2) United States Patent
‘Travis
‘USOOTLOS68SB2
US 7,105,685 B2
Sep. 12, 2006
(10) Patent No.
(4s) Date of Patent:
(34) CANNABINOL DERIVATIVES
(96) Inventor: Craig R. Travis, $901 SW. 87" St,
South Miami, FL (US) 33143
() Notice: Subject wo any diteluimer the tem of this
patent is extended or adjusted under 35
USC. 154(b) by 83 days
(21) Appl. Now 10/928,242
(22) Filed: Dee, 22, 2002
6s) Prior Publication Data
{US 20080158191 AL Avg, 21, 2003
Related U.S. Application Data
(63) Continuation of appiaton No, 09928685, fed on Aus.
1,200, mow Pat No.6 506,560 which 3 entiation:
inp of appicion No. 09'S88385, ied on Mie
Bon, now Pat No. 8278835,
(G0) Provisional splication No. 60125674 ied on Mat. 2,
199, and provisional application No, 60151595, fled on
Aug. 30. 199,
(1) Incl.
C7 31180 (2006001)
Cord 3114 (2006.01)
€or 31178 (2006.01)
(2) US. ‘549/990; 49/200, 5491356;
‘49/381; 540/385; 549/388; 549/389, 549/391
(58) Fleld of Classitication Search S6WTIS,
‘68/716, 731, 732, 733; 549/200, 356, 381,
‘49/385, 388, 390 X, 380, 391
See application file for complete search history.
66) References Cited
US. PATENT DOCUMENTS.
$65527 A 101896 Adame
2308669 A 12/1982 Adame
Dsw.a86 A 51950 Adan
S386 A 61968 Taster
SSOTSES A 411970. Fahenbole
31972. Ravfnn eta
1972 Petia
+ 34974 Loev ea 23483
* 2174 Loew dass
11974 Loew
SADIE Bender eta osonon 6013483
38ol402 A 21975 Fager tal
387.876 AMOS Palla
38973105 A TIDIS Vidi ta
3019322 A 111975 Bross et
BoINSOR A L2I97S Atcher
UIT 41977 Brown et
OIRT77 A 41977. Zag et
$020098 841977 Goto
0S4SK3 A 101977 Blanchard
Seto 121977 Fukuda sta
AUS7S45 —BIDTH Archer et a
a 81978 Fok oa
(6 STS Reaan ot
440701 421979 Ryan
(Continved
FOREIGN PATENT DOCUMENTS
ep 494 665 BL V1992
HU 18829 B 31986
2 o.t010%6 411990
» “4208280 A 11/1990
» 2000191520 872000
Wo WOUTIIGE A 41997
WO WOoT0006 8 101997
WO Wov920266 AL 4199
WO WO9932107 AL__T1999
WO WO9SISHO AL 10199
WO WOosrs24 A 19199
WO WO90S017 A 10199
(OTHER PUBLICATIONS
Yoshida etal, Chem. & pharmaceutical Bulle
2), pp. 335-337; abstract only.
Pitt et al. 1. Org: Chem, 1979, 445), pp. 677-683.
Beak et al, rch Pharmacal Res, 19, 228-230, 1996,
Beak et al, sch Pharmacal Res, 21(3), 383-356, 1998
Beutler et ai, J. Nar. Prod. 61, 1809-1812, 1998,
Bhargave, General Pharm.” 9, 195-213, 1978.
Burstein etal. Biochemicul Pharmacology, 29, 2183-2156,
1980.
Cabral et a, Ade Biosci, 80, 93-105, 1991
Carchman et al, Marihuana Chem, Biochem. Cell Ef,
Proc. Saell. Symp., 392-345, 1976,
Elkin et al. Federation of American Societies for Experi
‘mental Biology. 71 Annual Meeting, Abstracts of Papers,
Mar. 29 to Apr. 2, 1987,
Haris etal, Pharm. Of Marihuana, 749-762, 1976.
Hartman et al, J Med, Chem, 23, 881-848, 1980,
Kawakami etal, dnt J. Immunopharmacol. 10, 485-488,
198s,
Iyman et al, Joursal of Neuroimmunologs, 12, 73-81,
1989.
Nahas et al, CR. Hebd, Seances Acad, Sol, 279(19),
1607-1608, 1974,
Nichols et ab, Life Sciences, 21, 1245-1248, 1977.
Signh etal, J. Org. Chem, 61, 7727-7737, 1996,
Specter etal, Federation of American Societies for Experi
‘mental Biology. 4. A1021, 1980.
Spocter et a, Druge of Abuse and Immune Function, 75-86,
1990.
Srivastava etal, mmunopharmacofogr, 40, 179-185, 1998.
Timpone etal, tds Res. Hom. Retroviruses, 13, 305-315,
sor.
‘Waksman, Journal of Autoinmamity, $6, 1999.
Wata etal, Jat. J. Immunopharmacol, 1091-1097, 1991
Wat etal, Ads Exp. Med. Biol, 288, 63.70, 1991
Zeng et al, Int. J. Dmumopharmacol, 14, 1445-1452,
1902.
Zuri eta, Arthritis & Rheumatism, 41, 168-170, 1998,
‘Abrams, J- of deg. Immus. Def. Syn 25, 74-80 (2000)
(Coutinved)
(1995), 8
Primary Esaminer—Elvis 0. Price
(74) Auornes, Agent, or Firm—Ash Tank,
on ABSTRACT
‘The invention provides eannahinol derivatives ad pharma.
ceutical preparations thereof.
6 Claims, No DrawingsUS 7,105,685 B2
Page 2
U.S. PATENT DOCUMENTS.
SishasT
51638530,
51997 Tio ea
1997 Mechoslam ot al
31998 Leet
1908 Callin et
S817651 A 101998 DrAmbra a
ES24688 A 101908 Kalish et
SRA7.128 A 12/190 Matin tl
SRATI65 A 121998 Loe tal
S856323 A 1/1999 Cai eal
S839.067 A 1/1999. Rowfogais a.
S872.148 A 2/1909 Maksjanns eta
Ssoide A 411999 Amtem
S916 365 A 6'1999 Bene ea
5925768 A 7/1999. Banh eta
181999. Shoham ta.
$1999 Kuno et
911909 Render al
1/1999 Delia alle ota
1/2000 Rial ta
42000, Meyer e
9000 Pak ea
48.1398 1979 Bindi
480669 121979 Winn
SU9S078 A “H1980 Conine
420.027 A 21981 Goto
443004885 411982 Johnson
SBIS862 A 21982 Elsohly etal
43560 & 91982 Pine
4408626 & 911983 Johnson
S608 A RID84. Husain
415003327 A T1986. Noga ot
‘4601505 41987 Marshall ta
4758397 8 TIDS8. Martine a
4577298 A 10/1988 Marshall ta
SSHLOTS A SIBSD. MeNally ta
4837228 61989 Elsohly etal.
AS4L078 A GID80 Eggler etal.
X Su1989 tin
A 1018 Mecho ca
AD8368 A 61990. Sstsinger ea.
497.603 1171990 Bustin
112800 A 5/1002 Ward
5227537 A 711993 Sooke
S250551 A 101993 Mien ta
SSw759 A “¥1904 rstein et
Sha971 A 8004 Herta
S30.375 A 21995 Elohly
51440052 A 81995 Maksyannis ta
Sao8419 A 1900 Par
SSani9e A $1996 Zucksaman
5527819 A 611996 Williams eta
Ss32257 A 71996 Gallant ea
Si0s906 A 21997 Law
51605928 A 21907 Mechoulam etal
Sgn4od1 A 4/1907 Banh eta
a
a
a
a
a
a
a
a
a
a
a
eutesr
(OTHER PUBLICATIONS
Adams, etal, J. Med Chem, 70, 662-68 (1947),
Adams et al. “New Analogs of Tetraydrocannabinl,” 71
1624-28 (1949),
Akamanchi etal, Pharm, Pharmacol. Commun. $,323-329
(1999),
Arisawa et al, Chem. Pharm. Bull, 37, 9, 2431-2434
(1989),
Baeverle et al, lnm, Rex: Immunol, 12, 141-79 (1994)
Barth, Exp. Opin. Ther Patents, 8, 3, 01-313, (1998).
Bennet etal, Marihuana and Medicine, 717-721 (Humana
Press 1999),
Biswas et al, J. of dog. loumun. Def. Sym and Hum,
Retrovirol, 18, 426-34 (1998),
Bomhcim, Biochem. Pharm., 36, 985-961 (2000).
Pombeim, “Cansabidiol Effet on Cytochro PASO
Isozymes,” Abstract, ILI Grant No. SROIDADS265-13,
Bombeim, Chem. Res. Tasicol, UL, 1209-16 (1998),
[Baitsein etal, AIDS 2001, 15, 4, 532-533 (2000),
Brunneisen et al. Int J. of Clin Pharmacol. Ther, 34,
446-52 (1996),
Buchwald etal, Pharamacie, 5S, 196-201 (2000),
Burstein otal, J. Pharmacol. and Fxperimemtal Therapew-
ties, 51, 2, 581-535 (1989)
Burstein etal, Pharmacol. Ther, 82, 81-96 (1909),
Tuseh-Petersea etal, J. Med. Chem.» 39, 3790-96 (1996).
Bustos etal, J. Clin vest, 100, §, 1150-1158 (1997),
Butlers et a Aide Res. Hum, Retrovir, 8, 991-95 (1992),
Charalambous etal, Pharm Biochem. Behav, 40, $09-12
991),
Chea etal, Chem. Commun., 2769-2770 (1998),
Colasanti eta, Exp. Eye Res., 38, 63-71 (1984),
CColasanti etal, Exp. Eye Res., 39, 251-259 (1984),
Corr etal, "Selected metabolic alterations in the ischemic
‘bert and their contributions to arraythmogenesis." Abstract,
NIH Grant No, 7543431 0198362134
Daaka etal, DNA Cell Biol, 16, 301-09 (1997),
el Real eta, AIDS. 12, 865-72 (1998.
Desoize, Anticancer Res. 14, 2291-94 (1994).
Dewhirst, Prostaglandins, 20, 209-22 (1980),
Di Franco, AEP, 6, 283-89 (1996).
Dol etal, Fur Jt Ong. Chem, 389-64 (1998).
Dominianai et al, J Org. Chem., 42. 344-46 (1977).
Dumais et al, J Bio! Chem, 42, 27306-14 (1998).
Eisohly etal of Pharm. Sciences, 71, 12, 1319-1323
(1982),
Evans etal, Biochem. Pharm.. 36, 2088-37 (1987),
Folder etal, Mol. Pharmool., 42, 838 48 (1992),
Fiddler et al, Supp. I Circulation. 81,1, 1-69-1-78 (1990)
Formukong e& al. Dept of Pharm, School of Pharm.
University of London, 79P Nbstract.
Ponmukong et al, Pharm. Pharmacol, 4
(1989),
Faye otal, Prine: Med. Chemistry, ourth Eition, 246-98
(Williams & Wilkins 1995),
Plirstner etal, J. Org. Chem., 62, 2832-36 (1997),
Gallly et al. JL Pharmacol. R'sp. Ther, 283, 918-924
1997)
Galve Roper etal, Naz Med. 6, 313-19 (2000),
Garvan et al, Bioorg. Med. Chem. Let, 6, 189-4 (1996),
Gervaix etal, Proc. Natl Acad. Sei (U.S.A. 94, 4653-58
«1997,
Gollapudi et al, Aids Res. Hum. Reirovir, 14, 499-504
(1998),
Gorter etal, Cannabis in der Behandlung krebsirander and
HIV-positiver Patienten Die erste Kinische Cannabis
‘Studie in Deutschland, Brohanf Syzuposium, 691-92 (1997)
(vith translation)
Granelli-Piperno e ab, Proc. Natl Acad. Sei. (U.S.A), 92,
1094448 (1995)
Grillin et al, Br J. Pharmacol, 126, 1575-84, (1999),
Gruol, “Drug Facts on Nouronal Development in Pediatric
Aids," Abstract NIH Grant No. IROIDATOL87-O1A2,
Gurwivz etal, Molecular Medicine Today, May, 196-200
(1998)
Hammer et al, The Scientist, 13, Feb. 15, 1999.
708-709US 7,105,685 B2
Page 3
Hanis et al, The Pharmacologist, 17, 2, Abstract 492
(1975),
Harvey ot al, Biomed. Mass Spect, 4, 364-70 (1977).
Hembree Ill et al, Marihuana and Medicine, (1999),
Herring et al, Biochem. Pharmacol. $5, 1013-23 (1998),
ladyszowski otal, Free Rad. Res,, 28, 359-68 (1997),
Huang etal, Marihuana and Medicine, (1999).
Hulman, “Synthesis “of Cannabinoids Analogues and
Metabolites” Abstrct, NIH Grant No. SRO1DA03590-11
Hollman etal, Bloor Med. Chem. 6, 2383-96 (1998).
Huflman etal, Bioorg. Med. Chem. 6, 2281-88 (1998).
Hofman et al, J. Med. Chem,. 39, 3875-77 (1996),
Hiufiman etal, Lyfe Set, $6, 2021-24 (1998),
Tokawa et al, Chem. Pharm. Bull, 35, 7, 3016-3020
(ass,
Jobin et al, Thromb, Diath, Haemorrh, 22, 3, 466-481
(4969),
Joy etal, “Consequences of Marijuana Use and Abuse." ia
‘Mariana and Medicine, 115-21, (National Academy
Press, 1999.
Kalofoutiset al, Pharm. Biochem. & Behavior, 12, 697-699
(1979),
Kaminski, J. Neuroimmunol, 83, 124-32 (1998),
Kaminski, Toviev! Ler, 102108, 59-63 (1998).
Kapeghian etal, Gen. Pharmacol, 14, 3, 361-363 (1983).
Khanotkar etal, Chem and Physics of Lipids, 18, 37-82
(2000,
Kitagawa et al, Chem, Pharm, Bull, 39, 4, 1062-1064
(199),
Klein etal, J. Newrolmmunol, 83, 102-15 (1998)
Koch e€ al. Shmesis of $-Ailylresorcnols, (Unclassified
Report) (1962),
Konubek eal, Chem Revs, 99, 1-25 (1999.
Lanez etal, Proc. Soe. Exp. Biol. Med 4, 401-«
Lembenger et al
(1973),
Liddle etal, Bioorg. Med. Chem. Let. 8, 2223-26 (1988).
Lpev etal, J Med. Chem. 11, 1234-35 (1974).
Loev et al, J; Med Chem, 16, 1200-06 (1973).
Lytolls etal, J. Am. Chem. Soe, 117, 12683-90 (1995).
Madani etal, Proc. Nath, ded. Sci, (U.S.A. 95, 8005-10
(1998),
Mahadevan etal. J. Med, Chem, 43, 3778-3785 (2000)
Makriyannis ota, Life Soi, 47, 2173-84 (1990)
Main etal, Pharm. Biochem. Behav, 46, 295-301 (1983).
Matsuyama etal, AIDS, 5 1405-17 (1991),
MeFerling, Chicago Tribune, Dec. 18, 1998
MePartland etal lr Ther, §, 57-62 (1990),
Mishkin et aly Proc. Soc Exp. Biol, Med., 185, 41-48
(1987),
Mon et al. Biochem. Pharmacol, 30, 31-43 (198)
Mon et al. Biochem. Pharmacol. 30, 45-58 (1981).
Morse etal, Life Sei. 56, 1957-62 (1995),
Nahas et al, Fed. Pro., 36, 1748-52 (1977)
Nahas et al, Pharmacology, poster session 1848,
Nathan et al, Cam. Physiol. Pharmacol, 70, 1308-1308
(1992),
Noe et al, Drugs of Abuse, Inmunomodulation and AIDS,
25, 223-24 (Plenum Press, 198),
Now etal. Advances in Experimental Medicine and Biology,
437, 223-29 (1998),
Novak etal, farahedron Let, 283-$4 (1982).
‘Ongradi et al, Patho! Oncol Res. 4, 191-199 (1998),
Papahatjs et al, J. Med. Chem, 41, 1195-200 (1998).
(i990,
Clin. Pharmacol. Ther, 18, 720-26
ars ota, J. Med. Chem, 19, 455-53 (1976).
ate, J. Int Hemp. Assoe., 2, 74.76 (1095).
Pearce et al, J. of Med. Chem., 37, 826-541 (1994)
Penglis etal, J. Immunol, 165, 3, 1605-1611 (2000),
Petite etal, Life Sei. 63, PL 1-6 (1998)
Pillai etal veh Tacol, 68, 609-617 (1991),
Piomelli, Nat Med., 6, 255-56 (2000),
Polansky etal, “Eivosanoid preduetion and ylucocorticoid
regulatory mechanisms jn eultuted human trabecular mesh-
‘work eels, "Abstract, NIH Grant No, 25081211190017695.
Pop, Cur. Op. Chem. Biol. 3, 418-425 (1998),
Promes etal, Emergency Medicine Report, 19, 24, 258-268
(1998)
Razdan etal, J. Med. Chem. 19, 454-60 (1976),
Rardan, Pharmacolog Rev. 38, 75-148 (1986).
Razdan, “Synthesis of Tetrahydrocannabino/related com-
pounds.” Abstract, NIH Grant No. SROIDADSAS8-12.
Reggio et al, J. Med. Chem. 40, 3812-18 (1997),
Rega et al Life Se, $6, 2025-32 (199)
Rhee et al. J Med. Chem, 40, 3228-33 (1997),
Rhee et al. J. Newroohem. 71, 1525-34 (1998),
Ritch, Current Opinion in Ophthalmology, U1
(2000),
Rome otal, Proc. Nat. Acad. Sci, 72, 4863-486 (1975),
Ross etal, Br J. Pharmacol. 126, 665-72 (1998).
Scannell etal, J. Am. Chem: Soe:, 110, 3651-83 (1988).
Schuel etal, Marihuana and Medicine, (1999).
Seltzman, Cur Med. Chem, 6, 685-704 (1999),
Shen et al, Prostaglandin Synthetase Inhibitors, 19-31
Angel Mateo Echanagorria Et Al - Pharmaceutical Formulations For The Safe Administration of Drugs Used in The Treatment of Drug Addiction and Processes For Obtaining The Same
David W. Pate Et Al - Anandamides Useful For The Treatment of Intraocular Hypertension, Opthalmic Compositions Containing The Same and Methods of Use of The Same
Rajender S. Varma and Rajender Dahiya - Copper (II) Nitrate On Clay (Claycop) - Hydrogen Peroxide: Selective and Solvent-Free Oxidations Using Microwaves
Laurence Perreux and Andre Loupy - A Tenative Rationalization of Microwave Effects in Organic Synthesis According To The Reaction Medium, and Mechanistic Considerations