리디닐, 피라지닐, 피페라지닐, 피리미디닐, 피리다지닐, 옥사졸릴, 옥사졸리디닐, 이속사졸릴, 이속사졸리디닐, 모르폴리닐, 티오모르폴리닐, 티아졸릴, 티아졸리디닐, 이소티아졸릴, 이소티아졸리디닐, 인돌릴, 퀴놀리닐, 이소퀴놀리닐, 벤즈이미다졸릴, 벤조티아졸릴, 벤족사졸릴, 푸릴, 티에닐, 티아졸리디닐, 이소티아졸릴, 이소인다조일, 트리아졸릴, 테트라졸릴, 옥사디아졸릴, 우리실, 티아디아졸릴, 피리미딜, 테트라하이드로푸라닐, 디하이드로푸라닐, 테트라하이드로티에닐, 디하이드로티에닐, 디하이드로인돌릴, 테트라하이드로퀴놀릴, 테트라하이드로이소퀴놀릴, 피라닐, 디하이드로피라닐, 디티아졸릴, 벤조푸라닐, 벤조티에닐 등이 있다. 헤테로사이클릭 그룹에는 또한 화학식화합물[여기서, F는 -CH2-, -CH2O- 및 -O-로 이루어진 그룹 중에서 선택되고, G는 -C(O)- 및 -(C(R')(R"))-로 이루어진 그룹(여기서, R' 및 R"는 수소 또는 탄소수 1 내지 4의 알킬로 이루어진 그룹 중에서 독립적으로 선택된다) 중에서 선택되며, 되고, v는 1 내지 3이다]이 포함되고, 이의 예로는 1,3-벤조디옥솔릴, 1,4-벤조디옥사닐 등이 있다. 본원에 언급된 어떠한 헤테로사이클 그룹도 (1) 탄소수 1 내지 6의 알카노일; (2) 탄소수 1 내지 6의 알킬; (3) 탄소수 1 내지 6의 알콕시; (4) 알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (5) 탄소수 1 내지 6의 알킬설피닐; (6) 알킬설피닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (7) 탄소수 1 내지 6의 알킬설포닐; (8) 알킬설포닐알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (9) 아릴; (10) 아릴알킬(여기서, 알킬 그룹은 탄소수 1 내지 6의 그룹이다); (11) 아미노; (12) 탄소수 1 내지 6의 아미노알킬; (13) 아릴; (14) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (15) 아릴로일; (16) 아지도; (17) 탄소수 1 내지 6의 아지도알킬; (18) 카복스알데히드; (19) (카복스알데히드)알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (20) 탄소수 3 내지 8의 사이클로알킬; (21) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다); (22) 할로; (23) 탄소수 1 내지 6의 할로알킬; (24) 헤테로사이클; (25) (헤테로사이클)옥시; (26) (헤테로사이클)오일; (27) 하이드록시; (28) 탄소수 1 내지 6의 하이드록시알킬; (29) 니트로; (30) 탄소수 1 내지 6의 니트로알킬; (31) N-보호된 아미노; (32) N-보호된 아미노알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (33) 옥소; (34) 탄소수 1 내지 6의 티오알콕시; (35) 티오알콕시알킬(여기서, 알킬 및 알킬렌 그룹은 독립적으로 탄소수 1 내지 6의 그룹이다); (36) -(CH2)qCO2R2(여기서, q는 0 내지 4이다); (37) -(CH2)qC(O)NR2R3; (38) -(CH2)qSO2R4[여기서, R4는 (a) 알킬, (b) 아릴 및 (c) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택된다]; (39) -(CH2)qSO2NR5R6[여기서, R5및 R6은 (a) 수소, (b) 알킬, (c) 아릴 및 (d) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택된다]; (40) -(CH2)qNR7R8[여기서, R7및 R8은 (a) 수소; (b) N-보호 그룹; (c) 탄소수 1 내지 6의 알킬; (d) 탄소수 2 내지 6의 알케닐; (e) 탄소수 2 내지 6의 알키닐; (f) 아릴; (g) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); (h) 탄소수 3 내지 8의 사이클로알킬 및 (i) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)으로 이루어진 그룹 중에서 독립적으로 선택되며, 단 2개의 그룹이 카보닐 그룹 또는 설포닐 그룹을 통하여 질소 원자에 결합되지는 않는다]; (41) 옥소; (42) 퍼플루오로알킬; (43) 퍼플루오로알콕시; (44) 아릴옥시; (45) 사이클로알콕시; (46) 사이클로알킬알콕시; 및 (47) 아릴알콕시로 이루어진 그룹 중에서 독립적으로 선택된 1개, 2개, 3개, 4개 또는 5개의 치환체로 임의로 치환될 수 있다.The term “heterocycle” as used herein refers to a five, six or seven membered ring containing one, two or three heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur. 5-membered rings have 0 to 2 double bonds and 6- and 7-membered rings have 0 to 3 double bonds. The term "heterocycle" includes aryl rings, cyclohexane rings, cyclohexene rings, cyclopentane rings, cyclopentene rings and other monocyclic heterocyclic rings, such as indolyl, quinolyl, isoquinolyl, tetra Bicyclic, tricyclic and tetracyclic groups are included which are fused to one or two rings independently selected from the group consisting of hydroquinolyl, benzofuryl, benzothienyl and the like. Heterocycles include pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl , Pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothia Zolyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, isodazoyl, tria Zolyl, tetrazolyl, oxadizolyl, uricyl, thiadiazolyl, pyrimidyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, dihydroindolyl, tetrahydroquinolyl, tetra Hydroisoquinolyl, pyranyl, diha Idropyranyl, dithiazolyl, benzofuranyl, benzothienyl and the like. Heterocyclic groups also include Compound wherein F is selected from the group consisting of -CH 2- , -CH 2 O- and -O-, and G is -C (O)-and-(C (R ') (R "))- And R 'and R "are independently selected from hydrogen or a group consisting of alkyl having 1 to 4 carbon atoms, and v is 1 to 3, and examples thereof include 1, 3-benzodioxolyl, 1,4-benzodioxanyl, and the like. Any heterocycle group mentioned herein may be selected from (1) alkanoyl of 1 to 6 carbon atoms; (2) alkyl having 1 to 6 carbon atoms; (3) alkoxy having 1 to 6 carbon atoms; (4) alkoxyalkyl, wherein alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (5) alkylsulfinyl having 1 to 6 carbon atoms; (6) alkylsulfinylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (7) alkylsulfonyl having 1 to 6 carbon atoms; (8) alkylsulfonylalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (9) aryl; (10) arylalkyl, wherein the alkyl group is a group of 1 to 6 carbon atoms; (11) amino; (12) aminoalkyl of 1 to 6 carbon atoms; (13) aryl; (14) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (15) aryloyl; (16) azido; (17) azidoalkyl having 1 to 6 carbon atoms; (18) carboxaldehyde; (19) (carboxaldehyde) alkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; (20) cycloalkyl having 3 to 8 carbon atoms; (21) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms; (22) halo; (23) haloalkyl having 1 to 6 carbon atoms; (24) heterocycle; (25) (heterocycle) oxy; (26) (heterocycle) oils; (27) hydroxy; (28) hydroxyalkyl having 1 to 6 carbon atoms; (29) nitro; (30) nitroalkyl having 1 to 6 carbon atoms; (31) N-protected amino; (32) N-protected aminoalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (33) oxo; (34) thioalkoxy having 1 to 6 carbon atoms; (35) thioalkoxyalkyl, wherein the alkyl and alkylene groups are independently a group having 1 to 6 carbon atoms; (36)-(CH 2 ) q CO 2 R 2 , where q is 0 to 4; (37)-(CH 2 ) q C (O) NR 2 R 3 ; (38)-(CH 2 ) q SO 2 R 4 , wherein R 4 is (a) alkyl, (b) aryl and (c) arylalkyl, wherein the alkylene group is a group having from 1 to 6 carbon atoms Selected from the group consisting of; (39)-(CH 2 ) q SO 2 NR 5 R 6 wherein R 5 and R 6 are (a) hydrogen, (b) alkyl, (c) aryl and (d) arylalkyl (where alkylene groups Is independently selected from the group consisting of 1 to 6 carbon atoms; (40)-(CH 2 ) q NR 7 R 8 wherein R 7 and R 8 are (a) hydrogen; (b) an N-protecting group; (c) alkyl of 1 to 6 carbon atoms; (d) alkenyl having 2 to 6 carbon atoms; (e) alkynyl having 2 to 6 carbon atoms; (f) aryl; (g) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; independently from a group consisting of (h) cycloalkyl of 3 to 8 carbon atoms and (i) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms, and the alkylene group is a group of 1 to 10 carbon atoms. Wherein only two groups are not bonded to the nitrogen atom via a carbonyl group or sulfonyl group; (41) oxo; (42) perfluoroalkyl; (43) perfluoroalkoxy; (44) aryloxy; (45) cycloalkoxy; (46) cycloalkylalkoxy; And (47) arylalkoxy, which may be optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of arylalkoxy.

본원에 사용된 바와 같은 용어 "(헤테로사이클)옥시"는 산소를 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 헤테로사이클 그룹을 나타낸다.The term "(heterocycle) oxy", as used herein, refers to a heterocycle group, as defined herein, appended to the parent molecular group via oxygen.

본원에 사용된 바와 같은 용어 "(헤테로사이클)오일"은 카보닐 그룹을 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 헤테로사이클 그룹을 나타낸다.As used herein, the term “(heterocycle) oil” refers to a heterocycle group, as defined herein, appended to the parent molecular group through a carbonyl group.

본원에 사용된 바와 같은 용어 "하이드록시"는 -OH 그룹을 나타낸다.The term "hydroxy" as used herein refers to an -OH group.

본원에 사용된 바와 같은 용어 ""하이드록시알킬"은 1 내지 3개의 하이드록시 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 나타내며, 단 1개 이상의 하이드록시 그룹이 알킬 그룹의 단일 탄소 원자에 결합될 수 없으며, 이의 예로는 하이드록시메틸, 디하이드록시프로필 등이 있다.As used herein, the term “hydroxyalkyl” refers to an alkyl group, as defined herein, substituted with one to three hydroxy groups, provided that at least one hydroxy group is a single carbon atom of the alkyl group. It may not be bonded to, examples thereof include hydroxymethyl, dihydroxypropyl and the like.

본원에 사용된 바와 같은 용어 "메틴"은 =C(H)- 그룹을 나타낸다.The term "methine" as used herein refers to a = C (H)-group.

본원에 사용된 바와 같은 용어 "N-보호된 아미노"는 본원에 정의된 바와 같은 N-보호 또는 질소-보호 그룹에 결합된, 본원에 정의된 바와 같은 아미노 그룹을 지칭한다.The term “N-protected amino” as used herein refers to an amino group as defined herein, appended to an N-protecting or nitrogen-protecting group as defined herein.

본원에 사용된 바와 같은 용어 ""N-보호된 아미노알킬"은 본원에 정의된 바와 같은 N-보호 또는 질소-보호 그룹으로 치환된, 본원에 정의된 바와 같은 알킬 그룹을 지칭한다.As used herein, the term “N-protected aminoalkyl” refers to an alkyl group, as defined herein, substituted with an N-protecting or nitrogen-protecting group, as defined herein.

본원에 사용된 바와 같은 용어 "니트로"는 -NO2그룹을 나타낸다.As used herein, the term “nitro” refers to a —NO 2 group.

본원에 사용된 바와 같은 용어 "니트로알킬"은 -NO2그룹으로 치환된 알킬 그룹을 나타낸다.The term "nitroalkyl" as used herein refers to an alkyl group substituted with a -NO 2 group.

본원에 사용된 바와 같은 용어 "N-보호 그룹" 또는 "질소 보호 그룹"은 합성 과정 동안 목적하지 않는 반응에 대하여 아미노 그룹을 보호하도록 고안된 그룹을 나타낸다. 통상적으로 사용되는 N-보호 그룹은 본원에서 참조로 인용하는 문헌[Greene, "Protective Groups In Organic Synthesis", (John Wiley & Sons, New York(1981)]에 기재되어 있다. N-보호 그룹은 아실 그룹, 예를 들면, 포밀, 아세틸, 프로피오닐, 피발로일, t-부틸아세틸, 2-클로로아세틸, 2-브로모아세틸, 트리플루오로아세틸, 트리클로로아세틸, 프탈릴, o-니트로페녹시아세틸, α-클로로부티릴, 벤조일, 4-클로로벤조일, 4-브로모벤조일, 4-니트로벤조일, 및 키랄 보조제, 예를 들면, 알라닌, 로이신, 페닐알라닌 등의 보호되거나 보호되지 않은 D, L 또는 D,L-아미노산; 벤젠설포닐, p-톨루엔설포닐 등의 설포닐 그룹; 벤질옥시카보닐, p-클로로벤질옥시카보닐, p-메톡시벤질옥시카보닐, p-니트로벤질옥시카보닐, 2-니트로벤질옥시카보닐, p-브로모벤질옥시카보닐, 3,4-디메톡시벤질옥시카보닐, 3,5-디메톡시벤질옥시카보닐, 2,4-디메톡시벤질옥시카보닐, 4-메톡시벤질옥시카보닐, 2-니트로-4,5-디메톡시벤질옥시카보닐, 3,4,5-트리메톡시벤질옥시카보닐, 1-(p-비페닐)-1-메틸에톡시카보닐, α,α-디메틸-3,5-디메톡시벤질옥시카보닐, 벤즈하이드릴옥시카보닐, t-부틸옥시카보닐, 디이소프로필메톡시카보닐, 이소프로필옥시카보닐, 에톡시카보닐, 메톡시카보닐, 알릴옥시카보닐, 2,2,2-트리클로로에톡시카보닐, 페녹시카보닐, 4-니트로페녹시 카보닐, 플루오레닐-9-메톡시카보닐, 사이클로펜틸옥시카보닐, 아다만틸옥시카보닐, 사이클로헥실옥시카보닐, 페닐티오카보닐 등의 카바메이트 형성 그룹; 벤질, 트리페닐메틸, 벤질옥시메틸 등의 아릴알킬 그룹; 및 트리메틸실릴 등의 실릴 그룹을 포함한다. 바람직한 N-보호 그룹은 포밀, 아세틸, 벤조일, 피발로일, t-부틸아세틸, 알라닐, 페닐설포닐, 벤질, t-부틸옥시카보닐(Boc) 및 벤질옥시카보닐(Cbz)이다.As used herein, the term “N-protecting group” or “nitrogen protecting group” refers to a group designed to protect amino groups against undesired reactions during the course of the synthesis. Commonly used N-protective groups are described in Greene, "Protective Groups In Organic Synthesis", John Wiley & Sons, New York (1981), which is incorporated herein by reference. Groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxy Protected or unprotected D, L, such as acetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and chiral adjuvants such as alanine, leucine, phenylalanine, or the like D, L-amino acids; sulfonyl groups such as benzenesulfonyl, p-toluenesulfonyl, benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl , 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbon , 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4 , 5-trimethoxybenzyloxycarbonyl, 1- (p-biphenyl) -1-methylethoxycarbonyl, α, α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxycarbon Neyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl Phenoxycarbonyl, 4-nitrophenoxy carbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl and the like Carbamate forming groups, arylalkyl groups such as benzyl, triphenylmethyl, benzyloxymethyl, and silyl groups such as trimethylsilyl, etc. Preferred N-protecting groups include formyl, acetyl, benzoyl, pival Day, t- butyl, acetyl, alanyl, phenylsulfonyl, benzyl, t- butyloxycarbonyl (Boc) and benzyloxycarbonyl (Cbz).

본원에 사용된 바와 같은 용어 "옥소"는 =O를 나타낸다.The term "oxo" as used herein denotes = 0.

본원에 사용된 바와 같은 용어 "퍼플루오로알킬"은 알킬 그룹에 결합된 각각의 수소 라디칼을 플루오라이드 라디칼로 대체시킨, 본원에 정의된 바와 같은 알킬 그룹을 나타낸다. 퍼플루오로알킬 그룹은 트리플루오로메틸, 펜타플루오로에틸 등으로 예시된다.The term "perfluoroalkyl" as used herein denotes an alkyl group as defined herein, replacing each hydrogen radical bonded to an alkyl group with a fluoride radical. Perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl and the like.

본원에 사용된 바와 같은 용어 "퍼플루오로알콕시"는 산소 원자를 통하여 모 분자 그룹에 결합된, 본원에 정의된 바와 같은 퍼플루오로알킬 그룹을 나타낸다.The term “perfluoroalkoxy” as used herein refers to a perfluoroalkyl group, as defined herein, attached to the parent molecular group via an oxygen atom.

본원에 사용된 바와 같은 용어 "약제학적으로 허용되는 염"은 철저한 의학적 판단하에서 해로운 독성, 자극, 알레르기성 반응 등을 유발시키지 않으면서 사람과 하등 동물의 조직과 접촉해서 사용하는데 적합하고 합리적인 이점/위험비로 균형 잡힌 염을 지칭한다. 약제학적으로 허용되는 염은 당해 분야에 널리 공지되어 있다. 예를 들면, 문헌[참조: S.M Berge et al., J. Pharmaceutical Sciences, 66:1-19(1977)]에 약제학적으로 허용되는 염이 상세히 기재되어 있다. 이러한 염은 본 발명의 화합물을 최종적으로 분리 및 정제하는 동안에 동일계 반응내에서 제조할 수 있거나, 또는 유리 염기 그룹을 적합한 유기 산과 반응시킴으로써 별도로 제조할 수 있다. 대표적인 산 부가염으로는 아세테이트, 아디페이트, 알기네이트, 아스코르베이트, 아스파테이트, 벤젠설포네이트, 벤조에이트, 비설페이트, 보레이트, 부티레이트, 캄포레이트, 캄포설포네이트, 시트레이트, 사이클로펜탄프로피오네이트, 디글루코네이트, 도데실설페이트, 에탄설포네이트, 푸마레이트, 글루코헵토네이트, 글리세로포스페이트, 헤미설페이트, 헵토네이트, 헥사노에이트, 하이드로브로마이드, 하이드로클로라이드, 하이드로요오다이드, 2-하이드록시-에탄설포네이트, 락토비오네이트, 락테이트, 라우레이트, 라우릴 설페이트, 말레이트, 말레에이트, 말로네이트, 메탄설포네이트, 2-나프탈렌설포네이트, 니코티네이트, 니트레이트, 올레에이트, 옥살레이트, 팔미테이트, 파모에이트, 펙티네이트, 퍼설페이트, 3-페닐프로피오네이트, 포스페이트, 피크레이트, 피발레이트, 프로피오네이트, 스테아레이트, 석시네이트, 설페이트, 타르트레이트, 티오시아네이트, 톨루엔설포네이트, 운데카노에이트, 발레레이트 염 등이 있다. 대표적인 알칼리 또는 알칼리 토금속 염으로는 나트륨, 리튬, 칼륨, 칼슘, 마그네슘 등 뿐만 아니라, 이로서 제한되는 것은 아니나, 암모늄, 테트라메틸암모늄, 테트라에틸암모늄, 메틸아민, 디메틸아민, 트리메틸아민, 트리에틸아민, 에틸아민 등을 포함하는 비독성 암모늄, 4급 암모늄 및 아민 양이온이 있다. 본원에 사용된 바와 같은 용어 "약제학적으로 허용되는 에스테르"는 생체내에서 가수분해되는 에스테르를 지칭하고 이에는 사람 체내에서 용이하게 분해되어 모 화합물 또는 이의 염을 유리시키는 것이 포함된다. 적합한 에스테르 그룹으로는, 예를 들면, 약제학적으로 허용되는 지방족 카복실산, 특히, 알카노산, 알케노산, 사이클로알카노산 및 알칸디오산(여기서, 각각의 알킬 또는 알케닐 그룹은 바람하게는 6개 이하의 탄소 원자를 갖는다)으로부터 유도된 것이 있다. 특정한 에스테르의 예로는 포르메이트, 아세테이트, 프로피오네이트, 부티레이트, 아크릴레이트 및 에틸석시네이트가 있다.As used herein, the term "pharmaceutically acceptable salt" is suitable and reasonable for use in contact with human and lower animal tissues without causing harmful toxicity, irritation, allergic reactions, etc. under thorough medical judgment. Refers to salts balanced at risk. Pharmaceutically acceptable salts are well known in the art. For example, pharmaceutically acceptable salts are described in detail in S.M Berge et al., J. Pharmaceutical Sciences, 66: 1-19 (1977). Such salts may be prepared in situ during the final separation and purification of the compounds of the present invention, or may be prepared separately by reacting the free base group with a suitable organic acid. Representative acid addition salts include acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate , Digluconate, dodecyl sulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy- Ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, maleate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, Palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, force And the like sites, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts. Representative alkali or alkaline earth metal salts include, but are not limited to, sodium, lithium, potassium, calcium, magnesium, and the like, but are not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, Non-toxic ammonium, quaternary ammonium and amine cations including ethylamine and the like. As used herein, the term “pharmaceutically acceptable ester” refers to an ester that is hydrolyzed in vivo and includes those that are readily degraded in the human body to liberate the parent compound or salts thereof. Suitable ester groups include, for example, pharmaceutically acceptable aliphatic carboxylic acids, in particular alkanoic acid, alkenoic acid, cycloalkanoic acid and alkanedioic acid, wherein each alkyl or alkenyl group is preferably at most 6 Has a carbon atom of). Examples of specific esters are formate, acetate, propionate, butyrate, acrylate and ethyl succinate.

본원에서 사용된 바와 같은 용어 "약제학적으로 허용되는 프로드럭"은 철저한 의학적 판단하에서 해로운 독성, 자극, 알레르기성 반응 등을 유발시키지 않으면서 사람과 하등 동물의 조직과 접촉해서 사용하는데 적합하고 합리적인 이점/위험비로 균형 잡히며 의도하는 목적에 효과적인, 본 발명의 화합물의 프로드럭을 지칭할 뿐만 아니라 가능한 경우 본 발명의 화합물의 쯔비터이온 형태를 지칭한다.As used herein, the term "pharmaceutically acceptable prodrug" is suitable and reasonable for use in contact with tissues of humans and lower animals without causing harmful toxicity, irritation, allergic reactions, etc. under thorough medical judgment. It refers not only to prodrugs of the compounds of the present invention, which are balanced at a risk / ratio and effective for the intended purpose, but also to the zwitterionic forms of the compounds of the present invention, where possible.

본원에 사용된 바와 같은 용어 "프로드럭"은, 예를 들면, 혈중에서 가수분해에 의해 생체내에서 신속하게 변환되어 상기 화학식의 모 화합물을 생성하는 화합물을 지칭한다. 이에 대한 철저한 논의가 본원에 참조 문헌으로 삽입된 문헌[참조: T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol.14 of thd A.C.S. Symposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, and Judkins, et al. Synthetic Communications, 26(23), 4351-4367(1996)]에 제공되어 있다.As used herein, the term “prodrug” refers to a compound that is rapidly converted in vivo, for example, by hydrolysis in blood to produce the parent compound of the formula. A thorough discussion of this is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of thd A.C.S. Symposium Series, Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, and Judkins, et al. Synthetic Communications, 26 (23), 4351-4367 (1996).

본원에 사용된 바와 같은 용어 "스피로알킬"은 양 말단이 모 그룹의 동일한 탄소 원자에 결합되어 스피로사이클릭 그룹을 형성하는 알킬렌 디라디칼을 나타낸다.As used herein, the term “spiroalkyl” refers to alkylene diradicals whose both ends are bonded to the same carbon atom of the parent group to form a spirocyclic group.

본원에 사용된 바와 같은 용어 "설포닐"은 -SO2- 그룹을 나타낸다.The term "sulfonyl" as used herein refers to a -SO 2 -group.

본원에 사용된 바와 같은 용어 "티오알콕시"는 황 원자를 통하여 모 분자 그룹에 결합된 알킬 그룹을 나타낸다.The term "thioalkoxy" as used herein refers to an alkyl group bonded to the parent molecular group via a sulfur atom.

본원에 사용된 바와 같은 용어 ""티오알콕시알킬"은 티오알콕시 그룹으로 치환된 알킬 그룹을 나타낸다.The term "" thioalkoxyalkyl "as used herein refers to an alkyl group substituted with a thioalkoxy group.

비대칭 또는 키랄 중심이 본 발명의 화합물에 존재할 수 있다. 본 발명은 각종 입체이성체 및 이의 혼합물을 고려한다. 본 발명의 화합물의 개개의 입체 이성체는 비대칭 또는 키랄 중심을 함유하는 시판용 출발 물질로부터 합성적으로 제조하거나, 또는 에난티오머성 화합물의 혼합물을 제조한 다음 당해 분야의 숙련인에게 널리 공지된 분할 방법에 의해 제조한다. 이들 분할 방법의 예로는 (1) (±)로 나타내는, 에난티오머의 라세미 혼합물을 키랄 보조제에 결합시키고, 생성된 부분입체이성체를 재결정화 또는 크로마토그래피에 의해 분리한 다음, 광학적으로 순수한 생성물을 상기 보조제로부터 유리시키는 방법 또는 (2) 광학 에난티오머의 혼합물을 키랄 크로마토그래피 칼럼 상에서 직접 분리시키는 방법이 있다. 에난티오머는 본원에서 키랄 탄소 원자 주변 치환체의 배위에 따라서 부호 "R" 또는 "S"로 명명된다.Asymmetric or chiral centers may be present in the compounds of the present invention. The present invention contemplates various stereoisomers and mixtures thereof. Individual stereoisomers of the compounds of the present invention may be prepared synthetically from commercially available starting materials containing asymmetric or chiral centers, or a mixture of enantiomeric compounds may be prepared and then subjected to cleavage methods well known to those skilled in the art. Manufactured by Examples of these splitting methods include (1) a racemic mixture of enantiomers, represented by (±), to a chiral adjuvant, the resulting diastereomers are separated by recrystallization or chromatography, and then optically pure product. And (2) separating the mixture of optical enantiomers directly on a chiral chromatography column. Enantiomers are named herein as "R" or "S" depending on the configuration of the substituents around the chiral carbon atom.

기하 이성체가 본 발명의 화합물에 존재할 수도 있다. 본 발명은 탄소-탄소 이중 결합 주변 치환체의 배열로부터 발생되는 각종 기하 이성체 및 이의 혼합물을 고려하며, 이러한 이성체는 Z 또는 E 배위로서 명명되고, 용어 "Z"는 탄소-탄소 이중 결합의 동일한 면 상의 치환체를 나타내고 용어 "E"는 탄소-탄소 이중 결합의 반대편 면 상의 치환체를 나타낸다.Geometric isomers may be present in the compounds of the present invention. The present invention contemplates various geometric isomers resulting from the arrangement of substituents around carbon-carbon double bonds and mixtures thereof, which isomers are designated as Z or E configuration, and the term "Z" is on the same side of Substituent and the term “E” refers to a substituent on the opposite side of the carbon-carbon double bond.

바람직한 양태Preferred Embodiment

본 발명의 바람직한 화합물은Preferred compounds of the invention

A 및 C가 수소이고,A and C are hydrogen,

B가 -LBRB이며,B is -L B R B ,

-LB-이 -O-이고,-L B -is -O-,

RB가 탄소수 2 내지 6의 알킬(여기서, 알킬 그룹은 치환된다)인 화학식 Ⅰ의 화합물이다.Is a compound of Formula I wherein R B is alkyl having 2 to 6 carbon atoms, wherein the alkyl group is substituted.

본 발명의 보다 바람직한 양태는More preferred aspect of the present invention

A가 -LARA이고,A is -L A R A ,

B 및 C가 수소이며,B and C are hydrogen,

-LA-가-L A-

(1) 공유 결합,(1) covalent bonds,

(2) -(CH2)m-,(2)-(CH 2 ) m- ,

(3) -NR2C(X)-,(3) -NR 2 C (X)-,

(4) -C(X)NR2-,(4) -C (X) NR 2- ,

(5) -NR2C(X)NR3-,(5) -NR 2 C (X) NR 3- ,

(6) -C≡C-,(6) -C≡C-,

(7) -CH=CH-,(7) -CH = CH-,

(8) -C(X)NR2(CH2)nC≡C-,(8) -C (X) NR 2 (CH 2 ) n C≡C-,

(9) -C(X)-,(9) -C (X)-,

(10) -O-,(10) -O-,

(11) -OC(O)NR2- 및(11) -OC (O) NR 2 -and

(12)으로 이루어진 그룹 중에서 선택되며;(12) It is selected from the group consisting of;

RA가R A

(1) 아미노;(1) amino;

(2) 아릴;(2) aryl;

(3) 탄소수 1 내지 10의 알킬;(3) alkyl having 1 to 10 carbon atoms;

(4) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다);(4) arylalkyl, wherein the alkylene group is a group of 1 to 10 carbon atoms;

(5) 탄소수 3 내지 8의 사이클로알킬;(5) cycloalkyl having 3 to 8 carbon atoms;

(6) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다); 및(6) arylalkoxy, wherein the alkylene group is a group of 1 to 10 carbon atoms; And

(7) (1) 푸라닐,(7) (1) furanyl,

(2) 티에닐 및(2) thienyl and

(3) 이미다졸릴로 이루어진 그룹 중에서 선택된 헤테로사이클로 이루어진 그룹 중에서 선택되고;(3) is selected from the group consisting of heterocycles selected from the group consisting of imidazolyl;

각 경우에, R2가In each case, R 2

(1) 수소 및(1) hydrogen and

(2) 탄소수 1 내지 6의 알킬로 이루어진 그룹 중에서 선택되며;(2) selected from the group consisting of alkyl having 1 to 6 carbon atoms;

각 경우에, m이 2이고,In each case m is 2,

n이 1이며,n is 1,

R1및 R3이 수소이고,R 1 and R 3 are hydrogen,

W 및 X가 O이며,W and X are O,

아릴이 페닐이고,Aryl is phenyl,

알킬 그룹 및 아릴 그룹이 임의로 치환되며,Alkyl groups and aryl groups are optionally substituted,

알케닐 그룹이 치환된 화학식 Ⅰ의 화합물에 관한 것이다.A compound of formula I is substituted with an alkenyl group.

또한, 보다 바람직한 본 발명의 화합물은Moreover, the more preferable compound of this invention is

A 및 B가 수소이고;A and B are hydrogen;

C가 -LCRC이며;C is -L C R C ;

LC가L C

(1) 공유 결합,(1) covalent bonds,

(2) -OC(O)NR2-,(2) -OC (O) NR 2- ,

(3) -SO2NR2-,(3) -SO 2 NR 2- ,

(4) C(X)NR2-,(4) C (X) NR 2- ,

(5) -NR1- 및(5) -NR 1 -and

(6) -O-로 이루어진 그룹 중에서 선택되며;(6) it is selected from the group consisting of -O-;

RC가R C

(1) 탄소수 1 내지 6의 알킬;(1) alkyl having 1 to 6 carbon atoms;

(2) 아릴;(2) aryl;

(3) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다); 및(3) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; And

(4) 헤테로사이클(여기서, 헤테로사이클은(4) heterocycle, wherein the heterocycle

(1) 푸라닐;(1) furanyl;

(2) 피리미디닐; 및(2) pyrimidinyl; And

(3)[여기서, F는 -O-이고, G는 -(C(R')(R"))v-이며, R' 및 R"는 수소이고, v는 1이다]로 이루어진 그룹 중에서 선택된다)로 이루어진 그룹 중에서 선택되고;(3) Wherein F is -O-, G is-(C (R ') (R ")) v- , R' and R" are hydrogen and v is 1). Selected from the group consisting of;

X가 O이며;X is O;

각 경우에, R1및 R2는 H이고;In each case R 1 and R 2 are H;

아릴은 페닐이며;Aryl is phenyl;

알킬은 임의로 치환된 화학식 Ⅰ의 화합물이다.Alkyl is an optionally substituted compound of formula (I).

더욱 더 바람직한 본 발명의 화합물은Even more preferred compounds of the invention

A가 -LARA이고,A is -L A R A ,

B가 -LBRB이며,B is -L B R B ,

C가 수소이고,C is hydrogen,

-LA- 및 -LB-가 -O-이며,-L A -and -L B -are -O-,

RA및 RB가 탄소수 1 내지 6의 알킬인 화학식 Ⅰ의 화합물이다.R A and R B are compounds of formula I wherein C 1-6 alkyl is alkyl.

더욱 더 바람직한 본 발명의 화합물은Even more preferred compounds of the invention

A가 -LARA이고,A is -L A R A ,

B가 -LBRB이며,B is -L B R B ,

C가 -LCRC이고,C is -L C R C ,

-LA-, -LB- 및 -LC-가 -O이며,-L A- , -L B -and -L C -are -O,

RA, RB및 RC가 탄소수 1 내지 6의 알킬인 화학식 Ⅰ의 화합물이다.R A , R B and R C are alkyl of Formula I wherein C 1-6 alkyl.

더욱 더 바람직한 본 발명의 화합물은Even more preferred compounds of the invention

A가 수소이고,A is hydrogen,

B가 -LBRB이며,B is -L B R B ,

C가 -LCRC이고,C is -L C R C ,

-LB-가 -O이며,-L B -is -O,

-LC-가-L C -going

(1) 공유 결합,(1) covalent bonds,

(2) -O-,(2) -O-,

(3) -CH=CH-,(3) -CH = CH-,

(4) -NR1- 및(4) -NR 1 -and

(5) -NR2C(O)O-로 이루어진 그룹 중에서 선택되고,(5) -NR 2 C (O) O-, and

RB가 (1) 알킬 및R B is (1) alkyl and

(2) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다)로 이루어진 그룹 중에서 선택되며;(2) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms;

RC가R C

(1) 탄소수 1 내지 6의 알킬,(1) alkyl having 1 to 6 carbon atoms,

(2) 탄소수 1 내지 6의 알케닐,(2) alkenyl having 1 to 6 carbon atoms,

(3) 할로겐,(3) halogen,

(4) 아릴 및(4) aryl and

(5) 헤테로사이클{여기서, 헤테로사이클은(5) heterocycle, wherein the heterocycle

(1) 벤조푸라닐,(1) benzofuranyl,

(2) 테트라하이드로푸라닐,(2) tetrahydrofuranyl,

(3) 피리미디닐,(3) pyrimidinyl,

(4) 피라졸릴,(4) pyrazolyl,

(5) 푸라닐,(5) furanyl,

(6) 피리미디닐,(6) pyrimidinyl,

(7) 티아졸릴 및(7) thiazolyl and

(8)[여기서, F는 -O-이고, G는 -(C(R')(R"))v-이며, R' 및 R"는 수소이고, v는 1이다]로 이루어진 그룹 중에서 선택된다}로 이루어진 그룹 중에서 선택되고;(8) Wherein F is -O-, G is-(C (R ') (R ")) v- , R' and R" are hydrogen and v is 1). Selected from the group consisting of;

각 경우에,In each case,

아릴은 페닐이며;Aryl is phenyl;

알킬, 아릴 및 헤테로사이클은 임의로 치환된 화학식 Ⅰ의 화합물이다.Alkyl, aryl and heterocycles are optionally substituted compounds of formula (I).

화학식 Ⅰ의 범주에 속하는 바람직한 화합물은 다음과 같다:Preferred compounds falling within the scope of formula (I) are as follows:

7,8-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트)염;7,8-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6,7,8-트리메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6,7,8-trimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6,7-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6,7-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt;

7-벤질옥시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-benzyloxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

메틸 [(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세테이트 모노(트리플루오로아세테이트) 염;Methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetate mono (trifluoroacetate) salt;

2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-일-아세트산 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -yl-acetic acid mono (trifluoroacetate) salt;

N-[4-(아미노메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염;N- [4- (aminomethyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt;

N-[4-(아미노)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염;N- [4- (amino) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt;

1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-하이드록시프로판 모노(트리플루오로아세테이트) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-hydroxypropane mono (trifluoroacetate) salt;

페닐메틸 [7-(아미노이미노메틸)-1-나프탈레닐)카바메이트 모노(트리플루오로아세테이트) 염;Phenylmethyl [7- (aminoiminomethyl) -1-naphthalenyl) carbamate mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐)아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl) acetamide mono (trifluoroacetate) salt;

메틸 [7-(아미노이미노메틸)-1-나프탈레닐)카바메이트 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -1-naphthalenyl) carbamate mono (trifluoroacetate) salt;

메틸 3-[[7-(아미노이미노메틸)-1-나프탈레닐]아미노]-3-옥소프로파노에이트 모노(트리플루오로아세테이트) 염;Methyl 3-[[7- (aminoiminomethyl) -1-naphthalenyl] amino] -3-oxopropanoate mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-(페닐메톡시)아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2- (phenylmethoxy) acetamide mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]-1,3-벤조디옥솔-5-카복스아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -1,3-benzodioxol-5-carboxamide mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]벤젠메탄설폰아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] benzenemethanesulfonamide mono (trifluoroacetate) salt;

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염;1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt;

3-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]프로펜 모노(트리플루오로아세테이트) 염;3-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] propene mono (trifluoroacetate) salt;

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판 모노(하이드로클로라이드) 염;1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane mono (hydrochloride) salt;

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]프로판 모노(하이드로클로라이드) 염;1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] propane mono (hydrochloride) salt;

7-메톡시-8-(2-푸라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (2-furanyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

메틸 6-(아미노이미노메틸)-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실레이트 모노(트리플루오로아세테이트) 염;Methyl 6- (aminoiminomethyl) -4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylate mono (trifluoroacetate) salt;

(E)-(7-메톡시-8-[2-(페닐)에테닐])-2-나프탈렌이미드아미드 모노(트리플루오로아세테이트) 염;(E)-(7-methoxy-8- [2- (phenyl) ethenyl])-2-naphthaleneimideamide mono (trifluoroacetate) salt;

6-(4-페닐부티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (4-phenylbutynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-(2-하이드록시에톡시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(4-메틸-1-펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (4-methyl-1-pentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(5-페닐펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (5-phenylpentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(3-페닐-1-프로피닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (3-phenyl-1-propynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(페닐에티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (phenylethynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

3-아미노-N-[3-[6-(아미노이미노메틸)-2-나프탈레닐]-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염;3-amino-N- [3- [6- (aminoiminomethyl) -2-naphthalenyl] -2-propynyl] benzamide mono (trifluoroacetate) salt;

4-아미노-N-[3-(6-아미노이미노메틸-2-나프탈레닐)-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염;4-amino-N- [3- (6-aminoiminomethyl-2-naphthalenyl) -2-propynyl] benzamide mono (trifluoroacetate) salt;

(S)-2-아미노-N-[1-[(6-아미노이미노메틸-2-나프탈레닐)카보닐]사이클로헥실]프로피온아미드 비스(트리플루오로아세테이트) 염;(S) -2-amino-N- [1-[(6-aminoiminomethyl-2-naphthalenyl) carbonyl] cyclohexyl] propionamide bis (trifluoroacetate) salt;

6-메톡시-8-벤질옥시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-methoxy-8-benzyloxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

2-[(7-아미노이미노메틸)-3-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl) -3-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenylurea mono (trifluoroacetate) salt;

(E)-6-[2-(페닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (phenyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-[2-(페닐)에틸]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- [2- (phenyl) ethyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-프로폭시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-propoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(±)-6-(3-페닐옥시라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(±) -6- (3-phenyloxyranyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(E)-6-[2-(2-티에닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (2-thienyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(3-옥소부틸)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (3-oxobutyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(3-메톡시페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (3-methoxyphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

N-[3-(메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(트리플루오로아세테이트) 염;N- [3- (methyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide mono (trifluoroacetate) salt;

6-(2-포밀페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (2-formylphenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(2-포밀페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (2-formylphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-[2-(하이드록시메틸)페닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- [2- (hydroxymethyl) phenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

6-(3-옥소-1-부테닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- (3-oxo-1-butenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

N-페닐-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(메탄설포네이트) 염;N-phenyl-6-aminoiminomethyl-2-naphthalenecarboxamide mono (methanesulfonate) salt;

4-[(6-아미노이미노메틸-2-나프탈레닐)옥시]-N-메틸벤젠아세트아미드 모노(트리플루오로아세테이트) 염;4-[(6-aminoiminomethyl-2-naphthalenyl) oxy] -N-methylbenzeneacetamide mono (trifluoroacetate) salt;

6-[2-(메틸티오)페닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;6- [2- (methylthio) phenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt;

6-[2-(2-티오메톡시에틸)페닐]나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염;6- [2- (2-thiomethoxyethyl) phenyl] naphthalene-2-carboximideamide mono (methanesulfonate) salt;

7-메톡시-8-(3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;7-methoxy-8- (3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt;

7-메톡시-8-(2-벤조푸라닐)나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염;7-methoxy-8- (2-benzofuranyl) naphthalene-2-carboximideamide mono (methanesulfonate) salt;

(E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt;

(±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt;

6-[[4-(2-아미노에틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-[[4- (2-aminoethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-[2-티아조일(옥시)]나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-thiazoyl (oxy)] naphthalene-2-carboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-[N-2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [N-2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzylurea mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-메틸우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-methylurea mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-이소프로필우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-isopropylurea mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐-N'-메틸우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenyl-N'-methylurea mono (trifluoroacetate) salt;

6-아미노나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-aminonaphthalene-2-carboximideamide mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-사이클로헥실우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-cyclohexylurea mono (trifluoroacetate) salt;

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질옥시우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzyloxyurea mono (trifluoroacetate) salt;

1,1-디메틸에틸 [4-[[(6-시아노-2-나프탈레닐)아미노]카보닐]페닐]카바메이트 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [4-[[(6-cyano-2-naphthalenyl) amino] carbonyl] phenyl] carbamate mono (trifluoroacetate) salt;

N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-(아미노메틸)벤즈아미드 모노(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl] -4- (aminomethyl) benzamide mono (trifluoroacetate) salt;

에틸 [6-(아미노이미노메틸)-2-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염;Ethyl [6- (aminoiminomethyl) -2-naphthalenyl] carbamate mono (trifluoroacetate) salt;

1,1-디메틸에틸 [4-[[[(6-아미노이미노메틸)-2-나프탈레닐)아미노]카보닐]아미노]페닐]카바메이트 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [4-[[[(6-aminoiminomethyl) -2-naphthalenyl) amino] carbonyl] amino] phenyl] carbamate mono (trifluoroacetate) salt;

(E)-6-[2-(페닐티오)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (phenylthio) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(E)-6-[2-(2-푸라닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (2-furanyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(E)-6-[2-(1H-이미다졸-1-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (1H-imidazol-1-yl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤젠설폰아미드 모노(트리플루오로아세테이트) 염;(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzenesulfonamide mono (trifluoroacetate) salt;

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤조산 모노(트리플루오로아세테이트) 염;(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzoic acid mono (trifluoroacetate) salt;

4-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]디하이드로-2(3H)-푸란온 모노(트리플루오로아세테이트) 염;4- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] dihydro-2 (3H) -furanone mono (trifluoroacetate) salt;

7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤즈아미드 모노(트리플루오로아세테이트) 염;(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzamide mono (trifluoroacetate) salt;

6-[2-(4-아미노페닐)에톡시]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- [2- (4-aminophenyl) ethoxy] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt;

메틸 [3-메톡시-6-(아미노이미노메틸)-4-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염;Methyl [3-methoxy-6- (aminoiminomethyl) -4-naphthalenyl] carbamate mono (trifluoroacetate) salt;

7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염;7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide bis (trifluoroacetate) salt;

프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;Phthalenecarboxamide, mono (trifluoroacetate) salts;

6-(4-아미노페닐)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;6- (4-aminophenyl) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

메틸 2-[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]카보닐]아미노]페녹시]아세테이트, 모노(트리플루오로아세테이트) 염;Methyl 2- [4-[[[6- (aminoiminomethyl) -2-naphthalenyl] carbonyl] amino] phenoxy] acetate, mono (trifluoroacetate) salt;

(E)-6-[2-[(3-하이드록시메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;(E) -6- [2-[(3-hydroxymethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-(2-페닐-1-사이클로프로필)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;6- (2-phenyl-1-cyclopropyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

(E)-6-[2-[4-(아미노메틸)페닐]에테닐]-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;(E) -6- [2- [4- (aminomethyl) phenyl] ethenyl] -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

(E)-6-[2-[4-(1,2-디하이드록시)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;(E) -6- [2- [4- (1,2-dihydroxy) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

(E)-6-[2-[4-(1R-아미노-2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;(E) -6- [2- [4- (1R-amino-2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

7-메톡시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7-methoxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

(E)-6-[2-[[4-(디메틸아미노)메틸]페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;(E) -6- [2-[[4- (dimethylamino) methyl] phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

(E)-6-[2-[4-(하이드록시메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;(E) -6- [2- [4- (hydroxymethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

4-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-L-페닐알라닌, 모노(트리플루오로아세테이트) 염;4-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -L-phenylalanine, mono (trifluoroacetate) salt;

6-(3-포밀페닐)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;6- (3-formylphenyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

(E)-6-[2-(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;(E) -6- [2- (1,2,3,4-tetrahydro-6-isoquinolinyl) ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

(E)-6-[2-[3-(2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;(E) -6- [2- [3- (2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(2,3-디하이드로-1H-인덴-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (2,3-dihydro-1H-inden-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-[(4-아미노페닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;6-[(4-aminophenyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

1,1-디메틸에틸[2-[3-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-6-메톡시페닐]에틸]카바메이트, 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [2- [3-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -6-methoxyphenyl] ethyl] carbamate, mono (trifluoroacetate) salt;

1,1-디메틸에틸[[4-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [[4-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -phenyl] methyl] carbamate, mono (trifluoroacetate) salt;

6-[[4-(아미노메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;6-[[4- (aminomethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

6-[[3-(2-아미노메틸)-4-메톡시페닐]에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;6-[[3- (2-aminomethyl) -4-methoxyphenyl] ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

6-[[4-(하이드록시메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;6-[[4- (hydroxymethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-[(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;6-[(1,2,3,4-tetrahydro-6-isoquinolinyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(4-메틸페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (4-methylphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

1,1-디메틸에틸[[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] phenyl] methyl] carbamate, mono (trifluoroacetate) salt;

N-[6-(아미노이미노메틸)-2-나프탈레닐)벤즈아미드, 모노(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl) benzamide, mono (trifluoroacetate) salt;

1,1-디메틸에틸[[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]사이클로헥실]메틸]카바메이트, 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] cyclohexyl] methyl] carbamate, mono (trifluoroacetate) salt;

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-(4-아미노페닐)우레아, 비스(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-(4-aminophenyl) urea, bis (trifluoroacetate) salt;

N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-4-(아미노메틸)사이클로헥산카복스아미드, 비스(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl] -4-4- (aminomethyl) cyclohexanecarboxamide, bis (trifluoroacetate) salt;

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-[(4-아미노메틸)페닐]우레아, 비스(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-[(4-aminomethyl) phenyl] urea, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(4-에틸페닐)-2-나프탈레닐카복스아미드, 아세테이트 염;6- (aminoiminomethyl) -N- (4-ethylphenyl) -2-naphthalenylcarboxamide, acetate salt;

6-(아미노이미노메틸)-N-(2-나프탈레닐)-2-나프탈레닐카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (2-naphthalenyl) -2-naphthalenylcarboxamide, mono (trifluoroacetate) salt;

6-(5-페닐-2-옥사졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;6- (5-phenyl-2-oxazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-(5-페닐-2-티아졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;6- (5-phenyl-2-thiazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-[아미노(하이드록시이미노)메틸]-N-페닐-2-나프탈렌카복스아미드;6- [amino (hydroxyimino) methyl] -N-phenyl-2-naphthalenecarboxamide;

6-[4-[(하이드록시메틸)페닐]메톡시]-2-나프탈렌카복스이미드아미드, 메틸렌설포네이트 염;6- [4-[(hydroxymethyl) phenyl] methoxy] -2-naphthalenecarboximideamide, methylenesulfonate salt;

6-(2-피리디닐에티닐)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세티이트) 염;6- (2-pyridinylethynyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

N-[4-(아미노카보닐)페닐]-6-(아미노이미노메틸)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;N- [4- (aminocarbonyl) phenyl] -6- (aminoiminomethyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(2-티아졸릴)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N- (2-thiazolyl) -2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-(6-메톡시-3-피리디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N- (6-methoxy-3-pyridinyl) -2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-(1,3-벤조디옥솔-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1,3-benzodioxol-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-2,4-디옥소-5-피리미디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-2,4-dioxo-5-pyrimidinyl) -2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-(3,5-디플루오로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3,5-difluorophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(5-메틸-3-이속사졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (5-methyl-3-isoxazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(피라지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (pyrazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(6-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (6-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(3,4,5-트리메톡시페닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N- (3,4,5-trimethoxyphenyl) -2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-(3-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3-methyl-2-pyridinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(5-브로모-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (5-bromo-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(5-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (5-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(4-메틸-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (4-methyl-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1H-인다졸-6-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1H-indazol-6-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1H-인다졸-5-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1H-indazol-5-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1H-인돌-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1H-indol-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(5-피리미디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (5-pyrimidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(3-피리다지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3-pyridazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(5-브로모-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (5-bromo-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[3-(1-메틸에톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [3- (1-methylethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(1H-이미다졸릴)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (1H-imidazolyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-[2-[4-(하이드록시메틸)페닐]-1-사이클로프로필]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- [2- [4- (hydroxymethyl) phenyl] -1-cyclopropyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

N-(에톡시카보닐)-6-(2-페닐-1-사이클로프로필)-2-나프탈렌카복스이미드아미드;N- (ethoxycarbonyl) -6- (2-phenyl-1-cyclopropyl) -2-naphthalenecarboximideamide;

6-(아미노이미노메틸)-N-(2-메틸-6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (2-methyl-6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(3-프로폭시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3-propoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[3-(1-에틸프로폭시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [3- (1-ethylpropoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[3-(사이클로펜틸옥시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [3- (cyclopentyloxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(3-페녹시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3-phenoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[3-(페닐메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [3- (phenylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(3-에톡시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (3-ethoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-(4-니트로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- (4-nitrophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[3-(사이클로부틸메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [3- (cyclobutylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-[아미노(에톡시카보닐)이미노]-N-[3-(1-메틸에톡시)페닐]-2-나프탈렌카복스아미드;6- [amino (ethoxycarbonyl) imino] -N- [3- (1-methylethoxy) phenyl] -2-naphthalenecarboxamide;

6-(아미노이미노메틸)-4-[5-(에틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (ethylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

메틸 [7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)카바메이트, 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) carbamate, mono (trifluoroacetate) salt;

7-메톡시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7-methoxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

7-메톡시-8-[(페닐메틸)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8-[(phenylmethyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

7-메톡시-8-(페닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8- (phenylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

7-메톡시-8-[(4-메톡시페닐)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8-[(4-methoxyphenyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

(E)-3-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]-2-프로펜아미드, 모노(트리플루오로아세테이트) 염;(E) -3- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] -2-propenamide, mono (trifluoroacetate) salt;

7-메톡시-8-(3-옥스-1-사이클로펜텐-1-일)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8- (3-ox-1-cyclopenten-1-yl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

메틸 4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염;Methyl 4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt;

4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조산, 모노(트리플루오로아세테이트) 염;4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoic acid, mono (trifluoroacetate) salt;

7-메톡시-8-(피라지닐옥시)-2-나프탈렌카복스이미드아미드, 디메탄설포네이트 염;7-methoxy-8- (pyrazinyloxy) -2-naphthalenecarboximideamide, dimethanesulfonate salt;

7-메톡시-8-(페닐티오)-2-나프탈렌카복스이미드아미드, 메틸렌설포네이트,7-methoxy-8- (phenylthio) -2-naphthalenecarboximideamide, methylenesulfonate,

7-메톡시-8-(피라지닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7-methoxy-8- (pyrazinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

메틸 5-[7-[(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노에이트, 모노(트리플루오로아세테이트) 염;Methyl 5- [7-[(aminoiminomethyl) -2-naphthalenyl] oxy] pentanoate, mono (trifluoroacetate) salt;

5-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노산, 모노(트리플루오로아세테이트) 염;5-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] pentanoic acid, mono (trifluoroacetate) salt;

메틸 4-[[[7-아미노(하이드록시이미노)메틸]-2-나프탈레닐]옥시]메틸]벤조에에트;Methyl 4-[[[7-amino (hydroxyimino) methyl] -2-naphthalenyl] oxy] methyl] benzoate;

메틸 2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세테이트, 모노(트리플루오로아세테이트) 염;Methyl 2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetate, mono (trifluoroacetate) salt;

7-[2-(4-모르폴리닐)에톡시]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7- [2- (4-morpholinyl) ethoxy] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세트산, 모노(트리플루오로아세테이트) 염;2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetic acid, mono (trifluoroacetate) salt;

메틸 4-[6-(아미노이미노메틸)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염;Methyl 4- [6- (aminoiminomethyl) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt;

메틸 [7-(아미노이미노메틸)-1-나프탈레닐]메틸카바메이트, 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -1-naphthalenyl] methylcarbamate, mono (trifluoroacetate) salt;

프로필 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염;Propyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]-N'-메틸우레아, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -N'-methylurea, mono (trifluoroacetate) salt;

에틸 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염;Ethyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]프로판아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] propanamide, mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-메톡시아세트아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-methoxyacetamide, mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]우레아, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] urea, mono (trifluoroacetate) salt;

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-하이드록시아세트아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-hydroxyacetamide, mono (trifluoroacetate) salt;

8-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;8- (2-pyrimidinylamino) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

8-아미노-2-나프탈레닐카복스이미드아미드, 비스(트리플루오로아세테이트) 염;8-amino-2-naphthalenylcarboximideamide, bis (trifluoroacetate) salt;

8-(2-피리디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;8- (2-pyridinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt;

N-하이드록시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;N-hydroxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-[4-(트리플루오로메틸)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -4- (3-furanyl) -N- [4- (trifluoromethyl) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(4-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (4-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, dihydrochloride;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(3-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (3-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride;

메틸 [7-(아미노이미노메틸)-3-[[[4-(아미노메틸)페닐]아미노]카보닐]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(2-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (2-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride;

6-(아미노이미노메틸)-4-(3-푸라닐)-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[1-(메틸설포닐)-1H-피라졸-4-일]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [1- (methylsulfonyl) -1H-pyrazol-4-yl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[5-(메틸티오)-3-푸라닐)]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (methylthio) -3-furanyl)]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-[4-(아미노메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 트리스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [4- (aminomethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, tris (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

N-[(4-(아미노메틸)페닐]-6-[아미노(하이드록시이미노)메틸]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;N-[(4- (aminomethyl) phenyl] -6- [amino (hydroxyimino) methyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt;

6-(아미노이미노메틸)-N-[4-(하이드록시메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [4- (hydroxymethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

메틸 [3-[[[4-(아미노메틸)페닐]아미노]카보닐]-7-[4-아미노(하이드록시이미노)메틸]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염;Methyl [3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -7- [4-amino (hydroxyimino) methyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate ) Salts;

6-(아미노이미노메틸)-N-페닐-4-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N-phenyl-4- (tetrahydro-3-furanyl) -2-naphthalenecarboxamide, monohydrochloride;

6-[아미노(하이드록시이미노)메틸]-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드;6- [amino (hydroxyimino) methyl] -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboxamide;

6-(아미노이미노메틸)-4-[5-(에틸티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (ethylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[5-(프로필티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (propylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-N-페닐-4-(2-피롤리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N-phenyl-4- (2-pyrrolidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt;

6-(아미노이미노메틸)-4-[5-(프로필설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (propylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[5-(메틸티오)메틸]-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (methylthio) methyl] -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[5-(메톡시메틸)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (methoxymethyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride;

6-(아미노이미노메틸)-4-[5-(메틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염; 및6- (aminoiminomethyl) -4- [5- (methylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, mono (trifluoroacetate) salt; And

6-(아미노이미노메틸)-4-[5-(에틸티오)테트라하이드로-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드.6- (aminoiminomethyl) -4- [5- (ethylthio) tetrahydro-3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride.

유로키나제 억제 결정Eurokinase Inhibition Determination

본 발명의 화합물의 유로키나제 억제제로서의 효능은 구조식 피로Glu-Arg-pNA-HCl(Chromogenix의 배급업자인 DiaPharma Group, Inc.)의, 기질 S-2444에 대한 유로키나제 효소 애보키나제(Abbokinase; Abbott Laboratories, Abbott Park, IL)의 억제를 200μM로 측정함으로써 결정한다.Efficacy as a urokinase inhibitor of a compound of the present invention is shown by the structural fatigue Glu-Arg-pNA-HCl (DiaPharma Group, Inc., a distributor of Chromogenix), the urokinase enzyme avokinase (Abbokinase; Abbott Laboratories, Abbott Park) on substrate S-2444. , Inhibition of IL) is determined by measuring 200 μM.

본 검정은 50mM 트리스/0.15M NaCl + 0.5% 플루로닉 F-68(제조원: Sigma P-5556), pH 7.4(HCl 사용) 완충액 중에서 96웰 폴리스티렌 평편 바닥 평판에서 수행한다. DMSO 중의 본 발명의 화합물 10mM을 DMSO로 희석시켜 8가지 1/2 로그 농도, 예를 들면, 1200μM, 400μM, 120μM, 40μM, 12μM, 4μM, 1μM 및 0.4μM가 되게 한다. 4가지 농도를 선택한 다음, 각각의 5㎕를 희석시켜 총 검정 용량이 200㎕가 되게 한다. 상기 예에 따르는, 본 검정에서의 최종 화합물 농도는 각각 30μM, 10μM, 3μM, 1μM, 0.3μM, 0.1μM, 0.03μM 및 0.01μM이다. 본 검정에서 기질 S-2444는 200μM로 사용한다. 수 개의 바이알을 이러한 바이알에 대해 지시된 바와 같이 재구성하고, 등량으로 나누어 동결 저장한다. 이 효소를 검정용 완충액으로 추가로 희석시키고 이중 10㎕를 본 검정에 사용한다. 이 검정에서의 효소 농도는 2 내지 3nM이다. 이러한 검정은 다음과 같이 수행한다. 완충액 175㎕를 폴리스티렌 평판에 피펫팅하고, DMSO 중의 본 발명의 화합물 5㎕ 용액을 가하며, 혼합물을 와동시킨 다음, 완충액 중의 효소 10㎕를 가하고, 이 혼합물을 와동시킨 다음, 수중 기질 10㎕를 가하며, 혼합물을 와동시킨 다음, 상기 판을 스펙트로맥스R(Molecular Devices Corporation, Sunnyvale, Ca) 평판 판독기에 놓은 다음, 405nm에서 15분 동안 반응시킨다. 이러한 스펙트로맥스R는 임의의 억제제의 부재하에서 효소의 반응 속도에 대한 본 발명의 화합물의 억제율(%)을 산출하는데 사용되는 반응 속도를 산출한다. 이러한 억제제의 Ki는 억제율(%)로부터 산출되며 앞서 Km으로 정립되었다. 본 발명의 화합물은 표 1a 내지 1i에서의 대표적인 예에 대한 데이타가 제시하는 바와 같이 유로키나제를 억제한다.This assay is performed on 96-well polystyrene flat bottom plates in 50 mM Tris / 0.15 M NaCl + 0.5% Pluronic F-68 (Sigma P-5556), pH 7.4 (using HCl) buffer. Dilute 10 mM of the compound of the present invention in DMSO with DMSO to 8 1/2 log concentrations, such as 1200 μM, 400 μM, 120 μM, 40 μM, 12 μM, 4 μM, 1 μM and 0.4 μM. Four concentrations are selected and each 5 μl is diluted to a total assay volume of 200 μl. According to the above examples, the final compound concentrations in this assay are 30 μM, 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM and 0.01 μM, respectively. Substrate S-2444 is used at 200 μM in this assay. Several vials are reconstituted as indicated for these vials, divided into equal portions and stored frozen. This enzyme is further diluted with assay buffer and 10 μl of this is used for this assay. Enzyme concentration in this assay is 2-3 nM. This assay is performed as follows. 175 μl of the buffer is pipetted into a polystyrene plate, 5 μl of a compound of the invention in DMSO is added, the mixture is vortexed, 10 μl of enzyme in buffer is added, the mixture is vortexed, and then 10 μl of substrate in water After vortexing the mixture, the plate is placed in a Spectromax R (Molecular Devices Corporation, Sunnyvale, Ca) plate reader and allowed to react at 405 nm for 15 minutes. This Spectromax R yields the reaction rate used to calculate the percent inhibition of the compounds of the present invention over the reaction rate of the enzyme in the absence of any inhibitor. Ki of these inhibitors is calculated from% inhibition and was previously defined as Km. Compounds of the invention inhibit urokinase, as the data for representative examples in Tables 1A-1I show.

약제학적 조성물Pharmaceutical composition

본 발명은 하나 이상의 비독성의 약제학적으로 허용되는 담체와 함께 제형화된 본 발명의 화합물을 포함하는 약제학적 조성물을 제공한다. 당해 약제학적 조성물은 고형 또는 액상형의 경구 투여용, 비경구 주사용 또는 직장 투여용으로 특별히 제형화될 수 있다.The present invention provides a pharmaceutical composition comprising a compound of the present invention formulated with one or more nontoxic pharmaceutically acceptable carriers. The pharmaceutical compositions may be specially formulated for oral, parenteral or rectal administration in solid or liquid form.

본 발명의 약제학적 조성물은 사람과 기타 동물에게 경구, 직장, 비경구, 지망막하조내, 질내, 복강내, 국부(산제, 연고 또는 점적제에 의함), 볼내, 또는 경구 또는 비내 분무로서 투여할 수 있다. 본원에 사용된 바와 같은 용어 "비경구" 투여는 정맥내, 근육내, 복강내, 흉골내, 피하 및 관절내 주사 및 주입을 포함하는 투여 양식을 지칭한다.The pharmaceutical composition of the present invention is administered to humans and other animals as oral, rectal, parenteral, subretinal alveolar, intravaginal, intraperitoneal, topical (by powder, ointment or drop), intranasal, or oral or nasal spray can do. The term “parenteral” administration as used herein refers to a dosage form comprising intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion.

비경구 주사용의 본 발명의 약제학적 조성물은 약제학적으로 허용되는 멸균성의 수성 또는 비수성 액제, 분산제, 현탁제 또는 유제 뿐만 아니라 사용 직전에 멸균성의 주사 가능한 액제 또는 분산제로 재구성하기 위한 멸균성 산제를 포함한다. 적합한 수성 및 비수성 담체, 희석제, 용매 또는 부형제로는 물, 에탄올, 폴리올(예를 들면, 글리세롤, 프로필렌 글리콜, 폴리에틸렌 글리콜 등), 및 이들의 적합한 혼합물, 식물성 오일(예를 들면, 올리브유) 및 주사 가능한 유기 에스테르(예를 들면, 에틸 올레에이트)가 있다. 예를 들면, 레시틴 등의 코팅 물질을 사용하고, 분산제의 경우에 요구된 입자 크기를 유지하며, 계면활성제를 사용함으로써 적절한 유동성을 유지할 수 있다.Pharmaceutical compositions of the present invention for parenteral injection include pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersants, suspensions or emulsions, as well as sterile powders for reconstitution with sterile injectable solutions or dispersants immediately prior to use. It includes. Suitable aqueous and non-aqueous carriers, diluents, solvents or excipients include water, ethanol, polyols (eg glycerol, propylene glycol, polyethylene glycol, etc.), and suitable mixtures thereof, vegetable oils (eg olive oil), and Injectable organic esters (eg ethyl oleate). For example, proper fluidity can be maintained by using a coating material such as lecithin, maintaining the required particle size in the case of dispersants, and by using surfactants.

이들 조성물은 또한, 보존제, 습윤제, 유화제 및 분산제 등의 보조제를 함유할 수도 있다. 각종 항균제 및 항진균제, 예를 들면, 파라벤, 클로로부탄올, 페놀 소르브산 등을 포함시킴으로써 미생물의 작용을 방지할 수 있다. 또한, 당, 염화나트륨 등의 등장성 제제를 포함시키는 것이 바람직할 수도 있다. 흡수를 지연시키는 제제(예: 알루미늄 모노스테아레이트 및 젤라틴)를 포함시킴으로써 주사 가능한 약제학적 형태의 흡수를 지속시킬 수 있다.These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers and dispersants. The action of microorganisms can be prevented by including various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like. Absorption of injectable pharmaceutical forms can be continued by including agents that delay absorption, such as aluminum monostearate and gelatin.

몇몇 경우에 있어서, 약물의 효과를 지속시키기 위하여, 피하 또는 근육내 주사액으로부터의 약물의 흡수를 느리게하는 것이 바람직하다. 이는 수 용해도가 낮은 결정성 또는 무정형 물질의 액상 현탁제를 사용함으로써 수행할 수 있다. 이때, 약물의 흡수 속도는 결정 크기와 결정성 형태에 따라 좌우될 수 있는 이의 용해 속도에 의존된다. 또 다르게는, 비경구적으로 투여된 약물형의 흡수 지연은 약물을 오일 부형제에 용해 또는 현탁시킴으로써 수행된다.In some cases, to sustain the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injections. This can be done by using liquid suspensions of crystalline or amorphous materials with low water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of the parenterally administered drug type is performed by dissolving or suspending the drug in an oil excipient.

주사용 데포 형태는 폴리락타이드-폴리글리콜라이드 등의 생분해 가능한 중합체 내에 약물의 미세캡슐 매트릭스를 형성시킴으로써 제조한다. 중합체에 대한 약물의 비율 및 이용된 특정한 중합체의 성질에 따라서, 약물 방출 속도가 조절될 수 있다. 기타 생분해 가능한 중합체의 예로는 폴리(오르토에스테르) 및 폴리(무수물)이 있다. 데포 주사용 제형은 또한, 약물을 신체 조직과 상용성인 리포좀 또는 마이크로에멀젼에 포획시킴으로써 제조한다. 이러한 주사용 제형은, 예를 들면, 세균-보유 필터로 여과시키거나, 또는 사용 직전에 멸균수 또는 기타 멸균성의 주사용 매질에 용해 또는 분산시킬 수 있는 멸균성 고형 조성물의 형태로 멸균제를 혼입시킴으로써 멸균시킬 수 있다.Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers are poly (orthoesters) and poly (anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissue. Such injectable formulations may be incorporated, for example, with a sterilizing agent in the form of a sterile solid composition which can be filtered with a bacterial-retaining filter or dissolved or dispersed in sterile water or other sterile injectable media immediately prior to use. By sterilization.

경구 투여용의 고형 제형으로는 캅셀제, 정제, 환제, 산제 및 과립제가 있다. 이러한 고형 제형에서는, 활성 화합물을 불활성이고 약제학적으로 허용되는 하나 이상의 부형제 또는 담체, 예를 들면, 나트륨 시트레이트 또는 인산이칼슘 및/또는 a) 전분, 락토즈, 슈크로즈, 글루코즈, 만니톨 및 규산 등의 충전제 또는 점증제, b) 카복시메틸 셀룰로즈, 알기네이트, 젤라틴, 폴리비닐피롤리돈, 슈크로즈 및 아카시아 등의 결합제, c) 글리세롤 등의 보습제, d) 한천-한천, 탄산칼슘, 감자 또는 타피오카 전분, 알긴산, 특정 실리케이트 및 탄산나트륨 등의 붕해제, e) 파라핀 등의 용해 지연제, f) 4급 암모늄 화합물 등의 흡수 촉진제, g) 세틸 알콜 및 글리세롤 모노스테아레이트 등의 습윤제, h) 카올린 및 벤토나이트 점토 등의 흡수제 및 i) 탈크, 칼슘 스테아레이트, 마그네슘 스테아레이트, 고체 폴리에틸렌 글리콜, 나트륨 라우릴 설페이트 등의 윤활제, 및 이들의 혼합물과 혼합한다. 캅셀제, 정제 및 환제의 경우에는, 제형은 완충제를 포함할 수도 있다. 유사한 유형의 고형 조성물은 락토즈 또는 밀크 당과 같은 부형제 및 고분자량 폴리에틸렌 글리콜 등을 사용하여 연질 및 경질 충전된 젤라틴 캅셀제에서 충전제로서 이용할 수도 있다.Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is inert and one or more pharmaceutically acceptable excipients or carriers, for example sodium citrate or dicalcium phosphate and / or a) starch, lactose, sucrose, glucose, mannitol and silicic acid Fillers or thickeners, such as b) carboxymethyl cellulose, alginate, gelatin, binders such as polyvinylpyrrolidone, sucrose and acacia, c) humectants such as glycerol, d) agar-agar, calcium carbonate, potatoes or Disintegrants such as tapioca starch, alginic acid, certain silicates and sodium carbonate, e) dissolution retardants such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as cetyl alcohol and glycerol monostearate, h) kaolin And absorbents such as bentonite clay and i) talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate Lubricants, and mixtures thereof. In the case of capsules, tablets and pills, the formulation may comprise a buffer. Solid compositions of a similar type may also be used as fillers in soft and hard filled gelatin capsules using excipients such as lactose or milk sugar and high molecular weight polyethylene glycols and the like.

정제, 당의정, 캅셀제, 환제 및 과립제의 고형 제형은 약제학적 제형화 분야에 널리 공지된 장용성 코팅제 및 기타 코팅제와 같은 코팅제 및 쉘을 사용하여 제조할 수 있다. 이들은 유백제를 임의로 함유할 수 있고 또한, 임의로 또는 지연된 방식으로, 활성 성분(들)을 단지 장관의 특정 부분에서 또는 우선적으로 방출시키는 조성물일 수 있다. 사용될 수 있는 매봉 조성물의 예에는 중합체성 물질 및 왁스가 포함된다.Solid formulations of tablets, dragees, capsules, pills, and granules can be prepared using coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They may optionally contain a bleach and may also be compositions which, in an optional or delayed manner, release only or preferentially the active ingredient (s) in a specific part of the intestine. Examples of embedding compositions that can be used include polymeric substances and waxes.

당해 활성 화합물은 또한, 경우에 따라 상기 언급된 하나 이상의 부형제를 갖는 미세-캡슐화된 형태일 수 있다.The active compound may also be in micro-encapsulated form, optionally with one or more excipients mentioned above.

경구 투여용 액상 제형으로는 약제학적으로 허용되는 유제, 액제, 현탁제, 시럽제 및 엘릭서제가 있다. 이러한 액상 제형은 활성 화합물 이외에, 당해 분야에서 통상적으로 사용되는 불활성 희석제, 예를 들면, 물 또는 기타 용매, 가용화제 및 유화제, 예를 들면, 에틸 알콜, 이소프로필 알콜, 에틸 카보네이트, 에틸 아세테이트, 벤질 알콜, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸렌 글리콜, 디메틸 포름아미드, 오일(특히, 면실유, 땅콩유, 옥수수유, 발아유, 올리브유, 피마자유, 및 참깨유), 글리세롤, 테트라하이드로푸르푸릴 알콜, 폴리에틸렌 글리콜 및 솔비탄의 지방산 에스테르, 및 이들의 혼합물을 함유할 수 있다. 불활성 희석제 이외에도, 상기 경구용 조성물은 습윤제, 유화제 및 현탁화제, 감미제, 향미제 및 향료 등의 보조제를 포함할 수 있다. 현탁제는 활성 화합물 이외에, 예를 들면, 에톡시화 이소스테아릴 알콜, 폴리옥시에틸렌 솔비톨 및 솔비탄 에스테르, 미세결정성 셀룰로즈, 알루미늄 메타하이드록사이드, 벤토나이트, 한천-한천 및 트라가칸트 등의 현탁화제 및 이들의 혼합물을 함유할 수 있다. 직장 또는 질내 투여용 조성물은 본 발명의 화합물을 적합한 무-자극성 부형제 또는 담체, 예를 들면, 코코아 버터, 폴리에틸렌 글리콜, 또는 실온에서는 고체이지만 신체 온도에서는 액체이기 때문에 직장 또는 질내에서 용융되어 활성 화합물을 방출시키는 좌제용 왁스와 혼합함으로써 제조될 수 있는 좌제가 바람직하다.Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. Such liquid formulations, in addition to the active compounds, are inert diluents commonly used in the art, such as water or other solvents, solubilizers and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl Alcohols, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (especially cottonseed oil, peanut oil, corn oil, germinated oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydro Fatty acid esters of furfuryl alcohol, polyethylene glycol and sorbitan, and mixtures thereof. In addition to the inert diluent, the oral composition may include auxiliaries such as wetting agents, emulsifiers and suspending agents, sweetening agents, flavoring agents and flavoring agents. Suspending agents in addition to the active compounds, for example, suspending such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth Agents and mixtures thereof. Compositions for rectal or vaginal administration may contain the compounds of the present invention in a suitable non-irritating excipient or carrier such as cocoa butter, polyethylene glycol, or in the rectum or vagina, because they are solid at room temperature but liquid at body temperature. Preference is given to suppositories which can be prepared by mixing with the releasing suppository wax.

본 발명의 화합물을 또한, 리포좀의 형태로 투여할 수 있다. 당해 분야에 공지된 바와 같이, 리포좀은 일반적으로 인지질 또는 기타 지질 물질로부터 유도된다. 리포좀은 수성 매질에 분산된 단층 또는 다층의 수화된 액정에 의해 형성된다. 리포좀을 형성시킬 수 있는 어떠한 비-독성의 생리학적으로 허용되고 대사 가능한 지질도 사용될 수 있다. 리포좀 형태의 본 발명의 조성물은 본 발명의 화합물 이외에도, 안정화제, 보존제, 부형제 등을 함유할 수 있다. 바람직한 지질은 천연 및 합성의 인지질 및 포스파티딜 콜린(레시틴)이다. 리포좀을 형성하는 방법은 당해 분야에 공지되어 있다[참조: Prescott, Ed., Methods in Cell Biology, Volume ⅩⅣ, Academic Press, New York, N.Y. (1976), p.33 et seq].The compounds of the invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by monolayer or multilayer hydrated liquid crystal dispersed in an aqueous medium. Any non-toxic physiologically acceptable and metabolizable lipid that can form liposomes can be used. The composition of the present invention in liposome form may contain, in addition to the compound of the present invention, stabilizers, preservatives, excipients and the like. Preferred lipids are natural and synthetic phospholipids and phosphatidyl choline (lecithin). Methods of forming liposomes are known in the art. See Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq.

본 발명에 따르는 화합물의 국부 투여용 제형으로는 산제, 분무제, 연고 및 흡입제가 있다. 활성 화합물을 멸균성 조건하에서 약제학적으로 허용되는 담체 및 필요에 따라 요구되는 보존제, 완충제 또는 추진제와 혼합한다. 안과용 제형, 안 연고, 산제 및 액제가 본 발명의 범위 내에 속하는 것으로 간주된다.Formulations for topical administration of the compounds according to the invention include powders, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and, if desired, a preservative, buffer or propellant. Ophthalmic formulations, eye ointments, powders and solutions are considered to be within the scope of the present invention.

본 발명의 약제학적 조성물 중에서의 활성 성분의 실제적인 투여량 수준은 특정 환자, 조성물 및 투여 방식에 대한 목적하는 치료학적 반응을 달성하기에 유효한 활성 화합물(들)의 양을 획득하도록 다양할 수 있다. 선택된 투여량 수준은 특정한 화합물의 활성; 투여 경로; 치료받는 질환의 중증도; 및 치료받는 환자의 상태 및 이전 병력에 의해 결정될 것이다. 그러나, 목적하는 치료학적 효과를 달성하는데 요구되는 양보다 적은 수준의 화합물 용량부터 시작하고 목적하는 효과가 달성될 때까지 투여량을 점차적으로 증가시키는 것은 당해 분야의 기술 내에 속한다. 일반적으로, 1일 활성 화합물 약 1 내지 약 50mg/체중kg, 더욱 바람직하게는 약 5 내지 약 20mg/체중kg의 투여량을 포유동물 환자에게 경구 투여한다. 경우에 따라, 이러한 유효한 1일 투여량을 수회 분복 용량, 예를 들면, 1일 2 내지 4회의 분복 용량으로 나누어 투여할 수 있다.Actual dosage levels of active ingredients in the pharmaceutical compositions of the invention may vary to obtain an amount of active compound (s) effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration. . The dosage level chosen will depend on the activity of the particular compound; Route of administration; Severity of the disease being treated; And the condition and previous medical history of the patient being treated. However, it is within the skill in the art to start with a compound dose of less than the amount required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. In general, dosages of about 1 to about 50 mg / kg body weight, more preferably about 5 to about 20 mg / kg body weight of active compound per day are orally administered to mammalian patients. If desired, such effective daily dosages may be administered in several divided doses, for example two to four divided doses per day.

본 발명의 화합물의 제조Preparation of Compounds of the Invention

본 발명의 화합물은 각종 합성 경로로 제조할 수 있다. 대표적인 과정이 다음 반응식 1 내지 6에 요약되어 있다.The compounds of the present invention can be prepared by various synthetic routes. Representative procedures are summarized in the following schemes 1-6.

약어Abbreviation

다음의 반응식과 실시예를 기술하는데 사용된 약어는 다음과 같다: THF - 테트라하이드로푸란; DMF - N,N-디메틸포름아미드; OEt2- 디에틸 에테르 ; EDC - 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 하이드로클로라이드; NMM - N-메틸모르폴린; LDA - 리튬 디이소프로필아미드; TFA - 트리플루오로아세트산; DMSO - 디메틸설폭사이드; DMAP - 4-(N,N-디메틸아미노)피리딘; HATU - O-(아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄헥사플루오로포스페이트; Boc - 3급 부틸카보닐옥시; DDQ - 2,3-디클로로-5,6-디시아노-1,4-벤조퀴논; Bn - 벤질; DPPA -디페닐포스포릴 아지드; DCC - 디사이클로헥실카보디이미드; EDC - 1-(3-디메틸아미노프로필)-3-에틸카보디이미드 하이드로클로라이드; SEM -2-(트리메틸실릴)에톡시메틸; dppf - 1,1'-비스(디페닐포스피노)페로센; 및 dba - 디벤질리덴아세톤. 출발 물질, 시약 및 용매는 알드리치 케미칼 캄파니(Aldrich Chemical Company, Milwaukee, Wi)로부터 구입한다.The abbreviations used to describe the following schemes and examples are as follows: THF-tetrahydrofuran; DMF-N, N-dimethylformamide; OEt 2 -diethyl ether; EDC-1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride; NMM-N-methylmorpholine; LDA-lithium diisopropylamide; TFA-trifluoroacetic acid; DMSO-Dimethylsulfoxide; DMAP-4 (N, N-dimethylamino) pyridine; HATU-O- (Azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate; Boc-tertiary butylcarbonyloxy; DDQ-2,3-dichloro-5,6-dicyano-1,4-benzoquinone; Bn-benzyl; DPPA-diphenylphosphoryl azide; DCC-dicyclohexylcarbodiimide; EDC-1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride; SEM-2- (trimethylsilyl) ethoxymethyl; dppf-1,1'-bis (diphenylphosphino) ferrocene; And dba-dibenzylideneacetone. Starting materials, reagents and solvents are purchased from Aldrich Chemical Company, Milwaukee, Wi.

반응식 1에 제시된 바와 같이, 3-시아노프로피온알데히드 디에틸 아세탈 2을 리튬 디이소프로필아미드 등의 강 염기로 처리한 다음 생성된 음이온을 적절하게 치환된 벤즈알데히드 1로 처리한 후, 상응하는 시아노하이드린 3을 황산 등의 루이스산으로 폐환 및 방향족화시킴으로써 나프탈렌카보니트릴 4, 5 및 6을 제조한다:As shown in Scheme 1, 3-cyanopropionaldehyde diethyl acetal 2 is treated with a strong base such as lithium diisopropylamide, and then the resulting anions are treated with an appropriately substituted benzaldehyde 1, followed by corresponding cyanohighs. Naphthalenecarbonitriles 4, 5, and 6 are prepared by ring closure and aromatization of Drin 3 with Lewis acids such as sulfuric acid:

반응식 2에 제시된 바와 같이, 4를 AlCl3또는 BBr3등의 루이스산, 바람직하게는 AlCl3로 선택적으로 탈메틸화하여 7을 제공한다. 7을 탄산칼륨, 수소화나트륨 또는 불화세슘 등의 염기로 처리한 다음, RC-X(여기서, X는 이탈 그룹이다)로 처리하여 8(여기서, -LC-은 -O-이다)을 제공한다. 또 다른 방법으로는, 7을 트리플루오로메탄설폰산 무수물 또는 1,1,1-트리플루오로-N-페닐-N-[(트리플루오로메틸)설포닐]메탄설폰아미드로 처리하여 9를 제공하며, 이를 팔라듐 촉매, 바람직하게는 Pd(Ⅱ)Cl2(dba) 또는 Pd(Ph3P)4및 염기, 바람직하게는 불화세슘 또는 탄산칼륨의 존재하에서 RC-B(OH)2,, RC-I 또는(여기서, RC는 치환되지 않거나 치환된 아릴 또는 헤테로사이클이다)로 처리하여 10을 제공할 수 있다. 또 다른 방법으로는, 9를 칼륨 t-부톡사이드 등의 강 염기, 및 Pd(Ⅱ)Cl2(dba) 등의 촉매의 존재하에서 RC-NR1R2(여기서, RC는 치환되지 않거나 치환된 아릴 또는 헤테로사이클이고, R1및 R2중의 하나 이상은 수소이다)로 처리하여 11을 제공할 수 있다.As shown in Scheme 2, 4 is selectively demethylated with a Lewis acid such as AlCl 3 or BBr 3 , preferably AlCl 3 to provide 7. 7 is treated with a base such as potassium carbonate, sodium hydride or cesium fluoride and then treated with R C -X where X is a leaving group to give 8 where -L C -is -O-. do. Alternatively, 7 is treated with trifluoromethanesulfonic anhydride or 1,1,1-trifluoro-N-phenyl-N-[(trifluoromethyl) sulfonyl] methanesulfonamide to give 9 provided, and this palladium catalyst, preferably Pd (ⅱ) Cl 2 (dba ) or Pd (Ph 3 P) 4 and a base, preferably under the presence of cesium fluoride or potassium carbonate R C -B (OH) 2, , R C -I or Where R C is unsubstituted or substituted aryl or heterocycle, to provide 10. In another method, 9 is R C -NR 1 R 2 , wherein R C is unsubstituted in the presence of a strong base such as potassium t-butoxide and a catalyst such as Pd (II) Cl 2 (dba). Substituted aryl or heterocycle, and at least one of R 1 and R 2 is hydrogen).

RC는 치환되지 않거나 치환된 아릴 또는 헤테로사이클이다R C is unsubstituted or substituted aryl or heterocycle

10: -LC-는 공유 결합이다10: -L C -is a covalent bond

11: -LC-는 -NR1-이다11: -L C -is -NR 1-

반응식 3에 제시된 바와 같이, 12를 선택적으로 O-트리플화한 다음, 생성된 13의 아미노 그룹을 산-불안정한 카보벤질옥시로 보호시켜 14를 수득한다. 14를 팔라듐 촉매, 바람직하게는 트리스(디벤질리덴아세톤)디팔라듐(0)-클로로포름 부가물의 존재하에서 KCN을 사용하여 15로 전환시키고, 산, 바람직하게는 아세트산 중의 30% HBr을 사용하여 15를 탈보호시켜 16을 수득한다. 15를 아실화제 RCC(O)Cl 및 염기, 바람직하게는 트리에틸아민, 디이소프로필에틸아민 또는 탄산칼륨으로 처리하여 중간체 17을 수득한다:As shown in Scheme 3, 12 is optionally O-tripled, and then the resulting amino group of 13 is protected with acid-labile carbobenzyloxy to yield 14. 14 is converted to 15 using KCN in the presence of a palladium catalyst, preferably tris (dibenzylideneacetone) dipalladium (0) -chloroform adduct, and 15 using 30% HBr in acid, preferably acetic acid Deprotection yields 16. 15 is treated with an acylating agent R C C (O) Cl and a base, preferably triethylamine, diisopropylethylamine or potassium carbonate, to give intermediate 17:

-LC-는 -C(O)NR1- 또는 -OC(O)NR1-이고-L C -is -C (O) NR 1 -or -OC (O) NR 1 -and

RC는 치환되지 않거나 치환된 알킬, 알케닐, 헤테로사이클 또는 아릴이다.R C is unsubstituted or substituted alkyl, alkenyl, heterocycle or aryl.

반응식 4에 제시된 바와 같이, 18의 8-메톡시 그룹을 AlCl3또는 BBr3등의 루이스산, 바람직하게는 AlCl3로 선택적으로 탈메틸화한 다음, 페놀 19를 탄산칼륨, 수소화나트륨 또는 불화세슘 등의 염기의 존재하에서 Bn-X[여기서, X는 Cl, Br 또는 I이다]로 알킬화시킴으로써 이를 재보호시킨다. 이러한 중간체를 리튬, 나트륨 또는 칼륨 디이소프로필아미드 또는 알콕사이드 등의 비-친핵성 강 염기로 탈양성자화시킨 다음, 알킬 포르메이트, 바람직하게는 에틸 포르메이트로 처리하여 에놀 20을 수득함으로써 20을 제조한다. 20을 하이드록실아민으로 처리하여 이속사졸 21을 수득하고, 이를 리튬, 나트륨 또는 칼륨 알콕사이드, 바람직하게는 나트륨 메톡사이드로 개환시켜 22를 수득할 수 있다. 수소화붕소나트륨을 이용하여 카보닐 환원시키면서 동시에 알켄 형성시켜 23을 수득하고; DDQ로 방향족화시키고 수소 및 팔라듐 촉매, 바람직하게는 탄소상 팔라듐으로 촉매적 탈벤질화하여 24를 수득한다. 24를 탄산칼륨, 수소화나트륨 또는 불화세슘 등의 염기로 처리한 다음 RC-X로 처리함으로써 알킬화한다.As shown in Scheme 4, the 8-methoxy group of 18 is selectively demethylated with a Lewis acid such as AlCl 3 or BBr 3 , preferably AlCl 3 , and then phenol 19 is converted to potassium carbonate, sodium hydride or cesium fluoride or the like. It is reprotected by alkylation with Bn-X, wherein X is Cl, Br or I in the presence of a base of. 20 is prepared by deprotonation of this intermediate with a non-nucleophilic strong base such as lithium, sodium or potassium diisopropylamide or alkoxide and then treatment with alkyl formate, preferably ethyl formate to obtain enol 20. do. 20 can be treated with hydroxylamine to yield isoxazole 21, which can be ring-opened with lithium, sodium or potassium alkoxides, preferably sodium methoxide, to give 22. Alkene formation simultaneously with carbonyl reduction with sodium borohydride to give 23; Aromatization with DDQ and catalytic debenzylation with hydrogen and a palladium catalyst, preferably palladium on carbon yields 24. 24 is alkylated by treatment with a base such as potassium carbonate, sodium hydride or cesium fluoride and then with R C -X.

반응식 5에 제시된 바와 같이, 25를 수산화리튬, 수산화나트륨 또는 수산화칼륨 등의 염기 1당량으로 일가수분해시켜 산-에스테르 26을 수득한다. 26을 티오닐 클로라이드 또는 옥살릴 클로라이드/DMF로 처리한 다음 암모니아로 처리하여 아미드 27을 수득한다. 27을 티오닐 클로라이드 또는 옥시염화인 등의 탈수제로 처리하여 니트릴 28을 수득한다.As shown in Scheme 5, monohydrolysis 25 to 1 equivalent of a base such as lithium hydroxide, sodium hydroxide or potassium hydroxide to yield acid-ester 26. 26 is treated with thionyl chloride or oxalyl chloride / DMF followed by ammonia to give amide 27. 27 is treated with a dehydrating agent such as thionyl chloride or phosphorus oxychloride to give nitrile 28.

28을 질산/질화칼륨으로 위치 선택적으로 질소화시킨 다음, 니트로 그룹을 팔라듐 촉매, 바람직하게는 탄소상 팔라듐으로 환원시켜 중간체 31을 수득하고, 이를 RCC(O)Cl 또는 RCOC(O)Cl 및 염기, 바람직하게는 디이소프로필에틸아민 또는 탄산칼륨으로 처리하여 37을 수득한다.Regioselective nitrogenization of 28 with nitric acid / potassium nitride, and then the nitro group is reduced with a palladium catalyst, preferably palladium on carbon, to obtain intermediate 31, which is either R C C (O) Cl or R C OC 37) is obtained by treatment with Cl and a base, preferably diisopropylethylamine or potassium carbonate.

28을 수산화리튬, 수산화나트륨 또는 수산화칼륨 1당량으로 가수분해시켜 카복실산 29를 형성시킨 다음, DPPA 또는 티에닐 클로라이드로 처리한 후 나트륨 아지드로 처리하고, 이러한 중간체 이소시아네이트 32를 산, 바람직하게는 황산으로 가수분해시켜 아민 33을 수득한다. 또 다른 방법으로는, 32를 1급 또는 2급 아민으로 처리하여 우레아 34(여기서, -LA-는 -NR1C(X)R2-이고 X는 O이다)를 수득한다.Hydrolysis of 28 to 1 equivalent of lithium hydroxide, sodium hydroxide or potassium hydroxide to form carboxylic acid 29, followed by treatment with DPPA or thienyl chloride followed by sodium azide, and the intermediate isocyanate 32 with acid, preferably sulfuric acid Hydrolysis yields amine 33. Alternatively, 32 is treated with primary or secondary amines to yield urea 34, where -L A -is -NR 1 C (X) R 2 -and X is O.

29를 1급 또는 2급 아민과 커플링시키고 33을 카복실산과 커플링시켜 각각 아미드 35 및 36을 형성할 수 있다. 어떠한 경우에서든, 상기 아민과 카복실산을 DCC, EDC 또는 HATU를 이용하여 커플링시킨다.29 may be coupled with primary or secondary amines and 33 with carboxylic acids to form amides 35 and 36, respectively. In any case, the amine and carboxylic acid are coupled using DCC, EDC or HATU.

반응식 6에 제시된 바와 같이, 38을 트리플레이트제, 바람직하게는 트리플루오로메탄설포닐 무수물로 처리하여 39를 형성시킨 다음, 적절하게 치환된 알켄 또는 치환되지 않거나 치환된 알킨을 팔라듐 촉매, 바람직하게는 팔라듐(Ⅱ) 아세테이트를 이용하여 커플링시켜 40을 형성함으로써 -LA-가 -C≡C- 또는 -C=C-인 중간체를 제조한다.As shown in Scheme 6, 38 is treated with a triflate agent, preferably trifluoromethanesulfonyl anhydride, to form 39, and then an appropriately substituted alkene or unsubstituted alkyne is preferably a palladium catalyst, preferably Is coupled with palladium (II) acetate to form 40 to produce an intermediate in which -L A -is -C≡C- or -C = C-.

반응식 7에 제시된 바와 같이, 니트릴 중간체를 카복스이미드아미드 유로키나제 억제제 41로 전환시키는 것은 다음 3가지 방법에 의해 수행한다: (1) 중간체 카보니트릴을 리튬, 나트륨 또는 칼륨 비스(트리메틸실릴아미드), 바람직하게는 리튬 비스(트리메틸실릴아미드) 등의 비-친핵성 염기로 처리한 다음, 산, 바람직하게는 HCl로 가수분해시키는 방법; (2) 니트릴을 산, 바람직하게는 HCl로 처리한 다음 암모늄 아세테이트로 처리하는 방법; 및 (3) 니트릴을 H2S로 처리한 다음 메탄올 중의 암모니아 기체로 처리하는 방법. 이들 3가지 방법 중에서, H2S/NH3/메탄올 방법이 바람직하다. 본 발명의 화합물을 하이드로클로라이드 또는 메탄 설포네이트 염으로서 침전시키거나, 또는 역상 중간압 크로마토그래피로 정제하여 모노- 또는 비스-트리플루오로아세테이트 염을 형성시킨다.As shown in Scheme 7, the conversion of the nitrile intermediate to the carboximideamide urokinase inhibitor 41 is carried out by three methods: (1) the intermediate carbonitrile is lithium, sodium or potassium bis (trimethylsilylamide), preferably Preferably by treatment with a non-nucleophilic base such as lithium bis (trimethylsilylamide) and then hydrolyzed with an acid, preferably HCl; (2) treating nitrile with acid, preferably HCl, followed by ammonium acetate; And (3) treating nitrile with H 2 S followed by ammonia gas in methanol. Of these three methods, the H 2 S / NH 3 / methanol method is preferred. Compounds of the invention are precipitated as hydrochloride or methane sulfonate salts or purified by reverse phase medium pressure chromatography to form mono- or bis-trifluoroacetate salts.

합성법Synthesis

전술한 내용은 본 발명의 화합물을 제조할 수 있는 방법을 예시하고 있고 첨부된 청구의 범위에 규정된 본 발명의 범위를 제한하지 않는 다음 실시예를 참조로 하여 더욱 잘 이해될 수 있다.The foregoing may be better understood with reference to the following examples which illustrate how a compound of the present invention may be prepared and do not limit the scope of the invention as defined in the appended claims.

실시예 1Example 1

7,8-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7,8-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1AExample 1A

7,8-디메톡시-2-나프탈렌카보니트릴7,8-dimethoxy-2-naphthalenecarbonitrile

-78℃하의 신선하게 제조된 THF 중의 LDA의 용액을 THF(5ml) 중의 3-시아노프로피온알데히드 디에틸 아세탈(3.0g)로 적가 처리하고, 1시간 동안 교반하며, THF(5ml) 중의 2,3-디메톡시벤즈알데히드(3.2g)로 처리하고, 90분에 걸쳐 실온으로 가온하며, 물(40ml)로 처리하고, 농축시킨 다음 클로로포름으로 추출한다. 유기 층을 염수로 세척하고, 건조시키며(MgSO4) 농축시켜 황색 오일을 1.5g 수득한다. MS(DCI/NH3) m/e 341(M+H2O)+.A solution of LDA in freshly prepared THF at −78 ° C. was treated dropwise with 3-cyanopropionaldehyde diethyl acetal (3.0 g) in THF (5 ml), stirred for 1 hour, stirred in 2, THF (5 ml), Treat with 3-dimethoxybenzaldehyde (3.2 g), warm to room temperature over 90 minutes, treat with water (40 ml), concentrate and extract with chloroform. The organic layer is washed with brine, dried (MgSO 4 ) and concentrated to give 1.5 g of yellow oil. MS (DCI / NH 3 ) m / e 341 (M + H 2 O) + .

이러한 메탄올(5ml) 중의 오일 용액을 90℃에서 20% 수성 황산(100ml)에 적가한다. 이 용액을 90분 동안 가열하고, 실온으로 냉각시키며 클로로포름으로 추출한다. 합한 유기 추출물을 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 갈색 고체를 1.0g 수득하고, 이를 3:1 헥산/에틸 아세테이트를 이용하여 실리카 겔 상에서 플래쉬 크로마토그래피로 정제하여 표제 화합물을 800mg 수득한다. MS(DCI/NH3) m/e 231(M+H2O)+.This oil solution in methanol (5 ml) is added dropwise at 20 ° C. to 20% aqueous sulfuric acid (100 ml). The solution is heated for 90 minutes, cooled to room temperature and extracted with chloroform. The combined organic extracts were washed with brine, dried (MgSO 4 ) and concentrated to afford 1.0 g of a brown solid, which was purified by flash chromatography on silica gel using 3: 1 hexanes / ethyl acetate to give 800 mg of the title compound. To obtain. MS (DCI / NH 3 ) m / e 231 (M + H 2 O) + .

실시예 1BExample 1B

7,8-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7,8-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

0℃하의 THF(5ml) 중의 실시예 1(200mg) 용액을 리튬 비스(트리메틸실릴아미드)(헥산 중 1.0M, 1.1ml)로 처리하고, 실온에서 18시간 동안 교반하며, 10% HCl(10ml)로 처리하며, 실온에서 24시간 동안 교반하고, 농축시킨 다음, 5ml/min의 유속으로 160분에 걸쳐 90%A(0.1% 수성 TFA)/10%B(메탄올) 내지 10%A/90%B의 구배 범위로 용매 혼합물을 사용하여 250nM에서 UV 검출하면서 30cm x 2cm C-18 칼럼(40마이크론, J.T. Baker) 상에서 중간압 액체 크로마토그래피로 정제하여(100분 동안 매 2분마다 분획을 수집하고 생성물에 대해 TLC(10:1:1 아세토니트릴/물/아세트산)으로 분석한다) 표제 화합물을 100mg 수득한다.A solution of Example 1 (200 mg) in THF (5 ml) at 0 ° C. was treated with lithium bis (trimethylsilylamide) (1.0 M in hexane, 1.1 ml), stirred at room temperature for 18 h, 10% HCl (10 ml) , Stirred at room temperature for 24 hours, concentrated, and then 90% A (0.1% aqueous TFA) / 10% B (methanol) to 10% A / 90% B over 160 minutes at a flow rate of 5 ml / min. Purification by medium pressure liquid chromatography on a 30 cm x 2 cm C-18 column (40 microns, JT Baker) with UV detection at 250 nM using a solvent mixture with a gradient range of (collecting fractions every 2 minutes for 100 minutes Is analyzed by TLC (10: 1: 1 acetonitrile / water / acetic acid)) to 100 mg of the title compound.

1H NMR(300MHz, DMSO-d6) δ 4.41(s, 3H), 4.62(s, 3H), 7.41(d, 1H), 7.43(dd, 1H), 7.60(d, 1H), 7.80(d, 1H), 8.49(d, 1H), 9.31(bs, 2H), 9.48(bs, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.41 (s, 3H), 4.62 (s, 3H), 7.41 (d, 1H), 7.43 (dd, 1H), 7.60 (d, 1H), 7.80 (d , 1H), 8.49 (d, 1H), 9.31 (bs, 2H), 9.48 (bs, 2H);

MS(DCI/NH3) m/e 231 (M+H)+.MS (DCI / NH 3 ) m / e 231 (M + H) + .

C13H14N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 13 H 14 N 2 O 2 · TFA:

계산치: C, 52.33; H, 4.39; N, 8.14.Calc .: C, 52.33; H, 4. 39; N, 8.14.

실측치: C, 51.91; H, 4.35; N, 8.05.Found: C, 51.91; H, 4. 35; N, 8.05.

실시예 2Example 2

6,7,8-트리메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6,7,8-trimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 2AExample 2A

6,7,8-트리메톡시-2-나프탈렌카보니트릴6,7,8-trimethoxy-2-naphthalenecarbonitrile

2,3-디메톡시벤즈알데히드를 2,3,4-트리메톡시벤즈알데히드로 대체하는 것을 제외하고는 실시예 1A에 기재된 바와 같이 표제 화합물을 제조한다. MS(DCI/NH3) m/e 261(M+H2O)+.The title compound is prepared as described in Example 1A, except that 2,3-dimethoxybenzaldehyde is replaced by 2,3,4-trimethoxybenzaldehyde. MS (DCI / NH 3 ) m / e 261 (M + H 2 O) + .

실시예 2BExample 2B

6,7,8-트리메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6,7,8-trimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 표제 화합물을 제조 및 정제하여 표제 화합물을 100mg 수득한다.The title compound is prepared and purified as described in Example 1B to yield 100 mg of the title compound.

1H NMR(DMSO-d6300MHz) δ 3.91(s, 3H), 3.98(s, 3H), 4.06(s, 3H), 7.36(s, 1H), 7.75(dd, 1H), 7.99(d, 1H), 8.49(d, 1H), 9.18(bs, 2H), 9.38(bs, 2H); 1 H NMR (DMSO-d 6 300 MHz) δ 3.91 (s, 3H), 3.98 (s, 3H), 4.06 (s, 3H), 7.36 (s, 1H), 7.75 (dd, 1H), 7.99 (d, 1H), 8.49 (d, 1H), 9.18 (bs, 2H), 9.38 (bs, 2H);

MS (DCI/NH3) m/e 261 (M+H)+.MS (DCI / NH 3 ) m / e 261 (M + H) + .

C14H16N2O3·TFA에 대한 원소분석치:Elemental Analysis for C 14 H 16 N 2 O 3 TFA:

계산치: C, 51.34; H, 4.58; N, 7.48.Calc .: C, 51.34; H, 4.58; N, 7.48.

실측치: C, 50.91; H, 4.25; N, 7.35.Found: C, 50.91; H, 4. 25; N, 7.35.

실시예 3Example 3

6,7-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6,7-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 3AExample 3A

6,7-디메톡시-2-나프탈렌카보니트릴6,7-dimethoxy-2-naphthalenecarbonitrile

2,3-디메톡시벤즈알데히드를 3,4-디메톡시벤즈알데히드로 대체하는 것을 제외하고는 실시예 1A에 기재된 바와 같이 표제 화합물을 1.3g 제조한다. MS(DCI/NH3) m/e 231(M+H2O)+.1.3 g of the title compound is prepared as described in Example 1A except that 2,3-dimethoxybenzaldehyde is replaced by 3,4-dimethoxybenzaldehyde. MS (DCI / NH 3 ) m / e 231 (M + H 2 O) + .

실시예 3BExample 3B

6,7-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6,7-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 표제 화합물을 제조 및 정제하여 표제 화합물을 100mg 수득한다.The title compound is prepared and purified as described in Example 1B to yield 100 mg of the title compound.

1H NMR(DMSO-d6, 300MHz) δ 3.92(s, 3H), 3.94(s, 3H), 7.41(s, 1H), 7.44(s, 1H), 7.69(dd, 1H), 7.93(d, 1H), 8.49(d, 1H), 9.18(bs, 2H), 9.38(bs, 2H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 3.92 (s, 3H), 3.94 (s, 3H), 7.41 (s, 1H), 7.44 (s, 1H), 7.69 (dd, 1H), 7.93 (d , 1H), 8.49 (d, 1H), 9.18 (bs, 2H), 9.38 (bs, 2H);

MS(DCI/NH3) m/e 231 (M+H)+.MS (DCI / NH 3 ) m / e 231 (M + H) + .

C13H14N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 13 H 14 N 2 O 2 · TFA:

계산치: C, 52.33; H, 4.39; N, 8.14.Calc .: C, 52.33; H, 4. 39; N, 8.14.

실측치: C, 52.15; H, 4.20; N, 8.10.Found: C, 52.15; H, 4. 20; N, 8.10.

실시예 4Example 4

2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt

실시예 4AExample 4A

7-메톡시-8-하이드록시나프탈렌-2-카보니트릴7-methoxy-8-hydroxynaphthalene-2-carbonitrile

0℃하의 메틸렌 클로라이드(100ml) 중의 실시예 1A(1g) 용액을 AlCl3로 처리하고, 0℃에서 4시간 동안 교반하며 실온에서 18시간 동안 교반하고, 6N HCl(20ml)을 함유하는 물(200ml)에 붓고, 1시간 동안 교반한 다음, 메틸렌 클로라이드(100ml)로 희석시킨다. 층들을 분리시키고, 유기 층을 염수로 세척하며 건조시켜(MgSO4) 회백색 고체로서의 표제 화합물을 810mg 수득한다. MS(DCI/NH3) m/e 217(M+H2O)+.A solution of Example 1A (1 g) in methylene chloride (100 ml) at 0 ° C. was treated with AlCl 3 , stirred at 0 ° C. for 4 h and stirred at rt for 18 h, water containing 6N HCl (20 ml) (200 ml) ), Stirred for 1 h and diluted with methylene chloride (100 ml). The layers are separated and the organic layer is washed with brine and dried (MgSO 4 ) to give 810 mg of the title compound as an off-white solid. MS (DCI / NH 3 ) m / e 217 (M + H 2 O) + .

실시예 4BExample 4B

1,1-디메틸에틸 2-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]아세테이트1,1-dimethylethyl 2-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] acetate

DMF(3ml) 중의 실시예 4A(100mg), K2CO3(70mg), t-부틸 브로모아세테이트(120mg) 및 테트라부틸암모늄 요오다이드(25mg)의 슬러리를 실온에서 18시간 동안 교반하고, 물(20mg)로 희석시킨 다음, 에틸 아세테이트로 추출한다. 유기 추출물을 포화 NaHCO3및 염수로 세척하고, 건조시키며(Na2SO4) 농축시켜 청정한 오일로서의 표제 화합물을 200mg 수득한다. MS(DCI/NH3) m/e 331(M+H2O)+.A slurry of Example 4A (100 mg), K 2 CO 3 (70 mg), t-butyl bromoacetate (120 mg) and tetrabutylammonium iodide (25 mg) in DMF (3 ml) was stirred at room temperature for 18 hours, Dilute with water (20 mg) then extract with ethyl acetate. The organic extract is washed with saturated NaHCO 3 and brine, dried (Na 2 SO 4 ) and concentrated to give 200 mg of the title compound as a clear oil. MS (DCI / NH 3 ) m / e 331 (M + H 2 O) + .

실시예 4CExample 4C

2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt

0℃하의 메탄올(5ml) 중의 실시예 4B(100mg)을 HCl(g)으로 처리하고, 실온에서 18시간 동안 교반한 다음 농축시켜 회백색 고체를 수득한다. 이 고체를 메탄올(10ml) 중의 2N NH3로 처리하고, 50℃에서 3.5시간 동안 가열하며, 냉각시킨 다음 농축시켜 황색 고체를 수득하고, 이를 실시예 1B에 기재된 바와 같이 정제하여 표제 화합물을 10mg 수득한다.Example 4B (100 mg) in methanol (5 ml) at 0 ° C. is treated with HCl (g), stirred at room temperature for 18 hours and then concentrated to yield an off-white solid. This solid was treated with 2N NH 3 in methanol (10 ml), heated at 50 ° C. for 3.5 h, cooled and concentrated to give a yellow solid which was purified as described in Example 1B to give 10 mg of the title compound. do.

1H NMR(300MHz, DMSO-d6) δ 3.93(s, 3H), 4.79(s, 2H), 7.55(d, 2H), 7.65(dd, 1H), 7.72(d, 1H), 7.85(d, 1H), 8.09(d, 1H), 8.7(d, 1H), 9.03(bs, 2H), 9.45(bs, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.93 (s, 3H), 4.79 (s, 2H), 7.55 (d, 2H), 7.65 (dd, 1H), 7.72 (d, 1H), 7.85 (d , 1H), 8.09 (d, 1H), 8.7 (d, 1H), 9.03 (bs, 2H), 9.45 (bs, 2H);

MS (DCI/NH3) m/e 274 (M+H)+.MS (DCI / NH 3 ) m / e 274 (M + H) + .

C14H15N3O3·TFA에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 3 · TFA:

계산치: C, 49.62; H, 4.16; N, 10.85.Calc .: C, 49.62; H, 4. 16; N, 10.85.

실측치: C, 49.33; H, 4.03; N, 10.50.Found: C, 49.33; H, 4.03; N, 10.50.

실시예 5Example 5

7-벤질옥시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-benzyloxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 5AExample 5A

7-벤질옥시-8-요오도-2-나프탈렌카보니트릴7-benzyloxy-8-iodo-2-naphthalenecarbonitrile

프로필 요오다이드를 벤질 브로마이드로 대체하는 것을 제외하고는 실시예 43A에 기재된 바와 같이 표제 화합물을 제조한다. MS(DCI/NH3) m/e 403(M+NH4)+.The title compound is prepared as described in Example 43A except that propyl iodide is replaced with benzyl bromide. MS (DCI / NH 3 ) m / e 403 (M + NH 4 ) + .

실시예 5BExample 5B

7-벤질옥시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-benzyloxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 5A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 5A following the procedure of Example 1B.

1H NMR (300MHz, DMSO-d6) δ 9.30(br, 4H), 8.44(s, 1H), 8.12(d, 1H), 7.71(d, 2H), 7.67(dd, 1H), 7.57(d, 2H), 7.45-7.34(m, 3H), 5.45(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 9.30 (br, 4H), 8.44 (s, 1H), 8.12 (d, 1H), 7.71 (d, 2H), 7.67 (dd, 1H), 7.57 (d , 2H), 7.45-7.34 (m, 3H), 5.45 (s, 2H);

MS (DCI/NH3) m/e 403 (M+H)+.MS (DCI / NH 3 ) m / e 403 (M + H) + .

C18H15N2OI·TFA에 대한 원소분석치:Elemental Analysis for C 18 H 15 N 2 OI · TFA:

계산치: C, 46.53; H, 3.12; N, 5.43.Calc .: C, 46.53; H, 3. 12; N, 5.43.

실측치: C, 46.55; H, 3.10; N, 5.19.Found: C, 46.55; H, 3.10; N, 5.19.

실시예 6Example 6

메틸 [(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세테이트 모노(트리플루오로아세테이트) 염Methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetate mono (trifluoroacetate) salt

실시예 6AExample 6A

메틸 [(7-시아노-2-메톡시-1-나프탈레닐)옥시]아세테이트Methyl [(7-cyano-2-methoxy-1-naphthalenyl) oxy] acetate

DMF(15ml) 중의 실시예 4A(600mg), Cs2CO3(500mg), t-부틸 브로모아세테이트(120mg) 및 테트라부틸암모늄 요오다이드(25mg)의 용액을 실온에서 18시간 동안 교반하고, 물(20ml)로 희석시킨 다음, 에틸 아세테이트로 추출한다. 유기 추출물을 포화 NaHCO3및 염수로 세척하고, 건조시키며(Na2SO4) 농축시켜 투명한 오일로서의 표제 화합물을 800mg 수득한다. MS(DCI/NH3) m/e 331(M+H2O)+.A solution of Example 4A (600 mg), Cs 2 CO 3 (500 mg), t-butyl bromoacetate (120 mg) and tetrabutylammonium iodide (25 mg) in DMF (15 ml) was stirred at room temperature for 18 hours, Dilute with water (20 ml) then extract with ethyl acetate. The organic extract is washed with saturated NaHCO 3 and brine, dried (Na 2 SO 4 ) and concentrated to give 800 mg of the title compound as a clear oil. MS (DCI / NH 3 ) m / e 331 (M + H 2 O) + .

실시예 6BExample 6B

메틸 [(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세테이트 모노(트리플루오로아세테이트) 염Methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetate mono (trifluoroacetate) salt

0℃하의 메탄올(30ml) 중의 실시예 6A(100mg)을 HCl(g)으로 처리하고, 실온에서 18시간 동안 교반한 다음 농축시켜 회백색 고체를 수득한다. 이 고체를 메탄올(10ml) 중의 암모늄 아세테이트(100mg)로 처리하고, 40℃에서 15시간 동안 가열하며, 냉각시킨 다음 농축시켜 황색 고체를 수득하고, 이를 실시예 1B에 기재된 바와 같이 정제하여 표제 화합물을 10mg 수득한다.Example 6A (100 mg) in methanol (30 ml) at 0 ° C. was treated with HCl (g), stirred at room temperature for 18 hours and then concentrated to yield an off-white solid. This solid was treated with ammonium acetate (100 mg) in methanol (10 ml), heated at 40 ° C. for 15 h, cooled and concentrated to give a yellow solid, which was purified as described in Example 1B to give the title compound. 10 mg is obtained.

1H NMR(300MHz, DMSO-d6) δ 3.65(s, 3H), 3.93(s, 3H), 4.79(s, 2H), 7.65(dd, 1H), 7.72(d, 1H), 7.85(d, 1H), 8.09(d, 1H), 8.7(d, 1H), 9.03(bs, 2H), 9.45(bs, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.65 (s, 3H), 3.93 (s, 3H), 4.79 (s, 2H), 7.65 (dd, 1H), 7.72 (d, 1H), 7.85 (d , 1H), 8.09 (d, 1H), 8.7 (d, 1H), 9.03 (bs, 2H), 9.45 (bs, 2H);

MS(DCI/NH3) m/e 289(M+H)+.MS (DCI / NH 3 ) m / e 289 (M + H) + .

C15N16N2O4·TFA에 대한 원소분석치:Elemental Analysis for C 15 N 16 N 2 O 4 · TFA:

계산치: C, 50.75; H, 4.26; N, 6.96.Calc .: C, 50.75; H, 4. 26; N, 6.96.

실측치: C, 50.42; H, 4.03; N, 6.77.Found: C, 50.42; H, 4.03; N, 6.77.

실시예 7Example 7

[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트산 모노(트리플루오로아세테이트) 염[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetic acid mono (trifluoroacetate) salt

5℃하의 1:1 THF/H2O(10ml) 중의 실시예 6B(100mg) 및 LiOH·H2O(150mg)의 용액을 45분 동안 교반하고 농축시켜 회백색 고체를 수득한다. 이 고체를 1N HCl(20ml)에 용해시키고, 실온에서 48시간 동안 교반한 다음 여과한다. 생성된 백색 고체를 실시예 1B에 기재된 바와 같이 정제하여 표제 화합물을 20mg 수득한다.A solution of Example 6B (100 mg) and LiOH.H 2 O (150 mg) in 1: 1 THF / H 2 O (10 ml) at 5 ° C. was stirred for 45 minutes and concentrated to yield an off-white solid. This solid is dissolved in 1N HCl (20 ml), stirred at room temperature for 48 hours and then filtered. The resulting white solid is purified as described in Example 1B to give 20 mg of the title compound.

1H NMR(300MHz, DMSO-d6) δ 3.93 (s, 3H), 4.79 (s, 2H), 7.65 (dd, 1H), 7.72 (d, 1H), 7.85(d, 1H), 8.09(d, 1H), 8.7(d, 1H), 9.23(bs, 2H), 9.45(bs, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.93 (s, 3H), 4.79 (s, 2H), 7.65 (dd, 1H), 7.72 (d, 1H), 7.85 (d, 1H), 8.09 (d , 1H), 8.7 (d, 1H), 9.23 (bs, 2H), 9.45 (bs, 2H);

MS (DCI/NH3) m/e 275 (M+H)+.MS (DCI / NH 3 ) m / e 275 (M + H) + .

C14H14N2O4·TFA에 대한 원소분석치:Elemental analysis for C 14 H 14 N 2 O 4 · TFA:

계산치 : C, 49.49; H, 3.89; N, 7.21.Calculated: C, 49.49; H, 3.89; N, 7.21.

실측치 : C, 47.53; H, 3.71; N, 6.83.Found: C, 47.53; H, 3.71; N, 6.83.

실시예 8Example 8

N-[4-(아미노메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염N- [4- (aminomethyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt

실시예 8AExample 8A

2,6-나프탈렌디카복실산, 모노메틸 에스테르2,6-naphthalenedicarboxylic acid, monomethyl ester

디옥산(1.20L) 중의 디메틸 2,6-나프탈렌디카복실산(39.6g, 162mmole)의 현탁액을 고체가 모두 용해될 때까지 70 내지 80℃에서 가열하고, 메탄올 중의 KOH 1당량으로 서서히 처리하며, 70℃에서 30분 더 교반하고, 실온으로 냉각시키며, 여과한 다음, 디옥산 및 디에틸 에테르로 세척하고, 물에 용해시키며, 수성 층이 pH지에 산성으로 나타날 때까지 1N HCl로 처리하며, 여과하고, 물로 세척한 다음 진공하에 건조시켜 백색 분말을 33g 수득한다. MS(DCI/NH3) m/e 231(M+H)+.A suspension of dimethyl 2,6-naphthalenedicarboxylic acid (39.6 g, 162 mmol) in dioxane (1.20 L) is heated at 70 to 80 ° C. until all of the solids are dissolved, and slowly treated with 1 equivalent of KOH in methanol, 70 Stir another 30 minutes at C, cool to room temperature, filter, wash with dioxane and diethyl ether, dissolve in water, treat with 1N HCl until the aqueous layer appears acidic in pH paper, filter and , Washed with water and dried in vacuo to give 33 g of a white powder. MS (DCI / NH 3 ) m / e 231 (M + H) + .

실시예 8BExample 8B

6-(클로로카보닐)-2-나프탈렌카복실산, 메틸 에스테르6- (chlorocarbonyl) -2-naphthalenecarboxylic acid, methyl ester

톨루엔(190ml) 중의 실시예 8A(15g, 65mmol)의 현탁액을 티오닐 클로라이드(20ml, 276mmol)로 처리한 다음 DMAP(15mg)으로 처리하고, 환류하에 1시간 동안 가열하며 85℃에서 35분 더 가열한다. 콘덴서를 증류 헤드로 대체하고 용매 60ml를 제거한다. 실온으로 냉각시키는 동안 형성된 농후한 침전을 헥산으로 연마하고 여과하여 백색 고체를 14.8g 수득한다. MS(DCI/NH3) m/e 249(M+H)+.A suspension of Example 8A (15 g, 65 mmol) in toluene (190 ml) was treated with thionyl chloride (20 ml, 276 mmol) followed by DMAP (15 mg), heated at reflux for 1 h and further 35 min at 85 ° C. do. Replace the condenser with the distillation head and remove 60 ml of solvent. The concentrated precipitate formed during cooling to room temperature was triturated with hexane and filtered to give 14.8 g of a white solid. MS (DCI / NH 3 ) m / e 249 (M + H) + .

실시예 8CExample 8C

6-(아미노카보닐)-2-나프탈렌카복실산, 메틸 에스테르6- (aminocarbonyl) -2-naphthalenecarboxylic acid, methyl ester

실온하의 메틸렌 클로라이드(400ml) 중의 실시예 8B(15g, 60.3mmole)의 용액을 무수 암모니아 기체로 처리하여 생성물을 침전시킨다. 이 혼합물을 15분 더 교반한 다음 여과한다. 이 용액을 물로 세척한 다음 진공하에 건조시켜 백색 분말을 13.3g 수득한다. MS(DCI/NH3) m/e 230(M+H)+.A solution of Example 8B (15 g, 60.3 mmol) in methylene chloride (400 ml) at room temperature is treated with anhydrous ammonia gas to precipitate the product. The mixture is stirred for another 15 minutes and then filtered. The solution is washed with water and dried in vacuo to yield 13.3 g of a white powder. MS (DCI / NH 3 ) m / e 230 (M + H) + .

실시예 8DExample 8D

6-시아노-2-나프탈렌카복실산, 메틸 에스테르6-cyano-2-naphthalenecarboxylic acid, methyl ester

트리메틸 포스페이트(450ml) 중의 실시예 8C(31g, 135mmole)의 현탁액을 트리포스겐(27g, 136mmole)으로 처리하고, 실온에서 20분 동안 교반하며, 80℃하의 오일 욕 속에서 1시간 동안 가열한다. 실온으로 냉각시키는 동안 상기 용액으로부터 생성물이 침전된다. 이러한 농후한 슬러리를 물로 처리하고, 여과하며, 백색 고체를 물로 철저하게 세척한 다음 진공하에 건조시켜 표제 화합물을 26.3g 수득한다. MS(DCI/NH3) m/e 212(M+H)+.A suspension of Example 8C (31 g, 135 mmol) in trimethyl phosphate (450 ml) is treated with triphosgen (27 g, 136 mmol), stirred at room temperature for 20 minutes and heated in an oil bath at 80 ° C. for 1 hour. The product precipitates out of the solution while cooling to room temperature. This thick slurry is treated with water, filtered and the white solid is washed thoroughly with water and dried in vacuo to yield 26.3 g of the title compound. MS (DCI / NH 3 ) m / e 212 (M + H) + .

실시예 8EExample 8E

6-시아노-2-나프탈렌카복실산6-cyano-2-naphthalenecarboxylic acid

1:1 THF/H2O(40ml) 중의 실시예 8D(1.9g, 9mmole)을 LiOH·H2O(1.9g, 45mmole)으로 처리하고, 실온에서 90분 동안 교반한 다음 농후한 슬러리로 농축시킨다. 이 슬러리를 물(20ml)에 용해시키고, 고체 시트르산을 사용하여 pH 2로 산성화시키며, 에틸 아세테이트로 추출한다. 합한 유기 추출물을 염수로 세척하고, 건조시키며(Na2SO4) 농축시켜 백색 고체로서의 표제 화합물을 1.6g 수득한다. MS(DCI/NH3) m/e 197(M+H)+.Example 8D (1.9 g, 9 mmole) in 1: 1 THF / H 2 O (40 ml) was treated with LiOH.H 2 O (1.9 g, 45 mmol), stirred at room temperature for 90 minutes and then concentrated to a thick slurry. Let's do it. This slurry is dissolved in water (20 ml), acidified to pH 2 with solid citric acid and extracted with ethyl acetate. The combined organic extracts are washed with brine, dried (Na 2 SO 4 ) and concentrated to give 1.6 g of the title compound as a white solid. MS (DCI / NH 3 ) m / e 197 (M + H) + .

실시예 8FExample 8F

3급-부톡시카보닐아미노-4-아미노메틸아닐린Tert-butoxycarbonylamino-4-aminomethylaniline

2:1 THF/H2O(30ml) 중의 4-아미노메틸아닐린(2g)을 Boc 무수물(3.93g)로 처리하고, 실온에서 18시간 동안 교반하며, 물로 희석시키고 백색 슬러리로 농축시킨다. 이 슬러리를 에틸 아세테이트에 용해시키고, 물 및 염수로 세척하며, 건조시킨 다음(Na2SO4) 농축시켜 황색 고체를 2.4g 수득한다. MS(DCI/NH3) m/e 223(M+H)+.4-aminomethylaniline (2 g) in 2: 1 THF / H 2 O (30 ml) was treated with Boc anhydride (3.93 g), stirred at rt for 18 h, diluted with water and concentrated to a white slurry. This slurry is dissolved in ethyl acetate, washed with water and brine, dried (Na 2 SO 4 ) and concentrated to give 2.4 g of a yellow solid. MS (DCI / NH 3 ) m / e 223 (M + H) + .

실시예 8GExample 8G

N-[4-(아미노메틸)페닐]-6-시아노-2-나프탈렌카복스아미드N- [4- (aminomethyl) phenyl] -6-cyano-2-naphthalenecarboxamide

5℃하의 DMF(5ml) 중의 실시예 8E(200mg) 및 휘니히 염기(180㎕)의 용액을 HATU(193mg)로 처리하고, 5℃에서 1시간 동안 교반하며, DMF(5ml) 중의 실시예 8F(120mg) 및 디이소프로필에틸아민(100㎕)으로 처리하고, 실온에서 8시간 동안 교반하며, 에틸 아세테이트(100ml)로 희석시키고, 1N H3PO4, 포화 중탄산나트륨 및 염수로 순차적으로 세척하며, 건조시킨 다음(Na2SO4) 농축시켜 황색 오일을 수득하고, 이를 1% 메탄올/메틸렌 클로라이드를 이용하여 실리카 겔 상에서 정제하여 표제 화합물을 200mg 수득한다. MS(DCI/NH3) m/e 419(M+H2O)+.A solution of Example 8E (200 mg) and Hunich base (180 μl) in DMF (5 ml) at 5 ° C. was treated with HATU (193 mg), stirred at 5 ° C. for 1 hour, and Example 8F in DMF (5 ml) (120 mg) and diisopropylethylamine (100 μl), stirred at room temperature for 8 hours, diluted with ethyl acetate (100 ml), washed sequentially with 1N H 3 PO 4 , saturated sodium bicarbonate and brine , Dried (Na 2 SO 4 ) and concentrated to afford a yellow oil, which was purified on silica gel with 1% methanol / methylene chloride to give 200 mg of the title compound. MS (DCI / NH 3 ) m / e 419 (M + H 2 O) + .

실시예 8HExample 8H

N-[4-(아미노메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염N- [4- (aminomethyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt

실시예 5B로부터의 과정 및 정제에 의해 실시예 8G(200mg)로부터 표제 화합물을 37mg 수득한다.37 mg of the title compound is obtained from Example 8G (200 mg) by the procedure and purification from Example 5B.

1H NMR (300MHz, DMSO-d6) δ 4.08(m, 2H), 7.45(d, 2H), 7.88(d, 2H), 7.95(dd, 1H), 8.18(dd, 1H), 8.20(bs, 3H), 8.23(d, 1H), 8.35(d, 1H), 8.58(s, 1H), 8.70(s, 1H), 9.39(s, 2H), 9.55(s, 2H), 10.68(s, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.08 (m, 2H), 7.45 (d, 2H), 7.88 (d, 2H), 7.95 (dd, 1H), 8.18 (dd, 1H), 8.20 (bs , 3H), 8.23 (d, 1H), 8.35 (d, 1H), 8.58 (s, 1H), 8.70 (s, 1H), 9.39 (s, 2H), 9.55 (s, 2H), 10.68 (s, 1H);

MS (DCI/NH3) m/e 319 (M+H)+.MS (DCI / NH 3 ) m / e 319 (M + H) + .

C19H17N4O·TFA에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 4 O · TFA:

계산치: C, 50.56; H, 3.69; N, 10.25.Calc .: C, 50.56; H, 3.69; N, 10.25.

실측치: C, 50.18; H, 3.59; N, 10.11.Found: C, 50.18; H, 3.59; N, 10.11.

실시예 9Example 9

N-[4-(아미노)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염N- [4- (amino) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt

실시예 9AExample 9A

N-[4-(아미노)페닐]-6-시아노-2-나프탈렌카복스아미드N- [4- (amino) phenyl] -6-cyano-2-naphthalenecarboxamide

실시예 8F를 1,4-디아미노벤젠으로 대체하는 것을 제외하고는 실시예 8G에 대해 기재된 과정에 따라서 표제 화합물을 제조한다. MS(DCI/NH3) m/e 288(M+H)+.The title compound is prepared following the procedure described for Example 8G except that Example 8F is replaced by 1,4-diaminobenzene. MS (DCI / NH 3 ) m / e 288 (M + H) + .

실시예 9BExample 9B

N-[4-(아미노)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 비스(트리플루오로아세테이트) 염N- [4- (amino) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide bis (trifluoroacetate) salt

실시예 6B로부터의 과정 및 정제를 수행하면서 실시예 9A(100mg)로 표제 화합물을 제조한다.The title compound is prepared in Example 9A (100 mg) while following the procedure and purification from Example 6B.

1H NMR (300MHz, DMSO-d6) δ 7.15(d, 2H), 7.75(d, 2H), 7.95(dd, 1H), 8.18(dd, 1H), 8.23(d, 1H), 8.35(d, 1H), 8.58(s, 1H), 8.70(s, 1H), 9.25(s, 2H), 9.48(s, 2H), 10.58(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.15 (d, 2H), 7.75 (d, 2H), 7.95 (dd, 1H), 8.18 (dd, 1H), 8.23 (d, 1H), 8.35 (d , 1H), 8.58 (s, 1H), 8.70 (s, 1H), 9.25 (s, 2H), 9.48 (s, 2H), 10.58 (s, 1H);

MS (DCI/NH3) m/e 305 (M+H)+.MS (DCI / NH 3 ) m / e 305 (M + H) + .

C18H16N4O·2TFA에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 4 O · 2TFA:

계산치: C, 49.63; H, 3.41; N, 10.52;Calc .: C, 49.63; H, 3.41; N, 10.52;

실측치: C, 46.57; H, 3.62; N, 10.66.Found: C, 46.57; H, 3.62; N, 10.66.

실시예 10Example 10

1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-하이드록시프로판 모노(트리플루오로아세테이트) 염1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-hydroxypropane mono (trifluoroacetate) salt

실시예 10AExample 10A

1-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]-3-[(2-테트라하이드로-2H-피라닐)옥시]프로판 모노(트리플루오로아세테이트) 염1-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] -3-[(2-tetrahydro-2H-pyranyl) oxy] propane mono (trifluoroacetate) salt

DMF(15ml) 중의 실시예 4A(200mg) 및 Cs2CO3(0.32g)의 현탁액을 2-(3-브로모프로필)-테트라하이드로-2H-피란(0.25g)으로 처리하고, 실온에서 18시간 동안 교반한 다음, 물(100ml) 및 에틸 아세테이트(50ml)로 희석시킨다. 유기 층을 분리하고, 10% 시트르산, 물 및 염수로 세척하며, 건조시킨 다음(MgSO4) 농축시켜 오일을 320mg 수득한다. MS(DCI/NH3) m/e 323(M+H)+.A suspension of Example 4A (200 mg) and Cs 2 CO 3 (0.32 g) in DMF (15 ml) was treated with 2- (3-bromopropyl) -tetrahydro-2H-pyran (0.25 g) and 18 at room temperature. Stir for hours and then dilute with water (100 ml) and ethyl acetate (50 ml). The organic layer is separated, washed with 10% citric acid, water and brine, dried (MgSO 4 ) and concentrated to give 320 mg of oil. MS (DCI / NH 3 ) m / e 323 (M + H) + .

실시예 10BExample 10B

1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-하이드록시프로판 모노(트리플루오로아세테이트) 염1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-hydroxypropane mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 10A(0.3g)을 가공 및 정제하여 회백색 고체를 110mg 수득한다.Example 10A (0.3 g) was processed and purified according to the procedure of Example 1B to yield 110 mg of an off-white solid.

1H NMR (300MHz, DMSO-d6) δ 1.97(q, 2H), 3.67(t, 2H), 4.20(t, 2H), 7.61-7.70(m, 3H), 7.84(d, 1H), 8.08(d, 1H), 8.50(d, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 1.97 (q, 2H), 3.67 (t, 2H), 4.20 (t, 2H), 7.61-7.70 (m, 3H), 7.84 (d, 1H), 8.08 (d, 1 H), 8.50 (d, 1 H);

MS (DCI/NH3) m/e 275 (M+H)+.MS (DCI / NH 3 ) m / e 275 (M + H) + .

C13H13N3O2·TFA·0.75H2O에 대한 원소분석치:Elemental Analysis for C 13 H 13 N 3 O 2 · TFA · 0.75H 2 O:

계산치: C, 50.81; H, 5.14; N, 6.97.Calc .: C, 50.81; H, 5. 14; N, 6.97.

실측치: C, 51.23; H, 5.28; N, 6.97.Found: C, 51.23; H, 5. 28; N, 6.97.

실시예 11Example 11

8-아미노-2-나프탈렌카보니트릴 하이드로브로마이드8-amino-2-naphthalenecarbonitrile hydrobromide

실시예 11AExample 11A

2-트리플루오로메탄설포닐옥시-8-아미노나프탈렌2-trifluoromethanesulfonyloxy-8-aminonaphthalene

디옥산(200ml) 중의 8-아미노-2-나프톨(10g) 및 트리에틸아민(12ml)의 용액을 디옥산(80ml) 중의 N-페닐트리플루오로메탄 설폰이미드(25g)로 처리하고, 4시간 동안 교반한 다음 농축시킨다. 생성된 농후한 갈색 고체를 헥산으로 연마하고 여과하여 갈색 고체로서의 표제 화합물을 12g 수득한다. MS(DCI/NH3) m/e 292(M+H)+.A solution of 8-amino-2-naphthol (10 g) and triethylamine (12 ml) in dioxane (200 ml) was treated with N-phenyltrifluoromethane sulfonimide (25 g) in dioxane (80 ml) and 4 Stir for hours and then concentrate. The resulting thick brown solid is triturated with hexane and filtered to give 12 g of the title compound as a brown solid. MS (DCI / NH 3 ) m / e 292 (M + H) + .

실시예 11BExample 11B

2-트리플루오로메탄설포닐옥시-8-카보닐벤질옥시아미노나프탈렌2-trifluoromethanesulfonyloxy-8-carbonylbenzyloxyaminonaphthalene

10% 수성 Na2CO3(20ml) 및 디옥산(250ml) 중의 실시예 11A(2g)의 용액을 디옥산(20ml) 중의 벤질클로로포르메이트(2ml)로 처리하고, 실온에서 5시간 동안 교반한 다음 에틸 아세테이트로 추출한다. 유기 층을 건조시키고(MgSO4) 농축시키며, 조 생성물을 7:1 헥산/에틸 아세테이트를 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 2.5g(86%) 수득한다. MS(DCI/NH3) m/e 443(M+NH4)+.A solution of Example 11A (2 g) in 10% aqueous Na 2 CO 3 (20 ml) and dioxane (250 ml) was treated with benzylchloroformate (2 ml) in dioxane (20 ml) and stirred at room temperature for 5 hours. Then extracted with ethyl acetate. The organic layer is dried (MgSO 4 ) and concentrated, and the crude product is chromatographed on silica gel with 7: 1 hexanes / ethyl acetate to give 2.5 g (86%) of the title compound. MS (DCI / NH 3 ) m / e 443 (M + NH 4 ) + .

실시예 11CExample 11C

8-(N-카보닐벤질옥시)-2-나프탈렌카보니트릴8- (N-carbonylbenzyloxy) -2-naphthalenecarbonitrile

트리스(디벤질리덴아세톤)디팔라듐(0)-클로로포름 부가물(120mg), 1,1'-비스(디페닐포스피노)-페로센(260mg), 시안화칼륨(766mg), 실시예 11B(2.5g) 및 N-메틸-2-피롤리돈(5ml)을 순차적으로 합하고, 황색 반응 착물이 형성될 때까지 실온에서 교반한 다음 40분 동안 80℃로 가온한다. 진한 갈색 반응 혼합물을 실온으로 냉각시키고, 9:1 헥산/에틸 아세테이트를 이용하여 실리카 겔 상에서 크로마토그래피하여 무색 고체로서의 표제 화합물을 1.5g 수득한다. MS(DCI/NH3) m/e 292(M+NH4)+.Tris (dibenzylideneacetone) dipalladium (0) -chloroform adduct (120 mg), 1,1'-bis (diphenylphosphino) -ferrocene (260 mg), potassium cyanide (766 mg), Example 11B (2.5 g) ) And N-methyl-2-pyrrolidone (5 ml) are combined sequentially, stirred at room temperature until a yellow reaction complex is formed and then warmed to 80 ° C. for 40 minutes. The dark brown reaction mixture is cooled to room temperature and chromatographed on silica gel with 9: 1 hexanes / ethyl acetate to give 1.5 g of the title compound as a colorless solid. MS (DCI / NH 3 ) m / e 292 (M + NH 4 ) + .

실시예 11DExample 11D

8-아미노-2-나프탈렌카보니트릴 하이드로브로마이드8-amino-2-naphthalenecarbonitrile hydrobromide

실시예 11C(1.4g)를 아세트산(5ml) 중의 30% HBr 용액으로 처리하고 실온에서 6시간 동안 교반한다. 반응 혼합물을 디에틸 에테르로 처리한 다음 여과시켜 황색 고체로서의 표제 화합물을 1.1g 수득한다. MS(DCI/NH3) m/e 186(M+NH4)+.Example 11C (1.4 g) is treated with a 30% HBr solution in acetic acid (5 ml) and stirred at room temperature for 6 hours. The reaction mixture is treated with diethyl ether and then filtered to give 1.1 g of the title compound as a yellow solid. MS (DCI / NH 3 ) m / e 186 (M + NH 4 ) + .

실시예 12Example 12

일반적인 아실화 과정General Acylation Process

메틸렌 클로라이드(0.3M) 중의 실시예 10D(1당량), 트리에틸아민(1당량) 및 DMAP(0.25당량)의 현탁액을 메틸렌 클로라이드(0.3M) 중의 적절한 산 클로라이드(1.1당량)로 적가 처리하고, 실온에서 30분 동안 교반하며, 물(50ml)로 처리한다. 유기 층을 건조시키고(MgSO4), 농축시킨 다음, 이를 추가의 정제없이 다음 반응에 사용한다.A suspension of Example 10D (1 equiv), triethylamine (1 equiv) and DMAP (0.25 equiv) in methylene chloride (0.3 M) was added dropwise treated with the appropriate acid chloride (1.1 equiv) in methylene chloride (0.3 M), Stir at room temperature for 30 minutes and treat with water (50 ml). The organic layer is dried (MgSO 4 ), concentrated and used for the next reaction without further purification.

실시예 13Example 13

일반적인 아미딘 합성 과정Common Amidine Synthesis Process

실온하에서 10:1 피리딘:트리에틸아민(10ml) 중의 실시예 12로부터의 조 아실화 생성물(약 100mg)의 용액을 5분 동안 황화수소로 처리하고, 실온에서 18시간 동안 교반하며, 물(50ml)로 희석시킨 다음 에틸 아세테이트로 추출한다. 에틸 아세테이트를 건조시키고(MgSO4) 농축시킨다. 잔사를 아세톤(30ml)에 용해시키고, 메틸 요오다이드(2ml)로 처리하며, 1시간 동안 환류시킨 다음, 증발 건조시키고, 메탄올(25ml)에 재용해시키고, 암모늄 아세테이트(100mg)로 처리하며, 실온에서 18시간 동안 교반하고, 농축시키며 실시예 1B에 기재된 바와 같이 정제하여 백색 고체로서의 실시예 14 내지 20을 제공한다.A solution of the crude acylated product (about 100 mg) from Example 12 in 10: 1 pyridine: triethylamine (10 ml) at room temperature was treated with hydrogen sulfide for 5 minutes, stirred at room temperature for 18 hours, and water (50 ml). Dilute with and extract with ethyl acetate. Ethyl acetate is dried (MgSO 4 ) and concentrated. The residue was dissolved in acetone (30 ml), treated with methyl iodide (2 ml), refluxed for 1 hour, then evaporated to dryness, redissolved in methanol (25 ml) and treated with ammonium acetate (100 mg), Stir at room temperature for 18 hours, concentrate and purify as described in Example 1B to provide Examples 14-20 as a white solid.

실시예 14Example 14

8-(카보닐벤질옥시)아미노-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염8- (carbonylbenzyloxy) amino-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 5.14(s, 2H), 7.36-7.50(m, 5H), 7.67-7.90(m, 4H), 8.14(d, 1H), 8.67(s, 1H), 9.08(s, 2H), 9.37(s, 2H), 9.78(s, 1H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 5.14 (s, 2H), 7.36-7.50 (m, 5H), 7.67-7.90 (m, 4H), 8.14 (d, 1H), 8.67 (s, 1H) , 9.08 (s, 2 H), 9.37 (s, 2 H), 9.78 (s, 1 H);

MS (DCI/NH3) m/e 320 (M+H)+.MS (DCI / NH 3 ) m / e 320 (M + H) + .

C19H15N3O2·1.5TFA·0.5H2O에 대한 원소분석치:Elemental Analysis for C 19 H 15 N 3 O 2 1.5TFA0.5H 2 O:

계산치: C, 52.91; H, 3.94; N, 8.41.Calc .: C, 52.91; H, 3.94; N, 8.41.

실측치: C, 52.86; H, 4.07; N, 8.18.Found: C, 52.86; H, 4.07; N, 8.18.

실시예 15Example 15

N-[7-(아미노이미노메틸)-1-나프탈레닐)아세트아미드 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl) acetamide mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 4.19(s, 3H), 7.66-7.88(m, 3H), 8.12-8.16(m, 2H), 8.69(s, 1H), 8.98(d, 1H), 9.16(s, 2H), 9.47(s, 2H), 10.14(s, 1H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 4.19 (s, 3H), 7.66-7.88 (m, 3H), 8.12-8.16 (m, 2H), 8.69 (s, 1H), 8.98 (d, 1H) , 9.16 (s, 2 H), 9.47 (s, 2 H), 10.14 (s, 1 H);

MS (DCI/NH3) m/e 228 (M+H)+.MS (DCI / NH 3 ) m / e 228 (M + H) + .

C14H12N3O·1.2TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 14 H 12 N 3 O · 1.2TFA · 0.25H 2 O:

계산치: C, 50.18; H, 4.02; N, 11.40.Calc .: C, 50.18; H, 4.02; N, 11.40.

실측치: C, 50.62; H, 4.47; N, 10.90.Found: C, 50.62; H, 4. 47; N, 10.90.

실시예 16Example 16

메틸 [7-(아미노이미노메틸)-1-나프탈레닐)카바메이트 모노(트리플루오로아세테이트) 염Methyl [7- (aminoiminomethyl) -1-naphthalenyl) carbamate mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 3.88(s, 3H), 7.67-7.85(m, 4H), 8.14(d, 1H), 8.6(s, 1H), 8.28(s, 3H), 9.67(s, 1H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 3.88 (s, 3H), 7.67-7.85 (m, 4H), 8.14 (d, 1H), 8.6 (s, 1H), 8.28 (s, 3H), 9.67 (s, 1 H);

MS (DCI/NH3) m/e 244 (M+H)+.MS (DCI / NH 3 ) m / e 244 (M + H) + .

C13H13N3O2·TFA에 대한 원소분석치:Elemental Analysis for C 13 H 13 N 3 O 2 · TFA:

계산치: C, 50.43; H, 3.95; N, 11.76.Calc .: C, 50.43; H, 3.95; N, 11.76.

실측치: C, 50.12; H, 4.05; N, 11.61.Found: C, 50.12; H, 4.05; N, 11.61.

실시예 17Example 17

메틸 3-[[7-(아미노이미노메틸)-1-나프탈레닐]아미노]-3-옥소프로피오네이트 모노(트리플루오로아세테이트) 염Methyl 3-[[7- (aminoiminomethyl) -1-naphthalenyl] amino] -3-oxopropionate mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 3.69(s, 2H), 3.71(s, 3H), 7.69(m, 4H), 8.18(d, 1H), 8.58(s, 1H), 9.11(s, 2H), 9.48(s, 2H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 3.69 (s, 2H), 3.71 (s, 3H), 7.69 (m, 4H), 8.18 (d, 1H), 8.58 (s, 1H), 9.11 (s , 2H), 9.48 (s, 2H);

MS (DCI/NH3) m/e 286 (M+H)+.MS (DCI / NH 3 ) m / e 286 (M + H) + .

C15H14N3O3·1TFA·H2O에 대한 원소분석치:Elemental Analysis for C 15 H 14 N 3 O 3 · 1TFA · H 2 O:

계산치: C, 48.18; H, 4.26; N, 9.80.Calc .: C, 48.18; H, 4. 26; N, 9.80.

실측치: C, 48.30; H, 4.09; N, 9.58.Found: C, 48.30; H, 4.09; N, 9.58.

실시예 18Example 18

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-(페닐메톡시)아세트아미드 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] -2- (phenylmethoxy) acetamide mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 4.29(s, 2H), 4.73(s, 2H), 7.33-7.48(m, 5H), 7.69(m, 4H), 8.17(d, 1H), 8.47(s, 1H), 9.21(br, 4H), 10.0(s, 1H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 4.29 (s, 2H), 4.73 (s, 2H), 7.33-7.48 (m, 5H), 7.69 (m, 4H), 8.17 (d, 1H), 8.47 (s, 1 H), 9.21 (br, 4 H), 10.0 (s, 1 H);

MS (DCI/NH3) m/e 334 (M+H)+.MS (DCI / NH 3 ) m / e 334 (M + H) + .

C20H18N3O2·1TFA·H2O에 대한 원소분석치:Elemental Analysis for C 20 H 18 N 3 O 2 · 1TFA · H 2 O:

계산치: C, 56.77; H, 4.76; N, 9.03.Calc .: C, 56.77; H, 4.76; N, 9.03.

실측치: C, 56.84; H, 4.49; N, 8.93.Found: C, 56.84; H, 4. 49; N, 8.93.

실시예 19Example 19

N-[7-(아미노이미노메틸)-1-나프탈레닐]-1,3-벤조디옥솔-5-카복스아미드 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] -1,3-benzodioxol-5-carboxamide mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 6.19(1H, 2H), 7.12(d, 1H), 7.65-7.79(m, 5H), 7.97(d, 1H), 8.20(s, 1H), 8.53(s, 1H), 9.2(br, s, 3H), 10.35(s, 2H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 6.19 (1H, 2H), 7.12 (d, 1H), 7.65-7.79 (m, 5H), 7.97 (d, 1H), 8.20 (s, 1H), 8.53 (s, 1 H), 9.2 (br, s, 3 H), 10.35 (s, 2H);

MS (DCI/NH3) m/e 334 (M+H)+.MS (DCI / NH 3 ) m / e 334 (M + H) + .

C18H14N3O2·TFA에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 3 O 2 · TFA:

계산치: C, 55.82; H, 3.68; N, 9.30.Calc .: C, 55.82; H, 3.68; N, 9.30.

실측치: C, 55.69; H, 33.61; N, 9.23.Found: C, 55.69; H, 33.61; N, 9.23.

실시예 20Example 20

N-[7-(아미노이미노메틸)-1-나프탈레닐]벤젠메탄설폰아미드 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] benzenemethanesulfonamide mono (trifluoroacetate) salt

1H NMR (DMSO-d6, 300MHz) δ 4.60(s, 2H), 7.32-7.33(m, 5H), 7.67-7.70(m, 2H), 7.82(d, 1H), 7.92(d, 1H), 8.17(s, 1H), 8.70(s, 1H), 9,14(s, 2H), 9.35(s, 2H), 9.19(s, 1H); 1 H NMR (DMSO-d 6 , 300 MHz) δ 4.60 (s, 2H), 7.32-7.33 (m, 5H), 7.67-7.70 (m, 2H), 7.82 (d, 1H), 7.92 (d, 1H) 8.17 (s, 1H), 8.70 (s, 1H), 9,14 (s, 2H), 9.35 (s, 2H), 9.19 (s, 1H);

MS(DCI/NH3) m/e 340 (M+H)+.MS (DCI / NH 3 ) m / e 340 (M + H) + .

C18H17N3O2S·TFA·H2O에 대한 원소분석치:Elemental Analysis for C 18 H 17 N 3 O 2 STFAH 2 O:

계산치: C, 50.95, H, 4.28; N, 8.91.Calc .: C, 50.95, H, 4.28; N, 8.91.

실측치: C, 50.76, H, 3.70; N, 8.65.Found: C, 50.76, H, 3.70; N, 8.65.

실시예 21Example 21

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt

실시예 21AExample 21A

1-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염1-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt

실시예 4A, 1,3-디브로모프로판 및 실시예 10A의 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 337(M+NH4)+.The title compound is prepared from the procedure of Example 4A, 1,3-dibromopropane and Example 10A. MS (DCI / NH 3 ) m / e 337 (M + NH 4 ) + .

실시예 21BExample 21B

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt

실시예 1B의 과정에 따라서 실시예 21A로부터 표제 화합물을 제조한다. HCl 가수분해 후, 용액을 0℃로 냉각시키고, 침전되는 백색 고체를 여과한 다음 건조시켜 표제 화합물을 수득한다.The title compound is prepared from Example 21A following the procedure of Example 1B. After HCl hydrolysis, the solution is cooled to 0 ° C. and the white solid that precipitates is filtered and then dried to afford the title compound.

1H NMR (300MHz, DMSO-d6) δ 2.35(m, 2H), 3.86(t, 2H), 4.00(s, 3H), 4.25(t, 2H), 7.65(dd, 1H), 7.70(d, 1H), 7.90(d, 1H), 8.10(d, 1H), 8.55(s, 1H), 9.15(br s, 2H), 9.42(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.35 (m, 2H), 3.86 (t, 2H), 4.00 (s, 3H), 4.25 (t, 2H), 7.65 (dd, 1H), 7.70 (d , 1H), 7.90 (d, 1H), 8.10 (d, 1H), 8.55 (s, 1H), 9.15 (br s, 2H), 9.42 (br s, 2H);

MS (DCI/NH3) m/e 337 (M+H)+.MS (DCI / NH 3 ) m / e 337 (M + H) + .

C15H17BrN2O2·HCl·0.75H2O에 대한 원소분석치:Elemental Analysis for C 15 H 17 BrN 2 O 2 HCl0.75H 2 O:

계산치: C, 46.53; H, 5.08; N, 7.23.Calc .: C, 46.53; H, 5.08; N, 7.23.

실측치: C, 46.65; H, 5.11; N, 7.16.Found: C, 46.65; H, 5.11; N, 7.16.

실시예 22Example 22

3-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]프로펜 모노(트리플루오로아세테이트) 염3-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] propene mono (trifluoroacetate) salt

실시예 22AExample 22A

3-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]프로펜3-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] propene

실시예 21A의 과정으로부터 이중 생성물로서의 표제 화합물을 수득한다. MS(DCI/NH3) m/e 257(M+NH4)+.From the procedure of Example 21A the title compound is obtained as a double product. MS (DCI / NH 3 ) m / e 257 (M + NH 4 ) + .

실시예 22BExample 22B

3-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]프로펜 모노(트리플루오로아세테이트) 염3-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] propene mono (trifluoroacetate) salt

실시예 1B의 과정 및 정제에 따라서 실시예 22A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 22A following the procedure and purification of Example 1B.

1H NMR (300MHz, DMSO-d6) δ 4.00(s, 3H), 4.70(d, 2H), 5.22(d, 1H), 5.42(d, 1H), 6.18(m, 1H), 7.62(dd, 1H), 7.85(d, 1H), 8.10(d, 1H), 8.50(s, 1H), 9.12(br s, 2H), 9.45(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.00 (s, 3H), 4.70 (d, 2H), 5.22 (d, 1H), 5.42 (d, 1H), 6.18 (m, 1H), 7.62 (dd , 1H), 7.85 (d, 1H), 8.10 (d, 1H), 8.50 (s, 1H), 9.12 (br s, 2H), 9.45 (br s, 2H);

MS(DCI/NH3) m/e 257(M+H)+.MS (DCI / NH 3 ) m / e 257 (M + H) + .

C15H16N2O2·TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 15 H 16 N 2 O 2 TFA0.25H 2 O:

계산치; C, 54.47; H, 4.71; N, 7.47.Calculated value; C, 54.47; H, 4.71; N, 7.47.

실측치; C, 54.61; H, 4.38; N, 7.40.Found; C, 54.61; H, 4.38; N, 7.40.

실시예 23Example 23

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane mono (hydrochloride) salt

실시예 23AExample 23A

1-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판1-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane

실시예 4A, 1-브로모-3-페닐프로판, 및 실시예 10A의 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 335(M+NH4)+.The title compound is prepared from the procedure of Example 4A, 1-bromo-3-phenylpropane, and Example 10A. MS (DCI / NH 3 ) m / e 335 (M + NH 4 ) + .

실시예 23BExample 23B

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane mono (hydrochloride) salt

실시예 21B의 과정에 따라서 실시예 23A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 23A following the procedure of Example 21B.

1H NMR (300MHz, CD3OD) δ 2.21(m, 2H), 2.94(t, 2H), 4.00(s, 3H), 4.22(t, 2H), 7.18(m, 1H), 7.28(m, 4H), 7.62(m, 2H), 7.79(d, 1H), 8.02(d, 1H), 8.62(s, 1H); 1 H NMR (300 MHz, CD 3 OD) δ 2.21 (m, 2H), 2.94 (t, 2H), 4.00 (s, 3H), 4.22 (t, 2H), 7.18 (m, 1H), 7.28 (m, 4H), 7.62 (m, 2H), 7.79 (d, 1H), 8.02 (d, 1H), 8.62 (s, 1H);

MS (DCI/NH3) m/e 335 (M+H)+.MS (DCI / NH 3 ) m / e 335 (M + H) + .

C21H23N2O2·HCl에 대한 HRMS(FAB)치:HRMS (FAB) for C 21 H 23 N 2 O 2 HCl:

계산치 355.1762(M+H)+.Calc. 355.1762 (M + H) + .

실측치 m/e 335.1762Found m / e 335.1762

실시예 24Example 24

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] propane mono (hydrochloride) salt

실시예 24AExample 24A

1-브로모-3-(3,4-디메톡시페닐)프로판1-bromo-3- (3,4-dimethoxyphenyl) propane

본원에 참조 문헌으로 삽입된 문헌[Journal of the American Chemical Society, 95, 8749(1973)]에 기재된 바와 같이 3-(3,4-디메톡시페닐)-1-프로판올로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 276(M+NH4)+.The title compound is prepared from 3- (3,4-dimethoxyphenyl) -1-propanol as described in the Journal of the American Chemical Society, 95, 8749 (1973), incorporated herein by reference. MS (DCI / NH 3 ) m / e 276 (M + NH 4 ) + .

실시예 24BExample 24B

1-[(7-시아노-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]프로판1-[(7-cyano-2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] propane

실시예 4A 및 24A로부터 실시예 10A의 과정에 따라서 표제 화합물을 제조한다. MS(DCI/NH3) m/e 395(M+NH4)+.The title compound is prepared following the procedure of Example 10A from Examples 4A and 24A. MS (DCI / NH 3 ) m / e 395 (M + NH 4 ) + .

실시예 24CExample 24C

1-[(7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]프로판 모노(하이드로클로라이드) 염1-[(7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] propane mono (hydrochloride) salt

실시예 21B의 과정에 따라서 실시예 24A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 24A following the procedure of Example 21B.

1H NMR (300MHz, DMSO-d6) δ 2.11(m, 2H), 2.80(t, 2H), 3.74(s, 6H), 3.98(s, 3H), 4.15(t, 2H), 6.75-6.92(m, 3H), 7.65(dd, 1H), 7.70(d, 1H), 7.86(d, 1H), 8.10(d, 1H), 8.55(s, 1H), 9.15(br s, 2H), 9.53(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.11 (m, 2H), 2.80 (t, 2H), 3.74 (s, 6H), 3.98 (s, 3H), 4.15 (t, 2H), 6.75-6.92 (m, 3H), 7.65 (dd, 1H), 7.70 (d, 1H), 7.86 (d, 1H), 8.10 (d, 1H), 8.55 (s, 1H), 9.15 (br s, 2H), 9.53 (br s, 2H);

MS (DCI/NH3) m/e 395 (M+H)+.MS (DCI / NH 3 ) m / e 395 (M + H) + .

C23H26N2O4·HCl·0.5H2O에 대한 원소분석치:Elemental Analysis for C 23 H 26 N 2 O 4 HCl0.5H 2 O:

계산치: C, 62.79; H, 6.42; N, 6.37.Calc .: C, 62.79; H, 6. 42; N, 6.37.

실측치: C, 63.08; H, 6.38; N, 6.17.Found: C, 63.08; H, 6. 38; N, 6.17.

실시예 25Example 25

7-메톡시-8-(2-푸라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (2-furanyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 25AExample 25A

7-메톡시-8-트리플루오로메탄설포닐옥시-2-나프탈렌카보니트릴7-methoxy-8-trifluoromethanesulfonyloxy-2-naphthalenecarbonitrile

0℃하의 메틸렌 클로라이드(5ml) 중의 실시예 4A(310mg)의 용액을 1,1,1-트리플루오로-N-페닐-N-[(트리플루오로메틸)설포닐]메탄설폰아미드(614mg) 및 트리에틸아민(240ml)으로 처리하고, 실온에서 18시간 동안 교반하며, 메틸렌 클로라이드(100ml)로 희석시키고, 물 및 20% 수성 NaOH로 세척하며, 건조시킨 다음(MgSO4) 농축시켜 백색 고체로서의 표제 화합물을 560mg 수득한다. MS(DCI) m/e 349(M+H2O)+.A solution of Example 4A (310 mg) in methylene chloride (5 ml) at 0 ° C. was added 1,1,1-trifluoro-N-phenyl-N-[(trifluoromethyl) sulfonyl] methanesulfonamide (614 mg). And triethylamine (240 ml), stirred at room temperature for 18 hours, diluted with methylene chloride (100 ml), washed with water and 20% aqueous NaOH, dried (MgSO 4 ) and concentrated to a white solid. 560 mg of the title compound are obtained. MS (DCI) m / e 349 (M + H 2 O) + .

실시예 25BExample 25B

푸란-2-보론산Furan-2-boronic acid

-20℃하의 디에틸 에테르(67ml) 중의 푸란(5.3ml, 73mmole)의 용액을 n-부틸리튬(헥산중 2.5M, 26ml, 65mmole)로 처리하고, -20℃에서 2시간 동안 교반한 다음, 캐뉼라를 통해 디에틸 에테르(17ml) 중의 트리이소프로필 보레이트(33ml, 147mmole)의 -20℃ 용액에 옮긴다. 농후한 혼합물을 실온으로 가온하고, 3N HCl(200ml)로 처리하고, 디에틸 에테르로 추출한다. 이러한 추출물을 1N KOH로 세척하고, KOH 층을 0℃로 냉각시키며 6N HCl로 산성화시킨다. 이 산성 용액을 디에틸 에테르로 추출하고, 산성 에테르 추출물을 염수로 세척하며, 건조시키고(MgSO4) 농축시켜 표제 화합물을 수득한다.A solution of furan (5.3 ml, 73 mmol) in diethyl ether (67 ml) at −20 ° C. was treated with n-butyllithium (2.5 M in hexanes, 26 ml, 65 mmol) and stirred at −20 ° C. for 2 hours, Transfer via cannula to a -20 ° C. solution of triisopropyl borate (33 ml, 147 mmol) in diethyl ether (17 ml). The thick mixture is warmed to room temperature, treated with 3N HCl (200 ml) and extracted with diethyl ether. This extract is washed with 1N KOH, the KOH layer is cooled to 0 ° C. and acidified with 6N HCl. The acidic solution is extracted with diethyl ether and the acid ether extract is washed with brine, dried (MgSO 4 ) and concentrated to afford the title compound.

1H NMR(300MHz, DMSO-d6) δ 6.45(dd, 1H), 7.05(t, 1H), 7.80(dd, 1H), 8.19(s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 6.45 (dd, 1H), 7.05 (t, 1H), 7.80 (dd, 1H), 8.19 (s, 2H).

실시예 25CExample 25C

7-메톡시-8-(2-푸라닐)-2-나프탈렌카보니트릴7-methoxy-8- (2-furanyl) -2-naphthalenecarbonitrile

실시예 25A(1.10mmol)를 DMF(5ml) 중의 Pd(OAc)2(0.11mmol) 및 1,1'-비스(디페닐포스피노)페로센(0.22mmol)과 합하고, 10분 동안 교반하며, 실시예 25B(1.32mmol) 및 Cs2CO3(3.3mmol)로 처리하고, 85℃에서 6시간 동안 가열하며, 실온으로 냉각시킨 다음, 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 250(M+H)+.Example 25A (1.10 mmol) was combined with Pd (OAc) 2 (0.11 mmol) and 1,1′-bis (diphenylphosphino) ferrocene (0.22 mmol) in DMF (5 ml) and stirred for 10 minutes Example 25B (1.32 mmol) and Cs 2 CO 3 (3.3 mmol), heated at 85 ° C. for 6 hours, cooled to room temperature and chromatographed on silica gel with 10% ethyl acetate / hexanes to give the title Obtain the compound. MS (DCI / NH 3 ) m / e 250 (M + H) + .

실시예 25DExample 25D

8-(2-푸라닐)-7-메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염8- (2-furanyl) -7-methoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정 및 정제에 따라서 실시예 25C로부터 표제 화합물을 제조한다.The title compound is prepared from Example 25C following the procedure and purification of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.97(s, 3H), 6.73(m, 1H), 6.80(m, 1H), 7.64(dd, 1H), 7.78(d, 1H), 7.91(m, 1H), 8.16(d, 1H), 8.20(d, 1H), 8.30(s, 1H), 9.08(br s, 2H), 9.40(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.97 (s, 3H), 6.73 (m, 1H), 6.80 (m, 1H), 7.64 (dd, 1H), 7.78 (d, 1H), 7.91 (m , 1H), 8.16 (d, 1H), 8.20 (d, 1H), 8.30 (s, 1H), 9.08 (br s, 2H), 9.40 (br s, 2H);

MS(DCI/NH3) m/e 267(M+H)+.MS (DCI / NH 3 ) m / e 267 (M + H) + .

C16H14N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 16 H 14 N 2 O 2 · TFA:

계산치: C, 56.85; H, 3.98; N, 7.37.Calc .: C, 56.85; H, 3.98; N, 7.37.

실측치: C, 56.68; H, 3.67; N, 7.35.Found: C, 56.68; H, 3.67; N, 7.35.

실시예 26Example 26

메틸 6-(아미노이미노메틸)-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실레이트 모노(트리플루오로아세테이트) 염Methyl 6- (aminoiminomethyl) -4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylate mono (trifluoroacetate) salt

실시예 26AExample 26A

2-시아노-1-니트로-6-카복시나프탈렌 메틸 에스테르2-cyano-1-nitro-6-carboxynaphthalene methyl ester

0℃하의 진한 황산(75ml) 중의 2-시아노-6-메틸나프토에이트(5.2g)의 용액을 질화칼륨(1.03당량) 1분획으로 처리하고, 10분 동안 교반하며, 얼음(500g)에 붓고, 에틸 아세테이트로 추출한다. 에틸 아세테이트 층을 물, 1N NaOH 및 염수로 세척하고, 건조시키며(MgSO4), 실리카 겔로 처리한 다음 여과한다. 에틸 아세테이트를 약 200ml로 농축시키면 생성물이 침전된다. 이 혼합물을 고체가 모두 용해될 때까지 가열하고, MeOH(20ml) 및 에테르(20ml)로 처리한 다음 밤새 교반한다. 생성된 고체를 여과하고 메탄올로 세척하여 크림색 고체로서의 표제 화합물을 2.31g 수득한다. 모액을 증발시키고, 메틸렌 클로라이드(250ml)로 처리한 다음 고체 실리카 겔로 처리하며, 여과한 다음 농축시킨다. 에틸 아세테이트/메탄올로 결정화하여 생성물 1.6g을 추가로 수득한다[총 수율: 3.91g(62%)]. MS(DCI/NH3) m/e 257(M+H)+.A solution of 2-cyano-6-methylnaphthoate (5.2 g) in concentrated sulfuric acid (75 ml) at 0 ° C. was treated with one portion of potassium nitride (1.03 equiv.), Stirred for 10 minutes, and poured onto ice (500 g). Pour and extract with ethyl acetate. The ethyl acetate layer is washed with water, 1N NaOH and brine, dried (MgSO 4 ), treated with silica gel and filtered. Concentration of ethyl acetate to about 200 ml precipitates the product. The mixture is heated until all solids are dissolved, treated with MeOH (20 ml) and ether (20 ml) and stirred overnight. The resulting solid is filtered and washed with methanol to give 2.31 g of the title compound as a cream solid. The mother liquor is evaporated, treated with methylene chloride (250 ml) followed by solid silica gel, filtered and concentrated. Crystallization with ethyl acetate / methanol gave further 1.6 g of product [total yield: 3.91 g (62%)]. MS (DCI / NH 3 ) m / e 257 (M + H) + .

실시예 26BExample 26B

2-시아노-1-아미노-6-카복시나프탈렌 메틸 에스테르2-cyano-1-amino-6-carboxynaphthalene methyl ester

에틸 아세테이트(80ml) 중의 실시예 26A(1g, 3.9mmole) 및 탄소상 10% Pd(112mg)의 용액을 1수소압 하에서 9시간 동안 교반하고, 1시간 동안 질소로 퍼징하며, 여과한 다음 증발시켜 황색 고체로서의 표제 화합물을 810mg(92%) 수득한다. MS(DCI/NH3) m/e 227(M+NH4)+.A solution of Example 26A (1 g, 3.9 mmol) and 10% Pd on carbon (112 mg) in ethyl acetate (80 ml) was stirred for 9 hours under hydrogen pressure, purged with nitrogen for 1 hour, filtered and evaporated 810 mg (92%) of the title compound as a yellow solid are obtained. MS (DCI / NH 3 ) m / e 227 (M + NH 4 ) + .

실시예 26CExample 26C

6-시아노-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실산, 메틸 에스테르6-cyano-4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylic acid, methyl ester

메틸렌 클로라이드(40ml) 중의 실시예 26B(2.50mmole)의 용액을 디이소프로필에틸아민(2ml) 및 메틸클로로포르메이트(195㎕, 2.52mmole)로 순차적으로 처리하고, 2시간 동안 교반하며, 메탄올(10ml)로 처리하고, 10분 더 교반하며, 메틸렌 클로라이드(60ml)로 희석시키고, 물 및 염수로 세척하며, 건조시킨 다음(MgSO4) 증발시킨다. 잔사를 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 연황색 고체를 280mg(59%) 수득한다. MS(DCI/NH3) m/e 285(M+H)+.A solution of Example 26B (2.50 mmol) in methylene chloride (40 ml) was treated sequentially with diisopropylethylamine (2 ml) and methylchloroformate (195 μl, 2.52 mmole), stirred for 2 hours, and methanol ( 10 ml), further stirred for 10 minutes, diluted with methylene chloride (60 ml), washed with water and brine, dried (MgSO 4 ) and evaporated. The residue was purified on silica gel using 10% ethyl acetate / hexanes to give 280 mg (59%) of a pale yellow solid. MS (DCI / NH 3 ) m / e 285 (M + H) + .

실시예 26DExample 26D

메틸 6-(아미노이미노메틸)-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실레이트 모노(트리플루오로아세테이트) 염Methyl 6- (aminoiminomethyl) -4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylate mono (trifluoroacetate) salt

실시예 40D의 과정 및 실시예 26C(125mg, 0.44mmol)를 이용하여 백색 고체로서의 표제 화합물을 35mg 수득한다.The procedure of Example 40D and Example 26C (125 mg, 0.44 mmol) gave 35 mg of the title compound as a white solid.

1H NMR(DMSO-d6) δ 3.78(s, 3H), 3.95(s, 3H), 7.89(dd, 1H), 8.37-8.40(m, 3H), 8.53(s, 1H), 8.740(s, 1H) 9.18(br s, 2H), 9.45(br s, 2H), 9.90(s, 1H), 8.42(s, 1H), 8.63(d, 1H), 9.18(br s, 4H), 10.58(s, 1H); 1 H NMR (DMSO-d 6 ) δ 3.78 (s, 3H), 3.95 (s, 3H), 7.89 (dd, 1H), 8.37-8.40 (m, 3H), 8.53 (s, 1H), 8.740 (s , 1H) 9.18 (br s, 2H), 9.45 (br s, 2H), 9.90 (s, 1H), 8.42 (s, 1H), 8.63 (d, 1H), 9.18 (br s, 4H), 10.58 ( s, 1 H);

MS(DCI/NH3) m/e 302(M+H)+.MS (DCI / NH 3 ) m / e 302 (M + H) + .

C15H15N3O4·TFA·1.5H2O에 대한 원소분석치:Elemental Analysis for C 15 H 15 N 3 O 4 TFA1.5H 2 O:

계산치: C, 46.16; H, 4.33; N, 9.50.Calc .: C, 46.16; H, 4.33; N, 9.50.

실측치: C, 45.96; 46.16; H, 4.06; N, 9.12.Found: C, 45.96; 46.16; H, 4.06; N, 9.12.

실시예 27Example 27

(E)-{7-메톡시-8-[2-(페닐)에테닐]}-2-나프탈렌이미드아미드 모노(트리플루오로아세테이트) 염(E)-{7-methoxy-8- [2- (phenyl) ethenyl]}-2-naphthaleneimideamide mono (trifluoroacetate) salt

실시예 27AExample 27A

(E)-{7-메톡시-8-[2-(페닐)에테닐]}-2-나프탈렌카보니트릴(E)-{7-methoxy-8- [2- (phenyl) ethenyl]}-2-naphthalenecarbonitrile

본원에 참조 문헌으로 삽입된 문헌[Journal of the American Chemical Society, 97 5249(1975)]의 과정에 따라서 제조된 스티렌 보론산 에스테르 및 실시예 25A를 실시예 26B에 기재된 과정에 따라서 처리하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 303(M+NH4)+.Styrene boronic acid esters prepared according to the procedures of Journal of the American Chemical Society, 97 5249 (1975), incorporated herein by reference and Example 25A, were subjected to the procedures described in Example 26B to obtain the title compound. To obtain. MS (DCI / NH 3 ) m / e 303 (M + NH 4 ) + .

실시예 27BExample 27B

(E)-{7-메톡시-8-[2-(페닐)에테닐]}-2-나프탈렌이미드아미드 모노(트리플루오로아세테이트) 염(E)-{7-methoxy-8- [2- (phenyl) ethenyl]}-2-naphthaleneimideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 27A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 27A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6)δ3.98(s, 3H), 7.28(t, 2H), 7.39(t, 2H), 7.64(m, 5H), 8.00(d, 1H), 8.10(d, 1H), 8.62(s, 1H), 9.22(br s, 2H), 9.42(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ3.98 (s, 3H), 7.28 (t, 2H), 7.39 (t, 2H), 7.64 (m, 5H), 8.00 (d, 1H), 8.10 ( d, 1H), 8.62 (s, 1H), 9.22 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 303(M+NH4)+.MS (DCI / NH 3 ) m / e 303 (M + NH 4 ) + .

C20H18N2O·TFA에 대한 원소분석치:Elemental Analysis for C 20 H 18 N 2 O · TFA:

계산치: C, 63.46; H, 4.60; N, 6.73.Calc .: C, 63.46; H, 4. 60; N, 6.73.

실측치: C, 63.10; H, 4.73; N, 6.43.Found: C, 63.10; H, 4.73; N, 6.43.

실시예 28Example 28

6-(4-페닐부티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (4-phenylbutynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 28AExample 28A

6-하이드록시-2-나프탈렌카보니트릴6-hydroxy-2-naphthalenecarbonitrile

DMF(30ml) 중의 6-브로모-2-나프톨(25.0g, 112mmol) 및 구리(Ⅰ) 시아나이드(11g, 123mmol)의 용액을 135℃에서 18시간 동안 가열하고, 냉각시키며, 에틸 아세테이트(50ml)로 희석시키고, 10% 수성 수산화나트륨으로 연마한 다음 셀라이트R를 통해 여과한다. 여액을 pH 2로 산성화시키고 에틸 아세테이트로 추출한다. 합한 추출물을 농축시키고 에탄올(150ml)에 용해시키며, 물로 연마하여 표제 화합물 14.01g을 침전시킨다. MS(DCI/NH3) m/e 170(M+H)+.A solution of 6-bromo-2-naphthol (25.0 g, 112 mmol) and copper (I) cyanide (11 g, 123 mmol) in DMF (30 ml) was heated at 135 ° C. for 18 hours, cooled and ethyl acetate (50 ml ), Triturated with 10% aqueous sodium hydroxide and filtered through Celite R. The filtrate is acidified to pH 2 and extracted with ethyl acetate. The combined extracts are concentrated, dissolved in ethanol (150 ml) and triturated with water to precipitate 14.01 g of the title compound. MS (DCI / NH 3 ) m / e 170 (M + H) + .

실시예 28BExample 28B

6-(트리플루오로메탄설포닐옥시)-2-나프탈렌카보니트릴6- (trifluoromethanesulfonyloxy) -2-naphthalenecarbonitrile

0℃하의 메틸렌 클로라이드(40ml) 중의 실시예 28A(14.01g, 82.8mmol) 및 트리에틸아민(9.2g, 91.1mmol)의 용액을 트리플루오로메틸설폰산 무수물(28g, 99.4mmol)로 적가 처리하고, 48시간 동안 25℃로 가온시키며, 농축시키고, 에탄올(50ml)에 재용해시킨 다음 물로 연마하여 표제 화합물 8.4g을 침전시킨다. MS(DCI/NH3) m/e 319(M+NH4)+.A solution of Example 28A (14.01 g, 82.8 mmol) and triethylamine (9.2 g, 91.1 mmol) in methylene chloride (40 ml) at 0 ° C. was added dropwise with trifluoromethylsulfonic anhydride (28 g, 99.4 mmol) Warmed to 25 ° C. for 48 h, concentrated, redissolved in ethanol (50 ml) and ground with water to precipitate 8.4 g of the title compound. MS (DCI / NH 3 ) m / e 319 (M + NH 4 ) + .

실시예 28CExample 28C

6-(4-페닐부티닐)-2-나프탈렌카보니트릴6- (4-phenylbutynyl) -2-naphthalenecarbonitrile

실시예 28B, 4-페닐-1-부틴 및 실시예 57B의 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 299(M+NH4)+.The title compound is prepared from the procedure of Example 28B, 4-phenyl-1-butyne and Example 57B. MS (DCI / NH 3 ) m / e 299 (M + NH 4 ) + .

실시예 28DExample 28D

6-(4-페닐부티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (4-phenylbutynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정을 이용하여 실시예 28C로부터 표제 화합물을 제조한다.The title compound is prepared from Example 28C using the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 2.80(t, 2H), 2.95(t, 2H), 7.22(m, 1H), 7.36(m, 4H), 7.58(d, 1H), 7.82(d, 1H), 8.05(d, 1H), 8.10(d, 2H), 8.45(s, 1H), 9.10(br s, 2H), 9.42(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.80 (t, 2H), 2.95 (t, 2H), 7.22 (m, 1H), 7.36 (m, 4H), 7.58 (d, 1H), 7.82 (d , 1H), 8.05 (d, 1H), 8.10 (d, 2H), 8.45 (s, 1H), 9.10 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 299(M+H)+.MS (DCI / NH 3 ) m / e 299 (M + H) + .

C21H18N2·TFA·0.75H2O에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 2 TFA0.75H 2 O:

계산치: C, 64.86; H, 4.85; N, 6.58.Calc .: C, 64.86; H, 4. 85; N, 6.58.

실측치: C, 64.78; H, 4.64; N, 6.03.Found: C, 64.78; H, 4. 64; N, 6.03.

실시예 29Example 29

7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 29AExample 29A

3-[[(1,1-디메틸에틸)디메틸실릴]옥시]-1-프로판올, 4-니트로벤젠설포네이트3-[[(1,1-dimethylethyl) dimethylsilyl] oxy] -1-propanol, 4-nitrobenzenesulfonate

0℃하의 메틸렌 클로라이드(200ml) 중의, 본원에 참조문헌으로 삽입된 문헌[McDougal, et al., JOC, 1986, 51, 3388]의 방법에 의해 제조된 3-t-부틸디메틸실록시-1-프로판올(7.6g, 40mmol), 및 디이소프로필에틸아민(10.4ml, 60mmol)의 용액을 p-니트로페닐설포닐 클로라이드(9.7g, 44mmol)로 처리하고, 3시간 동안 교반하며, 포화 NaHCO3에 붓고 디에틸 에테르로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시킨다. 잔사를 5% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 6.00g 수득한다. MS(DCI/NH3) m/e 395(M+NH4)+.3-t-butyldimethylsiloxy-1- prepared by the method of McDougal, et al., JOC, 1986, 51, 3388 in methylene chloride (200 ml) at 0 ° C., incorporated herein by this reference. A solution of propanol (7.6 g, 40 mmol), and diisopropylethylamine (10.4 ml, 60 mmol) was treated with p-nitrophenylsulfonyl chloride (9.7 g, 44 mmol), stirred for 3 h, and saturated saturated NaHCO 3 Pour and extract with diethyl ether. The extract is washed with brine, dried (Na 2 SO 4 ) and concentrated. The residue is chromatographed on silica gel with 5% ethyl acetate / hexanes to give 6.00 g of the title compound. MS (DCI / NH 3 ) m / e 395 (M + NH 4 ) + .

실시예 29BExample 29B

7-[2-[[(1,1-디메틸에틸)디메틸실릴]옥시]에톡시]-8-요오도-2-나프탈렌카보니트릴7- [2-[[(1,1-dimethylethyl) dimethylsilyl] oxy] ethoxy] -8-iodo-2-naphthalenecarbonitrile

프로필 요오다이드를 실시예 29A로 대체하는 것을 제외하고는 실시예 43A의 방법과 유사한 방법으로 표제 화합물을 제조한다. MS(DCI/NH3) m/e 468(M+H)+.The title compound is prepared in a manner similar to that of Example 43A, except that propyl iodide is replaced with Example 29A. MS (DCI / NH 3 ) m / e 468 (M + H) + .

실시예 29CExample 29C

7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카보니트릴7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarbonitrile

실시예 53E를 실시예 29B로 대체하는 것을 제외하고는 실시예 53F의 방법과 유사한 방법으로 표제 화합물을 제조한다. MS(DCI/NH3) m/e 357(M+H)+.The title compound is prepared in a similar manner as in Example 53F, except that Example 53E is replaced with Example 29B. MS (DCI / NH 3 ) m / e 357 (M + H) + .

실시예 29DExample 29D

7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 29B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 29B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 1.96(m, 2H), 3.69(t, 2H), 4.33(t, 2H), 4.58(br, 1H), 7.63(d, 1H), 7.66(dd, 1H), 8.12(dd, 2H), 8.42(s, 1H), 9.20(s, 2H), 9.53(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.96 (m, 2H), 3.69 (t, 2H), 4.33 (t, 2H), 4.58 (br, 1H), 7.63 (d, 1H), 7.66 (dd , 1H), 8.12 (dd, 2H), 8.42 (s, 1H), 9.20 (s, 2H), 9.53 (s, 2H);

MS(DCI/NH3) m/e 245(M+H)+.MS (DCI / NH 3 ) m / e 245 (M + H) + .

C13H12N2O2I·TFA·0.21H2O에 대한 원소분석치:Elemental Analysis for C 13 H 12 N 2 O 2 I · TFA · 0.21H 2 O:

계산치: C, 53.07; H, 4.85; N, 7.74.Calc .: C, 53.07; H, 4. 85; N, 7.74.

실측치: C, 53.07; H, 4.75; N, 7.65.Found: C, 53.07; H, 4.75; N, 7.65.

실시예 30Example 30

7-(2-하이드록시에톡시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7- (2-hydroxyethoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 30AExample 30A

7-(2-하이드록시에톡시)-2-나프탈렌카보니트릴7- (2-hydroxyethoxy) -2-naphthalenecarbonitrile

실시예 29B(120mg, 0.26mmol), 팔라듐(Ⅱ)Cl2dppf(46mg, 0.03mmol) 및 디이소프로필아민(263mg, 2.6mmol)을 100℃하의 밀봉된 튜브에서 2시간 동안 가열하고, 실온으로 냉각시키며, 에틸 아세테이트로 희석시키고, 물로 세척하며, 건조시킨 다음(Na2SO4) 농축시킨다. 잔사를 15% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 표제 화합물을 85mg 수득한다. MS(DCI/NH3) m/e 342(M+H)+.Example 29B (120 mg, 0.26 mmol), palladium (II) Cl 2 dppf (46 mg, 0.03 mmol) and diisopropylamine (263 mg, 2.6 mmol) were heated in a sealed tube at 100 ° C. for 2 hours and returned to room temperature. Cool, dilute with ethyl acetate, wash with water, dry (Na 2 SO 4 ) and concentrate. The residue was purified on silica gel using 15% ethyl acetate / hexanes to give 85 mg of the title compound. MS (DCI / NH 3 ) m / e 342 (M + H) + .

실시예 30BExample 30B

7-(2-하이드록시에톡시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7- (2-hydroxyethoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 29B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 29B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 1.96(m, 2H), 3.69(t, 2H), 4.33(t, 2H), 4.58(br, 1H), 7.63(d, 1H), 7.66(dd, 1H), 8.12(dd, 2H), 8.42(s, 1H), 9.20(s, 2H), 9.53(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.96 (m, 2H), 3.69 (t, 2H), 4.33 (t, 2H), 4.58 (br, 1H), 7.63 (d, 1H), 7.66 (dd , 1H), 8.12 (dd, 2H), 8.42 (s, 1H), 9.20 (s, 2H), 9.53 (s, 2H);

MS(DCI/NH3) m/e 228(M+H)+.MS (DCI / NH 3 ) m / e 228 (M + H) + .

C14H15N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 2 O 2 · TFA:

계산치: C, 53.78; H, 4.51; N, 7.84.Calc .: C, 53.78; H, 4.51; N, 7.84.

실측치: C, 53.60; H, 4.30; N, 7.81.Found: C, 53.60; H, 4. 30; N, 7.81.

실시예 31Example 31

6-(4-메틸-1-펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (4-methyl-1-pentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 31AExample 31A

6-(4-메틸-1-펜티닐)-2-나프탈렌카보니트릴6- (4-methyl-1-pentynyl) -2-naphthalenecarbonitrile

실시예 28B, 4-메틸-1-펜틴, 및 실시예 57B의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 251(M+NH4)+.The title compound is obtained from the procedure of Example 28B, 4-methyl-1-pentin, and Example 57B. MS (DCI / NH 3 ) m / e 251 (M + NH 4 ) + .

실시예 31BExample 31B

6-(4-메틸-1-펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (4-methyl-1-pentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 31A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 31A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 1.05(d, 6H), 1.90(m, 1H), 2.20(d, 2H), 7.62(dd, 1H), 7.82(dd, 1H), 8.09(d, 1H), 8.12(d, 1H), 8.18(s, 1H), 9.12(br s, 2H), 9.42(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.05 (d, 6H), 1.90 (m, 1H), 2.20 (d, 2H), 7.62 (dd, 1H), 7.82 (dd, 1H), 8.09 (d , 1H), 8.12 (d, 1H), 8.18 (s, 1H), 9.12 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 251(M+H)+.MS (DCI / NH 3 ) m / e 251 (M + H) + .

C17H18N2·TFA에 대한 원소분석치:Elemental Analysis for C 17 H 18 N 2 TFA:

계산치: C, 62.63; H, 5.26; N, 7.69.Calc .: C, 62.63; H, 5. 26; N, 7.69.

실측치: C, 64.85; H, 5.32; N, 7.46.Found: C, 64.85; H, 5. 32; N, 7.46.

실시예 32Example 32

6-(5-페닐펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (5-phenylpentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 32AExample 32A

6-(5-페닐펜티닐)-2-나프탈렌카보니트릴6- (5-phenylpentynyl) -2-naphthalenecarbonitrile

실시예 28B, 5-페닐-1-펜틴, 및 실시예 57B의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 313(M+NH4)+.The title compound is obtained from the procedure of Example 28B, 5-phenyl-1-pentin, and Example 57B. MS (DCI / NH 3 ) m / e 313 (M + NH 4 ) + .

실시예 32BExample 32B

6-(5-페닐펜티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (5-phenylpentynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 32A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 32A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 1.90(m, 2H), 2.80(t, 2H), 3.39(t, 2H), 7.19-7.37(m, 5H), 7.62(dd, 1H), 7.82(dd, 1H), 8.08(d, 1H), 8.15(d, 1H), 8.18(s, 1H), 8.48(s, 1H), 9.15-9.45(br d, 4H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.90 (m, 2H), 2.80 (t, 2H), 3.39 (t, 2H), 7.19-7.37 (m, 5H), 7.62 (dd, 1H), 7.82 (dd, 1H), 8.08 (d, 1H), 8.15 (d, 1H), 8.18 (s, 1H), 8.48 (s, 1H), 9.15-9.45 (br d, 4H);

MS(DCI/NH3) m/e 313(M+H)+.MS (DCI / NH 3 ) m / e 313 (M + H) + .

C22H20N2·TFA에 대한 원소분석치:Elemental Analysis for C 22 H 20 N 2 · TFA:

계산치: C, 67.60; H, 4.96; N, 6.57.Calc .: C, 67.60; H, 4.96; N, 6.57.

실측치: C, 67.32; H, 5.21; N, 6.27.Found: C, 67.32; H, 5. 21; N, 6.27.

실시예 33Example 33

6-(3-페닐-1-프로피닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-phenyl-1-propynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 33AExample 33A

6-(3-페닐-1-프로피닐)-2-나프탈렌카보니트릴6- (3-phenyl-1-propynyl) -2-naphthalenecarbonitrile

실시예 28B, 3-페닐-1-프로핀, 및 실시예 57B의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 285(M+NH4)+.The title compound is obtained from the procedure of Example 28B, 3-phenyl-1-propyne, and Example 57B. MS (DCI / NH 3 ) m / e 285 (M + NH 4 ) + .

실시예 33BExample 33B

6-(3-페닐-1-프로피닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-phenyl-1-propynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 5B의 과정에 따라서 실시예 33A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 33A following the procedure of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 4.00(s, 2H), 7.28-7.50(m, 5H), 7.70(dd, 1H), 7.85(dd, 1H), 8.09(d, 1H), 8.15(d, 1H), 8.21(s, 1H), 8.49(s, 1H), 9.21(br s, 2H), 9.45(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.00 (s, 2H), 7.28-7.50 (m, 5H), 7.70 (dd, 1H), 7.85 (dd, 1H), 8.09 (d, 1H), 8.15 (d, 1H), 8.21 (s, 1H), 8.49 (s, 1H), 9.21 (br s, 2H), 9.45 (br s, 2H);

MS(DCI/NH3) m/e 285(M+H)+.MS (DCI / NH 3 ) m / e 285 (M + H) + .

C20H16N2·TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 2 TFA0.25H 2 O:

계산치: C, 65.59; H, 4.38; N, 6.95.Calc .: C, 65.59; H, 4.38; N, 6.95.

실측치: C, 65.43; H, 3.95; N, 6.70.Found: C, 65.43; H, 3.95; N, 6.70.

실시예 34Example 34

6-(페닐에티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (phenylethynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 34AExample 34A

6-(페닐에티닐)-2-나프탈렌카보니트릴6- (phenylethynyl) -2-naphthalenecarbonitrile

실시예 28B, 페닐아세틸렌, 및 실시예 57B의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 271(M+NH4)+.The title compound is obtained from the procedure of Example 28B, phenylacetylene, and Example 57B. MS (DCI / NH 3 ) m / e 271 (M + NH 4 ) + .

실시예 34BExample 34B

6-(페닐에티닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (phenylethynyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 34A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 34A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6)δ7.49(t, 3H), 7.62(m, 2H), 7.80(dd, 1H), 7.86(dd, 1H), 8.15(d, 1H), 8.19(d, 1H), 8.38(s, 1H), 8.52(s, 1H), 9.38(br s, 4H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.49 (t, 3H), 7.62 (m, 2H), 7.80 (dd, 1H), 7.86 (dd, 1H), 8.15 (d, 1H), 8.19 ( d, 1 H), 8.38 (s, 1 H), 8.52 (s, 1 H), 9.38 (br s, 4 H);

MS(DCI/NH3) m/e 271(M+H)+.MS (DCI / NH 3 ) m / e 271 (M + H) + .

C19H14N2·TFA에 대한 원소분석치:Elemental Analysis for C 19 H 14 N 2 · TFA:

계산치: C, 65.62; H, 3.93; N, 7.29.Calc .: C, 65.62; H, 3.93; N, 7.29.

실측치: C, 65.64; H, 4.11; N, 7.21.Found: C, 65.64; H, 4.11; N, 7.21.

실시예 35Example 35

3-아미노-N-[3-[6-(아미노이미노메틸)-2-나프탈레닐]-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염3-amino-N- [3- [6- (aminoiminomethyl) -2-naphthalenyl] -2-propynyl] benzamide mono (trifluoroacetate) salt

실시예 35AExample 35A

6-(3-아미노-1-프로피닐)-2-나프탈렌카보니트릴6- (3-amino-1-propynyl) -2-naphthalenecarbonitrile

실시예 28B, 프로파질 아민, 및 실시예 41A의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 207(M+NH4)+.The title compound is obtained from the procedure of Example 28B, propazyl amine, and Example 41A. MS (DCI / NH 3 ) m / e 207 (M + NH 4 ) + .

실시예 35BExample 35B

3-아미노-N-[3-(6-시아노-2-나프탈레닐)-2-프로피닐]벤즈아미드3-amino-N- [3- (6-cyano-2-naphthalenyl) -2-propynyl] benzamide

THF(5.5ml) 중의 실시예 35A(100mg, 0.49mmole), 3-아미노벤조산(73mg, 0.53mmole), EDC(141mg, 0.74mmole) 및 DMAP(89mg, 0.74mmole)의 용액을 실온에서 2.5시간 동안 교반한 다음 농축시킨다. 잔사를 메틸렌 클로라이드에 용해시키고, 1N HCl, 물, 포화 NaHCO3및 염수로 세척하며, 건조시키고(MgSO4), 농축시킨 다음 2% 에탄올/메틸렌 클로라이드를 이용하여 실리카 겔 상에서 플래쉬 크로마토그래피로 정제하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 326(M+H)+.A solution of Example 35A (100 mg, 0.49 mmol), 3-aminobenzoic acid (73 mg, 0.53 mmol), EDC (141 mg, 0.74 mmol) and DMAP (89 mg, 0.74 mmol) in THF (5.5 ml) for 2.5 hours at room temperature Stir and concentrate. The residue was dissolved in methylene chloride, washed with 1N HCl, water, saturated NaHCO 3 and brine, dried (MgSO 4 ), concentrated and purified by flash chromatography on silica gel using 2% ethanol / methylene chloride. Obtain the title compound. MS (DCI / NH 3 ) m / e 326 (M + H) + .

실시예 35CExample 35C

3-아미노-N-[3-[6-(아미노이미노메틸)-2-나프탈레닐]-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염3-amino-N- [3- [6- (aminoiminomethyl) -2-naphthalenyl] -2-propynyl] benzamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 35B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 35B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 4.32(d, 2H), 5.69(br s, 2H), 6.58(d, 2H), 7.62(m, 3H), 7.82(d, 1H), 8.08(d, 1H), 8.14(d, 1H), 8.20(s, 1H), 8.43(s, 1H), 8.60(t, 1H), 9.19(br s, 2H), 9.42(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.32 (d, 2H), 5.69 (br s, 2H), 6.58 (d, 2H), 7.62 (m, 3H), 7.82 (d, 1H), 8.08 ( d, 1H), 8.14 (d, 1H), 8.20 (s, 1H), 8.43 (s, 1H), 8.60 (t, 1H), 9.19 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 343(M+H)+.MS (DCI / NH 3 ) m / e 343 (M + H) + .

C21H18N4O·TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 4 O · TFA · 0.25H 2 O:

계산치: C, 59.93; H, 4.26; N, 12.16.Calc .: C, 59.93; H, 4. 26; N, 12.16.

실측치: C, 59.86; H, 3.97; N, 11.93.Found: C, 59.86; H, 3.97; N, 11.93.

실시예 36Example 36

4-아미노-N-[3-(6-아미노이미노메틸-2-나프탈레닐)-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염4-amino-N- [3- (6-aminoiminomethyl-2-naphthalenyl) -2-propynyl] benzamide mono (trifluoroacetate) salt

실시예 36AExample 36A

4-아미노-N-[3-(6-시아노-2-나프탈레닐)-2-프로피닐]벤즈아미드4-amino-N- [3- (6-cyano-2-naphthalenyl) -2-propynyl] benzamide

실시예 35B에 기재된 조건을 실시예 35A 및 4-아미노벤조산에 적용하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 326(M+H)+.The conditions described in Example 35B were applied to Examples 35A and 4-aminobenzoic acid to afford the title compound. MS (DCI / NH 3 ) m / e 326 (M + H) + .

실시예 36BExample 36B

4-아미노-N-[3-(6-아미노이미노메틸-2-나프탈레닐)-2-프로피닐]벤즈아미드 모노(트리플루오로아세테이트) 염4-amino-N- [3- (6-aminoiminomethyl-2-naphthalenyl) -2-propynyl] benzamide mono (trifluoroacetate) salt

실시예 5B의 과정에 따라서 실시예 36A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 36A following the procedure of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 4.38(d, 2H), 6.89(m, 1H), 7.20(m, 2H), 7.22(s, 1H), 7.63(dd, 1H), 7.82(dd, 1H), 8.09(d, 1H), 8.12(d, 1H), 8.20(s, 1H), 8.46(s, 1H), 8.95(t, 1H), 9.19(br s, 2H), 9.42(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.38 (d, 2H), 6.89 (m, 1H), 7.20 (m, 2H), 7.22 (s, 1H), 7.63 (dd, 1H), 7.82 (dd , 1H), 8.09 (d, 1H), 8.12 (d, 1H), 8.20 (s, 1H), 8.46 (s, 1H), 8.95 (t, 1H), 9.19 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 343(M+H)+.MS (DCI / NH 3 ) m / e 343 (M + H) + .

C21G16N4O·2.5TFA에 대한 원소분석치:Elemental Analysis for C 21 G 16 N 4 O · 2.5TFA:

계산치: C, 49.27; H, 3.19; N, 8.54.Calc .: C, 49.27; H, 3. 19; N, 8.54.

실측치: C, 49.27; H, 3.33; N, 8.89.Found: C, 49.27; H, 3.33; N, 8.89.

실시예 37Example 37

(S)-2-아미노-N-[1-[(6-아미노이미노메틸-2-나프탈레닐)카보닐]사이클로헥실]프로피온아미드 비스(트리플루오로아세테이트) 염(S) -2-amino-N- [1-[(6-aminoiminomethyl-2-naphthalenyl) carbonyl] cyclohexyl] propionamide bis (trifluoroacetate) salt

실시예 37AExample 37A

6-[(1-아미노사이클로헥실)에티닐]-2-나프탈렌카보니트릴6-[(1-aminocyclohexyl) ethynyl] -2-naphthalenecarbonitrile

실시예 28B, 1-에티닐사이클로헥실아민, 및 실시예 41A의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 275(M+NH4)+.The title compound is obtained from the process of Example 28B, 1-ethynylcyclohexylamine, and Example 41A. MS (DCI / NH 3 ) m / e 275 (M + NH 4 ) + .

실시예 37BExample 37B

(S)-2-아미노-N-[1-[(6-시아노-2-나프탈레닐)카보닐]사이클로헥실]프로피온아미드(S) -2-amino-N- [1-[(6-cyano-2-naphthalenyl) carbonyl] cyclohexyl] propionamide

실시예 35B에 기재된 조건을 실시예 37A 및 N-(t-부톡시카보닐)-L-알라닌에 적용하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 446(M+H)+.The conditions described in Example 35B were applied to Example 37A and N- (t-butoxycarbonyl) -L-alanine to afford the title compound. MS (DCI / NH 3 ) m / e 446 (M + H) + .

실시예 37CExample 37C

(S)-2-아미노-N-[1-[(6-아미노이미노메틸-2-나프탈레닐)카보닐]사이클로헥실]프로피온아미드 비스(트리플루오로아세테이트) 염(S) -2-amino-N- [1-[(6-aminoiminomethyl-2-naphthalenyl) carbonyl] cyclohexyl] propionamide bis (trifluoroacetate) salt

표제 화합물은 실시예 5B의 과정으로부터 생성된 실시예 37B의 전위 생성물이다.The title compound is the potential product of Example 37B resulting from the process of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 1.24(d, 3H), 1.40-1.62(m, 8H), 2.15-2.26(s, 1H), 2.29-2.38(s, 1H), 3.51(d, 1H), 3.78(d, 1H), 3.82(s, 1H), 7.90(dd, 2H), 8.09(dd, 1H), 8.18(d, 1H), 8.37(d, 1H), 8.55(s, 1H), 8.78(s, 1H), 9.31(s, 2H), 9.50(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.24 (d, 3H), 1.40-1.62 (m, 8H), 2.15-2.26 (s, 1H), 2.29-2.38 (s, 1H), 3.51 (d, 1H), 3.78 (d, 1H), 3.82 (s, 1H), 7.90 (dd, 2H), 8.09 (dd, 1H), 8.18 (d, 1H), 8.37 (d, 1H), 8.55 (s, 1H) ), 8.78 (s, 1 H), 9.31 (s, 2 H), 9.50 (s, 2 H);

MS(DCI/NH3)m/e381(M+H)+.MS (DCI / NH 3 ) m / e 381 (M + H) + .

C23H28N4O2·TFA·2H2O에 대한 원소분석치:Elemental Analysis for C 23 H 28 N 4 O 2 · TFA · 2H 2 O:

계산치: C, 49.39; H, 5.22; N, 8.53.Calc .: C, 49.39; H, 5. 22; N, 8.53.

실측치: C, 49.15; H, 4.79; N, 8.70.Found: C, 49.15; H, 4.79; N, 8.70.

실시예 38Example 38

6-메톡시-8-벤질옥시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6-methoxy-8-benzyloxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 38AExample 38A

8-하이드록시-6-메톡시-3,4-디하이드로-2H-나프탈렌-1-온8-hydroxy-6-methoxy-3,4-dihydro-2H-naphthalen-1-one

0℃하의 메틸렌 클로라이드(150ml) 중의, 본원에 참조 문헌으로 삽입된 문헌[J. Chem. Soc., London 2782(1955)]의 과정에 따라서 제조된 6,8-디메톡시-3,4-디하이드로-2H-나프탈렌-1-온(15g, 72.8mmole)의 용액을 AlCl3(14.3g, 107mmole)로 나누어 처리하고, 실온에서 20시간 동안 교반하며, 교반하면서 얼음에 붓고, 얼음이 용융되면 메틸렌 클로라이드로 추출한다. 이 추출물을 물 및 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 표제 화합물을 13.8g 수득한다. MS(DCI/NH3) m/e 193(M+H)+.In methylene chloride (150 ml) at 0 ° C., incorporated herein by this reference. Chem. Soc., London 2782 (1955)]. A solution of 6,8-dimethoxy-3,4-dihydro-2H-naphthalen-l-one (15 g, 72.8 mmol) prepared according to the procedure of AlCl 3 (14.3 g) was prepared. , 107mmole), the mixture is stirred at room temperature for 20 hours, poured into ice with stirring, and extracted with methylene chloride when the ice melts. The extract is washed with water and brine, dried (MgSO 4 ) and concentrated to give 13.8 g of the title compound. MS (DCI / NH 3 ) m / e 193 (M + H) + .

실시예 38BExample 38B

8-벤질옥시-6-메톡시-3,4-디하이드로-2H-나프탈렌-1-온8-benzyloxy-6-methoxy-3,4-dihydro-2H-naphthalen-1-one

실시예 38A(2.5g, 13mmole), 벤질 브로마이드(2.1ml, 17.8mmole), K2CO3분말(14.3g, 100mmole) 및 2-부탄올(88ml)의 혼합물을 환류하에 4시간 동안 교반하고, 추가의 벤질 브로마이드(1.0ml, 8.5mmole)로 처리하며, 환류하에 3시간 더 교반하고, 실온으로 냉각시키며, 여과한 다음 농축시킨다. 잔사를 메틸렌 클로라이드에 용해시키고, 1N HCl, 물 및 염수로 세척하며, 건조시킨 다음(MgSO4) 농축시킨다. 조 생성물을 30% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 283(M+H)+.Example 38A (2.5 g, 13 mmole), benzyl bromide (2.1 ml, 17.8 mmole), K 2 CO 3 powder (14.3 g, 100 mmole) and 2-butanol (88 ml) were stirred under reflux for 4 hours and further Treated with benzyl bromide (1.0 ml, 8.5 mmol), stirred for 3 hours under reflux, cooled to room temperature, filtered and concentrated. The residue is dissolved in methylene chloride, washed with 1N HCl, water and brine, dried (MgSO 4 ) and concentrated. The crude product is purified on silica gel using 30% ethyl acetate / hexanes to afford the title compound. MS (DCI / NH 3 ) m / e 283 (M + H) + .

실시예 38CExample 38C

3,4-디하이드로-2-(하이드록시메틸렌)-6-메톡시-8-(페닐메톡시)-1(2H)-나프탈렌온3,4-dihydro-2- (hydroxymethylene) -6-methoxy-8- (phenylmethoxy) -1 (2H) -naphthalenone

나트륨 금속(1.29g, 55.9mmole)을 에탄올(4.2ml)과 벤젠(15ml)의 혼합물에 나누어 가한다. 이 혼합물을 환류하에 1.5시간 동안 교반하고, 0℃로 냉각시키며, 에틸 포르메이트(5.6ml, 70mmole)로 적가 처리한 다음 벤젠(20ml) 중의 실시예 38B(6.7g, 23.8mmole)의 용액으로 적가 처리하고, 실온에서 2시간 동안 교반하며, 0℃로 냉각시키고, 얼음/물 및 6N HCl(75ml)로 순차적으로 처리한 다음, 에틸 아세테이트로 추출한다. 추출물을 염수로 세척하고, 건조시킨 다음(MgSO) 농축시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 311(M+H)+.Sodium metal (1.29 g, 55.9 mmol) is added in portions to a mixture of ethanol (4.2 ml) and benzene (15 ml). The mixture was stirred at reflux for 1.5 h, cooled to 0 ° C., treated dropwise with ethyl formate (5.6 ml, 70 mmol) and then dropwise with a solution of Example 38B (6.7 g, 23.8 mmol) in benzene (20 ml). Treat, stir at room temperature for 2 hours, cool to 0 ° C., treat sequentially with ice / water and 6N HCl (75 ml), then extract with ethyl acetate. The extract is washed with brine, dried (MgSO) and concentrated to afford the title compound. MS (DCI / NH 3 ) m / e 311 (M + H) + .

실시예 38DExample 38D

4,5-디하이드로-7-메톡시-9-(페닐메톡시)나프트[2,1-d]이속사졸[2,1-d]이속사졸4,5-dihydro-7-methoxy-9- (phenylmethoxy) naphth [2,1-d] isoxazole [2,1-d] isoxazole

실시예 38C(7.5g, 24.3mmole), 하이드록실아민 하이드로클로라이드(4.0g, 57.6mmole) 및 아세트산(63ml)의 현탁액을 110℃에서 7분 동안 교반하고, 실온으로 냉각시키며, 물로 희석시킨 다음 메틸렌 클로라이드로 추출한다. 추출물을 물 및 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시킨다. 조 생성물을 30% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 플래쉬 크로마토그래피로 정제하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 308(M+H)+.Example 38C (7.5 g, 24.3 mmol), a suspension of hydroxylamine hydrochloride (4.0 g, 57.6 mmol) and acetic acid (63 ml) was stirred at 110 ° C. for 7 minutes, cooled to room temperature, diluted with water and then methylene Extract with chloride. The extract is washed with water and brine, dried (MgSO 4 ) and concentrated. The crude product is purified by flash chromatography on silica gel using 30% ethyl acetate / hexanes to afford the title compound. MS (DCI / NH 3 ) m / e 308 (M + H) + .

실시예 38EExample 38E

8-벤질옥시-2-시아노-6-메톡시-3,4-디하이드로나프탈렌-1-온8-benzyloxy-2-cyano-6-methoxy-3,4-dihydronaphthalen-1-one

메탄올(3.9ml) 중의 나트륨 금속(0.17g, 7.35mmole)으로부터 제조된 수산화나트륨을 벤젠(50ml) 중의 실시예 38D(1.5g, 4.9mmole)의 용액으로 적가 처리하고, 실온에서 4.5시간 동안 교반하며, 물 및 1N HCl로 순차적으로 처리한 다음 에틸 아세테이트로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 308(M+H)+.Sodium hydroxide prepared from sodium metal (0.17 g, 7.35 mmol) in methanol (3.9 ml) was added dropwise with a solution of Example 38D (1.5 g, 4.9 mmol) in benzene (50 ml) and stirred at room temperature for 4.5 hours. Treated sequentially with water and 1N HCl, then extracted with ethyl acetate. The extract is washed with brine, dried (MgSO 4 ) and concentrated to afford the title compound. MS (DCI / NH 3 ) m / e 308 (M + H) + .

실시예 38FExample 38F

2-시아노-6-메톡시-8-벤질옥시-3,4-디하이드로나프탈렌2-cyano-6-methoxy-8-benzyloxy-3,4-dihydronaphthalene

실온하의 무수 에탄올(25ml) 중의 실시예 38E(2.6g, 8.6mmole)의 현탁액을 NaBH4(1.6g)로 나누어 처리하고, 실온에서 20분 동안 교반한 다음 환류하에 20분 동안 교반하고, 실온으로 냉각시키며, 물(20ml)로 처리한 다음 농축시킨다. 잔사를 메틸렌 클로라이드에 용해시키고, 물 및 염수로 세척하며, 건조시킨 다음(MgSO4), 여과하고, 농축시켜 오렌지색 기포상 물질을 2.6g 수득한다. 이러한 기포상 물질을 환류하에 벤젠(52ml) 중의 p-톨루엔설폰산 모노하이드레이트(0.52g, 2.7mmole)과 함께 20분 동안 교반하고, 실온으로 냉각시키며, 에틸 아세테이트로 희석시키고, 물 및 염수로 세척하며, 건조시킨 다음(MgSO4) 농축시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 309(M+NH4)+.A suspension of Example 38E (2.6 g, 8.6 mmol) in anhydrous ethanol (25 ml) at room temperature was treated by dividing with NaBH 4 (1.6 g), stirred at room temperature for 20 minutes and then stirred at reflux for 20 minutes, and returned to room temperature. Cool, treat with water (20 ml) and concentrate. The residue is dissolved in methylene chloride, washed with water and brine, dried (MgSO 4 ), filtered and concentrated to give 2.6 g of orange foamy material. This foamy material is stirred with p-toluenesulfonic acid monohydrate (0.52 g, 2.7 mmol) in benzene (52 ml) under reflux for 20 minutes, cooled to room temperature, diluted with ethyl acetate, washed with water and brine , Dried (MgSO 4 ) and concentrated to afford the title compound. MS (DCI / NH 3 ) m / e 309 (M + NH 4 ) + .

실시예 38GExample 38G

2-시아노-6-메톡시-8-벤질옥시나프탈렌2-cyano-6-methoxy-8-benzyloxynaphthalene

벤젠(40ml) 중의 실시예 38F(0.4g, 1.4mmole), 2,3-디하이드로-5,6-디시아노-1,4-벤조퀴논(0.79g, 3.5mmole)의 용액을 환류하에 4시간 동안 교반하고, 추가의 2,3-디클로로-5,6-디시아노-1,4-벤조퀴논(0.4g, 1.8mmole)으로 처리하며, 환류하에 5시간 더 교반하며, 실온으로 냉각시키고, 에틸 아세테이트로 희석시키며, 포화 NaHCO3및 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 290(M+H)+.A solution of Example 38F (0.4 g, 1.4 mmol), 2,3-dihydro-5,6-dicyano-1,4-benzoquinone (0.79 g, 3.5 mmol) in benzene (40 ml) was refluxed for 4 hours. Stirred for 4 hours, treated with additional 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.4 g, 1.8 mmole), stirred for further 5 hours at reflux, cooled to room temperature, ethyl Dilute with acetate, wash with saturated NaHCO 3 and brine, dry (MgSO 4 ) and concentrate to afford the title compound. MS (DCI / NH 3 ) m / e 290 (M + H) + .

실시예 38HExample 38H

8-벤질옥시-6-메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염8-benzyloxy-6-methoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 38G로부터 표제 화합물을 제조한다.The title compound is prepared from Example 38G following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 4.38(d, 2H), 6.89(m, 1H), 7.20(m, 2H), 7.22(s, 1H), 7.63(dd, 1H), 7.82(dd, 1H), 8.09(d, 1H), 8.12(d, 1H), 8.20(s, 1H), 8.46(s, 1H), 8.95(t, 1H), 9.19(br s, 2H), 9.42(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.38 (d, 2H), 6.89 (m, 1H), 7.20 (m, 2H), 7.22 (s, 1H), 7.63 (dd, 1H), 7.82 (dd , 1H), 8.09 (d, 1H), 8.12 (d, 1H), 8.20 (s, 1H), 8.46 (s, 1H), 8.95 (t, 1H), 9.19 (br s, 2H), 9.42 (br s, 2H);

MS(DCI/NH3) m/e 307(M+H)+.MS (DCI / NH 3 ) m / e 307 (M + H) + .

C19H18N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 19 H 18 N 2 O 2 · TFA:

계산치: C, 60.00; H, 4.56; N, 6.66.Calc .: C, 60.00; H, 4.56; N, 6.66.

실측치: C, 59.93; H, 4.46; N, 6.51.Found: C, 59.93; H, 4. 46; N, 6.51.

실시예 39Example 39

2-[(7-아미노이미노메틸)-3-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염2-[(7-aminoiminomethyl) -3-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt

실시예 39AExample 39A

6-메톡시-8-하이드록시-2-나프탈렌카보니트릴6-methoxy-8-hydroxy-2-naphthalenecarbonitrile

메탄올(150ml) 중의 실시예 38G(1.62g, 5.6mmole) 및 10% 무수 Pd/C(0.50g)의 혼합물을 4atm하에서 실온에서 파르 진탕기에서 30시간 동안 수소화시킨다. 이 혼합물을 여과하고 농축시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 217(M+NH4)+.A mixture of Example 38G (1.62 g, 5.6 mmol) and 10% anhydrous Pd / C (0.50 g) in methanol (150 ml) is hydrogenated in a Parr shaker for 30 hours at room temperature under 4 atm. This mixture is filtered and concentrated to afford the title compound. MS (DCI / NH 3 ) m / e 217 (M + NH 4 ) + .

실시예 39BExample 39B

2-[(7-시아노-3-메톡시-1-나프탈레닐)옥시]아세트아미드2-[(7-cyano-3-methoxy-1-naphthalenyl) oxy] acetamide

실시예 5A에 기재된 조건을 실시예 39A 및 2-브로모아세트아미드에 적용하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 274(M+NH4)+.The conditions described in Example 5A were applied to Example 39A and 2-bromoacetamide to afford the title compound. MS (DCI / NH 3 ) m / e 274 (M + NH 4 ) + .

실시예 39CExample 39C

2-[(7-아미노이미노메틸)-3-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염2-[(7-aminoiminomethyl) -3-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 39B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 39B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.93(s, 3H), 4.70(s, 2H), 6.70(d, 1H), 7.09(d, 1H), 7.65(s, 2H), 7.82(dd, 1H), 7.99(d, 1H), 8.70(s, 1H), 9.05(s, 2H), 9.38(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.93 (s, 3H), 4.70 (s, 2H), 6.70 (d, 1H), 7.09 (d, 1H), 7.65 (s, 2H), 7.82 (dd , 1H), 7.99 (d, 1H), 8.70 (s, 1H), 9.05 (s, 2H), 9.38 (s, 2H);

MS(DCI/NH3) m/e 274(M+H)+.MS (DCI / NH 3 ) m / e 274 (M + H) + .

C14H15N3O3·TFA에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 3 · TFA:

계산치: C, 49.62; H, 4.16; N, 10.85.Calc .: C, 49.62; H, 4. 16; N, 10.85.

실측치: C, 49.68; H, 4.24; N, 10.61Found: C, 49.68; H, 4. 24; N, 10.61

실시예 40Example 40

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenylurea mono (trifluoroacetate) salt

실시예 40AExample 40A

6-시아노--2-나프탈렌카보닐 클로라이드6-cyano-2--2-naphthalenecarbonyl chloride

톨루엔(100ml) 중의 실시예 8E(4.4g, 22.3mmole)의 현탁액을 티오닐 클로라이드(6.0ml) 및 DMAP(5mg)로 처리하고, 55℃에서 1시간 동안 가열하며, 추가의 티오닐 클로라이드(3ml)로 처리하고, 1시간 동안 95℃로 가온하며, 실온으로 냉각시키고, 헥산(75ml) 중에서 2.5시간 동안 교반한 다음 여과시켜 백색 분말로서의 표제 화합물을 3.62g 수득한다. 여액을 농축시키고, 에테르로 연마하여 표제 화합물을 1.02g 더 수득한다. MS(DCI/NH3) m/e 215(M+H)+.A suspension of Example 8E (4.4 g, 22.3 mmol) in toluene (100 ml) was treated with thionyl chloride (6.0 ml) and DMAP (5 mg), heated at 55 ° C. for 1 hour, and further thionyl chloride (3 ml) ), Warmed to 95 ° C. for 1 h, cooled to rt, stirred for 2.5 h in hexane (75 ml) and filtered to afford 3.62 g of the title compound as a white powder. The filtrate is concentrated and triturated with ether to afford 1.02 g more of the title compound. MS (DCI / NH 3 ) m / e 215 (M + H) + .

실시예 40BExample 40B

2-시아노-6-나프토일 아지드2-cyano-6-naphthoyl azide

실온하의 아세톤(600ml) 중의 실시예 40A(1.65g, 7.65mmole)의 용액을 수(10ml) 중의 나트륨 아지드(3g, 46mmole)의 용액으로 처리하고, 1.5시간 동안 교반한 다음 물(60ml)로 희석시킨다. 생성된 고체를 여과하고, 물로 세척한 다음 건조시켜 백색 분말로서의 표제 화합물을 4.24g 수득한다. MS(DCI/NH3) m/e 240(M+NH4)+.A solution of Example 40A (1.65 g, 7.65 mmol) in acetone (600 ml) at room temperature was treated with a solution of sodium azide (3 g, 46 mmol) in water (10 ml), stirred for 1.5 h and then with water (60 ml). Dilute. The resulting solid is filtered, washed with water and dried to give 4.24 g of the title compound as a white powder. MS (DCI / NH 3 ) m / e 240 (M + NH 4 ) + .

실시예 40CExample 40C

N-(6-시아노-2-나프탈레닐)-N'-페닐우레아N- (6-cyano-2-naphthalenyl) -N'-phenylurea

톨루엔(18ml) 중의 실시예 40B(221.2mg, 1mmole)의 용액을 85℃에서 1시간 동안 가열한 다음 95℃에서 1.5시간 동안 가열하고, 실온으로 냉각시키며, 아닐린(240㎕, 2.63mmole)으로 처리하고, 25분 동안 교반하며, 에테르(10ml)로 처리한다. 생성된 고체를 수집하고, 에테르로 세척한 다음 진공하에 건조시켜 백색 분말을 230mg 수득한다. MS(DCI/NH3) m/e 305(M+NH4)+.A solution of Example 40B (221.2 mg, 1 mmol) in toluene (18 ml) was heated at 85 ° C. for 1 hour and then at 95 ° C. for 1.5 hours, cooled to room temperature and treated with aniline (240 μl, 2.63 mmol) And stir for 25 minutes and treat with ether (10 ml). The resulting solid is collected, washed with ether and dried in vacuo to give 230 mg of white powder. MS (DCI / NH 3 ) m / e 305 (M + NH 4 ) + .

실시예 40DExample 40D

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenylurea mono (trifluoroacetate) salt

10:1 피리딘:트리에틸아민(10ml) 중의 실시예 40C(148mg, 0.5mmole)의 용액을 5분 동안 H2S로 처리하고, 실온에서 18시간 동안 교반한 다음 농축시킨다. 생성된 고체를 아세톤(15ml)에 용해시키고, 요오도메탄(0.8ml, 12.8mmole)으로 처리하며, 2시간 동안 교반하고, 에테르(10ml)로 희석시키고, 여과시키며, 에테르로 세척한 다음 진공하에 건조시킨다. 생성된 고체를 메탄올에 용해시키고, 메탄올(2ml) 중의 2N NH3로 처리하며, 4시간 동안 50℃로 가온시킨 다음 농축시킨다. 생성물을 실시예 1B에 기재된 과정에 따라서 정제하여 표제 화합물을 62mg 수득한다.A solution of Example 40C (148 mg, 0.5 mmol) in 10: 1 pyridine: triethylamine (10 ml) was treated with H 2 S for 5 minutes, stirred at room temperature for 18 hours and then concentrated. The resulting solid is dissolved in acetone (15 ml), treated with iodomethane (0.8 ml, 12.8 mmol), stirred for 2 hours, diluted with ether (10 ml), filtered, washed with ether and then under vacuum To dry. The resulting solid is dissolved in methanol, treated with 2N NH 3 in methanol (2 ml), warmed to 50 ° C. for 4 h and then concentrated. The product was purified following the procedure in Example 1B to yield 62 mg of the title compound.

1H NMR(300MHz, DMSO-d6) δ 7.00(t, 1H), 7.31(dd, 2H), 7.52(d, 1H), 7.65 (dd, 1H), 7.76 (dd, 1H), 8.02 (d, 2H), 8.30(s, 1H), 8.39(s, 1H), 9.05(br s, 2H), 9.11(s, 1H), 9.33(br s, 2H), 9.42(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.00 (t, 1H), 7.31 (dd, 2H), 7.52 (d, 1H), 7.65 (dd, 1H), 7.76 (dd, 1H), 8.02 (d , 2H), 8.30 (s, 1H), 8.39 (s, 1H), 9.05 (br s, 2H), 9.11 (s, 1H), 9.33 (br s, 2H), 9.42 (s, 1H);

MS(DCI/NH3) m/e 305 (M+H)+.MS (DCI / NH 3 ) m / e 305 (M + H) + .

C18H16N4O·TFA에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 4 O · TFA:

계산치: C, 57.42; H, 4.10; N, 13.39.Calc .: C, 57.42; H, 4.10; N, 13.39.

실측치: C, 57.50; H, 4.05; N, 13.08.Found: C, 57.50; H, 4.05; N, 13.08.

실시예 41Example 41

(E)-6-[2-(페닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (phenyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 41AExample 41A

(E)-6-[2-(페닐)에테닐]-2-나프탈렌카보니트릴(E) -6- [2- (phenyl) ethenyl] -2-naphthalenecarbonitrile

최소 헤드 용량의 밀봉된 튜브 속의 실시예 28B(350mg, 1.16mmole), 스티렌(157mg, 1.51mmol), 팔라듐(Ⅱ) 아세테이트(26mg, 0.12mmol), 트리페닐포스핀(61mg, 0.23mmol), 트리에틸아민(2ml) 및 아세토니트릴(1ml)의 용액을 100℃에서 19시간 동안 가열하고, 에틸 아세테이트(20ml)로 희석시키며, 물로 세척하고, 건조시킨 다음(MgSO4) 실리카 겔(4g)을 사용하여 농축시킨다. 이 혼합물을 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 160mg 수득한다. MS(DCI/NH3) m/e 273(M+NH4)+.Example 28B (350 mg, 1.16 mmol), styrene (157 mg, 1.51 mmol), palladium (II) acetate (26 mg, 0.12 mmol), triphenylphosphine (61 mg, 0.23 mmol), tree in a sealed tube of minimum head capacity A solution of ethylamine (2 ml) and acetonitrile (1 ml) was heated at 100 ° C. for 19 hours, diluted with ethyl acetate (20 ml), washed with water, dried (MgSO 4 ) and silica gel (4 g) using Concentrated. This mixture is chromatographed on silica gel with 10% ethyl acetate / hexanes to give 160 mg of the title compound. MS (DCI / NH 3 ) m / e 273 (M + NH 4 ) + .

실시예 41BExample 41B

(E)-6-[2-(페닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (phenyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 41A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 41A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 7.33(t, 1H), 7.4(t, 2H), 7.5(d, 2H), 7.69(d, 1H), 7.70(d, 1H), 7.81(dd, 1H), 8.03(dd, 1H), 8.10(d, 1H), 8.13(d, 1H), 8.17(s, 1H), 8.44(s, 1H), 8.97(s, 2H), 9.41(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 7.33 (t, 1H), 7.4 (t, 2H), 7.5 (d, 2H), 7.69 (d, 1H), 7.70 (d, 1H), 7.81 (dd , 1H), 8.03 (dd, 1H), 8.10 (d, 1H), 8.13 (d, 1H), 8.17 (s, 1H), 8.44 (s, 1H), 8.97 (s, 2H), 9.41 (s, 2H);

MS(DCI/NH3) m/e 273 (M+H)+.MS (DCI / NH 3 ) m / e 273 (M + H) + .

C19H16N2O·TFA에 대한 원소분석치:Elemental Analysis for C 19 H 16 N 2 O · TFA:

계산치: C, 65.28; H, 4.43; N, 7.25.Calc .: C, 65.28; H, 4. 43; N, 7.25.

실측치: C, 64.95; H, 4.60; N, 6.42.Found: C, 64.95; H, 4. 60; N, 6.42.

실시예 42Example 42

6-[2-(페닐)에틸]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (phenyl) ethyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 42AExample 42A

6-[2-(페닐)에틸]-2-나프탈렌카보니트릴6- [2- (phenyl) ethyl] -2-naphthalenecarbonitrile

메탄올(5ml) 중의 실시예 57B(80mg, 0.31mmol) 및 탄소상 팔라듐(20% 물, 50mg)의 혼합물을 수소 1기압하에서 0.5시간 동안 교반하고, 여과한 다음 농축시켜 표제 화합물을 72mg 수득한다. MS(DCI/NH3) m/e 275(M+NH4)+.A mixture of Example 57B (80 mg, 0.31 mmol) and palladium on carbon (20% water, 50 mg) in methanol (5 ml) was stirred under 1 atmosphere of hydrogen for 0.5 h, filtered and concentrated to give 72 mg of the title compound. MS (DCI / NH 3 ) m / e 275 (M + NH 4 ) + .

실시예 42BExample 42B

6-[2-(페닐)에틸]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (phenyl) ethyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 42A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 42A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.03(m, 2H), 7.23(m, 5H), 7.60(dd, 1H), 7.76(dd, 1H), 7.85(s, 1H), 8.03(t, 2H), 8.42(s, 1H), 8.99(s, 2H), 9.39(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 3.03 (m, 2H), 7.23 (m, 5H), 7.60 (dd, 1H), 7.76 (dd, 1H), 7.85 (s, 1H), 8.03 (t , 2H), 8.42 (s, 1H), 8.99 (s, 2H), 9.39 (s, 2H);

MS(DCI/NH3) m/e 275 (M+H)+.MS (DCI / NH 3 ) m / e 275 (M + H) + .

C19H18N2O·1.33TFA에 대한 원소분석치:Elemental Analysis for C 19 H 18 N 2 O · 1.33TFA:

계산치: C, 61.29; H, 4.59; N, 6.61.Calc .: C, 61.29; H, 4.59; N, 6.61.

실측치: C, 61.56; H, 4.62; N, 5.21.Found: C, 61.56; H, 4. 62; N, 5.21.

실시예 43Example 43

7-프로폭시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-propoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 43AExample 43A

7-프로폭시-8-요오도-2-나프탈렌카보니트릴7-propoxy-8-iodo-2-naphthalenecarbonitrile

DMF(2ml) 중의 실시예 53A(65mg, 0.25mmol)을 프로필 요오다이드(40ml)로 처리하고, 65℃에서 1시간 동안 교반하며, 물로 희석시키고 디에틸 에테르로 추출한다. 유기 추출물을 건조시키고(MgSO4) 농축시키며, 잔사를 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 표제 화합물을 160mg 수득한다. MS(DCI/NH3) m/e 355(M+H)+.Example 53A (65 mg, 0.25 mmol) in DMF (2 ml) is treated with propyl iodide (40 ml), stirred at 65 ° C. for 1 h, diluted with water and extracted with diethyl ether. The organic extract is dried (MgSO 4 ) and concentrated, and the residue is purified on silica gel using 10% ethyl acetate / hexanes to give 160 mg of the title compound. MS (DCI / NH 3 ) m / e 355 (M + H) + .

실시예 43BExample 43B

7-프로폭시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-propoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 43A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 43A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 1.09(t, 3H), 1.82(m, 2H), 4.23(t, 2H), 7.62(d, 1H), 7.65(dd, 1H), 8.12(dd, 2H), 9.15(s, 2H), 9.42(s, 1H), 9.53(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.09 (t, 3H), 1.82 (m, 2H), 4.23 (t, 2H), 7.62 (d, 1H), 7.65 (dd, 1H), 8.12 (dd , 2H), 9.15 (s, 2H), 9.42 (s, 1H), 9.53 (s, 2H);

MS(DCI/NH3) m/e 355 (M+H)+.MS (DCI / NH 3 ) m / e 355 (M + H) + .

C14H15N2OI·TFA·0.26C7H8에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 2 OI · TFA · 0.26C 7 H 8 :

계산치: C, 43.49; H, 3.70; N, 5.69.Calc .: C, 43.49; H, 3. 70; N, 5.69.

실측치: C, 43.50; H, 3.59; N, 5.75.Found: C, 43.50; H, 3.59; N, 5.75.

실시예 44Example 44

(±)-6-(3-페닐옥시라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(±) -6- (3-phenyloxyranyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 44AExample 44A

(±)-6-(3-페닐옥시라닐)-2-나프탈렌카보니트릴(±) -6- (3-phenyloxyranyl) -2-naphthalenecarbonitrile

메틸렌 클로라이드(3ml) 중의 실시예 41A(69mg, 0.27mmol) 및 m-클로로퍼벤조산(70mg, 0.41mmol)의 용액을 25℃에서 3일 동안 교반하고, 농축시키며, 실리카 겔 칼럼(에틸 아세테이트 중의 0.1% 트리에틸아민으로 예비처리되고 10% 에틸 아세테이트/헥산으로 용출됨) 상에 로딩하여 표제 화합물을 72mg 수득한다. MS(DCI/NH3) m/e 289(M+NH4)+.A solution of Example 41A (69 mg, 0.27 mmol) and m-chloroperbenzoic acid (70 mg, 0.41 mmol) in methylene chloride (3 ml) was stirred at 25 ° C. for 3 days, concentrated and a silica gel column (0.1 in ethyl acetate). Pretreated with% triethylamine and eluted with 10% ethyl acetate / hexanes to afford 72 mg of the title compound. MS (DCI / NH 3 ) m / e 289 (M + NH 4 ) + .

실시예 44BExample 44B

(±)-6-(3-페닐옥시라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(±) -6- (3-phenyloxyranyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 44A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 44A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 4.24(d, 1H), 4.35(d, 1H), 7.43(m, 5H), 7.67(dd, 1H), 7.83(dd, 1H), 8.12(s, 1H), 8.13(d, 1H), 8.16(d, 1H), 8.50(s, 1H), 9.03(s, 2H), 9.44(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.24 (d, 1H), 4.35 (d, 1H), 7.43 (m, 5H), 7.67 (dd, 1H), 7.83 (dd, 1H), 8.12 (s , 1H), 8.13 (d, 1H), 8.16 (d, 1H), 8.50 (s, 1H), 9.03 (s, 2H), 9.44 (s, 2H);

MS(DCI/NH3) m/e 289 (M+H)+.MS (DCI / NH 3 ) m / e 289 (M + H) + .

C19H16N2O·1.3TFA에 대한 원소분석치:Elemental Analysis for C 19 H 16 N 2 O · 1.3TFA:

계산치: C, 64.52; H, 4.55; N, 6.51.Calc .: C, 64.52; H, 4.55; N, 6.51.

실측치: C, 64.35; H, 4.60; N, 5.87.Found: C, 64.35; H, 4. 60; N, 5.87.

실시예 45Example 45

(E)-6-[2-(2-티에닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (2-thienyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 45AExample 45A

2-비닐티오펜2-vinylthiophene

THF(100ml) 중의 메틸트리페닐포스포늄 브로마이드(19.13g, 53.5mmol)의 현탁액을 THF(17.8mg) 중의 2M 부틸리튬으로 적가 처리한 다음 2-카복시티오펜(5g, 44.6mmol)로 적가 처리하며, 30분 동안 교반한 후, 74 내지 78℃에서 증류시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 111 (M+H)+.A suspension of methyltriphenylphosphonium bromide (19.13 g, 53.5 mmol) in THF (100 ml) was added dropwise with 2M butyllithium in THF (17.8 mg) followed by dropwise addition with 2-carboxythiophene (5 g, 44.6 mmol). After stirring for 30 minutes, distillation at 74-78 ° C. yields the title compound. MS (DCI / NH 3 ) m / e 111 (M + H) + .

실시예 45BExample 45B

(E)-6-[2-(2-티에닐)에테닐]-2-나프탈렌카보니트릴(E) -6- [2- (2-thienyl) ethenyl] -2-naphthalenecarbonitrile

실시예 41A의 과정에 따라서 실시예 45의 생성물로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 279(M+NH4)+.The title compound is prepared from the product of Example 45 following the procedure of Example 41A. MS (DCI / NH 3 ) m / e 279 (M + NH 4 ) + .

실시예 45CExample 45C

(E)-6-[2-(2-티에닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (2-thienyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 45B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 45B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 7.12(dd, 2H), 7.15(d, 1H), 7.32(d, 1H), 7.6(d, 1H), 7.74(d, 1H), 7.80(dd, 1H), 7.9-8.1(m, 3H), 8.14(s, 1H), 8.43(s, 1H), 9.03(s, 2H), 9.42(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.12 (dd, 2H), 7.15 (d, 1H), 7.32 (d, 1H), 7.6 (d, 1H), 7.74 (d, 1H), 7.80 (dd , 1H), 7.9-8.1 (m, 3H), 8.14 (s, 1H), 8.43 (s, 1H), 9.03 (s, 2H), 9.42 (s, 2H);

MS(DCI/NH3) m/e 279 (M+H)+.MS (DCI / NH 3 ) m / e 279 (M + H) + .

C17H14N2O2S·TFA에 대한 원소분석치:Elemental Analysis for C 17 H 14 N 2 O 2 S · TFA:

계산치: C, 53.77; H, 3.56; N, 6.60.Calc .: C, 53.77; H, 3.56; N, 6.60.

실측치: C, 54.88; H, 3.66; N, 6.45.Found: C, 54.88; H, 3. 66; N, 6.45.

실시예 46Example 46

6-(3-옥소부틸)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-oxobutyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 46AExample 46A

6-(3-옥소부틸)-2-나프탈렌카보니트릴6- (3-oxobutyl) -2-naphthalenecarbonitrile

실시예 28B, 1-부텐-3-올, 및 실시예 41A의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 241(M+NH4)+.The title compound is obtained from the procedure of Example 28B, 1-butene-3-ol, and Example 41A. MS (DCI / NH 3 ) m / e 241 (M + NH 4 ) + .

실시예 46BExample 46B

6-(3-옥소부틸)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-oxobutyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 46A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 46A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 2.13(s, 1H), 2.94(m, 4H), 7.57(dd, 1H), 7.78(dd, 1H), 7.85(s, 1H), 8.01(d, 1H), 8.05(d, 1H), 8.43(s, 1H), 8.48(m, 2H), 9.06(s, 2H), 9.40(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.13 (s, 1H), 2.94 (m, 4H), 7.57 (dd, 1H), 7.78 (dd, 1H), 7.85 (s, 1H), 8.01 (d , 1H), 8.05 (d, 1H), 8.43 (s, 1H), 8.48 (m, 2H), 9.06 (s, 2H), 9.40 (s, 2H);

MS(DCI/NH3) m/e 241 (M+H)+.MS (DCI / NH 3 ) m / e 241 (M + H) + .

C15H16N2O·1.3TFA에 대한 원소분석치:Elemental Analysis for C 15 H 16 N 2 O · 1.3TFA:

계산치: C, 54.31; H, 4.48; N, 7.19.Calc .: C, 54.31; H, 4. 48; N, 7.19.

실측치: C, 54.33; H, 4.35; N, 7.27.Found: C, 54.33; H, 4. 35; N, 7.27.

실시예 47Example 47

6-(3-메톡시페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-methoxyphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 47AExample 47A

6-(3-메톡시페닐)-2-나프탈렌카보니트릴6- (3-methoxyphenyl) -2-naphthalenecarbonitrile

실시예 28B(300mg, 1mmol), 팔라듐(Ⅱ) 아세테이트(22mg, 0.1mmol) 및 1,1'-비스(디페닐포스피노)페로센(111mg, 0.2mmol)의 용액을 DMF(3ml) 중에서 15분 동안 교반하고, Cs2CO3(813mg, 2.5mmol) 및 3-메톡시페닐보론산(228mg, 1.5mmol)로 처리하며, 80℃에서 20분 동안 교반하고, 냉각시키고, pH 7 완충액(10ml)으로 처리한 다음 디에틸 에테르로 추출한다. 에테르 추출물을 건조시키고(MgSO4), 농축시킨 다음, 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 백색 고체로서의 표제 화합물을 140mg 수득한다. MS(DCI/NH3) m/e 277(M+NH4)+.Example 28B (300 mg, 1 mmol), palladium (II) acetate (22 mg, 0.1 mmol) and a solution of 1,1′-bis (diphenylphosphino) ferrocene (111 mg, 0.2 mmol) in DMF (3 ml) for 15 minutes Stirred, treated with Cs 2 CO 3 (813 mg, 2.5 mmol) and 3-methoxyphenylboronic acid (228 mg, 1.5 mmol), stirred at 80 ° C. for 20 minutes, cooled, pH 7 buffer (10 ml) After treatment with diethyl ether. The ether extract is dried (MgSO 4 ), concentrated and purified on silica gel using 10% ethyl acetate / hexanes to give 140 mg of the title compound as a white solid. MS (DCI / NH 3 ) m / e 277 (M + NH 4 ) + .

실시예 47BExample 47B

6-(3-메톡시페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-methoxyphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 47A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 47A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.88(s, 3H), 7.03(m, 1H), 7.44(m, 3H), 7.84(dd, 1H), 8.05(dd, 1H), 8.19(d, 1H), 8.21(d, 1H), 8.41(s, 1H), 8.51(s, 2H), 9.11(s, 2H), 9.45(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.88 (s, 3H), 7.03 (m, 1H), 7.44 (m, 3H), 7.84 (dd, 1H), 8.05 (dd, 1H), 8.19 (d , 1H), 8.21 (d, 1H), 8.41 (s, 1H), 8.51 (s, 2H), 9.11 (s, 2H), 9.45 (s, 2H);

MS(DCI/NH3) m/e 277 (M+H)+.MS (DCI / NH 3 ) m / e 277 (M + H) + .

C18H16N2O·TFA·0.2H2O에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 2 O · TFA · 0.2H 2 O:

계산치: C, 61.03; H, 4.45; N, 7.12.Calc .: C, 61.03; H, 4. 45; N, 7.12.

실측치: C, 61.03; H, 4.11; N, 6.86.Found: C, 61.03; H, 4.11; N, 6.86.

실시예 48Example 48

N-[3-(메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(트리플루오로아세테이트) 염N- [3- (methyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide mono (trifluoroacetate) salt

실시예 48AExample 48A

N-[3-(메틸)페닐]-6-시아노-2-나프탈렌카복스아미드N- [3- (methyl) phenyl] -6-cyano-2-naphthalenecarboxamide

3-메틸 페닐이소시아네이트, 실시예 55C, 및 실시예 55C의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 287(M+H)+.The title compound is obtained from the process of 3-methyl phenylisocyanate, Example 55C, and Example 55C. MS (DCI / NH 3 ) m / e 287 (M + H) + .

실시예 48BExample 48B

N-[3-(메틸)페닐]-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(트리플루오로아세테이트) 염N- [3- (methyl) phenyl] -6-aminoiminomethyl-2-naphthalenecarboxamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 48A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 48A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 2.34(s, 3H), 6.96(d, 1H), 7.27(t, 1H), 7.62(d, 1H), 7.66(s, 1H), 7.91(dd, 1H), 8.15(dd, 1H), 8.29(d, 1H), 8.31(d, 1H), 8.54(s, 1H), 8.68(s, 1H), 9.15(s, 2H), 9.49(s, 2H), 10.46(s, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.34 (s, 3H), 6.96 (d, 1H), 7.27 (t, 1H), 7.62 (d, 1H), 7.66 (s, 1H), 7.91 (dd , 1H), 8.15 (dd, 1H), 8.29 (d, 1H), 8.31 (d, 1H), 8.54 (s, 1H), 8.68 (s, 1H), 9.15 (s, 2H), 9.49 (s, 2H), 10.46 (s, 1 H);

MS(DCI/NH3) m/e 304 (M+H)+.MS (DCI / NH 3 ) m / e 304 (M + H) + .

C19H17N3O·TFA·0.12C7H8에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 3 O · TFA · 0.12C 7 H 8 :

계산치: C, 61.23; H, 4.46; N, 9.81.Calc .: C, 61.23; H, 4. 46; N, 9.81.

실측치: C, 61.12; H, 4.42; N, 9.43.Found: C, 61.12; H, 4. 42; N, 9.43.

실시예 49Example 49

6-(2-포밀페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (2-formylphenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 49AExample 49A

6-(2-포밀페녹시)-2-나프탈렌카보니트릴6- (2-formylphenoxy) -2-naphthalenecarbonitrile

DMF(10ml) 중의 2-하이드록시벤즈알데히드(72mg, 0.59mmol), 6-브로모-1-시아노나프탈렌(150mg, 0.65mmol) 및 Cs2CO3(248mg, 0.76mmol)의 용액을 90℃에서 2일 동안 가열하고, 물로 처리한 다음 에틸 아세테이트로 추출한다. 합한 유기 추출물을 건조시키고(MgSO4) 농축시키며, 조 생성물을 10% 에틸 아세테이트/헥산을 사용하여 칼럼 크로마토그래피하여 정제하여 표제 화합물을 40mg 수득한다. MS(DCI/NH3) m/e 291(M+NH4)+.A solution of 2-hydroxybenzaldehyde (72 mg, 0.59 mmol), 6-bromo-1-cyanonaphthalene (150 mg, 0.65 mmol) and Cs 2 CO 3 (248 mg, 0.76 mmol) in DMF (10 ml) was prepared at 90 ° C. Heat for 2 days, treat with water and extract with ethyl acetate. The combined organic extracts are dried (MgSO 4 ) and concentrated and the crude product is purified by column chromatography using 10% ethyl acetate / hexanes to give 40 mg of the title compound. MS (DCI / NH 3 ) m / e 291 (M + NH 4 ) + .

실시예 49BExample 49B

6-(2-포밀페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (2-formylphenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 49A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 49A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 7.19(d, 1H), 7.44(t, 1H), 7.56(s, 1H), 7.60(d, 1H), 7.79(m, 2H), 7.94(dd, 1H), 8.01(d, 1H), 8.2(d, 1H), 8.51(s, 1H), 9.03(s, 2H), 9.41(s, 2H), 10.35(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.19 (d, 1H), 7.44 (t, 1H), 7.56 (s, 1H), 7.60 (d, 1H), 7.79 (m, 2H), 7.94 (dd) , 1H), 8.01 (d, 1H), 8.2 (d, 1H), 8.51 (s, 1H), 9.03 (s, 2H), 9.41 (s, 2H), 10.35 (s, 1H);

MS(DCI/NH3) m/e 291 (M+H)+.MS (DCI / NH 3 ) m / e 291 (M + H) + .

C18H14N2O2·TFA·1.7H2O에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 2 O 2 · TFA · 1.7H 2 O:

계산치: C, 55.16; H, 4.27; N, 6.43.Calc .: C, 55.16; H, 4. 27; N, 6.43.

실측치: C, 55.17; H, 3.92; N, 5.94.Found: C, 55.17; H, 3.92; N, 5.94.

실시예 50Example 50

6-(2-포밀페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (2-formylphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 50AExample 50A

6-(2-포밀페닐)-2-나프탈렌카보니트릴6- (2-formylphenyl) -2-naphthalenecarbonitrile

실시예 28B, 2-포밀페닐보론산, 및 실시예 47A의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 275(M+NH4)+.The title compound is obtained from the procedure of Example 28B, 2-formylphenylboronic acid, and Example 47A. MS (DCI / NH 3 ) m / e 275 (M + NH 4 ) + .

실시예 50BExample 50B

6-(2-포밀페닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (2-formylphenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 50A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 50A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 7.71-7.64(m, 2H), 7.79(d, 1H), 7.81(s, 1H), 7.88(dd, 1H), 7.9(d, 1H), 8.16(d, 1H), 8.23(t, 2H), 8.56(s, 1H), 9.05(s, 2H), 9.48(s, 2H), 9.92(s, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 7.71-7.64 (m, 2H), 7.79 (d, 1H), 7.81 (s, 1H), 7.88 (dd, 1H), 7.9 (d, 1H), 8.16 (d, 1H), 8.23 (t, 2H), 8.56 (s, 1H), 9.05 (s, 2H), 9.48 (s, 2H), 9.92 (s, 1H);

MS(DCI/NH3) m/e 275 (M+H)+.MS (DCI / NH 3 ) m / e 275 (M + H) + .

C18H14N2O·TFA에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 2 O · TFA:

계산치: C, 61.86; H, 3.89; N, 7.21Calc .: C, 61.86; H, 3.89; N, 7.21

실측치: C, 61.98; H, 3.59; N, 6.88.Found: C, 61.98; H, 3.59; N, 6.88.

실시예 51Example 51

6-[2-(하이드록시메틸)페닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (hydroxymethyl) phenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 51AExample 51A

6-[2-(하이드록시메틸)]-2-나프탈렌카보니트릴6- [2- (hydroxymethyl)]-2-naphthalenecarbonitrile

실시예 50A(98mg, 0.38mmol) 및 수소화붕소나트륨(15mg, 0.80mmol)을 메탄올(10ml)에 용해시키고 0.5시간 동안 교반한다. 이 용액을 농축시키고, 잔사를 30% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 표제 화합물을 90mg 수득한다. MS(DCI/NH3) m/e 277(M+NH4)+.Example 50A (98 mg, 0.38 mmol) and sodium borohydride (15 mg, 0.80 mmol) are dissolved in methanol (10 ml) and stirred for 0.5 h. The solution is concentrated and the residue is purified on silica gel using 30% ethyl acetate / hexanes to give 90 mg of the title compound. MS (DCI / NH 3 ) m / e 277 (M + NH 4 ) + .

실시예 51BExample 51B

6-[2-(하이드록시메틸)페닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (hydroxymethyl) phenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 51A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 51A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 9.46(s, 2H), 9.06(s, 2H), 8.54(s, 1H), 8.16(t, 2H), 8.07(s, 1H), 7.85(dd, 1H), 7.74(dd, 1H), 7.63(d, 1H), 7.49-7.34(m, 3H), 4.46(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 9.46 (s, 2H), 9.06 (s, 2H), 8.54 (s, 1H), 8.16 (t, 2H), 8.07 (s, 1H), 7.85 (dd , 1H), 7.74 (dd, 1H), 7.63 (d, 1H), 7.49-7.34 (m, 3H), 4.46 (s, 2H);

MS(DCI/NH3) m/e 277 (M+H)+.MS (DCI / NH 3 ) m / e 277 (M + H) + .

C18H16N2O·1.44TFA에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 2 O · 1.44TFA:

계산치: C, 56.93; H, 3.99; N, 6.36.Calc .: C, 56.93; H, 3.99; N, 6.36.

실측치: C, 56.94; H, 3.88; N, 6.46.Found: C, 56.94; H, 3.88; N, 6.46.

실시예 52Example 52

6-(3-옥소-1-부테닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-oxo-1-butenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 52AExample 52A

6-(3-옥소-1-부테닐)-2-나프탈렌카보니트릴6- (3-oxo-1-butenyl) -2-naphthalenecarbonitrile

메틸 아크릴레이트, 실시예 28B, 및 실시예 41A의 과정으로부터 표제 화합물을 수득한다. MS(DCI/NH3) m/e 222(M+H)+.The title compound is obtained from the procedure of methyl acrylate, Example 28B, and Example 41A. MS (DCI / NH 3) m / e 222 (M + H) +.

실시예 52BExample 52B

6-(3-옥소-1-부테닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- (3-oxo-1-butenyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 52A로부터 표제 화합물을 제조한다.The title compound is prepared from Example 52A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 9.46(s, 2H), 9.13(s, 2H), 8.48(s, 1H), 8.38(s, 1H), 8.18(d, 1H), 8.15(d, 1H), 8.01(dd, 1H), 7.85(dd, 1H), 7.82(d, 1H), 7.03(d, 1H), 2.40(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.46 (s, 2H), 9.13 (s, 2H), 8.48 (s, 1H), 8.38 (s, 1H), 8.18 (d, 1H), 8.15 (d , 1H), 8.01 (dd, 1H), 7.85 (dd, 1H), 7.82 (d, 1H), 7.03 (d, 1H), 2.40 (s, 1H);

MS(DCI/NH3) m/e 239 (M+H)+.MS (DCI / NH 3 ) m / e 239 (M + H) + .

C15H14N2O·1.58TFA에 대한 원소분석치:Elemental Analysis for C 15 H 14 N 2 O · 1.58TFA:

계산치: C, 52.13; H, 3.75; N, 6.69Calc .: C, 52.13; H, 3.75; N, 6.69

실측치: C, 52.09; H, 3.63; N, 6.64.Found: C, 52.09; H, 3.63; N, 6.64.

실시예 53Example 53

7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarboximideamide bis (trifluoroacetate) salt

실시예 53AExample 53A

7-하이드록시-8-요오도-2-나프탈렌카보니트릴7-hydroxy-8-iodo-2-naphthalenecarbonitrile

0℃하의 물(500ml) 및 THF(80ml) 중의 7-시아노-2-나프톨(22.3g, 131.8mmol), 탄산나트륨(29.3g, 277mmol) 및 I2(31.8mg, 125.2mmol)의 혼합물을 실온에서 3시간 동안 교반하고, 1M HCl로 산성화하며 에틸 아세테이트로 추출한다. 이 추출물을 포화 Na2S2O3및 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시킨다. 생성물을 에틸 아세테이트로부터 재결정화하여 표제 화합물을 33g수득한다. MS(DCI/NH3) m/e 313(M+NH4)+.A mixture of 7-cyano-2-naphthol (22.3 g, 131.8 mmol), sodium carbonate (29.3 g, 277 mmol) and I 2 (31.8 mg, 125.2 mmol) in water (500 ml) and THF (80 ml) at 0 ° C. was cooled to room temperature. Stirred for 3 h, acidified with 1M HCl and extracted with ethyl acetate. The extract is washed with saturated Na 2 S 2 O 3 and brine, dried (Na 2 SO 4 ) and concentrated. The product is recrystallized from ethyl acetate to give 33 g of the title compound. MS (DCI / NH 3 ) m / e 313 (M + NH 4 ) + .

실시예 53BExample 53B

7-메톡시-8-요오도-2-나프탈렌카보니트릴7-methoxy-8-iodo-2-naphthalenecarbonitrile

메탄올(500ml) 및 에틸 아세테이트(300ml) 중의 실시예 53A(36.7g, 124.2mmol)을 3시간에 걸쳐 헥산(260ml) 중의 2M 트리메틸실릴디아조메탄으로 처리하고, 24시간 동안 교반하며, 농축시킨 다음 에틸 아세테이트로 재결정화하여 표제 화합물을 36.4g 수득한다. MS(DCI/NH3) m/e 327(M+NH4)+.Example 53A (36.7 g, 124.2 mmol) in methanol (500 ml) and ethyl acetate (300 ml) was treated with 2M trimethylsilyldiazomethane in hexane (260 ml) over 3 hours, stirred for 24 hours, concentrated and then Recrystallization from ethyl acetate gives 36.4 g of the title compound. MS (DCI / NH 3 ) m / e 327 (M + NH 4 ) + .

실시예 53CExample 53C

4-요오도-1-[[2-(트리메틸실릴)에톡시]메틸]-1H-피라졸4-iodo-1-[[2- (trimethylsilyl) ethoxy] methyl] -1H-pyrazole

0℃하의 THF(40ml) 중의 NaH(1.94mg, 48.5mmol)의 슬러리를 THF(20ml) 중의 4-요오도피라졸(8.97g, 46.2mmol)의 용액으로 처리하고, 1시간 동안 교반하며, SEM 클로라이드(9.00ml, 50.8mmol)로 처리하고, 실온에서 1시간 동안 교반하며, 물에 붓고 에틸 아세테이트로 추출한다. 추출물을 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시킨다. 잔사를 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 14.4g 수득한다. MS(DCI/NH3) m/e 325(M+H)+.A slurry of NaH (1.94 mg, 48.5 mmol) in THF (40 ml) at 0 ° C. was treated with a solution of 4-iodopyrazole (8.97 g, 46.2 mmol) in THF (20 ml), stirred for 1 hour, and SEM Treat with chloride (9.00ml, 50.8mmol), stir at room temperature for 1 hour, pour into water and extract with ethyl acetate. The extract is washed with brine, dried (MgSO 4 ) and concentrated. The residue is chromatographed on silica gel with 10% ethyl acetate / hexanes to give 14.4 g of the title compound. MS (DCI / NH 3 ) m / e 325 (M + H) + .

실시예 53DExample 53D

[1-[[2-(트리메틸실릴)에톡시]메틸]-1H-피라졸-4-일]보론산[1-[[2- (trimethylsilyl) ethoxy] methyl] -1H-pyrazol-4-yl] boronic acid

-78℃하의 THF(250ml) 중의 실시예 53C(12.97g, 40mmol)을 헥산 중의 2.5M 부틸리튬(17.6ml, 44mmol)로 처리하고, -78℃에서 10분 동안 교반하며, 트리메틸 보레이트(11.36ml, 100mmol)로 처리하고, 실온으로 가온시키며, 3M HCl(400ml)로 처리한 다음 에틸 아세테이트로 추출한다. 이 추출물을 농축시키고, 잔사를 1M NaOH(500ml)에 용해시키며, 디에틸 에테르로 추출시키고, 진한 HCl로 산성화시킨 다음 에틸 아세테이트로 추출한다. 추출물을 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시킨다. 잔사를 에틸 아세테이트를 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 2.20g 수득한다. MS(DCI/NH3) m/e 199(M-B(OH)2)+.Example 53C (12.97 g, 40 mmol) in THF (250 ml) at −78 ° C. was treated with 2.5 M butyllithium (17.6 ml, 44 mmol) in hexanes, stirred at −78 ° C. for 10 minutes, and trimethyl borate (11.36 ml) , 100 mmol), warmed to room temperature, treated with 3M HCl (400 ml) and extracted with ethyl acetate. The extract is concentrated, the residue is dissolved in 1M NaOH (500 ml), extracted with diethyl ether, acidified with concentrated HCl and extracted with ethyl acetate. The extract is washed with brine, dried (Na 2 SO 4 ) and concentrated. The residue is chromatographed on silica gel with ethyl acetate to give 2.20 g of the title compound. MS (DCI / NH 3 ) m / e 199 (MB (OH) 2 ) + .

실시예 53EExample 53E

7-메톡시-8-[1-[[2-(트리메틸실릴)에톡시]메틸]-1H-피라졸-4-일]-2-나프탈렌카보니트릴7-methoxy-8- [1-[[2- (trimethylsilyl) ethoxy] methyl] -1H-pyrazol-4-yl] -2-naphthalenecarbonitrile

실시예 47A에 기재된 과정을 실시예 53B(1.55g, 5mmol) 및 53D(1.45g, 6mmol)에 적용하여 표제 화합물을 1.64g 수득한다. MS(DCI/NH3) m/e 380(M+H)+.The procedure described in Example 47A was applied to Examples 53B (1.55 g, 5 mmol) and 53D (1.45 g, 6 mmol) to afford 1.64 g of the title compound. MS (DCI / NH 3 ) m / e 380 (M + H) + .

실시예 53FExample 53F

7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카보니트릴7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarbonitrile

THF(10ml) 중의 실시예 53E(1.84g, 4.85mmol)의 용액을 THF(24ml) 중의 1M 테트라부틸암모늄 플루오라이드로 처리하고, 6시간 동안 환류시킨 다음 농축시킨다. 잔사를 1:1 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 0.88g 수득한다. MS(DCI/NH3) m/e 267(M+NH4)+.A solution of Example 53E (1.84 g, 4.85 mmol) in THF (10 ml) was treated with 1M tetrabutylammonium fluoride in THF (24 ml), refluxed for 6 hours and then concentrated. The residue is chromatographed on silica gel with 1: 1 ethyl acetate / hexanes to give 0.88 g of the title compound. MS (DCI / NH 3 ) m / e 267 (M + NH 4 ) + .

실시예 53GExample 53G

7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarboximideamide bis (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 53F로부터 표제 화합물을 제조한다.The title compound is prepared from Example 53F following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.89(s, 3H), 7.60(dd, 1H), 7.71(d, 1H), 7.92(s, 2H), 8.05(d, 1H), 8.12(d, 1H), 8.29(s, 1H), 9.33(s, 2H), 9.34(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.89 (s, 3H), 7.60 (dd, 1H), 7.71 (d, 1H), 7.92 (s, 2H), 8.05 (d, 1H), 8.12 (d , 1H), 8.29 (s, 1H), 9.33 (s, 2H), 9.34 (s, 2H);

MS(DCI/NH3) m/e 267 (M+H)+.MS (DCI / NH 3 ) m / e 267 (M + H) + .

C15H14N4O·2.8TFA에 대한 원소분석치:Elemental Analysis for C 15 H 14 N 4 O · 2.8TFA:

계산치: C, 42.30; H, 2.90; N, 9.59.Calc .: C, 42.30; H, 2.90; N, 9.59.

실측치: C, 42.54; H, 3.11; N, 9.03.Found: C, 42.54; H, 3.11; N, 9.03.

실시예 54Example 54

7-메톡시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 53B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 53B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 4.01(s, 3H), 7.65(m, 2H), 8.12(d, 1H), 8.15(d, 1H), 8.42(s, 1H), 9.14(s, 2H), 9.52(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 4.01 (s, 3H), 7.65 (m, 2H), 8.12 (d, 1H), 8.15 (d, 1H), 8.42 (s, 1H), 9.14 (s , 2H), 9.52 (s, 2H);

MS (DCI/NH3) m/e 327 (M+H)+.MS (DCI / NH 3 ) m / e 327 (M + H) + .

C12H12N2OI·1.2TFA에 대한 원소분석치:Elemental Analysis for C 12 H 12 N 2 OI · 1.2TFA:

계산치: C, 37.28; H, 2.87; N, 6.04.Calc .: C, 37.28; H, 2.87; N, 6.04.

실측치: C, 37.35; H, 2.47; N, 5.93.Found: C, 37.35; H, 2.47; N, 5.93.

실시예 55Example 55

N-페닐-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(메탄설포네이트) 염N-phenyl-6-aminoiminomethyl-2-naphthalenecarboxamide mono (methanesulfonate) salt

실시예 55AExample 55A

2-트리플루오로메탄설포닐옥시-6-브로모나프탈렌2-trifluoromethanesulfonyloxy-6-bromonaphthalene

메틸렌 클로라이드(25ml) 중의 6-브로모-2-나프톨(4.96g, 22.25mmol), N-페닐트리플루오로메탄설포네이트(7.95g, 22.25mmol) 및 디이소프로필에틸아민(7.75ml, 44.5mmol)의 용액을 실온에서 3시간 동안 교반하고, 물에 붓고 디에틸 에테르로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시킨다. 잔사를 3% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 7.89g 수득한다. MS(DCI/NH3) m/e 354 및 356(M+H)+.6-bromo-2-naphthol (4.96 g, 22.25 mmol), m-phenyltrifluoromethanesulfonate (7.95 g, 22.25 mmol) and diisopropylethylamine (7.75 ml, 44.5 mmol) in methylene chloride (25 ml) ) Solution is stirred at room temperature for 3 hours, poured into water and extracted with diethyl ether. The extract is washed with brine, dried (MgSO 4 ) and concentrated. The residue is chromatographed on silica gel with 3% ethyl acetate / hexanes to give 7.89 g of the title compound. MS (DCI / NH 3 ) m / e 354 and 356 (M + H) + .

실시예 55BExample 55B

6-브로모-2-나프탈렌카보니트릴6-bromo-2-naphthalenecarbonitrile

실시예 55A(7.89g, 22.2mmol)를 DMF(50ml) 중의 Zn(CN)2(1.33g, 11.33mmol) 및 Pd(PPh3)4(256mg, 0.22mmol)과 합하고, 90℃에서 3시간 동안 가열하며, 실온으로 냉각시키고, 포화 NaHCO3로 처리하며 디에틸 에테르로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시킨다. 이 잔사를 5% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 2.67g 수득한다. MS(DCI/NH3) m/e 231 및 233(M+H)+.Example 55A (7.89 g, 22.2 mmol) was combined with Zn (CN) 2 (1.33 g, 11.33 mmol) and Pd (PPh 3 ) 4 (256 mg, 0.22 mmol) in DMF (50 ml) and at 90 ° C. for 3 hours. Heat, cool to room temperature, treat with saturated NaHCO 3 and extract with diethyl ether. The extract is washed with brine, dried (MgSO 4 ) and concentrated. This residue is chromatographed on silica gel with 5% ethyl acetate / hexanes to afford 2.67 g of the title compound. MS (DCI / NH 3 ) m / e 231 and 233 (M + H) + .

실시예 55CExample 55C

N-페닐-6-시아노-2-나프탈렌카복스아미드N-phenyl-6-cyano-2-naphthalenecarboxamide

-100℃하의 THF(3ml) 및 헥산(1ml) 중의 실시예 55B(224mg, 0.965mmol)의 용액을 헥산 중의 2.5M 부틸리튬(0.386ml, 0.965mmol)로 처리하고, -100℃에서 5분 동안 교반하며, 페닐 이소시아네이트(0.115ml, 1.06mmol)로 처리하고, 실온으로 가온시키며 pH 7 완충액(0.5ml)로 처리한 다음 농축시킨다. 잔사를 20% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 54mg 수득한다. MS(DCI/NH3) m/e 273(M+H)+.A solution of Example 55B (224 mg, 0.965 mmol) in THF (3 ml) and hexane (1 ml) at −100 ° C. was treated with 2.5M butyllithium (0.386 ml, 0.965 mmol) in hexanes, and at −100 ° C. for 5 minutes. Stir, treat with phenyl isocyanate (0.115 ml, 1.06 mmol), warm to room temperature, treat with pH 7 buffer (0.5 ml) and concentrate. The residue is chromatographed on silica gel with 20% ethyl acetate / hexanes to give 54 mg of the title compound. MS (DCI / NH 3 ) m / e 273 (M + H) + .

실시예 55DExample 55D

N-페닐-6-아미노이미노메틸-2-나프탈렌카복스아미드 모노(메탄설포네이트) 염N-phenyl-6-aminoiminomethyl-2-naphthalenecarboxamide mono (methanesulfonate) salt

THF(2ml) 중의 실시예 55C(52mg, 0.191mmol)의 용액을 THF(0.6ml) 중의 1M 리튬 비스(트리메틸실릴)아미드로 처리하고, 18시간 동안 교반하며, 2M HCl(4ml)로 처리하고, 24시간 더 교반하며, 포화 Na2CO3로 염기성이 되도록 하고 에틸 아세테이트로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시킨다. 조 생성물을 최소량의 메탄올(약 1ml)에 용해시키고, 메탄설폰산(1방울)로 처리하며, 디에틸 에테르(400ml)로 희석시키고 여과시켜 표제 화합물을 15mg 수득한다.A solution of Example 55C (52 mg, 0.191 mmol) in THF (2 ml) was treated with 1 M lithium bis (trimethylsilyl) amide in THF (0.6 ml), stirred for 18 h, treated with 2 M HCl (4 ml), Stir for another 24 hours, make basic with saturated Na 2 CO 3 and extract with ethyl acetate. The extract is washed with brine, dried (Na 2 SO 4 ) and concentrated. The crude product is dissolved in a minimum amount of methanol (about 1 ml), treated with methanesulfonic acid (1 drop), diluted with diethyl ether (400 ml) and filtered to give 15 mg of the title compound.

1H NMR(300MHz, DMSO-d6) δ 2.32(s, 3H), 7.15(dd, 1H), 7.40(dd, 2H), 7.83(d, 2H), 7.90(dd, 1H), 8.17(dd, 1H), 8.25(d, 1H), 8.34(d, 1H), 8.57(s, 1H), 8.70(s, 1H), 9.09(br s, 2H), 9.51(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.32 (s, 3H), 7.15 (dd, 1H), 7.40 (dd, 2H), 7.83 (d, 2H), 7.90 (dd, 1H), 8.17 (dd , 1H), 8.25 (d, 1H), 8.34 (d, 1H), 8.57 (s, 1H), 8.70 (s, 1H), 9.09 (br s, 2H), 9.51 (br s, 2H);

MS(DCI/NH3) m/e 290 (M+H)+.MS (DCI / NH 3 ) m / e 290 (M + H) + .

C18H16N3O·1.1CH3SO3H에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 3 O · 1.1CH 3 SO 3 H:

계산치: C, 57.96; H, 4.95; N, 10.61.Calc .: C, 57.96; H, 4.95; N, 10.61.

실측치: C, 58.03; H, 4.48; N, 10.36.Found: C, 58.03; H, 4. 48; N, 10.36.

실시예 56Example 56

4-[(6-아미노이미노메틸-2-나프탈레닐)옥시]-N-메틸벤젠아세트아미드 모노(트리플루오로아세테이트) 염4-[(6-aminoiminomethyl-2-naphthalenyl) oxy] -N-methylbenzeneacetamide mono (trifluoroacetate) salt

실시예 56AExample 56A

N-메틸-3-하이드록시페닐아세트아미드N-methyl-3-hydroxyphenylacetamide

메틸렌 클로라이드(20ml) 중의 3-하이드록시페닐아세트산(1.00g, 6.57mmol) 및 옥살릴 클로라이드(0.63ml, 7.22mmol)의 용액을 피리딘(0.6ml, 7.37mmol)으로 적가 처리하고, 90분 동안 교반하며, 40% 수성 메틸아민(30ml)에 붓고, 15분 동안 교반하며, 농축시키고, 1M HCl에 용해시킨 다음 에틸 아세테이트로 추출한다. 이 추출물을 염수로 세척하고, 건조시키며(MgSO4) 농축시킨다. 잔사를 에틸 아세테이트를 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 260mg 수득한다. MS(DCI/NH3) m/e 166(M+H)+.A solution of 3-hydroxyphenylacetic acid (1.00 g, 6.57 mmol) and oxalyl chloride (0.63 ml, 7.22 mmol) in methylene chloride (20 ml) was added dropwise with pyridine (0.6 ml, 7.37 mmol) and stirred for 90 minutes. Pour into 40% aqueous methylamine (30 ml), stir for 15 minutes, concentrate, dissolve in 1M HCl and extract with ethyl acetate. The extract is washed with brine, dried (MgSO 4 ) and concentrated. The residue is chromatographed on silica gel with ethyl acetate to give 260 mg of the title compound. MS (DCI / NH 3 ) m / e 166 (M + H) + .

실시예 56BExample 56B

4-[(6-시아노-2-나프탈레닐)옥시]-N-메틸벤젠아세트아미드4-[(6-cyano-2-naphthalenyl) oxy] -N-methylbenzeneacetamide

DMF(3ml) 중의 실시예 56A(245mg, 1.48mmol), 실시예 55B(344mg, 1.48mmol) 및 Cs2CO3(530mg, 1.63mmol)의 혼합물을 120℃에서 72시간 동안 교반하고, 냉각시키며 1:1 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 54mg 수득한다. MS(DCI/NH3) m/e 317(M+H)+.A mixture of Example 56A (245 mg, 1.48 mmol), Example 55B (344 mg, 1.48 mmol) and Cs 2 CO 3 (530 mg, 1.63 mmol) in DMF (3 ml) was stirred at 120 ° C. for 72 hours, cooled and 1 Chromatography on silica gel using: 1 ethyl acetate / hexanes affords 54 mg of the title compound. MS (DCI / NH 3 ) m / e 317 (M + H) + .

실시예 56CExample 56C

4-[(6-아미노이미노메틸-2-나프탈레닐)옥시]-N-메틸벤젠아세트아미드 모노(트리플루오로아세테이트) 염4-[(6-aminoiminomethyl-2-naphthalenyl) oxy] -N-methylbenzeneacetamide mono (trifluoroacetate) salt

실시예 55D의 과정에 따라서 실시예 56B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 56B following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.33(s, 3H), 2.58(d, 3H), 3.42(s, 2H), 7.05(m, 2H), 7.12(d, 10H), 7.40(dd, 1H), 7.45(m, 2H), 7.79(dd, 1H), 7.98(q, 1H), 8.02(d, 1H), 8.15(d, 1H), 8.49(s, 1H), 8.99(br s, 2H), 9.39(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.33 (s, 3H), 2.58 (d, 3H), 3.42 (s, 2H), 7.05 (m, 2H), 7.12 (d, 10H), 7.40 (dd , 1H), 7.45 (m, 2H), 7.79 (dd, 1H), 7.98 (q, 1H), 8.02 (d, 1H), 8.15 (d, 1H), 8.49 (s, 1H), 8.99 (br s , 2H), 9.39 (br s, 2H);

MS(DCI/NH3) m/e 334 (M+H)+.MS (DCI / NH 3 ) m / e 334 (M + H) + .

C19H17N3O2·1.5CH3SO3H에 대한 원소분석치: C 19 H 17 N 3 O 2 · 1.5CH 3 SO 3 H Elemental analysis for:

계산치: C, 54.08; H, 5.28; N, 8.80.Calc .: C, 54.08; H, 5. 28; N, 8.80.

실측치: C, 53.80; H, 5.37; N, 8.52.Found: C, 53.80; H, 5. 37; N, 8.52.

실시예 57Example 57

6-[2-(메틸티오)페닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염6- [2- (methylthio) phenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 57AExample 57A

2-시아노나프탈렌-6-보론산2-cyanonaphthalene-6-boronic acid

-100℃하의 THF(220ml) 및 헥산(50ml) 중의 실시예 55B(6.37g, 27.45mmol)의 용액을 헥산 중의 2.5M 부틸리튬(11.0ml, 27.5mmol)로 처리하고, -100℃에서 10분 동안 교반하며, 트리메틸 보레이트(7.8ml, 68.6mmol)로 처리하고, 실온으로 가온시키며 3M HCl(400ml)로 처리한 다음 에틸 아세테이트로 추출한다. 이 추출물을 농축시키고, 잔사를 1M NaOH(500ml)에 용해시키며, 디에틸 에테르로 추출하고, 12M HCl로 산성화한 다음 에틸 아세테이트로 추출한다. 이 추출물을 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시킨다. 잔사를 최소 메탄올 및 에틸 아세테이트에 용해시키고 헥산으로 연마하여 표제 화합물을 2.74g 수득한다. MS(DCI/NH3) m/e 215(M+NH4)+.A solution of Example 55B (6.37 g, 27.45 mmol) in THF (220 ml) and hexane (50 ml) at −100 ° C. was treated with 2.5 M butyllithium (11.0 ml, 27.5 mmol) in hexane and 10 minutes at −100 ° C. Stirred for 3 hours, treated with trimethyl borate (7.8 ml, 68.6 mmol), warmed to room temperature, treated with 3M HCl (400 ml) and extracted with ethyl acetate. The extract is concentrated, the residue is dissolved in 1M NaOH (500 ml), extracted with diethyl ether, acidified with 12M HCl and extracted with ethyl acetate. The extract is washed with brine, dried (Na 2 SO 4 ) and concentrated. The residue is dissolved in minimal methanol and ethyl acetate and triturated with hexane to afford 2.74 g of the title compound. MS (DCI / NH 3 ) m / e 215 (M + NH 4 ) + .

실시예 57BExample 57B

6-[2-(메틸티오)페닐]-2-나프탈렌카보니트릴6- [2- (methylthio) phenyl] -2-naphthalenecarbonitrile

DMF(5ml) 중의 2-브로모티오아니졸(0.147ml, 1.10mmol), Pd(OAc)2(24mg, 0.11mmol) 및 1,1'-비스(디페닐포스피노페로센)(120mg, 0.22mmol)의 용액을 10분 동안 교반하고, 실시예 57A(260mg, 1.32mmol) 및 Cs2CO3(1.07g, 3.3mmol)으로 처리하며, 85℃에서 6시간 동안 가열하고, 실온으로 냉각시키며 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 155mg 수득한다. MS(DCI/NH3) m/e 231(M+NH4)+.2-bromothioanisol (0.147 ml, 1.10 mmol), Pd (OAc) 2 (24 mg, 0.11 mmol) and 1,1′-bis (diphenylphosphinoferrocene) in DMF (5 ml) (120 mg, 0.22 mmol ) Is stirred for 10 minutes, treated with Example 57A (260 mg, 1.32 mmol) and Cs 2 CO 3 (1.07 g, 3.3 mmol), heated at 85 ° C. for 6 hours, cooled to room temperature and 10% Chromatography on silica gel using ethyl acetate / hexanes yields 155 mg of the title compound. MS (DCI / NH 3 ) m / e 231 (M + NH 4 ) + .

실시예 57CExample 57C

6-[2-(메틸티오)페닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염6- [2- (methylthio) phenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서 실시예 57B로부터 표제 화합물을 제조한다.The title compound is prepared from Example 57B following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.32(s, 3H), 2.40(s, 3H), 7.34(m, 2H), 7.45(m, 2H), 7.82(dd, 2H), 7.95(dd, 1H), 8.06(s, 1H), 8.15(d, 1H), 8.20(d, 1H), 8.55(s, 1H), 9.03(br s, 2H), 9.56(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.32 (s, 3H), 2.40 (s, 3H), 7.34 (m, 2H), 7.45 (m, 2H), 7.82 (dd, 2H), 7.95 (dd , 1H), 8.06 (s, 1H), 8.15 (d, 1H), 8.20 (d, 1H), 8.55 (s, 1H), 9.03 (br s, 2H), 9.56 (br s, 2H);

MS(DCI/NH3) m/e 293 (M+H)+.MS (DCI / NH 3 ) m / e 293 (M + H) + .

C18H17N2S·CH3SO3H에 대한 원소분석치:Elemental Analysis for C 18 H 17 N 2 S · CH 3 SO 3 H:

계산치: C, 58.18; H, 5.18; N, 7.12.Calc .: C, 58.18; H, 5. 18; N, 7.12.

실측치: C, 57.97; H, 5.31; N, 6.97.Found: C, 57.97; H, 5.31; N, 6.97.

실시예 58Example 58

6-[2-(2-티오메톡시에틸)페닐]나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염6- [2- (2-thiomethoxyethyl) phenyl] naphthalene-2-carboximideamide mono (methanesulfonate) salt

실시예 58AExample 58A

2-(2-브로모에틸)브로모벤젠2- (2-bromoethyl) bromobenzene

아세토니트릴(60ml) 중의 2-브로모펜에틸 알콜(5.05g, 25.1mmol) 및 피리딘(3.65ml, 45.2mmol)의 용액을 Ph3PBr2(13.8g, 32.65mmol)로 처리하고, 0℃에서 2시간 동안 교반하며, 헥산으로 희석시키고, 25% 디에틸 에테르/헥산을 사용하여 실리카 겔의 플러그를 통하여 여과시켜 표제 화합물을 6.0g 수득한다. MS(DCI/NH3) m/e 263(M+H)+.A solution of 2-bromophenethyl alcohol (5.05 g, 25.1 mmol) and pyridine (3.65 ml, 45.2 mmol) in acetonitrile (60 ml) was treated with Ph 3 PBr 2 (13.8 g, 32.65 mmol) and 2 at 0 ° C. Stir for hours, dilute with hexanes and filter through a plug of silica gel using 25% diethyl ether / hexanes to give 6.0 g of the title compound. MS (DCI / NH 3 ) m / e 263 (M + H) + .

실시예 58BExample 58B

2-(2-티오메톡시에틸)브로모벤젠2- (2-thiomethoxyethyl) bromobenzene

DMF(5ml) 중의 실시예 58A(990mg, 3.75mmol) 및 나트륨 티오메톡사이드(290mg, 4.12mmol)의 용액을 90℃에서 5시간 동안 가열하고, 냉각시킨 다음, 1% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 646mg 수득한다. MS(DCI/NH3) m/e 231, 233(M+H)+.A solution of Example 58A (990 mg, 3.75 mmol) and sodium thiomethoxide (290 mg, 4.12 mmol) in DMF (5 ml) was heated at 90 ° C. for 5 hours, cooled, and then using 1% ethyl acetate / hexanes. Chromatography on silica gel yields 646 mg of the title compound. MS (DCI / NH 3 ) m / e 231, 233 (M + H) + .

실시예 58CExample 58C

6-[2-(2-티오메톡시에틸)페닐]-2-나프탈렌카보니트릴6- [2- (2-thiomethoxyethyl) phenyl] -2-naphthalenecarbonitrile

실시예 58B(300mg, 1.30mmol), 실시예 57A(260mg, 1.32mmol), 및 실시예 57B에 기재된 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 321(M+NH4)+.The title compound is prepared from the procedure described in Example 58B (300 mg, 1.30 mmol), Example 57A (260 mg, 1.32 mmol), and Example 57B. MS (DCI / NH 3 ) m / e 321 (M + NH 4 ) + .

실시예 58DExample 58D

6-[2-(2-티오메톡시에틸)페닐]나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염6- [2- (2-thiomethoxyethyl) phenyl] naphthalene-2-carboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서 실시예 58C로부터 표제 화합물을 제조한다.The title compound is prepared from Example 58C following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 1.78(s, 3H) 2.31(s, 3H), 2.55(m, 2H), 2.85(m, 2H), 7.30-7.48(m, 4H), 7.66(dd, 1H), 7.85(dd, 1H), 8.04(s, 1H), 8.18(d, 1H), 8.20(d, 1H), 8.55(s, 1H), 9.01(br s, 2H), 9.43(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 1.78 (s, 3H) 2.31 (s, 3H), 2.55 (m, 2H), 2.85 (m, 2H), 7.30-7.48 (m, 4H), 7.66 ( dd, 1H), 7.85 (dd, 1H), 8.04 (s, 1H), 8.18 (d, 1H), 8.20 (d, 1H), 8.55 (s, 1H), 9.01 (br s, 2H), 9.43 ( br s, 2H);

MS(DCI/NH3) m/e 321 (M+H)+.MS (DCI / NH 3 ) m / e 321 (M + H) + .

C20H20N2S2ㆍ1.35CH3SO3H에 대한 원소분석치:Elemental Analysis for C 20 H 20 N 2 S 2 ㆍ 1.35CH 3 SO 3 H:

계산치: C, 56.96; H, 5.69; N, 6.22.Calc .: C, 56.96; H, 5.69; N, 6.22.

실측치: C, 57.08; H, 5.49; N, 6.14.Found: C, 57.08; H, 5.49; N, 6.14.

실시예 59Example 59

7-메톡시-8-(3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염7-methoxy-8- (3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 59AExample 59A

7-메톡시-8-(3-푸라닐)-2-나프탈렌카보니트릴7-methoxy-8- (3-furanyl) -2-naphthalenecarbonitrile

실시예 53B, 푸란-3-보론산(873mg, 7.80mmol), 및 실시예 57B에 기재된 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 267(M+NH4)+.The title compound is prepared from the procedure described in Example 53B, furan-3-boronic acid (873 mg, 7.80 mmol), and Example 57B. MS (DCI / NH 3 ) m / e 267 (M + NH 4 ) + .

실시예 59BExample 59B

7-메톡시-8-(3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염7-methoxy-8- (3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서 실시예 58C로부터 표제 화합물을 제조한다.The title compound is prepared from Example 58C following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.34(s, 3H) 3.91(s, 3H), 6.76(s, 2H), 7.62(dd, 1H), 7.74(d, 1H), 7.87(dd, 1H), 7.96(s, 1H), 8.12(d, 1H), 8.25(s, 1H), 8.96(br s, 2H), 9.35(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.34 (s, 3H) 3.91 (s, 3H), 6.76 (s, 2H), 7.62 (dd, 1H), 7.74 (d, 1H), 7.87 (dd, 1H), 7.96 (s, 1H), 8.12 (d, 1H), 8.25 (s, 1H), 8.96 (br s, 2H), 9.35 (br s, 2H);

MS(DCI/NH3) m/e 267 (M+H)+.MS (DCI / NH 3 ) m / e 267 (M + H) + .

C16H14N2O2ㆍCH3SO3H에 대한 원소분석치:Elemental Analysis for C 16 H 14 N 2 O 2 ㆍ CH 3 SO 3 H:

계산치: C, 55.77; H, 5.00; N, 7.63.Calc .: C, 55.77; H, 5.00; N, 7.63.

실측치: C, 55.73; H, 4.61; N, 7.48.Found: C, 55.73; H, 4.61; N, 7.48.

실시예 60Example 60

7-메톡시-8-(2-벤조푸라닐)나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염7-methoxy-8- (2-benzofuranyl) naphthalene-2-carboximideamide mono (methanesulfonate) salt

실시예 60AExample 60A

7-메톡시-8-(2-벤조푸라닐)-2-나프탈렌카보니트릴7-methoxy-8- (2-benzofuranyl) -2-naphthalenecarbonitrile

실시예 53B(166mg, 0.50mmol), 벤조푸란-2-보론산(113mg, 0.70mmol), 및 실시예 57B에 기재된 과정으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 317(M+NH4)+.The title compound is prepared from the procedure described in Example 53B (166 mg, 0.50 mmol), benzofuran-2-boronic acid (113 mg, 0.70 mmol), and Example 57B. MS (DCI / NH 3 ) m / e 317 (M + NH 4 ) + .

실시예 60BExample 60B

7-메톡시-8-(2-벤조푸라닐)나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염7-methoxy-8- (2-benzofuranyl) naphthalene-2-carboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서 실시예 60A(72mg, 0.240mmol)로부터 표제 화합물을 제조한다.The title compound is prepared from Example 60A (72 mg, 0.240 mmol) following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.30(s, 3H) 3.98(s, 3H), 7.24(s, 1H), 7.36(m, 2H), 7.67(m, 2H), 7.75(m, 1H), 7.84(d, 1H), 8.21(d, 1H), 8.30(d, 1H), 8.32(s, 1H), 8.88(br s, 2H), 9.39(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.30 (s, 3H) 3.98 (s, 3H), 7.24 (s, 1H), 7.36 (m, 2H), 7.67 (m, 2H), 7.75 (m, 1H), 7.84 (d, 1H), 8.21 (d, 1H), 8.30 (d, 1H), 8.32 (s, 1H), 8.88 (br s, 2H), 9.39 (br s, 2H);

MS(DCI/NH3) m/e 317 (M+H)+.MS (DCI / NH 3 ) m / e 317 (M + H) + .

C20H16N2O2ㆍ1.3CH3SO3H 에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 2 O 2 · 1.3CH 3 SO 3 H:

계산치: C, 57.98; H, 4.84; N, 6.35.Calc .: C, 57.98; H, 4. 84; N, 6.35.

실측치: C, 57.79; H, 4.78; N, 6.22.Found: C, 57.79; H, 4.78; N, 6.22.

실시예 61Example 61

(E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 61AExample 61A

(E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카보니트릴(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarbonitrile

N-메틸피롤리딘온(2ml) 중의 실시예 53B(75mg, 0.243mmol), PDCl2(dppf)(20mg, 0.024mmol), 3,4-메틸렌디옥시스티렌(43mg, 0.291mmol) 및 디이소프로필에틸아민(0.170ml, 0.97mmol)을 90℃에서 18시간 동안 교반하고, 실온으로 냉각시킨 다음, 20% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 46mg 수득한다. MS(DCI/NH3) m/e 347(M+NH4)+.Example 53B (75 mg, 0.243 mmol), PDCl 2 (dppf) (20 mg, 0.024 mmol), 3,4-methylenedioxystyrene (43 mg, 0.291 mmol) and diisopropyl in N-methylpyrrolidinone (2 ml) Ethylamine (0.170 ml, 0.97 mmol) was stirred at 90 ° C. for 18 hours, cooled to room temperature and chromatographed on silica gel with 20% ethyl acetate / hexanes to give 46 mg of the title compound. MS (DCI / NH 3 ) m / e 347 (M + NH 4 ) + .

실시예 61BExample 61B

(E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서 실시예 61A(43mg, 0.131mmol)로부터 표제 화합물을 제조한다.The title compound is prepared from Example 61A (43 mg, 0.131 mmol) following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.32(s, 3H), 4.01(s, 3H), 6.07(s, 2H), 6.96(d, 2H), 7.10(d, 2H), 7.32(d, 2H), 7.45(s, 1H), 7.56(d, 1H), 7.66(d, 2H), 7.72(d, 1H), 8.06(s, 1H), 8.03(d, 1H), 8.12(d, 1H), 8.66(s, 1H), 8.96(br s, 2H), 9.44(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.32 (s, 3H), 4.01 (s, 3H), 6.07 (s, 2H), 6.96 (d, 2H), 7.10 (d, 2H), 7.32 (d , 2H), 7.45 (s, 1H), 7.56 (d, 1H), 7.66 (d, 2H), 7.72 (d, 1H), 8.06 (s, 1H), 8.03 (d, 1H), 8.12 (d, 1H), 8.66 (s, 1H), 8.96 (br s, 2H), 9.44 (br s, 2H);

MS(DCI/NH3) m/e 347 (M+H)+.MS (DCI / NH 3 ) m / e 347 (M + H) + .

C21H18N2O2ㆍ1.1CH3SO3H에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 2 O 2 · 1.1CH 3 SO 3 H:

계산치: C, 58.72; H, 4.99; N, 6.20.Calc .: C, 58.72; H, 4.99; N, 6.20.

실측치: C, 58.77; H, 5.07; N, 5.99.Found: C, 58.77; H, 5.07; N, 5.99.

실시예 62Example 62

(±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 62AExample 62A

(±)-7-메톡시-8-[3-하이드록시-1-(하이드록시메틸)-1-프로페닐]-2-나프탈렌카보니트릴(±) -7-methoxy-8- [3-hydroxy-1- (hydroxymethyl) -1-propenyl] -2-naphthalenecarbonitrile

N-메틸피롤리딘온(10ml) 중의 실시예 53B(3.09g, 10mmol), PDCl2(120mg, 1mmol), 시스-2-부텐-1,4-디올(1.23ml, 15mmol) 및 NaHCO3(1.01g, 12mmol)의 용액을 130℃에서 1시간 동안 교반하고, 실온으로 냉각시키며, 30% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 부분입체이성체의 혼합물로서의 표제 화합물을 2.19g 수득한다. MS(DCI/NH3) m/e 269(M+H)+.Example 53B (3.09 g, 10 mmol), PDCl 2 (120 mg, 1 mmol), cis-2-butene-1,4-diol (1.23 ml, 15 mmol) and NaHCO 3 (1.01) in N-methylpyrrolidinone (10 ml) g, 12 mmol) is stirred at 130 ° C. for 1 h, cooled to rt and chromatographed on silica gel with 30% ethyl acetate / hexanes to afford 2.19 g of the title compound as a mixture of diastereomers. MS (DCI / NH 3 ) m / e 269 (M + H) + .

실시예 62BExample 62B

(±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카보니트릴(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarbonitrile

0℃ 하의 메틸렌 클로라이드(3ml) 중의 실시예 62A(140mg, 0.52mmol)를 트리에틸실란(0.166ml, 1.04mmol) 및 BF3·OEt2(0.096ml, 0.78mmol)로 처리하고, 실온에서 4시간 동안 교반하며, 농축시킨 다음 25% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 100mg 수득한다. MS(DCI/NH3) m/e 271(M+NH4)+.Example 62A (140 mg, 0.52 mmol) in methylene chloride (3 ml) at 0 ° C. was treated with triethylsilane (0.166 ml, 1.04 mmol) and BF 3 · OEt 2 (0.096 ml, 0.78 mmol) and 4 h at room temperature. Stirred, concentrated and chromatographed on silica gel with 25% ethyl acetate / hexanes to afford 100 mg of the title compound. MS (DCI / NH 3 ) m / e 271 (M + NH 4 ) + .

실시예 62CExample 62C

(±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt

실시예 55D의 과정에 따라서, 실시예 62B(96mg, 0.379mmol)로부터 표제 화합물을 제조한다.Following the procedure of Example 55D, the title compound is prepared from Example 62B (96 mg, 0.379 mmol).

1H NMR(300MHz, DMSO-d6) δ 2.20(m, 1H), 2.33(m, 1H), 2.39(s, 3H), 3.99(s, 3H), 3.90-4.03(m, 3H), 4.11(m, 1H), 4.42(m, 1H), 7.64(d, 1H), 7.68(d, 1H), 8.01(d, 1H), 8.10(d, 1H), 8.70(s, 1H), 9.01(br s, 2H), 9.41(br s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.20 (m, 1H), 2.33 (m, 1H), 2.39 (s, 3H), 3.99 (s, 3H), 3.90-4.03 (m, 3H), 4.11 (m, 1H), 4.42 (m, 1H), 7.64 (d, 1H), 7.68 (d, 1H), 8.01 (d, 1H), 8.10 (d, 1H), 8.70 (s, 1H), 9.01 ( br s, 2 H), 9.41 (br s, 2 H).

MS(DCI/NH3) m/e 271 (M+H)+.MS (DCI / NH 3 ) m / e 271 (M + H) + .

C16H18N2O2ㆍ1.2CH3SO3H에 대한 원소분석치:Elemental Analysis for C 16 H 18 N 2 O 2 ㆍ 1.2CH 3 SO 3 H:

계산치: C, 53.57; H, 5.96; N, 7.26.Calc .: C, 53.57; H, 5.96; N, 7.26.

실측치: C, 53.67; H, 5.78; N, 6.72.Found: C, 53.67; H, 5.78; N, 6.72.

실시예 63Example 63

6-[[4-(2-아미노에틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6-[[4- (2-aminoethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 63AExample 63A

6-(트리메틸실릴에티닐)-2-나프탈렌카보니트릴6- (trimethylsilylethynyl) -2-naphthalenecarbonitrile

실시예 28B 및 트리메틸실릴아세틸렌을 실시예 42C에 기재된 조건에 적용하여 표제 화합물을 제조한다. MS(DCI/NH3) m/e 267(M+NH4)+.Example 28B and trimethylsilylacetylene were subjected to the conditions described in Example 42C to prepare the title compound. MS (DCI / NH 3 ) m / e 267 (M + NH 4 ) + .

실시예 63BExample 63B

6-에티닐-2-나프탈렌카보니트릴6-ethynyl-2-naphthalenecarbonitrile

메탄올(16ml) 중의 실시예 63A(0.4g, 1.6mmol)와 K2CO3(0.4g, 3.2mmol)의 혼합물을 실온에서 18시간 동안 교반하고, 농축시키며, 물로 처리한 다음 메틸렌 클로라이드로 추출한다. 유기 층을 0.5N NHCl 및 염수로 세척하고, 건조시키며(MgSO4) 증발시켜 표제 화합물을 수득한다. MS(DCI/NH3) m/e 195(M+NH4)+.A mixture of Example 63A (0.4 g, 1.6 mmol) and K 2 CO 3 (0.4 g, 3.2 mmol) in methanol (16 ml) is stirred at room temperature for 18 hours, concentrated, treated with water and extracted with methylene chloride . The organic layer is washed with 0.5N NHCl and brine, dried (MgSO 4 ) and evaporated to afford the title compound. MS (DCI / NH 3 ) m / e 195 (M + NH 4 ) + .

실시예 63CExample 63C

4-브로모-(N-3급-부톡시카보닐)펜에틸아민4-bromo- (N-tert-butoxycarbonyl) phenethylamine

문헌[참조: Synthesis, 48, 1986]에 기재된 조건을 4-브로모펜에틸아민 및 디-t-부틸디카보네이트에 적용하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 319(M+NH4)+.The conditions described in Synthesis, 48, 1986 are applied to 4-bromophenethylamine and di-t-butyldicarbonate to afford the title compound. MS (DCI / NH 3 ) m / e 319 (M + NH 4 ) + .

실시예 63DExample 63D

6-[[4-(2-N-3급-부톡시카보닐아미노에틸)페닐]에티닐]-2-나프탈렌카보니트릴6-[[4- (2-N-tert-butoxycarbonylaminoethyl) phenyl] ethynyl] -2-naphthalenecarbonitrile

실시예 57B에 기재된 과정에 따라서 실시예 63B 및 63C를 사용하여 표제 화합물을 수득한다. MS(DCI/NH3) m/e 414(M+NH4)+.Examples 63B and 63C were used following the procedure described in Example 57B to afford the title compound. MS (DCI / NH 3 ) m / e 414 (M + NH 4 ) + .

실시예 63EExample 63E

6-[[4-(2-아미노에틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6-[[4- (2-aminoethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 5B의 과정에 따라서 실시예 63D를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 63D following the procedure of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 2.90(t, 2H), 3.09(m, 2H) 7.36(d, 2H), 7.60(d, 2H), 7.76(d, 2H), 7.76(dd, 1H), 7.85(s, 2H), 7.87(dd, 1H), 8.13(d, 1H), 8.18(d, 1H), 8.31(s, 1H), 8.50(s, 1H), 9.18(s, 2H), 9.45(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.90 (t, 2H), 3.09 (m, 2H) 7.36 (d, 2H), 7.60 (d, 2H), 7.76 (d, 2H), 7.76 (dd, 1H), 7.85 (s, 2H), 7.87 (dd, 1H), 8.13 (d, 1H), 8.18 (d, 1H), 8.31 (s, 1H), 8.50 (s, 1H), 9.18 (s, 2H ), 9.45 (s, 2 H);

MS(DCI/NH3) m/e 314 (M+H)+.MS (DCI / NH 3 ) m / e 314 (M + H) + .

C21H19N3ㆍ2TFAㆍH2O에 대한 원소분석치:Elemental Analysis for C 21 H 19 N 3 2TFAH 2 O:

계산치: C, 53.67; H, 4.14; N, 7.15.Calc .: C, 53.67; H, 4.14; N, 7.15.

실측치: C, 53.37; H, 3.93; N, 7.17.Found: C, 53.37; H, 3.93; N, 7.17.

실시예 64Example 64

7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 64AExample 64A

7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카보니트릴7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarbonitrile

실시예 4A(125mg, 0.627mmol) 및 2-클로로피리미딘(143mg, 1.25mmol)을 실시예 6A에 기재된 과정에 적용하여 표제 화합물을 101mg 수득한다. MS(DCI/NH3) m/e 278(M+H)+.Example 4A (125 mg, 0.627 mmol) and 2-chloropyrimidine (143 mg, 1.25 mmol) were subjected to the procedure described in Example 6A to give 101 mg of the title compound. MS (DCI / NH 3 ) m / e 278 (M + H) + .

실시예 64BExample 64B

7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 64A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 64A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 2.51(s, 3H), 3.83(s, 3H), 7.18(t, 1H), 7.70(dd, 1H), 7.80(d, 1H), 8.05(d, 1H), 8.19(d, 1H), 8.34(s, 1H), 8.62(d, 2H), 9.07(br s, 2H), 9.45(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.51 (s, 3H), 3.83 (s, 3H), 7.18 (t, 1H), 7.70 (dd, 1H), 7.80 (d, 1H), 8.05 (d , 1H), 8.19 (d, 1H), 8.34 (s, 1H), 8.62 (d, 2H), 9.07 (br s, 2H), 9.45 (br s, 2H);

MS(DCI/NH3) m/e 295 (M+H)+.MS (DCI / NH 3 ) m / e 295 (M + H) + .

C20H16N4O4ㆍ1.33TFA에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 4 O 4 ㆍ 1.33TFA:

계산치: C, 40.48; H, 2.60; N, 8.35.Calc .: C, 40.48; H, 2. 60; N, 8.35.

실측치: C, 40.25; H, 2.94; N, 8.92.Found: C, 40.25; H, 2.94; N, 8.92.

실시예 65Example 65

7-메톡시-8-[2-티아조일(옥시)]나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [2-thiazoyl (oxy)] naphthalene-2-carboximideamide mono (trifluoroacetate) salt

실시예 65AExample 65A

7-메톡시-8-[2-티아조일(옥시)]-2-나프탈렌카보니트릴7-methoxy-8- [2-thiazoyl (oxy)]-2-naphthalenecarbonitrile

DMSO(4ml) 중의 실시예 4A(250mg, 1.25mmol), 2-브로모티아졸(225ml, 2.50mmol) 및 CsF(209mg, 1.38mmol)의 혼합물을 120℃에서 4일 동안 교반하고, 냉각시킨 다음 30% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 162mg 수득한다. MS(DCI/NH3) m/e 283(M+H)+.A mixture of Example 4A (250 mg, 1.25 mmol), 2-bromothiazole (225 ml, 2.50 mmol) and CsF (209 mg, 1.38 mmol) in DMSO (4 ml) was stirred at 120 ° C. for 4 days, cooled and 30 Chromatography on silica gel using% ethyl acetate / hexanes affords 162 mg of the title compound. MS (DCI / NH 3 ) m / e 283 (M + H) + .

실시예 65BExample 65B

7-메톡시-8-[2-티아조일(옥시)]나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [2-thiazoyl (oxy)] naphthalene-2-carboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 65A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 65A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 3.98(s, 3H), 7.25(m, 2H), 7.73(dd, 1H), 7.86(d, 1H), 8.12(d, 1H), 8.22(d, 1H), 8.35(bs, 2H), 9.09(s, 1H), 9.48(bs, 2H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.98 (s, 3H), 7.25 (m, 2H), 7.73 (dd, 1H), 7.86 (d, 1H), 8.12 (d, 1H), 8.22 (d , 1H), 8.35 (bs, 2H), 9.09 (s, 1H), 9.48 (bs, 2H).

MS(DCI/NH3) m/e 300 (M+H)+.MS (DCI / NH 3 ) m / e 300 (M + H) + .

C15H13N3O2SㆍTFA에 대한 원소분석치:Elemental Analysis for C 15 H 13 N 3 O 2 S · TFA:

계산치: C, 49.40; H, 3.41; N, 10.70.Calc .: C, 49.40; H, 3.41; N, 10.70.

실측치: C, 49.10; H, 3.40; N, 10.69.Found: C, 49.10; H, 3. 40; N, 10.69.

실시예 66Example 66

7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 66AExample 66A

7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카보니트릴7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarbonitrile

실시예 65A의 과정에 따라서 실시예 4A(125mg, 0.627mmol), 1,4-디니트로벤젠(143mg, 1.25mmol)로부터 표제 화합물을 227mg 수득한다. MS(DCI/NH3) m/e 338(M+NH4)+.227 mg of the title compound is obtained from Example 4A (125 mg, 0.627 mmol), 1,4-dinitrobenzene (143 mg, 1.25 mmol) following the procedure of Example 65A. MS (DCI / NH 3 ) m / e 338 (M + NH 4 ) + .

실시예 66BExample 66B

7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 55D의 과정에 따라서 실시예 66A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 66A following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 9.43(br s, 2H), 8.94(br s, 2H), 8.25(m, 4H), 8.15(d, 1H), 7.88(d, 1H), 7.72(dd, 1H), 7.05(d, 2H), 3.91(s, 3H), 2.30(s, 3H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.43 (br s, 2H), 8.94 (br s, 2H), 8.25 (m, 4H), 8.15 (d, 1H), 7.88 (d, 1H), 7.72 (dd, 1H), 7.05 (d, 2H), 3.91 (s, 3H), 2.30 (s, 3H);

MS(DCI/NH3) m/e 338 (M+H)+.MS (DCI / NH 3 ) m / e 338 (M + H) + .

C18H15N3O4ㆍ1.75CH3SO3H에 대한 원소분석치:Elemental Analysis for C 18 H 15 N 3 O 4 ㆍ 1.75CH 3 SO 3 H:

계산치: C, 46.93; H, 4.39; N, 8.31.Calc .: C, 46.93; H, 4. 39; N, 8.31.

실측치: C, 47.17; H, 4.32; N, 8.12.Found: C, 47.17; H, 4. 32; N, 8.12.

실시예 67Example 67

7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 67AExample 67A

7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카보니트릴7-methoxy-8-pentafluorophenoxy-2-naphthalenecarbonitrile

실시예 65A에 기재된 과정에 따라서, 실시예 4A(100mg, 0.50mmol) 및 헥사플루오로벤젠(115ml, 1.00mmol)으로부터 표제 화합물을 150mg 수득한다. MS(DCI/NH3) m/e 383(M+NH4)+.According to the procedure described in Example 65A, 150 mg of the title compound are obtained from Example 4A (100 mg, 0.50 mmol) and hexafluorobenzene (115 ml, 1.00 mmol). MS (DCI / NH 3 ) m / e 383 (M + NH 4 ) + .

실시예 67BExample 67B

7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 55D의 과정에 따라서 실시예 67A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 67A following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 2.31(s, 3H), 3.82(s, 3H), 7.87(dd, 1H), 7.88(d, 1H), 8.02(d, 1H), 8.20(d, 1H), 8.65(s, 1H), 9.04(br s, 2H), 9.47(br s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.31 (s, 3H), 3.82 (s, 3H), 7.87 (dd, 1H), 7.88 (d, 1H), 8.02 (d, 1H), 8.20 (d , 1H), 8.65 (s, 1H), 9.04 (br s, 2H), 9.47 (br s, 2H);

MS(DCI/NH3) m/e 383 (M+H)+.MS (DCI / NH 3 ) m / e 383 (M + H) + .

C18H11N2F5O2ㆍ1.2CH3SO3H에 대한 원소분석치:Elemental Analysis for C 18 H 11 N 2 F 5 O 2 ㆍ 1.2CH 3 SO 3 H:

계산치: C, 46.67; H, 3.19; N, 5.68.Calc .: C, 46.67; H, 3. 19; N, 5.68.

실측치: C, 46.55; H, 3.00; N, 5.58.Found: C, 46.55; H, 3.00; N, 5.58.

실시예 68Example 68

7-메톡시-8-(N-2-페닐아미노)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (N-2-phenylamino) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 68AExample 68A

7-메톡시-8-[N-2-페닐(아미노)]-2-나프탈렌카보니트릴7-methoxy-8- [N-2-phenyl (amino)]-2-naphthalenecarbonitrile

톨루엔(5ml) 중의 실시예 25A(309mg, 1.00mmol), 아닐린(0.109ml, 1.2mmol), NaOtBu(115mg, 1.2mmol), Pd(dba)3(10mg, 0.01mmol) 및 dppf(17mg, 0.03mmol)의 용액을 100℃에서 3시간 동안 교반하고, 냉각시키며 10% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 175mg 수득한다. MS(DCI/NH3) m/e 275(M+H)+.Carried out in toluene (5ml) Example 25A (309mg, 1.00mmol), aniline (0.109ml, 1.2mmol), NaO t Bu (115mg, 1.2mmol), Pd (dba) 3 (10mg, 0.01mmol) and dppf (17mg, 0.03 mmol) is stirred at 100 ° C. for 3 hours, cooled and chromatographed on silica gel with 10% ethyl acetate / hexanes to give 175 mg of the title compound. MS (DCI / NH 3 ) m / e 275 (M + H) + .

실시예 68BExample 68B

7-메톡시-8-(N-2-페닐아미노)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (N-2-phenylamino) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 55D의 과정에 따라서 실시예 68A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 68A following the procedure of Example 55D.

1H NMR(300MHz, DMSO-d6) δ 3.95(s, 3H), 5.92(bs, 1H), 6.61(d, 2H), 6.94(t, 1H), 7.16(dd, 2H), 7.45(dd, 1H), 7.48(d, 1H), 7.76(d, 1H), 7.88(d, 1H), 8.13(d, 1H), 9.08(bs, 2H), 9.31(bs, 2H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.95 (s, 3H), 5.92 (bs, 1H), 6.61 (d, 2H), 6.94 (t, 1H), 7.16 (dd, 2H), 7.45 (dd , 1H), 7.48 (d, 1H), 7.76 (d, 1H), 7.88 (d, 1H), 8.13 (d, 1H), 9.08 (bs, 2H), 9.31 (bs, 2H).

MS(DCI/NH3) m/e 292 (M+H)+.MS (DCI / NH 3 ) m / e 292 (M + H) + .

C18H17N3OㆍTFA에 대한 원소분석치:Elemental Analysis for C 18 H 17 N 3 O · TFA:

계산치: C, 59.26; H, 4.48; N, 10.37.Calc .: C, 59.26; H, 4. 48; N, 10.37.

실측치: C, 59.20; H, 4.32; N, 10.15.Found: C, 59.20; H, 4. 32; N, 10.15.

실시예 69Example 69

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzylurea mono (trifluoroacetate) salt

실시예 69AExample 69A

N-(6-시아노-2-나프탈레닐)-N'-벤질우레아N- (6-cyano-2-naphthalenyl) -N'-benzylurea

실시예 40B의 과정에 따라서 실시예 40A 및 벤질아민으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 302(M+H)+.The title compound is prepared from Example 40A and benzylamine following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 302 (M + H) + .

실시예 69BExample 69B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzylurea mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 69A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 69A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 4.35(d, 2H), 6.91(t, 1H), 7.35-7.24(m, 5H), 7.59(dd, 1H), 7.72(dd, 1H), 7.95(d, 1H), 7.96(d, 1H), 8.22(d, 1H), 8.35(d, 1H), 8.92(br s, 2H), 9.13(s, 1H), 9.32(br s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.35 (d, 2H), 6.91 (t, 1H), 7.35-7.24 (m, 5H), 7.59 (dd, 1H), 7.72 (dd, 1H), 7.95 (d, 1H), 7.96 (d, 1H), 8.22 (d, 1H), 8.35 (d, 1H), 8.92 (br s, 2H), 9.13 (s, 1H), 9.32 (br s, 2H).

MS(DCI/NH3) m/e 319 (M+H)+.MS (DCI / NH 3 ) m / e 319 (M + H) + .

C19H18N4OㆍTFA에 대한 원소분석치:Elemental Analysis for C 19 H 18 N 4 O · TFA:

계산치: C, 50.57; H, 4.24; N, 15.72.Calc .: C, 50.57; H, 4. 24; N, 15.72.

실측치: C, 50.34; H, 4.15; N, 15.54.Found: C, 50.34; H, 4. 15; N, 15.54.

실시예 70Example 70

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-메틸우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-methylurea mono (trifluoroacetate) salt

실시예 70AExample 70A

N-(6-시아노-2-나프탈레닐)-N'-메틸우레아N- (6-cyano-2-naphthalenyl) -N'-methylurea

실시예 40B의 과정에 따라서 THF(10ml) 중의 실시예 40A(221.2mg, 1.00mmol) 및 메틸아민(2.3ml, 2.34mmol)으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 226(M+H)+.The title compound is prepared from Example 40A (221.2 mg, 1.00 mmol) and methylamine (2.3 ml, 2.34 mmol) in THF (10 ml) following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 226 (M + H) + .

실시예 70BExample 70B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-메틸우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-methylurea mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 70A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 70A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 2.69(d, 3H), 6.32(q, 1H), 7.60(dd, 1H), 7.73(dd, 1H), 7.93(d, 1H), 7.95(d, 1H), 8.19(d, 1H), 8.49(d, 1H), 9.09(s, 1H), 9.15(br. s, 4H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.69 (d, 3H), 6.32 (q, 1H), 7.60 (dd, 1H), 7.73 (dd, 1H), 7.93 (d, 1H), 7.95 (d , 1H), 8.19 (d, 1H), 8.49 (d, 1H), 9.09 (s, 1H), 9.15 (br. S, 4H);

MS(DCI/NH3) m/e 243 (M+H)+.MS (DCI / NH 3 ) m / e 243 (M + H) + .

C13H14N4OㆍTFA에 대한 원소분석치:Elemental Analysis for C 13 H 14 N 4 O · TFA:

계산치: C, 50.57; H, 4.24; N, 15.72.Calc .: C, 50.57; H, 4. 24; N, 15.72.

실측치: C, 50.34; H, 4.15; N, 15.54.Found: C, 50.34; H, 4. 15; N, 15.54.

실시예 71Example 71

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-이소프로필우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-isopropylurea mono (trifluoroacetate) salt

실시예 71AExample 71A

N-(6-시아노-2-나프탈레닐)-N'-이소프로필우레아N- (6-cyano-2-naphthalenyl) -N'-isopropylurea

실시예 40B의 과정에 따라서 실시예 40A 및 이소프로필아민으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 254(M+H)+.The title compound is prepared from Example 40A and isopropylamine following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 254 (M + H) + .

실시예 71BExample 71B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-이소프로필우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-isopropylurea mono (trifluoroacetate) salt

실시예 5B의 과정에 따라서 실시예 71A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 71A following the procedure of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 1.13(d, 6H), 3.76-3.84(m, 1H), 6.28(d, 1H), 7.55(dd, 1H), 7.72(dd, 1H), 7.94(d, 1H), 7.95(d, 1H), 8.19(d, 1H), 8.34(d, 1H), 8.85(s, 1H), 9.3(br s, 2H), 9.0(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.13 (d, 6H), 3.76-3.84 (m, 1H), 6.28 (d, 1H), 7.55 (dd, 1H), 7.72 (dd, 1H), 7.94 (d, 1H), 7.95 (d, 1H), 8.19 (d, 1H), 8.34 (d, 1H), 8.85 (s, 1H), 9.3 (br s, 2H), 9.0 (br s, 2H);

MS(DCI/NH3) m/e 271 (M+H)+.MS (DCI / NH 3 ) m / e 271 (M + H) + .

C15H18N4OㆍTFA에 대한 원소분석치:Elemental Analysis for C 15 H 18 N 4 O · TFA:

계산치: C, 53.12; H, 4.98; N, 14.58.Calc .: C, 53.12; H, 4.98; N, 14.58.

실측치: C, 15.13; H, 4.84; N, 14.50.Found: C, 15.13; H, 4. 84; N, 14.50.

실시예 72Example 72

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐-N'-메틸우레아 모노(트리플루오로아N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenyl-N'-methylurea mono (trifluoroa

세테이트) 염Cate) salt

실시예 72AExample 72A

N-(6-시아노-2-나프탈레닐)-N'-페닐-N'-메틸우레아N- (6-cyano-2-naphthalenyl) -N'-phenyl-N'-methylurea

실시예 40B의 과정에 따라서 실시예 40A 및 N-메틸-N-페닐아민으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 302(M+H)+.The title compound is prepared from Example 40A and N-methyl-N-phenylamine according to the procedure of Example 40B. MS (DCI / NH 3 ) m / e 302 (M + H) + .

실시예 72BExample 72B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐-N'-메틸우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenyl-N'-methylurea mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 72A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 72A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 3.33(s, 3H), 7.25-7.47(m, 5H), 7.71-7.77(m, 2H), 7.95(2개의 중첩 이중선, 2H), 8.16(d, 1H), 8.35(d, 1H), 8.64(s, 1H), 8.96(br s, 2H), 9.34(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 3.33 (s, 3H), 7.25-7.47 (m, 5H), 7.71-7.77 (m, 2H), 7.95 (two overlapping double lines, 2H), 8.16 (d , 1H), 8.35 (d, 1H), 8.64 (s, 1H), 8.96 (br s, 2H), 9.34 (br s, 2H);

MS(DCI/NH3) m/e 319 (M+H)+.MS (DCI / NH 3 ) m / e 319 (M + H) + .

C20H17N4OㆍTFA에 대한 원소분석치:Elemental Analysis for C 20 H 17 N 4 O · TFA:

계산치: C, 58.33; H, 4.43; N, 11.96.Calc .: C, 58.33; H, 4. 43; N, 11.96.

실측치: C, 58.38; H, 4.69; N, 11.82.Found: C, 58.38; H, 4.69; N, 11.82.

실시예 73Example 73

6-아미노나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염6-aminonaphthalene-2-carboximideamide mono (trifluoroacetate) salt

실시예 73AExample 73A

6-페닐카바모일-2-나프탈렌카보니트릴6-phenylcarbamoyl-2-naphthalenecarbonitrile

실시예 40B의 과정에 따라서 실시예 40A 및 페놀로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 289(M+H)+.The title compound is prepared from Example 40A and phenol following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 289 (M + H) + .

실시예 73BExample 73B

6-아미노나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염6-aminonaphthalene-2-carboximideamide mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 73A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 73A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 6.01(br s, 2H), 6.86(d, 1H), 7.06(dd, 1H), 7.58-7.67(m, 2H), 7.74(d, 1H), 8.21(d, 1H), 8.74(br s, 2H), 9.16(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 6.01 (br s, 2H), 6.86 (d, 1H), 7.06 (dd, 1H), 7.58-7.67 (m, 2H), 7.74 (d, 1H), 8.21 (d, 1 H), 8.74 (br s, 2 H), 9.16 (br s, 2 H);

MS(DCI/NH3) m/e 196 (M+H)+.MS (DCI / NH 3 ) m / e 196 (M + H) + .

C12H10N3ㆍTFA에 대한 원소분석치:Elemental Analysis for C 12 H 10 N 3 ㆍ TFA:

계산치: C, 52.18; H, 4.04; N, 14.04.Calc .: C, 52.18; H, 4.04; N, 14.04.

실측치: C, 51.92; H, 3.87; N, 13.80.Found: C, 51.92; H, 3.87; N, 13.80.

실시예 74Example 74

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-사이클로헥실우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-cyclohexylurea mono (trifluoroacetate) salt

실시예 74AExample 74A

N-(6-시아노-2-나프탈레닐)-N'-사이클로헥실우레아N- (6-cyano-2-naphthalenyl) -N'-cyclohexylurea

실시예 40B의 과정에 따라서 실시예 40A 및 사이클로헥실아민으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 294(M+H)+.The title compound is prepared from Example 40A and cyclohexylamine following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 294 (M + H) + .

실시예 74BExample 74B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-사이클로헥실우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-cyclohexylurea mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 74A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 74A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 1.14-1.39(m, 5H), 1.54-1.58(m, 1H), 1.65-1.72(m, 2H), 1.81-1.86(m, 2H), 3.46-.52(m, 1H), 6.36(d, 1H), 7.55(dd, 1H), 7.72(dd, 1H), 7.93(d, 1H), 7.95(d, 1H), 8.18(d, 1H), 8.35(d, 1H), 8.87(s, 1H), 9.00(br s, 2H), 9.28(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.14-1.39 (m, 5H), 1.54-1.58 (m, 1H), 1.65-1.72 (m, 2H), 1.81-1.86 (m, 2H), 3.46- .52 (m, 1H), 6.36 (d, 1H), 7.55 (dd, 1H), 7.72 (dd, 1H), 7.93 (d, 1H), 7.95 (d, 1H), 8.18 (d, 1H), 8.35 (d, 1 H), 8.87 (s, 1 H), 9.00 (br s, 2 H), 9.28 (br s, 2H);

MS(DCI/NH3) m/e 311 (M+H)+.MS (DCI / NH 3 ) m / e 311 (M + H) + .

C19H21N4OㆍTFA에 대한 원소분석치:Elemental Analysis for C 19 H 21 N 4 O · TFA:

계산치: C, 56.60; H, 5.46; N, 13.20.Calc .: C, 56.60; H, 5. 46; N, 13.20.

실측치: C, 56.61; H, 5.72; N, 13.03.Found: C, 56.61; H, 5.72; N, 13.03.

실시예 75Example 75

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질옥시우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzyloxyurea mono (trifluoroacetate) salt

실시예 75AExample 75A

N-(6-시아노-2-나프탈레닐)-N'-벤질옥시우레아N- (6-cyano-2-naphthalenyl) -N'-benzyloxyurea

실시예 40B의 과정에 따라서 실시예 40A 및 O-벤질하이드록실아민으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 318(M+H)+.The title compound is prepared from Example 40A and O-benzylhydroxylamine following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 318 (M + H) + .

실시예 75BExample 75B

N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질옥시우레아 모노(트리플루오로아세테이트) 염N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzyloxyurea mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 75A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 75A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 4.87(s, 2H), 7.25-7.42(m, 3H), 7.48-7.51(m, 2H), 7.75(dd, 1H), 7.75(dd, 1H), 7.97(d, 2H), 8.30(d, 1H), 8.38(d, 1H), 8.97(br s, 2H), 9.21(s, 1H), 9.35(br s, 2H), 9.77(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.87 (s, 2H), 7.25-7.42 (m, 3H), 7.48-7.51 (m, 2H), 7.75 (dd, 1H), 7.75 (dd, 1H) , 7.97 (d, 2H), 8.30 (d, 1H), 8.38 (d, 1H), 8.97 (br s, 2H), 9.21 (s, 1H), 9.35 (br s, 2H), 9.77 (s, 1H );

MS(DCI/NH3) m/e 335 (M+H)+.MS (DCI / NH 3 ) m / e 335 (M + H) + .

C19H18N4O2ㆍTFA에 대한 원소분석치:Elementary Analysis for C 19 H 18 N 4 O 2 ㆍ TFA:

계산치: C, 56.25; H, 4.27; N, 12.49.Calc .: C, 56.25; H, 4. 27; N, 12.49.

실측치: C, 56.26; H, 4.39; N, 12.30.Found: C, 56.26; H, 4. 39; N, 12.30.

실시예 76Example 76

1,1-디메틸에틸 [4-[[(6-아미노이미노메틸-2-나프탈레닐)아미노]카보닐]페닐]카바메이트 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [4-[[(6-aminoiminomethyl-2-naphthalenyl) amino] carbonyl] phenyl] carbamate mono (trifluoroacetate) salt

실시예 76AExample 76A

6-아미노-2-나프탈렌카보니트릴6-amino-2-naphthalenecarbonitrile

황산(45ml)을 실시예 40B(6.5g)로 처리하고, 30분 동안 교반하며, 20분 동안 실온으로 가온시키며, 얼음에 붓고, 물로 약 500ml가 되게 희석시키며, 0℃로 냉각시키고 50% 수성 수산화나트륨으로 처리하여 온도가 35℃를 초과하지 않도록 한다. 침전되는 가벼운 고체를 여과하고, 물로 세척하여 pH 7이 되게 하며, 진공하에 건조시킨 다음, 20% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 정제하여 표제 화합물을 3.3g 수득한다. MS(DCI/NH3) m/e 169(M+H)+.Sulfuric acid (45 ml) was treated with Example 40B (6.5 g), stirred for 30 minutes, warmed to room temperature for 20 minutes, poured into ice, diluted to about 500 ml with water, cooled to 0 ° C. and 50% aqueous Treatment with sodium hydroxide ensures that the temperature does not exceed 35 ° C. The light solid that precipitates is filtered, washed with water to pH 7, dried in vacuo and purified on silica gel using 20% ethyl acetate / hexanes to give 3.3 g of the title compound. MS (DCI / NH 3 ) m / e 169 (M + H) + .

실시예 76BExample 76B

1,1-디메틸에틸 [4-[[(6-시아노-2-나프탈레닐)아미노]카보닐]페닐]카바메이트 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [4-[[(6-cyano-2-naphthalenyl) amino] carbonyl] phenyl] carbamate mono (trifluoroacetate) salt

THF 대신 메틸렌 클로라이드를 사용하여, 실시예 35B의 과정에 따라서 실시예 76A 및 4-N-Boc-아미노메틸벤조산으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 417(M+H)+.Using methylene chloride instead of THF, the title compound is prepared from Example 76A and 4-N-Boc-aminomethylbenzoic acid following the procedure of Example 35B. MS (DCI / NH 3 ) m / e 417 (M + H) + .

실시예 76CExample 76C

1,1-디메틸에틸 [4-[[(6-아미노이미노메틸-2-나프탈레닐)아미노]카보닐]페닐]카바메이트 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [4-[[(6-aminoiminomethyl-2-naphthalenyl) amino] carbonyl] phenyl] carbamate mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 76B를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 76B following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 3.30(s, 9H), 4.22(d, 2H), 7.42(d, 2H), 7.49(t, 1H), 7.79(dd, 1H), 7.95-8.00(m, 3H), 8.09(d, 2H), 8.42(s, 1H), 8.63(d, 1H), 9.18(br s, 4H), 10.58(s, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.30 (s, 9H), 4.22 (d, 2H), 7.42 (d, 2H), 7.49 (t, 1H), 7.79 (dd, 1H), 7.95-8.00 (m, 3H), 8.09 (d, 2H), 8.42 (s, 1H), 8.63 (d, 1H), 9.18 (br s, 4H), 10.58 (s, 1H);

MS(DCI/NH3) m/e 434 (M+H)+.MS (DCI / NH 3 ) m / e 434 (M + H) + .

C24H27N5O3ㆍTFA에 대한 원소분석치:Elemental Analysis for C 24 H 27 N 5 O 3 ㆍ TFA:

계산치: C, 59.56; H, 5.00; N, 10.29.Calc .: C, 59.56; H, 5.00; N, 10.29.

실측치: C, 58.55; H, 4.85; N, 10.41.Found: C, 58.55; H, 4. 85; N, 10.41.

실시예 77Example 77

N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-(아미노메틸)벤즈아미드 모노(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -4- (aminomethyl) benzamide mono (trifluoroacetate) salt

실시예 77AExample 77A

N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-(아미노메틸)벤즈아미드 모노(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -4- (aminomethyl) benzamide mono (trifluoroacetate) salt

1:1 TFA/메틸렌 클로라이드 중의 실시예 76B(35mg, 0.07mmol)의 용액을 실온에서 1시간 동안 교반한 다음 농축시킨다. 잔사를 물(12ml)에 용해시키고, 0.45μ 필터를 통하여 여과한 다음 농축시킨다. 고체를 디에틸 에테르에 현탁시키고 여과시켜 백색 고체로서의 표제 화합물을 27mg 수득한다.A solution of Example 76B (35 mg, 0.07 mmol) in 1: 1 TFA / methylene chloride is stirred at room temperature for 1 hour and then concentrated. The residue is dissolved in water (12 ml), filtered through a 0.45 μ filter and concentrated. The solid is suspended in diethyl ether and filtered to give 27 mg of the title compound as a white solid.

1H NMR(300MHz, DMSO-d6) δ 4.17(q, 2H), 7.65(d, 2H), 7.80(dd, 1H), 7.99(dd, 1H), 8.06-8.12(m, 4H), 8.30(br s, 2H), 8.44(d, 1H), 8.64(d, 1H), 9.13(br s, 2H), 9.40(br s, 2H), 10.70(s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 4.17 (q, 2H), 7.65 (d, 2H), 7.80 (dd, 1H), 7.99 (dd, 1H), 8.06-8.12 (m, 4H), 8.30 (br s, 2H), 8.44 (d, 1H), 8.64 (d, 1H), 9.13 (br s, 2H), 9.40 (br s, 2H), 10.70 (s, 1H);

MS(DCI/NH3) m/e 319 (M+H)+.MS (DCI / NH 3 ) m / e 319 (M + H) + .

C19H18N4Oㆍ2.25TFA·0.5H2O에 대한 원소분석치:Elemental Analysis for C 19 H 18 N 4 O · 2.25TFA · 0.5H 2 O:

계산치: C, 48.34; H, 3.67; N, 9.59.Calc .: C, 48.34; H, 3.67; N, 9.59.

실측치: C, 48.45; H, 3.74; N, 9.45.Found: C, 48.45; H, 3. 74; N, 9.45.

실시예 78Example 78

에틸 [6-(아미노이미노메틸)-2-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염Ethyl [6- (aminoiminomethyl) -2-naphthalenyl] carbamate mono (trifluoroacetate) salt

실시예 78AExample 78A

에틸 (6-시아노-2-나프탈레닐)카바메이트 모노(트리플루오로아세테이트) 염Ethyl (6-cyano-2-naphthalenyl) carbamate mono (trifluoroacetate) salt

실시예 40B의 과정에 따라서 실시예 40A 및 에탄올로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 241(M+H)+.The title compound is prepared from Example 40A and ethanol following the procedure of Example 40B. MS (DCI / NH 3 ) m / e 241 (M + H) + .

실시예 78BExample 78B

에틸 [6-(아미노이미노메틸-2-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염Ethyl [6- (aminoiminomethyl-2-naphthalenyl] carbamate mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 78A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 78A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 1.29(t, 3H), 4.19(q, 2H), 7.69(dd, 1H), 7.76(dd, 1H), 8.1(d, 2H), 8.23(d, 1H), 8.38(d, 1H), 9.03(br s, 2H), 9.33(br s, 2H), 10.11(s, 1H); 1 H NMR (300MHz, DMSO-d 6 ) δ 1.29 (t, 3H), 4.19 (q, 2H), 7.69 (dd, 1H), 7.76 (dd, 1H), 8.1 (d, 2H), 8.23 (d , 1H), 8.38 (d, 1H), 9.03 (br s, 2H), 9.33 (br s, 2H), 10.11 (s, 1H);

MS(DCI/NH3) m/e 258 (M+H)+.MS (DCI / NH 3 ) m / e 258 (M + H) + .

C14H15N3O2ㆍTFA에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 2 ㆍ TFA:

계산치: C, 51.76; H, 4.34; N, 11.32.Calc .: C, 51.76; H, 4. 34; N, 11.32.

실측치: C, 51.32; H, 4.15; N, 10.93.Found: C, 51.32; H, 4. 15; N, 10.93.

실시예 79Example 79

1,1-디메틸에틸 [4-[[[(6-아미노이미노메틸)-2-나프탈레닐)아미노]카보닐]아미노]페닐]카바메이트 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [4-[[[(6-aminoiminomethyl) -2-naphthalenyl) amino] carbonyl] amino] phenyl] carbamate mono (trifluoroacetate) salt

실시예 79AExample 79A

1,1-디메틸 [4-[[[(6-시아노-2-나프탈레닐)아미노]카보닐]아미노]페닐]카바메이트1,1-dimethyl [4-[[[(6-cyano-2-naphthalenyl) amino] carbonyl] amino] phenyl] carbamate

실시예 40C의 과정에 따라서 실시예 40B 및 4-(N-3급-부톡시카보닐아미노)-아미노벤젠으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 403(M+H)+.The title compound is prepared from Examples 40B and 4- (N-tert-butoxycarbonylamino) -aminobenzene following the procedure of Example 40C. MS (DCI / NH 3 ) m / e 403 (M + H) + .

실시예 79BExample 79B

1,1-디메틸에틸 [4-[[[(6-아미노이미노메틸)-2-나프탈레닐)아미노]카보닐]아미노]페닐]카바메이트 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [4-[[[(6-aminoiminomethyl) -2-naphthalenyl) amino] carbonyl] amino] phenyl] carbamate mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 79A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 79A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 1.22(s, 3H), 7.83(s, 4H), 7.62(dd, 1H), 7.75(dd, 1H), 8.00(d, 2H), 8.27(d, 1H), 8.38(d, 1H), 8.77(s, 1H), 8.90(br s, 2H), 9.16(s, 1H), 9.20(s, 1H), 9.33(br s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.22 (s, 3H), 7.83 (s, 4H), 7.62 (dd, 1H), 7.75 (dd, 1H), 8.00 (d, 2H), 8.27 (d , 1H), 8.38 (d, 1H), 8.77 (s, 1H), 8.90 (br s, 2H), 9.16 (s, 1H), 9.20 (s, 1H), 9.33 (br s, 2H);

MS(DCI/NH3) m/e 420 (M+H)+.MS (DCI / NH 3 ) m / e 420 (M + H) + .

C23H25N5O3ㆍ2TFA에 대한 원소분석치:Elemental Analysis for C 23 H 25 N 5 O 3 ㆍ 2TFA:

계산치: C, 56.28; H, 4.91; N, 13.13.Calc .: C, 56.28; H, 4.91; N, 13.13.

실측치: C, 56.18; H, 5.07; N, 12.44.Found: C, 56.18; H, 5.07; N, 12.44.

실시예 80Example 80

(E)-6-[2-(페닐티오)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (phenylthio) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 80AExample 80A

(E)-6-[2-(페닐티오)에테닐]-2-나프탈렌카보니트릴(E) -6- [2- (phenylthio) ethenyl] -2-naphthalenecarbonitrile

실시예 57B에 기재된 과정에 따라서, 실시예 55B 및 페닐비닐 설파이드로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 305(M+NH4)+.Following the procedure described in Example 57B, the title compound is prepared from Example 55B and phenylvinyl sulfide. MS (DCI / NH 3 ) m / e 305 (M + NH 4 ) + .

실시예 80BExample 80B

(E)-6-[2-(페닐티오)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (phenylthio) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 80A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 80A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 6.91(d, 1H), 7.52-7.33(m, 5H), 7.50(d, 1H), 7.75-7.83(m, 1H), 7.98-8.89(m, 1H), 8.08-8.80(m, 3H), 8.44(m, 1H), 9.03(s, 2H), 9.40(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 6.91 (d, 1H), 7.52-7.33 (m, 5H), 7.50 (d, 1H), 7.75-7.83 (m, 1H), 7.98-8.89 (m, 1H), 8.08-8.80 (m, 3H), 8.44 (m, 1H), 9.03 (s, 2H), 9.40 (s, 2H);

MS(DCI/NH3) m/e 305 (M+H)+.MS (DCI / NH 3 ) m / e 305 (M + H) + .

C19H16N2S·1.1TFA에 대한 원소분석치:Elemental Analysis for C 19 H 16 N 2 S · 1.1TFA:

계산치 : C, 59.55; H, 4.03; N, 6.57Calculated: C, 59.55; H, 4.03; N, 6.57

실측치 : C, 59.53; H, 4.12; N, 6.60Found: C, 59.53; H, 4. 12; N, 6.60

실시예 81Example 81

(E)-6-[2-(2-푸라닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (2-furanyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 81AExample 81A

2-비닐푸란2-vinylfuran

톨루엔(80ml) 중의 메틸(트리페닐포스포늄)브로마이드(26.78g, 75mmol)의 용액을 헥산 중의 부틸리튬(27.5ml, 68.75mmol)으로 처리한 다음 푸르푸랄(6g, 62.5mmol)로 처리하고, 0.5시간 동안 교반하며 69 내지 72℃에서 증류시켜 약간의 톨루엔 오염물이 있는 투명한 무색 액체로서의 표제 화합물을 수득한다. MS(DCI/NH3) m/e 83(M+H)+.A solution of methyl (triphenylphosphonium) bromide (26.78g, 75mmol) in toluene (80ml) was treated with butyllithium (27.5ml, 68.75mmol) in hexanes followed by furfural (6g, 62.5mmol), 0.5 Distillation at 69-72 ° C. with stirring for hours affords the title compound as a clear colorless liquid with some toluene contaminants. MS (DCI / NH 3 ) m / e 83 (M + H) + .

실시예 81BExample 81B

(E)-6-[2-(2-푸라닐)에테닐]-2-나프탈렌카보니트릴(E) -6- [2- (2-furanyl) ethenyl] -2-naphthalenecarbonitrile

실시예 57B에 기재된 과정에 따라서, 실시예 55B 및 81A로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 263(M+NH4)+.Following the procedure described in Example 57B, the title compound is prepared from Examples 55B and 81A. MS (DCI / NH 3 ) m / e 263 (M + NH 4 ) + .

실시예 81CExample 81C

(E)-6-[2-(2-푸라닐)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (2-furanyl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 81B를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 81B following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 6.61(dd, 1H), 6.66(d, 1H), 7.19(d, 1H), 7.38(d, 1H), 7.77(d, 1H), 7.80(dd, 1H), 8.14-7.97(m, 3H), 8.44(s, 1H), 9.05(s, 2H), 9.42(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 6.61 (dd, 1H), 6.66 (d, 1H), 7.19 (d, 1H), 7.38 (d, 1H), 7.77 (d, 1H), 7.80 (dd , 1H), 8.14-7.97 (m, 3H), 8.44 (s, 1H), 9.05 (s, 2H), 9.42 (s, 2H);

MS(DCI/NH3) m/e 263 (M+H)+.MS (DCI / NH 3 ) m / e 263 (M + H) + .

C17H13N2O·1.2TFA에 대한 원소분석치:Elemental Analysis for C 17 H 13 N 2 O · 1.2TFA:

계산치 : C, 58.49; H, 3.85; N, 7.04Calculated: C, 58.49; H, 3. 85; N, 7.04

실측치 : C, 58.45; H, 3.78; N, 7.36Found: C, 58.45; H, 3.78; N, 7.36

실시예 82Example 82

(E)-6-[2-(1H-이미다졸-1-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (1H-imidazol-1-yl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 82AExample 82A

(E)-6-[2-(1H-이미다졸-1-일)에테닐]-2-나프탈렌카보니트릴(E) -6- [2- (1H-imidazol-1-yl) ethenyl] -2-naphthalenecarbonitrile

실시예 42C에 기재된 과정에 따라서, 실시예 55B 및 1-비닐이미다졸로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 263(M+NH4)+.Following the procedure described in Example 42C, the title compound is prepared from Example 55B and 1-vinylimidazole. MS (DCI / NH 3 ) m / e 263 (M + NH 4 ) + .

실시예 82BExample 82B

(E)-6-[2-(1H-이미다졸-1-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2- (1H-imidazol-1-yl) ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 82B를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 82B following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 9.44(s, 2H), 9.14(s, 2H), 8.15(d, 1H), 8.17-8.05(m, 4H), 7.93(d, 1H), 7.84(dd, 1H), 7.59(s, 1H), 7.49(d, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.44 (s, 2H), 9.14 (s, 2H), 8.15 (d, 1H), 8.17-8.05 (m, 4H), 7.93 (d, 1H), 7.84 (dd, 1 H), 7.59 (s, 1 H), 7.49 (d, 1 H);

MS(DCI/NH3) m/e 263 (M+H)+.MS (DCI / NH 3 ) m / e 263 (M + H) + .

C16H13N4·2.7TFA에 대한 원소분석치:Elemental analysis for C 16 H 13 N 4 · 2.7TFA:

계산치 : C, 45.28; H, 2.97; N, 9.91.Calculated: C, 45.28; H, 2.97; N, 9.91.

실측치 : C, 45.33; H, 3.52; N, 9.79.Found: C, 45.33; H, 3.52; N, 9.79.

실시예 83Example 83

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤젠설폰아미드 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzenesulfonamide mono (trifluoroacetate) salt

실시예 83AExample 83A

4-비닐설폰아미드4-vinylsulfonamide

0℃하의 DMF(9ml) 중의 티오닐 클로라이드(7.5ml) 및 4-t-부틸카타콜(45mg, 0.3mmol)의 용액을 4-비닐벤젠 설폰산 나트륨 염(3g, 14.6mmol)으로 처리하고, 6시간 동안 교반하며, -10℃에서 3일 동안 저장하고, 얼음 물에 붓고 벤젠으로 추출한다. 유기 층을 물로 세척하고, 건조시키며(Na2SO4), 여과한 다음 농축시켜 투명한 무색 오일로서의 4-비닐 설포닐 클로라이드를 제공한다. 일정 분획의 클로라이드(1g, 4.95mmol)를 THF(10ml)에 용해시키고, 0℃로 냉각시키며, 기체 방출이 중단될 때까지 진한 수산화나트륨을 적가한 다음 에틸 아세테이트로 추출한다. 합한 추출물을 건조시키고(Na2SO4) 농축시켜 담황색 고체로서의 표제 화합물을 707mg 수득한다. MS(DCI/NH3) m/e 201(M+NH4)+.A solution of thionyl chloride (7.5 ml) and 4-t-butylcatacol (45 mg, 0.3 mmol) in DMF (9 ml) at 0 ° C. was treated with 4-vinylbenzene sulfonic acid sodium salt (3 g, 14.6 mmol), Stir for 6 hours, store for 3 days at −10 ° C., pour into ice water and extract with benzene. The organic layer is washed with water, dried (Na 2 SO 4 ), filtered and concentrated to give 4-vinyl sulfonyl chloride as a clear colorless oil. A portion of chloride (1 g, 4.95 mmol) is dissolved in THF (10 ml), cooled to 0 ° C., concentrated sodium hydroxide is added dropwise until gas evolution stops and then extracted with ethyl acetate. The combined extracts are dried (Na 2 SO 4 ) and concentrated to give 707 mg of the title compound as a pale yellow solid. MS (DCI / NH 3 ) m / e 201 (M + NH 4 ) + .

실시예 83BExample 83B

(E)-4-[2-(6-시아노-2-나프탈레닐)에테닐]벤젠설폰아미드(E) -4- [2- (6-cyano-2-naphthalenyl) ethenyl] benzenesulfonamide

실시예 57B에 기재된 과정에 따라서, 실시예 55B 및 83A로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 352(M+NH4)+.Following the procedure described in Example 57B, the title compound is prepared from Examples 55B and 83A. MS (DCI / NH 3 ) m / e 352 (M + NH 4 ) + .

실시예 83CExample 83C

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤젠설폰아미드 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzenesulfonamide mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 83B를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 83B following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 9.43(s, 2H), 9.05(s, 2H), 8.46(s, 1H), 8.21(s, 1H), 8.16-7.95(m, 3H), 7.86(s, 2H), 7.84-7.67(m, 2H), 7.62(d, 1H), 7.4-7.36(m, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 9.43 (s, 2H), 9.05 (s, 2H), 8.46 (s, 1H), 8.21 (s, 1H), 8.16-7.95 (m, 3H), 7.86 (s, 2H), 7.84-7.67 (m, 2H), 7.62 (d, 1H), 7.4-7.36 (m, 2H);

MS(DCI/NH3) m/e 352 (M+H)+.MS (DCI / NH 3 ) m / e 352 (M + H) + .

C19H17N3O2S·1.5C2F3O2H에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 3 O 2 S · 1.5C 2 F 3 O 2 H:

계산치 : C, 50.84; H, 3.59; N, 8.11.Calculated: C, 50.84; H, 3.59; N, 8.11.

실측치 : C, 50.83; H, 3.89; N, 7.88.Found: C, 50.83; H, 3.89; N, 7.88.

실시예 84Example 84

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤조산 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzoic acid mono (trifluoroacetate) salt

실시예 84AExample 84A

(E)-4-[2-(6-시아노-2-나프탈레닐)에테닐]벤조산(E) -4- [2- (6-cyano-2-naphthalenyl) ethenyl] benzoic acid

실시예 57B에 기재된 과정에 따라서, 실시예 55B 및 4-비닐벤조산으로부터 표제 화합물을 제조한다. MS(DCI/NH3) m/e 300(M+H)+.Following the procedure described in Example 57B, the title compound is prepared from Example 55B and 4-vinylbenzoic acid. MS (DCI / NH 3 ) m / e 300 (M + H) + .

실시예 84BExample 84B

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤조산 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzoic acid mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 84A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 84A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 7.62-7.58(m, 2H), 7.90(d, 2H), 7.98(d, 1H), 8.12-8.04(m, 3H), 8.20(s, 1H), 8.56(s, 1H), 9.07(bs, 2H), 9.35(bs, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.62-7.58 (m, 2H), 7.90 (d, 2H), 7.98 (d, 1H), 8.12-8.04 (m, 3H), 8.20 (s, 1H) , 8.56 (s, 1 H), 9.07 (bs, 2 H), 9.35 (bs, 2 H).

MS(DCI/NH3) m/e 317 (M+H)+.MS (DCI / NH 3 ) m / e 317 (M + H) + .

C20H16N2O2·TFA에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 2 O 2 · TFA:

계산치 : C, 61.40; H, 3.98; N, 6.51.Calculated: C, 61.40; H, 3.98; N, 6.51.

실측치 : C, 61.10; H, 3.63; N, 6.45.Found: C, 61.10; H, 3.63; N, 6.45.

실시예 85Example 85

4-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]디하이드로-2(3H)-푸란온 모노(트리플루오로아세테이트) 염4- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] dihydro-2 (3H) -furanone mono (trifluoroacetate) salt

실시예 85AExample 85A

4-(7-시아노-2-메톡시-1-나프탈레닐)디하이드로-2(3H)-푸란온4- (7-cyano-2-methoxy-1-naphthalenyl) dihydro-2 (3H) -furanone

메틸렌 클로라이드(15ml) 중의 실시예 62A(269mg, 1.00mmol) 및 피리디늄 클로로크로메이트(360mg, 1.67mmol)을 실온에서 24시간 동안 교반하고, 셀라이트를 통하여 여과한 다음 농축시킨다. 잔사를 20% 에틸 아세테이트/헥산을 사용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 170mg 수득한다. MS(DCI/NH3) m/e 285(M+NH4)+.Example 62A (269 mg, 1.00 mmol) and pyridinium chlorochromate (360 mg, 1.67 mmol) in methylene chloride (15 ml) are stirred at room temperature for 24 hours, filtered through celite and concentrated. The residue is chromatographed on silica gel with 20% ethyl acetate / hexanes to give 170 mg of the title compound. MS (DCI / NH 3 ) m / e 285 (M + NH 4 ) + .

실시예 85BExample 85B

4-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]디하이드로-2(3H)-푸란온 모노(트리플루오로아세테이트) 염4- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] dihydro-2 (3H) -furanone mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 85A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 85A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 2.96-2.75(m, 2H), 3.96(s, 3H), 4.33(m, 1H), 4.66(t, 1H), 8.85(m, 1H), 7.68(dd, 1H), 7.73(d, 1H), 8.08(d, 1H), 8.12(d, 1H), 8.67(s, 1H), 9.14(s, 2H), 9.43(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.96-2.75 (m, 2H), 3.96 (s, 3H), 4.33 (m, 1H), 4.66 (t, 1H), 8.85 (m, 1H), 7.68 (dd, 1H), 7.73 (d, 1H), 8.08 (d, 1H), 8.12 (d, 1H), 8.67 (s, 1H), 9.14 (s, 2H), 9.43 (s, 2H);

MS(DCI/NH3) m/e 285 (M+H)+.MS (DCI / NH 3 ) m / e 285 (M + H) + .

C16H16N2O3·1.1TFA에 대한 원소분석치:Elemental Analysis for C 16 H 16 N 2 O 3 · 1.1TFA:

계산치 : C, 53.72; H, 4.24; N, 6.91.Calc .: C, 53.72; H, 4. 24; N, 6.91.

실측치 : C, 53.75; H, 4.26; N, 6.94.Found: C, 53.75; H, 4. 26; N, 6.94.

실시예 86Example 86

7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 86AExample 86A

7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카보니트릴7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarbonitrile

THF(2ml) 중의 실시예 53F(90mg, 0.361mmol)의 용액을 톨루엔 중의 칼륨 비스(트리메틸실릴)아미드(0.866ml, 0.433mmol)의 0.5M 용액으로 처리하고, 5분 동안 교반하며, 아세틸 클로라이드(38ml, 0.542mmol)로 처리하며, 10분 동안 교반한 다음 농축시킨다. 조 생성물을 25% 에틸 아세테이트/헥산을 이용하여 실리카 겔 상에서 크로마토그래피하여 표제 화합물을 67mg 수득한다. MS(DCI/NH3) m/e 309(M+NH4)+.A solution of Example 53F (90 mg, 0.361 mmol) in THF (2 ml) was treated with a 0.5 M solution of potassium bis (trimethylsilyl) amide (0.866 ml, 0.433 mmol) in toluene, stirred for 5 minutes, and acetyl chloride ( 38 ml, 0.542 mmol), stirred for 10 minutes and then concentrated. The crude product is chromatographed on silica gel with 25% ethyl acetate / hexanes to give 67 mg of the title compound. MS (DCI / NH 3 ) m / e 309 (M + NH 4 ) + .

실시예 86BExample 86B

7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 86A를 사용하여 표제 화합물을 제조한다.Prepare for the title compound using Example 86A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 3.89(s, 3H), 7.59(d, 1H), 7.92(s, 2H), 8.06(d, 1H), 8.12(d, 1H), 8.28(s, 1H), 8.94(s, 2H), 9.34(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 3.89 (s, 3H), 7.59 (d, 1H), 7.92 (s, 2H), 8.06 (d, 1H), 8.12 (d, 1H), 8.28 (s , 1H), 8.94 (s, 2H), 9.34 (s, 2H);

MS(DCI/NH3) m/e 309 (M+H)+.MS (DCI / NH 3 ) m / e 309 (M + H) + .

C17H16N4O2·1.9TFA에 대한 원소분석치:Elemental Analysis for C 17 H 16 N 4 O 2 · 1.9TFA:

계산치 : C, 47.59; H, 3.44; N, 10.67.Calculated: C, 47.59; H, 3. 44; N, 10.67.

실측치 : C, 54.03; H, 4.06; N, 13.26.Found: C, 54.03; H, 4.06; N, 13.26.

실시예 87Example 87

7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 87AExample 87A

7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카보니트릴7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarbonitrile

실시예 86A의 과정에 따라서 실시예 53F(190mg, 0.762mmol) 및 메탄설포닐 클로라이드(0.088ml, 1.14mmol)로부터 표제 화합물을 122mg 수득한다. MS(DCI/NH3) m/e 345(M+NH4)+.122 mg of the title compound are obtained from Example 53F (190 mg, 0.762 mmol) and methanesulfonyl chloride (0.088 ml, 1.14 mmol) following the procedure of Example 86A. MS (DCI / NH 3 ) m / e 345 (M + NH 4 ) + .

실시예 87BExample 87B

7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 87A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 87A following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 2.75(s, 3H), 3.98(s, 3H), 7.64(dd, 1H), 7.78(d, 1H), 8.15(s, 1H), 8.18(s, 1H), 8.21(s, 1H), 8.24(s, 1H), 8.62(s, 1H), 8.97(s, 2H), 9.40(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 2.75 (s, 3H), 3.98 (s, 3H), 7.64 (dd, 1H), 7.78 (d, 1H), 8.15 (s, 1H), 8.18 (s , 1H), 8.21 (s, 1H), 8.24 (s, 1H), 8.62 (s, 1H), 8.97 (s, 2H), 9.40 (s, 2H);

MS(DCI/NH3) m/e 345 (M+H)+.MS (DCI / NH 3 ) m / e 345 (M + H) + .

C16H16N4O3S·1.4TFA에 대한 원소분석치:Elemental Analysis for C 16 H 16 N 4 O 3 S · 1.4TFA:

계산치 : C, 44.75; H, 3.47; N, 11.09.Calculated: C, 44.75; H, 3.47; N, 11.09.

실측치 : C, 44.59; H, 3.86; N, 11.38.Found: C, 44.59; H, 3.86; N, 11.38.

실시예 88Example 88

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤즈아미드 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzamide mono (trifluoroacetate) salt

실시예 88AExample 88A

(E)-4-[2-(6-시아노-2-나프탈레닐)에테닐]벤즈아미드(E) -4- [2- (6-cyano-2-naphthalenyl) ethenyl] benzamide

티오닐 클로라이드(4ml) 중의 실시예 85A(160mg, 0.54mmol)을 0.5시간 동안 환류시키고, 0℃로 냉각시키며, 기체 방출이 중단될 때까지 진한 수성 암모니아로 처리하며, 에틸 아세테이트로 희석시키고, 가열하여 잔류 고체를 용해시키며, 물로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 오렌지색 고체로서의 표제 화합물을 100mg 수득한다. MS(DCI/NH3) m/e 316(M+NH4)+.Example 85A (160 mg, 0.54 mmol) in thionyl chloride (4 ml) was refluxed for 0.5 h, cooled to 0 ° C., treated with concentrated aqueous ammonia until gas evolution ceased, diluted with ethyl acetate and heated To dissolve the remaining solid, washed with water, dried (MgSO 4 ) and concentrated to give 100 mg of the title compound as an orange solid. MS (DCI / NH 3 ) m / e 316 (M + NH 4 ) + .

실시예 88BExample 88B

(E)-4-[2-(6-아미노이미노메틸-2-나프탈레닐)에테닐]벤즈아미드 모노(트리플루오로아세테이트) 염(E) -4- [2- (6-aminoiminomethyl-2-naphthalenyl) ethenyl] benzamide mono (trifluoroacetate) salt

실시예 1B의 과정에 따라서 실시예 88A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 88A following the procedure of Example 1B.

1H NMR(300MHz, DMSO-d6) δ 7.34(br, 1H), 7.51(d, 1H), 7.56(d, 2H), 7.73(d, 2H), 7.82(m, 2H), 7.90(d, 2H), 7.96(br, 1H), 8.09(q, 3H), 8.17(s, 1H), 8.43(s, 1H), 9.01(s, 2H), 9.40(s, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.34 (br, 1H), 7.51 (d, 1H), 7.56 (d, 2H), 7.73 (d, 2H), 7.82 (m, 2H), 7.90 (d , 2H), 7.96 (br, 1H), 8.09 (q, 3H), 8.17 (s, 1H), 8.43 (s, 1H), 9.01 (s, 2H), 9.40 (s, 2H);

MS(DCI/NH3) m/e 316 (M+H)+.MS (DCI / NH 3 ) m / e 316 (M + H) + .

C20H17N3O·1.1TFA에 대한 원소분석치:Elemental Analysis for C 20 H 17 N 3 O · 1.1TFA:

계산치 : C, 60.09; H, 4.11; N, 9.44.Calculated: C, 60.09; H, 4.11; N, 9.44.

실측치 : C, 60.22; H, 4.13; N, 8.79.Found: C, 60.22; H, 4.13; N, 8.79.

실시예 89Example 89

6-[2-(4-아미노페닐)에톡시]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (4-aminophenyl) ethoxy] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 89AExample 89A

6-[2-(4-아미노페닐)에톡시]-2-나프탈렌카보니트릴6- [2- (4-aminophenyl) ethoxy] -2-naphthalenecarbonitrile

DMF(5ml) 중의 실시예 4A(300mg), Cs2CO3(1.2g), 4-아미노펜에틸브로마이드(470mg) 및 테트라부틸암모늄 요오다이드(10mg)의 용액을 실온에서 18시간 동안 교반하고, 물로 희석시킨 다음 에틸 아세테이트로 추출한다. 유기 추출물을 포화 수성 NaHCO3및 염수로 세척하고, 건조시킨 다음(Na2SO4) 농축시켜 짙은 갈색 오일로서의 표제 화합물을 200mg 수득한다. MS(DCI/NH3) m/e 306(M+NH4)+.A solution of Example 4A (300 mg), Cs 2 CO 3 (1.2 g), 4-aminophenethylbromide (470 mg) and tetrabutylammonium iodide (10 mg) in DMF (5 ml) was stirred at room temperature for 18 hours, Dilute with water and extract with ethyl acetate. The organic extract is washed with saturated aqueous NaHCO 3 and brine, dried (Na 2 SO 4 ) and concentrated to give 200 mg of the title compound as a dark brown oil. MS (DCI / NH 3 ) m / e 306 (M + NH 4 ) + .

실시예 89BExample 89B

6-[2-(4-아미노페닐)에톡시]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염6- [2- (4-aminophenyl) ethoxy] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 5B의 과정에 따라서 실시예 89A를 사용하여 표제 화합물을 제조한다.Prepare the title compound using Example 89A following the procedure of Example 5B.

1H NMR(300MHz, DMSO-d6) δ 3.15(t, 2H), 3.6(bs, 3H), 4.35(t, 2H), 6.93(d, 2H), 7.24(d, 2H), 7.38(dd, 2H), 7.55(d, 1H), 7.78(dd, 1H), 7.98(dd, 1H), 8.21(d, 1H), 8.4(d, 2H), 9.21(bs, 2H), 9.39(bs, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 3.15 (t, 2H), 3.6 (bs, 3H), 4.35 (t, 2H), 6.93 (d, 2H), 7.24 (d, 2H), 7.38 (dd , 2H), 7.55 (d, 1H), 7.78 (dd, 1H), 7.98 (dd, 1H), 8.21 (d, 1H), 8.4 (d, 2H), 9.21 (bs, 2H), 9.39 (bs, 2H);

MS(DCI/NH3) m/e 306 (M+H)+.MS (DCI / NH 3 ) m / e 306 (M + H) + .

C19H19N3O·2TFA에 대한 원소분석치:Elemental Analysis for C 19 H 19 N 3 O · 2TFA:

계산치 : C, 51.79; H, 3.97; N, 7.88.Calculated: C, 51.79; H, 3.97; N, 7.88.

실측치 : C, 50.99; H, 4.68; N, 7.59.Found: C, 50.99; H, 4.68; N, 7.59.

실시예 90Example 90

메틸 [3-메톡시-6-(아미노이미노메틸)-4-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염Methyl [3-methoxy-6- (aminoiminomethyl) -4-naphthalenyl] carbamate mono (trifluoroacetate) salt

실시예 90AExample 90A

7-메톡시-2-트리플루오로메탄설포닐옥시 나프탈렌7-methoxy-2-trifluoromethanesulfonyloxy naphthalene

DMF(20ml) 및 메틸렌 클로라이드(20ml) 중의 7-메톡시-2-나프톨(3.24g, 18mmol)의 용액을 N-페닐 트리플루오로메탄설폰아미드(6.6g, 18mmol) 및 트리에틸아민(5.2ml, 37mmol)로 처리하고, 실온에서 20시간 동안 교반하며, CH2Cl2(100ml)로 희석시키며, 증류수, 20% KOH 및 염수로 순차적으로 세척하며, 건조시킨 다음(MgSO4) 농축시켜 투명한 오일로서의 표제 화합물을 수득한다. MS(DCI/NH3) m/e 272(M+NH4)+.A solution of 7-methoxy-2-naphthol (3.24 g, 18 mmol) in DMF (20 ml) and methylene chloride (20 ml) was added N-phenyl trifluoromethanesulfonamide (6.6 g, 18 mmol) and triethylamine (5.2 ml). , 37 mmol), stirred at room temperature for 20 hours, diluted with CH 2 Cl 2 (100 ml), washed sequentially with distilled water, 20% KOH and brine, dried (MgSO 4 ) and concentrated to a clear oil. The title compound as is obtained. MS (DCI / NH 3 ) m / e 272 (M + NH 4 ) + .

실시예 90BExample 90B

7-메톡시-2-나프탈렌카보니트릴7-methoxy-2-naphthalenecarbonitrile

DMF(40ml) 중의 실시예 90A(12mmol), 시안화아연(12mmol), Pd(OAc)2(0.3mmol) 및 트리페닐포스핀(1.2mmol)을 85℃에서 6시간 동안 가열하고, 에틸 아세테이트(200ml)로 희석시키며, 포화 NaHCO3, 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 짙은 오일상 잔사를 수득한다. 이 잔사를 1:1 헥산:메틸렌 클로라이드를 사용한 다음 CH2Cl2을 사용하여 실리카 겔 상에서 정제하여 백색 고체로서의 표제 화합물을 1.8g 수득한다. MS(DCI/NH3) m/e 201(M+NH4)+.Example 90A (12 mmol), zinc cyanide (12 mmol), Pd (OAc) 2 (0.3 mmol) and triphenylphosphine (1.2 mmol) in DMF (40 ml) were heated at 85 ° C. for 6 hours and ethyl acetate (200 ml) ), Washed with saturated NaHCO 3 , brine, dried (MgSO 4 ) and concentrated to afford a dark oily residue. This residue was purified on silica gel using 1: 1 hexanes: methylene chloride and then CH 2 Cl 2 to afford 1.8 g of the title compound as a white solid. MS (DCI / NH 3 ) m / e 201 (M + NH 4 ) + .

실시예 90CExample 90C

7-메톡시-8-니트로-2-나프탈렌카보니트릴7-methoxy-8-nitro-2-naphthalenecarbonitrile

0℃하의 아세트산 무수물(30ml) 중의 실시예 90B(3g, 16.4mmol)를 발화 HNO3(1.2ml)로 처리하고, 생성된 두꺼운 슬러리를 물(20ml)로 희석시키며, 20분 동안 교반한 다음 여과하고 진공하에 건조시켜 황색 고체로서의 표제 화합물을 3.69g 수득한다. MS(DCI/NH3) m/e 246(M+NH4)+.Treat Example 90B (3 g, 16.4 mmol) in acetic anhydride (30 ml) at 0 ° C. with ignited HNO 3 (1.2 ml), dilute the resulting thick slurry with water (20 ml), stir for 20 minutes and then filter And dried in vacuo to afford 3.69 g of the title compound as a yellow solid. MS (DCI / NH 3 ) m / e 246 (M + NH 4 ) + .

실시예 90DExample 90D

7-메톡시-8-아미노-2-나프토니트릴7-methoxy-8-amino-2-naphtonitrile

에틸 아세테이트(100ml) 중의 실시예 90C(3.69g, 16.1mmol) 및 10% Pd/C(0.4g)을 실온에서 수소압하에 2시간 동안 교반하고, 여과한 다음 농축시켜 황색 고체로서의 표제 화합물을 3g 수득한다. MS(DCI/NH3) m/e 217(M+NH4)+.Example 90C (3.69 g, 16.1 mmol) and 10% Pd / C (0.4 g) in ethyl acetate (100 ml) were stirred at room temperature under hydrogen pressure for 2 hours, filtered and concentrated to give 3 g of the title compound as a yellow solid. To obtain. MS (DCI / NH 3 ) m / e 217 (M + NH 4 ) + .

실시예 90EExample 90E

메틸 [3-메톡시-6-시아노-4-나프탈레닐]카바메이트Methyl [3-methoxy-6-cyano-4-naphthalenyl] carbamate

디옥산(7ml) 및 10% NaOH(15ml) 중의 실시예 90D(81mg, 0.41mmol)을 메틸 클로로포르메이트(112mg, 0.98mmol)로 처리하고, 2시간 동안 교반하며, 에틸 아세테이트로 희석시키고, 물로 세척하며 건조시킨 다음(MgSO4) 농축시켜 표제 화합물을 105mg 수득한다. MS(DCI/NH3) m/e 274(M+NH3)+.Example 90D (81 mg, 0.41 mmol) in dioxane (7 ml) and 10% NaOH (15 ml) was treated with methyl chloroformate (112 mg, 0.98 mmol), stirred for 2 hours, diluted with ethyl acetate and diluted with water. Wash, dry (MgSO 4 ) and concentrate to give 105 mg of the title compound. MS (DCI / NH 3 ) m / e 274 (M + NH 3 ) + .

실시예 90FExample 90F

메틸 [3-메톡시-6-(아미노이미노메틸)-4-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염Methyl [3-methoxy-6- (aminoiminomethyl) -4-naphthalenyl] carbamate mono (trifluoroacetate) salt

실시예 40D의 과정에 따라서 실시예 90E로부터 표제 화합물을 제조한다.The title compound is prepared from Example 90E following the procedure of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 9.48(s, 2H), 8.99(s, 2H), 8.93(br, 1H), 8.34(s, 1H), 8.12(d, 1H), 8.04(d, 1H), 7.72(d, 1H), 7.65(dd, 1H), 3.95(s, 3H); 1 H NMR (300MHz, DMSO-d 6 ) δ 9.48 (s, 2H), 8.99 (s, 2H), 8.93 (br, 1H), 8.34 (s, 1H), 8.12 (d, 1H), 8.04 (d , 1H), 7.72 (d, 1H), 7.65 (dd, 1H), 3.95 (s, 3H);

MS (DCI/NH3) m/e 274 (M+H)+.MS (DCI / NH 3 ) m / e 274 (M + H) + .

C14H15N3O3·1.8TFA에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 3 1.8TFA:

계산치 : C, 44.07; H, 3.53; N, 8.74.Calculated: C, 44.07; H, 3.53; N, 8.74.

실측치 : C, 44.14; H, 3.20; N, 8.53.Found: C, 44.14; H, 3. 20; N, 8.53.

실시예 91Example 91

7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide bis (trifluoroacetate) salt

실시예 91AExample 91A

7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카보니트릴7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarbonitrile

톨루엔(5ml) 중의 실시예 90D(230mg, 1.2mmol), 2-클로로피리미딘(280mg, 2mmol), 나트륨-3급-부톡사이드(120mg, 1.2mmol), Pd(dba)3·CHCl3및 dppf의 용액을 100℃ 하의 밀봉된 튜브에서 18시간 동안 가열하고, 에틸 아세테이트(100ml)로 희석시키며, 염수로 세척하고, 건조시킨 다음(MgSO4) 농축시켜 갈색 오일을 100mg 수득한다. MS(DCI/NH3) m/e 294(M+NH4)+.Example 90D (230 mg, 1.2 mmol), 2-chloropyrimidine (280 mg, 2 mmol), sodium tert-butoxide (120 mg, 1.2 mmol), Pd (dba) 3 CHCl 3 and dppf in toluene (5 ml) The solution of was heated for 18 h in a sealed tube at 100 ° C., diluted with ethyl acetate (100 ml), washed with brine, dried (MgSO 4 ) and concentrated to give 100 mg of brown oil. MS (DCI / NH 3 ) m / e 294 (M + NH 4 ) + .

실시예 91BExample 91B

7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide bis (trifluoroacetate) salt

실시예 40D의 것과 유사한 방식으로 표제 화합물을 제조한다.The title compound is prepared in a manner similar to that of Example 40D.

1H NMR(300MHz, DMSO-d6) δ 9.43(s, 2H), 9.11(s, 2H), 8.46(s, 1H), 8.16(br, 3H), 8.15(d, 1H), 8.04(d, 1H), 7.82(dd, 1H), 7.75(d, 1H), 7.54(s, 1H), 7.50(d, 1H), 4.08(d, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.43 (s, 2H), 9.11 (s, 2H), 8.46 (s, 1H), 8.16 (br, 3H), 8.15 (d, 1H), 8.04 (d , 1H), 7.82 (dd, 1H), 7.75 (d, 1H), 7.54 (s, 1H), 7.50 (d, 1H), 4.08 (d, 2H);

MS (DCI/NH3) m/e 294 (M+H)+.MS (DCI / NH 3 ) m / e 294 (M + H) + .

C16H15N5O·3.8TFA에 대한 원소분석치:Elemental Analysis for C 16 H 15 N 5 O · 3.8TFA:

계산치 : C, 39.01; H, 2.61; N, 9.64.Calculated: C, 39.01; H, 2.61; N, 9.64.

실측치 : C, 39.01; H, 3.06; N, 9.63.Found: C, 39.01; H, 3.06; N, 9.63.

실시예 92Example 92

6-(아미노이미노메틸)-N-[4-(하이드록시메틸)페닐]-2-나프탈렌카복스아미드 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [4- (hydroxymethyl) phenyl] -2-naphthalenecarboxamide mono (trifluoroacetate) salt

실시예 92AExample 92A

4-아미노-벤질옥시-3급-부틸디메틸실릴 에테르4-amino-benzyloxy-tert-butyldimethylsilyl ether

DMF(20ml) 중의 4-아미노벤질 알콜(1g, 8.1mmol)의 용액을 이미다졸(0.54g, 8.1mmol) 및 3급-부틸 디메틸실릴 클로라이드(1.22g, 8.12mmol)로 처리하고, 실온에서 밤새 교반하며, 에틸 아세테이트(100ml)로 희석시키고, 1N H3PO4, 포화 NaHCO3및 10% NaCl로 세척하며, 건조시킨 다음(Na2SO4) 농축시켜 오일을 수득하고, 이를 3:1 헥산:에틸 아세테이트를 사용하여 실리카 겔 상에서 정제하여 투명한 오일 0.5g을 수득한다. MS m/z 238(M+H)+.A solution of 4-aminobenzyl alcohol (1 g, 8.1 mmol) in DMF (20 ml) was treated with imidazole (0.54 g, 8.1 mmol) and tert-butyl dimethylsilyl chloride (1.22 g, 8.12 mmol) and overnight at room temperature Stirred, diluted with ethyl acetate (100 ml), washed with 1N H 3 PO 4 , saturated NaHCO 3 and 10% NaCl, dried (Na 2 SO 4 ) and concentrated to give an oil, which was 3: 1 hexane Purification on silica gel using ethyl acetate yields 0.5 g of a clear oil. MS m / z 238 (M + H) + .

실시예 92BExample 92B

실시예 92A(0.3g, 1.1mmol), 6-카복시-2-나프토니트릴 및 실시예 8E(0.2g, 1mmol)을 실시예 95C에 기재된 바와 같이 처리하여 목적 화합물을 100mg 수득한다. MS m/z 434(M+NH4)+.Example 92A (0.3 g, 1.1 mmol), 6-carboxy-2-naphtonitrile and Example 8E (0.2 g, 1 mmol) were treated as described in Example 95C to give 100 mg of the target compound. MS m / z 434 (M + NH 4 ) + .

실시예 92CExample 92C

1M 테트라부틸 암모늄 플루오라이드 THF 용액(2ml) 중의 실시예 92B의 용액을 실온에서 1시간 동안 교반하고, 10% NH4Cl 용액(50ml)으로 켄칭시키며, 에틸 아세테이트(100ml)로 희석시킨다. 이 층을 분리하고, 유기 층을 10% NaCl로 세척하며, 건조시킨 다음(MgSO4) 농축시켜 연갈색 오일을 수득하고, 이를 메틸렌 클로라이드로 연마하고 여과하여 백색 고체로서의 목적 화합물을 0.1g 수득한다. MS m/z 320(M+NH4)+.The solution of Example 92B in 1M tetrabutyl ammonium fluoride THF solution (2 ml) is stirred at room temperature for 1 hour, quenched with 10% NH 4 Cl solution (50 ml) and diluted with ethyl acetate (100 ml). The layer is separated, the organic layer is washed with 10% NaCl, dried (MgSO 4 ) and concentrated to give a light brown oil which is triturated with methylene chloride and filtered to give 0.1 g of the desired compound as a white solid. MS m / z 320 (M + NH 4 ) + .

실시예 92DExample 92D

6-(아미노이미노메틸)-N-[4-(하이드록시메틸)페닐]-2-나프탈렌카복스아미드 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [4- (hydroxymethyl) phenyl] -2-naphthalenecarboxamide mono (trifluoroacetate) salt

실시예 92C(0.1g, 0.33mmol)를 실시예 95D에서의 과정에 따라서 처리 및 정제하여 표제 화합물을 15mg 수득한다. MS m/z 434(M+NH4)+.Example 92C (0.1 g, 0.33 mmol) was treated and purified following the procedure in Example 95D to give 15 mg of the title compound. MS m / z 434 (M + NH 4 ) + .

1H NMR(300MHz, DMSO-d6) δ 10.45(s, 1H), 9.45(bs, 4H), 8.75(s, 1H), 8.59(s, 1H), 8.32(d, 1H), 8.22(d, 1H), 8.18(dd, 1H), 7.92(dd, 1H), 7.85(d, 2H), 7.45(d, 2H), 4.20(s, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 10.45 (s, 1H), 9.45 (bs, 4H), 8.75 (s, 1H), 8.59 (s, 1H), 8.32 (d, 1H), 8.22 (d , 1H), 8.18 (dd, 1H), 7.92 (dd, 1H), 7.85 (d, 2H), 7.45 (d, 2H), 4.20 (s, 2H);

C19H17N3O2·TFA에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 3 O 2 · TFA:

계산치 : C, 58.20; H, 4.19; N, 9.70.Calculated: C, 58.20; H, 4. 19; N, 9.70.

실측치 : C, 57.80; H, 3.91; N, 9.35.Found: C, 57.80; H, 3.91; N, 9.35.

실시예 93Example 93

6-(4-아미노페닐)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6- (4-aminophenyl) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 93AExample 93A

6-시아노-2-나프탈렌 보론산(0.3g, 1.64mmol), 4-요오도아닐린(0.36g, 1.64mmol), 팔라듐[1,1'-비스(디페닐포스피노)-페로센]디클로라이드(0.13g, 0.164mmol) 및 CsF(0.75g, 4.92mmol)를 DMF(8ml) 중에서 함께 혼합한 다음 80℃에서 20시간 동안 가열한다. 이 혼합물을 에틸 아세테이트(100ml)로 희석시키고, 1N H3PO4, 포화 NaHCO3, 10% NaCl로 세척하며, 무수 황산나트륨으로 건조시킨다. 건조제를 여과하고, 용매를 진공하에 제거하면 갈색 고체가 남는다. 이 고체를 3:1 헥산:에틸 아세테이트로 용출시키면서 실리카 겔 상에서 정제한다. 목적 화합물에 상응하는 분획을 진공하에 농축시키면 황색 고체(2g, 75%)가 생성된다. MS (M+NH4)+: 262.6-cyano-2-naphthalene boronic acid (0.3 g, 1.64 mmol), 4-iodoaniline (0.36 g, 1.64 mmol), palladium [1,1'-bis (diphenylphosphino) -ferrocene] dichloride (0.13 g, 0.164 mmol) and CsF (0.75 g, 4.92 mmol) are mixed together in DMF (8 ml) and then heated at 80 ° C. for 20 hours. The mixture is diluted with ethyl acetate (100 ml), washed with 1N H 3 PO 4 , saturated NaHCO 3 , 10% NaCl and dried over anhydrous sodium sulfate. The drying agent is filtered off and the solvent is removed in vacuo leaving a brown solid. This solid is purified on silica gel eluting with 3: 1 hexanes: ethyl acetate. Concentration of the fraction corresponding to the desired compound under vacuum yielded a yellow solid (2 g, 75%). MS (M + NH 4 ) + : 262.

실시예 93BExample 93B

6-(4-아미노페닐)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6- (4-aminophenyl) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 94D에 기재된 과정을 사용하여 실시예 93A에서 제조된 물질(0.1g, 0.41mmol)로부터 목적 화합물을 수득한다. 수율: 35mg, 53%. MS (M+H)+262.The desired compound is obtained from the material prepared in Example 93A (0.1 g, 0.41 mmol) using the procedure described in Example 94D. Yield: 35 mg, 53%. MS (M + H) + 262.

1H NMR(300MHz, DMSO-d6) δ 9.45(bs, 2H), 9.35(bs, 2H), 8.45(d, 1H), 8.22(s, 1H), 8.15(d, 1H), 8.10(d, 1H), 7.99(dd, 1H), 7.79(dd, 1H), 7.65(d, 2H), 6.95(d, 2H), 4.80(bs, 3H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.45 (bs, 2H), 9.35 (bs, 2H), 8.45 (d, 1H), 8.22 (s, 1H), 8.15 (d, 1H), 8.10 (d , 1H), 7.99 (dd, 1H), 7.79 (dd, 1H), 7.65 (d, 2H), 6.95 (d, 2H), 4.80 (bs, 3H);

C21H17N3O6F6에 대한 원소분석치:Elemental Analysis for C 21 H 17 N 3 O 6 F 6 :

계산치 : C, 51.54; H, 3.50; N, 8.59.Calculated: C, 51.54; H, 3.50; N, 8.59.

실측치 : C, 51.95; H, 3.84.Found: C, 51.95; H, 3.84.

실시예 95Example 95

메틸 2-[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]카보닐]아미노]페녹시]아세테이트 모노(트리플루오로아세테이트) 염Methyl 2- [4-[[[6- (aminoiminomethyl) -2-naphthalenyl] carbonyl] amino] phenoxy] acetate mono (trifluoroacetate) salt

실시예 95AExample 95A

4-아세트아미도페놀(5g, 33mmol)을 THF(100ml)에 용해시키고, 탄산세슘(10.25g, 33mmol) 및 메틸 브로모아세테이트(3.4ml, 36mmol)로 처리하고 실온에서 24시간 동안 교반한다. 이 반응 혼합물을 물(100ml)로 희석시키고 진공하에 농축시킨다. 잔사를 에틸 아세테이트(100ml)에 용해시키고, 1N H3PO4(20ml), 포화 NaHCO3(20ml), 10% NaCl(20ml)로 세척하며, 무수 Na2SO4상에서 건조시킨다. 건조제를 여과하고 용매를 진공하에 제거하여 백색 고체로서의 목적 화합물을 수득한다(6.8g, 92%). MS (M+NH4)+: 241.4-acetamidophenol (5 g, 33 mmol) is dissolved in THF (100 ml), treated with cesium carbonate (10.25 g, 33 mmol) and methyl bromoacetate (3.4 ml, 36 mmol) and stirred at room temperature for 24 hours. The reaction mixture is diluted with water (100 ml) and concentrated in vacuo. The residue is dissolved in ethyl acetate (100 ml), washed with 1N H 3 PO 4 (20 ml), saturated NaHCO 3 (20 ml), 10% NaCl (20 ml) and dried over anhydrous Na 2 SO 4 . The desiccant is filtered off and the solvent is removed in vacuo to afford the desired compound as a white solid (6.8 g, 92%). MS (M + NH 4 ) + : 241.

실시예 95BExample 95B

실시예 95A에서 수득된 물질을 2N HCl(75ml)로 처리하고 3시간 동안 환류시킨다. 투명한 혼합물을 실온으로 냉각시킨 다음 진공하에 농축시켜 목적 화합물로서 회백색 고체를 수득한다(6g, 92%). MS (M+NH4)+:198.The material obtained in Example 95A is treated with 2N HCl (75 ml) and refluxed for 3 hours. The clear mixture is cooled to room temperature and then concentrated in vacuo to yield an off white solid as the desired compound (6 g, 92%). MS (M + NH 4 ) + : 198.

실시예 95CExample 95C

6-카복시-2-나프토니트릴(0.1g, 51mmol)을 DMF(5ml)에 용해시키고, 얼음 욕 속에서 5℃로 냉각시킨다. 이러한 균질한 혼합물에 디이소프로필에틸아민(0.18ml, 1.05mmol) 및 O-(7-아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄 헥사플루오로포스페이트(HATU)를 가한다. 생성된 슬러리를 5℃에서 45분 동안 교반한다. 이 슬러리에 실시예 95B(0.12g, 0.56mmol)에서 수득된 물질을 가하고, 혼합물을 실온에서 밤새 교반한다. 다음 날, 반응 혼합물을 에틸 아세테이트(100ml)로 희석시키고, 1N H3PO4(20ml), 포화 NaHCO3(20ml), 10% NaCl로 세척하며, 무수 Na2SO4상에서 건조시키며, 여과한 다음, 용매를 진공하에 제거하여 갈색 고체로서의 목적 화합물을 수득한다(0.28g, 65%). MS (M+NH4)+:378.6-Carboxy-2-naphtonitrile (0.1 g, 51 mmol) is dissolved in DMF (5 ml) and cooled to 5 ° C. in an ice bath. In this homogeneous mixture diisopropylethylamine (0.18 ml, 1.05 mmol) and O- (7-azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluoro Phosphate (HATU) is added. The resulting slurry is stirred at 5 ° C. for 45 minutes. To this slurry the material obtained in Example 95B (0.12 g, 0.56 mmol) is added and the mixture is stirred overnight at room temperature. The next day, the reaction mixture was diluted with ethyl acetate (100 ml), washed with 1N H 3 PO 4 (20 ml), saturated NaHCO 3 (20 ml), 10% NaCl, dried over anhydrous Na 2 SO 4 , filtered The solvent is removed in vacuo to afford the desired compound as a brown solid (0.28 g, 65%). MS (M + NH 4 ) + : 378.

실시예 95DExample 95D

메틸 2-[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]카보닐]아미노]페녹시]아세테이트 모노(트리플루오로아세테이트) 염Methyl 2- [4-[[[6- (aminoiminomethyl) -2-naphthalenyl] carbonyl] amino] phenoxy] acetate mono (trifluoroacetate) salt

실시예 95C에서 수득된 물질(0.28g, 0.78mmol)을 메탄올에 용해시키고, HCl(g)(30ml)로 포화시킨 다음, 실온에서 18시간 동안 교반한다. 용매를 진공하에 제거하고 생성된 황색 고체를 2M NH3/메탄올(20ml)로 처리한다. 이 용액을 6시간 동안 환류시키고, 냉각시키며, 용매를 감압하에 제거하고, 생성된 갈색 고체를 역상 HPLC에 의해 정제한다. 동결건조시켜 목적 화합물을 수득한다(19.3mg, 20%). MS (M+H)+: 378.The material obtained in Example 95C (0.28 g, 0.78 mmol) is dissolved in methanol, saturated with HCl (g) (30 ml) and stirred at room temperature for 18 hours. The solvent is removed in vacuo and the resulting yellow solid is treated with 2M NH 3 / methanol (20 ml). The solution is refluxed for 6 hours, cooled, the solvent is removed under reduced pressure and the resulting brown solid is purified by reverse phase HPLC. Lyophilization gave the desired compound (19.3 mg, 20%). MS (M + H) + : 378.

1H NMR(300MHz, DMSO-d6) δ 10.45(s, 1H), 9.45(bs, 4H), 8.65(d, 1H), 8.59(s, 1H), 8.15(d, 1H), 8.10(d, 1H), 8.08(d, 1H), 7.92(d, 1H), 7.75(d, 2H), 6.98(d, 2H), 4.80(s, 2H), 3.75(s, 3H). 1 H NMR (300MHz, DMSO-d 6 ) δ 10.45 (s, 1H), 9.45 (bs, 4H), 8.65 (d, 1H), 8.59 (s, 1H), 8.15 (d, 1H), 8.10 (d , 1H), 8.08 (d, 1H), 7.92 (d, 1H), 7.75 (d, 2H), 6.98 (d, 2H), 4.80 (s, 2H), 3.75 (s, 3H).

C23H21N3O6F3에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 3 O 6 F 3 :

계산치 : C, 56.10; H, 4.3; N, 8.53.Calculated: C, 56.10; H, 4.3; N, 8.53.

실측치 : C, 55.80; H, 3.93; N, 8.33.Found: C, 55.80; H, 3.93; N, 8.33.

실시예 96Example 96

(E)-6-[2-[(3-하이드록시메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2-[(3-hydroxymethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 96AExample 96A

실시예 41A에서의 과정을 사용하여 3-요오도벤질 알콜로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+NH3)+303.The compound is prepared from 3-iodobenzyl alcohol using the procedure in Example 41A. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 303.

실시예 96BExample 96B

(E)-6-[2-[(3-하이드록시메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염(E) -6- [2-[(3-hydroxymethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt

실시예 40D로부터의 방법을 사용하여 실시예 96A로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+NH4)+303;The compound is prepared from Example 96A using the method from Example 40D. MS (DCI / NH 3 ) m / z (M + NH 4 ) + 303;

1H NMR(300MHz, DMSO-d6) δ 9.18(br, 4H), 8.45(s, 1H), 8.17(s, 1H), 8.13-8.04(m, 3H), 7.81(dd, 1H), 7.64(s, 1H), 7.57(d, 2H), 7.51(d, 1H), 7.39(t, 1H), 7.28(d, 1H), 5.27(t, 1H), 4.55(d, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.18 (br, 4H), 8.45 (s, 1H), 8.17 (s, 1H), 8.13-8.04 (m, 3H), 7.81 (dd, 1H), 7.64 (s, 1H), 7.57 (d, 2H), 7.51 (d, 1H), 7.39 (t, 1H), 7.28 (d, 1H), 5.27 (t, 1H), 4.55 (d, 2H);

C22H19N2O3F33/10 TFA에 대한 원소분석치:Elemental Analysis for C 22 H 19 N 2 O 3 F 3 3/10 TFA:

계산치 : C, 60.64; H, 4.35; N, 6.28.Calculated: C, 60.64; H, 4. 35; N, 6.28.

실측치 : C, 60.53; H, 4.87; N, 6.57.Found: C, 60.53; H, 4.87; N, 6.57.

실시예 97Example 97

6-(2-페닐-1-사이클로프로필)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (2-phenyl-1-cyclopropyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 97AExample 97A

염화구리(Ⅰ)(43mg, 0.4mmol) 및 분말 아연(26mg, 0.4mmol)을 1ml 디옥산에 18시간 동안 현탁시킨다. 실시예 41B로부터의 생성물(60mg, 0.2mmol)을 가하고 교반한 다음, 95℃에서 20시간 동안 가열한다. 반응 혼합물을 실리카 겔 상에서 농축시키고 실리카 겔 크로마토그래피하여 정제하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z (M+NH3)+287.Copper (I) chloride (43 mg, 0.4 mmol) and powdered zinc (26 mg, 0.4 mmol) are suspended in 1 ml dioxane for 18 hours. The product from Example 41B (60 mg, 0.2 mmol) is added and stirred, then heated at 95 ° C. for 20 hours. The reaction mixture is concentrated on silica gel and purified by silica gel chromatography to afford the desired compound. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 287.

실시예 97BExample 97B

6-(2-페닐-1-사이클로프로필)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (2-phenyl-1-cyclopropyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 1B로부터의 방법을 사용하여 실시예 1로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+287.The compound is prepared from Example 1 using the method from Example 1B. MS (DCI / NH 3 ) m / z (M + H) + 287.

1H NMR(300MHz, DMSO-d6) δ 9.41(s, 2H), 9.16(s, 2H), 8.46(s, 1H), 7.83(d, 2H), 7.62(s, 1H), 7.58(dd, 1H), 7.34(dd, 1H), 7.35-7.29(m, 3H), 7.25-7.17(m, 2H), 2.38-2.28(m, 2H), 1.61(t, 2H); 1 H NMR (300MHz, DMSO-d 6 ) δ 9.41 (s, 2H), 9.16 (s, 2H), 8.46 (s, 1H), 7.83 (d, 2H), 7.62 (s, 1H), 7.58 (dd , 1H), 7.34 (dd, 1H), 7.35-7.29 (m, 3H), 7.25-7.17 (m, 2H), 2.38-2.28 (m, 2H), 1.61 (t, 2H);

C22H19N2O2F31/10 TFA에 대한 원소분석치:Elemental Analysis for C 22 H 19 N 2 O 2 F 3 1/10 TFA:

계산치 : C, 65.00; H, 4.70; N, 6.84.Calculated: C, 65.00; H, 4. 70; N, 6.84.

실측치 : C, 65.22; H, 5.23; N, 5.10.Found: C, 65.22; H, 5. 23; N, 5.10.

실시예 98Example 98

(E)-6-[2-[4-(아미노메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염(E) -6- [2- [4- (aminomethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide bis (trifluoroacetate) salt

실시예 98AExample 98A

실시예 41A와 유사한 방식으로, 500대기압 하에 에텐을 사용하여 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+NH3)+197.In a similar manner to Example 41A, ethene is used to prepare the desired compound under 500 atmospheres. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 197.

실시에 98B98B to implementation

4-(아미노메틸)-요오도벤젠 하이드로클로라이드(1g, 3.7mmol) 및 Boc 무수물(1.22g, 5.6mmol)을 10% NaOH(15ml), 에틸 아세테이트(20ml)와 혼합하고 2시간 동안 교반한다. 유기 층을 5% 중탄산나트륨(2 x 10ml)으로 세척하고, 건조시킨 다음(황산마그네슘) 농축시켜 목적 화합물을 1.22g 수득한다. MS(DCI/NH3) m/z (M+NH3)+351.4- (aminomethyl) -iodobenzene hydrochloride (1 g, 3.7 mmol) and Boc anhydride (1.22 g, 5.6 mmol) are mixed with 10% NaOH (15 ml), ethyl acetate (20 ml) and stirred for 2 hours. The organic layer is washed with 5% sodium bicarbonate (2 x 10 ml), dried (magnesium sulphate) and concentrated to give 1.22 g of the desired compound. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 351.

실시예 98CExample 98C

실시예 41A와 유사한 방식으로 실시예 98A 및 98B로부터의 생성물을 사용하여 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+NH3)+402.The desired compound is prepared using the products from Examples 98A and 98B in a similar manner to Example 41A. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 402.

실시예 98DExample 98D

(E)-6-[2-[4-(아미노메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2- [4- (aminomethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

Boc 그룹을 제거하기 위해 메틸렌 클로라이드 중의 트리플루오로아세트산을 가하면서 실시예 40D와 유사한 방식으로 상기 생성물을 제조한다. MS(DCI/NH3) m/z (M+H)+302.The product is prepared in a similar manner to Example 40D with the addition of trifluoroacetic acid in methylene chloride to remove the Boc group. MS (DCI / NH 3 ) m / z (M + H) + 302.

1H-NMR(300MHz, DMSO-d6) δ 9.43(s, 2H), 9.11(s, 2H), 8.46(s, 1H), 8.16(br, 3H), 8.15(d, 1H), 8.04(d, 1H), 7.82(dd, 1H), 7.75(d, 1H), 7.54(s, 1H) 7.50(d, 1H), 4.08(d, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.43 (s, 2H), 9.11 (s, 2H), 8.46 (s, 1H), 8.16 (br, 3H), 8.15 (d, 1H), 8.04 ( d, 1H), 7.82 (dd, 1H), 7.75 (d, 1H), 7.54 (s, 1H) 7.50 (d, 1H), 4.08 (d, 2H);

C24H21N3O4F62/5·TFA에 대한 원소분석치:Elemental Analysis for C 24 H 21 N 3 O 4 F 6 2/5 · TFA:

계산치: C, 50.46; H, 3.63; N, 6.99.Calc .: C, 50.46; H, 3.63; N, 6.99.

실측치: C, 50.37; H, 3.86; N, 7.05.Found: C, 50.37; H, 3.86; N, 7.05.

실시예 99Example 99

메틸 [7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)카바메이트, 모노(트리플루오로아세테이트) 염Methyl [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) carbamate, mono (trifluoroacetate) salt

실시예 91A 및 40D에 기재된 과정을 사용하고 실시예 90D에 기재된 바와 같은 물질을 이용하여 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+306.The desired compound is prepared using the procedure described in Examples 91A and 40D and using the material as described in Example 90D. MS (DCI / NH 3 ) m / z (M + H) + 306.

1H-NMR(300MHz, DMSO-d6) δ 9.33(s, 2H), 8.98(s, 2H), 8.63(s, 1H), 7.99(d, 1H), 7.60(dd, 1H), 7.58(s, 1H), 7.54(d, 1H), 7.35-7.20(m, 5H), 4.52(s, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.33 (s, 2H), 8.98 (s, 2H), 8.63 (s, 1H), 7.99 (d, 1H), 7.60 (dd, 1H), 7.58 ( s, 1H), 7.54 (d, 1H), 7.35-7.20 (m, 5H), 4.52 (s, 2H);

C21H20N3O3F313/5 TFA에 대한 원소분석치:Elemental Analysis for C 21 H 20 N 3 O 3 F 3 13/5 TFA:

계산치: C, 44.03; H, 3.19; N, 5.89.Calc .: C, 44.03; H, 3. 19; N, 5.89.

실측치: C, 43.97; H, 3.55; N, 6.10.Found: C, 43.97; H, 3.55; N, 6.10.

실시예 100Example 100

7-메톡시-8-(2-피리미디닐아미노)-2-나프탈레카복스이미드아미드, 비스(트리플루오로아세테이트) 염7-methoxy-8- (2-pyrimidinylamino) -2-naphthalecarboximideamide, bis (trifluoroacetate) salt

실시예 91A 및 40D에 기재된 과정을 사용하고 실시예 90D에 기재된 바와 같은 물질을 이용하여 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+322.The desired compound is prepared using the procedure described in Examples 91A and 40D and using the material as described in Example 90D. MS (DCI / NH 3 ) m / z (M + H) + 322.

1H-NMR(300MHz, DMSO-d6) δ 9.35(s, 2H), 8.90(s, 2H), 8.34(s, 1H), 8.11(d, 1H), 7.90(d, 1H), 7.72(d, 1H), 7.60(dd, 1H), 7.47(s, 2H), 6.70(d, 2H) 6.49(d, 2H), 3.88(s, 3H), 3.64(s, 3H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.35 (s, 2H), 8.90 (s, 2H), 8.34 (s, 1H), 8.11 (d, 1H), 7.90 (d, 1H), 7.72 ( d, 1H), 7.60 (dd, 1H), 7.47 (s, 2H), 6.70 (d, 2H) 6.49 (d, 2H), 3.88 (s, 3H), 3.64 (s, 3H);

C21H20N3O4F31/10 TFA에 대한 원소분석치:Elemental Analysis for C 21 H 20 N 3 O 4 F 3 1/10 TFA:

계산치: C, 56.90; H, 4.53; N, 9.38.Calc .: C, 56.90; H, 4.53; N, 9.38.

실측치: C, 56.88; H, 4.41; N, 9.43.Found: C, 56.88; H, 4.41; N, 9.43.

실시예 101Example 101

7-메톡시-8-[(페닐메틸)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8-[(phenylmethyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 101AExample 101A

4-브로모스티렌(4.8g, 26.2mmol)을 100ml THF에 용해시키고 -78℃로 냉각시킨다. 부틸 리튬(헥산 중 2.5M, 28.8mmol)을 적가하고 5분 동안 교반한다. THF 중의 요오드를 오렌지/적색으로 유지될 때까지 적가한다. 진한 수성 염화암모늄(20ml)을 가하고, 반응물을 실온으로 가온시키며, 에테르로 희석시키고 10% Na2S2O5용액(1 x 50ml) 및 염수(1 x 50ml)로 세척하며, 건조시킨 다음(황산마그네슘) 농축시켜 목적 화합물을 수득한다. MS(DCI/NH3) m/z 122.4-bromostyrene (4.8 g, 26.2 mmol) is dissolved in 100 ml THF and cooled to -78 ° C. Butyl lithium (2.5 M in hexane, 28.8 mmol) is added dropwise and stirred for 5 minutes. Iodine in THF is added dropwise until it remains orange / red. Concentrated aqueous ammonium chloride (20 ml) was added, the reaction was allowed to warm to room temperature, diluted with ether, washed with 10% Na 2 S 2 O 5 solution (1 x 50 ml) and brine (1 x 50 ml), dried ( Magnesium sulfate) to afford the desired compound. MS (DCI / NH 3 ) m / z 122.

실시예 101BExample 101B

실시예 104A로부터의 생성물(2.35g, 10.2mmol), 1.6ml 60% N-메틸모르폴린-N-옥사이드/물 용액, 3.75ml 아세톤, 0.1ml 물을 1시간 동안 교반한다. 20ml 사산화오스뮴/3급-부탄올 용액(0.02mmol/ml)을 가하고 0℃에서 20시간 동안 교반한다. 반응물을 실리카 겔 상에서 농축시키고 실리카 겔 크로마토그래피로 정제하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z (M+NH3)+282.The product from Example 104A (2.35 g, 10.2 mmol), 1.6 ml 60% N-methylmorpholine-N-oxide / water solution, 3.75 ml acetone, 0.1 ml water are stirred for 1 hour. 20 ml osmium tetraoxide / tert-butanol solution (0.02 mmol / ml) is added and stirred at 0 ° C. for 20 hours. The reaction is concentrated on silica gel and purified by silica gel chromatography to afford the desired compound. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 282.

실시예 101CExample 101C

방법 41A를 사용하여 실시예 104B로부터의 목적 화합물을 커플링시킨다. MS(DCI/NH3) m/z (M+NH3)+333.Method 41A is used to couple the desired compound from Example 104B. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 333.

실시예 101DExample 101D

7-메톡시-8-[(페닐메틸)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8-[(phenylmethyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 104C로부터 상기 화합물을 제조한다.The compound is prepared from Example 104C using the method described in Example 40D.

1H-NMR(300MHz, DMSO-d6) δ 9.42(s, 2H), 9.12(s, 2H), 8.45(s, 1H), 8.15-8.05(m, 4H), 7.81(dd, 1H), 7.63(d, 2H), 7.48(d, 2H), 7.39(d, 2H), 4.56(t, 1H), 3.45(d, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.42 (s, 2H), 9.12 (s, 2H), 8.45 (s, 1H), 8.15-8.05 (m, 4H), 7.81 (dd, 1H), 7.63 (d, 2H), 7.48 (d, 2H), 7.39 (d, 2H), 4.56 (t, 1H), 3.45 (d, 2H);

C23H21N2O4F32/5 TFA에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 2 O 4 F 3 2/5 TFA:

계산치: C, 58.19; H, 4.39; N, 5.71.Calc .: C, 58.19; H, 4. 39; N, 5.71.

실측치: C, 58.17; H, 4.41; N, 5.87.Found: C, 58.17; H, 4.41; N, 5.87.

실시예 102Example 102

7-메톡시-8-[(페닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8-[(phenylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 102AExample 102A

3급-부틸카바메이트(3.62g, 15.7mmol)를 63ml 프로판올에 용해시킨다. 50ml 프로판올 중의 118ml NaOH/물 용액(0.4N), 3급-부틸 하이드로클로라이드(5.5ml, 47.8mmol) 및 (DHQD)2PHAL(612mg, 0.61mmol)을 가하고 10분 동안 교반한다. 실시예 2로부터의 생성물(3.62g, 15.7mmol) 및 K2OsO4·2H2O(211mg, 0.63mmol)을 가하고 24시간 동안 교반한다. 반응물을 농축시키고 에탄올/헥산으로 재결정화하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z (M+NH3)+381.Tert-butylcarbamate (3.62 g, 15.7 mmol) is dissolved in 63 ml propanol. 118 ml NaOH / water solution (0.4 N), tert-butyl hydrochloride (5.5 ml, 47.8 mmol) and (DHQD) 2 PHAL (612 mg, 0.61 mmol) in 50 ml propanol are added and stirred for 10 minutes. The product from Example 2 (3.62 g, 15.7 mmol) and K 2 OsO 4 .2H 2 O (211 mg, 0.63 mmol) were added and stirred for 24 hours. The reaction is concentrated and recrystallized from ethanol / hexanes to give the desired compound. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 381.

실시예 102BExample 102B

실시예 41A에 기재된 방법을 사용하여 실시예 102로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+415.The compound is prepared from Example 102 using the method described in Example 41A. MS (DCI / NH 3 ) m / z (M + H) + 415.

실시예 102CExample 102C

7-메톡시-8-(페닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8- (phenylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 94D에 기재된 방법을 사용하여 실시예 102B로부터 상기 화합물을 제조한다.The compound is prepared from Example 102B using the method described in Example 94D.

1H-NMR(300MHz, DMSO-d6) δ 9.42(s, 2H), 9.07(s, 2H), 8.45(s, 1H), 8.33(br, 3H), 8.16-8.03(m, 4H) 7.75(d, 2H), 7.56(s, 2H), 7.49(d, 2H), 5.49(br 1 h), 4.28(br 1H), 3.62(m, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.42 (s, 2H), 9.07 (s, 2H), 8.45 (s, 1H), 8.33 (br, 3H), 8.16-8.03 (m, 4H) 7.75 (d, 2H), 7.56 (s, 2H), 7.49 (d, 2H), 5.49 (br 1 h), 4.28 (br 1H), 3.62 (m, 2H);

MS(DCI/NH3) m/z (M+H)+264;MS (DCI / NH 3 ) m / z (M + H) + 264;

C25H23N3O5F6·5TFA에 대한 원소분석치:Elemental Analysis for C 25 H 23 N 3 O 5 F 6 · TFA:

계산치: C, 37.30; H, 2.51; N, 3.74.Calc .: C, 37.30; H, 2.51; N, 3.74.

실측치: C, 37.06; H, 3.12; N, 4.42.Found: C, 37.06; H, 3. 12; N, 4.42.

실시예 103Example 103

7-메톡시-8-[(4-메톡시페닐)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8-[(4-methoxyphenyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 103AExample 103A

4-브로모벤즈알데히드(600mg, 3.24mmol), THF 중의 16.2ml 디메틸아민(32.4mmol), 및 나트륨 트리아세톡시보로하이드라이드(1.24g, 5.8mmol)를 디클로로에탄(10ml)에 현탁시킨다. 반응 혼합물을 농축시키고, 물로 희석시키며 pH 2로 산성화시키고 에테르(3 x 20ml)로 추출한다. 수용액을 NaOH/물을 이용하여 pH 12로 염기성화하고 메틸렌 클로라이드(3 x 30ml)로 추출하며, HCl/메탄올로 산성화한 다음 농축시켜 목적 화합물을 수득한다. MS(DCI/NH3) m/z (M)+214.4-bromobenzaldehyde (600 mg, 3.24 mmol), 16.2 ml dimethylamine (32.4 mmol) in THF, and sodium triacetoxyborohydride (1.24 g, 5.8 mmol) are suspended in dichloroethane (10 ml). The reaction mixture is concentrated, diluted with water, acidified to pH 2 and extracted with ether (3 x 20 ml). The aqueous solution is basified to pH 12 with NaOH / water, extracted with methylene chloride (3 × 30 ml), acidified with HCl / methanol and concentrated to afford the desired compound. MS (DCI / NH 3 ) m / z (M) + 214.

실시예 103BExample 103B

실시예 41A에 기재된 방법을 사용하여 실시예 107A로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+313.The compound is prepared from Example 107A using the method described in Example 41A. MS (DCI / NH 3 ) m / z (M + H) + 313.

실시예 103CExample 103C

7-메톡시-8-[(4-메톡시페닐)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8-[(4-methoxyphenyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 103으로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+294.The compound is prepared from Example 103 using the method described in Example 40D. MS (DCI / NH 3 ) m / z (M + H) + 294.

1H-NMR(300MHz, DMSO-d6) δ 9.43(s, 2H), 9.11(s, 2H), 8.46(s, 1H), 8.18-8.06(m, 4H), 7.84(d, 4H), 7.60(s, 2H), 7.56(s, 1H), 4.53(s, 2H), 3.05(s, 6H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.43 (s, 2H), 9.11 (s, 2H), 8.46 (s, 1H), 8.18-8.06 (m, 4H), 7.84 (d, 4H), 7.60 (s, 2 H), 7.56 (s, 1 H), 4.53 (s, 2 H), 3.05 (s, 6 H);

C26H25N3O5F47/5 TFA에 대한 원소분석치:Elemental Analysis for C 26 H 25 N 3 O 5 F 4 7/5 TFA:

계산치: C, 48.46; H, 3.73; N, 5.91.Calc .: C, 48.46; H, 3.73; N, 5.91.

실측치: C, 48.36; H, 4.25; N, 6.19.Found: C, 48.36; H, 4. 25; N, 6.19.

실시예 104Example 104

(E)-6-[2-[4-(1,2-디하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염(E) -6- [2- [4- (1,2-dihydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 104AExample 104A

실시예 41A에 기재된 방법을 사용하여 실시예 98A에서 제조된 화합물 및 4-브로모벤질 알콜로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+HH3)+303.The compound is prepared from the compound prepared in Example 98A and 4-bromobenzyl alcohol using the method described in Example 41A. MS (DCI / NH 3 ) m / z (M + HH 3 ) + 303.

실시예 104BExample 104B

(E)-6-[2-[4-(1,2-디하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염(E) -6- [2- [4- (1,2-dihydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 104A로부터 상기 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+303.The compound is prepared from Example 104A using the method described in Example 40D. MS (DCI / NH 3 ) m / z (M + H) + 303.

1H-NMR(300MHz, DMSO-d6) δ 9.00(br, 4H), 8.44(s, 1H), 8.15-8.01(m, 4H), 7.81(dd, 1H), 7.64(d, 2H), 7.48(d, 1H), 7.36(d, 2H), 5.21(br, 1H) 4.53(s, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.00 (br, 4H), 8.44 (s, 1H), 8.15-8.01 (m, 4H), 7.81 (dd, 1H), 7.64 (d, 2H), 7.48 (d, 1 H), 7.36 (d, 2 H), 5.21 (br, 1 H) 4.53 (s, 2 H);

C22H19N2O3F34/5 TFA에 대한 원소분석치:Elemental Analysis for C 22 H 19 N 2 O 3 F 3 4/5 TFA:

계산치: C, 55.84; H, 3.93; N, 5.52.Calc .: C, 55.84; H, 3.93; N, 5.52.

실측치: C, 55.60; H, 3.93; N, 6.41.Found: C, 55.60; H, 3.93; N, 6.41.

실시예 105Example 105

(E)-6-[2-[4-(1R-아미노-2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2- [4- (1R-amino-2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 105AExample 105A

실시예 121A에 기재된 과정을 사용하고 4-요오도아닐린을 N-BOC-p-요오도페닐알라닌(BACHEM Bioscience Inc.)으로 대체하여 목적 화합물을 수득한다.Using the procedure described in Example 121A and replacing 4-iodoaniline with N-BOC-p-iodophenylalanine (BACHEM Bioscience Inc.) to afford the desired compound.

MS(DCI/NH3) m/z 458(M+NH4)+;MS (DCI / NH 3 ) m / z 458 (M + NH 4 ) + ;

1H-NMR(300MHz, CDCl3) δ 1.35(s, 9H), 2.90(t, 1H), 3.09(dd, 1H), 4.15(m, 1H), 7.20(d, 1H), 7.36(d, 2H), 7.56(d, 2H), 7.78(d, 1H), 7.85(d, 1H), 8.12(d, 1H), 8.17(d, 1H), 8.32(s, 1H), 8.62(s, 1H). 1 H-NMR (300 MHz, CDCl 3 ) δ 1.35 (s, 9H), 2.90 (t, 1H), 3.09 (dd, 1H), 4.15 (m, 1H), 7.20 (d, 1H), 7.36 (d, 2H), 7.56 (d, 2H), 7.78 (d, 1H), 7.85 (d, 1H), 8.12 (d, 1H), 8.17 (d, 1H), 8.32 (s, 1H), 8.62 (s, 1H) ).

실시예 105BExample 105B

실시예 40D에 기재된 방법을 사용하여 실시예 105A에서 수득된 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+458.The desired compound is prepared from the product obtained in Example 105A using the method described in Example 40D. MS (DCI / NH 3 ) m / z (M + H) + 458.

1H-NMR(300MHz, DMSO-d6) δ 1.35(s, 9H), 2.90(dd, 1H), 3.10(dd, 1H), 4.13(m, 1H), 7.10(d, 1H), 7.36(d, 2H), 7.55(d, 2H), 7.78(dd, 1H), 7.85(dd, 1H), 8.13(d, 1H), 8.19(d, 1H), 8.30(s, 1H), 8.50(s, 1H), 9.22(s, 2H), 9.42(s, 2H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.35 (s, 9H), 2.90 (dd, 1H), 3.10 (dd, 1H), 4.13 (m, 1H), 7.10 (d, 1H), 7.36 ( d, 2H), 7.55 (d, 2H), 7.78 (dd, 1H), 7.85 (dd, 1H), 8.13 (d, 1H), 8.19 (d, 1H), 8.30 (s, 1H), 8.50 (s , 1H), 9.22 (s, 2H), 9.42 (s, 2H).

실시예 105CExample 105C

(E)-6-[2-[4-(1R-아미노-2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2- [4- (1R-amino-2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 124D에 기재된 방법을 사용하여 실시예 105B에서 수득된 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+358.The desired compound is prepared from the product obtained in Example 105B using the method described in Example 124D. MS (DCI / NH 3 ) m / z (M + H) + 358.

1H-NMR(300MHz, DMSO) δ 3.02(m, 1H), 3.19(dd, 1H), 3.63(t, 1H), 7.39(d, 2H), 7.58(d, 2H), 7.76(d, 1H), 7.88(d, 1H), 8.15(d, 1H), 8.19(d, 1H), 8.30(s, 1H), 8.51(s, 1H), 9.41(s, 2H), 9.80(s, 2H); 1 H-NMR (300 MHz, DMSO) δ 3.02 (m, 1H), 3.19 (dd, 1H), 3.63 (t, 1H), 7.39 (d, 2H), 7.58 (d, 2H), 7.76 (d, 1H ), 7.88 (d, 1H), 8.15 (d, 1H), 8.19 (d, 1H), 8.30 (s, 1H), 8.51 (s, 1H), 9.41 (s, 2H), 9.80 (s, 2H) ;

C24H20F3N3O4·H2O에 대한 원소분석치: C 24 H 20 F 3 N 3 O 4 · H 2 O element for analysis:

계산치: C, 58.90; H, 4.53; N, 8.59.Calc .: C, 58.90; H, 4.53; N, 8.59.

실측치: C, 58.75; H, 4.22; N, 8.28.Found: C, 58.75; H, 4. 22; N, 8.28.

실시예 106Example 106

7-메톡시-8-(2-피리미디닐아미노)-2-나프탈레카복스이미드아미드, 비스(트리플루오로아세테이트) 염7-methoxy-8- (2-pyrimidinylamino) -2-naphthalecarboximideamide, bis (trifluoroacetate) salt

실시예 106AExample 106A

수소화붕소나트륨(0.22g, 5.8mmol)을 (4-브로모벤조일)메탄올(2.5g, 11.6mmol, Maybridge Chem. Co.) 및 25ml 무수 에탄올의 현탁액에 가한다. 반응 혼합물을 1시간 동안 환류 교반한다. 실온으로 냉각시킨 후, 에탄올을 진공하에 증발시키고, 물을 잔사에 가한다. 이 혼합물을 CH2Cl2로 추출한다. 추출물을 포화 수성 염화나트륨으로 세척하고, MgSO4로 건조시키며, 여과하고 진공하에 증발시켜 목적 화합물을 수득한다. MS(DCl/NH3) m/z 234/236 (M+NH4)+;Sodium borohydride (0.22 g, 5.8 mmol) is added to a suspension of (4-bromobenzoyl) methanol (2.5 g, 11.6 mmol, Maybridge Chem. Co.) and 25 ml anhydrous ethanol. The reaction mixture is stirred at reflux for 1 hour. After cooling to room temperature, ethanol is evaporated in vacuo and water is added to the residue. This mixture is extracted with CH 2 Cl 2 . The extract is washed with saturated aqueous sodium chloride, dried over MgSO 4 , filtered and evaporated in vacuo to afford the desired compound. MS (DCl / NH 3 ) m / z 234/236 (M + NH 4 ) + ;

1H NMR(300MHz, CDCl3) δ 2.10(t, 1H), 2.62(d, 1H), 3.63(m, 1H), 3.78(m, 1H), 4.81(m, 1H), 7.25(d, 2H), 7.50(d, 2H). 1 H NMR (300MHz, CDCl 3 ) δ 2.10 (t, 1H), 2.62 (d, 1H), 3.63 (m, 1H), 3.78 (m, 1H), 4.81 (m, 1H), 7.25 (d, 2H ), 7.50 (d, 2 H).

실시예 106BExample 106B

실시예 A-226218-A에 기재된 과정을 사용하여, 실시예 106A에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z 331(M+NH4)+;Using the procedure described in Example A-226218-A, the desired compound is obtained from the product obtained in Example 106A. MS (DCI / NH 3 ) m / z 331 (M + NH 4 ) + ;

1H NMR(300MHz, CDCl3) δ 3.45(t, 1H), 4.59(q, 1H), 4.76(t, 1H), 5.36(d, 1H), 7.42(d, 2H), 7.59(d, 2H), 7.78(dd, 1H), 7.85(dd, 1H), 8.10(d, 1H), 8.15(d, 1H), 8.30(s, 1H), 8.61(s, 1H). 1 H NMR (300 MHz, CDCl 3 ) δ 3.45 (t, 1H), 4.59 (q, 1H), 4.76 (t, 1H), 5.36 (d, 1H), 7.42 (d, 2H), 7.59 (d, 2H ), 7.78 (dd, 1H), 7.85 (dd, 1H), 8.10 (d, 1H), 8.15 (d, 1H), 8.30 (s, 1H), 8.61 (s, 1H).

실시예 106CExample 106C

7-메톡시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염7-methoxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 106B에서 수득된 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z (M+H)+331.The desired compound is prepared from the product obtained in Example 106B using the method described in Example 40D. MS (DCI / NH 3 ) m / z (M + H) + 331.

1H-NMR(300MHz, DMSO) δ 3.45(t, 1H), 4.59(q, 1H), 4.78(t, 1H), 5.38(d, 1H), 7.42(d, 2H), 7.59(d, 2H), 7.78(dd, 1H), 7.84(dd, 1H), 8.12(d, 1H), 8.18(d, 1H), 8.31(s, 1H), 8.50(s, 1H), 9.20(s, 2H), 9.43(s, 2H); 1 H-NMR (300 MHz, DMSO) δ 3.45 (t, 1H), 4.59 (q, 1H), 4.78 (t, 1H), 5.38 (d, 1H), 7.42 (d, 2H), 7.59 (d, 2H ), 7.78 (dd, 1H), 7.84 (dd, 1H), 8.12 (d, 1H), 8.18 (d, 1H), 8.31 (s, 1H), 8.50 (s, 1H), 9.20 (s, 2H) , 9.43 (s, 2 H);

C23H19F3N2O4·H2O에 대한 원소분석치: C 23 H 19 F 3 N 2 O 4 · H 2 O element for analysis:

계산치: C, 59.74; H, 4.58; N, 6.06.Calc .: C, 59.74; H, 4.58; N, 6.06.

실측치: C, 59.95; H, 4.17; N, 6.13.Found: C, 59.95; H, 4. 17; N, 6.13.

실시예 107Example 107

(E)-6-[2-[[4-(디메틸아미노)메틸]페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2-[[4- (dimethylamino) methyl] phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 107AExample 107A

실시예 121A에 기재된 방법을 사용하고 4-요오도아닐린을 3-벤질옥시브로모벤젠[Chem. Ber. 124(1), 163, 1991]로 대체하여 목적 화합물을 수득한다.Using the method described in Example 121A and using 4-iodoaniline to 3-benzyloxybromobenzene [Chem. Ber. 124 (1), 163, 1991 to afford the desired compound.

MS(DCI/NH3) m/z (M+NH4)+;MS (DCI / NH 3 ) m / z (M + NH 4 ) + ;

1H-NMR(300MHz, CDCl3) δ 5.11(s, 2H), 7.02(d, 1H), 7.20(m, 2H), 7.29(d, 1H), 7.31(d, 1H), 7.42(m, 3H), 7.60-7.75(m, 3H), 7.89(t, 2H), 8.08(s, 1H), 8.21(s, 1H). 1 H-NMR (300 MHz, CDCl 3 ) δ 5.11 (s, 2H), 7.02 (d, 1H), 7.20 (m, 2H), 7.29 (d, 1H), 7.31 (d, 1H), 7.42 (m, 3H), 7.60-7.75 (m, 3H), 7.89 (t, 2H), 8.08 (s, 1H), 8.21 (s, 1H).

실시예 107BExample 107B

(E)-6-[2-[[4-(디메틸아미노)메틸]페닐]에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2-[[4- (dimethylamino) methyl] phenyl] ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 108B에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(ESI) m/z 377(M+H)+;The desired compound is obtained from the product obtained in Example 108B using the method described in Example 40D. MS (ESI) m / z 377 (M + H) + ;

1H-NMR(300MHz, DMSO) δ 5.18(s, 2H), 7.12(dd, 1H), 7.22(d, 1H), 7.28(m, 1H), 7.40(t, 3H), 7.45(t, 3H), 7.79(dd, 1H), 7.85(dd, 1H), 8.16(d, 1H), 8.20(d, 1H), 8.35(s, 1H), 8.50(s, 1H), 9.30(s, 1H); 1 H-NMR (300 MHz, DMSO) δ 5.18 (s, 2H), 7.12 (dd, 1H), 7.22 (d, 1H), 7.28 (m, 1H), 7.40 (t, 3H), 7.45 (t, 3H ), 7.79 (dd, 1H), 7.85 (dd, 1H), 8.16 (d, 1H), 8.20 (d, 1H), 8.35 (s, 1H), 8.50 (s, 1H), 9.30 (s, 1H) ;

C28H21F3N2O3·0.25H2O에 대한 원소분석치:Elementary Analysis for C 28 H 21 F 3 N 2 O 3 · 0.25H 2 O:

계산치: C, 67.94; H, 4.38; N, 5.66.Calc .: C, 67.94; H, 4.38; N, 5.66.

실측치: C, 67.80; H, 4.48; N, 5.43.Found: C, 67.80; H, 4. 48; N, 5.43.

실시예 108Example 108

(E)-6-[2-[4-(하이드록시메틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염(E) -6- [2- [4- (hydroxymethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 94D에 기재된 방법을 사용하여 실시예 108A에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(ESI) m/z 287 (M+H)+;The desired compound is obtained from the product obtained in Example 108A using the method described in Example 94D. MS (ESI) m / z 287 (M + H) + ;

1H-NMR(300MHz, DMSO) δ 6.89(m, 1H), 6.98(t, 1H), 7.03(d, 1H), 7.29(t, 1H), 7.78(dd, 1H), 7.88(dd, 1H), 8.13(d, 1H), 8.17(d, 1H), 8.32(s, 1H), 8.50(s, 1H), 9.40(s, 5H); 1 H-NMR (300 MHz, DMSO) δ 6.89 (m, 1H), 6.98 (t, 1H), 7.03 (d, 1H), 7.29 (t, 1H), 7.78 (dd, 1H), 7.88 (dd, 1H ), 8.13 (d, 1H), 8.17 (d, 1H), 8.32 (s, 1H), 8.50 (s, 1H), 9.40 (s, 5H);

C21H15F3N2O3·0.5H2O에 대한 원소분석치: C 21 H 15 F 3 N 2 O 3 · Elemental analysis for 0.5H 2 O:

계산치: C, 61.62; H, 3.94; N, 6.84.Calc .: C, 61.62; H, 3.94; N, 6.84.

실측치: C, 61.29; H, 3.81; N, 6.59.Found: C, 61.29; H, 3.81; N, 6.59.

실시예 109Example 109

4-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-L-페닐알라닌, 모노(트리플루오로아세테이트) 염4-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -L-phenylalanine, mono (trifluoroacetate) salt

실시예 109AExample 109A

THF(5ml) 중의 실시예 8D로부터의 생성물(2.13g, 10.08mmol) 및 LiBH4(121mg, 5.55mmol)의 용액에 톨루엔(2ml)을 가하고, THF를 수 시간에 걸쳐 단거리 증류 장치를 사용하여 비등시킨다. 이어서, 반응물을 70℃에서 2시간 동안 가열하고, 냉각시키며, 1M HCl로 켄칭시키고, 2 x 에틸 아세테이트로 추출한다. 추출물을 물 및 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 생성물을 용출제로서 50% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 1.12g(61%) 수득한다. MS(DCI(NH3)) m/z 201(M+NH4)+;Toluene (2 ml) was added to a solution of the product from Example 8D (2.13 g, 10.08 mmol) and LiBH 4 (121 mg, 5.55 mmol) in THF (5 ml), and the THF was boiled using a short distance distillation apparatus over several hours. Let's do it. The reaction is then heated at 70 ° C. for 2 hours, cooled, quenched with 1M HCl and extracted with 2 × ethyl acetate. The extract is washed with water and brine, dried over Na 2 S0 4 and concentrated. The crude product is chromatographed on SiO 2 using 50% ethyl acetate / hexane as eluent to yield 1.12 g (61%) of the title compound. MS (DCI (NH 3 )) m / z 201 (M + NH 4 ) + ;

1H-NMR(300MHz, CDCl3) δ 8.22(s, 1H), 7.90(m, 3H), 7.61(m, 2H), 4.92(d, 2H), 1.84(t, 1H). 1 H-NMR (300 MHz, CDCl 3 ) δ 8.22 (s, 1H), 7.90 (m, 3H), 7.61 (m, 2H), 4.92 (d, 2H), 1.84 (t, 1H).

실시예 109BExample 109B

DMF(100ml) 중의 실시예 109A로부터의 생성물(2.12g, 11.57mmol) 및 LiBr(1.11g, 12.73mmol)의 용액에 0℃에서 PBr3(1.21ml, 12.73mmol)를 가하고, 반응물을 실온으로 가온시키며, 1시간 동안 교반한다. 이어서, 반응물을 pH 7 완충액으로 켄칭하고, 3x 디에틸 에테르/헥산으로 추출한다. 이 추출물을 2x 물 및 2x 염수로 세척하고, Na2SO4상에서 건조시킨 다음 농축시켜 목적 화합물을 2.72g(96%) 수득한다. MS(DCI/(NH3)) m/z 185 (M+NH4-Br)+;To a solution of product from Example 109A (2.12 g, 11.57 mmol) and LiBr (1.11 g, 12.73 mmol) in DMF (100 ml) was added PBr 3 (1.21 ml, 12.73 mmol) at 0 ° C. and the reaction was allowed to warm to room temperature. And stir for 1 hour. The reaction is then quenched with pH 7 buffer and extracted with 3x diethyl ether / hexanes. The extract is washed with 2x water and 2x brine, dried over Na 2 S0 4 and concentrated to give 2.72 g (96%) of the title compound. MS (DCI / (NH 3 )) m / z 185 (M + NH 4 -Br) + ;

1H-NMR(300MHz, CDCl3) δ 8.22(s, 1H), 7.92(s, 1H), 7.90(s, 2H), 7.62(dd, 2H), 4.64(s, 2H). 1 H-NMR (300 MHz, CDCl 3 ) δ 8.22 (s, 1H), 7.92 (s, 1H), 7.90 (s, 2H), 7.62 (dd, 2H), 4.64 (s, 2H).

실시예 109CExample 109C

DMF(5ml) 중의 NaH(광유 중의 60%, 44mg, 1.1mmol)의 용액에 4-에틸페놀(122mg, 1.0mmol)을 가하고, 반응물을 실온에서 20분 동안 교반한다. 이어서, 실시예 109B로부터의 생성물(270mg, 1.1mmol)을 가하고, 반응물을 10분 동안 교반한다. 조 반응 혼합물을 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 220mg(77%) 수득한다. MS(DCI(NH3)) m/z 305(M+NH4)+;To a solution of NaH (60% in mineral oil, 44 mg, 1.1 mmol) in DMF (5 ml) is added 4-ethylphenol (122 mg, 1.0 mmol) and the reaction is stirred at room temperature for 20 minutes. The product from Example 109B (270 mg, 1.1 mmol) is then added and the reaction stirred for 10 minutes. The crude reaction mixture is chromatographed on SiO 2 using hexane as eluent to give 220 mg (77%) of the title compound. MS (DCI (NH 3 )) m / z 305 (M + NH 4 ) + ;

1H-NMR(300MHz, CDCl3) δ 8.22(s, 1H), 7.95(s, 1H), 7.93(s, 1H), 7.91(s, 1H), 7.66(dd, 1H), 7.61(dd, 1H), 7.15(d, 2H), 6.94(d, 2H), 5.22(d, 2H), 2.60(q, 2H), 1.21(t, 3H). 1 H-NMR (300 MHz, CDCl 3 ) δ 8.22 (s, 1H), 7.95 (s, 1H), 7.93 (s, 1H), 7.91 (s, 1H), 7.66 (dd, 1H), 7.61 (dd, 1H), 7.15 (d, 2H), 6.94 (d, 2H), 5.22 (d, 2H), 2.60 (q, 2H), 1.21 (t, 3H).

실시예 109DExample 109D

4-[[6-(2-아미노이미노메틸)-2-나프탈레닐]에티닐]-L-페닐알라닌, 모노(트리플루오로아세테이트) 염4-[[6- (2-aminoiminomethyl) -2-naphthalenyl] ethynyl] -L-phenylalanine, mono (trifluoroacetate) salt

실시예 55D에 기재된 방법을 사용하여 실시예 109C에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z 305(M+H)+;The desired compound is obtained from the product obtained in Example 109C using the method described in Example 55D. MS (DCI / NH 3 ) m / z 305 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 1.15(t, 3H), 2.14(s, 3H), 2.56(q, 2H), 5.30(s, 2H), 6.98(d, 2H), 7.14(d, 2H), 7.74(dd, 1H), 7.82(dd, 1H), 8.15(m, 3H), 8.48(s, 1H), 9.01(br s, 2H), 9.62(br s, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.15 (t, 3H), 2.14 (s, 3H), 2.56 (q, 2H), 5.30 (s, 2H), 6.98 (d, 2H), 7.14 ( d, 2H), 7.74 (dd, 1H), 7.82 (dd, 1H), 8.15 (m, 3H), 8.48 (s, 1H), 9.01 (br s, 2H), 9.62 (br s, 2H);

C20H20N2O·1.4CH4SO3에 대한 원소분석치:Elemental Analysis for C 20 H 20 N 2 O · 1.4CH 4 SO 3 :

계산치: C, 58.56; H, 5.88; N, 6.38.Calc .: C, 58.56; H, 5.88; N, 6.38.

실측치: C, 58.55; H, 5.56; N, 6.39.Found: C, 58.55; H, 5.56; N, 6.39.

실시예 111Example 111

6-(3-포밀페닐)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (3-formylphenyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 111AExample 111A

실시예 28B로부터의 생성물(334mg, 1.11mmol), 팔라듐 아세테이트(25mg, 0.11mmol), dppf(123mg, 0.22mmol)을 탈기 DMF(5ml)에 용해시키고 실온에서 1/2시간 동안 교반한다. 탄산세슘(902mg, 2.8mmol) 및 2-포밀페닐보론산(251mg, 1.27mmol)을 가하고, 질소 하에 80℃에서 1시간 동안 교반하며, pH 7 완충액에 붓고, 디에틸 에테르(3 x 20ml)로 추출한 다음 건조시킨다. 10% 에틸 아세테이트/헥산으로 용출시키면서 목적 화합물을 크로마토그래피하여 정제한다. MS(DCI/NH3) m/z (M+NH3)+275.The product from Example 28B (334 mg, 1.11 mmol), palladium acetate (25 mg, 0.11 mmol), dppf (123 mg, 0.22 mmol) is dissolved in degassing DMF (5 ml) and stirred at room temperature for 1/2 hour. Cesium carbonate (902 mg, 2.8 mmol) and 2-formylphenylboronic acid (251 mg, 1.27 mmol) are added, stirred at 80 ° C. under nitrogen for 1 hour, poured into pH 7 buffer, and diethyl ether (3 × 20 ml). Extract and dry. The desired compound is purified by chromatography eluting with 10% ethyl acetate / hexanes. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 275.

실시예 111BExample 111B

6-(3-포밀페닐)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (3-formylphenyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 1B와 유사한 방법으로 상기 생성물을 수득한다.The product is obtained in a similar manner to Example 1B.

MS(DCI/NH3) m/z (M+H)+274;MS (DCI / NH 3 ) m / z (M + H) + 274;

1H-NMR(300MHz, DMSO-d6)δ10.16(s, 1H), 9.47(s, 2H), 9.10(s, 2H), 8.54(s, 1H), 8.52(s, 1H), 8.41(s, 1H), 8.28-8.23(m, 3H), 8.12(dd, 1H), 8.00(dd, 1H), 7.87(dd, 1H), 7.80(t, 1H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ10.16 (s, 1H), 9.47 (s, 2H), 9.10 (s, 2H), 8.54 (s, 1H), 8.52 (s, 1H), 8.41 (s, 1H), 8.28-8.23 (m, 3H), 8.12 (dd, 1H), 8.00 (dd, 1H), 7.87 (dd, 1H), 7.80 (t, 1H);

C20H15N2O3F32/5 TFA에 대한 원소분석치:Elemental Analysis for C 20 H 15 N 2 O 3 F 3 2/5 TFA:

계산치: C, 59.28; H, 3.70; N, 6.34.Calc .: C, 59.28; H, 3. 70; N, 6.34.

실측치: C, 59.36; H, 3.89; N, 7.21.Found: C, 59.36; H, 3.89; N, 7.21.

실시예 112Example 112

(E)-6-[2-(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2- (1,2,3,4-tetrahydro-6-isoquinolinyl) ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 112AExample 112A

실시예 41A에 기재된 방법을 사용하여 실시예 127에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z (M+H)+411.The desired compound is obtained from the product obtained in Example 127 using the method described in Example 41A. MS (DCI / NH 3 ) m / z (M + H) + 411.

실시예 112BExample 112B

(E)-6-[2-(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에테닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염(E) -6- [2- (1,2,3,4-tetrahydro-6-isoquinolinyl) ethenyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 목적 화합물을 수득한다.The desired compound is obtained using the method described in Example 40D.

MS(DCI/NH3) m/z (M+H)+328;MS (DCI / NH 3 ) m / z (M + H) + 328;

1H-NMR(300MHz, DMSO-d6) δ 9.36(s, 2H), 9.25(s, 2H), 9.10(d, 2H), 8.41(s, 1H), 7.99(t, 2H), 7.89(d, 1H), 7.78(d, 1H). 7.71(dd, 1H), 7.56(m, 4H), 7.43(s, 1H), 3.11(br, 2H) 2.16(br 2H), 1.78(br, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.36 (s, 2H), 9.25 (s, 2H), 9.10 (d, 2H), 8.41 (s, 1H), 7.99 (t, 2H), 7.89 ( d, 1 H), 7.78 (d, 1 H). 7.71 (dd, 1H), 7.56 (m, 4H), 7.43 (s, 1H), 3.11 (br, 2H) 2.16 (br 2H), 1.78 (br, 2H);

C26H23N3O4F43/5 TFA에 대한 원소분석치:Elemental Analysis for C 26 H 23 N 3 O 4 F 4 3/5 TFA:

계산치: C, 52.31; H, 3.81; N, 6.72.Calc .: C, 52.31; H, 3.81; N, 6.72.

실측치: C, 52.13; H, 4.42; N, 7.23.Found: C, 52.13; H, 4. 42; N, 7.23.

실시예 113Example 113

(E)-6-[2-[3-(2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염(E) -6- [2- [3- (2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 113AExample 113A

실시예 41A에 기재된 방법을 사용하여 실시예 98A에서 수득된 화합물 및 2-브로모-3-(하이드록시에틸)알콜로부터 상기 화합물을 수득한다. MS(DCI/NH3) m/z (M+NH3)+317.The compound is obtained from the compound obtained in Example 98A and 2-bromo-3- (hydroxyethyl) alcohol using the method described in Example 41A. MS (DCI / NH 3 ) m / z (M + NH 3 ) + 317.

실시예 113BExample 113B

(E)-6-[2-[3-(2-하이드록시에틸)페닐]에테닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염(E) -6- [2- [3- (2-hydroxyethyl) phenyl] ethenyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 40D에 기재된 방법을 사용하여 실시예 113A에서 수득된 생성물로부터 상기 화합물을 수득한다. MS(DCI/NH3) m/z (M+H)+317;The compound is obtained from the product obtained in Example 113A using the method described in Example 40D. MS (DCI / NH 3 ) m / z (M + H) + 317;

1H-NMR(300MHz, DMSO-d6) δ 8.9(br, 4H), 8.46(s, 1H), 8.17(s, 1H), 8.13-8.03(m, 3H), 7.82(dd, 1H), 7.54(s, 2H), 7.49(s, 2H), 7.33(t, 1H) 7.18(d, 1H), 4.71(t, 1H), 3.66(m, 2H), 2.78(t, 2H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 8.9 (br, 4H), 8.46 (s, 1H), 8.17 (s, 1H), 8.13-8.03 (m, 3H), 7.82 (dd, 1H), 7.54 (s, 2H), 7.49 (s, 2H), 7.33 (t, 1H) 7.18 (d, 1H), 4.71 (t, 1H), 3.66 (m, 2H), 2.78 (t, 2H);

C23H21N2O3F33/10 TFA에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 2 O 3 F 3 3/10 TFA:

계산치: C, 61.41; H, 4.66; N, 6.09.Calc .: C, 61.41; H, 4. 66; N, 6.09.

실측치: C, 64.18; H, 4.92; N, 6.51.Found: C, 64.18; H, 4.92; N, 6.51.

실시예 114Example 114

6-(아미노이미노메틸)-4-(3-푸라닐)-N-[4-(트리플루오로메틸)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -4- (3-furanyl) -N- [4- (trifluoromethyl) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 114AExample 114A

실시예 152B로부터의 생성물(100mg, 0.36mmol), 4-(트리플루오로메틸)아닐린(86mg, 0.53mmol) 및 DMAP(5mg, 0.04mmol)을 THF(5ml)에 용해시키고 24시간 동안 교반한다. 반응 혼합물을 실리카 겔 상에서 농축시키고 에틸 아세테이트/헥산을 사용하여 크로마토그래피(Biotage Flash 40)하여 정제한다. MS(ESI) m/z (M+H)+406.The product from Example 152B (100 mg, 0.36 mmol), 4- (trifluoromethyl) aniline (86 mg, 0.53 mmol) and DMAP (5 mg, 0.04 mmol) are dissolved in THF (5 ml) and stirred for 24 hours. The reaction mixture is concentrated on silica gel and purified by chromatography using ethyl acetate / hexanes (Biotage Flash 40). MS (ESI) m / z (M + H) + 406.

실시예 114BExample 114B

6-(아미노이미노메틸)-4-(3-푸라닐)-N-[4-(트리플루오로메틸)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -4- (3-furanyl) -N- [4- (trifluoromethyl) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 방법을 사용하여 실시예 114A에서 수득된 생성물로부터 상기 화합물을 수득한다. MS(CI) m/z (M+H)+424;The compound is obtained from the product obtained in Example 114A using the method described in Example 1B. MS (CI) m / z (M + H) + 424;

1H-NMR(300MHz, DMSO-d6) δ 10.91(s, 1H), 9.51(s, 2H), 9.11(s, 2H), 8.69(s, 1H), 8.62(s, 1H), 8.43-8.35(m, 2H), 8.18(d, 1H), 8.06(d, 2H), 7.98(t, 1H), 7.92(dd, 1H), 7.78(dd, 2H) 7.14(m, 1H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.91 (s, 1H), 9.51 (s, 2H), 9.11 (s, 2H), 8.69 (s, 1H), 8.62 (s, 1H), 8.43- 8.35 (m, 2H), 8.18 (d, 1H), 8.06 (d, 2H), 7.98 (t, 1H), 7.92 (dd, 1H), 7.78 (dd, 2H) 7.14 (m, 1H);

C25H17N3O4F61/10 TFA에 대한 원소분석치:Elemental Analysis for C 25 H 17 N 3 O 4 F 6 1/10 TFA:

계산치: C, 55.37; H, 3.15; N, 7.70.Calc .: C, 55.37; H, 3. 15; N, 7.70.

실측치: C, 55.44; H, 3.15; N, 7.31.Found: C, 55.44; H, 3. 15; N, 7.31.

실시예 115Example 115

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(4-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (4-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 115AExample 115A

실시예 114A의 방식으로 상기 생성물을 수득한다. MS(ESI) m/z (M+H)+340.This product is obtained in the manner of Example 114A. MS (ESI) m / z (M + H) + 340.

실시예 115BExample 115B

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(4-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (4-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 1B에 기재된 방법을 사용하여 실시예 115A에서 수득된 생성물로부터 상기 화합물을 수득한다. MS(AP/CI) m/z (M+H)+357;The compound is obtained from the product obtained in Example 115A using the method described in Example 1B. MS (AP / CI) m / z (M + H) + 357;

1H-NMR(300MHz, DMSO-d6) δ 12.43(s, 1H), 9.69(s, 2H), 9.40(s, 2H), 8.94(s, 1H), 8.81(d, 2H), 8.65(s, 1H), 8.58-8.56(m, 2H), 8.49(s, 1H), 8.42(d, 1H), 8.30(m, 1H) 7.97-7.95(m, 2H), 7.27(s, 1H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 12.43 (s, 1H), 9.69 (s, 2H), 9.40 (s, 2H), 8.94 (s, 1H), 8.81 (d, 2H), 8.65 ( s, 1H), 8.58-8.56 (m, 2H), 8.49 (s, 1H), 8.42 (d, 1H), 8.30 (m, 1H) 7.97-7.95 (m, 2H), 7.27 (s, 1H);

C21H18N4O2Cl237/10 HCl에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 4 O 2 Cl 2 37/10 HCl:

계산치: C, 44.65; H, 3.88; N, 9.92.Calc .: C, 44.65; H, 3.88; N, 9.92.

실측치: C, 44.72; H, 3.70; N, 9.51.Found: C, 44.72; H, 3. 70; N, 9.51.

실시예 116Example 116

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, dihydrochloride

실시예 116AExample 116A

실시예 114A의 방식으로 상기 생성물을 수득한다. MS(ESI) m/z (M+H)+329.This product is obtained in the manner of Example 114A. MS (ESI) m / z (M + H) + 329.

실시예 116BExample 116B

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, dihydrochloride

실시예 1B에 기재된 방법을 사용하여 실시예 116A에서 수득된 생성물로부터 상기 화합물을 수득한다. MS(CI) m/z (M-H)+344;The compound is obtained from the product obtained in Example 116A using the method described in Example 1B. MS (CI) m / z (MH) + 344;

1H-NMR(300MHz, DMSO-d6) δ 11.16(s, 1H), 9.52(s, 2H), 9.10(s, 2H), 8.69(s, 1H), 8.61(s, 1H), 8.35(m, 2H), 8.24(s, 1H), 7.96-7.88(m, 3H), 7.69(m, 1H), 7.15(s, 1H), 6.69(m, 1H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 11.16 (s, 1H), 9.52 (s, 2H), 9.10 (s, 2H), 8.69 (s, 1H), 8.61 (s, 1H), 8.35 ( m, 2H), 8.24 (s, 1H), 7.96-7.88 (m, 3H), 7.69 (m, 1H), 7.15 (s, 1H), 6.69 (m, 1H);

C19H17N5O2Cl29/10 HCl에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 5 O 2 Cl 2 9/10 HCl:

계산치: C, 50.63; H, 4.00; N, 15.54.Calc .: C, 50.63; H, 4.00; N, 15.54.

실측치: C, 51.05; H, 4.62; N, 14.26.Found: C, 51.05; H, 4. 62; N, 14.26.

실시예 117Example 117

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(3-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (3-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 117AExample 117A

실시예 114A의 방식으로 상기 생성물을 제조한다. MS(ESI) m/z (M+H)+340.The product is prepared in the manner of Example 114A. MS (ESI) m / z (M + H) + 340.

실시예 117BExample 117B

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(3-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (3-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 1B에 기재된 방법을 사용하여 실시예 117B에서 수득된 생성물로부터 상기 화합물을 수득한다. MS(CI) m/z (M+H)+357;The compound is obtained from the product obtained in Example 117B using the method described in Example 1B. MS (CI) m / z (M + H) + 357;

1H-NMR(300MHz, DMSO-d6) δ 10.90(s, 1H), 9.59(s, 2H), 9.26(s, 2H), 9.03(s, 2H), 8.74(s, 1H). 8.63(s, 1H), 8.42-8.26(m, 3H), 8.22(s, 1H), 7.97-7.91(m, 2H), 7.47-7.43(m, 2H), 7.17(s, 1H); 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.90 (s, 1H), 9.59 (s, 2H), 9.26 (s, 2H), 9.03 (s, 2H), 8.74 (s, 1H). 8.63 (s, 1H), 8.42-8.26 (m, 3H), 8.22 (s, 1H), 7.97-7.91 (m, 2H), 7.47-7.43 (m, 2H), 7.17 (s, 1H);

C21H18N4O2Cl255/10 HCl에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 4 O 2 Cl 2 55/10 HCl:

계산치: C, 40.00; H, 3.76; N, 8.89.Calc .: C, 40.00; H, 3.76; N, 8.89.

실측치: C, 40.09; H, 3.78; N, 8.44.Found: C, 40.09; H, 3.78; N, 8.44.

실시예 118Example 118

6-(아미노이미노메틸)-N-(2,3-디하이드로-1H-인덴-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트)염6- (aminoiminomethyl) -N- (2,3-dihydro-1H-inden-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 118AExample 118A

THF(30ml) 및 프로필렌 옥사이드(15ml) 중의 실시예 8E에서 제조된 화합물(303mg, 1.4mmol)의 용액에 Et3N을 두 방울 적가한 다음 5-아미노인덴(300mg, 2.2mmol)을 적가한다. 반응물을 실온에서 밤새 교반한다. 용매를 증발시키고, 생성물을 에테르로 결정화함으로써 정제하여 백색 고체로서의 생성물을 226mg(56%0 수득한다. 질량 스펙트럼 (CI+), 313(M+1)+.To a solution of the compound (303 mg, 1.4 mmol) prepared in Example 8E in THF (30 ml) and propylene oxide (15 ml) were added dropwise two drops of Et 3 N followed by dropwise addition of 5-aminoindene (300 mg, 2.2 mmol). . The reaction is stirred overnight at room temperature. The solvent was evaporated and the product was purified by crystallization with ether to give 226 mg (56% 0) of the product as a white solid. Mass spectrum (CI +), 313 (M + 1) + .

실시예 118BExample 118B

6-(아미노이미노메틸)-N-(2,3-디하이드로-1H-인덴-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트)염6- (aminoiminomethyl) -N- (2,3-dihydro-1H-inden-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실온에서 THF(20ml) 중의 실시예 118A(205mg, 0.66mmol)에서 제조된 화합물을 부틸리튬(1ml, 1mmol)에 가한 다음 클로로트리메틸 실란(180㎕, 1.5mmol)에 가한다. 10분 후, 이 혼합물에 부틸리튬(3ml, 3mmol)을 더 가한다. 반응물을 실온에서 밤새 교반한다. 반응 혼합물을 디옥산 중의 4N HCl의 용액에 가하고 1시간 동안 교반한 다음 물을 가한 후, 증발시킨다. 생성물을 용출제 크로마토그래피로서 메탄올-물 및 0.1% TFA를 이용하여 MPLC RT C18에 의해 정제한다. 백색 고체로서, 0.25% 물을 함유하는 TFA 염으로서의 생성물의 수율은 51mg(17%)이다.Compounds prepared in Example 118A (205 mg, 0.66 mmol) in THF (20 ml) at room temperature are added to butyllithium (1 ml, 1 mmol) followed by chlorotrimethyl silane (180 μl, 1.5 mmol). After 10 minutes, further butyllithium (3 ml, 3 mmol) is added to this mixture. The reaction is stirred overnight at room temperature. The reaction mixture is added to a solution of 4N HCl in dioxane and stirred for 1 hour and then water is added and then evaporated. The product is purified by MPLC RT C 18 using methanol-water and 0.1% TFA as eluent chromatography. As a white solid, the yield of the product as a TFA salt containing 0.25% water is 51 mg (17%).

MS(ESI+) 330(M+1)+;MS (ESI < + >) 330 (M + 1) + ;

1H NMR(DMSO-d6) 10.45(s, 1H), 9.51(s, 2H), 9.21(s, 2H), 8.66(s, 1H), 8.55(s, 1H), 8.32(d, J=8.5Hz, 1H), 8.20(Abq, J=9.0Hz, 2H), 7.90(dd, J1=9.0Hz, J2=1.5Hz, 1H), 7.73(s, 1H), 7.53(dd, J1=8.0Hz, J2=1.5Hz, 1H), 7.22(d, J=8.1Hz, 1H), 2.91-2.82(m, 4H), 2.04(5중선, J=7.3Hz, 2H); 1 H NMR (DMSO-d 6 ) 10.45 (s, 1H), 9.51 (s, 2H), 9.21 (s, 2H), 8.66 (s, 1H), 8.55 (s, 1H), 8.32 (d, J = 8.5 Hz, 1H), 8.20 (Abq, J = 9.0 Hz, 2H), 7.90 (dd, J 1 = 9.0 Hz, J 2 = 1.5 Hz, 1H), 7.73 (s, 1H), 7.53 (dd, J 1 = 8.0 Hz, J 2 = 1.5 Hz, 1H), 7.22 (d, J = 8.1 Hz, 1H), 2.91-2.82 (m, 4H), 2.04 (quintet, J = 7.3 Hz, 2H);

C21H19N3O·TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 21 H 19 N 3 O · TFA · 0.25H 2 O:

계산치: C, 61.67; H, 4.61; N, 9.38.Calc .: C, 61.67; H, 4.61; N, 9.38.

실측치: C, 61.63, H, 4.43; N, 9.25.Found: C, 61.63, H, 4.43; N, 9.25.

실시예 119Example 119

메틸 5-[7-[(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노에이트, 모노(트리플루오로아세테이트) 염Methyl 5- [7-[(aminoiminomethyl) -2-naphthalenyl] oxy] pentanoate, mono (trifluoroacetate) salt

실시예 119AExample 119A

7-하이드록시-2-시아노나프탈렌7-hydroxy-2-cyanonaphthalene

7-메톡시-2-시아노나프탈렌(2.79g, 5.23mmol) 및 테트라부틸암모늄 요오다이드(17mg, 0.157mmol)를 벤젠(35ml)과 사이클록헥산(17.5ml)의 혼합물에서 합한다. 생성된 용액을 신속하게 교반하면서 불활성 대기하에서 벤젠(35ml)과 사이클로헥산(17.5ml)의 혼합물 중의 알루미늄 트리요오다이드(6.21g, 15.23mmol)의 냉각된(얼음/물) 현탁액에 가한다. 첨가 후, 생성된 현탁액을 환류하에 2.5시간동안 가열한다. 가열물을 제거하고 거의 실온으로 냉각시킨 후, 반응 혼합물을 얼음 욕 속에서 냉각시키고, 물(100ml)을 가하여 켄칭시킨다. 생성된 혼합물을 2M 수성 나트륨 티오설페이트 용액(50ml)으로 추가로 희석시키고 에틸 아세테이트(3 x 80ml)로 추출한다. 합한 유기 층을 건조시키고 증발시킨다. 생성된 고체를 최소량의 뜨거운 에틸 아세테이트에 용해시키고, 헥산을 이용하여 운점까지 뜨겁게 희석시킨 다음 냉동기에 2시간 동안 놓아둔다. 여과시켜 목적 화합물을 수집한다(1.99g, 77%). MS(DCI/NH3) m/z 187(M+NH4)+.7-methoxy-2-cyanonaphthalene (2.79 g, 5.23 mmol) and tetrabutylammonium iodide (17 mg, 0.157 mmol) are combined in a mixture of benzene (35 ml) and cyclohexane (17.5 ml). The resulting solution is added to a cooled (ice / water) suspension of aluminum triiodide (6.21 g, 15.23 mmol) in a mixture of benzene (35 ml) and cyclohexane (17.5 ml) under inert atmosphere with rapid stirring. After addition, the resulting suspension is heated at reflux for 2.5 h. After heating is removed and cooled to near room temperature, the reaction mixture is cooled in an ice bath and quenched by addition of water (100 ml). The resulting mixture is further diluted with 2M aqueous sodium thiosulfate solution (50 ml) and extracted with ethyl acetate (3 × 80 ml). The combined organic layers are dried and evaporated. The resulting solid is dissolved in a minimum amount of hot ethyl acetate, hot dilute to cloud point with hexane and left in the freezer for 2 hours. Filtration collects target compound (1.99 g, 77%). MS (DCI / NH 3 ) m / z 187 (M + NH 4 ) + .

실시예 119BExample 119B

실시예 119A로부터의 생성물을 실시예 119A에 기재된 바와 유사한 방식으로 메틸 5-브로모발레레이트로 처리한다. MS(DCI/NH3) m/z 301(M+NH4)+.The product from Example 119A is treated with methyl 5-bromovalerate in a similar manner as described in Example 119A. MS (DCI / NH 3 ) m / z 301 (M + NH 4 ) + .

실시예 119CExample 119C

메틸 5-[7-[(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노에이트, 모노(트리플루오로아세테이트) 염Methyl 5- [7-[(aminoiminomethyl) -2-naphthalenyl] oxy] pentanoate, mono (trifluoroacetate) salt

실시예 119B로부터의 생성물(380mg, 1.3412mmol)을 실시예 94D에 기재된 바와 유사한 방식으로 처리하여 목적 화합물(369mg, 73%)을 수득한다.The product from Example 119B (380 mg, 1.3412 mmol) was treated in a similar manner as described in Example 94D to afford the desired compound (369 mg, 73%).

MS(DCI(NH3)) m/z 301(M+H)+;MS (DCI (NH 3 )) m / z 301 (M + H) + ;

1H NMR(300MHz, DMSO-d6) δ 1.785(m, 4H), 2.425(t, 2H), 3.600(s, 3H), 4.150(t, 2H), 7.380(dd, 1H), 7.460(d, 1H), 7.640(dd, 1H), 7.980(d, 1H), 8.070(d, 1H), 8.322(d, 1H), 9.230(v br s, 3H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.785 (m, 4H), 2.425 (t, 2H), 3.600 (s, 3H), 4.150 (t, 2H), 7.380 (dd, 1H), 7.460 (d , 1H), 7.640 (dd, 1H), 7.980 (d, 1H), 8.070 (d, 1H), 8.322 (d, 1H), 9.230 (v br s, 3H);

C17H20N2O3·C2HO2F3에 대한 원소분석치:Elemental analysis for C 17 H 20 N 2 O 3 · C 2 HO 2 F 3:

계산치: C, 55.07; H, 5.11; N, 6.76.Calc .: C, 55.07; H, 5.11; N, 6.76.

실측치: C, 54.96; H, 5.22; N, 6.66.Found: C, 54.96; H, 5. 22; N, 6.66.

실시예 120Example 120

(E)-3-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)-2-프로펜아미드, 모노(트리플루오로아세테이트) 염(E) -3- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) -2-propenamide, mono (trifluoroacetate) salt

실시예 120AExample 120A

실시예 53B로부터 수득된 생성물 및 아크릴아미드를 실시예 41A에 기재된 조건에 적용시켜 목적 화합물을 수득한다. MS(DCI/NH3) m/z 253(M+H)+.The product obtained from Example 53B and acrylamide were subjected to the conditions described in Example 41A to afford the desired compound. MS (DCI / NH 3 ) m / z 253 (M + H) + .

실시예 120BExample 120B

(E)-3-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)-2-프로펜아미드, 모노(트리플루오로아세테이트) 염(E) -3- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) -2-propenamide, mono (trifluoroacetate) salt

실시예 120A로부터 수득된 생성물을 실시예 94D에 기재된 조건에 적용시켜 목적 화합물을 수득한다.The product obtained from Example 120A was subjected to the conditions described in Example 94D to afford the desired compound.

1H NMR(300MHz, DMSO) δ 4.02(s, 3H), 6.90(d, 1H), 7.22(s, 1H), 7.62-7.70(m, 2H), 7.74(d, 1H), 8.02(d, 1H), 8.11(d, 1H), 8.15(d, 1H), 8.58(s, 1H), 9.18(s, 2H), 9.50(s, 2H); 1 H NMR (300 MHz, DMSO) δ 4.02 (s, 3H), 6.90 (d, 1H), 7.22 (s, 1H), 7.62-7.70 (m, 2H), 7.74 (d, 1H), 8.02 (d, 1H), 8.11 (d, 1H), 8.15 (d, 1H), 8.58 (s, 1H), 9.18 (s, 2H), 9.50 (s, 2H);

MS(DCI/NH3) m/z 270(M+H)+;MS (DCI / NH 3 ) m / z 270 (M + H) + ;

C17H16F3N3O4·H2O에 대한 원소분석치: C 17 H 16 F 3 N 3 O 4 · Elemental analysis for H 2 O:

계산치: C, 50.88; H, 4.52; N, 10.47.Calc .: C, 50.88; H, 4.52; N, 10.47.

실측치: C, 50.89; H, 4.32; N, 10.43.Found: C, 50.89; H, 4. 32; N, 10.43.

실시예 121Example 121

6-[(4-아미노페닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[(4-aminophenyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 121AExample 121A

실시예 63B에서 수득된 생성물(130mg, 0.73mmol), 4-요오도아닐린(173mg, 0.79mmol), 디클로로비스(트리페닐포스핀)팔라듐(Ⅱ)(25mg, 0.0325mmol), 요오드화구리(Ⅰ)(2.7mg, 0.0186mmol), DMF(0.65ml) 및 트리에틸아민(1.95ml)의 혼합물을 N2로 탈기시키고 75 내지 80℃에서 1.5시간 동안 교반한다. 이 혼합물을 실온으로 냉각시키고, CH2Cl2로 희석시키며, 물로 세척하고, 건조시키며(MgSO4), 여과하고 진공하에 증발시켜 오일을 수득하고, 이를 3:1 헥산:에틸 아세테이트로 용출시키면서 플래쉬 크로마토그래피로 정제하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 269(M+H)+.Product obtained in Example 63B (130 mg, 0.73 mmol), 4-iodoaniline (173 mg, 0.79 mmol), dichlorobis (triphenylphosphine) palladium (II) (25 mg, 0.0325 mmol), copper iodide (I) (2.7 mg, 0.0186 mmol), a mixture of DMF (0.65 ml) and triethylamine (1.95 ml) are degassed with N 2 and stirred at 75-80 ° C. for 1.5 h. The mixture is cooled to room temperature, diluted with CH 2 Cl 2 , washed with water, dried (MgSO 4 ), filtered and evaporated in vacuo to give an oil which is flashed while eluting with 3: 1 hexanes: ethyl acetate. Purification by chromatography affords the desired compound. MS (DCI / NH 3 ) m / z 269 (M + H) + .

실시예 121BExample 121B

6-[(4-아미노페닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[(4-aminophenyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 121A에서 수득된 생성물을 사용하고 실시예 40D에 기재된 과정에 따라서 목적 화합물을 수득한다.The desired compound is obtained following the procedure described in Example 40D using the product obtained in Example 121A.

MS(DCI/NH3) m/z 286(M+H)+;MS (DCI / NH 3 ) m / z 286 (M + H) + ;

1H NMR(300MHz, DMSO) δ 6.80(d, 2H), 7.29(d, 2H), 7.70(dd, 1H), 7.85(dd, 1H), 8.09(d, 1H), 8.14(d, 1H), 8.20(s, 1H), 8.45(s, 1H), 9.09(s, 2H), 9.42(s, 2H); 1 H NMR (300 MHz, DMSO) δ 6.80 (d, 2H), 7.29 (d, 2H), 7.70 (dd, 1H), 7.85 (dd, 1H), 8.09 (d, 1H), 8.14 (d, 1H) , 8.20 (s, 1 H), 8.45 (s, 1 H), 9.09 (s, 2H), 9.42 (s, 2H);

C23H17F6N3O4·0.25H2O에 대한 원소분석치:Elemental Analysis for C 23 H 17 F 6 N 3 O 4 · 0.25H 2 O:

계산치: C, 53.34; H, 3.41; N, 8.11.Calc .: C, 53.34; H, 3.41; N, 8.11.

실측치: C. 53.45; H, 3.70; N, 7.76.Found: C. 53.45; H, 3. 70; N, 7.76.

실시예 122Example 122

1,1-디메틸에틸 [2-[3-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-6-메톡시페닐]에틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [2- [3-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -6-methoxyphenyl] ethyl] carbamate, mono (trifluoroacetate) salt

실시예 122AExample 122A

실시예 63C에 기재된 과정에 따라서, 5-브로모-2-메톡시펜에틸아민 하이드로브로마이드(Transworld)를 사용하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 330 (M+H)+.Following the procedure described in Example 63C, 5-bromo-2-methoxyphenethylamine hydrobromide (Transworld) is used to obtain the desired compound. MS (DCI / NH 3 ) m / z 330 (M + H) + .

실시예 122BExample 122B

실시예 121A에 기재된 과정을 사용하고 4-요오도아닐린을 실시예 122A에 수득된 생성물로 대체하여 목적 화합물을 수득한다. MS(ESI) m/z 427(M+H)+.Using the procedure described in Example 121A and replacing the 4-iodoaniline with the product obtained in Example 122A, the desired compound is obtained. MS (ESI) m / z 427 (M + H) + .

실시예 122CExample 122C

1,1-디메틸에틸 [2-[3-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]-6-메톡시페닐]에틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [2- [3-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] -6-methoxyphenyl] ethyl] carbamate, mono (trifluoroacetate) salt

실시예 40D에 기재된 과정에 따라서 실시예 A-226638-B에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example A-226638-B was used following the procedure described in Example 40D to afford the desired compound.

MS(DCI/NH3) m/z 444(M+H)+;MS (DCI / NH 3 ) m / z 444 (M + H) + ;

1H NMR(300MHz, DMSO) δ 1.38(s, 9H), 2.70(t, 2H), 3.15(q, 2H), 3.85(s, 3H), 6.89(t, 1H), 7.04(d, 1H), 7.37(d, 1H), 7.49(dd, 1H). 7.75(dd, 1H), 7.85(dd, 1H), 8.11(d, 1H), 8.16(d, 1H), 8.30(s, 1H), 8.48(s, 1H), 9.07(s, 2H), 9.42(s, 2H); 1 H NMR (300 MHz, DMSO) δ 1.38 (s, 9H), 2.70 (t, 2H), 3.15 (q, 2H), 3.85 (s, 3H), 6.89 (t, 1H), 7.04 (d, 1H) , 7.37 (d, 1 H), 7.49 (dd, 1 H). 7.75 (dd, 1H), 7.85 (dd, 1H), 8.11 (d, 1H), 8.16 (d, 1H), 8.30 (s, 1H), 8.48 (s, 1H), 9.07 (s, 2H), 9.42 (s, 2H);

C29H30F3N3O5·0.25H2O에 대한 원소분석치:Elemental Analysis for C 29 H 30 F 3 N 3 O 5 · 0.25H 2 O:

계산치: C, 61.97; H, 5.47; N, 7.48.Calc .: C, 61.97; H, 5.47; N, 7.48.

실측치: C. 61.81; H, 5.14; N, 7.21.Found: C. 61.81; H, 5. 14; N, 7.21.

실시예 123Example 123

1,1-디메틸에틸 [[4-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] phenyl] methyl] carbamate, mono (trifluoroacetate) salt

실시예 123AExample 123A

실시예 63C에 기재된 과정에 따라서 4-브로모벤질아민을 사용하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 303(M+NH4)+.4-bromobenzylamine is used following the procedure described in Example 63C to afford the desired compound. MS (DCI / NH 3 ) m / z 303 (M + NH 4 ) + .

실시예 123BExample 123B

실시예 121A에 기재된 과정을 사용하고 4-요오도아닐린을 실시예 123에 수득된 생성물로 대체하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 400(M+NH4)+.Using the procedure described in Example 121A and replacing the 4-iodoaniline with the product obtained in Example 123, the desired compound is obtained. MS (DCI / NH 3 ) m / z 400 (M + NH 4 ) + .

실시예 123CExample 123C

1,1-디메틸에틸 [[4-[[6-(아미노이미노메틸)-2-나프탈레닐]에티닐]페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[6- (aminoiminomethyl) -2-naphthalenyl] ethynyl] phenyl] methyl] carbamate, mono (trifluoroacetate) salt

실시예 40D에 기재된 과정에 따라서 실시예 123B에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 123B was used following the procedure described in Example 40D to afford the desired compound.

MS(DCI/NH3) m/z 400 (M+H)+;MS (DCI / NH 3 ) m / z 400 (M + H) + ;

1H NMR(300MHz, DMSO) δ 1.40(s, 9H), 4.18(d, 2H), 7.34(d, 2H), 7.45(t, 1H), 7.58(d, 2H), 7.78(dd, 1H), 7.86(dd, 1H), 8.15(d, 1H), 8.19(d, 1H), 8.31(s, 1H), 8.50(s, 1H), 9.10-9.42(s, 4H); 1 H NMR (300 MHz, DMSO) δ 1.40 (s, 9H), 4.18 (d, 2H), 7.34 (d, 2H), 7.45 (t, 1H), 7.58 (d, 2H), 7.78 (dd, 1H) , 7.86 (dd, 1H), 8.15 (d, 1H), 8.19 (d, 1H), 8.31 (s, 1H), 8.50 (s, 1H), 9.10-9.42 (s, 4H);

C27H26F3N3O4에 대한 원소분석치:Elemental Analysis for C 27 H 26 F 3 N 3 O 4 :

계산치: C, 63.15; H, 5.10; N, 8.18.Calc .: C, 63.15; H, 5. 10; N, 8.18.

실측치: C, 62.95; H, 4.97; N, 8.09.Found: C, 62.95; H, 4.97; N, 8.09.

실시예 124Example 124

6-[[4-(아미노메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[[4- (aminomethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

트리플루오로아세트산(0.73ml)을 실시예 123C에서 수득된 생성물(80mg, 0.2mmol) 및 1.5ml CH2Cl2의 현탁액에 적가한다. 반응 혼합물을 실온에서 0.25시간 동안 교반한 다음, 진공하에 증발 건조시킨다. 톨루엔을 가하고 진공하에 수회 동안 증발시켜 갈색 고체를 수득하고, 이를 메탄올/0.1% 수성 TFA로 용출시키면서 역상 크로마토그래피로 정제하여 목적 화합물을 수득한다.Trifluoroacetic acid (0.73 ml) is added dropwise to the suspension of product (80 mg, 0.2 mmol) and 1.5 ml CH 2 Cl 2 obtained in Example 123C. The reaction mixture is stirred at RT for 0.25 h and then evaporated to dryness in vacuo. Toluene was added and evaporated several times under vacuum to give a brown solid which was purified by reverse phase chromatography eluting with methanol / 0.1% aqueous TFA to afford the desired compound.

MS(APCI) m/z 300(M+H)+;MS (APCI) m / z 300 (M + H) + ;

1H NMR(300MHz, DMSO) δ 4.10(s, 2H), 7.55(s, 2H), 7.70(d, 2H), 7.79(dd, 1H), 7.89(dd, 1H), 8.16(d, 1H), 8.19(d, 1H), 8.20(s, 2H), 8.36(s, 1H), 8.53(S, 1H), 9.20(s, 2H), 9.44(s, 2H); 1 H NMR (300 MHz, DMSO) δ 4.10 (s, 2H), 7.55 (s, 2H), 7.70 (d, 2H), 7.79 (dd, 1H), 7.89 (dd, 1H), 8.16 (d, 1H) , 8.19 (d, 1H), 8.20 (s, 2H), 8.36 (s, 1H), 8.53 (S, 1H), 9.20 (s, 2H), 9.44 (s, 2H);

C24H19F6N3O4에 대한 원소분석치:Elemental Analysis for C 24 H 19 F 6 N 3 O 4 :

계산치: C, 54.66; H, 3.63; N, 7.97.Calc .: C, 54.66; H, 3.63; N, 7.97.

실측치: C, 54.42; H, 3.57; N, 7.76.Found: C, 54.42; H, 3.57; N, 7.76.

실시예 125Example 125

6-[[3-(2-아미노에틸)-4-메톡시페닐]에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[[3- (2-aminoethyl) -4-methoxyphenyl] ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 124의 과정에 따라서 실시예 122C에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.Following the procedure of Example 124, the product obtained in Example 122C was used to yield the desired compound.

MS(ESI) m/z 344(M+H)+;MS (ESI) m / z 344 (M + H) + ;

1H NMR(300MHz, DMSO) δ 2.90(t, 2H), 3.06(t, 2H), 3.88(s, 3H), 7.11(d, 1H), 7.44(d, 1H), 7.57(dd, 1H), 7.75(dd, 1H), 7.82(s, 2H), 7.88(dd, 1H), 8.12(d, 1H), 8.17(d, 1H), 8.28(s, 1H), 8.50(s, 1H), 9.20(s, 2H), 9.45(s, 2H); 1 H NMR (300 MHz, DMSO) δ 2.90 (t, 2H), 3.06 (t, 2H), 3.88 (s, 3H), 7.11 (d, 1H), 7.44 (d, 1H), 7.57 (dd, 1H) , 7.75 (dd, 1H), 7.82 (s, 2H), 7.88 (dd, 1H), 8.12 (d, 1H), 8.17 (d, 1H), 8.28 (s, 1H), 8.50 (s, 1H), 9.20 (s, 2 H), 9.45 (s, 2 H);

C26H23F6N3O5·0.5H2O에 대한 원소분석치: C 26 H 23 F 6 N 3 O 5 · 0.5H 2 O element for analysis:

계산치: C, 53.80; H, 4.17; N, 7.24.Calc .: C, 53.80; H, 4. 17; N, 7.24.

실측치: C, 53.89; H, 4.31; N, 6.83.Found: C, 53.89; H, 4.31; N, 6.83.

실시예 126Example 126

6-[[4-(하이드록시메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6-[[4- (hydroxymethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 126AExample 126A

실시예 121A에 기재된 과정을 사용하고 4-요오도아닐린을 4-브로모벤질 알콜로 대체하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 301(M+NH4)+.Using the procedure described in Example 121A and replacing 4-iodoaniline with 4-bromobenzyl alcohol, the desired compound is obtained. MS (DCI / NH 3 ) m / z 301 (M + NH 4 ) + .

실시예 126BExample 126B

6-[[4-(하이드록시메틸)페닐]에티닐]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6-[[4- (hydroxymethyl) phenyl] ethynyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 94B에 기재된 과정에 따라서 실시예 126A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 126A was used following the procedure described in Example 94B to afford the desired compound.

MS(ESI) m/z 301(M+H)+;MS (ESI) m / z 301 (M + H) + ;

1H NMR(300MHz, DMSO) δ 4.58(d, 2H), 5.32(t, 1H), 7.41(d, 2H), 7.59(d, 1H), 7.79(dd, 1H), 7.86(dd, 1H), 8.12(d, 1H), 8.18(d, 1H), 8.32(s, 1H), 8.50(s, 1H), 9.14(s, 2H), 9.46(s, 2H); 1 H NMR (300 MHz, DMSO) δ 4.58 (d, 2H), 5.32 (t, 1H), 7.41 (d, 2H), 7.59 (d, 1H), 7.79 (dd, 1H), 7.86 (dd, 1H) , 8.12 (d, 1H), 8.18 (d, 1H), 8.32 (s, 1H), 8.50 (s, 1H), 9.14 (s, 2H), 9.46 (s, 2H);

C22H17F3N2O3·0.5H2O에 대한 원소분석치: C 22 H 17 F 3 N 2 O 3 · 0.5H 2 O element for analysis:

계산치: C, 62.41; H, 4.29; N, 6.62.Calc .: C, 62.41; H, 4. 29; N, 6.62.

실측치: C, 62.56; H, 4.13; N, 6.65.Found: C, 62.56; H, 4.13; N, 6.65.

실시예 127Example 127

6-[(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[(1,2,3,4-tetrahydro-6-isoquinolinyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 127AExample 127A

삼브롬화붕소(1.2ml, 12.5mmol) 및 12.5ml CH2Cl2의 용액을 6-메톡시테트라하이드로이소퀴놀린(1.0g, 5.0mole, Org. Synth., 67, 60, 1988) 및 38ml CH2Cl2의 -78℃ 용액에 적가한다. 이 반응 혼합물을 -78℃에서 1시간, 0℃에서 1시간 및 실온에서 0.25시간 동안 교반한다. 이 반응 혼합물을 -78℃로 냉각시키고, 메탄올 20ml를 적가한다. 이 용액을 실온에서 1시간 동안 교반한다. 용매를 진공하에 증발시키고 잔사를 진공하에 건조시켜 목적 화합물을 수득한다. MS(DCI) m/z 150 (M+H)+.A solution of boron tribromide (1.2 ml, 12.5 mmol) and 12.5 ml CH 2 Cl 2 was charged with 6-methoxytetrahydroisoquinoline (1.0 g, 5.0 mole, Org. Synth., 67, 60, 1988) and 38 ml CH 2 Add dropwise to a -78 ° C solution of Cl 2 . The reaction mixture is stirred for 1 hour at −78 ° C., 1 hour at 0 ° C. and 0.25 hour at room temperature. The reaction mixture is cooled to -78 ° C and 20 ml of methanol is added dropwise. The solution is stirred at room temperature for 1 hour. The solvent is evaporated in vacuo and the residue is dried in vacuo to afford the desired compound. MS (DCI) m / z 150 (M + H) + .

실시예 127BExample 127B

실시예 127A에서 수득된 생성물(1.15g, 5.0mmol)을 대상으로 실시예 63C에 기재된 조건에 적용시킨다. 이 물질의 2.1g 분획을 환류하에 60ml 메탄올과 9ml 10% 수성 NaOH와 함께 1.5시간 동안 교반한다. 실온으로 냉각시킨 후, 메탄올을 진공하에 증발시킨다. 물을 가하고, 이 용액을 6N HCl로 산성화한다. 혼합물을 CH2Cl2로 추출한다. 유기 층을 물, 포화 수성 염화나트륨으로 세척하고, 건조시킨 다음(MgSO4), 여과하고, 용매를 진공하에 증발시켜 목적 화합물을 수득한다. MS(DCI/NH3) m/z 267(M+NH4)+.The product (1.15 g, 5.0 mmol) obtained in Example 127A was subjected to the conditions described in Example 63C. A 2.1 g fraction of this material is stirred under reflux with 60 ml methanol and 9 ml 10% aqueous NaOH for 1.5 h. After cooling to room temperature, methanol is evaporated in vacuo. Water is added and the solution is acidified with 6N HCl. The mixture is extracted with CH 2 Cl 2 . The organic layer is washed with water, saturated aqueous sodium chloride, dried (MgSO 4 ), filtered and the solvent is evaporated in vacuo to afford the desired compound. MS (DCI / NH 3 ) m / z 267 (M + NH 4 ) + .

실시예 127CExample 127C

실시예 28B에 기재된 과정에 따라서 실시예 127B로부터의 생성물을 사용하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 399(M+NH4)+.The product from Example 127B was used following the procedure described in Example 28B to afford the desired compound. MS (DCI / NH 3 ) m / z 399 (M + NH 4 ) + .

실시예 127DExample 127D

실시예 121A에 기재된 과정을 사용하고 4-요오도아닐린을 실시예 127C에 수득된 생성물로 대체하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 426(M+NH4)+.Using the procedure described in Example 121A and replacing 4-iodoaniline with the product obtained in Example 127C, the desired compound is obtained. MS (DCI / NH 3 ) m / z 426 (M + NH 4 ) + .

실시예 127EExample 127E

실시예 40D에 기재된 과정에 따라서 실시예 127D로부터의 생성물을 사용하여 목적 화합물을 수득한다. MS(ESI) m/z 426(M+H)+;The product from Example 127D was used following the procedure described in Example 40D to afford the desired compound. MS (ESI) m / z 426 (M + H) + ;

1H NMR(300MHz, DMSO) δ 1.45(s, 9H), 2.82(t, 2H), 3.59(t, 2H), 4.58(s, 2H), 7.29(d, 1H), 7.42(d, 2H), 7.76(dd, 1H), 7.83(dd, 1H), 8.15(d, 1H), 8.19(d, 1H), 8.35(s, 1H), 8.51(s, 1H), 9.20(s, 2H), 9.45(s, 2H). 1 H NMR (300 MHz, DMSO) δ 1.45 (s, 9H), 2.82 (t, 2H), 3.59 (t, 2H), 4.58 (s, 2H), 7.29 (d, 1H), 7.42 (d, 2H) , 7.76 (dd, 1H), 7.83 (dd, 1H), 8.15 (d, 1H), 8.19 (d, 1H), 8.35 (s, 1H), 8.51 (s, 1H), 9.20 (s, 2H), 9.45 (s, 2 H).

실시예 127FExample 127F

6-[(1,2,3,4-테트라하이드로-6-이소퀴놀리닐)에티닐]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염6-[(1,2,3,4-tetrahydro-6-isoquinolinyl) ethynyl] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 124D에 기재된 과정에 따라서 실시예 127E로부터의 생성물을 사용하여 목적 화합물을 수득한다. MS (ESI) m/z 326 (M+H)+;The product from Example 127E was used following the procedure described in Example 124D to afford the desired compound. MS (ESI) m / z 326 (M + H) + ;

1H NMR(300MHz, DMSO) δ 3.03(t, 2H), 3.42(t, 2H), 4.35(s, 2H), 7.35(d, 1H), 7.46(d, 2H), 7.78(dd, 1H), 7.89(dd, 1H), 8.15(d, 1H), 8.19(d, 1H), 8.35(s, 1H), 8.52(s, 1H), 9.17(s, 2H), 9.31(s, 2H), 9.48(s, 2H); 1 H NMR (300 MHz, DMSO) δ 3.03 (t, 2H), 3.42 (t, 2H), 4.35 (s, 2H), 7.35 (d, 1H), 7.46 (d, 2H), 7.78 (dd, 1H) , 7.89 (dd, 1H), 8.15 (d, 1H), 8.19 (d, 1H), 8.35 (s, 1H), 8.52 (s, 1H), 9.17 (s, 2H), 9.31 (s, 2H), 9.48 (s, 2 H);

C26H21F6N3O4에 대한 원소분석치:Elemental Analysis for C 26 H 21 F 6 N 3 O 4 :

계산치: C, 56.42; H, 3.82; N, 7.59.Calc .: C, 56.42; H, 3. 82; N, 7.59.

실측치: C, 56.31; H, 3.81; N, 7.42.Found: C, 56.31; H, 3.81; N, 7.42.

실시예 129Example 129

5-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노산, 모노(트리플루오로아세테이트) 염5-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] pentanoic acid, mono (trifluoroacetate) salt

실시예 129AExample 129A

실시예 119A로부터의 생성물(250mg, 1.477mmol)을 실시예 119B에 기재된 바와 유사한 방식으로 메틸 5-브로모발레레이트로 처리하여 목적 화합물(394mg, 94%)을 수득한다. MS(DCI/NH3) m/z 301(M+NH4)+.The product from Example 119A (250 mg, 1.477 mmol) was treated with methyl 5-bromovalerate in a similar manner as described in Example 119B to afford the desired compound (394 mg, 94%). MS (DCI / NH 3 ) m / z 301 (M + NH 4 ) + .

실시예 129BExample 129B

5-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노산, 모노(트리플루오로아세테이트) 염5-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] pentanoic acid, mono (trifluoroacetate) salt

실시예 129A로부터의 생성물(262mg, 0.8723mmol)을 실시예 94D에 기재된 바와 유사한 방식으로 처리하여 에스테르 아미딘 생성물을 수득한다. 이 생성물(140mg, 0.542mmol)을 메탄올(11ml)에 용해시킨다. 이에 수(3ml) 중 수산화리튬(68.2mg, 1.626mmol)의 용액을 가하고, 생성된 혼합물을 불활성 대기하에서 실온하에 18시간 동안 교반한다. 반응물을 증발시키고 잔사를 역상 크로마토그래피로 정제하여 목적 화합물(184mg, 74%)을 수득한다.The product from Example 129A (262 mg, 0.8723 mmol) was treated in a similar manner as described in Example 94D to yield the ester amidine product. This product (140 mg, 0.542 mmol) is dissolved in methanol (11 ml). To this was added a solution of lithium hydroxide (68.2 mg, 1.626 mmol) in water (3 ml) and the resulting mixture was stirred for 18 h at room temperature under an inert atmosphere. The reaction is evaporated and the residue is purified by reverse phase chromatography to yield the desired compound (184 mg, 74%).

MS(DCI(NH3)) m/z 287(M+H)+;MS (DCI (NH 3 )) m / z 287 (M + H) + ;

1H NMR(300MHz, DMSO-d6) δ 1.711(m, 2H), 1.817(m, 2H), 2.320(t, 2H), 4.144(t, 2H), 7.377(dd, 1H), 7.472(d, 1H), 7.632(dd, 1H), 7.980(d, 1H), 8.081(d, 1H), 8.329(s, 1H), 9.100(br s, 2H), 9.390(br s, 2H), 12.100(br s, 1H); 1 H NMR (300 MHz, DMSO-d6) δ 1.711 (m, 2H), 1.817 (m, 2H), 2.320 (t, 2H), 4.144 (t, 2H), 7.377 (dd, 1H), 7.472 (d, 1H), 7.632 (dd, 1H), 7.980 (d, 1H), 8.081 (d, 1H), 8.329 (s, 1H), 9.100 (br s, 2H), 9.390 (br s, 2H), 12.100 (br s, 1 H);

C16H18N2O3·(C2HO2F3)1.15·H2O 0.65에 대한 원소분석치:Elemental Analysis for C 16 H 18 N 2 O 3 · (C 2 HO 2 F 3 ) 1.15H 2 O 0.65:

계산치: C, 51.22; H, 4.80; N, 6.53.Calc .: C, 51.22; H, 4.80; N, 6.53.

실측치: C, 51.30; H, 5.07; N, 6.12.Found: C, 51.30; H, 5.07; N, 6.12.

실시예 131Example 131

7-메톡시-8-(3-옥소-1-사이클로펜텐-1-일)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8- (3-oxo-1-cyclopenten-1-yl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 131AExample 131A

실시예 25A에 기재된 바와 같이 제조된 물질(0.5g, 1.5mmol) 및 문헌[참조: Laborude et al. Tet Letters 31, (13), 1837-1840(1990)]에 기재된 바와 같이 제조된 3-트리부틸스타닐-2-사이클로펜텐온을 문헌[참조: Stille et al. JACS 109, 5478-5486(1987)]의 방법에 의해 기재된 바와 같은 Pd 촉매를 통하여 커플링시키고, 이를 3:1 헥산/에틸 아세테이트로 플래쉬 크로마토그래피한 후, 백색 고체를 300mg(72%) 수득한다. MS(DCI/NH3):281 (M+NH4).Materials prepared as described in Example 25A (0.5 g, 1.5 mmol) and Laborude et al. 3-tributylstannyl-2-cyclopentenone prepared as described in Tet Letters 31, (13), 1837-1840 (1990). Stille et al. JACS 109, 5478-5486 (1987)], coupled via a Pd catalyst as described by the method and flash chromatographed with 3: 1 hexanes / ethyl acetate to give 300 mg (72%) of a white solid. . MS (DCI / NH 3 ): 281 (M + NH 4 ).

실시예 131BExample 131B

7-메톡시-8-(3-옥소-1-사이클로펜텐-1-일)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염7-methoxy-8- (3-oxo-1-cyclopenten-1-yl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 40D에 기재된 H2S/피리딘 방법에 따라서 상기 제조된 물질(130mg, 4mmol)을 제조한다. 이를 역상 크로마토그래피한 후 회백색 고체로서의 목적 화합물을 수득한다(52mg, 45%).The above prepared material (130 mg, 4 mmol) was prepared according to the H 2 S / pyridine method described in Example 40D. After reverse phase chromatography, the desired compound is obtained as an off-white solid (52 mg, 45%).

MS(DCI/NH3): M+H+281MS (DCI / NH3): M + H + 281

1H NMR(DMSO-d6): 9.45(bs, 2H); 9.12(bs, 2H), 8.25-8.32(m, 2H), 8.20(dd, 1H), 7.86(d, 1H), 7.75(dd, 1H), 6.42(m, 1H), 4.05(s, 3H), 3.15(m, 2H), 2.75(m, 2H) ' H NMR (DMSOd6): 9.45 (bs, 2H); 9.12 (bs, 2H), 8.25-8.32 (m, 2H), 8.20 (dd, 1H), 7.86 (d, 1H), 7.75 (dd, 1H), 6.42 (m, 1H), 4.05 (s, 3H) , 3.15 (m, 2H), 2.75 (m, 2H)

C19H17N2O4F3·1.75TFA에 대한 원소분석치:Elemental Analysis for C 19 H 17 N 2 O 4 F 3 · 1.75TFA:

계산치: C, 57.87; H, 4.35; N, 7.10.Calc .: C, 57.87; H, 4. 35; N, 7.10.

실측치: C, 51.37; H, 4.21; N, 7.14.Found: C, 51.37; H, 4. 21; N, 7.14.

실시예 132Example 132

6-(아미노이미노메틸)-N-(4-메틸페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-methylphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 132AExample 132A

p-톨루이딘(0.11g, 1mmol), 및 실시예 8E에서 제조된 시아노 에스테르(0.2g, 1mmol)를 실시예 8G에 기재된 과정에 따라서 커플링시켜 목적 화합물로서의 회백색 고체(0.16g, 56%)를 수득한다. MS(ESI +,-):287(M+); 285(M-).p-toluidine (0.11 g, 1 mmol), and the cyano ester (0.2 g, 1 mmol) prepared in Example 8E were coupled according to the procedure described in Example 8G to yield an off-white solid (0.16 g, 56%) as the target compound. To obtain. MS (ESI +,-): 287 (M < + >); 285 (M−).

실시예 132BExample 132B

6-(아미노이미노메틸)-N-(4-메틸페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-methylphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 6B에 기재된 과정에 따라서 목적 화합물을 제조하고 실시예 1B에 기재된 바와 같이 정제하여 백색 고체(35mg, 35%)를 수득한다.The desired compound was prepared according to the procedure described in Example 6B and purified as described in Example 1B to yield a white solid (35 mg, 35%).

MS(ESI+): 304(M+)MS (ESI +): 304 (M +)

1H NMR(DMSO-d6): 10.55(s, 1H); 9.45(bs, 2H); 9.15(bs, 2H); 8.65(s, 1H); 8.58(s, 1H); 8.32(d, 1H), 8.20(d, 1H), 8.19(dd, 1H); 7.96(dd, 1H), 7.75(d, 2H), 7.12(d, 2H), 2.35(s, 3H); 1 H NMR (DMSO-d 6): 10.55 (s, 1 H); 9.45 (bs, 2 H); 9.15 (bs, 2 H); 8.65 (s, 1 H); 8.58 (s, 1 H); 8.32 (d, 1 H), 8.20 (d, 1 H), 8.19 (dd, 1 H); 7.96 (dd, 1H), 7.75 (d, 2H), 7.12 (d, 2H), 2.35 (s, 3H);

C21H18N3O3F3에 대한 원소분석치:Elemental Analysis for C 21 H 18 N 3 O 3 F 3 :

계산치: C, 60.43; H, 4.35; N, 10.07.Calc .: C, 60.43; H, 4. 35; N, 10.07.

실측치: C, 59.94; H, 4.06; N, 9.80.Found: C, 59.94; H, 4.06; N, 9.80.

실시예 133Example 133

메틸 4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염Methyl 4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt

실시예 133AExample 133A

실시예 91A에 기재된 물질을 실시예 119A에 기재된 과정에 따라서 AlI3로 처리하고 실시예 109B에 기재된 과정에 따라서 4-카보메톡시벤질브로마이드로 처리하여 백색 고체로서의 목적 화합물(100mg, 83%)을 수득한다. MS(ESI +,-):411(M+); 409(M-).The material described in Example 91A was treated with AlI 3 according to the procedure described in Example 119A and 4-carbomethoxybenzylbromide according to the procedure described in Example 109B to give the target compound (100 mg, 83%) as a white solid. To obtain. MS (ESI +,-): 411 (M < + >); 409 (M-).

실시예 133BExample 133B

메틸 4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염Methyl 4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt

실시예 40D에 기재된 과정에 따라서 목적 화합물을 제조하고 실시예 119B에 기재된 과정에 따라서 정제하여 밝은 황색 고체(49mg, 50%)를 수득한다.Prepare the desired compound according to the procedure described in Example 40D and purify according to the procedure described in Example 119B to yield a light yellow solid (49 mg, 50%).

MS(ESI+, -); 428(M+);426(M-)MS (ESI +,-); 428 (M < + >); 426 (M-)

1H NMR(DMSO-d6); 9.45(bs, 2H); 9.15(s, 1H); 8.97(bs, 2H); 8.45(dd, 1H); 8.38(d, 1H); 8.15(d, 1H), 8.09(d, 1H), 7.95(d, 2H); 7.76(d, 1H), 7.68(dd, 1H), 7.35(d, 2H), 6.85(d, 2H), 5.39(s, 2H); 3.85(s, 3H); 1 H NMR (DMSO-d 6); 9.45 (bs, 2 H); 9.15 (s, 1 H); 8.97 (bs, 2 H); 8.45 (dd, 1 H); 8.38 (d, 1 H); 8.15 (d, 1 H), 8.09 (d, 1 H), 7.95 (d, 2 H); 7.76 (d, 1 H), 7.68 (dd, 1 H), 7.35 (d, 2H), 6.85 (d, 2H), 5.39 (s, 2H); 3.85 (s, 3 H);

C26H22N5O5F3에 대한 원소분석치:Elemental Analysis for C 26 H 22 N 5 O 5 F 3 :

계산치: C, 57.67; H, 4.10; N, 12.93.Calc .: C, 57.67; H, 4.10; N, 12.93.

실측치: C, 55.34; H, 3.88; N, 12.05.Found: C, 55.34; H, 3.88; N, 12.05.

실시예 134Example 134

4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조산, 모노(트리플루오로아세테이트) 염4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoic acid, mono (trifluoroacetate) salt

실시예 134에서 제조된 물질(40mg)을 1:1 THF/물에 용해시킨다. 이러한 투명한 용액에 LiOH-물(9mg)을 가하고, 생성된 투명한 용액을 실온에서 18시간 동안 교반한다. 반응 혼합물을 농축시켜 황색 고체를 수득한다. 이 고체를 증류수에 용해시키고, 3N HCl를 사용하여 pH 2로 산성화하며, 실온에서 2시간 동안 교반한다. 목적 화합물을 여과시켜 분리하고, 진공하에 건조시켜 황색 고체를 수득한다. 수율: 39mg(46%).The material (40 mg) prepared in Example 134 is dissolved in 1: 1 THF / water. LiOH-water (9 mg) is added to this clear solution, and the resulting clear solution is stirred at room temperature for 18 hours. The reaction mixture is concentrated to give a yellow solid. This solid is dissolved in distilled water, acidified to pH 2 with 3N HCl and stirred at room temperature for 2 hours. The desired compound is isolated by filtration and dried under vacuum to give a yellow solid. Yield: 39 mg (46%).

MS(APCI): M+H+:414MS (APCI): M + H + : 414

1H NMR(DMSO-d6): 9.45(bs, 2H); 9.15(s, 1H); 8.97(bs, 2H); 8.45(dd, 1H); 8.38(d, 1H); 8.15(d, 1H), 8.09(d, 1H), 7.95(d, 2H); 7.76(d, 1H), 7.68(dd, 1H), 7.35(d, 2H), 6.85(d, 2H), 5.39(s, 2H); ' H NMR (DMSOd6): 9.45 (bs, 2H); 9.15 (s, 1 H); 8.97 (bs, 2 H); 8.45 (dd, 1 H); 8.38 (d, 1 H); 8.15 (d, 1 H), 8.09 (d, 1 H), 7.95 (d, 2 H); 7.76 (d, 1 H), 7.68 (dd, 1 H), 7.35 (d, 2H), 6.85 (d, 2H), 5.39 (s, 2H);

C25H20N5O5F3Cl·3H2O에 대한 원소분석치:Elemental Analysis for C 25 H 20 N 5 O 5 F 3 Cl3H 2 O:

계산치: C, 48.67; H, 4.25; N, 11.35.Calc .: C, 48.67; H, 4. 25; N, 11.35.

실측치: C, 49.64; H, 4.44; N, 11.69.Found: C, 49.64; H, 4. 44; N, 11.69.

실시예 135Example 135

1,1-디메틸에틸 [[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] phenyl] methyl] carbamate, mono (trifluoroacetate) salt

실시예 135AExample 135A

실시예 8B에서 제조된 물질을 찬(0℃) 황산(45ml)에 가한다. 0℃에서 1분 이내에 버블이 형성되기 시작한다. 0℃에서 30분 동안 버블링시킨 다음, 서서히 실온으로 가온시킨다. 실온에서 20분 동안 방치시킨 다음, 얼음에 붓고 물로 희석시킨다(약 500ml). 이 현탁액을 얼음 욕에 놓아두고 50% 수성 수산화나트륨 용액을 조심스럽게 가하여 온도가 35℃를 초과하지 않도록 한다. 밝은 황색 고체를 여과한 다음, 세척액이 pH지에 대해 중성이 될 때까지(7.0) 물로 세척한다. 생성물을 진공하에 건조시킨다. 이 생성물을 용출제로서 20% 에틸 아세테이트-80% 헥산을 사용하여 실리카 겔 칼럼 상에서 정제하여 밝은 황색 고체를 3.3g(67%) 수득한다. MS m/z 169(M+1)+.The material prepared in Example 8B is added to cold (0 ° C.) sulfuric acid (45 ml). Bubbles begin to form within 1 minute at 0 ° C. Bubble for 30 minutes at 0 ° C., then slowly warm to room temperature. It is left at room temperature for 20 minutes, then poured onto ice and diluted with water (about 500 ml). This suspension is placed in an ice bath and carefully added 50% aqueous sodium hydroxide solution so that the temperature does not exceed 35 ° C. The light yellow solid is filtered and then washed with water until the wash solution is neutral to pH paper (7.0). The product is dried under vacuum. This product is purified on a silica gel column using 20% ethyl acetate-80% hexane as eluent to yield 3.3 g (67%) of a light yellow solid. MS m / z 169 (M + l) + .

실시예 135BExample 135B

실온에서 메틸렌 클로라이드(25ml) 중의 실시예 135A(135mg, 0.8mmol), 4-N-Boc-아미노메틸벤조산(404mg, 1.6mmol) 및 EDCI(307mg, 1.6mmol)의 용액을 DMAP(3mg)에 가하고 밤새 교반한다. 이 반응 혼합물을 메틸렌 클로라이드(60ml)로 희석시킨 다음, 2% 수성 염산(2 x 30ml), 물(20ml), 0.5M 수성 수산화나트륨(2 x 50ml) 및 염수로 세척한다. 유기 상을 황산마그네슘으로 건조시킨 다음 증발시킨다. 생성물을 용출제로서 헥산 중의 25 내지 60% 에틸 아세테이트의 구배를 이용하여 실리카 칼럼을 통하여 정제한다. 백색 분말 수율 175mg(54%).A solution of Example 135A (135 mg, 0.8 mmol), 4-N-Boc-aminomethylbenzoic acid (404 mg, 1.6 mmol) and EDCI (307 mg, 1.6 mmol) in methylene chloride (25 ml) at room temperature was added to DMAP (3 mg) Stir overnight. The reaction mixture is diluted with methylene chloride (60 ml) and then washed with 2% aqueous hydrochloric acid (2 x 30 ml), water (20 ml), 0.5 M aqueous sodium hydroxide (2 x 50 ml) and brine. The organic phase is dried over magnesium sulfate and then evaporated. The product is purified through a silica column using a gradient of 25-60% ethyl acetate in hexane as eluent. White powder yield 175 mg (54%).

실시예 135CExample 135C

1,1-디메틸에틸 [[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]페닐]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] phenyl] methyl] carbamate, mono (trifluoroacetate) salt

실시예 40D에 기재된 바와 동일한 방식으로 반응을 수행한다. 수율: 110mg(64%).The reaction is carried out in the same manner as described in Example 40D. Yield: 110 mg (64%).

MS m/z 408(M+1)+.425(M+18)+ MS m / z 408 (M + l) +. 425 (M + 18) +

1H NMR: 3.30(s, 9H), 4.22(d, 2H. J=7.1Hz). 7.42(d, 2H, J=8.5Hz), 7.49(t, 1H, J=7.1Hz). 7.79(dd, 1H, J1=8.2Hz, J2=2.0Hz), 7.95-8.00(m, 3H), 8.09(d, 2H, J=8.4Hz), 8.42(s, 1H), 8.63(d, 1H, J=2.0Hz), 9.18(br s, 4H), 10.58(s, 1H); 1 H NMR: 3.30 (s, 9 H), 4.22 (d, 2 H. J = 7.1 Hz). 7.42 (d, 2H, J = 8.5 Hz), 7.49 (t, 1H, J = 7.1 Hz). 7.79 (dd, 1H, J1 = 8.2 Hz, J2 = 2.0 Hz), 7.95-8.00 (m, 3H), 8.09 (d, 2H, J = 8.4 Hz), 8.42 (s, 1H), 8.63 (d, 1H , J = 2.0 Hz), 9.18 (br s, 4H), 10.58 (s, 1H);

C26H27F3N4O에 대한 원소분석치:Elemental Analysis for C 26 H 27 F 3 N 4 O:

계산치: C, 58.55; H, 4.85; N, 10.41.Calc .: C, 58.55; H, 4. 85; N, 10.41.

실측치: C 58.64; H, 5.11; N, 10.52.Found: C 58.64; H, 5.11; N, 10.52.

실시예 136Example 136

N-[6-(아미노이미노메틸)-2-나프탈레닐]벤즈아미드, 모노(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] benzamide, mono (trifluoroacetate) salt

실시예 135에 기재된 바와 같이 목적 화합물을 제조한다.The desired compound is prepared as described in Example 135.

1H NMR(300MHz, DMSO-d6) 10.67(s, 1H), 9.25(br.s, 4H), 8.65(d, J=1.5Hz, 1H), 8.43(d, J=1.4Hz, 1H), 8.10(d, J=9.2Hz, 2H), 8.03-7.97(m, 3H), 7.81-7.78(m, 1H), 7.65-7.55(m, 3H). 1 H NMR (300MHz, DMSO-d6) 10.67 (s, 1H), 9.25 (br.s, 4H), 8.65 (d, J = 1.5Hz, 1H), 8.43 (d, J = 1.4Hz, 1H), 8.10 (d, J = 9.2 Hz, 2H), 8.03-7.97 (m, 3H), 7.81-7.78 (m, 1H), 7.65-7.55 (m, 3H).

MS(ESI/NH3) m/z 290(M+H)+;MS (ESI / NH 3 ) m / z 290 (M + H) + ;

C18H15N3O·CF3COOH에 대한 원소분석치:Elemental Analysis for C 18 H 15 N 3 O · CF 3 COOH:

계산치: C, 59.55; H, 4.00; F, 14.13; N, 10.42.Calc .: C, 59.55; H, 4.00; F, 14.13; N, 10.42.

실측치: C, 50.47; H, 3.88; F, 14.42; N, 10.30.Found: C, 50.47; H, 3.88; F, 14.42; N, 10.30.

실시예 137Example 137

1,1-디메틸에틸 [[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]사이클로헥실]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] cyclohexyl] methyl] carbamate, mono (trifluoroacetate) salt

실시예 137AExample 137A

실온에서 메틸렌 클로라이드(35ml) 중의 실시예 73에서 제조된 6-아미노-2-나프탈렌카보니트릴(100mg, 0.6mmol)의 용액에 1-카복시-4-(Boc-아미노메틸)사이클로헥산(280mg, 1.1mmol)을 가한 다음, 1-에틸-3-(3-디메틸아미노프로필)카보디이미드 하이드로클로라이드(EDAC, 225mg, 1.2mmol)을 가한다. 5분 후, 이 반응 혼합물에 DMAP(20mg 촉매량)을 가한다. 반응물을 실온에서 72시간 동안 교반한다. 반응 혼합물을 7:3 에틸 아세테이트:헥산으로 희석시킨 다음 실리카 겔을 통하여 여과한 다음, 동일한 용매 혼합물로 세척한다.To a solution of 6-amino-2-naphthalenecarbonitrile (100 mg, 0.6 mmol) prepared in Example 73 in methylene chloride (35 ml) at room temperature 1-carboxy-4- (Boc-aminomethyl) cyclohexane (280 mg, 1.1 mmol) is added, followed by 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC, 225 mg, 1.2 mmol). After 5 minutes, DMAP (20 mg catalyst amount) is added to this reaction mixture. The reaction is stirred at rt for 72 h. The reaction mixture is diluted with 7: 3 ethyl acetate: hexanes and then filtered through silica gel and washed with the same solvent mixture.

유기 용매를 수성 산(2% HCl, 2 x 50ml), 물 및 수성 염기(10% NaOH, 50ml)로 세척한다. 용매를 황산마그네슘으로 건조시키고, 여과한 다음 증발시킨다. 에테르/헥산으로 결정화하여 백색 고체로서의 생성물을 수득한다. 수율: 166mg(68%). MS(DCI/NH3) m/z 408(M+H)+.The organic solvent is washed with aqueous acid (2% HCl, 2 x 50 ml), water and aqueous base (10% NaOH, 50 ml). The solvent is dried over magnesium sulfate, filtered and evaporated. Crystallization with ether / hexanes affords the product as a white solid. Yield: 166 mg (68%). MS (DCI / NH 3 ) m / z 408 (M + H) + .

실시예 137BExample 137B

1,1-디메틸에틸 [[4-[[[6-(아미노이미노메틸)-2-나프탈레닐]아미노]카보닐]사이클로헥실]메틸]카바메이트, 모노(트리플루오로아세테이트) 염1,1-dimethylethyl [[4-[[[6- (aminoiminomethyl) -2-naphthalenyl] amino] carbonyl] cyclohexyl] methyl] carbamate, mono (trifluoroacetate) salt

Pyr:Et3N(10:1, 20ml) 중의 기질(실시예 137A)의 용액을 H2S를 통하여 5분 동안 버블링시킨다. 실온에서 밤새 교반한다. 이 반응 혼합물을 에틸 아세테이트(100ml)에 가한 다음 1% 수성 KHSO4(60ml)에 가한 다음 분리하고 유기 층을 물(2 x 50ml), 중탄산나트륨 및 염수로 세척하며, 황산마그네슘으로 건조시킨 다음 증발시킨다. 생성된 아세톤(25ml) 중의 고체의 현탁액에 MeI(1.0ml)를 가한다. 50℃에서 2시간 동안 교반시키면 모두 용해된다. 용매를 완전히 증발 건조시키고 메탄올(30ml) 및 암모늄 아세테이트(150mg)를 가한다. 이 혼합물을 실온에서 밤새 교반한다. 역상 C18MPLC에 의해 정제한다. 증발시킨 후, 톨루엔을 가하고 증발시킨다(2 x 40ml). 생성된 오일을 메탄올 및 에테르로 처리하면 생성물이 백색 고체로서 침전된다(72mg, 43%).A solution of substrate (Example 137A) in Pyr: Et 3 N (10: 1, 20 ml) was bubbled through H 2 S for 5 minutes. Stir overnight at room temperature. The reaction mixture was added to ethyl acetate (100 ml) and then to 1% aqueous KHSO 4 (60 ml), then separated and the organic layer washed with water (2 x 50 ml), sodium bicarbonate and brine, dried over magnesium sulfate and evaporated Let's do it. To the resulting suspension of solid in acetone (25 ml) is added MeI (1.0 ml). After stirring for 2 hours at 50 ℃, all are dissolved. The solvent is evaporated to dryness and methanol (30 ml) and ammonium acetate (150 mg) are added. The mixture is stirred overnight at room temperature. Purify by reverse phase C 18 MPLC. After evaporation, toluene is added and evaporated (2 × 40 ml). Treatment of the resulting oil with methanol and ether precipitates the product as a white solid (72 mg, 43%).

MS(ESI/NH3) m/z 425(M+H)+:MS (ESI / NH 3 ) m / z 425 (M + H) + :

1H NMR(300MHz, DMSO-d6) 10.24(s, 1H), 9.05(br.s, 4H), 8.49(s, 1H), 8.38(d, J=1.7Hz, 1H), 8.03-8.00(m, 2H), 7.77-7.74(m, 2H), 6.93-6.91(m, 1H), 2.83-2.79(m,2H), 2.40-2.30(ml), 1.92-1.75(m, 4H), 1.50-1.45(m, 1H), 1.39(s, 9H), 0.96-0.91(m, 4H); 1 H NMR (300MHz, DMSO-d 6 ) 10.24 (s, 1H), 9.05 (br.s, 4H), 8.49 (s, 1H), 8.38 (d, J = 1.7Hz, 1H), 8.03-8.00 ( m, 2H), 7.77-7.74 (m, 2H), 6.93-6.91 (m, 1H), 2.83-2.79 (m, 2H), 2.40-2.30 (ml), 1.92-1.75 (m, 4H), 1.50- 1.45 (m, 1 H), 1.39 (s, 9 H), 0.96-0.91 (m, 4H);

C24H32N4O3·CF3COOH에 대한 원소분석치:Elemental Analysis for C 24 H 32 N 4 O 3 · CF 3 COOH:

계산치: C, 57.98; H, 6.18; N, 10.40.Calc .: C, 57.98; H, 6. 18; N, 10.40.

실측치: C, 57.63; H, 6.24; N. 10.21.Found: C, 57.63; H, 6. 24; N. 10.21.

실시예 138Example 138

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-(4-아미노페닐)우레아, 비스(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-(4-aminophenyl) urea, bis (trifluoroacetate) salt

실시예 138AExample 138A

실온에서 디옥산(10ml) 중의 실시예 40B에서 제조된 화합물(194.2mg, 1mmol)의 용액에 4-페닐렌디아민 모노 Boc(416.5mg, 2mmol)을 가한다. 생성물이 수 분내에 침전되기 시작한다. 1시간 후, 반응 혼합물에 에테르(5ml)를 가하고, 백색 고체 생성물을 여과한 다음, 에테르로 세척하여 350mg(87%)을 수득한다. MS(DCI/NH3) m/z 403(M+H)+.To a solution of the compound prepared in Example 40B (194.2 mg, 1 mmol) in dioxane (10 ml) at room temperature is added 4-phenylenediamine mono Boc (416.5 mg, 2 mmol). The product begins to precipitate in minutes. After 1 h, ether (5 ml) is added to the reaction mixture and the white solid product is filtered and then washed with ether to give 350 mg (87%). MS (DCI / NH 3 ) m / z 403 (M + H) + .

실시예 138BExample 138B

Pyr:Et3N(10:1, 20ml) 중의 실시예 138A에서 제조된 상응하는 니트릴(105mg, 0.36mmol)의 용액을 H2S를 통하여 5분 동안 버블링시킨다. 실온에서 밤새 교반한다. 이 반응 혼합물을 에틸 아세테이트(100ml)로 희석시킨 다음 수성 0.25N HCl(25ml)로 세척한 다음 물(2 x 50ml), 포화 중탄산나트륨 용액 및 염수로 세척하며, 황산마그네슘으로 건조시킨 다음 증발시킨다. 생성된 아세톤(25ml) 중의 고체의 용액에 MeI(1.0ml)를 가하고 50℃에서 30분 동안 교반시키면, 매우 강력한 침전이 관찰된다. 에테르를 가하고 여과시키면 황색 생성물이 침전된다. 이러한 황색 고체에 메탄올(10ml) 및 암모늄 아세테이트(150mg)를 가하고 실온에서 밤새 교반한다. 실시예 1B에 기재된 바와 같이 정제하여 백색 고체를 69mg 수득한다. MS(DCI/NH3) m/z 420(M+H)+.A solution of the corresponding nitrile (105 mg, 0.36 mmol) prepared in Example 138A in Pyr: Et 3 N (10: 1, 20 ml) was bubbled through H 2 S for 5 minutes. Stir overnight at room temperature. The reaction mixture is diluted with ethyl acetate (100 ml) and then washed with aqueous 0.25 N HCl (25 ml) followed by water (2 x 50 ml), saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated. When MeI (1.0 ml) was added to the resulting solution of solid in acetone (25 ml) and stirred at 50 ° C. for 30 minutes, a very strong precipitate was observed. Add ether and filter to precipitate yellow product. To this yellow solid is added methanol (10 ml) and ammonium acetate (150 mg) and stirred overnight at room temperature. Purification as described in Example 1B yields 69 mg of a white solid. MS (DCI / NH 3 ) m / z 420 (M + H) + .

실시예 138CExample 138C

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-(4-아미노페닐)우레아, 비스(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-(4-aminophenyl) urea, bis (trifluoroacetate) salt

Boc 보호된 기질(실시예 138B)을 메틸렌 클로라이드:TFA 1:1(25ml)에 용해시키고 실온에서 1시간 동안 교반한다. 용매를 진공하에 증발시키고 톨루엔을 가한 다음 다시 증발시킨다. 물과 약간의 아세토니트릴을 가하고, 여과한 다음 동결건조시킨다. 백색 고체 36mg.Boc protected substrate (Example 138B) is dissolved in methylene chloride: TFA 1: 1 (25 ml) and stirred at room temperature for 1 hour. The solvent is evaporated in vacuo, toluene is added and then evaporated again. Water and some acetonitrile are added, filtered and lyophilized. White solid 36 mg.

MS(ESI/NH3) m/z 320(M+H)+;MS (ESI / NH 3 ) m / z 320 (M + H) + ;

1H NMR(300MHz, DMSO-d6) 9.26(br.s, 2H), 9.21(br.s, 1H), 8.85(br.s, 2H), 8.31(d, J=1.7Hz, 1H), 8.18(d, J=1.7Hz, 1H), 7.95-7.91(m, 2H), 7.68(dd, J1=6.6Hz, J2=2.0Hz, 1H), 7.57(dd, J1=9.2Hz, J2=1.4Hz, 1H), 7.34(d, J=8.8Hz, 2H), 6.91(d, J=8.4Hz, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) 9.26 (br.s, 2H), 9.21 (br.s, 1H), 8.85 (br.s, 2H), 8.31 (d, J = 1.7 Hz, 1H), 8.18 (d, J = 1.7Hz, 1H), 7.95-7.91 (m, 2H), 7.68 (dd, J1 = 6.6Hz, J2 = 2.0Hz, 1H), 7.57 (dd, J1 = 9.2Hz, J2 = 1.4 Hz, 1H), 7.34 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H);

C18H17N5O·2·CF3COOH·H2O에 대한 원소분석치:Elemental Analysis for C 18 H 17 N 5 O · 2 · CF 3 COOH · H 2 O:

계산치: C, 46.73; H, 3.74; N, 12.39.Calc .: C, 46.73; H, 3. 74; N, 12.39.

실측치: C, 47.03; H, 3.55: N, 12.36.Found: C, 47.03; H, 3.55: N, 12.36.

실시예 139Example 139

N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-4-(아미노메틸)사이클로헥산카복스아미드, 비스(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -4-4- (aminomethyl) cyclohexanecarboxamide, bis (trifluoroacetate) salt

메틸렌 클로라이드:TFA 1:1(20ml) 중의 TFA 염으로서의 실시예 137에서 제조된 기질(45mg)의 용액을 실온에서 1시간 동안 교반한다. 용매를 진공하에 증발시키고, 톨루엔을 가한 다음 증발시킨다(20ml x 2). 물에 용해시키고, 여과하고-0.45μ프릿, 동결건조시켜 비스 TFA 염으로서의 백색 고체를 35mg 수득한다.A solution of the substrate (45 mg) prepared in Example 137 as TFA salt in methylene chloride: TFA 1: 1 (20 ml) is stirred at room temperature for 1 hour. The solvent is evaporated in vacuo, toluene is added and then evaporated (20 ml x 2). Soluble in water, filtered and -4.55 mu frit, lyophilized to give 35 mg white solid as bis TFA salt.

MS(ESI/NH3) m/z 325(M+H)+.MS (ESI / NH 3 ) m / z 325 (M + H) + .

1H NMR(300MHz, DMSO-d6) 10.31(s, 1H), 9.31(br.s, 2H), 9.10(br.s, 2H), 8.49(s, 1H), 8.39(s, 1H), 8.04-8.00(m, 2H), 7.78-7.71(m, 2H), 2.71(d, J=7.0Hz, 2H), 2.44-2.36(m, 1H) 1.96-1.85(m, 4H), 1.61-1.42(m, 3H), 1.09-1.02(m, 2H); 1 H NMR (300 MHz, DMSO-d 6 ) 10.31 (s, 1H), 9.31 (br.s, 2H), 9.10 (br.s, 2H), 8.49 (s, 1H), 8.39 (s, 1H), 8.04-8.00 (m, 2H), 7.78-7.71 (m, 2H), 2.71 (d, J = 7.0 Hz, 2H), 2.44-2.36 (m, 1H) 1.96-1.85 (m, 4H), 1.61-1.42 (m, 3 H), 1.09-1.02 (m, 2 H);

C19H24N4O·2·CF3COOH에 대한 원소분석치:Elemental Analysis for C 19 H 24 N 4 O · 2 · CF 3 COOH:

계산치: C, 50.00; H, 4.74; N, 10.14.Calc .: C, 50.00; H, 4. 74; N, 10.14.

실측치: C, 49.95; H, 4.70; N, 09.96.Found: C, 49.95; H, 4. 70; N, 09.96.

실시예 140Example 140

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-[(4-아미노페닐)페닐]우레아, 비스(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-[(4-aminophenyl) phenyl] urea, bis (trifluoroacetate) salt

실시예 140AExample 140A

실온에서 디옥산(8.0ml) 중의 실시예 40B(140mg, 0.72mmol)에서 제조된 이소시아네이트의 용액에 4-N-Boc-아미노메틸벤조산(320mg, 1.44mmol)을 가한 다음 1시간 동안 교반한다. 이 생성물은 반응 동안 침전된다. 이 혼합물을 에테르(150ml)로 희석시키고, 여과한 다음 에테르로 세척하여 백색 고체를 215mg(72%) 수득한다. MS(DCI/NH3) m/z 417(M+H)+.To a solution of isocyanate prepared in Example 40B (140 mg, 0.72 mmol) in dioxane (8.0 ml) at room temperature is added 4-N-Boc-aminomethylbenzoic acid (320 mg, 1.44 mmol) and stirred for 1 hour. This product precipitates out during the reaction. The mixture is diluted with ether (150 ml), filtered and washed with ether to give 215 mg (72%) of a white solid. MS (DCI / NH 3 ) m / z 417 (M + H) + .

실시예 140BExample 140B

10:1 피리딘:트리에틸아민(10ml) 중의 니트릴(실시예 140A)(198mg, 0.47mmol)의 용액을 5분 동안 H2S로 처리하고, 실온에서 18시간 동안 교반하며 농축시킨다. 생성된 고체를 아세톤(15ml)에 용해시키고, 요오도메탄(0.8ml, 12.8mmol)으로 처리하며, 2시간 동안 교반하고, 에테르(10ml)로 희석시키며, 여과하고, 에테르로 세척한 다음 진공하에 건조시킨다. 생성된 고체를 메탄올(4ml)에 용해시키고 NH4OAc(200mg, 2.6mmol)를 실온에서 밤새 가한다. 이 생성물을 실시예 1B에 기재된 과정에 따라서 정제하여 상응하는 아미딘을 112mg(54%) 수득한다. MS(DCI/NH3) m/z 434(M+H)+.A solution of nitrile (Example 140A) (198 mg, 0.47 mmol) in 10: 1 pyridine: triethylamine (10 ml) is treated with H 2 S for 5 minutes and concentrated at room temperature with stirring for 18 hours. The resulting solid is dissolved in acetone (15 ml), treated with iodomethane (0.8 ml, 12.8 mmol), stirred for 2 hours, diluted with ether (10 ml), filtered, washed with ether and then under vacuum To dry. The resulting solid is dissolved in methanol (4 ml) and NH 4 OAc (200 mg, 2.6 mmol) is added overnight at room temperature. This product is purified following the procedure in Example 1B to yield 112 mg (54%) of the corresponding amidine. MS (DCI / NH 3 ) m / z 434 (M + H) + .

실시예 140CExample 140C

N-[6-(아미노이미노메틸)-2-나프탈레닐]-N'-[(4-아미노페닐)페닐]우레아, 비스(트리플루오로아세테이트) 염N- [6- (aminoiminomethyl) -2-naphthalenyl] -N '-[(4-aminophenyl) phenyl] urea, bis (trifluoroacetate) salt

메틸렌 클로라이드:TFA 1:1(20ml) 중의 기질(실시예 140B)의 용액을 실온에서 1시간 동안 교반한다. 용매를 진공하에 증발시키고, 톨루엔을 가한 다음 증발시킨다(20ml x 2). 물에 용해시키고, 여과시키며-0.45μ프릿, 동결건조시킨다. 백색 고체 38.1mg. MS(ESI/NH3) m/z 334(M+H)+;A solution of substrate (Example 140B) in methylene chloride: TFA 1: 1 (20 ml) is stirred at room temperature for 1 hour. The solvent is evaporated in vacuo, toluene is added and then evaporated (20 ml x 2). Soluble in water, filtered, -0.45μ frit, lyophilized. White solid 38.1 mg. MS (ESI / NH 3 ) m / z 334 (M + H) + ;

1H NMR(300MHz, DMSO-d6) 9.68(s, 1H), 9.45(s, 1H), 9.35(br.s, 2H), 9.08(br.s, 2H), 8.40(d, J=1.7Hz, 1H), 8.31(d, J=1.8Hz, 1H), 8.10(br.s, 3H), 8.04-7.99(m, 2H), 7.76(dd, J1=8.8Hz, J2=1.8Hz, 1H), 7.67(dd, J1=8.8Hz, J2=1.7Hz, 1H), 7.58(d, J=8.4Hz, 2H), 7.39(d, J=8.4Hz, 2H), 3.98(br. s, 2H). 1 H NMR (300MHz, DMSO-d 6 ) 9.68 (s, 1H), 9.45 (s, 1H), 9.35 (br.s, 2H), 9.08 (br.s, 2H), 8.40 (d, J = 1.7 Hz, 1H), 8.31 (d, J = 1.8 Hz, 1H), 8.10 (br.s, 3H), 8.04-7.99 (m, 2H), 7.76 (dd, J1 = 8.8 Hz, J2 = 1.8 Hz, 1H ), 7.67 (dd, J1 = 8.8 Hz, J2 = 1.7 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 3.98 (br.s, 2H ).

C19H19N5O1·2·CF3COOH·H2O에 대한 원소분석치:Elemental Analysis for C 19 H 19 N 5 O 1 · 2 · CF 3 COOH · H 2 O:

계산치: C, 47.67; H, 4.00; F, 19.67; N, 12.09.Calc .: C, 47.67; H, 4.00; F, 19.67; N, 12.09.

실측치: C, 47.33; H, 3.70; F, 19.59; N, 11.71.Found: C, 47.33; H, 3. 70; F, 19.59; N, 11.71.

실시예 141Example 141

메틸 [7-(아미노이미노메틸)-3-[[[4-(아미노메틸)페닐]아미노]카보닐]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염Methyl [7- (aminoiminomethyl) -3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate) salt

실시예 141AExample 141A

디옥산(10ml) 중의 실시예 26에서 기재된 바와 같이 제조된 에스테르(747mg, 2.63mmol)의 용액에 아세톤(1ml)과 과량의 수산화나트륨(수중 1N, 10ml)을 가한다. 1시간 후, 혼합물에 물(40ml) 및 에틸 아세테이트(85ml)를 가한 다음 10% 수성 HCl로 산성화시킨다. 에틸 아세테이트 층을 분리하고 물(2 X 20ml)로 세척한 다음 염수로 세척하고, 황산마그네슘으로 건조시키며 여과한 다음 증발시킨다. 생성물을 밝은 황색 고체로서 분리한다. MS m/z 271(M+1)+.To a solution of the ester (747 mg, 2.63 mmol) prepared as described in Example 26 in dioxane (10 ml) is added acetone (1 ml) and excess sodium hydroxide (1 N in water, 10 ml). After 1 hour, water (40 ml) and ethyl acetate (85 ml) are added to the mixture and then acidified with 10% aqueous HCl. The ethyl acetate layer was separated and washed with water (2 X 20 ml) then brine, dried over magnesium sulfate, filtered and evaporated. The product is separated as a light yellow solid. MS m / z 271 (M + l) + .

실시예 141BExample 141B

메틸렌 클로라이드(8.0ml) 중의 실시예 141A에서 제조된 나프토산 유도체(270mg, 1.1mmol)의 현탁액에 디이소프로필에틸아민(DIEA, 485㎕, 2.8mmol)을 가한 다음 O-(아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄헥사플루오로포스페이트(HATU, 527mg, 1.39mmol)를 가한다. 10분 후, 4-N-Boc-아미노메틸아닐린(370mg, 1.7mmol)을 가한다. 1시간 후, 에틸 아세테이트(120ml)를 가하고 유기 층을 5% 수성 시트르산(50ml), 물(2 x 40ml) 및 염수(50ml)로 세척한다. 이 반응물을 황산마그네슘으로 건조시키고, 소량의 실리카를 통하여 여과한 다음 증발시킨다. 헥산 중의 에틸 아세테이트로 용출시키면서 실리카 상에서 정제한다. 농축시킨 후, 생성물을 에틸 아세테이트 및 에테르에 가한 다음 여과시켜 황색 고체를 350.0mg(70%) 수득한다. MS m/z 447(M+1)+.To a suspension of the naphthoic acid derivative (270 mg, 1.1 mmol) prepared in Example 141A in methylene chloride (8.0 ml) was added diisopropylethylamine (DIEA, 485 μl, 2.8 mmol), followed by O- (azabenzotriazole- 1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate (HATU, 527 mg, 1.39 mmol) is added. After 10 minutes, 4-N-Boc-aminomethylaniline (370 mg, 1.7 mmol) is added. After 1 h, ethyl acetate (120 ml) is added and the organic layer is washed with 5% aqueous citric acid (50 ml), water (2 × 40 ml) and brine (50 ml). The reaction is dried over magnesium sulfate, filtered through a small amount of silica and evaporated. Purification on silica eluting with ethyl acetate in hexanes. After concentration, the product is added to ethyl acetate and ether and then filtered to give 350.0 mg (70%) of a yellow solid. MS m / z 447 (M + l) + .

실시예 141CExample 141C

에틸 아세테이트(20ml) 중의 나프 유도체(실시예 141B)(300mg, 0.67mmol)의 현탁액을 Pd 촉매 120mg에 가한 다음 실온에서 수소 대기압하에 1시간 동안 교반한다. 조 생성물을 어떠한 정제 또는 분석 없이 다음 단계에 수행한다.A suspension of naph derivative (Example 141B) (300 mg, 0.67 mmol) in ethyl acetate (20 ml) is added to 120 mg of Pd catalyst and stirred at room temperature under hydrogen atmospheric pressure for 1 hour. The crude product is carried to the next step without any purification or analysis.

디옥산(25ml) 및 10% 수성 탄산나트륨(2.5ml) 중의 조 아민의 용액에 메틸 클로로포르메이트(1.0ml, 과량)를 가한다. 2시간 후, 반응물을 메탄올로 켄칭시키고 에틸 아세테이트(80ml) 및 물(50ml)로 희석시킨다. 에틸 아세테이트 층을 분리하고, 황산마그네슘으로 건조시키며, 여과한 다음 증발시킨다. 이 생성물을 헥산 중의 에틸 아세테이트의 구배(헥산 중의 5 내지 30% 에틸 아세테이트)를 이용하여 실리카 칼럼 상에서 분리한다. 수율: 회백색 고체 140mg.To a solution of the crude amine in dioxane (25 ml) and 10% aqueous sodium carbonate (2.5 ml) is added methyl chloroformate (1.0 ml, excess). After 2 hours, the reaction is quenched with methanol and diluted with ethyl acetate (80 ml) and water (50 ml). The ethyl acetate layer is separated, dried over magnesium sulfate, filtered and evaporated. This product is separated on a silica column using a gradient of ethyl acetate in hexanes (5-30% ethyl acetate in hexanes). Yield: 140 mg of off-white solid.

MS m/z 492(M+18)+.MS m / z 492 (M + 18) + .

실시예 141DExample 141D

실시예 26에 기재된 바와 같이 목적 화합물을 제조한다. MS m/z 492(M+1)+.The desired compound is prepared as described in Example 26. MS m / z 492 (M + l) + .

실시예 141EExample 141E

메틸 [7-(아미노이미노메틸)-3-[[[4-(아미노메틸)페닐]아미노]카보닐]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염Methyl [7- (aminoiminomethyl) -3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate) salt

메틸렌 클로라이드:TFA 4:1(20ml)의 혼합물 중의 기질(실시예 141D)의 용액을 실온에서 15분 동안 교반한다. 용매를 진공하에 농축시키고 RP C18 MPLC 상에서 분리한다. 수율: 회백색 고체 21mg.A solution of the substrate (Example 141D) in a mixture of methylene chloride: TFA 4: 1 (20 ml) is stirred at room temperature for 15 minutes. The solvent is concentrated in vacuo and separated on RP C18 MPLC. Yield: 21 mg of off-white solid.

MS m/z 392 (M+H)+ MS m / z 392 (M + H) +

1H NMR(DMSO): 3.783(s, 3H), 4.03(q, 2H, J=5.5Hz), 7.47(d, 2H, j=8.4Hz), 7.85(d, 2H, j=8.4Hz), 7.94(d, 1H, j=8.8Hz), 8.15(넓은 s, 2H), 8.31(d, 1H, j=8.8Hz), 8.33(s, 1H), 8.47(s, 1H), 8.74(s, 1H), 9.29(s, 2H), 9.47(s, 2H), 9.90(s, 1H), 10.68(s, 1H). 1 H NMR (DMSO): 3.783 (s, 3H), 4.03 (q, 2H, J = 5.5 Hz), 7.47 (d, 2H, j = 8.4 Hz), 7.85 (d, 2H, j = 8.4 Hz), 7.94 (d, 1H, j = 8.8 Hz), 8.15 (wide s, 2H), 8.31 (d, 1H, j = 8.8 Hz), 8.33 (s, 1H), 8.47 (s, 1H), 8.74 (s, 1H), 9.29 (s, 2H), 9.47 (s, 2H), 9.90 (s, 1H), 10.68 (s, 1H).

C25H25F6N5O8(염기 분자 + 2TFA + 1H2O)에 대한 원소분석치:Elemental Analysis for C 25 H 25 F 6 N 5 O 8 (Base Molecule + 2TFA + 1H 2 O):

계산치: C, 47.04; H, 3.70; N, 10.52.Calc .: C, 47.04; H, 3. 70; N, 10.52.

실측치: C, 47.10; H, 3.95; N, 10.99.Found: C, 47.10; H, 3.95; N, 10.99.

실시예 142Example 142

6-(아미노이미노메틸)-N-(4-에틸페닐)-2-나프탈렌카복스아미드, 아세테이트 염6- (aminoiminomethyl) -N- (4-ethylphenyl) -2-naphthalenecarboxamide, acetate salt

실시예 142AExample 142A

실시예 141B에 기재된 바와 동일한 방식으로 반응을 수행한다. 수율: 백색 분말 374mg(61%). MS(DCI/NH3) m/z 301(M+NH4 +).The reaction is carried out in the same manner as described in Example 141B. Yield: 374 mg (61%) of white powder. MS (DCI / NH 3 ) m / z 301 (M + NH 4 + ).

실시예 142BExample 142B

6-(아미노이미노메틸)-N-(4-에틸페닐)-2-나프탈렌카복스아미드, 아세테이트 염6- (aminoiminomethyl) -N- (4-ethylphenyl) -2-naphthalenecarboxamide, acetate salt

실시예 141D에서 제조된 나프틸 유사체 313mg에 대해 기재된 바와 동일한 방식으로 반응을 수행한다. 최종 단계 동안에 침전되는 고체를 여과하고 에테르로 세척하여 아세테이트 염으로서의 백색 고체를 71mg(18%) 수득한다.The reaction is carried out in the same manner as described for 313 mg of the naphthyl analog prepared in Example 141D. The solid that precipitates during the final step is filtered and washed with ether to give 71 mg (18%) of a white solid as an acetate salt.

MS(ECI) m/z 301 (M+H)+;MS (ECI) m / z 301 (M + H) + ;

1H NMR(300MHz, DMSO-d6) δ 1.19(t, J=7.4Hz, 3H), 2.60(q, J=7.4Hz, 2H), 7.22(d, J=8.5Hz, 2H), 7.72(d, J=8.5Hz, 2H), 7.94(dd, J1=8.8Hz, J2=1.7Hz, 1H), 8.08-8.23(m, 3H), 8.47(d, J=1.7Hz, 1H), 8.63(s, 1H), 10.43(br. s, 1H); 1 H NMR (300 MHz, DMSO-d 6 ) δ 1.19 (t, J = 7.4 Hz, 3H), 2.60 (q, J = 7.4 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 7.72 ( d, J = 8.5 Hz, 2H), 7.94 (dd, J 1 = 8.8 Hz, J 2 = 1.7 Hz, 1H), 8.08-8.23 (m, 3H), 8.47 (d, J = 1.7 Hz, 1H), 8.63 (s, 1 H), 10.43 (br. S, 1 H);

C20H19N3O·AcOH·0.5H2O에 대한 원소분석치:Elemental Analysis for C 20 H 19 N 3 O · AcOH · 0.5H 2 O:

계산치: C, 68.38; H, 6.26; N, 10.87.Calc .: C, 68.38; H, 6. 26; N, 10.87.

실측치: C, 68.56; H, 6.21; N, 10.67.Found: C, 68.56; H, 6. 21; N, 10.67.

실시예 143Example 143

6-(아미노이미노메틸)-N-(2-나프탈레닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (2-naphthalenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 143AExample 143A

메틸렌 클로라이드(20ml) 중의 실시예 8B에 기재된 바와 같이 제조된 산 클로라이드(341mg, 1.6mmol)의 용액에 메틸렌 클로라이드(10ml) 및 프로필렌 옥사이드(12ml) 중의 2-아미노 나프탈렌(249mg, 1.74mmol)의 용액을 가한다. 반응물을 실온에서 밤새 교반한다. 반응 혼합물을 에테르에 가하고 생성물을 여과시키며, 에테르 및 헥산으로 세척하고 진공하에 건조시킨다. 수율: 440mg(86%). MS(DCI/NH3) m/z 340(M+NH4)+.Solution of 2-amino naphthalene (249 mg, 1.74 mmol) in methylene chloride (10 ml) and propylene oxide (12 ml) to a solution of acid chloride (341 mg, 1.6 mmol) prepared as described in Example 8B in methylene chloride (20 ml) Add. The reaction is stirred overnight at room temperature. The reaction mixture is added to ether and the product is filtered off, washed with ether and hexanes and dried under vacuum. Yield: 440 mg (86%). MS (DCI / NH 3 ) m / z 340 (M + NH 4 ) + .

실시예 143BExample 143B

6-(아미노이미노메틸)-N-(2-나프탈레닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (2-naphthalenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 141B에 기재된 바와 같이 목적 화합물을 제조한다. 수율: 백색 고체 40mg(10%).The desired compound is prepared as described in Example 141B. Yield: 40 mg (10%) of a white solid.

MS(ESI) m/z 340 (M+H)+.MS (ESI) m / z 340 (M + H) + .

1H NMR(300MHz, DMSO-d6) 7.43-7.55(m, 2H), 7.86-7.96(m, 5H), 8.20-8.28(m, 2H), 8.08-8.23(m, 3H), 8.34(d, J=8.8Hz, 1H), 8.50(d, J=1.7Hz, 1H), 8.57(d, J=1.3Hz, 1H), 8.75(s, 1H), 9.33(br. s, 4H) 10.75(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) 7.43-7.55 (m, 2H), 7.86-7.96 (m, 5H), 8.20-8.28 (m, 2H), 8.08-8.23 (m, 3H), 8.34 (d , J = 8.8 Hz, 1H), 8.50 (d, J = 1.7 Hz, 1H), 8.57 (d, J = 1.3 Hz, 1H), 8.75 (s, 1H), 9.33 (br. S, 4H) 10.75 ( s, 1 H).

C22H17N3O·TFA·0.25H2O에 대한 원소분석치:Elemental Analysis for C 22 H 17 N 3 O · TFA · 0.25H 2 O:

계산치: C, 62.95; H, 4.07; N, 9.18.Calc .: C, 62.95; H, 4.07; N, 9.18.

실측치: C, 63.09; H, 3.72; N, 8.99.Found: C, 63.09; H, 3.72; N, 8.99.

실시예 144Example 144

6-(5-페닐-2-옥사졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (5-phenyl-2-oxazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 144AExample 144A

실온에서 메틸렌 클로라이드(50ml)와 프로필렌 옥사이드(15ml)의 혼합물 중의 펜아실 아민 하이드로클로라이드(Aldrich)(415mg, 2.42mmol)의 현탁액에 메틸렌 클로라이드(30ml) 중의 2-니트릴-6-산 클로라이드(560mg, 2.6mmol)의 용액을 가한 다음 DMF(3.0ml)를 가한다. 이 반응물을 실온에서 밤새 교반한다. 반응 혼합물을 에테르(15ml)에 가하고 생성물을 여과한 다음 헥산으로 세척하여 백색 고체를 555mg(73%) 수득한다. MS(DCI/NH3) m/z 315(M+H)+.2-nitrile-6-acid chloride (560 mg, in methylene chloride (30 ml) in a suspension of phenacyl amine hydrochloride (Aldrich) (415 mg, 2.42 mmol) in a mixture of methylene chloride (50 ml) and propylene oxide (15 ml) at room temperature. 2.6 mmol) is added followed by DMF (3.0 ml). The reaction is stirred overnight at room temperature. The reaction mixture is added to ether (15 ml) and the product is filtered and washed with hexane to give 555 mg (73%) of a white solid. MS (DCI / NH 3 ) m / z 315 (M + H) + .

실시예 144BExample 144B

옥시염화인(3.5ml) 중의 기질(실시예 144A)(354mg, 1.12mmol)의 현탁액을 1.5시간 동안 비등시킨다. 반응 혼합물을 얼음에 붓고 이 혼합물을 에틸 아세테이트(80ml) 및 10% 탄산나트륨(100ml)의 수용액에 가한다. 유기 층을 분리하고, 염수로 세척하며, 황산마그네슘으로 건조시킨 다음 증발시킨다. 에테르를 가한 다음 여과한다. 249mg(75%). MS(DCI/NH3) m/z 297(M+H)+.A suspension of the substrate (Example 144A) (354 mg, 1.12 mmol) in phosphorus oxychloride (3.5 ml) is boiled for 1.5 hours. The reaction mixture is poured on ice and the mixture is added to an aqueous solution of ethyl acetate (80 ml) and 10% sodium carbonate (100 ml). The organic layer is separated, washed with brine, dried over magnesium sulfate and evaporated. Ether is added and then filtered. 249 mg (75%). MS (DCI / NH 3 ) m / z 297 (M + H) + .

실시예 144CExample 144C

6-(5-페닐-2-옥사졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (5-phenyl-2-oxazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실온에서 THF(20ml) 중의 기질 실시예 144B(132mg, 0.44mmol)의 용액에 헥산 중의 1N LiHMDS(1.5ml, 1.5mmol)의 용액을 가한 다음 밤새 교반한다. 디옥산(1ml) 중의 4N HCl로 켄칭시킨다. 10분 후, 물 몇방울을 가하고 30분 더 교반한다. 용매를 진공하에 증발시키고 잔사를 역상 크로마토그래피하여 정제한다. 수율: 백색 고체 58mg(41%).To a solution of Substrate Example 144B (132 mg, 0.44 mmol) in THF (20 ml) at room temperature is added a solution of 1N LiHMDS (1.5 ml, 1.5 mmol) in hexanes and then stirred overnight. Quench with 4N HCl in dioxane (1 ml). After 10 minutes, add a few drops of water and stir for another 30 minutes. The solvent is evaporated in vacuo and the residue is purified by reverse phase chromatography. Yield: 58 mg (41%) of white solid.

MS(ESI/NH3) m/z 314 (M+H)+.MS (ESI / NH 3 ) m / z 314 (M + H) + .

1H NMR(300MHz, DMSO-d6) 9.50(s, 2H), 9.19(s, 2H), 8.86(s, 1H), 8.55(s, 1H), 8.38-8.26(m, 3H), 7.98(s, 1H), 7.96-7.89(m, 3H), 7.58-7.54(m, 2H), 7.47-7.42(m, 1H). 1 H NMR (300 MHz, DMSO-d 6 ) 9.50 (s, 2H), 9.19 (s, 2H), 8.86 (s, 1H), 8.55 (s, 1H), 8.38-8.26 (m, 3H), 7.98 ( s, 1H), 7.96-7.89 (m, 3H), 7.58-7.54 (m, 2H), 7.47-7.42 (m, 1H).

C20H15N3O·1.15CF3COOH에 대한 원소분석치:Elemental Analysis for C 20 H 15 N 3 O · 1.15CF 3 COOH:

계산치: C, 60.26; H, 3.66; N, 9.45; F, 14.75.Calc .: C, 60.26; H, 3. 66; N, 9.45; F, 14.75.

실측치: C, 60.11; H, 3.81; N, 9.20; F, 14.81.Found: C, 60.11; H, 3.81; N, 9.20; F, 14.81.

실시예 145Example 145

6-(5-페닐-2-티아졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (5-phenyl-2-thiazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 145AExample 145A

실시예 144A에서 제조된 기질(340mg, 1.1mmol) 및 로숀 시약(Lawesson's reagent; 600mg, 1.48mmol)의 현탁액을 48시간 동안 85℃로 가열한다. 용매를 증발 건조시키고 생성물을 용출제로서 헥산 중의 10% 에틸 아세테이트를 사용하여 실리카 칼럼을 통하여 분리한다. 수율: 황색 고체 200.0mg(59%). MS(DCI/NH3) m/z 313(M+H)+.A suspension of the substrate (340 mg, 1.1 mmol) and lotion's reagent (600 mg, 1.48 mmol) prepared in Example 144A is heated to 85 ° C. for 48 hours. The solvent is evaporated to dryness and the product is separated through a silica column using 10% ethyl acetate in hexane as eluent. Yield: 200.0 mg (59%) yellow solid. MS (DCI / NH 3 ) m / z 313 (M + H) + .

실시예 145BExample 145B

6-(5-페닐-2-티아졸릴)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (5-phenyl-2-thiazolyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실온에서 THF(20ml) 중의 실시예 145A의 기질(180mg, 0.58mmol)의 용액에 헥산 중의 1N LiHMDS(2.0ml, 2.0mmol)의 용액을 가하고 밤새 교반한다. 디옥산(1ml) 중의 4N HCl로 켄칭시킨다. 10분 후, 몇방울의 물을 가하고 30분 더 교반한다. 용매를 진공하에 증발시키고 잔사를 MPLC RPC18 상에서 정제한다. 수율: 백색 고체 36mg(195). MS(ESl/NH3) m/z 330(M+H)+.To a solution of the substrate of Example 145A (180 mg, 0.58 mmol) in THF (20 ml) at room temperature is added a solution of 1N LiHMDS (2.0 ml, 2.0 mmol) in hexane and stirred overnight. Quench with 4N HCl in dioxane (1 ml). After 10 minutes, add a few drops of water and stir for another 30 minutes. The solvent is evaporated in vacuo and the residue is purified on MPLC RPC18. Yield: 36 mg (195) of white solid. MS (ESl / NH 3 ) m / z 330 (M + H) + .

1H NMR(300MHz, DMSO-d6) 9.49(s, 2H), 9.14(s, 2H), 8.71(s, 1H), 8.52(s, 1H), 8.47(s, 1H), 8.35-8.22(m, 3H), 7.90-7.78(m, 3H), 7.55-7.50(m, 2H), 7.46-7.43(m, 1H). 1 H NMR (300 MHz, DMSO-d 6 ) 9.49 (s, 2H), 9.14 (s, 2H), 8.71 (s, 1H), 8.52 (s, 1H), 8.47 (s, 1H), 8.35-8.22 ( m, 3H), 7.90-7.78 (m, 3H), 7.55-7.50 (m, 2H), 7.46-7.43 (m, 1H).

C20H15N3S·CF3COOH·H2O에 대한 원소분석치:Elemental Analysis for C 20 H 15 N 3 SCF 3 COOHH 2 O:

계산치: C, 57.26; H, 3.93; N, 9.11.Calc .: C, 57.26; H, 3.93; N, 9.11.

실측치: C, 56.83; H, 3.55; N, 8.79.Found: C, 56.83; H, 3.55; N, 8.79.

실시예 146Example 146

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(2-피리딜)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (2-pyridyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 146AExample 146A

실시예 114A의 방식으로 상기 생성물을 제조한다. MS(ESI) m/z (M+H)+340.The product is prepared in the manner of Example 114A. MS (ESI) m / z (M + H) + 340.

실시예 146BExample 146B

6-(아미노이미노메틸)-4-(3-푸라닐)-N-(2-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N- (2-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride

실시예 145B에 기재된 방법을 사용하여 실시예 146A로부터 상기 생성물을 제조한다.The product is prepared from Example 146A using the method described in Example 145B.

MS(CI) m/z (M+H)+357.MS (CI) m / z (M + H) + 357.

1H NMR(300MHz, DMSO-d6) δ 11.27(s, 1H), 9.56(s, 2H), 9.17(s, 2H), 8.76(s, 1H), 8.63(s, 1H), 8.45-8.24(m, 5H), 7.96-7.89(m, 3H), 7.25(m, 2H), 7.18(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 11.27 (s, 1H), 9.56 (s, 2H), 9.17 (s, 2H), 8.76 (s, 1H), 8.63 (s, 1H), 8.45-8.24 (m, 5H), 7.96-7.89 (m, 3H), 7.25 (m, 2H), 7.18 (s, 1H).

C21H18N4O2Cl219/10 HCl에 대한 원소분석치:Elemental analysis for C 21 H 18 N 4 O 2 Cl 2 19/10 HCl:

계산치: C, 54.33; H, 4.75; N, 12.07.Calc .: C, 54.33; H, 4.75; N, 12.07.

실측치: C, 54.89; H, 5.28; N, 9.81.Found: C, 54.89; H, 5. 28; N, 9.81.

실시예 147Example 147

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 147AExample 147A

6-아미노퀴놀린을 사용하여 실시예 118A에 대해 기재된 바와 동일한 방식으로 반응을 정확하게 수행하여 생성물을 72% 수율로 수득한다. 질량 스펙트럼 (CI+) 324(M+I)+.The reaction is carried out exactly in the same manner as described for Example 118A using 6-aminoquinoline to give the product in 72% yield. Mass spectrum (CI +) 324 (M + I) + .

실시예 147BExample 147B

실시예 118B에 대해 기재된 바와 동일한 방식으로 반응을 정확하게 수행하여 생성물을 45% 수율로 수득한다(회백색 고체). 질량 스펙트럼 (ESI+) 341(M+I)+.The reaction is carried out exactly in the same manner as described for Example 118B to give the product in 45% yield (grey white solid). Mass spectrum (ESI +) 341 (M + I) + .

실시예 147CExample 147C

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

탈기 메탄올(15ml) 중의 실시예 147B의 기질(261mg, 0.6mmol)의 현탁액에 산화백금(10mg, 촉매량)을 가한다. 이 반응 혼합물을 대기압하에서 수소로 채우고 밤새 격렬하게 교반한다. 다음날, 이 용액을 셀라이트를 통하여 여과시켜 촉매를 제거하고, 생성물을 용출제로서 메탄올(+0.1% TFA) 및 물(+0.1% TFA)를 사용하여 RPC18 실리카를 이용한 mplc 상에서 정제한다. 수율: 백색 고체 및 비스 TFA 염 122mg.To the suspension of the substrate of Example 147B (261 mg, 0.6 mmol) in degassed methanol (15 ml) was added platinum oxide (10 mg, catalyst amount). The reaction mixture is charged with hydrogen under atmospheric pressure and stirred vigorously overnight. The next day, the solution is filtered through celite to remove the catalyst and the product is purified on mplc with RPC18 silica using methanol (+ 0.1% TFA) and water (+ 0.1% TFA) as eluents. Yield: 122 mg of white solid and bis TFA salt.

MS(ESI+) 345 (M+1)+.MS (ESI < + >) 345 (M + 1) + .

1H NMR(DMSO-d6) 10.51(s, 1H), 9.65(s, 2H), 9.50(s, 2H), 8.64(s, 1H), 8.52(s, 1H), 8.22(d, J=8.0Hz, 1H), 8.12(Abq, J=9.0Hz, 2H), 7.86(d, J=9.0Hz, 1H), 7.61(s, 1H), 7.56(d, J=8.0Hz, 1H), 6.98(d, J=8.5Hz, 1H), 3.28(t, J=5.5Hz, 2H), 2.75(t, J=6.3Hz, 2H), 1.92-1.86(m, 2H); 1 H NMR (DMSO-d 6 ) 10.51 (s, 1H), 9.65 (s, 2H), 9.50 (s, 2H), 8.64 (s, 1H), 8.52 (s, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.12 (Abq, J = 9.0 Hz, 2H), 7.86 (d, J = 9.0 Hz, 1H), 7.61 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 8.5 Hz, 1H), 3.28 (t, J = 5.5 Hz, 2H), 2.75 (t, J = 6.3 Hz, 2H), 1.92-1.86 (m, 2H);

C21H2ON4O+2.25TFA+0.25H2O에 대한 원소분석치:Elemental Analysis for C 21 H 2 ON 4 O + 2.25TFA + 0.25H 2 O:

C,50.59(50.46); H, 3.79(3.79); N, 9.25(9.25); F, 21.18(20.83).C, 50.59 (50.46); H, 3.79 (3.79); N, 9.25 (9.25); F, 21.18 (20.83).

실시예 148Example 148

7-메톡시-8-(피라지닐옥시)-2-나프탈렌카복스이미드아미드, 디메탄설포네이트 염7-methoxy-8- (pyrazinyloxy) -2-naphthalenecarboximideamide, dimethanesulfonate salt

실시예 148AExample 148A

실시예 4A로부터의 생성물(125mg, 0.627mmol)을 N-메틸피롤리딘온(4ml) 중의 클로로피라진(112ml, 1.25mmol) 및 Cs2CO3(409mg, 1.25mmol)과 합하고, 반응물을 130℃에서 1시간 동안 교반한다. 반응물을 냉각시키고, 조 혼합물을 용출제로서 40% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 75mg(43%) 수득한다. MS(DCI/NH3) m/z 278(M+H)+.The product from Example 4A (125 mg, 0.627 mmol) was combined with chloropyrazine (112 ml, 1.25 mmol) and Cs 2 CO 3 (409 mg, 1.25 mmol) in N-methylpyrrolidinone (4 ml) and the reaction was at 130 ° C. Stir for 1 hour. The reaction is cooled and the crude mixture is chromatographed on SiO 2 using 40% ethyl acetate / hexane as eluent to yield 75 mg (43%) of the title compound. MS (DCI / NH 3 ) m / z 278 (M + H) + .

실시예 148BExample 148B

7-메톡시-8-(피라지닐옥시)-2-나프탈렌카복스이미드아미드, 디메탄설포네이트 염7-methoxy-8- (pyrazinyloxy) -2-naphthalenecarboximideamide, dimethanesulfonate salt

실시예 148A로부터의 생성물(70mg, 0.252mmol)에 실시예 1B에 기재된 과정을 적용하여 목적 화합물(106mg, 71%)을 수득한다. 융점 155℃.The procedure described in Example 1B was applied to the product from Example 148A (70 mg, 0.252 mmol) to afford the desired compound (106 mg, 71%). Melting point 155 캜.

MS(DCI(NH3)) m/z 295 (M+H)+.MS (DCI (NH 3 )) m / z 295 (M + H) + .

1H NMR(300MHz, DMSO) δ 9.42(br s, 2H), 9.04(br s, 2H), 8.72(s, 1H), 8.38(d, J=3Hz, 1H), 8.36(m, 1H), 8.21(d, J=9Hz, 1H), 8.09(m, 1H), 8.06(d, J=9Hz, 1H), 7.82(d, J=9Hz, 1H), 7.73(dd, J=9.2Hz, 1H), 3.83(s, 3H), 2.38(s, 3H). 1 H NMR (300 MHz, DMSO) δ 9.42 (br s, 2H), 9.04 (br s, 2H), 8.72 (s, 1H), 8.38 (d, J = 3 Hz, 1H), 8.36 (m, 1H), 8.21 (d, J = 9Hz, 1H), 8.09 (m, 1H), 8.06 (d, J = 9Hz, 1H), 7.82 (d, J = 9Hz, 1H), 7.73 (dd, J = 9.2Hz, 1H ), 3.83 (s, 3 H), 2.38 (s, 3 H).

C18H2N4S2O8·1.1CH4SO3에 대한 원소분석치:Elemental Analysis for C 18 H 2 N 4 S 2 O 8 · 1.1CH 4 SO 3 :

계산치: C, 38.74; H, 4.49; N, 9.46.Calc .: C, 38.74; H, 4. 49; N, 9.46.

실측치: C, 38.68; H, 4.53; N, 9.34.Found: C, 38.68; H, 4.53; N, 9.34.

실시예 149Example 149

7-메톡시-8-(페닐티오)-2-나프탈렌카복스이미드아미드, 메탄설포네이트7-methoxy-8- (phenylthio) -2-naphthalenecarboximideamide, methanesulfonate

실시예 149AExample 149A

HMPA(2ml) 중의 NaH(48mg, 60%, 1.2mmol)의 용액에 PhSH(0.133ml, 1.3mmol)을 가하고, 반응물을 5분 동안 교반한다. 이에 실시예 53B로부터의 생성물(309mg, 1mmol)을 가하고, 반응물을 100℃에서 3시간 동안 가열한다. 조 반응 혼합물을 용출제로서 20% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피한다. 이 생성물을 에틸 아세테이트(10ml) 및 메탄올(10ml)에 용해시키고, TMSCHN2(10ml)의 2M 용액으로 처리한다. 이 반응물을 60분 동안 교반하고 농축시킨다. 조 생성물을 15% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 115mg(39%) 수득한다. MS(DCI/NH3) m/z 309(M+NH4)+.To a solution of NaH (48 mg, 60%, 1.2 mmol) in HMPA (2 ml) is added PhSH (0.133 ml, 1.3 mmol) and the reaction is stirred for 5 minutes. To this was added the product from Example 53B (309 mg, 1 mmol) and the reaction was heated at 100 ° C. for 3 hours. The crude reaction mixture is chromatographed on SiO 2 using 20% ethyl acetate / hexanes as eluent. This product is dissolved in ethyl acetate (10 ml) and methanol (10 ml) and treated with a 2M solution of TMSCHN 2 (10 ml). The reaction is stirred for 60 minutes and concentrated. The crude product is chromatographed on SiO 2 with 15% ethyl acetate / hexanes to give 115 mg (39%) of the title compound. MS (DCI / NH 3 ) m / z 309 (M + NH 4 ) + .

실시예 149BExample 149B

7-메톡시-8-(페닐티오)-2-나프탈렌카복스이미드아미드, 메탄설포네이트7-methoxy-8- (phenylthio) -2-naphthalenecarboximideamide, methanesulfonate

실시예 55D의 과정에 따라서 실시예 149A로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 149A following the procedure of Example 55D.

MS(DCI/NH3) m/z 309 (M+H)+.MS (DCI / NH 3 ) m / z 309 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 2.33(s, 3H), 3.96(s, 3H), 6.96(d, 2H), 7.11(dd, 1H), 7.20(d, 1H), 7.22(d, 1H), 7.69(dd, 1H), 7.82(d, 1H), 8.22(d, 1H), 8.33(d, 1H), 8.81(s, 1H), 9.01(br s, 2H), 9.46(br s, 2H). 1 H NMR (300MHz, DMSO-d 6 ) δ 2.33 (s, 3H), 3.96 (s, 3H), 6.96 (d, 2H), 7.11 (dd, 1H), 7.20 (d, 1H), 7.22 (d , 1H), 7.69 (dd, 1H), 7.82 (d, 1H), 8.22 (d, 1H), 8.33 (d, 1H), 8.81 (s, 1H), 9.01 (br s, 2H), 9.46 (br s, 2H).

C18H16N2OS·1.15CH4SO3에 대한 원소분석치:Elemental Analysis for C 18 H 16 N 2 OS · 1.15CH 4 SO 3 :

계산치: C, 54.91; H, 4.96; N, 6.69.Calc .: C, 54.91; H, 4.96; N, 6.69.

실측치: C, 54.70; H, 5.15; N, 6.58.Found: C, 54.70; H, 5. 15; N, 6.58.

실시예 150Example 150

7-메톡시-8-(피라지닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염7-methoxy-8- (pyrazinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 91A에 기재된 방법을 사용하여 실시예 90D에서 제조된 생성물로부터 목적 화합물을 제조한 다음, 이를 실시예 40D에 기재된 바와 같은 아미딘으로 전환시킨다.The desired compound is prepared from the product prepared in Example 90D using the method described in Example 91A and then converted to amidine as described in Example 40D.

MS(DCI/NH3) m/z (M+H)+294.MS (DCI / NH 3 ) m / z (M + H) + 294.

1H NMR(300MHz, DMSO-d6) δ 9.39(s, 2H), 9.02(s, 2H), 8.95(s, 1H), 8.40(d, 1H), 8.14(d, 1H), 8.03(s, 2H), 7.92(dd, 1H), 7.84(d, 1H), 7.76(d, 1H) 7.66(dd, 1H), 3.90(s, 3H). 1 H NMR (300MHz, DMSO-d 6 ) δ 9.39 (s, 2H), 9.02 (s, 2H), 8.95 (s, 1H), 8.40 (d, 1H), 8.14 (d, 1H), 8.03 (s , 2H), 7.92 (dd, 1H), 7.84 (d, 1H), 7.76 (d, 1H) 7.66 (dd, 1H), 3.90 (s, 3H).

C20H17N5O5F61/2 TFA에 대한 원소분석치:Elemental Analysis for C 20 H 17 N 5 O 5 F 6 1/2 TFA:

계산치: C, 43.79; H, 3.07; N, 12.20.Calc .: C, 43.79; H, 3.07; N, 12.20.

실측치: C, 43.81; H, 3.22; N, 12.24.Found: C, 43.81; H, 3. 22; N, 12.24.

실시예 152Example 152

6-(아미노이미노메틸)-4-(3-푸라닐)-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 152AExample 152A

CH2Cl2(125ml) 중의 실시예 8D로부터의 생성물(5.50g, 26.04mmol)의 용액에 디브로모디메틸하이단토인(4.47g, 15.62mmol) 및 트리플루오로메탄설폰산(2.51ml, 28.41mmol)을 가하고, 반응물을 암실에서 23℃하에 18시간 동안 교반한다. 혼합물을 수성 NaHSO3에 붓고, 용액을 Na2CO3로 염기성이 되도록 하며 3x 에틸 아세테이트로 추출하고, 이 추출물을 염수로 세척하며, Na2SO4로 건조시킨 다음 농축시킨다. 생성물을 에탄올/에틸 아세테이트로 재결정화하여 목적 화합물을 5.80g(77%) 수득한다. MS(DCI/NH3) m/z 307(M+NH4)+.To a solution of the product from Example 8D (5.50 g, 26.04 mmol) in CH 2 Cl 2 (125 ml) dibromodimethylhydantoin (4.47 g, 15.62 mmol) and trifluoromethanesulfonic acid (2.51 ml, 28.41) mmol) is added and the reaction is stirred in the dark at 23 ° C. for 18 h. The mixture is poured into aqueous NaHSO 3 , the solution is made basic with Na 2 CO 3 and extracted with 3 × ethyl acetate, the extract is washed with brine, dried over Na 2 SO 4 and concentrated. The product is recrystallized from ethanol / ethyl acetate to give 5.80 g (77%) of the title compound. MS (DCI / NH 3 ) m / z 307 (M + NH 4 ) + .

실시예 152BExample 152B

THF(40ml), 물(10ml) 및 메탄올(10ml) 중의 실시예 152A로부터의 생성물(1.40g, 4.826mmol)의 용액에 LiOH·물(405mg, 9.65mmol)을 가하고, 반응물을 18시간 동안 교반한다. 혼합물을 1M HCl에 따라 붓고 3x 에틸 아세테이트로 추출하고, 추출물을 염수로 세척하며, Na2SO4로 건조시킨 다음 농축시켜 목적 화합물을 1.23g(92%) 수득한다. MS(DCI/NH3) m/z 295(M+NH4)+.To a solution of the product from Example 152A (1.40 g, 4.826 mmol) in THF (40 ml), water (10 ml) and methanol (10 ml) was added LiOH.water (405 mg, 9.65 mmol) and the reaction stirred for 18 hours. . The mixture is poured into 1M HCl and extracted with 3x ethyl acetate, the extract is washed with brine, dried over Na 2 S0 4 and concentrated to give 1.23 g (92%) of the desired compound. MS (DCI / NH 3 ) m / z 295 (M + NH 4 ) + .

실시예 152CExample 152C

톨루엔(25ml) 중의 실시예 152B로부터의 생성물(440mg, 1.60mmol)의 용액에 옥살릴 클로라이드(0.140ml, 1.6mmol)를 가하고, 반응물을 80℃에서 18시간 동안 교반한다. 톨루엔을 HCl 방출이 중단될 때까지 비등시키고, 반응물을 냉각시킨다. 아닐린(1ml, 11mmol)을 가하고 반응물을 10분 동안 교반하며, 1M HCl에 붓는다. 이 용액을 3x 에틸 아세테이트로 추출하고, 이 추출물을 염수로 세척하며 Na2SO4로 건조시킨 다음 농축시켜 목적 화합물을 560mg(99%) 수득한다. MS(DCI/NH3) m/z 370(M+NH4)+.To a solution of the product from Example 152B (440 mg, 1.60 mmol) in toluene (25 ml) is added oxalyl chloride (0.140 ml, 1.6 mmol) and the reaction is stirred at 80 ° C. for 18 hours. Toluene is boiled until HCl release is stopped and the reaction is cooled. Aniline (1 ml, 11 mmol) is added and the reaction is stirred for 10 minutes and poured into 1M HCl. The solution is extracted with 3x ethyl acetate and the extract is washed with brine, dried over Na 2 S0 4 and concentrated to give 560 mg (99%) of the title compound. MS (DCI / NH 3 ) m / z 370 (M + NH 4 ) + .

실시예 152DExample 152D

실시예 57B의 과정에 따라서 실시예 152C(408mg, 1.16mmol) 및 푸란-3-보론산(182mg, 1.62mmol)으로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 356(M+NH4)+.The desired compound is prepared from Example 152C (408 mg, 1.16 mmol) and furan-3-boronic acid (182 mg, 1.62 mmol) following the procedure of Example 57B. MS (DCI / NH 3 ) m / z 356 (M + NH 4 ) + .

실시예 152EExample 152E

6-(아미노이미노메틸)-4-(3-푸라닐)-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- (3-furanyl) -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 40D의 과정에 따라서 실시예 152D로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 152D according to the procedure of Example 40D.

MS(DCI/NH3) m/z 356 (M+H)+.MS (DCI / NH 3 ) m / z 356 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 7.15(m, 2H), 7.41(dd, 2H), 7.83(d, 2H), 7.91(d, 1H), 7.99(dd, 1H), 8.19(d, 1H), 8.38(s, 1H), 8.41(d, 1H), 8.62(s, 1H), 8.69(s, 1H), 9.15(br s, 2H), 9.55(br s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 7.15 (m, 2H), 7.41 (dd, 2H), 7.83 (d, 2H), 7.91 (d, 1H), 7.99 (dd, 1H), 8.19 (d , 1H), 8.38 (s, 1H), 8.41 (d, 1H), 8.62 (s, 1H), 8.69 (s, 1H), 9.15 (br s, 2H), 9.55 (br s, 2H).

C22H17N3O2·2.75HCl에 대한 원소분석치:Elemental Analysis for C 22 H 17 N 3 O 2 · 2.75HCl:

계산치: C, 57.99; H, 4.37; N, 9.22.Calc .: C, 57.99; H, 4. 37; N, 9.22.

실측치: C, 57.85; H, 4.84; N, 9.44.Found: C, 57.85; H, 4. 84; N, 9.44.

실시예 153Example 153

6-(아미노이미노메틸)-4-[1-(메틸설포닐)-1H-피라졸-4-일]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [1- (methylsulfonyl) -1H-pyrazol-4-yl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 153AExample 153A

실시예 47A의 과정에 따라서 실시예 53D로부터의 생성물 및 실시예 152A로부터의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 408(M+H)+.The desired compound is prepared from the product from Example 53D and the product from Example 152A according to the procedure of Example 47A. MS (DCI / NH 3 ) m / z 408 (M + H) + .

실시예 153BExample 153B

실시예 53F의 과정에 따라서 실시예 153A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 278(M+H)+.The desired compound is prepared from the product of Example 153A following the procedure of Example 53F. MS (DCI / NH 3 ) m / z 278 (M + H) + .

실시예 153CExample 153C

실시예 87A(86A)의 과정에 따라서 실시예 153B의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 373(M+NH4)+.The desired compound is prepared from the product of Example 153B following the procedure of Example 87A (86A). MS (DCI / NH 3 ) m / z 373 (M + NH 4 ) + .

실시예 153DExample 153D

실시예 152B 및 152C의 과정에 따라서 실시예 153C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 356(M-SO2Me+NH4)+.The desired compound is prepared from the product of Example 153C following the procedure of Examples 152B and 152C. MS (DCI / NH 3 ) m / z 356 (M-SO 2 Me + NH 4 ) + .

실시예 153EExample 153E

6-(아미노이미노메틸)-4-[1-(메톡시설포닐)-1H-피라졸-4-일]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [1- (methoxysulfonyl) -1H-pyrazol-4-yl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 40D의 과정에 따라서 실시예 153D의 생성물로부터 목적 화합물을 제조한다.The desired compound is prepared from the product of Example 153D following the procedure of Example 40D.

MS(DCI/NH3) 없음;MS (DCI / NH 3 ) absent;

1H NMR(300MHz, DMSO-d6) δ 3.99(s, 3H), 7.14(t, 1H), 7.40(t, 2H), 7.84(d, 2H), 7.91(d, 1H), 8.08(s, 1H), 8.15(d, 1H), 8.35(m, 2H), 8.65(br s, 2H), 9.33(br s, 2H), 9.61(br s, 2H), 10.58(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.99 (s, 3H), 7.14 (t, 1H), 7.40 (t, 2H), 7.84 (d, 2H), 7.91 (d, 1H), 8.08 (s , 1H), 8.15 (d, 1H), 8.35 (m, 2H), 8.65 (br s, 2H), 9.33 (br s, 2H), 9.61 (br s, 2H), 10.58 (s, 1H).

C22H19N5SO3·2.75HCl에 대한 원소분석치:Elemental Analysis for C 22 H 19 N 5 SO 3 · 2.75HCl:

계산치: C, 49.51; H, 4.11; N, 13.12.Calc .: C, 49.51; H, 4.11; N, 13.12.

실측치: C, 49.44; H, 3.83; N, 12.09.Found: C, 49.44; H, 3.83; N, 12.09.

실시예 154Example 154

6-(아미노이미노메틸)-4-[5-(메틸티오)-3-푸라닐)]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (methylthio) -3-furanyl)]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 154AExample 154A

-78℃에서 THF(40ml) 중의 2-트리메틸실릴-3-브로모푸란(4.17g, 19.03mmol)의 용액에 LDA(12.7ml, 19.03mmol)의 1.5M 용액을 가하고, 반응물을 -78℃에서 1시간 동안 교반한다. 이어서, 메틸 디설파이드(1.89ml, 20.93mmol)을 가하고, 반응물을 밤새 실온으로 가온시킨다. 반응물을 포화 수성 NH4Cl 용액에 붓고, 3x 디에틸 에테르로 추출한다. 합한 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 물질을 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 3.02g(60%) 수득한다. MS(DCI/NH3) m/z 265, 267(M+H)+.To a solution of 2-trimethylsilyl-3-bromofuran (4.17 g, 19.03 mmol) in THF (40 ml) at -78 ° C was added 1.5 M solution of LDA (12.7 ml, 19.03 mmol) and the reaction was added at -78 ° C. Stir for 1 hour. Methyl disulfide (1.89 ml, 20.93 mmol) is then added and the reaction is allowed to warm to room temperature overnight. The reaction is poured into saturated aqueous NH 4 Cl solution and extracted with 3 × diethyl ether. The combined extracts are washed with brine, dried over Na 2 S0 4 and concentrated. The crude material is chromatographed on SiO 2 using hexane as eluent to afford 3.02 g (60%) of the title compound. MS (DCI / NH 3 ) m / z 265, 267 (M + H) + .

실시예 154BExample 154B

THF(20ml) 중의 실시예 154A로부터의 생성물(2.68g, 10.1mmol) 및 TBAF(20.2ml)의 1M 용액을 30분 동안 교반한다. 반응물을 농축시키고 목적 화합물을 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 2-메틸티오-4-브로모푸란을 1.39g(71%) 수득한다. 이 물질을 다음 단계에 바로 사용한다. -78℃에서 THF(25ml) 중의 상기 생성물(7mmol)의 용액에 BuLi(2.8ml, 7mmol)의 2.5M 용액을 가하고, 반응물을 5분 동안 교반한다. 이어서, Bu3SnCl(1.90ml, 7mmol)을 가하고, 반응물을 30분 동안 교반한 다음 실온으로 가온시킨다. 반응물을 포화 수성 NH4Cl 용액에 붓고, 3x 디에틸 에테르로 추출한다. 합한 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 물질을 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 1.24g(30%) 수득한다. MS(DCI/NH3) m/z 404(M+H)+.The 1M solution of product from Example 154A (2.68 g, 10.1 mmol) and TBAF (20.2 ml) in THF (20 ml) is stirred for 30 minutes. The reaction is concentrated and the target compound is chromatographed on SiO 2 using hexane as eluent to yield 1.39 g (71%) of 2-methylthio-4-bromofuran. Use this material immediately for the next step. To a solution of the product (7 mmol) in THF (25 ml) at −78 ° C. add a 2.5 M solution of BuLi (2.8 ml, 7 mmol) and stir the reaction for 5 minutes. Then Bu 3 SnCl (1.90 ml, 7 mmol) is added and the reaction is stirred for 30 minutes and then allowed to warm to room temperature. The reaction is poured into saturated aqueous NH 4 Cl solution and extracted with 3 × diethyl ether. The combined extracts are washed with brine, dried over Na 2 S0 4 and concentrated. The crude material is chromatographed on SiO 2 using hexane as eluent to yield 1.24 g (30%) of the title compound. MS (DCI / NH 3 ) m / z 404 (M + H) + .

실시예 154CExample 154C

CH3CN(15ml) 중의 PDCl2(PPh3)2(161mg, 0.23mmol), 실시예 154B로부터의 생성물(920mg, 2.28mmol) 및 실시예 152A로부터의 생성물(662mg, 2.28mmol)의 용액을 80℃에서 18시간 동안 교반한다. 반응물을 농축시키고 조 물질을 용출제로서 20% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 671mg(91%) 수득한다. MS(DCI/NH3) m/z 324(M+H)+.A solution of PDCl 2 (PPh 3 ) 2 (161 mg, 0.23 mmol), product from Example 154B (920 mg, 2.28 mmol) and product from Example 152A (662 mg, 2.28 mmol) in CH 3 CN (15 ml) was added to 80 Stir at 18 ° C. for 18 hours. The reaction is concentrated and the crude is chromatographed on SiO 2 using 20% ethyl acetate / hexane as eluent to give 671 mg (91%) of the title compound. MS (DCI / NH 3 ) m / z 324 (M + H) + .

실시예 154DExample 154D

실시예 152B의 과정에 따라서 실시예 154C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 310(M+H)+.The desired compound is prepared from the product of Example 154C following the procedure of Example 152B. MS (DCI / NH 3 ) m / z 310 (M + H) + .

실시예 154EExample 154E

실시예 152C의 과정에 따라서 실시예 154D의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 402(M+NH4)+.The desired compound is prepared from the product of Example 154D following the procedure of Example 152C. MS (DCI / NH 3 ) m / z 402 (M + NH 4 ) + .

실시예 154FExample 154F

6-(아미노이미노메틸)-4-[5-(메틸티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (methylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정에 따라서 실시예 154E의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 402(M+H)+.The desired compound is prepared from the product of Example 154E following the procedure of Example 144C. MS (DCI / NH 3 ) m / z 402 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 2.54(s, 3H), 7.15(t, 1H), 7.24(s, 1H), 7.40(t, 2H), 7.84(d, 2H), 7.92(dd, 1H), 8.19(d, 1H), 8.39(d, 1H), 8.44(s, 1H), 8.61(s, 1H), 8.69(s, 1H), 9.35(br s, 4H), 10.61(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 2.54 (s, 3H), 7.15 (t, 1H), 7.24 (s, 1H), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 (dd , 1H), 8.19 (d, 1H), 8.39 (d, 1H), 8.44 (s, 1H), 8.61 (s, 1H), 8.69 (s, 1H), 9.35 (br s, 4H), 10.61 (s , 1H).

C23H19SO2·2.25HCl에 대한 원소분석치:Elemental Analysis for C 23 H 19 SO 2 · 2.25HCl:

계산치: C, 57.14; H, 4.43; N, 8.69.Calc .: C, 57.14; H, 4. 43; N, 8.69.

실측치: C, 57.13; H, 4.21; N, 8.56.Found: C, 57.13; H, 4. 21; N, 8.56.

실시예 155Example 155

메틸 [7-(아미노이미노메틸)-1-나프탈레닐]메틸카바메이트, 모노(트리플루오로아세테이트) 염Methyl [7- (aminoiminomethyl) -1-naphthalenyl] methylcarbamate, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 40mg(42%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 40 mg (42%) of a white solid.

MS m/z: 258 (M+H)+.MS m / z: 258 (M + H) + .

1H NMR(DMSO, 300MHz): 3.28(s, 3H), 3.82(br, 3H), 7.66(dd, 1H, J1=7.5Hz, J2=1.4Hz), 7.78(m, 1H), 8.89(Dd, 1H, J1=8.8Hz, J2=2.0Hz), 8.05(d, 1H, 8.1Hz), 8.24(d, 1H, 8.8Hz), 8.30(s, 1H), 9.09(s, 2H), 9.52(s, 2H). 1 H NMR (DMSO, 300 MHz): 3.28 (s, 3H), 3.82 (br, 3H), 7.66 (dd, 1H, J 1 = 7.5 Hz, J 2 = 1.4 Hz), 7.78 (m, 1H), 8.89 (Dd , 1H, J1 = 8.8Hz, J2 = 2.0Hz), 8.05 (d, 1H, 8.1Hz), 8.24 (d, 1H, 8.8Hz), 8.30 (s, 1H), 9.09 (s, 2H), 9.52 ( s, 2H).

C14H15N3O2·1.25C2F3O2H·0.25H2O에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 2 · 1.25C 2 F 3 O 2 H · 0.25H 2 O:

계산치: C, 49.02; H, 4.18; N, 10.39.Calc .: C, 49.02; H, 4. 18; N, 10.39.

실측치: C, 48.81; H, 3.91; N, 10.15.Found: C, 48.81; H, 3.91; N, 10.15.

실시예 156Example 156

프로필 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염Propyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 52mg(46%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 52 mg (46%) of white solid.

MS m/z: 272 (M+H)+.MS m / z: 272 (M + H) + .

1H NMR(DMSO, 300MHz): 0.97(t, 3H, J1=J2=7.1Hz), 1.67(6중선, 2H, J=7.1Hz), 4.19(t, 3H, J1=J2=6.8Hz), 7.71(d, 1H, 8.5Hz), 7.83(m, 3H), 8.14(d, 1H, J=8.5Hz), 8.67(s, 1H), 9.22(Br, 3H), 9.63(s, 1H). 1 H NMR (DMSO, 300 MHz): 0.97 (t, 3H, J 1 = J 2 = 7.1 Hz), 1.67 (hexadecimal, 2H, J = 7.1 Hz), 4.19 (t, 3H, J 1 = J 2 = 6.8 Hz), 7.71 (d, 1H, 8.5 Hz), 7.83 (m, 3H), 8.14 (d, 1H, J = 8.5 Hz), 8.67 (s, 1H), 9.22 (Br, 3H), 9.63 (s, 1H).

C15H17N3O2·0.25C2F3O2H·0.75H2O에 대한 원소분석치:Elemental Analysis for C 15 H 17 N 3 O 2 0.25C 2 F 3 O 2 H0.75H 2 O:

계산치: C, 49.18; H, 4.66; N, 9.83.Calc .: C, 49.18; H, 4. 66; N, 9.83.

실측치: C, 49.27; H, 4.87; N, 10.02.Found: C, 49.27; H, 4.87; N, 10.02.

실시예 157Example 157

N-[7-(아미노이미노메틸)-1-나프탈레닐]-N'-메틸우레아, 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] -N'-methylurea, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 36mg(54%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 36 mg (54%) of white solid.

MS m/z: 243 (M+H)+.MS m / z: 243 (M + H) + .

1H NMR(DMSO, 300MHz): 2.80(d, 1H), 6.45(d, H), 7.70(m, 2H), 7.82(dd, J1=8.9Hz, J2=2.1Hz), 8.08(dd, 7.4Hz, J=1.3Hz), 8.17(d, 1H, J=8.5Hz), 8.62(s, 1H), 8.72(s, 1H), 9.07(s, 2H), 9.47(s, 2H), (s, 2H). 1 H NMR (DMSO, 300 MHz): 2.80 (d, 1H), 6.45 (d, H), 7.70 (m, 2H), 7.82 (dd, J1 = 8.9 Hz, J2 = 2.1 Hz), 8.08 (dd, 7.4 Hz, J = 1.3 Hz, 8.17 (d, 1H, J = 8.5 Hz), 8.62 (s, 1H), 8.72 (s, 1H), 9.07 (s, 2H), 9.47 (s, 2H), (s , 2H).

C13H14N4O·1.5C2F3O2H·0.5H2O에 대한 원소분석치:Elemental Analysis for C 13 H 14 N 4 O · 1.5C 2 F 3 O 2 H · 0.5H 2 O:

계산치: C, 45.50; H, 3.94; N, 13.27.Calc .: C, 45.50; H, 3.94; N, 13.27.

실측치: C, 45.22; H, 3.86; N, 13.12.Found: C, 45.22; H, 3.86; N, 13.12.

실시예 158Example 158

에틸 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염Ethyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 70mg(76%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 70 mg (76%) of white solid.

MS m/z: 258 (M+H)+.MS m / z: 258 (M + H) + .

1H NMR(DMSO, 300MHz): 1.30(t, 3H, J1=J2=7.4Hz), 4.20(q, 2H, J=7.0Hz), 7.80(m, 4H), 8.15(d, 8.5Hz), 8.68(s, 1H), 9.13(s, 2H), 9.38(s, 2H), 9.66(s, 1H); 1 H NMR (DMSO, 300 MHz): 1.30 (t, 3H, J 1 = J 2 = 7.4 Hz), 4.20 (q, 2H, J = 7.0 Hz), 7.80 (m, 4H), 8.15 (d, 8.5 Hz), 8.68 (s, 1 H), 9.13 (s, 2 H), 9.38 (s, 2 H), 9.66 (s, 1 H);

C14H15N3O2·1.5C2F3O2H에 대한 원소분석치: C 14 H 15 N 3 O 2 · 1.5C 2 F 3 O 2 H Elemental analysis for:

계산치: C, 47.67; H, 3.88; N, 9.81.Calc .: C, 47.67; H, 3.88; N, 9.81.

실측치: C, 47.97; H, 3.85; N, 9.78.Found: C, 47.97; H, 3. 85; N, 9.78.

실시예 159Example 159

N-[7-(아미노이미노메틸)-1-나프탈레닐]프로판아미드, 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] propanamide, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 20mg(23%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 20 mg (23%) of a white solid.

MS m/z: 242 (M+H)+.MS m / z: 242 (M + H) + .

1H NMR(DMSO, 300MHz): 1.18(t, 3H, 7.4Hz), 3.38(m, 2H), 7.89(m, 3H), 7.81(dd, 1H, J1=8.4Hz, J2=1.9Hz), 7.87(d, 1H, 8.5Hz), 8.58(s, 1H), 9.02(s, 2H), 9.47(s, 2H), 9.97(s, 1H). 1 H NMR (DMSO, 300 MHz): 1.18 (t, 3H, 7.4 Hz), 3.38 (m, 2H), 7.89 (m, 3H), 7.81 (dd, 1H, J1 = 8.4 Hz, J2 = 1.9 Hz), 7.87 (d, 1H, 8.5 Hz), 8.58 (s, 1H), 9.02 (s, 2H), 9.47 (s, 2H), 9.97 (s, 1H).

C14H15N3O·1.15C2F3O2H·0.25H2O에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O · 1.15C 2 F 3 O 2 H · 0.25H 2 O:

계산치: C, 51.94; H, 4.45; N, 11.15.Calc .: C, 51.94; H, 4. 45; N, 11.15.

실측치: C, 52.02; H, 4.24; N, 10.76.Found: C, 52.02; H, 4. 24; N, 10.76.

실시예 160Example 160

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-메톡시아세트아미드, 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-methoxyacetamide, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 30mg(30%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 30 mg (30%) of a white solid.

MS m/z: 258 (M+H)+.MS m / z: 258 (M + H) + .

1H NMR(DMSO, 300MHz) δ 3.49(s, 3H), 4.18(s, 2H), 7.80(m, 3H), 7.93(d, 1H, 7.7Hz), 8.47(d, 1H, 8.5Hz), 8.47(s, 1H), 9.10(s, 2H), 9.46(s, 2H), 9.99(s, 2H). 1 H NMR (DMSO, 300 MHz) δ 3.49 (s, 3H), 4.18 (s, 2H), 7.80 (m, 3H), 7.93 (d, 1H, 7.7 Hz), 8.47 (d, 1H, 8.5 Hz), 8.47 (s, 1H), 9.10 (s, 2H), 9.46 (s, 2H), 9.99 (s, 2H).

C14H15N3O2·1C2F3O2H·1.25H2O에 대한 원소분석치:Elemental Analysis for C 14 H 15 N 3 O 2 · 1C 2 F 3 O 2 H · 1.25H 2 O:

계산치: C, 48.80; H, 4.73; N, 10.67.Calc .: C, 48.80; H, 4.73; N, 10.67.

실측치: C, 48.53; H, 4.34; N, 10.54Found: C, 48.53; H, 4. 34; N, 10.54

1H NMR(DMSO, 300MHz): 2.16(s, 3H), 4.85(s, 2H), 7.82(m, 4H), 8.18(d, 1H, J=8.18Hz,), 8.55(s, 1H), 9.10(s, 2H), 9.44(s, 2H), 10.24(s, 1H); 1 H NMR (DMSO, 300 MHz): 2.16 (s, 3H), 4.85 (s, 2H), 7.82 (m, 4H), 8.18 (d, 1H, J = 8.18 Hz,), 8.55 (s, 1H), 9.10 (s, 2 H), 9.44 (s, 2 H), 10.24 (s, 1 H);

C15H15N3O3·1C2F3O2H·1H2O에 대한 원소분석치:Elemental Analysis for C 15 H 15 N 3 O 3 · 1C 2 F 3 O 2 H · 1H 2 O:

계산치: C, 48.93; H, 4.35; N, 10.07.Calc .: C, 48.93; H, 4. 35; N, 10.07.

실측치: C, 48.82; H, 4.27; N, 10.00.Found: C, 48.82; H, 4. 27; N, 10.00.

실시예 161Example 161

N-[7-(아미노이미노메틸)-1-나프탈레닐]우레아, 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] urea, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 황색을 띠는 고체 35mg(54%).The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 35 mg (54%) of a yellowish solid.

MS m/z: 229(M+H)+.MS m / z: 229 (M + H) + .

1H NMR(DMSO, 300MHz): 6.22(s, 2H), 7.65(m, 2H), 7.77(dd, J1=8.8Hz, J2=1.5Hz), 8.57(s, 1H), 8.79(s, 1H), 9.07(s, 2H), 9.49(br, 2H). 1 H NMR (DMSO, 300 MHz): 6.22 (s, 2H), 7.65 (m, 2H), 7.77 (dd, J1 = 8.8 Hz, J2 = 1.5 Hz), 8.57 (s, 1H), 8.79 (s, 1H ), 9.07 (s, 2 H), 9.49 (br, 2 H).

C12H12N4O·1 C2F3O2H·0.75H2O에 대한 원소분석치:Elemental Analysis for C 12 H 12 N 4 O · 1 C 2 F 3 O 2 H · 0.75H 2 O:

계산치: C, 40.90; H, 3.33; N, 11.95.Calc .: C, 40.90; H, 3.33; N, 11.95.

실측치: C, 40.95; H, 3.64; N, 12.31.Found: C, 40.95; H, 3. 64; N, 12.31.

실시예 162Example 162

N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-하이드록시아세트아미드, 모노(트리플루오로아세테이트) 염N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-hydroxyacetamide, mono (trifluoroacetate) salt

실시예 12 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 백색 고체 24mg(37%). MS m/z: 244 (M+H)+ The desired compound is prepared according to the procedure described in Examples 12 and 13. Yield: 24 mg (37%) of white solid. MS m / z: 244 (M + H) +

1H NMR(DMSO, 300MHz): 4.18(s, 2H), 5.82(br, 1H), 7.67(m, 1H), 7.85(m, 3H), 8.20(d, 1H), 9.18(s, 2H), 9.42(s, 2H), 9.89(s, 1H); 1 H NMR (DMSO, 300 MHz): 4.18 (s, 2H), 5.82 (br, 1H), 7.67 (m, 1H), 7.85 (m, 3H), 8.20 (d, 1H), 9.18 (s, 2H) , 9.42 (s, 2 H), 9.89 (s, 1 H);

C13H13N3O2·1 C2F3O2H·0.75H2O에 대한 원소분석치:Elemental Analysis for C 13 H 13 N 3 O 2 · 1 C 2 F 3 O 2 H · 0.75H 2 O:

계산치: C, 48.59; H, 4.21; N, 11.33.Calc .: C, 48.59; H, 4. 21; N, 11.33.

실측치: C, 48.64; H, 3.89; N, 11.25.Found: C, 48.64; H, 3.89; N, 11.25.

실시예 163Example 163

8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 91A 및 13에 기재된 과정에 따라서 목적 화합물을 제조한다. 수율: 담황색 고체 28mg(28%). MS m/z: 264 (M+H)+ The desired compound is prepared following the procedure described in Examples 91A and 13. Yield: 28 mg (28%) of a pale yellow solid. MS m / z: 264 (M + H) +

1H NMR(DMSO, 300MHz): 6.90(t, 1H, J1=J2=4.7Hz), 7.69(d, J=7.8Hz), 7.80(1H, J=8.1Hz), 7.81(1H, dd, J1=8.4Hz, J2=2.1Hz), 8.08(1H, dd, J1=7.4Hz, J2=0.6Hz), 8.14(1H, d, J=8.5Hz), 8.49(d, 2H), 8.75(1H, d, J=1.7Hz), 9.06(s, 2H), 9.37(s, 2H), 9.60(s, 1H). 1 H NMR (DMSO, 300 MHz): 6.90 (t, 1H, J1 = J2 = 4.7 Hz), 7.69 (d, J = 7.8 Hz), 7.80 (1H, J = 8.1 Hz), 7.81 (1H, dd, J1 = 8.4 Hz, J2 = 2.1 Hz), 8.08 (1H, dd, J1 = 7.4 Hz, J2 = 0.6 Hz), 8.14 (1H, d, J = 8.5 Hz), 8.49 (d, 2H), 8.75 (1H, d, J = 1.7 Hz), 9.06 (s, 2H), 9.37 (s, 2H), 9.60 (s, 1H).

C15H13N5·2.25 C2F3O2H·0.25 H2O에 대한 원소분석치:Elemental Analysis for C 15 H 13 N 5 · 2.25 C 2 F 3 O 2 H · 0.25 H 2 O:

계산치: C, 44.67; H, 4.283.03; N, 13.36.Calc .: C, 44.67; H, 4.283.03; N, 13.36.

실측치: C, 44.49; H, 2.80; N, 13.40.Found: C, 44.49; H, 2. 80; N, 13.40.

실시예 164Example 164

8-아미노-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염8-amino-2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실온에서 10:1 피리딘:트리에틸아민(10ml) 중의 실시예 10에서 기재된 바와 같이 제조된 조 8-아미노-2-니트릴-나프탈렌의 용액에 황화수소를 5분 동안 버블링시키고 실온에서 밤새 교반한다. 이 반응 혼합물을 물(50ml)에 가하고 생성물을 에틸 아세테이트(3 x 30ml)로 추출한다. 합한 유기 용매를 황산마그네슘으로 건조시키고, 여과한 다음 증발시킨다. 생성된 황색 물질을 아세톤(30ml)에 용해시키고 메틸 요오다이드(2ml)를 가한다. 반응 혼합물을 1시간 동안 비등시킨 다음, 증발 건조시킨다. 생성된 메탄올(25ml) 중의 황색 물질에 암모늄 아세테이트(100mg)를 가하고 실온에서 밤새 교반한다. 용매를 진공하에 제거하고 생성물을 용출제로서 0.1% TFA/물 및 0.1% TFA/메탄올을 사용하여 역상 크로마토그래피를 통하여 정제한다.Hydrogen sulfide is bubbled in a solution of crude 8-amino-2-nitrile-naphthalene prepared as described in Example 10 in 10: 1 pyridine: triethylamine (10 ml) at room temperature for 5 minutes and stirred at room temperature overnight. The reaction mixture is added to water (50 ml) and the product is extracted with ethyl acetate (3 x 30 ml). The combined organic solvents are dried over magnesium sulfate, filtered and then evaporated. The resulting yellow substance is dissolved in acetone (30 ml) and methyl iodide (2 ml) is added. The reaction mixture is boiled for 1 hour and then evaporated to dryness. To the resulting yellow substance in methanol (25 ml) ammonium acetate (100 mg) is added and stirred at room temperature overnight. The solvent is removed in vacuo and the product is purified via reverse phase chromatography using 0.1% TFA / water and 0.1% TFA / methanol as eluent.

MS m/z: 186 (M+H)+.MS m / z: 186 (M + H) + .

1H NMR(DMSO, 300MHz): 5.14(br, 3H), 6.80(dd, 1H, J1=7.8Hz, J2=1Hz), 7.17(d, 1H, J=7.8Hz), 7.40(dd, 1H, J1=J2=7.8Hz), 7.70(dd, 1H, J1=8.9Hz, J2=2.1Hz), 7.91(d, 1H, J=8.5Hz), 8.65(s, 1H), 8.95(s, 2H), 9.23(s, 2H). 1 H NMR (DMSO, 300 MHz): 5.14 (br, 3H), 6.80 (dd, 1H, J1 = 7.8 Hz, J2 = 1 Hz), 7.17 (d, 1H, J = 7.8 Hz), 7.40 (dd, 1H, J1 = J2 = 7.8Hz), 7.70 (dd, 1H, J1 = 8.9Hz, J2 = 2.1Hz), 7.91 (d, 1H, J = 8.5Hz), 8.65 (s, 1H), 8.95 (s, 2H) , 9.23 (s, 2 H).

C11H11N3·2.5 C2F3O2H·0.75 H2O에 대한 원소분석치:Elemental Analysis for C 11 H 11 N 3 · 2.5 C 2 F 3 O 2 H · 0.75 H 2 O:

계산치: C, 39.72; H, 3.13; N, 8.69.Calc .: C, 39.72; H, 3.13; N, 8.69.

실측치: C, 40.01; H, 3.19; N, 8.88.Found: C, 40.01; H, 3. 19; N, 8.88.

실시예 165Example 165

6-(아미노이미노메틸)-N-[4-(아미노메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 트리스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [4- (aminomethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, tris (trifluoroacetate) salt

실시예 165AExample 165A

-5℃에서 진한 황산(5ml) 중의 2-니트릴-6-메틸에스테르 나프탈렌 실시예 8D(5.0g, 23mmol)의 현탁액에 고체 질산칼륨을 가한다. 반응 혼합물의 색이 점차적으로 진한 갈색으로 변한다. 이 반응 혼합물을 15분 동안 교반하고, 얼음-물에 붓는다. 침전을 수집하고 물로 세척한다. 조 생성물을 에틸 아세테이트로 및 에탄올로 재결정화한다. 담황색 분말 4.3g(68%).Solid potassium nitrate is added to a suspension of 2-nitrile-6-methylester naphthalene Example 8D (5.0 g, 23 mmol) in concentrated sulfuric acid (5 ml) at -5 ° C. The color of the reaction mixture gradually turns dark brown. The reaction mixture is stirred for 15 minutes and poured into ice-water. The precipitate is collected and washed with water. The crude product is recrystallized from ethyl acetate and ethanol. 4.3 g (68%) of pale yellow powder.

실시예 165BExample 165B

THF(100ml)와 에틸 아세테이트(120ml)의 혼합물 중의 2-니트릴-6-메틸에스테르-8-니트로-나프탈렌, 실시예 165A(3.5g, 13.6mmol)의 용액에 10% Pd-C(350mg)를 가한다. 반응 혼합물을 수소 대기압(풍선)하에 두고 실온에서 35시간 동안 교반한다. 혼합물을 셀라이트 및 실리카 겔을 통하여 여과하고, 에틸 아세테이트로 세척한 다음 증발시킨다. 생성된 고체를 에테르(200ml)로 세척한다. 수율: 황색 분말 2.20g(71%).To a solution of 2-nitrile-6-methylester-8-nitro-naphthalene, Example 165A (3.5 g, 13.6 mmol) in a mixture of THF (100 ml) and ethyl acetate (120 ml) was added 10% Pd-C (350 mg). Add. The reaction mixture is placed under hydrogen atmospheric pressure (balloon) and stirred at room temperature for 35 hours. The mixture is filtered through celite and silica gel, washed with ethyl acetate and then evaporated. The resulting solid is washed with ether (200 ml). Yield: 2.20 g (71%) yellow powder.

실시예 165CExample 165C

질소하에 오븐 건조된 플라스크 내에서 2-니트릴-6-메틸에스테르-8-아미노-나프탈렌, 실시예 165B(2.8g, 12.3mmol), BINAP(116mg, 0.186mmol), Pd(DBA)3(64mg, 0.061mmol), NaO-t-Bu(1.667g, 17.6mmol), 2-브로모피리미딘(2.363g, 14.9mmol) 및 톨루엔(80ml)을 함유하는 혼합물을 실온에서 10분 동안 교반한다. 이 반응 혼합물을 1시간 동안 80℃로 가열한다. 반응이 끝날 무렵(TLC, 헥산+에틸 아세테이트=4:1), 염수(9200ml)를 가한다. 이 혼합물을 CH2Cl2(4 x 250ml)로 추출한다. 용매를 증발시킨다. 수율: 담황색 분말 3.5g(93%).2-nitrile-6-methylester-8-amino-naphthalene, Example 165B (2.8 g, 12.3 mmol), BINAP (116 mg, 0.186 mmol), Pd (DBA) 3 (64 mg, in an oven dried flask under nitrogen 0.061 mmol), NaO-t-Bu (1.667 g, 17.6 mmol), 2-bromopyrimidine (2.363 g, 14.9 mmol) and toluene (80 ml) are stirred at room temperature for 10 minutes. The reaction mixture is heated to 80 ° C. for 1 hour. At the end of the reaction (TLC, hexane + ethyl acetate = 4: 1), brine (9200 ml) is added. This mixture is extracted with CH 2 Cl 2 (4 × 250 ml). Evaporate the solvent. Yield: 3.5 g (93%) of pale yellow powder.

실시예 165DExample 165D

에탄올(150ml) 중의 2-니트릴-6-메틸에스테르-8-N-(2-피리미딘)-나프탈렌, 실시예 165C(5.2g, 17.1mmol)의 현탁액에 수(200ml) 중 탄산칼륨(3.54g, 33.3mmol)을 가한다. 생성된 현탁액을 120℃에서 2시간 동안 가열하고, 이때 모든 현탁액이 투명한 용액으로 변하게 된다. 이 혼합물을 냉각시킨 다음, 2N HCl로 산성화시킨다. 생성된 침전물을 여과시켜 수집하여 담황색 분말을 4.5g(90%) 수득한다. 다음 단계를 위해 추가로 정제할 필요가 없다.To a suspension of 2-nitrile-6-methylester-8-N- (2-pyrimidine) -naphthalene, Example 165C (5.2 g, 17.1 mmol) in ethanol (150 ml) potassium carbonate (3.54 g) in water (200 ml) , 33.3 mmol) is added. The resulting suspension is heated at 120 ° C. for 2 hours, at which time all the suspension turns into a clear solution. The mixture is cooled and then acidified with 2N HCl. The resulting precipitate is collected by filtration to give 4.5 g (90%) of a pale yellow powder. No further purification is required for the next step.

실시예 165EExample 165E

DMF(150ml) 중의 2-니트릴-8-N-(2-피리미딘)-6-카복실산-나프탈렌 실시예 165D(5.0g, 17.2mmol)의 찬(0℃) 용액에 DIEA(7.6ml, 42.6mmol) 및 O-(7-아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄헥사플루오로포스페이트(9.8g, 25.7mmol)을 가한 다음, 3급-부톡시카보닐아미노-4-아미노메틸아닐린(5.74g, 20mmol)을 가한다. 생성된 반응 혼합물을 약 1시간 동안 교반한다. 반응물을 물(200ml)로 켄칭시키고 생성된 침전을 여과시켜 수집하여 담황색 분말을 3.26g(38%) 수득한다.2-nitrile-8-N- (2-pyrimidine) -6-carboxylic acid-naphthalene in DMF (150 ml) DIEA (7.6 ml, 42.6 mmol) in cold (0 ° C.) solution of Example 165D (5.0 g, 17.2 mmol). ) And O- (7-azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate (9.8 g, 25.7 mmol) were added, followed by tertiary-part Toxylcarbonylamino-4-aminomethylaniline (5.74 g, 20 mmol) is added. The resulting reaction mixture is stirred for about 1 hour. The reaction is quenched with water (200 ml) and the resulting precipitate is collected by filtration to give 3.26 g (38%) of a pale yellow powder.

실시예 165FExample 165F

피리딘(150ml) 중의 기질, 실시예 165E(3.0g, 6.07mmol)의 용액에 트리에틸아민(9ml)을 가한다. H2S를 10분 동안 통과시키고 생성된 혼합물을 실온에서 48시간 동안 교반한다. 물 100ml를 반응 혼합물에 가하고 침전을 여과시켜 수집한다. 수율: 황색 고체 3.0g(93%).Triethylamine (9 ml) is added to a solution of the substrate, Example 165E (3.0 g, 6.07 mmol) in pyridine (150 ml). Pass H 2 S for 10 minutes and stir the resulting mixture for 48 hours at room temperature. 100 ml of water are added to the reaction mixture and the precipitate is collected by filtration. Yield: 3.0 g (93%) of a yellow solid.

실시예 165GExample 165G

아세톤(200ml) 중의 티오아미드인 실시예 165F의 용액에 MeI(6ml)를 가하고, 이 혼합물을 실온에서 밤새 교반한다. 이 혼합물을 증발 건조시켜 황색 고체를 1.2g(78%) 수득한다.To a solution of Example 165F, a thioamide in acetone (200 ml), MeI (6 ml) is added and the mixture is stirred at rt overnight. The mixture is evaporated to dryness to yield 1.2 g (78%) of a yellow solid.

실시예 165HExample 165H

6-(아미노이미노메틸)-N-[4-(아미노메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 트리스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [4- (aminomethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, tris (trifluoroacetate) salt

메탄올(50ml) 중의 이미데이트 에스테르인 실시예 165G(1.5g, 2.2mmol)의 용액에 암모늄 아세테이트(0.5g, 6.4mmol)를 가하고 실온에서 밤새 교반한다. 용매를 증발시킨 후, 잔사를 에테르(3 x 25ml)로 처리하고 에테르를 경사 여과한다. 잔사를 10:1:1 아세토니트릴:물:아세트산의 혼합물(50ml)에 용해시킨다. 에테르(100ml)를 가한 후, Boc 보호된 생성물이 아세테이트 염으로서 침전되고 여과시켜 수집한다. 이 고체를 티오아니졸(0.5ml)을 함유하는 1:1 TFA:메틸렌 클로라이드(50ml)에 가한다. 반응 혼합물을 실온에서 밤새 교반한다. 생성물을 용출제로서 0.1% TFA를 함유하는 물:메탄올을 사용하여 RPC18크로마토그래피하여 정제한다. 동결건조시킨 후 수율: 담황색 고체 0.5g(54%).To a solution of Example 165G (1.5 g, 2.2 mmol), which is an imidate ester in methanol (50 ml), ammonium acetate (0.5 g, 6.4 mmol) was added and stirred overnight at room temperature. After evaporating the solvent, the residue is treated with ether (3 × 25 ml) and the ether is filtered off with gradient. The residue is dissolved in a mixture of 10: 1: 1 acetonitrile: water: acetic acid (50 ml). After addition of ether (100 ml), Boc protected product is precipitated as an acetate salt and collected by filtration. This solid is added to 1: 1 TFA: methylene chloride (50 ml) containing thioanisole (0.5 ml). The reaction mixture is stirred overnight at room temperature. The product is purified by RPC 18 chromatography using water: methanol containing 0.1% TFA as eluent. Yield after lyophilization: 0.5 g (54%) of a pale yellow solid.

MS m/z: 412 (M+H)+;MS m / z: 412 (M + H) + ;

1H NMR(DMSO, 300MHz): 4.02(q, 2H, J=5.8), 6.94(dd, 1H, J12=J2=4.8Hz), 7.45(d, 2H, J=8.5Hz), 7.84(d, 2H, J=8.4Hz), 7.92(dd, 1H, J1=8.5Hz, J2=1.7Hz), 8.13(br, 3H), 8.30(d, 1H, J=8.9Hz), 8.41(s, 1H), 8.52(d, 2H), 8.55(s, 1H), 8.81(s, 1H), 9.19(s, 2H), 9.43(s, 2H), 9.75(s, 1H), 10.62(s, 1H). 1 H NMR (DMSO, 300 MHz): 4.02 (q, 2H, J = 5.8), 6.94 (dd, 1H, J12 = J2 = 4.8 Hz), 7.45 (d, 2H, J = 8.5 Hz), 7.84 (d, 2H, J = 8.4Hz), 7.92 (dd, 1H, J1 = 8.5Hz, J2 = 1.7Hz), 8.13 (br, 3H), 8.30 (d, 1H, J = 8.9Hz), 8.41 (s, 1H) 8.52 (d, 2H), 8.55 (s, 1H), 8.81 (s, 1H), 9.19 (s, 2H), 9.43 (s, 2H), 9.75 (s, 1H), 10.62 (s, 1H).

C23H21N7O·2.5 C2F3O2H·1 H2O에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 7 O · 2.5 C 2 F 3 O 2 H · 1 H 2 O:

계산치: C, 43.49; H, 3.22; N, 11.83.Calc .: C, 43.49; H, 3. 22; N, 11.83.

실측치: C, 43.54; H, 3.34; N, 11.69.Found: C, 43.54; H, 3. 34; N, 11.69.

실시예 166Example 166

6-(아미노이미노메틸)-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

4-아미노벤질 아민을 아닐린으로 대체하면서 실시예 165에 기재된 바와 동일한 과정을 수행한다.The same procedure as described in Example 165 is performed while replacing 4-aminobenzyl amine with aniline.

MS m/z: 383 (M+H)+.MS m / z: 383 (M + H) + .

1H NMR(DMSO, 300MHz): 6.93-6.96(m, 1H), 7.14(dd, 1H, J1=7.3Hz, J2=7.4Hz), 7.40(dd, 2H, J1=J2=7.3Hz), 7.80(d, 2H, J=8.1Hz), 7.91(d, 1H, J=8.9Hz), 8.30(d, 1H, J=9.0Hz), 8.41(s, 1H), 8.52-8.54(m, 3H), 8.80(s, 1H), 9.16(s, 2H), 9.45(s, 2H), 9.78(s, 1H), 10.55(s, 1H). 1 H NMR (DMSO, 300 MHz): 6.93-6.96 (m, 1H), 7.14 (dd, 1H, J1 = 7.3 Hz, J2 = 7.4 Hz), 7.40 (dd, 2H, J1 = J2 = 7.3 Hz), 7.80 (d, 2H, J = 8.1Hz), 7.91 (d, 1H, J = 8.9Hz), 8.30 (d, 1H, J = 9.0Hz), 8.41 (s, 1H), 8.52-8.54 (m, 3H) , 8.80 (s, 1H), 9.16 (s, 2H), 9.45 (s, 2H), 9.78 (s, 1H), 10.55 (s, 1H).

C22H18N6O·2 C2F3O2H·0.25 H2O에 대한 원소분석치:Elemental Analysis for C 22 H 18 N 6 O · 2 C 2 F 3 O 2 H · 0.25 H 2 O:

계산치: C, 50.78; H, 3.28; N, 13.31.Calc .: C, 50.78; H, 3. 28; N, 13.31.

실측치: C, 50.85; H, 3.28; N, 13.31.Found: C, 50.85; H, 3. 28; N, 13.31.

실시예 167Example 167

N-[(4-아미노메틸)페닐]-6-[아미노(하이드록시이미노)메틸]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염N-[(4-aminomethyl) phenyl] -6- [amino (hydroxyimino) methyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

메탄올(40ml) 및 물(20ml) 중의 실시예 165E에서 제조된 화합물(0.20g, 0.40mmol)의 현탁액에 하이드록실아민 하이드로클로라이드(112mg, 1.75mmol) 및 탄산나트륨(85mg, 0.80mmol)을 가하고, 반응 혼합물을 실온에서 48시간 동안 교반시키면, TLC에 어떠한 반응도 나타나지 않는다. 이 반응 혼합물을 환류하에 10시간 동안 가열하고 대부분의 용매를 제거하고, 침전을 여과시켜 수집하여 담황색 고체를 1.2g 수득한다. 이 고체를 1:1 TFA+CH2Cl2(30ml)에 용해시키고 실온에서 24시간 동안 교반한다. 용매를 진공하에 제거하고 잔사를 R18 역상 칼럼에 로딩한다. 이 분획을 동결건조시켜 담황색 분말(80mg, 66%)을 수득한다.To a suspension of the compound prepared in Example 165E (0.20 g, 0.40 mmol) in methanol (40 ml) and water (20 ml) was added hydroxylamine hydrochloride (112 mg, 1.75 mmol) and sodium carbonate (85 mg, 0.80 mmol) and reacted. If the mixture is stirred at room temperature for 48 hours, no reaction appears in TLC. The reaction mixture is heated under reflux for 10 hours and most of the solvent is removed and the precipitate is collected by filtration to give 1.2 g of a pale yellow solid. This solid is dissolved in 1: 1 TFA + CH 2 Cl 2 (30 ml) and stirred at room temperature for 24 hours. The solvent is removed in vacuo and the residue is loaded on an R18 reversed phase column. This fraction is lyophilized to give a pale yellow powder (80 mg, 66%).

MS m/z: 428 (M+H)+.MS m / z: 428 (M + H) + .

1H NMR(DMSO, 300MHz): 4.02(q, 2H, J=6.1Hz), 6.92(dd, 1H, J1=J2=5.1Hz), 7.46(d, 2H, 8.4Hz), 7.85(d, 2H, J=8.5Hz), 7.88(d, 1H, 9Hz), 8.12(br, 3H), 8.22(d, 1H, J=8.9Hz), 8.40(s, 1H), 8.48(s, 1H), 8.51(d, 2H, J=4.8Hz), 8.64(s, 1H), 9.74(s, 2H), 10.61(s, 2H). 1 H NMR (DMSO, 300 MHz): 4.02 (q, 2H, J = 6.1 Hz), 6.92 (dd, 1H, J1 = J2 = 5.1 Hz), 7.46 (d, 2H, 8.4 Hz), 7.85 (d, 2H , J = 8.5 Hz), 7.88 (d, 1H, 9 Hz), 8.12 (br, 3H), 8.22 (d, 1H, J = 8.9 Hz), 8.40 (s, 1H), 8.48 (s, 1H), 8.51 (d, 2H, J = 4.8 Hz), 8.64 (s, 1H), 9.74 (s, 2H), 10.61 (s, 2H).

C23H21N7O2·2.9 C2F3O2H·1.25 H2O에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 7 O 2 · 2.9 C 2 F 3 O 2 H · 1.25 H 2 O:

계산치: C, 44.31; H, 3.41; N, 12.56; F, 21.17.Calc .: C, 44.31; H, 3.41; N, 12.56; F, 21.17.

실측치: C, 44.08; H, 3.30; N, 12.50, 4, 21.25.Found: C, 44.08; H, 3. 30; N, 12.50, 4, 21.25.

실시예 168Example 168

6-(아미노이미노메틸)-N-[4-(하이드록시메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [4- (hydroxymethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

4-아미노 벤질아민 대신 4-아미노 벤질 알콜을 사용하여 실시예 165에 기재된 바와 같이 목적 화합물을 수득한다.4-amino benzyl alcohol instead of 4-amino benzylamine is used to give the desired compound as described in Example 165.

MS m/z: 413 (M+H)+.MS m / z: 413 (M + H) + .

1H NMR(DMSO, 300MHz): 4.48(s, 2H), 6.94(dd, 1H, 2H, J=8.8Hz, J1=J2=4.8Hz), 7.32(d, 2H, J=8.8Hz), 7.90(dd, 1H, J1=8.5Hz, J2=1.7Hz), 8.28(d, 2H, J=8.8Hz), 8.41(s, 1H), 8.54(d, 2H, J=4.8Hz), 8.55(dd, 1H, J=1.3Hz), 8.80(s, 1H), 9.08(s, 2H), 9.43(s, 2H), 9.73(s, 1H), 10.48(s, 1H). 1 H NMR (DMSO, 300 MHz): 4.48 (s, 2H), 6.94 (dd, 1H, 2H, J = 8.8 Hz, J1 = J2 = 4.8 Hz), 7.32 (d, 2H, J = 8.8 Hz), 7.90 (dd, 1H, J1 = 8.5 Hz, J2 = 1.7 Hz), 8.28 (d, 2H, J = 8.8 Hz), 8.41 (s, 1H), 8.54 (d, 2H, J = 4.8 Hz), 8.55 (dd , 1H, J = 1.3 Hz, 8.80 (s, 1H), 9.08 (s, 2H), 9.43 (s, 2H), 9.73 (s, 1H), 10.48 (s, 1H).

C23H2ON6O2에 대한 원소분석치:Elemental Analysis for C 23 H 2 ON 6 O 2 :

계산치: C, 49.06; H, 3.83; N, 12.81; F, 16.50.Calc .: C, 49.06; H, 3.83; N, 12.81; F, 16.50.

실측치: C, 48.74; H, 3.86; N, 12.63, F, 16.54.Found: C, 48.74; H, 3.86; N, 12.63, F, 16.54.

실시예 170Example 170

메틸 [3-[[[4-(아미노메틸)페닐]아미노]카보닐]-7-[4-아미노(하이드록시이미노)메틸]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염Methyl [3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -7- [4-amino (hydroxyimino) methyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate ) Salt

실시예 170AExample 170A

메탄올(40ml) 및 물(5ml) 중의 니트릴인 실시예 141D(213mg, 0.45mmol) 및 하이드록실아민 하이드로클로라이드(338mg, 4.86mmol)의 현탁액에 탄산칼륨(538mg, 3.9mmol)을 가하고 실온에서 밤새 교반한다. 용매를 증발시키고 생성된 고체를 에테르 및 헥산으로 세척하여 백색 고체로서의 생성물을 153mg(62%) 수득한다. MS(ECI) m/z 508(M+H)+.To a suspension of Example 141D (213 mg, 0.45 mmol) and hydroxylamine hydrochloride (338 mg, 4.86 mmol), which is nitrile in methanol (40 ml) and water (5 ml), potassium carbonate (538 mg, 3.9 mmol) was added and stirred at room temperature overnight. do. The solvent is evaporated and the resulting solid is washed with ether and hexane to give 153 mg (62%) of the product as a white solid. MS (ECI) m / z 508 (M + H) +.

실시예 170BExample 170B

메틸 [3-[[[4-(아미노메틸)페닐]아미노]카보닐]-7-[4-아미노(하이드록시이미노)메틸]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염Methyl [3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -7- [4-amino (hydroxyimino) methyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate ) Salt

Boc 보호된 기질인 실시예 170A를 디옥산 중의 4N HCl 3ml에 가하고 실온에서 20분 동안 교반한다. 용매를 진공하에 증발시키고 생성물을 용출제로서 메탄올-물 +0.1% TFA를 사용하여 RPC18의 칼럼을 이용하여 MPLC 상에서 분리한다. 백색 고체 수율: 117mg(79%).Example 170A, a Boc protected substrate, is added to 3 ml of 4N HCl in dioxane and stirred at room temperature for 20 minutes. The solvent is evaporated in vacuo and the product is separated on MPLC using a column of RPC 18 using methanol-water + 0.1% TFA as eluent. White solid yield: 117 mg (79%).

MS (ECI) m/z 408 (M+H)+;MS (ECI) m / z 408 (M + H) + ;

1H NMR(300MHz, DMSO-d6) δ 3.77(s, 3H), 4.03(s, 2H), 4.01(q, J=5.9, 2H), 7.46(d, J=8.5Hz, 2H), 7.86(d, J=8.5Hz, 2H), 7.90(dd, J1=8.5, Hz, J2=1.4Hz, 1H), 8.09-8.15(m, 4H), 8.17(d, J=8.4Hz, 1H), 8.29(s, 1H), 8.42(s, 1H), 8.56(s, 1H), 9.80(s, 1H), 10.62(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.77 (s, 3H), 4.03 (s, 2H), 4.01 (q, J = 5.9, 2H), 7.46 (d, J = 8.5Hz, 2H), 7.86 (d, J = 8.5 Hz, 2H), 7.90 (dd, J 1 = 8.5, Hz, J 2 = 1.4 Hz, 1H), 8.09-8.15 (m, 4H), 8.17 (d, J = 8.4 Hz, 1H ), 8.29 (s, 1H), 8.42 (s, 1H), 8.56 (s, 1H), 9.80 (s, 1H), 10.62 (s, 1H).

C21H21N5O4·2.5 TEA·0.5 H2O에 대한 원소분석치:Elemental analysis for C 21 H 21 N 5 O 4 · 2.5 TEA · 0.5 H 2 O:

계산치: C, 44.52; H, 3.52; F, 20.31; N, 9.98.Calc .: C, 44.52; H, 3.52; F, 20.31; N, 9.98.

실측치: C, 44.78; H, 3.57; F, 19.82; N, 9.87.Found: C, 44.78; H, 3.57; F, 19.82; N, 9.87.

실시예 171Example 171

6-[아미노(하이드록시이미노)메틸]-N-페닐-2-나프탈렌카복스아미드6- [amino (hydroxyimino) methyl] -N-phenyl-2-naphthalenecarboxamide

표제 화합물을 문헌[참조: Judkins et al., Synthetic Communications 26(23), 4351-4367(1996)]에 기재된 바와 같이 제조한다. 실시예 55C에서 제조된 화합물(0.1g, 36mmol)을 톨루엔:메탄올의 10:1 혼합물에 용해시키고 하이드록실아민 하이드로클로라이드(3.6mmol) 및 칼륨 3급-부톡사이드(3.6mmol)를 가한다. 생성된 슬러리를 17시간 동안 환류시키고, 냉각시키며, 용매를 진공하에 제거한다. 잔사를 증류수(30ml)에 용해시키고, 에틸 아세테이트(2 x 100ml)로 추출한다. 합한 유기 추출물을 10% NaCl(50ml)로 세척하고, 무수 Na2SO4로 건조시킨다. 샘플을 건조제로 여과하고 용매를 진공하에 제거하면 백색 고체(65mg)가 남는다. 이 물질을 실시예 1에 기재된 바와 같이 중간압 역상 크로마토그래피하여 정제한다. 표제 화합물을 백색 고체(45mg)로서 수득한다. MS (m/z) M+H+: 306.The title compound is prepared as described in Judkins et al., Synthetic Communications 26 (23), 4351-4367 (1996). Compound (0.1 g, 36 mmol) prepared in Example 55C is dissolved in a 10: 1 mixture of toluene: methanol and hydroxylamine hydrochloride (3.6 mmol) and potassium tert-butoxide (3.6 mmol) are added. The resulting slurry is refluxed for 17 hours, cooled and the solvent is removed in vacuo. The residue is dissolved in distilled water (30 ml) and extracted with ethyl acetate (2 × 100 ml). The combined organic extracts are washed with 10% NaCl (50 ml) and dried over anhydrous Na 2 SO 4 . The sample was filtered through a desiccant and the solvent removed in vacuo leaving a white solid (65 mg). This material is purified by medium pressure reverse phase chromatography as described in Example 1. The title compound is obtained as a white solid (45 mg). MS (m / z) M + H + : 306.

1H NMR(300MHz, DMSO-d6): 10.51(s, 1H), 9.32(s, OH), 8.70(s, 1H), 8.57(s, 1H), 8.34(d, 1H), 8.25(d, 1H), 8.17(dd, 1H), 7.90(dd, 1H), 7.83(d, 2H), 7.40(dd, 2H), 7.15(dd, 1H), 6.25(bs, 2H). 1 H NMR (300MHz, DMSO-d 6 ): 10.51 (s, 1H), 9.32 (s, OH), 8.70 (s, 1H), 8.57 (s, 1H), 8.34 (d, 1H), 8.25 (d , 1H), 8.17 (dd, 1H), 7.90 (dd, 1H), 7.83 (d, 2H), 7.40 (dd, 2H), 7.15 (dd, 1H), 6.25 (bs, 2H).

C20H16N3O4F3에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 3 O 4 F 3 :

계산치: C, 57.28, H, 3.85, N, 10.02.Calculated: C, 57.28, H, 3.85, N, 10.02.

실측치: C, 56.89, H, 3.65, N, 9.90.Found: C, 56.89, H, 3.65, N, 9.90.

실시예 174Example 174

8-(2-피리디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염8- (2-pyridinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 174AExample 174A

톨루엔 5ml 중의 실시예 11D로부터의 생성물(168mg, 1.00mmol)의 용액에 2-브로모피리딘(0.105ml, 1.1mmol), NaOtBu(135mg, 1.4mmol), Pd2dba3(92mg, 0.1mmol) 및 P(o-톨릴)3(122mg, 0.4mmol)을 가하고 반응물을 100℃에서 24시간 동안 교반한다. 반응물을 냉각시키고, 조 반응 혼합물을 용출제로서 50% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 80mg(33%) 수득한다. MS(DCI/NH3) m/z 246(M+H)+.To a solution of the product from Example 11D (168 mg, 1.00 mmol) in 5 ml of toluene, 2-bromopyridine (0.105 ml, 1.1 mmol), NaOtBu (135 mg, 1.4 mmol), Pd 2 dba 3 (92 mg, 0.1 mmol) and P (o-tolyl) 3 (122 mg, 0.4 mmol) is added and the reaction is stirred at 100 ° C. for 24 h. The reaction is cooled and the crude reaction mixture is chromatographed on SiO 2 using 50% ethyl acetate / hexane as eluent to yield 80 mg (33%) of the title compound. MS (DCI / NH 3 ) m / z 246 (M + H) + .

실시예 174BExample 174B

8-(2-피리디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염8- (2-pyridinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 174A로부터의 생성물(121mg, 0.493mmol)을 THF(2ml)에 용해시키고 THF 중의 LiN(TMS)2의 1M 용액 0.543ml를 가한다. 반응물을 5분 동안 교반하고, TMSCl(0.096ml, 0.543mmol)을 가한다. 30분 동안 교반한 후, LiN(TMS)2의 1M 용액을 1.09ml 더 가한다. 반응물을 18시간 동안 교반하고, 2M 수성 HCl 용액 10ml를 가한다. 반응물을 24시간 더 교반하고 포화 수성 Na2CO3로 염기성화한다. 이 혼합물을 3 x 에틸 아세테이트로 추출하고 추출물을 염수로 세척하며, Na2SO4로 건조시킨 다음 농축시킨다. 조 생성물을 역상 HPLC에 의해 정제하여 목적 화합물(21mg, 7%)을 수득한다. 융점 137-147℃.The product from Example 174A (121 mg, 0.493 mmol) is dissolved in THF (2 ml) and 0.543 ml of a 1 M solution of LiN (TMS) 2 in THF is added. The reaction is stirred for 5 minutes and TMSCl (0.096 ml, 0.543 mmol) is added. After stirring for 30 minutes, an additional 1.09 ml of 1M solution of LiN (TMS) 2 is added. The reaction is stirred for 18 hours and 10 ml of 2M aqueous HCl solution is added. The reaction is stirred for another 24 hours and basified with saturated aqueous Na 2 CO 3 . The mixture is extracted with 3 x ethyl acetate and the extract is washed with brine, dried over Na 2 S0 4 and concentrated. The crude product is purified by reverse phase HPLC to give the desired compound (21 mg, 7%). Melting point 137-147 ° C.

MS(DCI(NH3)) m/z 263 (M+H)+.MS (DCI (NH 3 )) m / z 263 (M + H) + .

1H NMR(300MHz, DMSO) δ 9.98(br s, 1H), 9.46(br s, 2H), 9.27(br s, 2H), 8.74(s, 1H), 8.21(d, J=9Hz, 1H), 8.11(d, J=6Hz, 1H), 8.02(d, J=9Hz, 1H), 7.81-7.95(m, 3H), 7.75(dd, J=9, 9Hz, 1H), 7.16(m, 1H), 6.95(m, 1H), 2.55(s, 3H). 1 H NMR (300 MHz, DMSO) δ 9.98 (br s, 1H), 9.46 (br s, 2H), 9.27 (br s, 2H), 8.74 (s, 1H), 8.21 (d, J = 9 Hz, 1H) , 8.11 (d, J = 6 Hz, 1H), 8.02 (d, J = 9 Hz, 1H), 7.81-7.95 (m, 3H), 7.75 (dd, J = 9, 9 Hz, 1H), 7.16 (m, 1H ), 6.95 (m, 1 H), 2.55 (s, 3 H).

C16H14N4·3.1 C2HF3O2에 대한 원소분석치:Elementary Analysis for C 16 H 14 N 4 · 3.1 C 2 HF 3 O 2 :

계산치: C, 43.30; H, 2.80; N, 9.10.Calc .: C, 43.30; H, 2. 80; N, 9.10.

실측치: C, 43.14; H, 3.04; N, 9.90.Found: C, 43.14; H, 3.04; N, 9.90.

실시예 176Example 176

6-[4-[(하이드록시메틸)페닐]메톡시-2-나프탈렌카복스이미드아미드, 메탄설포네이트 염6- [4-[(hydroxymethyl) phenyl] methoxy-2-naphthalenecarboximideamide, methanesulfonate salt

실시예 176AExample 176A

THF(50ml) 중의 NaH(광유 중의 60%, 1.17g, 29.3mmol)의 용액에 THF(50ml) 중의 4-브로모벤질 알콜(5.22g, 27.9mmol)을 가하고 반응물을 실온에서 20분 동안 교반한다. 이어서, p-메톡시벤질 클로라이드(4.07ml, 30mmol)을 가하고, 반응물을 50℃에서 2시간 동안 교반한다. 이 혼합물을 물에 붓고 3 x 디에틸 에테르로 추출하며, 이 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 반응 혼합물을 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 7.39g(86%) 수득한다.To a solution of NaH (60% in mineral oil, 1.17 g, 29.3 mmol) in THF (50 ml) is added 4-bromobenzyl alcohol (5.22 g, 27.9 mmol) in THF (50 ml) and the reaction is stirred at room temperature for 20 minutes. . Then p-methoxybenzyl chloride (4.07 ml, 30 mmol) is added and the reaction is stirred at 50 ° C. for 2 hours. The mixture is poured into water and extracted with 3 x diethyl ether, which is washed with brine, dried over Na 2 S0 4 and concentrated. The crude reaction mixture is chromatographed on SiO 2 using hexane as eluent to yield 7.39 g (86%) of the title compound.

MS(DCI(NH3)) m/z 326 (M+NH4)+.MS (DCI (NH 3 )) m / z 326 (M + NH 4 ) + .

1H NMR(300MHz, CDCl3) δ 7.47(d, 2H), 7.28(d, 2H), 7.23(d, 2H), 6.90(d, 2H), 4.48(s, 3H), 4.47(s, 2H), 3.91(s, 3H). 1 H NMR (300 MHz, CDCl 3 ) δ 7.47 (d, 2H), 7.28 (d, 2H), 7.23 (d, 2H), 6.90 (d, 2H), 4.48 (s, 3H), 4.47 (s, 2H ), 3.91 (s, 3 H).

실시예 176BExample 176B

-100℃에서 THF(100ml) 및 헥산(20ml) 중의 실시예 176A로부터의 생성물(6.80g, 22.13mmol)의 용액에 BuLi(8.85ml, 22.13mmol)의 2.5M 용액을 가하고 반응물을 2분 동안 교반한다. 이어서, DMF(3.43ml, 43mmol)를 가하고, 반응물을 실온으로 가온시킨다. 이 혼합물을 물에 붓고 3 x 디에틸 에테르로 추출하고, 추출물을 염수로 세척하며, Na2SO4로 건조시킨 다음 농축시킨다. 반응 혼합물을 메탄올(100ml)에 용해시키고 NaBH4(1.0g, 26.2mmol)을 여러 분획으로 나누어 가한다. 물 몇 방울을 가하고, 혼합물을 농축시킨다. 잔사를 용출제로서 20% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 3.32g(58%) 수득한다.To a solution of the product from Example 176A (6.80 g, 22.13 mmol) in THF (100 ml) and hexane (20 ml) at −100 ° C. was added a 2.5 M solution of BuLi (8.85 ml, 22.13 mmol) and the reaction stirred for 2 minutes. do. DMF (3.43 ml, 43 mmol) is then added and the reaction is allowed to warm to room temperature. The mixture is poured into water and extracted with 3 x diethyl ether, the extract is washed with brine, dried over Na 2 S0 4 and concentrated. The reaction mixture is dissolved in methanol (100 ml) and NaBH 4 (1.0 g, 26.2 mmol) is added in portions. A few drops of water are added and the mixture is concentrated. The residue is chromatographed on SiO 2 using 20% ethyl acetate / hexane as eluent to yield 3.32 g (58%) of the title compound.

MS(DCI(NH3)) m/z 276(M+NH4)+.MS (DCI (NH 3 )) m / z 276 (M + NH 4 ) + .

1H NMR(300MHz, DMSO-d6) δ 7.38(s, 4H), 7.29(d, 2H), 6.90(d, 2H), 4.70(s, 2H), 4.54(s, 2H), 4.49(s, 2H), 3.81(s, 3H), 1.62(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 7.38 (s, 4H), 7.29 (d, 2H), 6.90 (d, 2H), 4.70 (s, 2H), 4.54 (s, 2H), 4.49 (s , 2H), 3.81 (s, 3H), 1.62 (s, 1H).

실시예 176CExample 176C

0℃에서 THF(10ml) 중의 실시예 176B로부터의 생성물(193mg, 0.747mmol), 실시예 28A로부터의 생성물(139mg, 0.822mmol) 및 Ph3P(216mg, 0.822mmol)의 용액에 디에틸아조디카복실레이트(0.129ml, 0.822mmol)를 가하고, 반응물을 실온에서 90분 동안 교반한다. 조 반응 혼합물을 농축시키고, 잔사를 용출제로서 10% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 225mg(74%) 수득한다.Diethylazodica in a solution of product from Example 176B (193 mg, 0.747 mmol), product from Example 28A (139 mg, 0.822 mmol) and Ph 3 P (216 mg, 0.822 mmol) in THF (10 ml) at 0 ° C. Voxylate (0.129 ml, 0.822 mmol) is added and the reaction is stirred at room temperature for 90 minutes. The crude reaction mixture is concentrated and the residue is chromatographed on SiO 2 using 10% ethyl acetate / hexane as eluent to give 225 mg (74%) of the title compound.

MS(DCI(NH3)) m/z 427 (M+NH4)+.MS (DCI (NH 3 )) m / z 427 (M + NH 4 ) + .

H NMR(300MHz, CDCl3) δ 8.15(s, 1H), 7.81(d, 1H), 7.77(d, 1H), 7.58(dd, 1H), 7.48(d, 2H), 7.42(d, 2H), 7.02-7.15(m, 4H), 6.90(d, 2H), 5.21(s, 2H), 4.56(s, 2H), 4.51(s, 2H), 3.91(s, 3H).H NMR (300 MHz, CDCl 3 ) δ 8.15 (s, 1H), 7.81 (d, 1H), 7.77 (d, 1H), 7.58 (dd, 1H), 7.48 (d, 2H), 7.42 (d, 2H) , 7.02-7.15 (m, 4H), 6.90 (d, 2H), 5.21 (s, 2H), 4.56 (s, 2H), 4.51 (s, 2H), 3.91 (s, 3H).

실시예 176DExample 176D

CH2Cl2(40ml) 및 물(7ml) 중의 실시예 176C로부터의 생성물(220mg, 0.537mmol)의 용액에 DDQ(244mg, 1.07mmol)을 가하고, 반응물을 90분 동안 교반한다. 조 반응 혼합물을 CH2Cl2에 용해시키고, 2x 수성 NaHCO3및 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 잔사를 용출제로서 50% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 89mg(57%) 수득한다.To a solution of the product from Example 176C (220 mg, 0.537 mmol) in CH 2 Cl 2 (40 ml) and water (7 ml) is added DDQ (244 mg, 1.07 mmol) and the reaction is stirred for 90 minutes. The crude reaction mixture is dissolved in CH 2 Cl 2 , washed with 2 × aqueous NaHCO 3 and brine, dried over Na 2 SO 4 and concentrated. The residue is chromatographed on SiO 2 using 50% ethyl acetate / hexane as eluent to yield 89 mg (57%) of the title compound.

MS(DCI(NH3)) m/z 307(M+NH4)+.MS (DCI (NH 3 )) m / z 307 (M + NH 4 ) + .

1H NMR(300MHz, CDCl3) δ 8.15(s, 1H), 7.81(d, 1H), 7.77(d, 1H), 7.57(dd, 1H), 7.49(d, 2H), 7.41(d, 2H), 7.33(dd, 1H), 7.21(d, 1H), 5.21(s, 2H), 4.74(s, 2H), 1.63(br s, 1H). 1 H NMR (300 MHz, CDCl 3 ) δ 8.15 (s, 1H), 7.81 (d, 1H), 7.77 (d, 1H), 7.57 (dd, 1H), 7.49 (d, 2H), 7.41 (d, 2H ), 7.33 (dd, 1H), 7.21 (d, 1H), 5.21 (s, 2H), 4.74 (s, 2H), 1.63 (br s, 1H).

실시예 176EExample 176E

6-[4-[(하이드록시메틸)페닐]메톡시-2-나프탈렌카복스이미드아미드, 메탄설포네이트 염6- [4-[(hydroxymethyl) phenyl] methoxy-2-naphthalenecarboximideamide, methanesulfonate salt

실시예 55D의 과정에 따라서 실시예 176D로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 176D following the procedure of Example 55D.

MS(DCI/NH3) m/z 307 (M+H)+.MS (DCI / NH 3 ) m / z 307 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 2.31(s, 3H), 4.52(s, 2H), 5.25(s, 2H), 7.37(d, 2H), 7.39(dd, 1H), 7.47(d, 2H), 7.59(d, 1H), 7.79(dd, 1H), 8.00(d, 1H), 8.03(d, 1H), 8.41(s, 1H), 8.89(br s, 2H), 9.34(br s, 2H). 1 H NMR (300MHz, DMSO-d 6 ) δ 2.31 (s, 3H), 4.52 (s, 2H), 5.25 (s, 2H), 7.37 (d, 2H), 7.39 (dd, 1H), 7.47 (d , 2H), 7.59 (d, 1H), 7.79 (dd, 1H), 8.00 (d, 1H), 8.03 (d, 1H), 8.41 (s, 1H), 8.89 (br s, 2H), 9.34 (br s, 2H).

C19H18N2O2·1.15 CH4SO3에 대한 원소분석치:Elemental Analysis for C 19 H 18 N 2 O 2 · 1.15 CH 4 SO 3 :

계산치: C, 58.06; H, 5.46; N, 6.72.Calc .: C, 58.06; H, 5. 46; N, 6.72.

실측치: C, 58.24; H, 5.62; N, 6.59.Found: C, 58.24; H, 5.62; N, 6.59.

실시예 177Example 177

N-하이드록시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염N-hydroxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 167에 기재된 과정을 이용하여, 실시예 163에 기재된 니트릴로부터 목적 화합물을 제조한다. 백색 분말로서의 수율: 50mg.Using the procedure described in Example 167, the desired compound is prepared from the nitrile described in Example 163. Yield as white powder: 50 mg.

MS m/z: 280 (M+H)+.MS m / z: 280 (M + H) + .

1H NMR(DMSO, 300MHz): 6.90(dd, 1H, J1=J2=5.2Hz), 7.45(m, 3H), 8.0(d, 1H, J=8.5Hz), 8.14(d, 1H, J=8.4Hz), 8.49(d, J=5.3Hz), 8.61(s, 1H), 9.58(s, 1H). 1 H NMR (DMSO, 300 MHz): 6.90 (dd, 1H, J1 = J2 = 5.2 Hz), 7.45 (m, 3H), 8.0 (d, 1H, J = 8.5 Hz), 8.14 (d, 1H, J = 8.4 Hz), 8.49 (d, J = 5.3 Hz), 8.61 (s, 1H), 9.58 (s, 1H).

C15H13N5O·2.0 C2F3O2H·0.5 H2O에 대한 원소분석치:Elemental Analysis for C 15 H 13 N 5 O · 2.0 C 2 F 3 O 2 H · 0.5 H 2 O:

계산치: C, 44.20; H, 3.12; N, 13.56.Calc .: C, 44.20; H, 3. 12; N, 13.56.

실측치: C, 44.24; H, 2.94; N, 13.49.Found: C, 44.24; H, 2.94; N, 13.49.

실시예 179Example 179

6-(2-피리디닐에티닐)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- (2-pyridinylethynyl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 179AExample 179A

실시예 121A에 기재된 과정에 따라서 실시예 28B에서 수득된 생성물, 2-에티닐피리딘(Lancaster Chemical Corp.)을 사용하여 목적 화합물을 수득한다. MS(DCI/NH3) m/z 255(M+H)+.The desired compound is obtained using the product obtained in Example 28B according to the procedure described in Example 121A, 2-ethynylpyridine (Lancaster Chemical Corp.). MS (DCI / NH 3 ) m / z 255 (M + H) + .

실시예 179BExample 179B

실시예 94D에 기재된 과정에 따라서 실시예 179A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 179A was used following the procedure described in Example 94D to afford the desired compound.

MS(DCI) m/z 272 (M+H)+.MS (DCI) m / z 272 (M + H) + .

1H NMR(300MHz, DMSO) δ 7.45-7.50(m, 1H), 7.72(d, 1H), 7.82(dd, 1H), 7.86-7.92(m, 2H), 8.18(d, 1H), 8.22(d, 1H), 8.42(s, 1H), 8.54(s, 1H), 8.68(m, 1H), 9.25(s, 2H), 9.49(s, 2H); 1 H NMR (300 MHz, DMSO) δ 7.45-7.50 (m, 1H), 7.72 (d, 1H), 7.82 (dd, 1H), 7.86-7.92 (m, 2H), 8.18 (d, 1H), 8.22 ( d, 1H), 8.42 (s, 1H), 8.54 (s, 1H), 8.68 (m, 1H), 9.25 (s, 2H), 9.49 (s, 2H);

C20H14F3N3O2·0.25 H2O에 대한 원소분석치: C 20 H 14 F 3 N 3 O 2 · 0.25 H 2 O element for analysis:

계산치: C, 61.62; H, 3.75; N, 10.78.Calc .: C, 61.62; H, 3.75; N, 10.78.

실측치: C, 61.72; H, 3.64; N, 10.66.Found: C, 61.72; H, 3. 64; N, 10.66.

실시예 180Example 180

6-(아미노이미노메틸)-N-페닐-4-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N-phenyl-4- (tetrahydro-3-furanyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 180AExample 180A

실시예 62A에 기재된 과정에 따라서 실시예 152에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z 340(M+H2O)+.The desired compound is obtained from the product obtained in Example 152 according to the procedure described in Example 62A. MS (DCI / NH 3 ) m / z 340 (M + H 2 O) + .

실시예 180BExample 180B

실시예 62B에 기재된 과정에 따라서 실시예 180A에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z 343(M+H)+.The desired compound is obtained from the product obtained in Example 180A according to the procedure described in Example 62B. MS (DCI / NH 3 ) m / z 343 (M + H) + .

실시예 180CExample 180C

실시예 55D에 기재된 과정에 따라서 실시예 180B에서 수득된 생성물로부터 목적 화합물을 수득한다. MS(DCI/NH3) m/z 360(M+H)+.The desired compound is obtained from the product obtained in Example 180B according to the procedure described in Example 55D. MS (DCI / NH 3 ) m / z 360 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 2.20(m, 1H), 2.52(m, 1H), 3.85(dd, 1H), 3.94(ddd, 1H), 4.08(ddd, 1h), 4.26(dddd, 1H), 4.39(dd, 1H), 7.14(t, 1H), 7.40(t, 2H), 7.81(d, 2H), 7.95(d, 1H), 8.08(s, 1H), 8.32(d, 1H), 8.59(s, 1H), 8.79(s, 1H), 9.25(br s, 2H), 9.61(br s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 2.20 (m, 1H), 2.52 (m, 1H), 3.85 (dd, 1H), 3.94 (ddd, 1H), 4.08 (ddd, 1h), 4.26 (dddd , 1H), 4.39 (dd, 1H), 7.14 (t, 1H), 7.40 (t, 2H), 7.81 (d, 2H), 7.95 (d, 1H), 8.08 (s, 1H), 8.32 (d, 1H), 8.59 (s, 1H), 8.79 (s, 1H), 9.25 (br s, 2H), 9.61 (br s, 2H).

C22H21N3O2·2.6 HCl에 대한 원소분석치:Elemental Analysis for C 22 H 21 N 3 O 2 2.6 HCl:

계산치: C, 58.18; H, 5.24; N, 9.25.Calc .: C, 58.18; H, 5. 24; N, 9.25.

실측치: C, 58.21; H, 4.91; N, 9.13.Found: C, 58.21; H, 4.91; N, 9.13.

실시예 181Example 181

6-[아미노(하이드록시이미노)메틸]-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드6- [amino (hydroxyimino) methyl] -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboximideamide

실시예 166에서 제조된 물질을 사용하여 실시예 177에 기재된 바와 동일한 방식으로 목적 화합물을 제조한다.The desired compound is prepared in the same manner as described in Example 177 using the material prepared in Example 166.

MS m/z: 399 (M+H)+.MS m / z: 399 (M + H) + .

1H NMR(DMSO, 300MHz): 6.88(dd, 1H, 4.7Hz), 7.11(dd, 1H, J1=J2=7.5Hz), 7.37(dd, 2H, J1=J2=7.5Hz), 7.82(d, 2H, J=8.8Hz), 7.94(dd, 1H, J1=8.5Hz, J2=1.4Hz), 8.04(d, 1H, J=8.8Hz), 8.31(s, 1H), 8.43(dd, 1H, J=14Hz), 8.74(d, 2H, J=4.7Hz), 8.52(s, 1H), 9.55(s, 1H), 9.85(s, 2H), 10.41(s, 1H). 1 H NMR (DMSO, 300 MHz): 6.88 (dd, 1H, 4.7 Hz), 7.11 (dd, 1H, J1 = J2 = 7.5 Hz), 7.37 (dd, 2H, J1 = J2 = 7.5 Hz), 7.82 (d , 2H, J = 8.8 Hz), 7.94 (dd, 1H, J1 = 8.5 Hz, J2 = 1.4 Hz), 8.04 (d, 1H, J = 8.8 Hz), 8.31 (s, 1H), 8.43 (dd, 1H , J = 14 Hz, 8.74 (d, 2H, J = 4.7 Hz), 8.52 (s, 1H), 9.55 (s, 1H), 9.85 (s, 2H), 10.41 (s, 1H).

C22H18N6O2·0.4 H2O에 대한 원소분석치:Elemental analysis for C 22 H 18 N 6 O 2 · 0.4 H 2 O:

계산치: C, 65.14; H, 4.67; N, 20.72.Calc .: C, 65.14; H, 4.67; N, 20.72.

실측치: C, 65.57; H, 4.45; N, 20.18.Found: C, 65.57; H, 4. 45; N, 20.18.

실시예 182Example 182

메틸 4-[[[7-아미노(하이드록시이미노)메틸]-2-나프탈레닐]옥시]메틸]벤조에이트Methyl 4-[[[7-amino (hydroxyimino) methyl] -2-naphthalenyl] oxy] methyl] benzoate

실시예 213A로부터의 생성물(110mg, 0.347mmol), 하이드록실아민 하이드로클로라이드(26.5mg, 0.381mmol), 트리에틸아민(53㎕, 0.381mmol) 및 N,N-디메틸포름아미드(12ml)를 4인치용 유기 압력 튜브에서 합한다. 이 튜브를 밀봉하고 24시간 동안 80℃로 가열한다. 이 튜브를 실온으로 냉각시키고 N,N-디메틸포름아미드(2ml) 중의 추가의 하이드록실아민 하이드로클로라이드(48.1mg, 0.693mmol) 및 트리에틸아민(96.6㎕, 0.693mmol)을 가한다. 이 튜브를 재밀봉하고 80℃에서 24시간 동안 가열한다. 첨가를 상기와 같이 2회 반복하고, 튜브를 재밀봉시킨 다음 80℃에서 72시간 동안 가열한다. 반응 혼합물을 고체 잔사로 농축시키고 이를 메틸렌 클로라이드 중의 15% 아세톤으로 용출시키는 실리카 겔(60g) 상에서 칼럼 크로마토그래피로 정제하여 백색 고체로서의 표적 화합물(43mg, 회수된 출발 물질을 기준으로 하여 50%)을 수득한다.4 inches of product from Example 213A (110 mg, 0.347 mmol), hydroxylamine hydrochloride (26.5 mg, 0.381 mmol), triethylamine (53 μl, 0.381 mmol) and N, N-dimethylformamide (12 ml) Combine in an organic pressure tube. The tube is sealed and heated to 80 ° C. for 24 hours. The tube is cooled to room temperature and additional hydroxylamine hydrochloride (48.1 mg, 0.693 mmol) and triethylamine (96.6 μl, 0.693 mmol) in N, N-dimethylformamide (2 ml) are added. The tube is resealed and heated at 80 ° C. for 24 hours. The addition is repeated twice as above, the tube is resealed and heated at 80 ° C. for 72 hours. The reaction mixture was concentrated to a solid residue and purified by column chromatography on silica gel (60 g) eluting with 15% acetone in methylene chloride to give the target compound (43 mg, 50% based on recovered starting material) as a white solid. To obtain.

MS(DCI/NH3) m/z 351 (M+H)+.MS (DCI / NH 3 ) m / z 351 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 3.860(s, 3H), 5.349(s, 2H), 5.860(s, 2H), 7.280(dd, 1H), 7.381(d, 1H), 7.660(d, 2H), 7.688(dd, 1H), 7.805(d, 1H), 7.850(d, 1H), 8.010(d, 2H), 8.070(s, 1H), 9.724(s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.860 (s, 3H), 5.349 (s, 2H), 5.860 (s, 2H), 7.280 (dd, 1H), 7.381 (d, 1H), 7.660 (d , 2H), 7.688 (dd, 1H), 7.805 (d, 1H), 7.850 (d, 1H), 8.010 (d, 2H), 8.070 (s, 1H), 9.724 (s, 1H).

C20H18N2O4·0.15 H2O에 대한 원소분석치:Elemental Analysis for C 20 H 18 N 2 O 4 0.15 H 2 O:

계산치: C, 68.04; H, 5.22; N, 7.93.Calc .: C, 68.04; H, 5. 22; N, 7.93.

실측치: C, 68.06; H, 5.05; N, 7.87.Found: C, 68.06; H, 5.05; N, 7.87.

실시예 184Example 184

N-[4-(아미노카보닐)페닐]-6-(아미노이미노메틸)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염N- [4- (aminocarbonyl) phenyl] -6- (aminoiminomethyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 184AExample 184A

실시예 8A에서 수득된 생성물(300mg, 1.39mmol) 및 디클로로메탄 5ml의 현탁액을 4-아미노벤즈아미드(207mg, 1.52mmol), 트리에틸아민(0.44ml, 3.2mmol) 및 디클로로메탄 10ml의 0℃ 용액에 적가한다. 반응 혼합물을 0℃에서 0.5시간 동안 교반한 다음 실온에서 18시간 동안 교반한다. 과량의 에테르를 교반하면서 가하고, 생성된 고체를 여과시키며, 1N HCl, 물로 세척하고 진공하에 건조시켜 목적 화합물을 수득한다. MS(DCI) m/z 333(M+NH3)+.A suspension of the product obtained in Example 8A (300 mg, 1.39 mmol) and 5 ml of dichloromethane was added to a 0 ° C. solution of 4-aminobenzamide (207 mg, 1.52 mmol), triethylamine (0.44 ml, 3.2 mmol) and 10 ml of dichloromethane. Drop by. The reaction mixture is stirred at 0 ° C. for 0.5 h and then at rt for 18 h. Excess ether is added with stirring and the resulting solid is filtered off, washed with 1N HCl, water and dried under vacuum to afford the desired compound. MS (DCI) m / z 333 (M + NH 3 ) + .

실시예 184BExample 184B

N-[4-(아미노카보닐)페닐]-6-(아미노이미노메틸)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염N- [4- (aminocarbonyl) phenyl] -6- (aminoiminomethyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 4C에 기재된 과정에 따라서 실시예 184A에서 수득된 생성물로부터 목적 화합물을 수득한다.The desired compound is obtained from the product obtained in Example 184A according to the procedure described in Example 4C.

MS(DCI) m/z 333 (M+H)+.MS (DCI) m / z 333 (M + H) + .

1H NMR(300MHz, DMSO) δ 10.76(S, 1H), 9.51(S, 2H), 9.14(S, 2H), 8.74(S, 1H), 8.56(S, 1H), 8.33(D, 1H, J=8.8Hz), 8.26(D, 1H, J=8.8HZ Hz), 8.16(DD, 1H, J=8.46, 1.11Hz), 7.91(M, 6H), 7.31(S, 1H). 1 H NMR (300 MHz, DMSO) δ 10.76 (S, 1H), 9.51 (S, 2H), 9.14 (S, 2H), 8.74 (S, 1H), 8.56 (S, 1H), 8.33 (D, 1H, J = 8.8 Hz), 8.26 (D, 1H, J = 8.8 HZ Hz), 8.16 (DD, 1H, J = 8.46, 1.11 Hz), 7.91 (M, 6H), 7.31 (S, 1H).

C20H17F3N4O4·1.5 H2O에 대한 원소분석치: C 20 H 17 F 3 N 4 O 4 · 1.5 H 2 O element for analysis:

계산치: C, 53.28; H, 4.26; N, 11.83.Calc .: C, 53.28; H, 4. 26; N, 11.83.

실측치: C, 53.47; H, 3.86; N, 11.96.Found: C, 53.47; H, 3.86; N, 11.96.

실시예 185Example 185

메틸 2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세테이트, 모노(트리플루오로아세테이트) 염Methyl 2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetate, mono (trifluoroacetate) salt

실시예 185AExample 185A

7-메톡시-2-시아노나프탈렌(2.79g, 5.23mmol) 및 테트라부틸암모늄 요오다이드(17mg, 0.157mmol)를 벤젠(35ml)과 사이클로헥산(17.5ml)의 혼합물에서 합한다. 생성된 용액을 신속하게 교반하면서, 불활성 대기하에 벤젠(35ml)과 사이클로헥산(17.5ml)의 혼합물 중의 알루미늄 트리요오다이드(6.21g, 15.23mmol)의 찬(얼음/물) 현탁액에 가한다. 첨가 후, 생성된 현탁액을 환류하에 2.5시간 동안 가열한다. 가열물을 꺼내고, 거의 실온으로 냉각시킨 후, 반응 혼합물을 얼음 욕 속에서 냉각시키고 물(100ml)을 가하여 켄칭시킨다. 생성된 혼합물을 2M 수성 나트륨 티오설페이트 용액(50ml)으로 추가로 희석시키고 에틸 아세테이트(3 x 80ml)로 추출한다. 합한 유기 층을 건조시킨 다음 증발시킨다. 생성된 고체를 소량의 뜨거운 에틸 아세테이트에 용해시키고, 헥산을 이용하여 운점까지 뜨겁게 희석시킨 다음 냉동기에서 2시간 동안 놓아둔다. 목적 화합물을 여과시켜 수집한다(1.99g, 77%). MS(DCI/NH3) m/z 187(M+NH4)+.7-methoxy-2-cyanonaphthalene (2.79 g, 5.23 mmol) and tetrabutylammonium iodide (17 mg, 0.157 mmol) are combined in a mixture of benzene (35 ml) and cyclohexane (17.5 ml). The resulting solution is added to a cold (ice / water) suspension of aluminum triiodide (6.21 g, 15.23 mmol) in a mixture of benzene (35 ml) and cyclohexane (17.5 ml) under inert atmosphere with rapid stirring. After addition, the resulting suspension is heated at reflux for 2.5 hours. After heating is taken out and cooled to near room temperature, the reaction mixture is cooled in an ice bath and quenched by addition of water (100 ml). The resulting mixture is further diluted with 2M aqueous sodium thiosulfate solution (50 ml) and extracted with ethyl acetate (3 × 80 ml). The combined organic layers are dried and then evaporated. The resulting solid is dissolved in a small amount of hot ethyl acetate, hot dilute to cloud point with hexane and left in the freezer for 2 hours. The desired compound is collected by filtration (1.99 g, 77%). MS (DCI / NH 3 ) m / z 187 (M + NH 4 ) + .

실시예 185BExample 185B

실시예 185A로부터의 생성물(217mg, 1.283mmol)을 DMF(7ml) 중의 탄산세슘(460mg, 1.411mmol) 및 테트라부틸암모늄 요오다이드(촉매량)와 합한다. 이에 t-부틸 브로모아세테이트(193㎕, 1.283mmol)을 가하고 생성된 혼합물을 불활성 대기하에서 2시간 동안 교반한다. 이 반응 혼합물을 물(100ml)로 희석시키고 에틸 아세테이트(2 x 50ml)로 추출한다. 합한 유기 층을 건조시킨 다음 증발시킨다. 잔사를 칼럼 크로마토그래피하여 정제하여 목적 화합물을 오일(332mg, 91%)로서 수득한다. MS(DCI/NH3) m/z 284(M+H)+, 301(M+NH4)+.The product from Example 185A (217 mg, 1.283 mmol) is combined with cesium carbonate (460 mg, 1.411 mmol) and tetrabutylammonium iodide (catalyst amount) in DMF (7 ml). To this was added t-butyl bromoacetate (193 μl, 1.283 mmol) and the resulting mixture was stirred for 2 hours under an inert atmosphere. The reaction mixture is diluted with water (100 ml) and extracted with ethyl acetate (2 x 50 ml). The combined organic layers are dried and then evaporated. The residue is purified by column chromatography to give the desired compound as an oil (332 mg, 91%). MS (DCI / NH 3 ) m / z 284 (M + H) + , 301 (M + NH 4 ) + .

실시예 185CExample 185C

메틸 2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세테이트, 모노(트리플루오로아세테이트) 염Methyl 2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetate, mono (trifluoroacetate) salt

실시예 185B로부터의 생성물(323mg, 1.140mmol)을 불활성 대기하에서 무수 메탄올(32ml)에 용해시키고 0℃로 냉각시킨다. 무수 염화수소를 상기 용액이 포화될 때까지 버블링시킨다. 반응물을 0℃에서 15분 동안 교반하고 무수 염화수소로 다시 포화시킨다. 0℃에서 20분 더 교반한 후, 용액을 무수 염화수소로 마지막 1회 포화시키고 실온으로 가온시키면서 18시간 동안 교반한다. 반응물을 증발시켜 고체를 수득하고 고진공하에서 2시간 동안 건조시킨다. 이 고체를 메탄올(64ml)로 슬러리화하고, 암모늄 아세테이트(220mg, 2.850mmol)를 가하고, 혼합물을 환류하에 2시간 동안 가열한다. 반응물을 증발시키고 역상 크로마토그래피로 정제하여 목적 화합물(265mg, 90%)을 수득한다.The product from Example 185B (323 mg, 1.140 mmol) was dissolved in anhydrous methanol (32 ml) under inert atmosphere and cooled to 0 ° C. Anhydrous hydrogen chloride is bubbled until the solution is saturated. The reaction is stirred at 0 ° C. for 15 minutes and saturated again with anhydrous hydrogen chloride. After another 20 minutes of stirring at 0 ° C., the solution is saturated once with anhydrous hydrogen chloride and stirred for 18 hours while warming to room temperature. The reaction is evaporated to give a solid and dried under high vacuum for 2 hours. This solid is slurried with methanol (64 ml), ammonium acetate (220 mg, 2.850 mmol) is added and the mixture is heated at reflux for 2 h. The reaction is evaporated and purified by reverse phase chromatography to yield the desired compound (265 mg, 90%).

MS(DCI(NH3)) m/z 259 (M+H)+.MS (DCI (NH 3 )) m / z 259 (M + H) + .

1H NMR(300MHz, DMSO-d6) δ 3.735(s, 3H), 4.995(s, 2H), 7.430(dd, 1H), 7.458(s, 1H), 7.669(dd, 1H), 8.025(d, 1H), 8.095(d, 1H), 8.325(d, 1H), 9.090(br s, 1H), 9.410(br s, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 3.735 (s, 3H), 4.995 (s, 2H), 7.430 (dd, 1H), 7.458 (s, 1H), 7.669 (dd, 1H), 8.025 (d , 1H), 8.095 (d, 1H), 8.325 (d, 1H), 9.090 (br s, 1H), 9.410 (br s, 1H).

C14H14N2O3·(C2HO2F3)에 대한 원소분석치:Elemental Analysis for C 14 H 14 N 2 O 3 · (C 2 HO 2 F 3 ):

계산치: C, 51.16; H, 4.01; N, 7.41.Calc .: C, 51.16; H, 4.01; N, 7.41.

실측치: C, 51.35; H, 3.98; N, 7.48.Found: C, 51.35; H, 3.98; N, 7.48.

실시예 186Example 186

6-(아미노이미노메틸)-N-(2-티아졸릴)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (2-thiazolyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 186AExample 186A

2-아미노티아졸을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+280.The product is prepared in the manner of Example 8A using 2-aminothiazole. MS (APCI) m / z (M + H) + 280.

실시예 186BExample 186B

6-(아미노이미노메틸)-N-(2-티아졸릴)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (2-thiazolyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 1B로부터 상기 생성물을 제조한다.The product is prepared from Example 1B.

MS(APCI) m/z (M+H)+297.MS (APCI) m / z (M + H) + 297.

1H NMR(300MHz, DMSO-d6) δ 12.88(s, 1H), 9.59(s, 2H), 9.30(s, 2H), 8.87(s, 1H), 8.59(s, 1H), 8.32-8.22(m, 4H), 7.93(dd, J=1.8, 8.4Hz, 1H), 7.61(d, J=3.3Hz, 1H), 7.33(d, J=3.3Hz, 1H). 1 H NMR (300MHz, DMSO-d 6 ) δ 12.88 (s, 1H), 9.59 (s, 2H), 9.30 (s, 2H), 8.87 (s, 1H), 8.59 (s, 1H), 8.32-8.22 (m, 4H), 7.93 (dd, J = 1.8, 8.4 Hz, 1H), 7.61 (d, J = 3.3 Hz, 1H), 7.33 (d, J = 3.3 Hz, 1H).

C15H13N4OCIS 2/5 HCl에 대한 원소분석치:Elemental Analysis for C 15 H 13 N 4 OCIS 2/5 HCl:

계산치: C, 52.03; H, 3.89; N, 16.18.Calc .: C, 52.03; H, 3.89; N, 16.18.

실측치: C, 52.01; H, 3.88; N, 16.12.Found: C, 52.01; H, 3.88; N, 16.12.

실시예 187Example 187

6-(아미노이미노메틸)-N-(6-메톡시-3-피리디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (6-methoxy-3-pyridinyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 187AExample 187A

5-아미노-2-메톡시피리딘을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+304.The product is prepared in the manner of Example 8A using 5-amino-2-methoxypyridine. MS (APCI) m / z (M + H) + 304.

실시예 187BExample 187B

6-(아미노이미노메틸)-N-(6-메톡시-3-피리디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (6-methoxy-3-pyridinyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 1B(144D)에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B 144D.

MS(CI) m/z (M+H)+321.MS (CI) m / z (M + H) + 321.

1H NMR(300MHz, DMSO-d6) δ 10.71(s, 1H), 9.60(s, 2H), 9.41(s, 2H), 8.76(s, 1H), 8.60(s, 2H), 8.30(d, J=9, 1H), 8.25-8.12(m, 4H), 7.93(dd, J=1.8, 8.7Hz, 1H), 6.89(d, J=9.0Hz, 1H), 3.87(s, 3H). 1 H NMR (300MHz, DMSO-d 6 ) δ 10.71 (s, 1H), 9.60 (s, 2H), 9.41 (s, 2H), 8.76 (s, 1H), 8.60 (s, 2H), 8.30 (d , J = 9, 1H), 8.25-8.12 (m, 4H), 7.93 (dd, J = 1.8, 8.7 Hz, 1H), 6.89 (d, J = 9.0 Hz, 1H), 3.87 (s, 3H).

C20H17N4O4F31/2 TEA에 대한 원소분석치:Elemental Analysis for C 20 H 17 N 4 O 4 F 3 1/2 TEA:

계산치: C, 51.47; H, 3.60; N, 11.45.Calc .: C, 51.47; H, 3. 60; N, 11.45.

실측치: C, 51.39; H, 3.88; N, 11.65.Found: C, 51.39; H, 3.88; N, 11.65.

실시예 188Example 188

6-(아미노이미노메틸)-N-(1,3-벤조디옥솔-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1,3-benzodioxol-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 188AExample 188A

3,4-메틸렌디옥시아닐린을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+317.The product is prepared in the manner of Example 8A using 3,4-methylenedioxyaniline. MS (APCI) m / z (M + H) + 317.

실시예 188BExample 188B

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+334.MS (CI) m / z (M + H) + 334.

1H NMR(300MHz, DMSO-d6) δ 9.70(s, 1H), 8.20(s, 2H), 9.96(s, 1H), 7.81-7.63(m, 3H), 7.31(dd, J=1.8, 8.4Hz, 1H), 7.11(d, J=4.2Hz, 1H), 6.91(dd, J=4.5, 10.8Hz), 6.4(d, J=8.4Hz, 1H), 5.59(s, 2H). 1 H NMR (300 MHz, DMSO-d 6 ) δ 9.70 (s, 1H), 8.20 (s, 2H), 9.96 (s, 1H), 7.81-7.63 (m, 3H), 7.31 (dd, J = 1.8, 8.4 Hz, 1H), 7.11 (d, J = 4.2 Hz, 1H), 6.91 (dd, J = 4.5, 10.8 Hz), 6.4 (d, J = 8.4 Hz, 1H), 5.59 (s, 2H).

C21H16N3O3F33/5 TFA에 대한 원소분석치:Elemental Analysis for C 21 H 16 N 3 O 3 F 3 3/5 TFA:

계산치: C, 55.44; H, 3.48; N, 8.77.Calc .: C, 55.44; H, 3. 48; N, 8.77.

실측치: C, 55.44; H, 3.52; N, 8.85.Found: C, 55.44; H, 3.52; N, 8.85.

실시예 189Example 189

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-2,4-디옥소-5-피리미디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-2,4-dioxo-5-pyrimidinyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 189AExample 189A

5-아미노우라실을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M-H)+305.The product is prepared in the manner of Example 8A using 5-aminouracil. MS (APCI) m / z (MH) + 305.

실시예 189BExample 189B

6-(아미노이미노메틸)-N-(1,2,3,4-테트라하이드로-2,4-디옥소-5-피리미디닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (1,2,3,4-tetrahydro-2,4-dioxo-5-pyrimidinyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+324;MS (CI) m / z (M + H) + 324;

1H-NMR(300MHz, DMSO-d6) δ 11.50(s, 1H), 9.53(s, 3H), 9.21(s, 2H), 8.70(s, 1H), 8.55(s, 1H), 8.33(d, J=8.4Hz, 1H), 8.20(d, J=8.7Hz, 1H), 8.13-8.09(m, 2H), 8.00(s, 1H), 7.88(dd, J=1.8, 8.4Hz, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 11.50 (s, 1H), 9.53 (s, 3H), 9.21 (s, 2H), 8.70 (s, 1H), 8.55 (s, 1H), 8.33 ( d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.7 Hz, 1H), 8.13-8.09 (m, 2H), 8.00 (s, 1H), 7.88 (dd, J = 1.8, 8.4 Hz, 1H ).

C16H14N5O3Cl 2/5 HCl에 대한 원소분석치:Elemental Analysis for C 16 H 14 N 5 O 3 Cl 2/5 HCl:

계산치: C, 51.49; H, 3.88; N, 18.76.Calc .: C, 51.49; H, 3.88; N, 18.76.

실측치: C, 51.87; H, 4.01; N, 17.68.Found: C, 51.87; H, 4.01; N, 17.68.

실시예 190Example 190

6-(아미노이미노메틸)-N-(3,5-디플루오로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3,5-difluorophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 190AExample 190A

3,5-디플루오로아닐린을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M-H)+307.The product is prepared in the manner of Example 8A using 3,5-difluoroaniline. MS (APCI) m / z (MH) + 307.

실시예 190BExample 190B

6-(아미노이미노메틸)-N-(3,5-디플루오로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3,5-difluorophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z(M+H)+326;MS (CI) m / z (M + H) + 326;

1H-NMR(300MHz, DMSO-d6) δ 10.93(s, 1H), 9.53(s, 2H), 9.34(s, 2H), 8.71(s, 1H), 8.58(s, 1H), 8.33(d, J=8.4Hz, 1H), 8.26(d, J=8.7Hz, 1H), 8.14(m, 1H), 7.92(dd, J=0.9, 8.1Hz, 1H), 7.61(d, J=7.8Hz, 2H), 7.04-6.97(m, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.93 (s, 1H), 9.53 (s, 2H), 9.34 (s, 2H), 8.71 (s, 1H), 8.58 (s, 1H), 8.33 ( d, J = 8.4 Hz, 1H), 8.26 (d, J = 8.7 Hz, 1H), 8.14 (m, 1H), 7.92 (dd, J = 0.9, 8.1 Hz, 1H), 7.61 (d, J = 7.8 Hz, 2H), 7.04-6.97 (m, 1H).

C20H14N3O2F52/5 TFA에 대한 원소분석치:Elemental Analysis for C 20 H 14 N 3 O 2 F 5 2/5 TFA:

계산치: C, 54.92; H, 3.21; N, 9.42.Calc .: C, 54.92; H, 3. 21; N, 9.42.

실측치: C, 54.96; H, 3.36; N, 9.37.Found: C, 54.96; H, 3. 36; N, 9.37.

실시예 191Example 191

6-(아미노이미노메틸)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 191AExample 191A

3-아미노피라졸을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+263.The product is prepared in the manner of Example 8A using 3-aminopyrazole. MS (APCI) m / z (M + H) + 263.

실시예 191BExample 191B

6-(아미노이미노메틸)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+280;MS (CI) m / z (M + H) + 280;

1H-NMR(300MHz, DMSO-d6) δ 11.13(s, 1H), 9.55(s, 2H), 9.37(s, 2H), 8.75(s, 1H), 8.55(s, 1H), 8.23(d, J=8.4Hz, 1H), 8.12(s, 2H), 7.90(d, J=8.4Hz, 1H), 7.70(s, 1H), 6.69(s, 1H) 1 H-NMR (300 MHz, DMSO-d 6 ) δ 11.13 (s, 1H), 9.55 (s, 2H), 9.37 (s, 2H), 8.75 (s, 1H), 8.55 (s, 1H), 8.23 ( d, J = 8.4 Hz, 1H), 8.12 (s, 2H), 7.90 (d, J = 8.4 Hz, 1H), 7.70 (s, 1H), 6.69 (s, 1H)

C17H14N5O3F37/10 TFA에 대한 원소분석치:Elemental Analysis for C 17 H 14 N 5 O 3 F 3 7/10 TFA:

계산치: C, 46.53; H, 3.12; N, 14.70.Calc .: C, 46.53; H, 3. 12; N, 14.70.

실측치: C, 46.47; H, 3.16; N, 14.85.Found: C, 46.47; H, 3. 16; N, 14.85.

실시예 192Example 192

6-(아미노이미노메틸)-N-(5-메틸-3-이속사졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-methyl-3-isoxazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 192AExample 192A

3-아미노-5-메틸이속사졸을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+278.The product is prepared in the manner of Example 8A using 3-amino-5-methylisoxazole. MS (APCI) m / z (M + H) + 278.

실시예 192BExample 192B

6-(아미노이미노메틸)-N-(5-메틸-3-이속사졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-methyl-3-isoxazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+295;MS (CI) m / z (M + H) + 295;

1H-NMR(300MHz, d6-DMSO) δ 11.62(s, 1H), 9.52(s, 2H), 9.33(s, 2H), 8.78(s, 1H), 8.55(dd, 1H), 8.31-8.16(m, 3H), 7.90(dd, 1H), 6.81(s, 1H), 2.44(s, 3H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 11.62 (s, 1H), 9.52 (s, 2H), 9.33 (s, 2H), 8.78 (s, 1H), 8.55 (dd, 1H), 8.31- 8.16 (m, 3H), 7.90 (dd, 1H), 6.81 (s, 1H), 2.44 (s, 3H).

C18H15N4O4F3에 대한 원소분석치:Elemental Analysis for C 18 H 15 N 4 O 4 F 3 :

계산치: C, 52.95; H, 3.70; N, 13.72.Calc .: C, 52.95; H, 3. 70; N, 13.72.

실측치: C, 52.73; H, 3.64; N, 13.24.Found: C, 52.73; H, 3. 64; N, 13.24.

실시예 193Example 193

6-(아미노이미노메틸)-N-(피라지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (pyrazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 193AExample 193A

2-아미노피라진을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M-H)+275.The product is prepared in the manner of Example 8A using 2-aminopyrazine. MS (APCI) m / z (MH) + 275.

실시예 193BExample 193B

6-(아미노이미노메틸)-N-(피라지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (pyrazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+292;MS (CI) m / z (M + H) + 292;

1H-NMR(300MHz, d6-DMSO) δ 11.41(s, 1H), 9.52(s, 2H), 9.49(s, 1H), 9.27(s, 2H), 8.83(s, 1H), 8.56(s, 1H), 8.53-8.46(m, 2H), 8.30(d, 1H), 8.23(s, 2H), 7.90(dd, 1H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 11.41 (s, 1H), 9.52 (s, 2H), 9.49 (s, 1H), 9.27 (s, 2H), 8.83 (s, 1H), 8.56 ( s, 1H), 8.53-8.46 (m, 2H), 8.30 (d, 1H), 8.23 (s, 2H), 7.90 (dd, 1H).

C18H14N5O3F3에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 5 O 3 F 3 :

계산치: C, 49.36; H, 3.16; N, 15.15 1/2 TFA.Calc .: C, 49.36; H, 3. 16; N, 15.15 1/2 TFA.

실측치: C, 49.53; H, 3.22; N, 14.87.Found: C, 49.53; H, 3. 22; N, 14.87.

실시예 194Example 194

6-(아미노이미노메틸)-N-(6-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (6-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 194AExample 194A

2-아미노-6-메틸피리딘을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+288.The product is prepared in the manner of Example 8A using 2-amino-6-methylpyridine. MS (APCI) m / z (M + H) + 288.

실시예 194BExample 194B

6-(아미노이미노메틸)-N-(6-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (6-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+305;MS (CI) m / z (M + H) + 305;

1H-NMR(300MHz, d6-DMSO) δ 11.02(s, 1H), 9.53(s, 2H), 9.37(s, 2H), 8.80(s, 1H), 8.55(s, 1H), 8.29(d, 1H), 8.20(s, 2H), 8.07(d, 1H), 7.89(d, 1H), 7.78(t, 1H), 7.08(d, 1H), 2.48(s, 3H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 11.02 (s, 1H), 9.53 (s, 2H), 9.37 (s, 2H), 8.80 (s, 1H), 8.55 (s, 1H), 8.29 ( d, 1H), 8.20 (s, 2H), 8.07 (d, 1H), 7.89 (d, 1H), 7.78 (t, 1H), 7.08 (d, 1H), 2.48 (s, 3H).

C20H17N4O3F3에 대한 원소분석치:Elemental Analysis for C 20 H 17 N 4 O 3 F 3 :

계산치: C, 48.74; H, 3.33; N, 10.20 7/5 TFA.Calc .: C, 48.74; H, 3.33; N, 10.20 7/5 TFA.

실측치: C, 48.74; H, 3.59; N, 10.11.Found: C, 48.74; H, 3.59; N, 10.11.

실시예 195Example 195

6-(아미노이미노메틸)-N-(3,4,5-트리메톡시페닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (3,4,5-trimethoxyphenyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 195AExample 195A

3,4,5-트리메톡시아닐린을 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+363.The product is prepared in the manner of Example 8A using 3,4,5-trimethoxyaniline. MS (APCI) m / z (M + H) + 363.

실시예 195BExample 195B

6-(아미노이미노메틸)-N-(3,4,5-트리메톡시페닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -N- (3,4,5-trimethoxyphenyl) -2-naphthalenecarboxamide, monohydrochloride

실시예 1B에 기재된 바와 같이 상기 생성물을 제조한다.The product is prepared as described in Example 1B.

MS(CI) m/z (M+H)+380;MS (CI) m / z (M + H) + 380;

1H-NMR(300MHz, d6-DMSO) δ 10.54(s, 1H), 9.61(s, 2H), 9.34(s, 2H), 8.72(s, 1H), 8.59(s, 1H), 8.33-8.15(m, 3H), 7.91(dd, 1H), 7.30(s, 2H), 3.80(s, 9H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.54 (s, 1H), 9.61 (s, 2H), 9.34 (s, 2H), 8.72 (s, 1H), 8.59 (s, 1H), 8.33- 8.15 (m, 3H), 7.91 (dd, 1H), 7.30 (s, 2H), 3.80 (s, 9H).

C21H22N3O4Cl에 대한 원소분석치:Elemental Analysis for C 21 H 22 N 3 O 4 Cl:

계산치: C, 39.09; H, 4.42; N, 6.51.Calc .: C, 39.09; H, 4. 42; N, 6.51.

실측치: C, 38.94; H, 4.60; N, 7.61.Found: C, 38.94; H, 4. 60; N, 7.61.

실시예 196Example 196

6-(아미노이미노메틸)-N-(3-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-methyl-2-pyridinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 196AExample 196A

실시예 184A에 대한 과정을 사용하고 4-아미노벤즈아미드를 2-아미노-3-피콜렌으로 대체하여 목적 화합물을 수득한다. MS(DCI) m/z 288(M+H)+.Use the procedure for Example 184A and replace 4-aminobenzamide with 2-amino-3-picolin to afford the desired compound. MS (DCI) m / z 288 (M + H) + .

실시예 196BExample 196B

6-(아미노이미노메틸)-N-(3-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-methyl-2-pyridinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 1B에 기재된 과정에 따라서 실시예 196A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 196A was used following the procedure described in Example 1B to afford the desired compound.

MS(DCI) m/z 305 (M+H)+.MS (DCI) m / z 305 (M + H) + .

1H-NMR(300MHz, DMSO) δ 10.85(s, 1H), 9.52(s, 2H), 9.22(s, 2H), 8.76(s, 1H), 8.56(s, 1H), 8.35(dd, 1H, J=4.41, 1.10), 8.32(d, 1H, J=8.80), 8.22(m, 2H), 7.90(dd, 1H, J=8.83, 1.84), 7.80(dd, 1H, J=7.73, 1.11), 7.31(dd, 1H, J=7.72, 4.78), 2.26(s, 1H). 1 H-NMR (300 MHz, DMSO) δ 10.85 (s, 1H), 9.52 (s, 2H), 9.22 (s, 2H), 8.76 (s, 1H), 8.56 (s, 1H), 8.35 (dd, 1H) , J = 4.41, 1.10), 8.32 (d, 1H, J = 8.80), 8.22 (m, 2H), 7.90 (dd, 1H, J = 8.83, 1.84), 7.80 (dd, 1H, J = 7.73, 1.11 ), 7.31 (dd, 1H, J = 7.72, 4.78), 2.26 (s, 1H).

C22H18F6N4O3·0.75 H2O에 대한 원소분석치:Elemental analysis for C 22 H 18 F 6 N 4 O 3 · 0.75 H 2 O:

계산치: C, 48.40; H, 3.60; N, 10.26.Calc .: C, 48.40; H, 3. 60; N, 10.26.

실측치: C, 48.81; H, 3.66; N, 10.43.Found: C, 48.81; H, 3. 66; N, 10.43.

실시예 197Example 197

6-(아미노이미노메틸)-N-(5-브로모-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-bromo-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 197AExample 197A

실시예 184A에 대한 과정을 사용하고 4-아미노벤즈아미드를 2-아미노-5-브로모티아졸로 대체하여 목적 화합물을 수득한다. MS(DCI) m/z 358(M+H)+.Use the procedure for Example 184A and replace 4-aminobenzamide with 2-amino-5-bromothiazole to afford the desired compound. MS (DCI) m / z 358 (M + H) + .

실시예 197BExample 197B

6-(아미노이미노메틸)-N-(5-브로모-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-bromo-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 과정에 따라서 실시예 197A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 197A was used following the procedure described in Example 1B to afford the desired compound.

MS(ESI+) m/z 375 (M+H)+.MS (ESI < + >) m / z 375 (M + H) + .

1H-NMR(300MHz, DMSO) δ 10.85(s, 1H), 9.55(s, 2H), 9.24(s, 2H), 8.87(s, 1H), 8.57(d, 1H, J=1.69), 8.31(d, 1H, J=8.47), 8.25(d, 1H, J=1.01), 7.92(dd, 1H, J=8.48, 2.04), 7.71(s, 1H). 1 H-NMR (300 MHz, DMSO) δ 10.85 (s, 1H), 9.55 (s, 2H), 9.24 (s, 2H), 8.87 (s, 1H), 8.57 (d, 1H, J = 1.69), 8.31 (d, 1H, J = 8.47), 8.25 (d, 1H, J = 1.01), 7.92 (dd, 1H, J = 8.48, 2.04), 7.71 (s, 1H).

C17H12BrF3SN4O3·1.25 H2O·0.25 TFA에 대한 원소분석치:Elemental Analysis for C 17 H 12 BrF 3 SN 4 O 3 · 1.25 H 2 O · 0.25 TFA:

계산치: C, 38.90; H, 2.75; N, 10.37.Calc .: C, 38.90; H, 2.75; N, 10.37.

실측치: C, 38.97; H, 3.24; N, 10.66.Found: C, 38.97; H, 3. 24; N, 10.66.

실시예 198Example 198

6-(아미노이미노메틸)-N-(5-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 198AExample 198A

실시예 184A에 대한 과정을 사용하고 4-아미노벤즈아미드를 2-아미노-5-피콜렌으로 대체하여 목적 화합물을 수득한다. MS(ESI+) m/z 288(M+H)+.Use the procedure for Example 184A and replace 4-aminobenzamide with 2-amino-5-picolin to afford the desired compound. MS (ESI < + >) m / z 288 (M + H) + .

실시예 198BExample 198B

6-(아미노이미노메틸)-N-(5-메틸-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-methyl-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 과정에 따라서 실시예 198A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 198A was used following the procedure described in Example 1B to afford the desired compound.

MS(DCI) m/z 305 (M+H)+.MS (DCI) m / z 305 (M + H) + .

1H-NMR(300MHz, DMSO) δ 11.01(s, 1H), 9.50(s, 2H), 9.16(s, 2H), 8.79(s, 1H), 8.54(s, 1H), 8.30(d, 1H, J=9.19), 8.27(d, 1H, J=1.47), 8.20(s, 2H), 8.15(d, 1H, J=8.83), 7.89(dd, 1H, J=8.46, 1.48), 7.72(dd, 1H, J=8.46, 1.84), 2.31(s, 3H). 1 H-NMR (300 MHz, DMSO) δ 11.01 (s, 1H), 9.50 (s, 2H), 9.16 (s, 2H), 8.79 (s, 1H), 8.54 (s, 1H), 8.30 (d, 1H , J = 9.19), 8.27 (d, 1H, J = 1.47), 8.20 (s, 2H), 8.15 (d, 1H, J = 8.83), 7.89 (dd, 1H, J = 8.46, 1.48), 7.72 ( dd, 1H, J = 8.46, 1.84), 2.31 (s, 3H).

C20H17F3N4O3·0.25 H2O·0.2 TFA에 대한 원소분석치:Elemental Analysis for C 20 H 17 F 3 N 4 O 3 0.25 H 2 O 0.2 TFA:

계산치: C, 54.98; H, 4.00; N, 12.57.Calc .: C, 54.98; H, 4.00; N, 12.57.

실측치: C, 54.99; H, 3.59; N, 12.43.Found: C, 54.99; H, 3.59; N, 12.43.

실시예 199Example 199

6-(아미노이미노메틸)-N-(4-메틸-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-methyl-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 199AExample 199A

실시예 184A에 대한 과정을 사용하고 4-아미노벤즈아미드를 2-아미노-5-메틸벤조티아졸로 대체하여 목적 화합물을 수득한다. MS(ESI-) m/z 293(M+H)-.Use the procedure for Example 184A and replace 4-aminobenzamide with 2-amino-5-methylbenzothiazole to afford the desired compound. MS (ESI-) m / z 293 (M + H) - .

실시예 199BExample 199B

6-(아미노이미노메틸)-N-(4-메틸-2-티아졸릴)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-methyl-2-thiazolyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 과정에 따라서 실시예 199A에서 수득된 생성물을 사용하여 목적 화합물을 수득한다.The product obtained in Example 199A was used following the procedure described in Example 1B to afford the desired compound.

MS(ESI+) m/z 311 (M+H)+.MS (ESI < + >) m / z 311 (M + H) + .

1H-NMR(300MHz, DMSO) δ 9.51(s, 2H), 9.25(s, 2H), 8.86(s, 1H), 8.55(s, 1H), 8.30(d, 1H, J=8.48), 8.25(d, 1H, J=2.03), 7.91(dd, 1H, J=8.48, 1.70), 6.87(s, 1H), 2.34(s, 3H). 1 H-NMR (300 MHz, DMSO) δ 9.51 (s, 2H), 9.25 (s, 2H), 8.86 (s, 1H), 8.55 (s, 1H), 8.30 (d, 1H, J = 8.48), 8.25 (d, 1H, J = 2.03), 7.91 (dd, 1H, J = 8.48, 1.70), 6.87 (s, 1H), 2.34 (s, 3H).

C18H15F3N4SO3·0.5 TFA에 대한 원소분석치: C 18 H 15 F 3 N 4 SO 3 · Elemental analysis for a 0.5 TFA:

계산치: C, 47.40; H, 3.25; N, 11.64.Calc .: C, 47.40; H, 3. 25; N, 11.64.

실측치: C, 47.90; H, 3.36; N, 11.71.Found: C, 47.90; H, 3. 36; N, 11.71.

실시예 200Example 200

6-(아미노이미노메틸)-4-[5-(에틸티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 200AExample 200A

실시예 154A의 과정에 의해 2-트리메틸실릴-3-브로모푸란 및 디에틸디설파이드로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 279, 281(M+H)+.The desired compound is prepared from 2-trimethylsilyl-3-bromofuran and diethyldisulfide by the procedure of Example 154A. MS (DCI / NH 3 ) m / z 279, 281 (M + H) + .

실시예 200BExample 200B

THF(20ml) 중의 실시예 200A(8.60g, 30.8mmol)로부터의 생성물의 용액 및 TBAF(61.6ml)의 1M 용액을 24시간 동안 교반한다. 반응물을 농축시키고 용출제로서 헥산을 사용하여 SiO2상에서 크로마토그래피하여 2-에틸티오-4-브로모푸란을 3.32g(52%) 수득한다. 실시예 57A의 과정에 의해 상기 물질로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 127(M-B(OH)2)+.A solution of the product from Example 200A (8.60 g, 30.8 mmol) and 1 M solution of TBAF (61.6 ml) in THF (20 ml) is stirred for 24 hours. The reaction is concentrated and chromatographed on SiO 2 using hexane as eluent to afford 3.32 g (52%) of 2-ethylthio-4-bromofuran. The desired compound is prepared from the material by the procedure of Example 57A. MS (DCI / NH 3 ) m / z 127 (MB (OH) 2 ) + .

실시예 200CExample 200C

실시예 57B의 과정에 의해 실시예 200B의 생성물 및 실시예 152C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 416(M+NH4)+.The desired compound is prepared from the product of Example 200B and the product of Example 152C by the procedure of Example 57B. MS (DCI / NH 3 ) m / z 416 (M + NH 4 ) + .

실시예 200DExample 200D

6-(아미노이미노메틸)-4-[5-(에틸티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정에 따라서 실시예 200C로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 200C following the procedure of Example 144C.

MS(DCI/NH3) m/z 416 (M+H)+.MS (DCI / NH 3 ) m / z 416 (M + H) + .

1H-NMR(300MHz, DMSO-d6) δ 1.30(t, 3H), 2.92(q, 2H), 7.15(t, 1H), 7.34(s, 1H), 7.40(t, 2H), 7.83(d, 2H), 7.92(dd, 1H), 8.20(d, 1H), 8.40(d, 1H), 8.47(s, 1H), 8.60(s, 1H), 8.69(s, 1H), 9.21(br s, 2H), 9.58(br s, 2H), 10.61(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.30 (t, 3H), 2.92 (q, 2H), 7.15 (t, 1H), 7.34 (s, 1H), 7.40 (t, 2H), 7.83 ( d, 2H), 7.92 (dd, 1H), 8.20 (d, 1H), 8.40 (d, 1H), 8.47 (s, 1H), 8.60 (s, 1H), 8.69 (s, 1H), 9.21 (br) s, 2H), 9.58 (br s, 2H), 10.61 (s, 1H).

C24H21N3SO2·1.5 HCl에 대한 원소분석치:Elemental analysis for C 24 H 21 N 3 SO 2 · 1.5 HCl:

계산치: C, 61.31; H, 4.82; N, 8.94.Calc .: C, 61.31; H, 4. 82; N, 8.94.

실측치: C, 61.39; H, 4.89; N, 9.03.Found: C, 61.39; H, 4.89; N, 9.03.

실시예 201Example 201

6-(아미노이미노메틸)-4-[5-(프로필티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (propylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 201AExample 201A

실시예 154A의 과정에 의해 2-트리메틸실릴-3-브로모푸란 및 디프로필디설파이드로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 293, 295(M+H)+.The desired compound is prepared from 2-trimethylsilyl-3-bromofuran and dipropyldisulfide by the procedure of Example 154A. MS (DCI / NH 3 ) m / z 293, 295 (M + H) + .

실시예 201BExample 201B

실시예 154B의 과정에 의해 실시예 201A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 432(M+H)+.The desired compound is prepared from the product of Example 201A by the procedure of Example 154B. MS (DCI / NH 3 ) m / z 432 (M + H) + .

실시예 201CExample 201C

실시예 154C의 과정에 의해 실시예 201B의 생성물 및 실시예 152C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 430(M+NH4)+.The desired compound is prepared from the product of Example 201B and the product of Example 152C by the procedure of Example 154C. MS (DCI / NH 3 ) m / z 430 (M + NH 4 ) + .

실시예 201DExample 201D

6-(아미노이미노메틸)-4-[5-(프로필티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (propylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정에 의해 실시예 201C로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 201C by the procedure of Example 144C.

MS(DCI/NH3) m/z 430 (M+H)+.MS (DCI / NH 3 ) m / z 430 (M + H) + .

1H-NMR(300MHz, DMSO-d6) δ 1.01(t, 3H), 1.66(qt, 2H), 2.89(t, 2H), 7.15(t, 1H), 7.34(s, 1H), 7.40(t, 2H), 7.84(d, 2H), 7.92(dd, 1H), 8.20(d, 1H), 8.40(d, 1H), 8.47(s, 1H), 8.60(s, 1H), 8.69(s, 1H), 9.22(br s, 2H), 9.58(br s, 2H), 10.61(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.01 (t, 3H), 1.66 (qt, 2H), 2.89 (t, 2H), 7.15 (t, 1H), 7.34 (s, 1H), 7.40 ( t, 2H), 7.84 (d, 2H), 7.92 (dd, 1H), 8.20 (d, 1H), 8.40 (d, 1H), 8.47 (s, 1H), 8.60 (s, 1H), 8.69 (s , 1H), 9.22 (br s, 2H), 9.58 (br s, 2H), 10.61 (s, 1H).

C25H23N3SO2·1.25 HCl에 대한 원소분석치:Elemental Analysis for C 25 H 23 N 3 SO 2 · 1.25 HCl:

계산치: C, 63.20; H, 5.14; N, 8.84.Calc .: C, 63.20; H, 5. 14; N, 8.84.

실측치: C, 63.24; H, 5.16; N, 8.93.Found: C, 63.24; H, 5. 16; N, 8.93.

실시예 202Example 202

6-(아미노이미노메틸)-N-(6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 202AExample 202A

실온에서 THF(15ml) 중의 산 클로라이드인 실시예 8B(331mg, 1.5mmol)의 용액에 프로필렌 옥사이드(10ml), DMAP(5mg), 1방울의 트리에틸아민 및 마지막으로 6-아미노퀴놀린(288mg, 2.0mmol)을 가한다. 실온에서 4시간 후, 에틸 아세테이트(10ml) 및 에테르(20ml)를 가하고 회백색 고체 생성물을 여과한다. 수율: 357mg(72%). MS(DCI/NH3) m/z 324(M+H)+.To a solution of Example 8B (331 mg, 1.5 mmol) which is an acid chloride in THF (15 ml) at room temperature, propylene oxide (10 ml), DMAP (5 mg), 1 drop of triethylamine and finally 6-aminoquinoline (288 mg, 2.0 mmol) is added. After 4 hours at room temperature, ethyl acetate (10 ml) and ether (20 ml) are added and the off-white solid product is filtered off. Yield: 357 mg (72%). MS (DCI / NH 3 ) m / z 324 (M + H) + .

실시예 202BExample 202B

6-(아미노이미노메틸)-N-(6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 목적 화합물을 제조한다.The desired compound is prepared as described in Example 1B.

MS(ESI+) m/z 341 (M+H)+, (ESI-) 339 (M-1)-.MS (ESI + ) m / z 341 (M + H) + , (ESI − ) 339 (M-1) − .

1H-NMR(300MHz, DMSO-d6) δ 10.98(s, 1H), 9.53(s, 2H), 9.25(s, 2H), 8.93-8.91(m, 1H), 8.77(s, 1H), 8.67(d, J=1.8Hz, 1H), 8.58(s, 1H), 8.53(d, J=8.5Hz, 1H), 8.37-8.09(m, 5H), 7.93(dd, J1=8.5Hz, J2=1.8Hz, 1H), 7.65-7.62(m, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.98 (s, 1H), 9.53 (s, 2H), 9.25 (s, 2H), 8.93-8.91 (m, 1H), 8.77 (s, 1H), 8.67 (d, J = 1.8 Hz, 1H), 8.58 (s, 1H), 8.53 (d, J = 8.5 Hz, 1H), 8.37-8.09 (m, 5H), 7.93 (dd, J1 = 8.5 Hz, J2 = 1.8 Hz, 1H), 7.65-7.62 (m, 1H).

C21H16N4O·0.2 TFA에 대한 원소분석치:Elemental Analysis for C 21 H 16 N 4 O · 0.2 TFA:

계산치: C, 52.83; H, 3.19; N, 9.86.Calc .: C, 52.83; H, 3. 19; N, 9.86.

실측치: C, 52.62; H, 2.94; N, 9.74.Found: C, 52.62; H, 2.94; N, 9.74.

실시예 203Example 203

6-(아미노이미노메틸)-N-(1H-인다졸-6-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indazol-6-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 203AExample 203A

6-아미노인다졸을 6-아미노퀴놀린으로 대체하는 것을 제외하고는 실시예 202A에 기재된 바와 같이 수행하여 목적 화합물을 285mg 수득한다. MS:ESI+: 313(M+1); ESI-311(M-1).Except for replacing 6-aminoindazole with 6-aminoquinoline, it was carried out as described in Example 202A to give 285 mg of the target compound. MS: ESI < + >: 313 (M + 1); ESI-311 (M-1).

실시예 203BExample 203B

6-(아미노이미노메틸)-N-(1H-인다졸-6-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indazol-6-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

0℃에서 톨루엔(2ml) 중의 염화암모늄(140mg, 2.6mmol)의 현탁액에 톨루엔 중의 2N 트리메틸알루미늄(871㎕, 1.74mmol)의 용액을 서서히 가한다. 5분 후, 반응 혼합물을 30분 동안 실온으로 가온시킨다. 실온에서 알루미늄 시약의 용액에 섹션(a)로부터의 실시예 203A, 니트릴을 가하고, 이 반응 혼합물을 48시간 동안 100℃로 가열한다. 반응 혼합물을 냉각시킨 다음, 클로로포름 중의 실리카의 현탁액에 붓고 1시간 동안 교반한다. 이 실리카를 여과한 다음 메탄올로 세척한다. 용매를 농축시키고, 5ml/min의 유속(100분 동안 매 2분마다 분획이 수집된다)으로 160분에 걸쳐 90%A(0.1% 수성 TFA)/10%B(메탄올) 내지 10%A/90%B 범위 구배의 용매 혼합물을 사용하여 250nM에서 UV 검출하면서 30cm x 2cm C-18 칼럼(40마이크론, J.T.Baker) 상에서 중간압 액체 크로마토그래피하여 정제하여, 목적 화합물을 42mg 수득한다.To a suspension of ammonium chloride (140 mg, 2.6 mmol) in toluene (2 ml) at 0 ° C. is slowly added a solution of 2N trimethylaluminum (871 μl, 1.74 mmol) in toluene. After 5 minutes, the reaction mixture is allowed to warm to room temperature for 30 minutes. Example 203A, nitrile from section (a) is added to a solution of aluminum reagent at room temperature and the reaction mixture is heated to 100 ° C. for 48 hours. The reaction mixture is cooled, then poured into a suspension of silica in chloroform and stirred for 1 hour. This silica is filtered off and washed with methanol. The solvent is concentrated and 90% A (0.1% aqueous TFA) / 10% B (methanol) to 10% A / 90 over 160 minutes at a flow rate of 5 ml / min (fractions are collected every 2 minutes for 100 minutes). Purification by medium pressure liquid chromatography on a 30 cm x 2 cm C-18 column (40 microns, JTBaker) with UV detection at 250 nM using a solvent mixture in the% B gradient, affords 42 mg of the desired compound.

MS(ESI+) m/z 330 (M+H)+, (ESI-) 328 (M-1)-.MS (ESI + ) m / z 330 (M + H) + , (ESI − ) 328 (M-1) − .

1H-NMR(300MHz, DMSO-d6) δ 10.65(s, 1H), 9.47(m, 4H), 8.65(s, 2H), 8.50(s, 2H), 8.25-8.23(m, 2H), 8.17-8.10(m, 2H), 7.94(s, 1H), 7.86-7.84(dd, J1=8.8Hz, J2=1.6Hz, 1H), 7.66(d, J=8.5Hz, 1H), 7.37(d, J=8.4Hz, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.65 (s, 1H), 9.47 (m, 4H), 8.65 (s, 2H), 8.50 (s, 2H), 8.25-8.23 (m, 2H), 8.17-8.10 (m, 2H), 7.94 (s, 1H), 7.86-7.84 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.37 (d , J = 8.4 Hz, 1H).

C19H15N50.2 TFA에 대한 원소분석치:Elemental Analysis for C 19 H 15 N 5 0.2 TFA:

계산치: C, 49.56; H, 3.07; N, 12.56.Calc .: C, 49.56; H, 3.07; N, 12.56.

실측치: C, 49.68; H, 3.10; N, 12.47.Found: C, 49.68; H, 3.10; N, 12.47.

실시예 204Example 204

6-(아미노이미노메틸)-N-(1H-인다졸-5-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indazol-5-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 204AExample 204A

5-아미노인다졸을 6-아미노퀴놀린으로 대체하는 것을 제외하고는 실시예 202A에 기재된 바와 같이 수행하여 목적 화합물을 362mg 수득한다. MS:ESI+: 313(M+1); ESI-311(M-1).Except for replacing 5-aminoindazole with 6-aminoquinoline, it was carried out as described in Example 202A to give 362 mg of the target compound. MS: ESI < + >: 313 (M + 1); ESI-311 (M-1).

실시예 204BExample 204B

6-(아미노이미노메틸)-N-(1H-인다졸-5-일)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indazol-5-yl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 203B에 대해 기재된 바와 같이 수행하여 목적 화합물을 55mg 수득한다.Performed as described for Example 203B to afford 55 mg of the target compound.

MS(ESI+) m/z 330 (M+H)+, (ESI-) 328 (M-1)-.MS (ESI + ) m / z 330 (M + H) + , (ESI − ) 328 (M-1) − .

1H-NMR(300MHz, DMSO-d6) δ 13.06(s, 1H), 10.58(s, 1H), 9.51(s, 2H), 9.15(s, 2H), 8.71(d, j=1.9Hz, 1H), 8.56(d, j=1.9Hz, 1H), 8.34-8.17(m, 4H), 8.10(s, 1H), 7.90(dd, J1=8.5Hz, J2=1.7Hz, 1H), 7.63(dd, J1=8.9Hz, J2=1.7Hz, 1H), 7.56(d, J=8.8Hz, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 13.06 (s, 1H), 10.58 (s, 1H), 9.51 (s, 2H), 9.15 (s, 2H), 8.71 (d, j = 1.9Hz, 1H), 8.56 (d, j = 1.9 Hz, 1H), 8.34-8.17 (m, 4H), 8.10 (s, 1H), 7.90 (dd, J1 = 8.5 Hz, J2 = 1.7 Hz, 1H), 7.63 ( dd, J1 = 8.9 Hz, J2 = 1.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H).

C19H15N5O·TFA·1.75 H2O에 대한 원소분석치:Elemental Analysis for C 19 H 15 N 5 O · TFA · 1.75 H 2 O:

계산치: C, 53.11; H, 4.14; N, 14.75.Calc .: C, 53.11; H, 4.14; N, 14.75.

실측치: C, 53.20; H, 3.99; N, 14.42.Found: C, 53.20; H, 3.99; N, 14.42.

실시예 205Example 205

6-(아미노이미노메틸)-N-(1H-인돌-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indol-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 205AExample 205A

6-아미노인돌을 6-아미노퀴놀린으로 대체하는 것을 제외하고는 실시예 202A에 기재된 바와 같이 수행하여 목적 화합물을 744mg 수득한다. MS:(ESI)+: 329(M+1)+ 및 (ESI)-: 327(M-1)-.744 mg of the desired compound are obtained as described in Example 202A, except that 6-aminoindole is replaced with 6-aminoquinoline. MS: (ESI) < + >: 329 (M + 1) < + > and (ESI)-: 327 (M-1)-.

실시예 205BExample 205B

6-(아미노이미노메틸)-N-(1H-인돌-5-일)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-indol-5-yl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 203B에 대해 기재된 바와 같이 수행하여 목적 화합물을 90mg 수득한다.Performed as described for Example 203B to afford 90 mg of the target compound.

MS(ESI+) m/z 329 (M+H)+, (ESI-) 327 (M-1)-.MS (ESI + ) m / z 329 (M + H) + , (ESI − ) 327 (M-1) − .

1H-NMR(300MHz, DMSO-d6) δ 11.09(s, 1H), 10.40(s, 1H), 9.51(s, 2H), 9.15(s, 2H), 8.71(s, 1H), 8.55(s, 1H), 8.32(d, J=8.4Hz, 1H), 8.26-8.17(m, 2H), 8.05(d, J=2.6Hz, 1H), 7.90(dd, J1=8.4Hz, J2=1.8Hz, 1H), 7.46-7.35(m, 3H), 6.45-6.43(m, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 11.09 (s, 1H), 10.40 (s, 1H), 9.51 (s, 2H), 9.15 (s, 2H), 8.71 (s, 1H), 8.55 ( s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.26-8.17 (m, 2H), 8.05 (d, J = 2.6 Hz, 1H), 7.90 (dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1H), 7.46-7.35 (m, 3H), 6.45-6.43 (m, 1H).

C20H16N4O·TFA에 대한 원소분석치:Elemental Analysis for C 20 H 16 N 4 O · TFA:

계산치: C, 59.73; H, 3.87; N, 12.66.Calc .: C, 59.73; H, 3.87; N, 12.66.

실측치: C, 59.27; H, 4.17; N, 12.74.Found: C, 59.27; H, 4. 17; N, 12.74.

실시예 206Example 206

7-[2-(4-모르폴리닐)에톡시]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염7- [2- (4-morpholinyl) ethoxy] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 206AExample 206A

2-클로로에틸모르폴린을 사용하여 실시예 119A에 기재된 바와 같이 니트릴을 제조한다. MS(DCI/NH3) m/z 283(M+H)+.Nitrile is prepared as described in Example 119A using 2-chloroethylmorpholine. MS (DCI / NH 3 ) m / z 283 (M + H) + .

실시예 206BExample 206B

7-[2-(4-모르폴리닐)에톡시]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염7- [2- (4-morpholinyl) ethoxy] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt

실시예 119B에 대해 기재된 바와 같이 수행하여 회백색 고체로서의 목적 화합물(50% 수율)을 수득한다.Perform as described for Example 119B to afford the desired compound (50% yield) as an off-white solid.

MS(DCI(NH3) m/z 300 (M+H)+.MS (DCI (NH 3 ) m / z 300 (M + H) + .

1H-NMR(300MHz, DMSO-d6) δ 3.500(br m, 4H), 3.700(br m, 2H), 3.990(br m, 4H), 4.490(br m, 2H), 7.435(dd, 1H), 7.530(d, 1H), 7.680(dd, 1H), 8.035(d, 1H), 8.100(d, 1H), 8.345(d, 1H), 9.165(br s, 2H), 9.420(br s, 2H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 3.500 (br m, 4H), 3.700 (br m, 2H), 3.990 (br m, 4H), 4.490 (br m, 2H), 7.435 (dd, 1H ), 7.530 (d, 1H), 7.680 (dd, 1H), 8.035 (d, 1H), 8.100 (d, 1H), 8.345 (d, 1H), 9.165 (br s, 2H), 9.420 (br s, 2H).

C17H21N3O2·(C2HO2F3)2.15에 대한 원소분석치:Elemental Analysis for C 17 H 21 N 3 O 2 · (C 2 HO 2 F 3 ) 2.15 :

계산치: C, 46.98; H, 4.29; N, 7.72.Calc .: C, 46.98; H, 4. 29; N, 7.72.

실측치: C, 47.00; H, 4.32; N, 7.77.Found: C, 47.00; H, 4. 32; N, 7.77.

실시예 207Example 207

6-(아미노이미노메틸)-N-페닐-4-(2-피롤리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N-phenyl-4- (2-pyrrolidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 207AExample 207A

실시예 68A의 과정에 의해 실시예 152A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 281(M+H)+.The desired compound is prepared from the product of Example 152A by the procedure of Example 68A. MS (DCI / NH 3 ) m / z 281 (M + H) + .

실시예 207BExample 207B

실시예 152B의 과정에 의해 실시예 207A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 267(M+H)+.The desired compound is prepared from the product of Example 207A by the procedure of Example 152B. MS (DCI / NH 3 ) m / z 267 (M + H) + .

실시예 207CExample 207C

DMF(10ml) 중의 실시예 207B의 생성물(220mg, 0.826mmol), 디이소프로필에틸 아민(0.288ml, 1.65mmol) 및 O-(7-아자벤조트리아졸-1-일)-N,N,N',N'-테트라메틸우로늄 헥사플루오로포스페이트(314mg, 0.826mmol)의 용액을 0℃에서 30분 동안 교반한다. 아닐린(0.083ml, 0.909mmol)을 가하고, 반응물을 실온에서 4시간 동안 교반한다. 반응물을 포화 수성 Na2CO3용액에 붓고 3 x 에틸 아세테이트로 추출한다. 합한 추출물을 물 및 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 물질을 에탄올/헥산으로 재결정화하여 목적 화합물을 212mg(75%) 수득한다. MS(DCI/NH3) m/z 342(M+H)+.Product of Example 207B (220 mg, 0.826 mmol), diisopropylethyl amine (0.288 ml, 1.65 mmol) and O- (7-azabenzotriazol-1-yl) -N, N, N in DMF (10 ml) A solution of ', N'-tetramethyluronium hexafluorophosphate (314 mg, 0.826 mmol) is stirred at 0 ° C. for 30 minutes. Aniline (0.083 ml, 0.909 mmol) is added and the reaction is stirred at rt for 4 h. The reaction is poured into saturated aqueous Na 2 CO 3 solution and extracted with 3 × ethyl acetate. The combined extracts are washed with water and brine, dried over Na 2 S0 4 and concentrated. The crude material is recrystallized from ethanol / hexane to give 212 mg (75%) of the desired compound. MS (DCI / NH 3 ) m / z 342 (M + H) + .

실시예 207DExample 207D

6-(아미노이미노메틸)-N-페닐-4-(2-피롤리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N-phenyl-4- (2-pyrrolidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B의 과정에 의해 실시예 207C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 359(M+H)+.The desired compound is prepared from the product of Example 207C by the procedure of Example 1B. MS (DCI / NH 3 ) m / z 359 (M + H) + .

1H-NMR(300MHz, DMSO-d6) δ 2.02(t, 4H), 3.55(t, 4H), 7.13(t, 1H), 7.38(t, 2H), 7.41(s, 1H), 7.80(m, 3H), 8.08(s, 1H), 8.18(d, 1H), 8.67(s, 1H), 9.10(br s, 2H), 9.43(br s, 2H), 10.41(br s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 2.02 (t, 4H), 3.55 (t, 4H), 7.13 (t, 1H), 7.38 (t, 2H), 7.41 (s, 1H), 7.80 ( m, 3H), 8.08 (s, 1H), 8.18 (d, 1H), 8.67 (s, 1H), 9.10 (br s, 2H), 9.43 (br s, 2H), 10.41 (br s, 1H).

C22H22N4O·1.0 C2HF3O2에 대한 원소분석치:Elemental Analysis for C 22 H 22 N 4 O · 1.0 C 2 HF 3 O 2 :

계산치: C, 61.01; H, 4.91; N, 11.86.Calc .: C, 61.01; H, 4.91; N, 11.86.

실측치: C, 60.47; H, 5.36; N, 7.39.Found: C, 60.47; H, 5. 36; N, 7.39.

실시예 208Example 208

6-(아미노이미노메틸)-N-(5-피리미디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-pyrimidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 208AExample 208A

5-아미노피리미딘으르 사용하여 실시예 8A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+275.The product is prepared in the manner of Example 8A using 5-aminopyrimidine. MS (APCI) m / z (M + H) + 275.

실시예 208BExample 208B

6-(아미노이미노메틸)-N-(5-피리미디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-pyrimidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에서와 같이 상기 생성물을 제조한다.Prepare the product as in Example 1B.

MS(CI) m/z (M+H)+292.MS (CI) m / z (M + H) + 292.

1H-NMR(300MHz, DMSO-d6) δ 10.99(s, 1H), 9.52(s, 2H), 9.27(s, 2H), 9.24(s, 2H), 8.98(s, 1H), 8.76(s, 1H), 8.58(s, 1H), 8.36-8.18(m, 3H), 7.92(dd, J=1.5, 8.4Hz, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 10.99 (s, 1H), 9.52 (s, 2H), 9.27 (s, 2H), 9.24 (s, 2H), 8.98 (s, 1H), 8.76 ( s, 1H), 8.58 (s, 1H), 8.36-8.18 (m, 3H), 7.92 (dd, J = 1.5, 8.4 Hz, 1H).

C18H14N5O3F37/10 TFA에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 5 O 3 F 3 7/10 TFA:

계산치: C, 47.97; H, 3.05; N, 14.40.Calc .: C, 47.97; H, 3.05; N, 14.40.

실측치: C, 47.78; H, 3.05; N, 14.67.Found: C, 47.78; H, 3.05; N, 14.67.

실시예 209Example 209

6-(아미노이미노메틸)-N-(3-피리다지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-pyridazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 209AExample 209A

3-아미노-6-클로로피리다진(1.05g, 8.2mmol)을 2ml 암모니아/메탄올을 함유하는 10ml 메탄올에 용해시킨다. 팔라듐/탄소(200mg, 10%)을 가하고 1수소압하에서 4시간 동안 교반한다. 반응물을 여과하고, 농축시킨 다음, 추가의 정제없이 사용한다. MS(CI) m/z(M+H)+96.3-amino-6-chloropyridazine (1.05 g, 8.2 mmol) is dissolved in 10 ml methanol containing 2 ml ammonia / methanol. Palladium / carbon (200 mg, 10%) is added and stirred for 4 hours under 1 hydrogen pressure. The reaction is filtered, concentrated and used without further purification. MS (CI) m / z (M + H) + 96.

실시예 209BExample 209B

실시예 12의 과정에 의해 실시예 209A의 생성물로부터 상기 화합물을 제조한다. MS(APCI) m/z (M+H)+275.The compound is prepared from the product of Example 209A by the procedure of Example 12. MS (APCI) m / z (M + H) + 275.

실시예 209CExample 209C

6-(아미노이미노메틸)-N-(3-피리다지닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-pyridazinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B의 과정에 의해 실시예 209B의 생성물로부터 상기 화합물을 제조한다. MS(CI) m/z (M+H)+292.The compound is prepared from the product of Example 209B by the procedure of Example 1B. MS (CI) m / z (M + H) + 292.

1H-NMR(300MHz, d6-DMSO) δ 11.72(s, 1H), 9.51(s, 2H), 9.22(s, 2H), 9.06(m, 1H), 8.86(s, 1H), 8.56(s, 1H), 8.45(d, 1H), 8.23(s, 2H), 7.90(dd, 1H), 7.78(dd, 1H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 11.72 (s, 1H), 9.51 (s, 2H), 9.22 (s, 2H), 9.06 (m, 1H), 8.86 (s, 1H), 8.56 ( s, 1H), 8.45 (d, 1H), 8.23 (s, 2H), 7.90 (dd, 1H), 7.78 (dd, 1H).

C18H14N5O3F31/2 TFA에 대한 원소분석치:Elemental Analysis for C 18 H 14 N 5 O 3 F 3 1/2 TFA:

계산치: C, 49.29; H, 3.16; N, 14.73.Calc .: C, 49.29; H, 3. 16; N, 14.73.

실측치: C, 49.56; H, 3.23; N, 14.73.Found: C, 49.56; H, 3. 23; N, 14.73.

실시예 210Example 210

6-(아미노이미노메틸)-N-(5-브로모-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-bromo-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 210AExample 210A

실시예 8G의 과정에 의해 실시예 8E의 생성물, 2-아미노-5-브로모피리딘으로부터 목적 화합물을 제조한다. MS(APCI+) m/z 352(M+H)+.The desired compound is prepared from the product of Example 8E, 2-amino-5-bromopyridine by the procedure of Example 8G. MS (APCI +) m / z 352 (M + H) + .

실시예 210BExample 210B

6-(아미노이미노메틸)-N-(5-브로모-2-피리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (5-bromo-2-pyridinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B의 과정에 의해 실시예 210A의 생성물로부터 목적 화합물을 제조한다. MS(DCI) m/z 369(M+H)+.The desired compound is prepared from the product of Example 210A by the procedure of Example 1B. MS (DCI) m / z 369 (M + H) + .

1H-NMR(300MHz, DMSO) δ 11.30(s, 1H), 9.51(s, 2H), 9.17(s, 2H), 8.80(s, 1H), 8.57(d, 1H, J=2.57), 8.55(s, 1H), 8.31(d, 1H, J=8.45), 8.26(d, 1H, J=8.82), 8.19-8.24(m, 2H), 8.14(dd, 1H, J=2.57, 9.19), 7.90(dd, 1H, J=1.83, 8.82). 1 H-NMR (300MHz, DMSO) δ 11.30 (s, 1H), 9.51 (s, 2H), 9.17 (s, 2H), 8.80 (s, 1H), 8.57 (d, 1H, J = 2.57), 8.55 (s, 1H), 8.31 (d, 1H, J = 8.45), 8.26 (d, 1H, J = 8.82), 8.19-8.24 (m, 2H), 8.14 (dd, 1H, J = 2.57, 9.19), 7.90 (dd, 1H, J = 1.83, 8.82).

C19H14BrF3N4O3에 대한 원소분석치:Elemental Analysis for C 19 H 14 BrF 3 N 4 O 3 :

계산치: C, 47.22; H, 2.92; N, 11.59.Calc .: C, 47.22; H, 2.92; N, 11.59.

실측치: C, 47.60; H, 3.01; N, 11.30.Found: C, 47.60; H, 3.01; N, 11.30.

실시예 211Example 211

6-(아미노이미노메틸)-N-[3-(1-메틸에톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (1-methylethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 211AExample 211A

3-이소프로폭시아닐린을 사용하여 실시예 12의 방식으로 상기 화합물을 제조한다. MS(APCI) m/z (M+H)+331.Prepare the compound in the manner of Example 12 using 3-isopropoxyaniline. MS (APCI) m / z (M + H) + 331.

실시예 211BExample 211B

6-(아미노이미노메틸)-N-[3-(1-메틸에톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (1-methylethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

방법 1B를 사용하여 실시예 211A로부터 상기 화합물을 제조한다.The compound is prepared from Example 211A using Method 1B.

MS(CI) m/z (M+H)+348;MS (CI) m / z (M + H) + 348;

1H-NMR(300MHz, d6-DMSO) δ 10.50(s, 1H), 9.50(s, 2H), 9.22(s, 2H), 8.67(s, 1H), 8.56(s, 1H), 8.31(d, 1H), 8.25-8.13(m, 2H), 7.90(dd, 1H), 7.51(m, 1H), 7.36(m, 1H), 7.26(t, 1H), 6.68(dd, 1H), 4.59(m, 1H), 1.30(d, 6H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.50 (s, 1H), 9.50 (s, 2H), 9.22 (s, 2H), 8.67 (s, 1H), 8.56 (s, 1H), 8.31 ( d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.51 (m, 1H), 7.36 (m, 1H), 7.26 (t, 1H), 6.68 (dd, 1H), 4.59 (m, 1 H), 1.30 (d, 6 H).

C23H22N3O4F31/5 TFA에 대한 원소분석치:Elemental Analysis for C 23 H 22 N 3 O 4 F 3 1/5 TFA:

계산치: C, 57.96; H, 4.61; N, 8.66Calc .: C, 57.96; H, 4.61; N, 8.66

실측치: C, 57.99; H, 4.90; N, 8.68Found: C, 57.99; H, 4. 90; N, 8.68

실시예 212Example 212

2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세트산, 모노(트리플루오로아세테이트) 염2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetic acid, mono (trifluoroacetate) salt

실시예 185C로부터의 생성물(140mg, 0.542mmol)을 메탄올(11ml)에 용해시킨다. 이에 물(3ml) 중의 수산화리튬(68.2mg, 1.626mmol)의 용액을 가하고 생성된 혼합물을 불활성 대기하에서 실온하에 18시간 동안 교반한다. 반응물을 증발시키고 잔사를 역상 크로마토그래피로 정제하여 목적 화합물(102mg, 52%)을 수득한다. MS(DCI(NH3)) m/z 245 (M+H)+;The product from Example 185C (140 mg, 0.542 mmol) is dissolved in methanol (11 ml). To this was added a solution of lithium hydroxide (68.2 mg, 1.626 mmol) in water (3 ml) and the resulting mixture was stirred for 18 hours at room temperature under an inert atmosphere. The reaction is evaporated and the residue is purified by reverse phase chromatography to yield the desired compound (102 mg, 52%). MS (DCI (NH 3 )) m / z 245 (M + H) + ;

1H-NMR (300MHz, DMSO-d6) δ 4.875(s, 2H), 7.420(s, 1H), 7.435(dd, 1H), 7.660(dd, 1H), 8.015(d, 1H), 8.100(d, 1H), 8.340(d, 1H), 9.125(br s, 1H), 9.420(br s, 1H) 1 H-NMR (300 MHz, DMSO-d 6 ) δ 4.875 (s, 2H), 7.420 (s, 1H), 7.435 (dd, 1H), 7.660 (dd, 1H), 8.015 (d, 1H), 8.100 ( d, 1H), 8.340 (d, 1H), 9.125 (br s, 1H), 9.420 (br s, 1H)

C13H12N2O3·(C2HO2F3)1.30에 대한 원소분석치:Elemental Analysis for C 13 H 12 N 2 O 3 · (C 2 HO 2 F 3 ) 1.30 :

계산치: C, 47.74; H, 3.42; N, 7.14.Calc .: C, 47.74; H, 3. 42; N, 7.14.

실측치: C, 47.93; H, 3.36; N, 7.17.Found: C, 47.93; H, 3. 36; N, 7.17.

실시예 213Example 213

메틸 4-[6-(아미노이미노메틸)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염Methyl 4- [6- (aminoiminomethyl) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt

실시예 213AExample 213A

실시예 185A의 생성물을 실시예 119B에 기재된 바와 유사한 방식으로 메틸 4-(브로모메틸)벤조에이트로 처리한다. MS(DCI/NH3) m/z 335(M+NH4)+.The product of Example 185A is treated with methyl 4- (bromomethyl) benzoate in a similar manner as described in Example 119B. MS (DCI / NH 3 ) m / z 335 (M + NH 4 ) + .

실시예 213BExample 213B

메틸 4-[6-(아미노이미노메틸)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염Methyl 4- [6- (aminoiminomethyl) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt

실시예 213A의 생성물(250mg, 0.788mmol)을 실시예 119C에 기재된 바와 유사한 방식으로 처리하여 목적 화합물(130mg, 79%)을 수득한다.The product of Example 213A (250 mg, 0.788 mmol) was treated in a similar manner as described in Example 119C to afford the desired compound (130 mg, 79%).

MS(DCI(NH3)) m/z 335(M+H)+;MS (DCI (NH 3 )) m / z 335 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 3.870(s, 3H), 5.400(s, 2H), 7.500(dd, 1H), 7.540(d, 1H), 7.619(dd, 1H), 7.620(d, 2H), 8.025(d, 2H), 8.026(d, 1H), 8.090(d, 1H), 8.410(d, 1H), 9.260(v br s, 3H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 3.870 (s, 3H), 5.400 (s, 2H), 7.500 (dd, 1H), 7.540 (d, 1H), 7.619 (dd, 1H), 7.620 ( d, 2H), 8.025 (d, 2H), 8.026 (d, 1H), 8.090 (d, 1H), 8.410 (d, 1H), 9.260 (v br s, 3H).

C14H14N2O3·C2HO2F3·H2O 0.70에 대한 원소분석치: C 14 H 14 N 2 O 3 · C 2 HO 2 F 3 · Elemental analysis for H 2 O 0.70:

계산치: C, 57.32; H, 4.46; N, 6.08.Calc .: C, 57.32; H, 4. 46; N, 6.08.

실측치: C, 57.33; H, 4.70; N, 5.95.Found: C, 57.33; H, 4. 70; N, 5.95.

실시예 214Example 214

6-(아미노이미노메틸)-N-(1H-이미다졸릴)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (1H-imidazolyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 214AExample 214A

실시예 8G의 과정에 의해 실시예 8E의 생성물, 2-아미노이미다졸로부터 목적 화합물을 제조한다. MS(ESI-) m/z 261(M+H)-.The desired compound is prepared from the product of Example 8E, 2-aminoimidazole by the procedure of Example 8G. MS (ESI-) m / z 261 (M + H) - .

실시예 214BExample 214B

실시예 1B의 과정에 의해 실시예 214A의 생성물로부터 목적 화합물을 제조한다. MS(ESI+) m/z 280 (M+H)+;The desired compound is prepared from the product of Example 214A by the procedure of Example 1B. MS (ESI < + >) m / z 280 (M + H) + ;

1H-NMR(300MHz, DMSO) δ 9.50(s, 2H), 9.16(s, 2H), 8.78(s, 1H), 8.53(s, 1H), 8.26-8.31(m, 2H), 8.20(d, 1H, J=8.46), 7.88(dd, 1H, J=1.84, 8.83), 6.95(s, 2H). 1 H-NMR (300 MHz, DMSO) δ 9.50 (s, 2H), 9.16 (s, 2H), 8.78 (s, 1H), 8.53 (s, 1H), 8.26-8.31 (m, 2H), 8.20 (d , 1H, J = 8.46), 7.88 (dd, 1H, J = 1.84, 8.83), 6.95 (s, 2H).

C17H14F3N5O3·0.2 TFA·H2O에 대한 원소분석치:Elemental Analysis for C 17 H 14 F 3 N 5 O 3 · 0.2 TFAH 2 O:

계산치: C, 48.14; H, 3.76; N, 16.13.Calc .: C, 48.14; H, 3.76; N, 16.13.

실측치: C, 48.54; H, 3.40; N, 16.02.Found: C, 48.54; H, 3. 40; N, 16.02.

실시예 215Example 215

6-[2-[4-(하이드록시메틸)페닐]-1-사이클로프로필]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염6- [2- [4- (hydroxymethyl) phenyl] -1-cyclopropyl] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt

실시예 215AExample 215A

실시예 104에 기재된 바와 같이 제조된 물질(210mg, 0.52mmol)을 THF(6ml)에 용해시키고 10ml 디아조메탄에 적가한 다음, 0℃로 냉각시키고 Pd(OAc)2(9.8mg)을 가한다. 5분 동안 격렬한 기포가 발생된다. 생성된 검정색 슬러리를 20분 동안 교반하고, 여과한 다음 용매를 진공하에 제거하면 투명한 오일이 0.1g 남는다. MS(DCI/NH3) m/z 316(M+NH4)+.The material prepared as described in Example 104 (210 mg, 0.52 mmol) was dissolved in THF (6 ml) and added dropwise to 10 ml diazomethane, then cooled to 0 ° C. and Pd (OAc) 2 (9.8 mg) was added. . Violent bubbles are generated for 5 minutes. The resulting black slurry was stirred for 20 minutes, filtered and the solvent removed in vacuo leaving 0.1 g of clear oil. MS (DCI / NH 3 ) m / z 316 (M + NH 4 ) + .

실시예 215BExample 215B

6-[2-[4-(하이드록시메틸)페닐]-1-사이클로프로필]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- [2- [4- (hydroxymethyl) phenyl] -1-cyclopropyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1에 기재된 바와 같이 목적 화합물을 제조하고, 이를 역상 크로마토그래피로 정제하여 회백색 고체를 19.9mg 수득한다.The desired compound was prepared as described in Example 1, which was purified by reverse phase chromatography to yield 19.9 mg of an off-white solid.

MS(DCI/NH3) m/z (M+H)+316;MS (DCI / NH 3 ) m / z (M + H) + 316;

1H-NMR(300MHz, DMSO-d6) δ 9.41(s, 2H), 9.16(s, 2H), 8.46(s, 1H), 8.08(d, 2H), 8.03(d, 1H), 7.85(s, 1H), 7.75(dd, 1H), 7.58(dd, 1H), 7.3-7.1(m, 4H), 4.49(s, 2H), 2.38-2.48(m, 2H), 1.61-1.70(m, 2H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.41 (s, 2H), 9.16 (s, 2H), 8.46 (s, 1H), 8.08 (d, 2H), 8.03 (d, 1H), 7.85 ( s, 1H), 7.75 (dd, 1H), 7.58 (dd, 1H), 7.3-7.1 (m, 4H), 4.49 (s, 2H), 2.38-2.48 (m, 2H), 1.61-1.70 (m, 2H).

C23H21N2O2F31 H2O에 대한 원소분석치:Elemental Analysis for C 23 H 21 N 2 O 2 F 3 1 H 2 O:

계산치: C, 62.10; H, 4.80; N, 6.29.Calc .: C, 62.10; H, 4.80; N, 6.29.

실측치: C, 62.00; H, 4.75; N, 6.25.Found: C, 62.00; H, 4.75; N, 6.25.

실시예 216Example 216

N-(에톡시카보닐)-6-(2-페닐-1-사이클로프로필)-2-나프탈렌카복스이미드아미드N- (ethoxycarbonyl) -6- (2-phenyl-1-cyclopropyl) -2-naphthalenecarboximideamide

실시예 97에 기재된 샘플(130mg, 45mmol)을 DMF(3ml)에 용해시킨 다음 0℃로 냉각시키고, 트리에틸아민(0.01ml) 및 에틸 클로로포르메이트(0.05ml)로 처리한다. 생성된 용액을 실온에서 3일 동안 교반한 다음, 100ml 에틸 아세테이트로 희석시키며, 증류수(20ml)로 세척하며, 무수 황산나트륨으로 건조시키고, 여과한 다음, 용매를 감압하에 제거하면 투명한 오일이 남는다. 이 오일을 2:1 헥산/에틸 아세테이트로 용출시키면서 실리카 겔 크로마토그래피로 정제하고, 동결건조시킨 다음 목적 화합물을 백색 분말(55mg)로서 분리한다. MS(DCI/NH3) m/z (M+H)+359.The sample described in Example 97 (130 mg, 45 mmol) was dissolved in DMF (3 ml) and then cooled to 0 ° C. and treated with triethylamine (0.01 ml) and ethyl chloroformate (0.05 ml). The resulting solution was stirred at room temperature for 3 days, then diluted with 100 ml ethyl acetate, washed with distilled water (20 ml), dried over anhydrous sodium sulfate, filtered and the solvent removed under reduced pressure leaving a clear oil. This oil is purified by silica gel chromatography eluting with 2: 1 hexanes / ethyl acetate, lyophilized and the target compound is isolated as a white powder (55 mg). MS (DCI / NH 3 ) m / z (M + H) + 359.

1H-NMR(300MHz, DMSO-d6) δ 9.21(s, 2H), 8.46(s, 1H), 7.83(d, 2H), 7.62(s, 1H), 7.58(dd, 1H), 7.34(dd, 1H), 7.35-7.29(m, 3H), 7.25-7.17(m, 2H) 4.1(q, 2H), 2.38-2.28(m, 2H), 1.61(t, 2H), 1.25(t, 3H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 9.21 (s, 2H), 8.46 (s, 1H), 7.83 (d, 2H), 7.62 (s, 1H), 7.58 (dd, 1H), 7.34 ( dd, 1H), 7.35-7.29 (m, 3H), 7.25-7.17 (m, 2H) 4.1 (q, 2H), 2.38-2.28 (m, 2H), 1.61 (t, 2H), 1.25 (t, 3H ).

C23H22N2O2에 대한 원소분석치:Elemental Analysis for C 23 H 22 N 2 O 2 :

계산치: C, 77.07; H, 6.19; N, 7.82.Calc .: C, 77.07; H, 6. 19; N, 7.82.

실측치: C, 76.63; H, 6.05; N, 7.45.Found: C, 76.63; H, 6.05; N, 7.45.

실시예 217Example 217

6-(아미노이미노메틸)-N-(2-메틸-6-퀴놀리닐)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (2-methyl-6-quinolinyl) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt

실시예 8E와 144C에 기재된 바와 동일한 방식으로 목적 화합물을 제조한다.Prepare the desired compound in the same manner as described in Examples 8E and 144C.

MS m/z 355(M+H)+;MS m / z 355 (M + H) + ;

1H-NMR(DMSO, 300MHz): 10.95(s, 1H), 9.51(s, 2H), 9.14(s, 2H), 8.75(s, 1H), 8.65(s, 1H), 8.57(s, 1H), 8.35(dd, 1H, J1=J2=8.5Hz), 8.28(dd, 1H, J1=J2=8.5Hz), 8.19(dd, 1H, J1=J2=8.8Hz), 8.15(dd, 1H, J1=J2=8.3Hz), 8.04(dd, 1H, J1=J2=8.8Hz), 7.91(dd, 1H, J1=8.4Hz, J2=8.8Hz), 7.60(dd, 1H, J1=J2=8.1Hz). 5.99(S, 3H). 1 H-NMR (DMSO, 300 MHz): 10.95 (s, 1H), 9.51 (s, 2H), 9.14 (s, 2H), 8.75 (s, 1H), 8.65 (s, 1H), 8.57 (s, 1H ), 8.35 (dd, 1H, J1 = J2 = 8.5 Hz), 8.28 (dd, 1H, J1 = J2 = 8.5 Hz), 8.19 (dd, 1H, J1 = J2 = 8.8 Hz), 8.15 (dd, 1H, J1 = J2 = 8.3 Hz), 8.04 (dd, 1H, J1 = J2 = 8.8 Hz), 7.91 (dd, 1H, J1 = 8.4 Hz, J2 = 8.8 Hz), 7.60 (dd, 1H, J1 = J2 = 8.1 Hz). 5.99 (S, 3 H).

C22H18N4O·2.25 C2F3O2H·2H2O에 대한 원소분석치:Elemental Analysis for C 22 H 18 N 4 O · 2.25 C 2 F 3 O 2 H · 2H 2 O:

계산치: C, 49.20; H, 3.78; N, 8.66; F, 19.82.Calc .: C, 49.20; H, 3.78; N, 8.66; F, 19.82.

실측치: C, 49.02; H, 3.36; N, 8.66.Found: C, 49.02; H, 3. 36; N, 8.66.

실시예 218Example 218

6-(아미노이미노메틸)-N-(3-프로폭시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-propoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 218AExample 218A

3-아미노페놀(1g, 7.2mmol), 트리페닐포스핀(2.25g, 8.6mmol) 및 1-프로판올(0.517g, 8.6mmol)을 무수 THF 25ml에 용해시킨다. 디에틸아조디카복실레이트(1.5g, 8.6mmol)을 1분 동안 적가한다. 이 용액을 15분 동안 교반하고 교반하면서 헥산에 서서히 붓는다. 실리카 겔/셀라이트를 통하여 여과시켜 점성 황색 오일로서의 생성물을 수득한다. MS(APCI) m/z (M+H)+152.3-Aminophenol (1 g, 7.2 mmol), triphenylphosphine (2.25 g, 8.6 mmol) and 1-propanol (0.517 g, 8.6 mmol) are dissolved in 25 ml of dry THF. Diethylazodicarboxylate (1.5 g, 8.6 mmol) was added dropwise for 1 minute. The solution is stirred for 15 minutes and slowly poured into hexane with stirring. Filtration through silica gel / celite gave the product as a viscous yellow oil. MS (APCI) m / z (M + H) + 152.

실시예 218BExample 218B

실시예 218A로부터의 생성물을 사용하여 실시예 12의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+331.The product is prepared in the manner of Example 12 using the product from Example 218A. MS (APCI) m / z (M + H) + 331.

실시예 218CExample 218C

6-(아미노이미노메틸)-N-(3-프로폭시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-propoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 218로부터 상기 화합물을 제조한다.The compound is prepared from Example 218 as described in Example 1B.

MS(CI) m/z (M+H)+348.MS (CI) m / z (M + H) + 348.

1H-NMR(300MHz, d6-DMSO) δ 10.51(s, 1H), 9.50(s, 2H), 9.18(s, 2H), 8.86(s, 1H), 8.55(s, 1H), 8.32(d, 1H), 8.25-8.13(m, 2H), 7.90(dd, 1H), 7.52-7.33(m, 2H), 7.27(t, 1H), 6.73(dd, 1H), 3.94(t, 2H), 1.75(m, 2H), 1.00(t, 3H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.51 (s, 1H), 9.50 (s, 2H), 9.18 (s, 2H), 8.86 (s, 1H), 8.55 (s, 1H), 8.32 ( d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.52-7.33 (m, 2H), 7.27 (t, 1H), 6.73 (dd, 1H), 3.94 (t, 2H) , 1.75 (m, 2 H), 1.00 (t, 3 H).

C23H22N3O4F3: 1/20 TFA에 대한 원소분석치:Elemental Analysis for C 23 H 22 N 3 O 4 F 3 : 1/20 TFA:

계산치: C, 59.49; H, 4.77; N, 9.02.Calc .: C, 59.49; H, 4.77; N, 9.02.

실측치: C, 59.43; H, 4.94; N, 9.10.Found: C, 59.43; H, 4.94; N, 9.10.

실시예 219Example 219

6-(아미노이미노메틸)-N-[3-(1-에틸프로폭시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (1-ethylpropoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 219AExample 219A

3-펜탄올을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCl) m/z (M+H)+180.The product is prepared in the manner of Example 218A using 3-pentanol. MS (APCl) m / z (M + H) + 180.

실시예 219BExample 219B

실시예 219A의 생성물을 사용하여 실시예 12의 방식으로 상기 생성물을 제조한다. MS(APCl) m/z(M+H)+359.The product is prepared in the manner of Example 12 using the product of Example 219A. MS (APCl) m / z (M + H) + 359.

실시예 219CExample 219C

6-(아미노이미노메틸)-N-[3-(1-에틸프로폭시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (1-ethylpropoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 219B로부터 상기 생성물을 제조한다. MS(CI) m/z (M+H)+376.The product is prepared from Example 219B as described in Example 1B. MS (CI) m / z (M + H) + 376.

1H-NMR(300MHz, d6-DMSO) δ 10.47(s, 1H), 9.49(s, 2H), 9.14(s, 2H), 8.67(s, 1H), 8.55(s, 1H), 8.31(d, 1H), 8.25-8.16(m, 2H), 7.90(dd, 1H), 7.51(s, 1H), 7.38(m, 1H), 7.26(t, 1H), 6.72(dd, 1H), 4.18(m, 1H), 1.65(m, 4H), 0.93(t, 6H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.47 (s, 1H), 9.49 (s, 2H), 9.14 (s, 2H), 8.67 (s, 1H), 8.55 (s, 1H), 8.31 ( d, 1H), 8.25-8.16 (m, 2H), 7.90 (dd, 1H), 7.51 (s, 1H), 7.38 (m, 1H), 7.26 (t, 1H), 6.72 (dd, 1H), 4.18 (m, 1H), 1.65 (m, 4H), 0.93 (t, 6H).

C25H26N3O4F3에 대한 원소분석치:Elemental analysis for C 25 H 26 N 3 O 4 F 3 :

계산치: C, 61.34; H, 5.35; N, 8.58.Calc .: C, 61.34; H, 5. 35; N, 8.58.

실측치: C, 61.05; H, 5.42; N, 8.22.Found: C, 61.05; H, 5. 42; N, 8.22.

실시예 220Example 220

6-(아미노이미노메틸)-N-[3-(사이클로펜틸옥시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (cyclopentyloxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 220AExample 220A

사이클로펜탄올을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+86.The product is prepared in the manner of Example 218A using cyclopentanol. MS (APCI) m / z (M + H) + 86.

실시예 220BExample 220B

실시예 220A의 생성물을 사용하여 실시예 12의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+357.The product is prepared in the manner of Example 12 using the product of Example 220A. MS (APCI) m / z (M + H) + 357.

실시예 220CExample 220C

6-(아미노이미노메틸)-N-[3-(사이클로펜틸옥시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (cyclopentyloxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 220B로부터 상기 생성물을 제조한다.The product is prepared from Example 220B as described in Example 1B.

MS(CI) m/z (M+H)+374;MS (CI) m / z (M + H) + 374;

1H-NMR(300MHz, d6-DMSO) δ 10.50(s, 1H), 9.51(s, 2H), 9.30(s, 2H), 8.68(s, 1H), 8.56(s, 1H), 8.32(d, 1H), 8.25-8.13(m, 2H), 7.90(dd, 1H), 7.49(m, 1H), 7.38(m, 1H), 7.26(t, 1H), 6.72(dd, 1H), 4.79(m, 1H), 1.96-1.08(m, 8H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.50 (s, 1H), 9.51 (s, 2H), 9.30 (s, 2H), 8.68 (s, 1H), 8.56 (s, 1H), 8.32 ( d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.49 (m, 1H), 7.38 (m, 1H), 7.26 (t, 1H), 6.72 (dd, 1H), 4.79 (m, 1 H), 1.96-1.08 (m, 8 H).

C25H24N3O4F32/5 TFA에 대한 원소분석치:Elemental Analysis for C 25 H 24 N 3 O 4 F 3 2/5 TFA:

계산치: C, 60.68; H, 5.06; N, 8.49.Calc .: C, 60.68; H, 5.06; N, 8.49.

실측치: C, 60.68; H, 5.33; N, 8.65.Found: C, 60.68; H, 5. 33; N, 8.65.

실시예 221Example 221

6-(아미노이미노메틸)-N-(3-페녹시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-phenoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 221AExample 221A

3-페녹시아닐린을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCl) m/z (M+H)+365.The product is prepared in the manner of Example 218A using 3-phenoxyaniline. MS (APCl) m / z (M + H) + 365.

실시예 221BExample 221B

6-(아미노이미노메틸)-N-(3-페녹시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-phenoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 221A로부터 상기 생성물을 제조한다.The product is prepared from Example 221A as described in Example 1B.

1H-NMR(300MHz, d6-DMSO) δ 10.61(s, 1H), 9.50(s, 2H), 9.20(s, 2H), 8.66(s, 1H), 8.54(s, 1H), 8.30(d, 1H), 8.22(d, 1H), 8.12(dd, 1H), 7.90(dd, 1H), 7.64-7.57(m, 2H), 7.46-7.37(m, 3H), 7.17(m, 1H), 7.06(m, 2H), 6.79(dd, 1H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.61 (s, 1H), 9.50 (s, 2H), 9.20 (s, 2H), 8.66 (s, 1H), 8.54 (s, 1H), 8.30 ( d, 1H), 8.22 (d, 1H), 8.12 (dd, 1H), 7.90 (dd, 1H), 7.64-7.57 (m, 2H), 7.46-7.37 (m, 3H), 7.17 (m, 1H) , 7.06 (m, 2 H), 6.79 (dd, 1 H).

MS(CI) m/z (M+H)+382;MS (CI) m / z (M + H) + 382;

C26H20N3O4F3에 대한 원소분석치:Elemental Analysis for C 26 H 20 N 3 O 4 F 3 :

계산치: C, 63.03; H, 4.07; N, 8.48.Calc .: C, 63.03; H, 4.07; N, 8.48.

실측치: C, 62.87; H, 4.24; N, 8.08.Found: C, 62.87; H, 4. 24; N, 8.08.

실시예 222Example 222

6-(아미노이미노메틸)-N-[3-(페닐메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (phenylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 222AExample 222A

3-벤질옥시아닐린을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+379.The product is prepared in the manner of Example 218A using 3-benzyloxyaniline. MS (APCI) m / z (M + H) + 379.

실시예 222BExample 222B

6-(아미노이미노메틸)-N-[3-(페닐메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (phenylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 222A로부터 상기 생성물을 제조한다.The product is prepared from Example 222A as described in Example 1B.

MS(CI) m/z (M+H)+396;MS (CI) m / z (M + H) + 396;

1H-NMR(300MHz, d6-DMSO) δ 10.53(s, 1H), 9.50(s, 2H), 9.22(s, 2H), 8.68(s, 1H), 8.55(s, 1H), 8.31(d, 1H), 8.23(d, 1H), 8.14(dd, 1H), 7.90(dd, 1H), 7.61-7.27(m, 8H), 6.80(dd, 1H), 5.13(s, 2H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.53 (s, 1H), 9.50 (s, 2H), 9.22 (s, 2H), 8.68 (s, 1H), 8.55 (s, 1H), 8.31 ( d, 1H), 8.23 (d, 1H), 8.14 (dd, 1H), 7.90 (dd, 1H), 7.61-7.27 (m, 8H), 6.80 (dd, 1H), 5.13 (s, 2H).

C27H22N3O4F3에 대한 원소분석치:Elemental Analysis for C 27 H 22 N 3 O 4 F 3 :

계산치: C, 63.65; H, 4.35; N, 8.25.Calc .: C, 63.65; H, 4. 35; N, 8.25.

실측치: C, 63.48; H, 4.27; N, 8.07.Found: C, 63.48; H, 4. 27; N, 8.07.

실시예 223Example 223

6-(아미노이미노메틸)-N-(3-에톡시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-ethoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 223AExample 223A

3-에톡시아닐린을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+317.The product is prepared in the manner of Example 218A using 3-ethoxyaniline. MS (APCI) m / z (M + H) + 317.

실시예 223BExample 223B

6-(아미노이미노메틸)-N-(3-에톡시페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (3-ethoxyphenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 223A로부터 상기 생성물을 제조한다.The product is prepared from Example 223A as described in Example 1B.

MS(CI) m/z (M+H)+334;MS (CI) m / z (M + H) + 334;

1H-NMR(300MHz, d6-DMSO) δ 10.52(s, 1H), 9.50(s, 2H), 9.24(s, 2H), 8.68(s, 1H), 8.55(s, 1H), 8.32(d, 1H), 8.25-8.13(m, 2H), 7.90(dd, 1H), 7.51(m, 1H), 7.38(m, 1H), 7.26(t, 1H), 6.72(dd, 1H), 4.04(q, 2H), 1.34(t, 3H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.52 (s, 1H), 9.50 (s, 2H), 9.24 (s, 2H), 8.68 (s, 1H), 8.55 (s, 1H), 8.32 ( d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.51 (m, 1H), 7.38 (m, 1H), 7.26 (t, 1H), 6.72 (dd, 1H), 4.04 (q, 2H), 1.34 (t, 3H).

C22H20N3O4F3에 대한 원소분석치:Elemental Analysis for C 22 H 20 N 3 O 4 F 3 :

계산치: C, 59.06; H, 4.51; N, 9.39.Calc .: C, 59.06; H, 4.51; N, 9.39.

실측치: C, 58.69; H, 4.54; N, 9.82.Found: C, 58.69; H, 4.54; N, 9.82.

실시예 224Example 224

6-(아미노이미노메틸)-N-(4-니트로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-nitrophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 224AExample 224A

4-니트로아닐린을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+318.The product is prepared in the manner of Example 218A using 4-nitroaniline. MS (APCI) m / z (M + H) + 318.

실시예 224BExample 224B

6-(아미노이미노메틸)-N-(4-니트로페닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- (4-nitrophenyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 224A로부터 상기 생성물을 제조한다.The product is prepared from Example 224A as described in Example 1B.

MS(CI) m/z (M+H)+335;MS (CI) m / z (M + H) + 335;

1H-NMR(300MHz, d6-DMSO) δ 11.15(s, 1H), 9.55(s, 2H), 9.22(s, 2H), 8.77(s, 1H), 8.58(s, 1H), 8.36-8.12(m, 6H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 11.15 (s, 1H), 9.55 (s, 2H), 9.22 (s, 2H), 8.77 (s, 1H), 8.58 (s, 1H), 8.36- 8.12 (m, 6 H).

C20H15N4O5F31/10 TFA에 대한 원소분석치:Elemental Analysis for C 20 H 15 N 4 O 5 F 3 1/10 TFA:

계산치: C, 52.54; H, 3.29; N, 12.10.Calc .: C, 52.54; H, 3. 29; N, 12.10.

실측치: C, 53.58; H, 3.37; N, 12.50.Found: C, 53.58; H, 3. 37; N, 12.50.

실시예 225Example 225

6-(아미노이미노메틸)-N-[3-(사이클로부틸메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (cyclobutylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 225AExample 225A

사이클로부틸메탄올을 사용하여 실시예 218A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z (M+H)+177.The product is prepared in the manner of Example 218A using cyclobutylmethanol. MS (APCI) m / z (M + H) + 177.

실시예 225BExample 225B

실시예 11의 생성물을 사용하여 실시예 225A의 방식으로 상기 생성물을 제조한다. MS(APCI) m/z(M+H)+357.This product is prepared in the manner of Example 225A using the product of Example 11. MS (APCI) m / z (M + H) + 357.

실시예 225CExample 225C

6-(아미노이미노메틸)-N-[3-(사이클로부틸메톡시)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -N- [3- (cyclobutylmethoxy) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 1B에 기재된 바와 같이 실시예 225B로부터 상기 생성물을 제조한다.The product is prepared from Example 225B as described in Example 1B.

MS(CI) m/z (M+H)+374;MS (CI) m / z (M + H) + 374;

1H-NMR(300MHz, d6-DMSO) δ 10.50(s, 1H), 9.50(s, 2H), 9.20(s, 2H), 8.68(s, 1H), 8.55(s, 1H), 8.32(d, 1H), 8.25-8.13(m, 2H), 7.90(dd, 1H), 7.51(m, 1H), 7.38(m, 1H), 7.26(t, 1H), 6.72(dd, 1H), 3.95(d, 2H), 2.11-1.81(m, 7H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.50 (s, 1H), 9.50 (s, 2H), 9.20 (s, 2H), 8.68 (s, 1H), 8.55 (s, 1H), 8.32 ( d, 1H), 8.25-8.13 (m, 2H), 7.90 (dd, 1H), 7.51 (m, 1H), 7.38 (m, 1H), 7.26 (t, 1H), 6.72 (dd, 1H), 3.95 (d, 2H), 2.11-1.81 (m, 7H).

C25H24N3O4F37/5 TFA에 대한 원소분석치:Elemental Analysis for C 25 H 24 N 3 O 4 F 3 7/5 TFA:

계산치: C, 59.09; H, 5.22; N 8.27.Calc .: C, 59.09; H, 5. 22; N 8.27.

실측치: C, 59.02; H, 5.20; N 8.55.Found: C, 59.02; H, 5.20; N 8.55.

실시예 226Example 226

6-[아미노(에톡시카보닐)이미노]-N-[3-(1-메틸에톡시)페닐]-2-나프탈렌카복스아미드6- [amino (ethoxycarbonyl) imino] -N- [3- (1-methylethoxy) phenyl] -2-naphthalenecarboxamide

실시예 216에 기재된 방법을 사용하여 실시예 211A로부터 상기 생성물을 수득한다.The product is obtained from Example 211A using the method described in Example 216.

MS(CI) m/z (M+H)+420;MS (CI) m / z (M + H) + 420;

1H-NMR(300MHz, d6-DMSO) δ 10.41(s, 1H), 9.24(br, 2H), 8.67(s, 1H), 8.59(s, 1H), 8.12-7.96(m, 4H), 7.47(s, 1H), 7.36(m, 1H), 7.25(t, 1H), 6.67(dd, 1H), 4.58(m, 1H), 4.11(q, 2H), 1.30(m, 9H). 1 H-NMR (300 MHz, d 6 -DMSO) δ 10.41 (s, 1H), 9.24 (br, 2H), 8.67 (s, 1H), 8.59 (s, 1H), 8.12-7.96 (m, 4H), 7.47 (s, 1H), 7.36 (m, 1H), 7.25 (t, 1H), 6.67 (dd, 1H), 4.58 (m, 1H), 4.11 (q, 2H), 1.30 (m, 9H).

C24H25N3O41/4 H2O에 대한 원소분석치:Elemental analysis for C 24 H 25 N 3 O 4 1/4 H 2 O:

계산치: C, 67.99; H, 6.06; N 9.91.Calc .: C, 67.99; H, 6.06; N 9.91.

실측치: C, 67.99; H, 6.07; N 9.64.Found: C, 67.99; H, 6.07; N 9.64.

실시예 227Example 227

6-(아미노이미노메틸)-4-[5-(에틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 227AExample 227A

CH2Cl2(25ml) 중의 실시예 200C의 생성물(670mg, 1.68mmol) 및 mCPBA(725mg, 3.36mmol)의 용액을 1시간 동안 교반한다. 이 반응물을 농축시키고 용출제로서 50% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 585mg(81%) 수득한다. MS(DCI/NH3) m/z 448(M+NH4)+.A solution of the product of Example 200C (670 mg, 1.68 mmol) and mCPBA (725 mg, 3.36 mmol) in CH 2 Cl 2 (25 ml) is stirred for 1 hour. The reaction was concentrated and chromatographed on SiO 2 using 50% ethyl acetate / hexane as eluent to give 585 mg (81%) of the title compound. MS (DCI / NH 3 ) m / z 448 (M + NH 4 ) + .

실시예 227BExample 227B

6-(아미노이미노메틸)-4-[5-(에틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 13의 과정을 사용하여 실시예 227A로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 227A using the procedure of Example 13.

MS(DCI/NH3) m/z 448(M+H)+;MS (DCI / NH 3 ) m / z 448 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 1.29(t, 1H), 3.50(q, 2H), 7.16(t, 1H), 7.42(t, 2H), 7.83(d, 2H), 7.95(dd, 1H), 8.05(s, 1H), 8.28(s, 1H), 8.43(d, 1H), 8.57(s, 1H), 8.74(s, 1H), 8.79(s, 1H), 9.19(br s, 2H), 9.59(br s, 2H), 10.61(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.29 (t, 1H), 3.50 (q, 2H), 7.16 (t, 1H), 7.42 (t, 2H), 7.83 (d, 2H), 7.95 ( dd, 1H), 8.05 (s, 1H), 8.28 (s, 1H), 8.43 (d, 1H), 8.57 (s, 1H), 8.74 (s, 1H), 8.79 (s, 1H), 9.19 (br s, 2H), 9.59 (br s, 2H), 10.61 (s, 1H).

C24H22N3SO4·1.0 HCl·1.0 H2O에 대한 원소분석치:Elemental Analysis for C 24 H 22 N 3 SO 4 · 1.0 HCl · 1.0 H 2 O:

계산치: C, 57.43; H, 4.82; N 8.37.Calc .: C, 57.43; H, 4. 82; N 8.37.

실측치: C, 57.21; H, 5.04; N 8.34.Found: C, 57.21; H, 5.04; N 8.34.

실시예 228Example 228

6-(아미노이미노메틸)-4-[5-(프로필설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (propylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 228AExample 228A

실시예 227A의 과정에 의해 실시예 201C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 462(M+NH4)+.The desired compound is prepared from the product of Example 201C by the procedure of Example 227A. MS (DCI / NH 3 ) m / z 462 (M + NH 4 ) + .

실시예 228BExample 228B

6-(아미노이미노메틸)-4-[5-(프로필설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (propylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 13의 과정을 사용하여 실시예 228A로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 228A using the procedure of Example 13.

MS(DCI/NH3) m/z 462(M+H)+;MS (DCI / NH 3 ) m / z 462 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 1.03(t, 3H), 1.75(qt, 2H), 3.48(s, 2H), 7.16(t, 1H), 7.41(t, 2H), 7.84(d, 2H), 7.95(dd, 1H), 8.05(s, 1H), 8.28(d, 1H), 8.42(d, 1H), 8.58(s, 1H), 8.77(s, 1H), 8.82(s, 1H), 9.28(br s, 2H), 9.63(br s, 2H), 10.66(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.03 (t, 3H), 1.75 (qt, 2H), 3.48 (s, 2H), 7.16 (t, 1H), 7.41 (t, 2H), 7.84 ( d, 2H), 7.95 (dd, 1H), 8.05 (s, 1H), 8.28 (d, 1H), 8.42 (d, 1H), 8.58 (s, 1H), 8.77 (s, 1H), 8.82 (s , 1H), 9.28 (br s, 2H), 9.63 (br s, 2H), 10.66 (s, 1H).

C25H24N3SO4·1.0 HCl·1.5H2O에 대한 원소분석치:Elemental analysis for C 25 H 24 N 3 SO 4 .1.0 HCl .1.5H 2 O:

계산치: C, 57.20; H, 5.18; N, 8.00.Calc .: C, 57.20; H, 5. 18; N, 8.00.

실측치: C, 56.86; H, 5.08; N, 8.28.Found: C, 56.86; H, 5.08; N, 8.28.

실시예 229Example 229

6-(아미노이미노메틸)-4-[5-[(메틸티오)메틸]-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5-[(methylthio) methyl] -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 229AExample 229A

-78℃에서 THF(100ml) 중의 2-트리메틸실릴-3-브로모푸란(10.41g, 47.5mmol)의 용액에 LDA(34.8ml, 52.25mmol)의 1M 용액을 가하고, 반응물을 -78℃에서 1시간 동안 교반한다. 이어서, DMF(4.41ml, 57.0mmol)를 가하고, 반응물을 실온으로 가온시킨 다음 1시간 동안 교반한다. 반응물을 포화 수성 NH4Cl 용액에 붓고, 3x 디에틸 에테르로 추출한다. 합한 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 물질을 메탄올(200ml)에 용해시키고 NaBH4(1.15g, 24.0mmol)을 여러 분획으로 나누어 상기 교반된 용액에 가한다. 30분 후, 이 용액을 농축시키고, pH 7 완충액에 용해시키며, 3 x 에틸 아세테이트로 추출한다. 합한 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 생성물을 용출제로서 30% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 5.52g(47%) 수득한다. MS(DCI/NH3) m/z 250(M+H)+.To a solution of 2-trimethylsilyl-3-bromofuran (10.41 g, 47.5 mmol) in THF (100 ml) at −78 ° C. was added 1M solution of LDA (34.8 ml, 52.25 mmol) and the reaction was reacted at 1 at −78 ° C. Stir for hours. DMF (4.41 ml, 57.0 mmol) is then added and the reaction is allowed to warm to room temperature and stirred for 1 hour. The reaction is poured into saturated aqueous NH 4 Cl solution and extracted with 3 × diethyl ether. The combined extracts are washed with brine, dried over Na 2 S0 4 and concentrated. The crude material is dissolved in methanol (200 ml) and NaBH 4 (1.15 g, 24.0 mmol) is added in portions to the stirred solution. After 30 minutes, this solution is concentrated, dissolved in pH 7 buffer and extracted with 3 x ethyl acetate. The combined extracts are washed with brine, dried over Na 2 S0 4 and concentrated. The crude product is chromatographed on SiO 2 with 30% ethyl acetate / hexane as eluent to give 5.52 g (47%) of the title compound. MS (DCI / NH 3 ) m / z 250 (M + H) + .

실시예 229BExample 229B

0℃에서 DMF(60ml) 중의 실시예 229A의 생성물(5.52g, 22.15mmol) 및 LiCl(1.03g, 24.36mmol)의 용액에 PCl3(2.12ml, 24.36mmol)을 가하고 반응물을 실온에서 1시간 동안 교반한다. 반응물을 포화 수성 NH4Cl 용액에 붓고 3x 디에틸 에테르/헥산으로 추출한다. 합한 추출물을 2x 물, 2x 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시켜 목적 화합물을 4.70g(79%) 수득한다.To a solution of the product of Example 229A (5.52 g, 22.15 mmol) and LiCl (1.03 g, 24.36 mmol) in DMF (60 ml) at 0 ° C. was added PCl 3 (2.12 ml, 24.36 mmol) and the reaction was allowed to stir at room temperature for 1 hour. Stir. The reaction is poured into saturated aqueous NH 4 Cl solution and extracted with 3 × diethyl ether / hexanes. The combined extracts are washed with 2x water, 2x brine, dried over Na 2 S0 4 and concentrated to give 4.70 g (79%) of the title compound.

실시예 229CExample 229C

DMF(40ml) 중의 실시예 229B의 생성물(4.70g, 17.56mmol) 및 MeSNa(1.35g, 19.3mmol)의 용액을 실온에서 3시간 동안 교반한다. 반응물을 포화 수성 NaHCO3용액에 붓고, 3 x 디에틸 에테르로 추출한다. 합한 추출물을 염수로 세척하고, Na2SO4로 건조시킨 다음 농축시킨다. 조 생성물을 용출제로서 30% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 4.00g(82%) 수득한다.A solution of the product of Example 229B (4.70 g, 17.56 mmol) and MeSNa (1.35 g, 19.3 mmol) in DMF (40 ml) is stirred at room temperature for 3 hours. The reaction is poured into saturated aqueous NaHCO 3 solution and extracted with 3 × diethyl ether. The combined extracts are washed with brine, dried over Na 2 S0 4 and concentrated. The crude product is chromatographed on SiO 2 using 30% ethyl acetate / hexane as eluent to afford 4.00 g (82%) of the title compound.

실시예 229DExample 229D

실시예 154B의 과정에 의해 실시예 D의 생성물 및 실시예 229C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 308(Bu3Sn+NH4)+.The desired compound is prepared from the product of Example D and the product of Example 229C by the procedure of Example 154B. MS (DCI / NH 3 ) m / z 308 (Bu 3 Sn + NH 4 ) + .

실시예 229EExample 229E

실시예 154C의 과정에 의해 실시예 D의 생성물 및 실시예 152C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 416(M+NH4)+.The desired compound is prepared from the product of Example D and the product of Example 152C by the procedure of Example 154C. MS (DCI / NH 3 ) m / z 416 (M + NH 4 ) + .

실시예 229FExample 229F

6-(아미노이미노메틸)-4-[5-(메틸티오)메틸]-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (methylthio) methyl] -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정을 사용하여 실시예 229E로부터 목적 화합물을 제조한다.Prepare the desired compound from Example 229E using the procedure of Example 144C.

MS(DCI/NH3) m/z 416(M+H)+;MS (DCI / NH 3 ) m / z 416 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 2.15(s, 3H), 3.87(s, 2H), 7.14(t, 1H), 7.40(t, 2H), 7.84(d, 2H), 7.92(dd, 1H), 8.19(d, 1H), 8.32(s, 1H), 8.39(d, 1H), 8.64(s, 1H), 8.69(s, 1H), 9.31(br s, 2H), 9.61(br s, 2H), 10.62(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 2.15 (s, 3H), 3.87 (s, 2H), 7.14 (t, 1H), 7.40 (t, 2H), 7.84 (d, 2H), 7.92 ( dd, 1H), 8.19 (d, 1H), 8.32 (s, 1H), 8.39 (d, 1H), 8.64 (s, 1H), 8.69 (s, 1H), 9.31 (br s, 2H), 9.61 ( br s, 2H), 10.62 (s, 1H).

C24H21N3SO4·1.4HCl에 대한 원소분석치:Elemental Analysis for C 24 H 21 N 3 SO 4 · 1.4HCl:

계산치: C, 61.79; H, 4.84; N, 9.01.Calc .: C, 61.79; H, 4. 84; N, 9.01.

실측치: C, 61.83; H, 4.82; N, 9.13.Found: C, 61.83; H, 4. 82; N, 9.13.

실시예 230Example 230

6-(아미노이미노메틸)-4-[5-(메톡시메틸)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (methoxymethyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 230AExample 230A

실시예 154A의 과정에 의해 2-트리메틸실릴-3-브로모푸란 및 클로로메틸 메틸 에테르로부터 목적 화합물을 제조한다.The desired compound is prepared from 2-trimethylsilyl-3-bromofuran and chloromethyl methyl ether by the procedure of Example 154A.

실시예 230BExample 230B

실시예 154B의 과정에 의해 실시예 230A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 308(Bu3Sn+NH4)+.The desired compound is prepared from the product of Example 230A by the procedure of Example 154B. MS (DCI / NH 3 ) m / z 308 (Bu 3 Sn + NH 4 ) + .

실시예 230CExample 230C

실시예 154C의 과정에 의해 실시예 230B의 생성물 및 실시예 152C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 400(M+NH4)+.The desired compound is prepared from the product of Example 230B and the product of Example 152C by the procedure of Example 154C. MS (DCI / NH 3 ) m / z 400 (M + NH 4 ) + .

실시예 230DExample 230D

6-(아미노이미노메틸)-4-[5-(메톡시메틸)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (methoxymethyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정을 사용하여 실시예 230C로부터 목적 화합물을 제조한다.Prepare the desired compound from Example 230C using the procedure of Example 144C.

MS(DCI/NH3) m/z 400(M+H)+;MS (DCI / NH 3 ) m / z 400 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 3.38(s, 3H), 4.49(s, 2H), 7.14(t, 1H), 7.18(t, 1H), 7.40(t, 2H), 7.84(d, 2H), 7.92(dd, 1H), 8.19(d, 1H), 8.38(s, 1H), 8.42(d, 1H), 8.64(s, 1H), 8.70(s, 1H), 9.32(br s, 2H), 9.62(br s, 2H), 10.68(s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 3.38 (s, 3H), 4.49 (s, 2H), 7.14 (t, 1H), 7.18 (t, 1H), 7.40 (t, 2H), 7.84 ( d, 2H), 7.92 (dd, 1H), 8.19 (d, 1H), 8.38 (s, 1H), 8.42 (d, 1H), 8.64 (s, 1H), 8.70 (s, 1H), 9.32 (br) s, 2H), 9.62 (br s, 2H), 10.68 (s, 1H).

C24H21N3O3·2.8HCl에 대한 원소분석치:Elemental Analysis for C 24 H 21 N 3 O 3 · 2.8HCl:

계산치: C, 57.48; H, 4.78; N, 8.38.Calc .: C, 57.48; H, 4.78; N, 8.38.

실측치: C, 57.40; H, 4.44; N, 8.38.Found: C, 57.40; H, 4. 44; N, 8.38.

실시예 231Example 231

6-(아미노이미노메틸)-4-[5-(메틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -4- [5- (methylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 231AExample 231A

실시예 227A의 과정에 의해 실시예 152C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 434(M+NH4)+.The desired compound is prepared from the product of Example 152C by the procedure of Example 227A. MS (DCI / NH 3 ) m / z 434 (M + NH 4 ) + .

실시예 231BExample 231B

6-(아미노이미노메틸)-4-[5-(메틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염6- (aminoiminomethyl) -4- [5- (methylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, mono (trifluoroacetate) salt

실시예 13의 과정을 사용하여 실시예 231A로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 231A using the procedure of Example 13.

MS(DCI/NH3) m/z 434(M+H)+;MS (DCI / NH 3 ) m / z 434 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 3.44(s, 3H), 7.16(t, 1H), 7.40(t, 2H), 7.82(d, 2H), 7.91(s, 1H), 7.95(dd, 1H), 8.00(s, 1H), 8.36(s, 1H), 8.43(d, 1H), 8.57(s, 1H), 8.75(s, 2H), 9.18(br s, 2H), 9.53(br s, 2H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 3.44 (s, 3H), 7.16 (t, 1H), 7.40 (t, 2H), 7.82 (d, 2H), 7.91 (s, 1H), 7.95 ( dd, 1H), 8.00 (s, 1H), 8.36 (s, 1H), 8.43 (d, 1H), 8.57 (s, 1H), 8.75 (s, 2H), 9.18 (br s, 2H), 9.53 ( br s, 2H).

C23H19N3SO4·1.0C2HF3O2에 대한 원소분석치:Elemental analysis for C 23 H 19 N 3 SO 4 · 1.0C 2 HF 3 O 2 :

계산치: C, 54.84; H, 3.68; N, 7.67.Calc .: C, 54.84; H, 3.68; N, 7.67.

실측치: C, 55.05; H, 3.74; N, 7.75.Found: C, 55.05; H, 3. 74; N, 7.75.

실시예 232Example 232

6-(아미노이미노메틸)-4-[5-(에틸티오)테트라하이드로-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylthio) tetrahydro-3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 232AExample 232A

실시예 62A의 과정에 의해 실시예 152A의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 315(M+NH4)+.The desired compound is prepared from the product of Example 152A by the procedure of Example 62A. MS (DCI / NH 3 ) m / z 315 (M + NH 4 ) + .

실시예 232BExample 232B

CHCl3(22ml) 중의 실시예 232A의 생성물(1.62g, 5.45mmol), 에탄티올(2.2ml) 및 진한 HCl(0.80ml)의 용액을 실온에서 3시간 동안 교반한 다음 농축시킨다. 조 생성물을 용출제로서 15% 에틸 아세테이트/헥산을 사용하여 SiO2상에서 크로마토그래피하여 목적 화합물을 1.20g(65%) 수득한다. MS(DCI/NH3) m/z 359(M+NH4)+.A solution of the product of Example 232A (1.62 g, 5.45 mmol), ethanethiol (2.2 ml) and concentrated HCl (0.80 ml) in CHCl 3 (22 ml) was stirred at room temperature for 3 hours and then concentrated. The crude product is chromatographed on SiO 2 using 15% ethyl acetate / hexane as eluent to yield 1.20 g (65%) of the title compound. MS (DCI / NH 3 ) m / z 359 (M + NH 4 ) + .

실시예 232CExample 232C

실시예 152B의 과정에 의해 실시예 232B의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 345(M+NH4)+.The desired compound is prepared from the product of Example 232B by the procedure of Example 152B. MS (DCI / NH 3 ) m / z 345 (M + NH 4 ) + .

실시예 232DExample 232D

실시예 207C의 과정에 의해 실시예 232C의 생성물로부터 목적 화합물을 제조한다. MS(DCI/NH3) m/z 420(M+NH4)+.The desired compound is prepared from the product of Example 232C by the procedure of Example 207C. MS (DCI / NH 3 ) m / z 420 (M + NH 4 ) + .

실시예 232EExample 232E

6-(아미노이미노메틸)-4-[5-(에틸티오)테트라하이드로-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드6- (aminoiminomethyl) -4- [5- (ethylthio) tetrahydro-3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride

실시예 144C의 과정을 사용하여 실시예 232D로부터 목적 화합물을 제조한다.The desired compound is prepared from Example 232D using the procedure of Example 144C.

MS(DCI/NH3) m/z 420(M+H)+;MS (DCI / NH 3 ) m / z 420 (M + H) + ;

1H-NMR(300MHz, DMSO-d6) δ 1.18(dt, 3H), 2.42(m, 1H), 3.50(dq, 2H), 3.74(m, 1H), 3.93(m, 1H), 4.39(m, 1H), 4.54(m, 1H), 5.38(dd, 0.5H), 5.42(dd, 0.5H), 7.14(t, 1H), 7.40(t, 2H), 7.82(d, 2H), 7.95(d, 1H), 8.06(s, 0.5H), 8.20(s, 0.5H), 8.32(d, 1H), 8.60(s, 1H), 8.71(s, 0.5H), 8.80(s, 0.5H), 9.32(br s, 2H), 9.62(br s, 2H), 10.59(br s, 1H). 1 H-NMR (300 MHz, DMSO-d 6 ) δ 1.18 (dt, 3H), 2.42 (m, 1H), 3.50 (dq, 2H), 3.74 (m, 1H), 3.93 (m, 1H), 4.39 ( m, 1H), 4.54 (m, 1H), 5.38 (dd, 0.5H), 5.42 (dd, 0.5H), 7.14 (t, 1H), 7.40 (t, 2H), 7.82 (d, 2H), 7.95 (d, 1H), 8.06 (s, 0.5H), 8.20 (s, 0.5H), 8.32 (d, 1H), 8.60 (s, 1H), 8.71 (s, 0.5H), 8.80 (s, 0.5H ), 9.32 (br s, 2H), 9.62 (br s, 2H), 10.59 (br s, 1H).

C24H25N3O2S·1.0HCl에 대한 원소분석치:Elemental Analysis for C 24 H 25 N 3 O 2 S · 1.0HCl:

계산치: C, 63.22; H, 5.75; N, 9.21.Calc .: C, 63.22; H, 5.75; N, 9.21.

실측치: C, 62.93; H, 5.58; N, 9.01.Found: C, 62.93; H, 5.58; N, 9.01.

Claims (16)

화학식 Ⅰ의 화합물.Compound of Formula (I). 화학식 ⅠFormula I 상기식에서,In the above formula, Z는 (1) 질소;Z is (1) nitrogen; (2) 메틴; 및(2) methine; And (3) -NR1R2로 치환된 메틴으로 이루어진 그룹 중에서 선택되고;(3) selected from the group consisting of methine substituted with -NR 1 R 2 ; A는 (1) 수소 및A is (1) hydrogen and (2) -LARA로 이루어진 그룹 중에서 선택되며;(2) -L A R A is selected from the group consisting of; B는 (1) 수소 및B is (1) hydrogen and (2) -LBRB로 이루어진 그룹 중에서 선택되고;(2) -L B R B is selected from the group consisting of; C는 (1) 수소 및C is (1) hydrogen and (2) -LCRC로 이루어진 그룹 중에서 선택되며,(2) -L C R C is selected from the group consisting of 단 A, B 및 C 중의 하나 이상은 수소가 아니며, A가 수소가 아닌 경우에는, B 및 C 중의 하나 이상이 수소가 아니고;Provided that at least one of A, B and C is not hydrogen, and when A is not hydrogen, at least one of B and C is not hydrogen; A, B 및 C에 대한 LA, LB및 LC는L A , L B and L C for A, B and C (1) 공유 결합,(1) covalent bonds, (2) -(CH2)m-,(2)-(CH 2 ) m- , (3) -NR1-,(3) -NR 1- , (4) -NR2C(X)NR3-,(4) -NR 2 C (X) NR 3- , (5) -C(X)-,(5) -C (X)-, (6) -NR2C(X)-,(6) -NR 2 C (X)-, (7) -C(X)NR2-,(7) -C (X) NR 2- , (8) -CH=CH-,(8) -CH = CH-, (9) -C≡C-,(9) -C≡C-, (10) -O-,(10) -O-, (11) -S(O)t-(11) -S (O) t- (12) -C≡C(CH2)nNR2C(X)-,(12) -C≡C (CH 2 ) n NR 2 C (X)-, (13) -C(X)NR2(CH2)nC≡C-,(13) -C (X) NR 2 (CH 2 ) n C≡C-, (14) -(CH2)nNSO2-,(14)-(CH 2 ) n NSO 2- , (15) -NR2SO2(CH2)nC≡C-,(15) -NR 2 SO 2 (CH 2 ) n C≡C-, (16) -C≡C(CH2)nNR2SO2NR3-,(16) -C≡C (CH 2 ) n NR 2 SO 2 NR 3- , (17) -NR2SO2NR3(CH2)nC≡C-,(17) -NR 2 SO 2 NR 3 (CH 2 ) n C≡C-, (18) -SO2NR2-,(18) -SO 2 NR 2- , (19) -NR2SO2-,(19) -NR 2 SO 2- , (20) -NR2SO2NR3-,(20) -NR 2 SO 2 NR 3- , (21) -N=N-,(21) -N = N-, (22) -C(X)N(OR2)-,(22) -C (X) N (OR 2 )-, (23) -N(OR2)C(X)-,(23) -N (OR 2 ) C (X)-, (24) -HC=CH(CH2)nNR2C(X)-,(24) -HC = CH (CH 2 ) n NR 2 C (X)-, (25) -(CH2)nNR2C(X)CH=CH-,(25)-(CH 2 ) n NR 2 C (X) CH = CH-, (26) -CH=CH(CH2)nNSO2-,(26) -CH = CH (CH 2 ) n NSO 2- , (27) -NR2SO2(CH2)nCH=CH-,(27) -NR 2 SO 2 (CH 2 ) n CH = CH-, (28) -(CH2)nNR2SO2NR3-,(28)-(CH 2 ) n NR 2 SO 2 NR 3- , (29) -NR2SO2NR3(CH2)nCH=CH-,(29) -NR 2 SO 2 NR 3 (CH 2 ) n CH = CH-, (30) -NR2C(O)O-,(30) -NR 2 C (O) O-, (31) -OC(O)NR2-,(31) -OC (O) NR 2- , (32) -CH=NO-,(32) -CH = NO-, (33) -ON=CH- 및(33) -ON = CH- and (34)[여기서, W는 (a) -O-, (b) -S-, (c) -NR1- 및 (d) -(CH2)m- 으로 이루어진 그룹 중에서 선택된다]으로 이루어진 그룹 중에서 독립적으로 선택되며;(34) Are independently selected from the group consisting of (a) -O-, (b) -S-, (c) -NR 1 -and (d)-(CH 2 ) m- . Selected; 여기서, 각각의 작용성 그룹은 나프틸 또는 퀴놀릴 환에 결합된 말단인 오른쪽 말단과 RA, RB또는 RC에 결합된 말단인 왼쪽 말단으로 나타내며;Wherein each functional group is represented by a right end which is the end bonded to a naphthyl or quinolyl ring and a left end which is the end bonded to R A , R B or R C ; RA, RB및 RC는R A , R B and R C are (1) 아릴;(1) aryl; (2) 아릴알콕시(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(2) arylalkoxy, wherein the alkylene group is a group of 1 to 6 carbon atoms; (3) 탄소수 1 내지 10의 알킬;(3) alkyl having 1 to 10 carbon atoms; (4) 탄소수 2 내지 10의 알케닐;(4) alkenyl having 2 to 10 carbon atoms; (5) 탄소수 1 내지 6의 알콕시카보닐;(5) alkoxycarbonyl having 1 to 6 carbon atoms; (6) 탄소수 2 내지 10의 알키닐;(6) alkynyl having 2 to 10 carbon atoms; (7) 할로겐;(7) halogen; (8) -NR1R2;(8) -NR 1 R 2 ; (9) 헤테로사이클;(9) heterocycles; (10) 탄소수 4 내지 12의 사이클로알케닐;(10) cycloalkenyl having 4 to 12 carbon atoms; (11) 탄소수 3 내지 12의 사이클로알킬;(11) cycloalkyl having 3 to 12 carbon atoms; (12) -NR1C(O)NR2R3; 및(12) -NR 1 C (O) NR 2 R 3 ; And (13) -NR1C(O)R50(여기서, R50은 탄소수 1 내지 6의 알킬이다)로 이루어진 그룹 중에서 독립적으로 선택되며;(13) -NR 1 C (O) R 50 wherein R 50 is alkyl having 1 to 6 carbon atoms; 각 경우에, R1은In each case, R 1 is (1) 수소;(1) hydrogen; (2) N-보호 그룹;(2) N-protecting groups; (3) 탄소수 1 내지 6의 알킬;(3) alkyl of 1 to 6 carbon atoms; (4) 탄소수 2 내지 6의 알케닐;(4) alkenyl having 2 to 6 carbon atoms; (5) 탄소수 2 내지 6의 알키닐;(5) alkynyl having 2 to 6 carbon atoms; (6) 아릴;(6) aryl; (7) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(7) arylalkyl, wherein the alkylene group is a group having 1 to 6 carbon atoms; (8) 탄소수 3 내지 8의 사이클로알킬; 및(8) cycloalkyl having 3 to 8 carbon atoms; And (9) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)로 이루어진 그룹 중에서 선택되고;(9) cycloalkylalkyl, wherein the cycloalkyl group is a group of 3 to 8 carbon atoms and the alkylene group is a group of 1 to 10 carbon atoms; 각 경우에, R2및 R3은In each case, R 2 and R 3 are (1) 수소;(1) hydrogen; (2) 탄소수 1 내지 6의 알킬;(2) alkyl having 1 to 6 carbon atoms; (3) 탄소수 2 내지 6의 알케닐;(3) alkenyl having 2 to 6 carbon atoms; (4) 탄소수 2 내지 6의 알키닐;(4) alkynyl having 2 to 6 carbon atoms; (5) 아릴;(5) aryl; (6) 아릴알킬(여기서, 알킬렌 그룹은 탄소수 1 내지 6의 그룹이다);(6) arylalkyl, wherein the alkylene group is a group of 1 to 6 carbon atoms; (7) 탄소수 3 내지 8의 사이클로알킬; 및(7) cycloalkyl having 3 to 8 carbon atoms; And (8) 사이클로알킬알킬(여기서, 사이클로알킬 그룹은 탄소수 3 내지 8의 그룹이고 알킬렌 그룹은 탄소수 1 내지 10의 그룹이다)로 이루어진 그룹 중에서 독립적으로 선택되며;(8) independently selected from the group consisting of cycloalkylalkyl, wherein the cycloalkyl group is a group having 3 to 8 carbon atoms and the alkylene group is a group having 1 to 10 carbon atoms; 각 경우에, X는In each case, X is (1) O 및(1) O and (2) S로 이루어진 그룹 중에서 선택되고;(2) is selected from the group consisting of S; 각 경우에, m은 1 내지 5이고;In each case m is 1 to 5; n은 0 내지 4이며;n is 0 to 4; t는 0 내지 2이고;t is 0 to 2; 각 경우에, 알킬, 알케닐, 알키닐, 아릴, 헤테로사이클, 사이클로알킬 및 사이클로알케닐 그룹은 임의로 치환된다.In each case, the alkyl, alkenyl, alkynyl, aryl, heterocycle, cycloalkyl and cycloalkenyl groups are optionally substituted. 제1항에 있어서, A 및 C가 수소이고 B가 -LBRB인 화합물.The compound of claim 1, wherein A and C are hydrogen and B is —L B R B. 제2항에 있어서,The method of claim 2, 7-(2-하이드록시에톡시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 5-[7-[(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노에이트 모노(트리플루오로아세테이트) 염;Methyl 5- [7-[(aminoiminomethyl) -2-naphthalenyl] oxy] pentanoate mono (trifluoroacetate) salt; 5-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]펜타노산, 모노(트리플루오로아세테이트) 염;5-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] pentanoic acid, mono (trifluoroacetate) salt; 메틸 [4-[[[7-아미노(하이드록시이미노)메틸]-2-나프탈레닐]옥시]메틸]벤조에이트;Methyl [4-[[[7-amino (hydroxyimino) methyl] -2-naphthalenyl] oxy] methyl] benzoate; 메틸 2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세테이트, 모노(트리플루오로아세테이트) 염;Methyl 2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetate, mono (trifluoroacetate) salt; 7-[2-(4-모르폴리닐)에톡시]-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7- [2- (4-morpholinyl) ethoxy] -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt; 2-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]아세트산, 모노(트리플루오로아세테이트) 염; 및2-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] acetic acid, mono (trifluoroacetate) salt; And 메틸 [4-[[6-(아미노이미노메틸)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염으로 이루어진 그룹으로부터 선택된 화합물.Methyl [4-[[6- (aminoiminomethyl) -2-naphthalenyl] oxy] methyl] benzoate, a compound selected from the group consisting of mono (trifluoroacetate) salts. 제1항에 있어서, A 및 B가 수소이고 C가 -LCRC인 화합물.The compound of claim 1, wherein A and B are hydrogen and C is -L C R C. 제4항에 있어서,The method of claim 4, wherein 8-(카보닐벤질옥시)아미노-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;8- (carbonylbenzyloxy) amino-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐)아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl) acetamide mono (trifluoroacetate) salt; 메틸 [7-(아미노이미노메틸)-1-나프탈레닐)카바메이트 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -1-naphthalenyl) carbamate mono (trifluoroacetate) salt; 메틸 3-[[7-(아미노이미노메틸)-1-나프탈레닐]아미노]-3-옥소프로피오네이트 모노(트리플루오로아세테이트) 염;Methyl 3-[[7- (aminoiminomethyl) -1-naphthalenyl] amino] -3-oxopropionate mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-(페닐메톡시)아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2- (phenylmethoxy) acetamide mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-1,3-벤조디옥솔-5-카복스아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -1,3-benzodioxol-5-carboxamide mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]벤젠메탄설폰아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] benzenemethanesulfonamide mono (trifluoroacetate) salt; 메틸 [7-(아미노이미노메틸)-1-나프탈레닐]메틸카바메이트, 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -1-naphthalenyl] methylcarbamate, mono (trifluoroacetate) salt; 프로필 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염;Propyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-N'-메틸우레아, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -N'-methylurea, mono (trifluoroacetate) salt; 에틸 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트, 모노(트리플루오로아세테이트) 염;Ethyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate, mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]프로판아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] propanamide, mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-메톡시아세트아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-methoxyacetamide, mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]우레아, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] urea, mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-하이드록시아세트아미드, 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2-hydroxyacetamide, mono (trifluoroacetate) salt; 8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt; 8-아미노-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;8-amino-2-naphthalenecarboximideamide, bis (trifluoroacetate) salt; 8-(2-피리디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염; 및8- (2-pyridinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt; And N-하이드록시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염으로 이루어진 그룹으로부터 선택된 화합물.N-hydroxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, a compound selected from the group consisting of mono (trifluoroacetate) salts. 제1항에 있어서, A가 -LARA이고 B가 -LBRB이며 C가 수소인 화합물.The compound of claim 1, wherein A is -L A R A , B is -L B R B and C is hydrogen. 제6항에 있어서, 6,7-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염인 화합물.The compound according to claim 6, which is a 6,7-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt. 제1항에 있어서, A가 -LARA이고 B가 수소이며 C가 -LCRC인 화합물.The compound of claim 1, wherein A is -L A R A , B is hydrogen and C is -L C R C. 제8항에 있어서,The method of claim 8, 메틸 6-(아미노이미노메틸)-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실레이트 모노(트리플루오로아세테이트) 염;Methyl 6- (aminoiminomethyl) -4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylate mono (trifluoroacetate) salt; 6-메톡시-8-벤질옥시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-methoxy-8-benzyloxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-3-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-3-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-[4-(트리플루오로메틸)페닐]-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -4- (3-furanyl) -N- [4- (trifluoromethyl) phenyl] -2-naphthalenecarboxamide, mono (trifluoroacetate) salt; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-(4-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (4-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-(1H-피라졸-3-일)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (1H-pyrazol-3-yl) -2-naphthalenecarboxamide, dihydrochloride; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-(3-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (3-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride; 메틸 [7-(아미노이미노메틸)-3-[[[4-(아미노메틸)페닐]아미노]카보닐]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -1-naphthalenyl] carbamate, bis (trifluoroacetate) salt; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-(2-피리디닐)-2-나프탈렌카복스아미드, 디하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N- (2-pyridinyl) -2-naphthalenecarboxamide, dihydrochloride; 6-(아미노이미노메틸)-4-(3-푸라닐)-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- (3-furanyl) -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[1-(메틸설포닐)-1H-피라졸-4-일]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [1- (methylsulfonyl) -1H-pyrazol-4-yl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[5-(메틸티오)-3-푸라닐)]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (methylthio) -3-furanyl)]-N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-N-[4-(아미노메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 트리스(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [4- (aminomethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, tris (trifluoroacetate) salt; 6-(아미노이미노메틸)-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt; N-[4-(아미노메틸)페닐]-6-[아미노(하이드록시이미노)메틸]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 비스(트리플루오로아세테이트) 염;N- [4- (aminomethyl) phenyl] -6- [amino (hydroxyimino) methyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, bis (trifluoroacetate) salt ; 6-(아미노이미노메틸)-N-[4-(하이드록시메틸)페닐]-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N- [4- (hydroxymethyl) phenyl] -4- (2-pyrimidinylamino) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt; 메틸 [3-[[[4-(아미노메틸)페닐]아미노]카보닐]-7-[[4-아미노(하이드록시이미노)메틸]-1-나프탈레닐]카바메이트, 비스(트리플루오로아세테이트) 염;Methyl [3-[[[4- (aminomethyl) phenyl] amino] carbonyl] -7-[[4-amino (hydroxyimino) methyl] -1-naphthalenyl] carbamate, bis (trifluoro Acetate) salts; 6-(아미노이미노메틸)-N-페닐-4-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -N-phenyl-4- (tetrahydro-3-furanyl) -2-naphthalenecarboxamide, monohydrochloride; 6-[아미노(하이드록시이미노)메틸]-N-페닐-4-(2-피리미디닐아미노)-2-나프탈렌카복스아미드;6- [amino (hydroxyimino) methyl] -N-phenyl-4- (2-pyrimidinylamino) -2-naphthalenecarboxamide; 6-(아미노이미노메틸)-4-[5-(에틸티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (ethylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[5-(프로필티오)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (propylthio) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-N-페닐-4-(2-피롤리디닐)-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염;6- (aminoiminomethyl) -N-phenyl-4- (2-pyrrolidinyl) -2-naphthalenecarboxamide, mono (trifluoroacetate) salt; 6-(아미노이미노메틸)-4-[5-(프로필설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (propylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[[5-(메틸티오)메틸]-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4-[[5- (methylthio) methyl] -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[5-(메톡시메틸)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드;6- (aminoiminomethyl) -4- [5- (methoxymethyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, monohydrochloride; 6-(아미노이미노메틸)-4-[5-(메틸설포닐)-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노(트리플루오로아세테이트) 염; 및6- (aminoiminomethyl) -4- [5- (methylsulfonyl) -3-furanyl] -N-phenyl-2-naphthalenecarboxamide, mono (trifluoroacetate) salt; And 6-(아미노이미노메틸)-4-[5-(에틸티오)테트라하이드로-3-푸라닐]-N-페닐-2-나프탈렌카복스아미드, 모노하이드로클로라이드로 이루어진 그룹으로부터 선택된 화합물.6- (aminoiminomethyl) -4- [5- (ethylthio) tetrahydro-3-furanyl] -N-phenyl-2-naphthalenecarboxamide, a compound selected from the group consisting of monohydrochloride. 제1항에 있어서, A가 -LARA이고 B가 -LBRB이며 C가 -LCRC인 화합물.The compound of claim 1, wherein A is -L A R A , B is -L B R B and C is -L C R C. 제10항에 있어서, 6,7,8-트리메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염인 화합물.The compound according to claim 10, which is a 6,7,8-trimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt. 제1항에 있어서, A가 수소이고 B가 -LBRB이며 C가 -LCRC인 화합물.The compound of claim 1, wherein A is hydrogen, B is -L B R B and C is -L C R C. 제12항에 있어서,The method of claim 12, 7,8-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7,8-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt; 7-벤질옥시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-benzyloxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 [(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세테이트 모노(트리플루오로아세테이트) 염;Methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetate mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-일-아세트산 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -yl-acetic acid mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-하이드록시프로판 모노(트리플루오로아세테이트) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-hydroxypropane mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt; 3-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]프로펜 모노(트리플루오로아세테이트) 염;3-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] propene mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane mono (hydrochloride) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] propane mono (hydrochloride) salt; 7-메톡시-8-(2-푸라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (2-furanyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; (E)-{7-메톡시-8-[2-(페닐)에테닐]}-2-나프탈렌이미드아미드 모노(트리플루오로아세테이트) 염;(E)-{7-methoxy-8- [2- (phenyl) ethenyl]}-2-naphthaleneimideamide mono (trifluoroacetate) salt; 7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-프로폭시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-propoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염;7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarboximideamide bis (trifluoroacetate) salt; 7-메톡시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (3-furanyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(2-벤조푸라닐)나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염;7-methoxy-8- (2-benzofuranyl) naphthalene-2-carboximideamide mono (methanesulfonate) salt; (E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt; (±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt; 7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[2-티아조일(옥시)]나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-thiazoyl (oxy)] naphthalene-2-carboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[N-2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [N-2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 4-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]디하이드로-2(3H)-푸라논 모노(트리플루오로아세테이트) 염;4- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] dihydro-2 (3H) -furanone mono (trifluoroacetate) salt; 7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 6-[2-(4-아미노페닐)에톡시]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6- [2- (4-aminophenyl) ethoxy] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 [3-메톡시-6-(아미노이미노메틸)-4-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염;Methyl [3-methoxy-6- (aminoiminomethyl) -4-naphthalenyl] carbamate mono (trifluoroacetate) salt; 7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염;7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide bis (trifluoroacetate) salt; 메틸 [7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐)카바메이트, 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl) carbamate, mono (trifluoroacetate) salt; 7-메톡시-8-(2-피리미디닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염;7-methoxy-8- (2-pyrimidinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt; 7-메톡시-8-[(페닐메틸)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8-[(phenylmethyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt; 7-메톡시-8-(페닐아미노)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8- (phenylamino) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt; 7-메톡시-8-[(4-메톡시페닐)아미노]-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8-[(4-methoxyphenyl) amino] -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt; (E)-3-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]-2-프로펜아미드, 모노(트리플루오로아세테이트) 염;(E) -3- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] -2-propenamide, mono (trifluoroacetate) salt; 7-메톡시-8-(3-옥소-1-사이클로펜텐-1-일)-2-나프탈렌카복스이미드아미드, 모노(트리플루오로아세테이트) 염;7-methoxy-8- (3-oxo-1-cyclopenten-1-yl) -2-naphthalenecarboximideamide, mono (trifluoroacetate) salt; 메틸 4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조에이트, 모노(트리플루오로아세테이트) 염;Methyl 4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoate, mono (trifluoroacetate) salt; 4-[[[7-(아미노이미노메틸)-1-(2-피리미디닐아미노)-2-나프탈레닐]옥시]메틸]벤조산, 모노(트리플루오로아세테이트) 염;4-[[[7- (aminoiminomethyl) -1- (2-pyrimidinylamino) -2-naphthalenyl] oxy] methyl] benzoic acid, mono (trifluoroacetate) salt; 7-메톡시-8-(피라지닐옥시)-2-나프탈렌카복스이미드아미드, 디메탄설포네이트 염;7-methoxy-8- (pyrazinyloxy) -2-naphthalenecarboximideamide, dimethanesulfonate salt; 7-메톡시-8-(페닐티오)-2-나프탈렌카복스이미드아미드, 메탄설포네이트; 및7-methoxy-8- (phenylthio) -2-naphthalenecarboximideamide, methanesulfonate; And 7-메톡시-8-(피라지닐아미노)-2-나프탈렌카복스이미드아미드, 비스(트리플루오로아세테이트) 염으로 이루어진 그룹으로부터 선택된 화합물.A compound selected from the group consisting of 7-methoxy-8- (pyrazinylamino) -2-naphthalenecarboximideamide, bis (trifluoroacetate) salt. 7,8-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7,8-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 6,7,8-트리메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6,7,8-trimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 6,7-디메톡시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6,7-dimethoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt; 7-벤질옥시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-benzyloxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 [(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]아세테이트 모노(트리플루오로아세테이트) 염;Methyl [(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] acetate mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-일-아세트산 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -yl-acetic acid mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-하이드록시프로판 모노(트리플루오로아세테이트) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-hydroxypropane mono (trifluoroacetate) salt; 페닐메틸 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염;Phenylmethyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate mono (trifluoroacetate) salts; N-[7-(아미노이미노메틸)-1-나프탈레닐]아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] acetamide mono (trifluoroacetate) salt; 메틸 [7-(아미노이미노메틸)-1-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염;Methyl [7- (aminoiminomethyl) -1-naphthalenyl] carbamate mono (trifluoroacetate) salt; 메틸 3-[[7-(아미노이미노메틸)-1-나프탈레닐]아미노]-3-옥소프로파노에이트 모노(트리플루오로아세테이트) 염;Methyl 3-[[7- (aminoiminomethyl) -1-naphthalenyl] amino] -3-oxopropanoate mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-2-(페닐메톡시)아세트아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -2- (phenylmethoxy) acetamide mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]-1,3-벤조디옥솔-5-카복스아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] -1,3-benzodioxol-5-carboxamide mono (trifluoroacetate) salt; N-[7-(아미노이미노메틸)-1-나프탈레닐]벤젠메탄설폰아미드 모노(트리플루오로아세테이트) 염;N- [7- (aminoiminomethyl) -1-naphthalenyl] benzenemethanesulfonamide mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-브로모프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-bromopropane mono (hydrochloride) salt; 3-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]프로펜 모노(트리플루오로아세테이트) 염;3-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] propene mono (trifluoroacetate) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-페닐프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3-phenylpropane mono (hydrochloride) salt; 1-[(7-아미노이미노메틸-2-메톡시-1-나프탈레닐)옥시]-3-[1-(3,4-디메톡시)페닐]-프로판 모노(하이드로클로라이드) 염;1-[(7-aminoiminomethyl-2-methoxy-1-naphthalenyl) oxy] -3- [1- (3,4-dimethoxy) phenyl] -propane mono (hydrochloride) salt; 7-메톡시-8-(2-푸라닐)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (2-furanyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 6-(아미노이미노메틸)-4-[(메톡시카보닐)아미노]-2-나프탈렌카복실레이트 모노(트리플루오로아세테이트) 염;Methyl 6- (aminoiminomethyl) -4-[(methoxycarbonyl) amino] -2-naphthalenecarboxylate mono (trifluoroacetate) salt; (E)-6-[2-(페닐)에틸]-2-나프탈렌이미드아미드 모노(트리플루오로아세테이트) 염;(E) -6- [2- (phenyl) ethyl] -2-naphthaleneimideamide mono (trifluoroacetate) salt; 7-(2-하이드록시에톡시)-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-(2-하이드록시에톡시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7- (2-hydroxyethoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 6-메톡시-8-벤질옥시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-methoxy-8-benzyloxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 2-[(7-아미노이미노메틸-3-메톡시-1-나프탈레닐)옥시]아세트아미드 모노(트리플루오로아세테이트) 염;2-[(7-aminoiminomethyl-3-methoxy-1-naphthalenyl) oxy] acetamide mono (trifluoroacetate) salt; 7-프로폭시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-propoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(1H-피라졸-4-일)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (1H-pyrazol-4-yl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-요오도-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-iodo-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;7-methoxy-8- (3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt; 7-메톡시-8-(2-벤조푸라닐)나프탈렌-2-카복스이미드아미드 모노(메탄설포네이트) 염;7-methoxy-8- (2-benzofuranyl) naphthalene-2-carboximideamide mono (methanesulfonate) salt; (E)-8-[2-(1,3-벤조디옥솔-5-일)에테닐]-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(E) -8- [2- (1,3-benzodioxol-5-yl) ethenyl] -2-naphthalenecarboximideamide mono (methanesulfonate) salt; (±)-7-메톡시-8-(테트라하이드로-3-푸라닐)-2-나프탈렌카복스이미드아미드 모노(메탄설포네이트) 염;(±) -7-methoxy-8- (tetrahydro-3-furanyl) -2-naphthalenecarboximideamide mono (methanesulfonate) salt; 7-메톡시-8-[2-피리미디닐(옥시)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-pyrimidinyl (oxy)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[2-티아조일(옥시)]나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [2-thiazoyl (oxy)] naphthalene-2-carboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-(4-니트로페녹시)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (4-nitrophenoxy) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-펜타플루오로페녹시-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8-pentafluorophenoxy-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[N-2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [N-2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzylurea mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-메탄우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-methaneurea mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-이소프로필우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-isopropylurea mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-페닐-N'-메틸우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-phenyl-N'-methylurea mono (trifluoroacetate) salt; 6-아미노나프탈렌-2-카복스이미드아미드 모노(트리플루오로아세테이트) 염;6-aminonaphthalene-2-carboximideamide mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-사이클로헥실우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-cyclohexylurea mono (trifluoroacetate) salt; N-(6-아미노이미노메틸-2-나프탈레닐)-N'-벤질옥시우레아 모노(트리플루오로아세테이트) 염;N- (6-aminoiminomethyl-2-naphthalenyl) -N'-benzyloxyurea mono (trifluoroacetate) salt; 1,1-디메틸에틸 [4-[[(6-시아노-2-나프탈레닐)아미노]카보닐]페닐]카바메이트 모노(트리플루오로아세테이트) 염;1,1-dimethylethyl [4-[[(6-cyano-2-naphthalenyl) amino] carbonyl] phenyl] carbamate mono (trifluoroacetate) salt; N-[6-(아미노이미노메틸)-2-나프탈레닐]-4-(아미노메틸)벤즈아미드 모노(트리플루오로아세테이트) 염;N- [6- (aminoiminomethyl) -2-naphthalenyl] -4- (aminomethyl) benzamide mono (trifluoroacetate) salt; 4-[7-(아미노이미노메틸)-2-메톡시-1-나프탈레닐]디하이드로-2(3H)-푸라논 모노(트리플루오로아세테이트) 염;4- [7- (aminoiminomethyl) -2-methoxy-1-naphthalenyl] dihydro-2 (3H) -furanone mono (trifluoroacetate) salt; 7-메톡시-8-(1-아세틸-1H-피라졸릴)-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- (1-acetyl-1H-pyrazolyl) -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 7-메톡시-8-[1-(메틸설포닐)-1H-4-피라졸릴]-2-나프탈렌카복스이미드아미드 모노(트리플루오로아세테이트) 염;7-methoxy-8- [1- (methylsulfonyl) -1H-4-pyrazolyl] -2-naphthalenecarboximideamide mono (trifluoroacetate) salt; 메틸 [3-메톡시-6-(아미노이미노메틸)-4-나프탈레닐]카바메이트 모노(트리플루오로아세테이트) 염; 및Methyl [3-methoxy-6- (aminoiminomethyl) -4-naphthalenyl] carbamate mono (trifluoroacetate) salt; And 7-메톡시-8-[2-피리미디닐(아미노)]-2-나프탈렌카복스이미드아미드 비스(트리플루오로아세테이트) 염으로 이루어진 그룹으로부터 선택된 화합물.7-methoxy-8- [2-pyrimidinyl (amino)]-2-naphthalenecarboximideamide bis (trifluoroacetate) salt. 제1항의 화합물을 유로키나제 억제가 필요한 포유동물에게 치료학적 유효량으로 투여함을 포함하여, 상기 포유동물에서 유로키나제를 억제하는 방법.A method of inhibiting urokinase in a mammal, comprising administering the compound of claim 1 to a mammal in need of urokinase inhibition. 치료학적 유효량의 제1항의 화합물과 약제학적 담체를 포함하는 유로키나제 억제용 조성물.A composition for inhibiting urokinase, comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutical carrier.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101228385B1 (en) * 2004-09-21 2013-02-04 빌렉스 아게 Stable dosing form of phenylalanine derivatives

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000005214A2 (en) * 1998-07-24 2000-02-03 Pfizer Inc. Isoquinolines as urokinase inhibitors
US6504031B1 (en) 1998-08-06 2003-01-07 Milan Bruncko Naphthamidine urokinase inhibitors
GB9914486D0 (en) 1999-06-21 1999-08-18 Smithkline Beecham Plc Medicaments
WO2001016121A1 (en) * 1999-08-31 2001-03-08 Merck & Co., Inc. Heterocyclic compounds and methods of use thereof
US20030232789A1 (en) * 1999-12-15 2003-12-18 Allen Darin Arthur Salicylamides as serine protease and factor xa inhibitors
US6495562B1 (en) 2000-04-25 2002-12-17 Abbott Laboratories Naphthamidine urokinase inhibitors
EP1276722B1 (en) * 2000-04-25 2006-03-08 Abbott Laboratories Naphthamidine urokinase inhibitors
DE10029014A1 (en) 2000-06-15 2001-12-20 Univ Schiller Jena Urokinase inhibitor, useful for treatment, prophylaxis or diagnosis of thromboembolic disease, comprising acylated 3- or 4-amidino-benzylamine derivative
US20100074949A1 (en) 2008-08-13 2010-03-25 William Rowe Pharmaceutical composition and administration thereof
EP1395548A1 (en) 2001-02-26 2004-03-10 4Sc Ag Derivatives of diphenylurea, diphenyloxalic acid diamide and diphenylsulfuric acid diamide and their use as medicaments
US7838560B2 (en) 2002-03-11 2010-11-23 The Medicines Company (Leipzig) Gmbh Urokinase inhibitors, production and use thereof
US7053112B2 (en) * 2002-09-24 2006-05-30 Schering Aktiengesellschaft Imidazolidinedione analogs useful as anticoagulants and antithrombotics
DE10301300B4 (en) 2003-01-15 2009-07-16 Curacyte Chemistry Gmbh Use of acylated 4-amidino- and 4-guanidinobenzylamines for the inhibition of plasma kallikrein
DE10342108A1 (en) 2003-09-11 2005-04-14 Curacyte Chemistry Gmbh Basic substituted benzylamine analogs as coagulation factor Xa inhibitors, their preparation and use
US7545495B2 (en) 2004-04-27 2009-06-09 Abbott Laboratories Methods for visualizing crystals and distinguishing crystals from other matter within a biological sample
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
CN101006076B (en) 2004-06-24 2010-09-29 沃泰克斯药物股份有限公司 Modulators of ATP-binding cassette transporters
JP2008543900A (en) 2005-06-24 2008-12-04 ヴィレックス アクチェンゲゼルシャフト Use of urokinase inhibitors for the treatment and / or prevention of neuropathological diseases
EP1917245A1 (en) 2005-08-21 2008-05-07 Abbott GmbH & Co. KG Heterocyclic compounds and their use as binding partners for 5-ht5 receptors
DK3219705T3 (en) 2005-12-28 2020-04-14 Vertex Pharma PHARMACEUTICAL COMPOSITIONS OF THE AMORPHIC FORM OF N- [2,4-BIS (1,1-DIMETHYLETHYL) -5-HYDROXYPHENYL] -1,4-DIHYDRO-4-OXOQUINOLIN-3-CARBOXAMIDE
DE102006050672A1 (en) 2006-10-24 2008-04-30 Curacyte Discovery Gmbh New glycylglycine derivatives with a benzylsulfonylamido group and an amidino-organylamido group at the opposite chain ends, used in drugs for reducing loss of blood, e.g. in operations
PT2408750E (en) 2009-03-20 2015-10-15 Vertex Pharma Process for making modulators of cystic fibrosis transmembrane conductance regulator
JP2011057661A (en) * 2009-08-14 2011-03-24 Bayer Cropscience Ag Pesticidal carboxamides
US8802700B2 (en) 2010-12-10 2014-08-12 Vertex Pharmaceuticals Incorporated Modulators of ATP-Binding Cassette transporters
EP2819670A1 (en) 2012-02-27 2015-01-07 Vertex Pharmaceuticals Incorporated Pharmaceutical composition and administration thereof
RU2749213C2 (en) 2014-10-07 2021-06-07 Вертекс Фармасьютикалз Инкорпорейтед Co-crystals of transmembrane conduction regulator modulators in cystic fibrosis
GB201617758D0 (en) 2016-10-20 2016-12-07 Almac Discovery Limited Pharmaceutical compounds
CA3158150A1 (en) 2019-10-18 2021-04-22 The Regents Of The University Of California 3-phenylsulphonyl-quinoline derivatives as agents for treating pathogenic blood vessels disorders
AR128577A1 (en) * 2022-03-01 2024-05-22 Syngenta Crop Protection Ag HERBICIDAL COMPOUNDS

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA928276B (en) * 1991-10-31 1993-05-06 Daiichi Seiyaku Co Aromatic amidine derivates and salts thereof.
US5340833A (en) * 1992-05-01 1994-08-23 Eisai Co., Ltd. Urokinase inhibitors
JP3457694B2 (en) * 1993-02-04 2003-10-20 第一製薬株式会社 Influenza prophylaxis and treatment
JP3004362B2 (en) * 1994-12-02 2000-01-31 山之内製薬株式会社 Novel amidinonaphthyl derivative or salt thereof
AU735144B2 (en) * 1997-07-23 2001-07-05 Yamanouchi Pharmaceutical Co., Ltd. Novel hexahydro-1,4-diazepine derivatives or their salts

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101228385B1 (en) * 2004-09-21 2013-02-04 빌렉스 아게 Stable dosing form of phenylalanine derivatives

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