PCT
`
`WORLD INTELLECTUAL PROPERTY ORGANIZATION
`International Bureau
`
`
`
`INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY(PCT)
`(51) International Patent Classification © :
`(11) International Publication Number:
`WO 95/29159
`
`Coe sae CHD47/2DOSE (43) International Publication Date:|2 November 1995 (02.11.95)
`
`233/36, 215/36, A61K 31/44, 31/47, 31/18
`
`
`21) International Application Number: PCT/US95/04956|(72) Inventors; and
`(21)
`International
`Application Number
`(75) Inventors/Applicants (for US only): FISHER, Michael, H.
`‘
`an
`.
`[US/US]; 126 East Lincoln Avenue, Rahway, NJ 07065
`(22) International Filing Date:
`(US), NAYLOR,Elisabeth, M. [GB/US]: 126 East Lincoln
`Avenue, Rahway, NJ 07065 (US). OK, Dong [US/US]; 126
`East Lincoln Avenue, Rahway, NJ 07065 (US). WEBER,
`
`§
`
`as
`
`OOPree
`
`triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.
`
`Substituted sulfonamides having formula (1), are selective 83 adrenergic receptor agonists with very little 6, and Bo adrenergic
`receptor activity and as such the compoundsare capable of increasing lipolysis and energy expenditure in cells. The compoundsthus have
`potent activity in the treatment of Type II diabetes and obesity. The compoundscan also be used to lowertriglyceride levels and cholesterol
`levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduce neurogenic
`inflammation or as antidepressant agents. The compoundsare prepared by coupling an aminoalkylpheny]-sulfonamide with an appropriately
`substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering
`
`‘
`21 April 1995 (21.04.95)
`
`26 April 1994 (26.04.94)
`
`Ann, E. [US/US]; 126 East Lincoln Avenue, Rahway, NJ
`
`.
`
`East Lincoln Avenue, Rahway, NJ 07065 (US).
`
`(74) Common Representative: MERCK & CO.,
`INC.; Patent
`60) Parent ApplicationsorGrants
`Gran
`Applications or
`Parent
`(60)
`Dept., 126 East Lincoln Avenue, Rahway, NJ 07065 (US).
`(63) Related by Continuation
`404,565 (CIP)
`US
`21 March 1995 (21.03.95)
`Filed on
`404,566 (CIP)|(81) Designated States: AM, AU, BB, BG, BR, BY, CA,CN,CZ,
`21 March 1995 (21.03.95)
`EE, FI, GE, HU, IS, JP, KG, KR, KZ, LK, LR, LT, LV,
`233,166 (CIP)
`MD, MG, MN, MX, NO, NZ, PL, RO, RU, SG, SI, SK,
`26 April 1994 (26.04.94)
`TJ, TT, UA, US, UZ, European patent (AT, BE, CH, DE,
`DK,ES, FR, GB, GR,IE, IT, LU, MC, NL, PT,
`SE), OAPI
`patent (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE,
`SN, TD, TG), ARIPO patent (KE, MW, SD, SZ, UG).
`
`Filed on
`
`(71) Applicant (for all designated States except US): MERCK &
`CO., INC. [US/US]; 126 East Lincoln Avenue, Rahway, NJ
`07065 (US).
`
`Published
`With international search report.
`
`(54) Title: SUBSTITUTED SULFONAMIDES AS SELECTIVE £3 AGONISTS FOR THE TREATMENT OF DIABETES AND
`OBESITY
`
`4
`
`R
`
`H
`
`HR?
`
`oA |
`openerL\-N-SOL(CH)A”
`3
`& Ae
`RY),
`8
`
`a)
`
`(57) Abstract
`
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`FOR THE PURPOSES OF INFORMATION ONLY
`
`Codes used to identify States party to the PCT on the front pages of pamphlets publishing international
`applications under the PCT.
`
`Viet Nam
`
`United Kingdom
`Georgia
`Guinea
`Greece
`Hungary
`Treland
`Italy
`Japan
`Kenya
`Kyrgystan
`Democratic People’s Republic
`of Korea
`Republic of Korea
`Kazakhstan
`Liechtenstein
`Sri Lanka
`Luxembourg
`Latvia
`Monaco
`Republic of Moldova
`Madagascar
`Mali
`Mongolia
`
`Austria
`Australia
`Barbados
`Belgium
`Burkina Faso
`Bulgaria
`Benin
`Brazil
`Belarus
`.
`Canada
`Central African Republic
`Congo
`Switzerland
`Céte d'Ivoire
`Cameroon
`China
`Czechoslovakia
`Czech Republic
`Germany
`Denmark
`Spain
`Finland
`France
`Gabon
`
`Mauritania
`Malawi
`Niger
`Netherlands
`Norway
`New Zealand
`Poland
`Portugal
`Romania
`Russian Federation
`Sudan
`Sweden
`Slovenia
`Slovakia
`Senegal
`Chad
`Togo
`Tajikistan
`Trinidad and Tobago
`Ukraine
`United States of America
`Uzbekistan
`
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`WO 95/29159
`
`.
`
`PCT/US95/04956
`
`-l-
`
`TITLE OF THE INVENTION
`SUBSTITUTED SULFONAMIDES AS SELECTIVE B3 AGONISTS
`FOR THE TREATMENTOF DIABETES AND OBESITY
`
`CROSS REFERENCE
`This is a continuation-in-part of co-pending application
`U.S.S.N. 08/233,166 filed April 26, 1994, which is hereby incorporated
`by referencein its entirety.
`
`10
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`
`BACKGROUND OF THE INVENTION
`§-Adrenoceptors have been subclassified as B] and B2 since
`Increased heart rate is the primary consequence of Bj-receptor
`1967.
`stimulation, while bronchodilation and smooth muscle relaxation
`typically result from B2 stimulation. Adipocyte lipolysis wasinitially
`thought to be solely a Bj-mediated process. However, more recent
`results indicate that the receptor-mediating lipolysis is atypical in
`nature. These atypical receptors, later called 83-adrenoceptors, are
`found on the cell surface of both white and brown adipocytes where
`their stimulation promotes both lipolysis (breakdown of fat) and energy
`expenditure.
`
`Early developmentsin this area produced compoundswith
`greater agonist activity for the stimulation of lipolysis (B3 activity) than
`for stimulation of atrial rate (61) and tracheal relaxation (62). These
`early developments disclosed in Ainsworthet al., U.S. Patents 4,478,849
`and 4,396,627, were derivatives of phenylethanolamines.
`Suchselectivity for B3-adrenoceptors could make
`compoundsof this type potentially useful as antiobesity agents. In
`addition, these compounds have beenreported to show
`antihyperglycemic effects in animal models of non-insulin-dependent
`diabetes mellitus.
`A major drawback in treatment of chronic diseases with B3
`agonists is the potential for stimulation of other B-receptors and
`subsequent sideeffects. The most likely of these include muscle tremor
`(62) and increased heart rate (B1). Although these phenylethanolamine
`
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`
`_2-
`
`derivatives do possess some $3selectivity, side effects of this type have
`been observed in human volunteers.
`It is reasonable to expect that these
`side effects resulted from partial 81 and/or B2 agonism.
`Morerecent developmentsin this area are disclosed in
`Ainsworth et al., U.S. Patent 5,153,210, Caulkett et al., U.S. Patent
`4,999,377, Alig et al., U.S. Patent 5,017,619, Lecountet al., European
`Patent 427480 and Bloom et al., European Patent 455006.
`Even though these more recent developments purport to
`describe compoundswith greater B3 selectivity over the By and B2
`activities, this selectivity was determined using rodents,in particular,
`rats as the test animal. Because even the mosthighly selective
`compounds, as determined by these assays, still show signs of side
`effects due to residual Bj and 82 agonist activity when the compounds
`are tested in humans, it has become apparentthat therodentis not a
`good model for predicting human £3selectivity.
`Recently, assays have been developed which more
`accurately predict the effects that can be expected in humans. These
`assays utilize cloned human £3 receptors which have been expressed in
`
`Chinese hamster ovary cells. See Emorineet al, Science, 1989,
`245:1118-1121; and Liggett, Mol. Pharmacol., 1992, 42:634-637. The
`agonist and antagonist effects of the various compounds on the
`cultivated cells provide an indication of the antiobesity and antidiabetic
`effects of the compoundsin humans.
`
`SUMMARY OF THE INVENTION
`
`The instant invention is concerned with substituted
`sulfonamides which are useful as antiobesity and antidiabetic
`compounds. Thus,it is an object of this invention to describe such
`compounds. It is a further object to describe the specific preferred
`stereoisomers of the substituted sulfonamides. A still further object is
`to describe processes for the preparation of such compounds. Another
`object is to describe methods and compositions which use the
`compoundsas the active ingredient thereof. Further objects will
`become apparent from reading the following description.
`
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`WO 95/29159
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`
`_3-
`
`DESCRIPTION OF THE INVENTION
`The present invention provides compoundshaving the
`
`formula I:
`
`where
`
`nis
`
`m is
`
`ris
`
`Ais
`
`10
`
`15
`
`20
`
`25
`
`30
`
`Rlis -
`
`veBootC-(x<-N-SoaCH,),-R
`
`(R')n
`
`0 to 5;
`0 or 1;
`0 to 3;
`(1) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatoms selected from oxygen, sulfur and nitrogen,
`(2) a benzene ring fused to a 5 or 6-memberedheterocyclic
`ring with from 1 to 4 heteroatoms selected from oxygen,
`sulfur and nitrogen,
`(3) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen
`fused to a 5 or 6-membered heterocyclic ring with from 1
`to 4 heteroatomsselected from oxygen, sulfur and
`nitrogen,
`(4) phenyl, or
`(5) a benzene ring fused to a C3-Cg cycloalkyl ring;
`(1) hydroxy,
`(2) oxo,-
`(3) halogen,
`(4) cyano,
`(5) NR8R8,
`
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`(6) SR8,
`(7) trifluoromethyl,
`(8) Cj-C10 alkyl,
`(9) ORS,
`(10) SO2RY,
`(11) OCORY,
`(12) NR8COR9,
`(13) CORY,
`(14) NR8SO2R9,
`(15) NR8CO2R8,or
`(16) Cj-C109 alkyl substituted by hydroxy, halogen, cyano,
`NR8R8, SR8,trifluoromethyl, OR8, C3-Cg cycloalkyl,
`phenyl, NR8COR9, COR?, SO2R9, OCOR?, NR8SO2R9or
`NR8CO2R8;
`R2 and R3 are independently
`(1) hydrogen,
`(2) C1-C10 alkyl or
`(3) Cj1-C10 alkyl with 1 to 4 substituents selected from
`hydroxy, Cj-C10 alkoxy, and halogen;
`(1) -CH2-,
`(2) -CH2-CH?2- ,
`(3) -CH=CH- or
`(4) -CH20-;
`R4 and RS are independently
`(1)hydrogen,
`(2) Cj-C10 alkyl,
`(3) halogen,
`(4) NHR8,
`(5) OR8,
`(6) SO2R9 or
`(7) NHSO2R9;
`(1) hydrogen or
`(2) C1-C10 alkyl,
`Z-(R1a)p;
`
`R6is
`
`R7is
`
`10
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`
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`30
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`
`Ria js
`
`R8 is
`
`10
`
`15
`
`20
`
`25
`
`30
`
`5.
`
`(1) RI, with the proviso that when A is phenyl, R14 is not
`C1-C10 alkyl,
`(2) C3-Cg cycloalkyl,
`(3) phenyl optionally substituted with up to 4 groups
`independently selected from R8, NR8R8, OR8, SR8 and
`halogen, or
`(4) 5 or 6-membered heterocycle with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen,
`optionally substituted with up to four groups independently
`selected from oxo, R83, NR8R8, OR8, SRE, and halogen;
`(1) phenyl,
`(2) naphthyl,
`(3) a 5 or 6-memberedheterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen,
`(4) a benzenering fused to a C3-Cg cycloalkylring,
`(5) a benzene ring fused to a 5 or 6-membered heterocyclic
`ring with from 1 to 4 heteroatomsselected from oxygen,
`sulfur and nitrogen,
`(6) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen
`fused to a 5 or 6-membered heterocyclic ring with from 1
`to 4 heteroatomsselected from oxygen, sulfur and
`nitrogen, or
`(7) a 5 or 6-memberedheterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen
`fused to a C3-Cg cycloalkylring;
`(1) hydrogen,
`(2) Cj1-C10 alkyl,
`(3) C3-Cg cycloalkyl,
`(4) Z optionally having 1 to 4 substituents selected from.
`halogen,nitro, oxo, NR!0R10, Cj-CyQ alkyl, C1-C10
`alkoxy, C1-C10 alkylthio, and Cj-C10 alkyl having 1 to 4
`substituents selected from hydroxy, halogen, CO2H, CO?2-
`Cj-Ci0 alkyl, SO2-C1-C10 alkyl, C3-Cg cycloalkyl, C1-
`
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`-6-
`
`10
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`30
`
`R9is
`
`R10 is
`
`C10 alkoxy, and Z optionally substituted by from 1 to 3 of
`halogen, Cj-C10 alkyl or C1-C10 alkoxy, or
`(5) C1-C10 alkyl having 1 to 4 substituents selected from
`hydroxy, halogen, CO2H, CO2-C1-C10 alkyl, SO2-C1-C10
`alkyl, C3-Cg cycloalkyl, Cj-C10 alkoxy, C1-C10 alkyl, and
`Z optionally substituted by from 1 to 4 of halogen, Cj-C10
`alkyl or Cj-C10 alkoxy;
`(1) R8 or
`(2) NR8R8;
`(1) C1-C10 alkyl, or
`(2) two R!0 groups together with the N to which they are
`attached formed a 5 or 6-memberedring optionally
`substituted with C1-C10 alkyl; or
`a pharmaceutically acceptable salt thereof,
`In one embodimentof the instant invention A is a 5 or 6-
`membered heterocyclic ring with from 1 to 4 heteroatoms selected from
`oxygen, sulfur and nitrogen, a benzene ring fused to a 5 or 6-membered
`heterocyclic ring with from 1 to 4 heteroatoms selected from oxygen,
`sulfur and nitrogen, or a 5 or 6-memberedheterocyclic ring with from
`1 to 4 heteroatomsselected from oxygen, sulfur and nitrogen fused to a
`5 or 6-memberedheterocyclic ring with from 1 to 4 heteroatoms
`selected from oxygen, sulfur and nitrogen.
`In another embodimentof the instant invention A is phenyl
`or benzene fused to a C3-Cg cycloalkyl ring.
`Preferred compoundsofthe instant invention are realized
`when in the abovestructural formula I:
`R2 and R3are hydrogen or methyl;
`X is
`-CH?-;
`nis
`0 to 3;
`m is
`1;
`r is
`0 to 2; and
`R4, RS and R6 are hydrogen.
`Other preferred compoundsofthe instant invention are
`
`realized when in the abovestructural formulaI:
`
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`-7-
`
`phenyl or a 6-memberedheterocyclic ring with 1 or 2
`heteroatomsselected from nitrogen and sulfur;
`hydroxy, halogen, cyano,trifluoromethyl, NR8R8,
`NR8SO2R9, NR8CORY, NR8CO2R8, Cj-C6 alkyl
`optionally substituted by hydroxy; and
`0 or 2.
`Morepreferred compounds are represented by the formula
`
`A is
`
`R1 is
`
`r is
`
`Ta:
`
`
`
`HR?
`OH
`|
`» Ar!
`|
`(R'), K JTSHCHAN-C-ia
`N
`R3
`
`;
`NH-SO,—Z-(R'*),
`
`Ja
`
`wherein
`0 to 3;
`nis
`m is |
`R! is
`(1) halogen or
`(2) NR8R8.
`R2, R3 are independently hydrogen or methyl;
`Ria is
`(1) halogen,
`(2) Cq-C10 alkyl,
`(3) NR8R8,
`(4) NR8CORY,
`(5) NR8CO2R8,
`(6) CORY,
`|
`(7) OCORY, or
`(8) a 5 or 6-membered heterocycle with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen,
`optionally substituted with up to four groups independently
`selected from oxo, halogen, Rs, NR8R8, or8, and SR8;
`(1) phenyl,
`(2) naphthyl,
`
`Zis-
`
`-
`
`10
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`30
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`WO 95/29159
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`8.
`
`(3) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatoms selected from oxygen, sulfur and nitrogen,
`(4) benzene ring fused to a 5 or 6-memberedheterocyclic
`ring with from 1 to 3 heteroatoms selected from oxygen,
`sulfur and nitrogen, or
`(5) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatoms selected from oxygen, sulfur and nitrogen
`fused to a C3-Cg cycloalkyl] ring;
`-CH?-; and
`X is
`R8 and R9are as defined under formulaI.
`Even more preferred compoundsare those represented by
`
`formula Id:
`
`15
`
`20
`
`25
`
`3
`
`H R?o »
`GH
`MESTconnc.cre(_\naSO.~-5 yniL,
`
`ae
`
`\.
`
`Id
`
`nis
`0 or 1;
`R1 is
`NR8R8;
`R2 and R3 are independently
`(1) hydrogen, or
`(2) methyl;
`(1) hydrogen,
`(2) benzene fused to the benzene ring to form naphthyl, or
`(3) a 5 or 6-memberedheterocycle with 1 to 4 heteroatoms
`selected from oxygen, sulfur and nitrogen atom fused to the
`benzenering;
`(1) halogen,
`(2) Cj-C10 alkyl,
`(3) NR8R8,
`(4) NR8CORY,
`(5) NR8CO2R8,
`
`Rla is
`
`_
`
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`(6) CORY,or
`(7) a 5 or 6-membered heterocycle with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen,
`optionally substituted with up to four groups independently —
`selected from oxo, R8, SR8, OR8, and NR8R8;
`whenBand the benzene ring form a fused ring system, R1a
`is attached to either ring;
`(1) hydrogen,
`(2) Cj1-C10 alkyl,
`(3) Z optionally having | to 4 substituents selected from
`nitro, oxo, and NR1OR10.or
`(5) Cj-C10 alkyl having 1 to 4 substituents selected from
`hydroxy, halogen, C1-C10 alkyl, C3-Cg cycloalkyl, and Z
`optionally substituted by from 1 to 4 of halogen, C1-C10
`alkyl or C1-C10 alkoxy;
`(1) R8 or
`(2) NR8R8;
`(1) C1-C10 alkyl, or
`(2) two R10 groupstogether with the N to which they are
`attached formed a 5 or 6-membered ring optionally
`substituted with C1-C10 alkyl; and
`(1) phenyl,
`(2) a 5 or 6-memberedheterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen,
`(3) a benzene ring fused to a 5 or 6-memberedheterocyclic
`ring with from 1 to 4 heteroatomsselected from oxygen,
`sulfur and nitrogen, or
`(4) a 5 or 6-membered heterocyclic ring with from 1 to 4
`heteroatomsselected from oxygen, sulfur and nitrogen
`fused to a C3-Cg cycloalkyl] ring.
`Other more preferred compounds are represented by
`
`10
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`
`R8is
`
`RY is
`
`R10 is
`
`formula Ib:
`
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`-10-
`
`(R')n
`
`OH
`
`R?
`
`o™| i
`Cr CHCHEN-C-(X)i
`
`RS
`
`{\
`
`'
`NH-SO,-
`Z-(R°*)
`-S0,- Z-(R'*),
`
`Ib
`
`wherein
`
`nis
`
`0 to 3;
`
`1 (
`
`m is
`Rl! is
`
`1) hydroxy,
`(2) cyano,
`(3) NR8R8 or
`(4) halogen;
`(1) halogen,
`(2) NR8R8,
`(3) NR8COR?,
`(4) NR8CO2R8,
`(5) OCORY,or
`(6) a 5 or 6-memberedheterocycle with from 1 to 4
`heteroatoms selected from oxygen, sulfur and nitrogen,
`optionally substituted with up to three groups independently
`selected from oxo, halogen, R8, NR8R8, OR8 and SR8;
`(1) phenyl,
`(2) naphthyl or
`(3) benzene ring fused to a 5 or 6-memberedheterocyclic
`ring with from 1 to 4 heteroatomsselected from oxygen,
`sulfur and nitrogen;
`-CH?-; and
`X 1s
`~-R2.and R3 are independently hydrogen or methyl.
`Representative antiobesity and antidiabetic compounds of
`the present invention include the following:
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-~yDethy!Jamino|ethy!|phenyl}-
`4-(hexylaminocarbonylamino)benzenesulfonamide
`
`Rlais
`
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`
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]ethyl}pheny]]-
`4-iodobenzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]ethyl]pheny]]-
`benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-ylethyl]amino]ethyl]phenyl]-
`2-naphthalenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethylJaminoJethyl]phenyl]-
`3-quinolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethy]Jamino]Jethyl]pheny]]-
`5-benzisoxazolesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethylJamino]ethyl]pheny]]-
`4-[(hexylmethylaminocarbonyl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]ethyl]pheny]]-
`4-[(dimethylaminocarbony])amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]ethyl]pheny]]-
`4-(3-hexyl-2-imidazolidon-1-yl)benzenesulfonamide
`N-[4-[3-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]propyl]-
`pheny]]-4-(hexylaminocarbonylamino)benzenesulfonamide
`N-[4-[3-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]propyl]-
`phenyl]-4-iodobenzenesulfonamide
`N-[4-[3-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]propyi]-
`phenyl]benzenesulfonamide
`N-[4-[3-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]propyl]-
`pheny]]-2-naphthalenesulfonamide
`N-[4-[3-[[2-hydroxy-2-(6-aminopyridin-3-yl)ethyl]amino]propyl]-
`phenyl]-3-quinolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]pheny1]-4-
`(hexylaminocarbonylamino)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethy]]phenyl]-4-
`isopropylbenzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`- 30
`
`N-[4-[2-[[2-hydroxy-2-(3-‘Pytidinylethyl]aminojethyi]pheny!)2-
`N-[4-[2-[[2-hydroxy-2--@-pytidinyDethyjminoetypheny3-
`
`naphthalenesulfonamide _
`
`quinolinesulfonamide
`
`SAWAI EX. 1013
`Page 13 of 103
`
`SAWAI EX. 1013
`Page 13 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`-12-
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-
`[(hexylmethylaminocarbony]l)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinylethyl]amino]ethyl]pheny1]-4-3
`hexyl-2-imidazolidinon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinylethyl]amino]ethyl]pheny1]-4-
`iodobenzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinylethyl]aminoJethyl]phenyl]-4-[5-(@-
`cyclopentylpropyl)-[1,2,4]-oxadiazol-3-yl]benzensulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny!]-4-[(1-
`oxoheptyl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[(1-
`oxo-4-phenylbutyl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl}]pheny]]-4-
`[(propoxycarbonyl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinylethyl]amino]ethyl]phenyl]]-4-[[[(fur-
`2-ylmethyl)amino]carbonyl]amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethylphenyl]-4-[[[(2-
`phenylethyl)amino]carbonyl]amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylamino]ethyl]phenyl]-4-[[[(2-
`indol-3-ylethyl)amino]carbony]]amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-
`[[(octylamino)carbonyl]amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethy]]amino]ethyl]phenyl]-1-
`[(hexylamino)carbony]]-5-indolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny]l)ethyl]amino]ethyl]phenyl]-1-
`[(octylamino)carbonyl]-5-indolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl}phenyl]-1-[(N-
`methyl-N-octylamino)carbony]]-5-indolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]]-1-(1-
`oxonony])-5-indolinesulfonamide
`N-[4-[2-[(2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenylj-1-(4-
`methylthiazol-2-yl)-5-indolinesulfonamide
`_ N-[4-[2-[[2-hydroxy-2-(3-pyridinylethylJaminoJethyl]phenyl]-1-(4-
`octylthiazol-2-y1)-5-indolinesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`SAWAI EX. 1013
`Page 14 of 103
`
`SAWAI EX. 1013
`Page 14 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`-13-
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-1-(4-
`ethyl-5-methylthiazol-2-yl)-5-indolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinylethyl]amino]ethyl]pheny]]-4-3
`aa2-imidazolidinon-1-yl)benzenesulfonamide
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-[3-
`(4,4,4-trifluorobutyl)-2-imidazolidinon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[3-(3-
`phenylpropyl)-2-imidazolidinon- 1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny1]-4-[3-
`(4,4,5,5,5-pentafluoropentyl)-2-imidazolidinon-1-
`yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]-4-[3-(2-
`cyclohexylethyl)-2-imidazolidinon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]Jethyl]pheny]]-4-[3-[3-
`(4-chlorophenyl)propy!]-2-imidazolidinon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]-4-(3-
`pentyl-2-imidazolidinon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[3-(3-
`cyclopentylpropy])-2-imidazolidinon- 1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy!]pheny!]-4-[3-(2-
`cyclopentylethyl)-2-imidazolidinon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethy]]amino]ethyl]pheny]]-4-[3-(3-
`cyclohexylpropyl)-2-imidazolidinon-1-yl]benzenesulfonamide
`N-(4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-[3-(2,2-
`dimethylhexy])-2-imidazolidinon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(3-
`hexy]-2-imidazolon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy!]phenyl]-4-[3-
`(4,4,4-trifluorobutyl)-2-imidazolon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-“Pyridiny)ethylJaminojethyl}pheny!]-4-(3-
`octyl-2-imidazolon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[3-(3-
`__ cyclopentylpropyl)-2-imidazolon-1-yl]benzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`SAWAI EX. 1013
`Page 15 of 103
`
`SAWAI EX. 1013
`Page 15 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`-14-
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny]l)ethylJamino]ethyl]pheny]]-4-(2-
`octyl-3-oxo-[1,2,4]-triazol-4-yl)benzenesulfonamide
`N-[4-(2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl1]-4-(4-
`hexyl-5-tetrazolon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]-4-(4-
`octyl-5-tetrazolon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]aminoJethyl]phenyl]-4-[(3-
`cyclopentylpropyl)-5-tetrazolon- 1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy]]pheny]]-4-(2-
`pentyloxazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyljamino]ethy]]phenyl]-4-(2-
`octyloxazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-[2-(2-
`cyclopentylethyl)oxazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-[(4-
`ethyl-5-methylthiazol-2-yl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethyl]pheny1]-4-
`[(4,5,6,7-tetrahydrobenzothiazol-2-yl)amino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethylJamino]ethyl]phenyl]-4-(2-
`hexylimidazol-4-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(1-
`methyl-2-octylimidazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny!]-4-[1-
`methy]-2-(2-cyclopentylethyl)imidazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[1-
`methyl-2-[2-(4-fluorophenyl)ethyl]imidazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`pentyl-[1,2,4]-oxadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethy]]phenyl]-4-[5-(2-
`cyclopentylethyl)-[1,2,4]-oxadiazol-3-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny]l)ethyl]amino]ethyl]pheny]]-4-(5-
`heptyl-[1,2,4]-oxadiazol-3-yl)benzenesulfonamide
`_ N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`octyl-[1,2,4]-oxadiazol-3-yl)benzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`SAWAI EX. 1013
`Page 16 of 103
`
`SAWAI EX. 1013
`Page 16 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`-15-
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny1]]-4-(5-
`hexylthio-[1,2,4]-triazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethy]]phenyl]-4-[[4-(4-
`propylpiperidin-1-yl)-1, 1-dioxo-[1,2,5]-thiadiazol-3-
`ylJamino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[[4-
`(hexylmethylamino)-1,1-dioxo-[1,2,5]-thiadiazol-3-
`ylJamino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyljaminoJethyl]phenyl]-4-[[4-(N-
`heptyl, N-methylamino)-1,1-dioxo-[1,2,5]-thiadiazol-3-
`ylJamino]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-_pyridinyl)ethyl]aminoJethyl]phenyl]-4-(1-
`octyl-2,4-imidazolidinedion-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny]l)ethylJamino]ethyl]phenyl]-4-[3-(3-
`nitrophenyl)-5-pyrazolon-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]-4-[4-(1-
`hydroxy- 1-hexylhepty]l)-5-methyl-[1,2,3]-triazol-2-yl]benzenesulfon-
`amide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-(1-
`hydroxyheptyl)-5-methyl]-[1,2,3]-triazol-2-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]-2-methylpropy]]-
`phenyl]-4-(3-hexyl-2-imidazolidinon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]-2-methylpropy]]-
`pheny1]-4-iodobenzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]-2-methylpropyl]-
`phenyl]-4-[[(hexylamino)carbonyl]amino]benzenesulfonamide
`N-[4-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]phenyl]-4-iodobenzene-
`sulfonamide
`-
`N-[4-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]pheny]]-2-naphthalene-
`sulfonamide
`~
`N-[4-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]phenyl]-3-quinoline-
`sulfonamide
`N-[4-[2-[[2-hydroxy-2-(3--chlorophenyl)ethyl]aminoethylphenyl]-3-
`isopropylbenzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`~
`
`SAWAI EX. 1013
`Page 17 of 103
`
`SAWAI EX. 1013
`Page 17 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`- 16 -
`
`N-[4-[2-[[2-hydroxy-2-(3-chlorophenyl)ethyl]amino]ethyl]phenyl]-2-
`naphthalenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-chlorophenyl)ethyl]amino]ethyl]phenyl]-3-
`quinolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-amino-3,5-dichlorophenyl)ethy]amino]ethyl]-
`phenyl]-4-(hexylaminocarbonylamino)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-amino-3,5-dichlorophenyl)ethyl]amino]ethy]]-
`phenyl]-1-[(octylamino)carbony]]-5-indolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-amino-3,5-dichlorophenyl)ethyl]amino]ethy]]-
`pheny]]-4-(3-hexyl-2-imidazolidinon- 1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-amino-3,5-dichlorophenyl)ethyl]aminoJethy]]-
`phenyl]-4-(3-octyl-2-imidazolidinon-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-hydroxyphenyl)ethyl]amino]ethyl]phenyl]-
`benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(4-hydroxypheny])ethyl]amino]Jethyl]pheny]]-4-
`iodobenzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-cyanophenyl)ethyl]amino]ethyl]phenyl]-4-
`(hexylaminocarbonylamino)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-cyanophenyl)ethyl]amino]ethy]]phenyl]-3-
`quinolinesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`hexyl-[1,2,4]-oxadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]]-4-(4-
`heptyl-5-methyl-[1,2,3]-triazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(3-
`hexyl-2,4-imidazolidinedion-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-(3-
`octy]-2,4-imidazolidinedion-1-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy!]phenyl]-4-[3-G-
`cyclopentylpropyl)-2,4-imidazolidinedion-1-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(3-
`pentyl-[1,2,4]-oxadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethy!]phenyl]-4-(3-
`hexyl-[1,2,4]-oxadiazol-5-yl)benzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`SAWAI EX. 1013
`Page 18 of 103
`
`SAWAI EX. 1013
`Page 18 of 103
`
`

`

`WO 95/29159
`
`PCT/US95/04956
`
`-17-
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl}-4-(3-
`heptyl-[1,2,4]-oxadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(3-
`octyl-[1,2,4]-oxadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]}-4-[3-(2-
`cyclopentylethyl)-[1,2,4]-oxadiazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[3-(3-
`cyclopentylpropy])-[1,2,4]-oxadiazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]aminoJethyl]pheny]]-4-(3-
`pentyl-[1,2,4]-thiadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-(3-
`hexyl-[1,2,4]-thiadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy!]phenyl]-4-(3-
`heptyl-[1,2,4]-thiadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(3-
`octyl-[1,2,4]-thiadiazol-5-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[3-(2-
`cyclopentylethyl)-[1,2,4]-thiadiazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]Jethyl]phenyl]-4-[3-(-
`cyclopentylpropyl)-[1,2,4]-thiadiazol-5-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny]]-4-(5-
`penty]-[1,2,4]-thiadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`hexyl-[1,2,4]-thiadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`heptyl-[1,2,4]-thiadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]]-4-(5-
`octyl-[1,2,4]-thiadiazol-3-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]pheny!]-4-[5-(2-
`cyclopentylethyl)-[1,2,4]-thiadiazol-3-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[5-(3-
`cyclopentylpropyl)-[1,2,4]-thiadiazol-3-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny]l)ethylJamino]ethyl]phenyl]-4-(4-
`pentyl-3-oxo-[1,2,4]-triazol-2-yl)benzenesulfonamide
`
`10
`
`15
`
`20
`
`25
`
`30
`
`SAWAI EX. 1013
`Page 19 of 103
`
`SAWAI EX. 1013
`Page 19 of 103
`
`

`

`WO 95/29 159
`
`PCT/US95/04956
`
`- 18 -
`
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethyl]phenyl]-4-(4-
`hexyl-3-oxo-[1,2,4]-triazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]phenyl]-4-(4-
`heptyl-3-oxo-[1,2,4]-triazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethylJamino]ethyl]}phenyl]-4-(4-
`octyl-3-oxo-[1,2,4]-triazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridiny])ethyl]amino]ethyl]phenyl]-4-[4-(2-
`cyclopentylethy])-3-oxo-[1,2,4]-triazol-2-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethy!]phenyl]-4-[4-(3-
`cyclopentylpropyl)-3-oxo-[1,2,4]-triazol-2-yl]benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`pentyloxazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`hexyloxazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`heptyloxazol-2-yl)benzenesulfonamide
`N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-(5-
`octyloxazol-2-yl)benze